WELCOME TO THE SYMPOSIUM ON OCT
TECHNOLOGY CELEBRATING
TRANSFORMATIVE IMPACT ON EYE
CARE AND BEYOND.
BEFORE WE GET STARTED, I WANTED
TO TAKE A MINUTE TO THANK THE
PEOPLE WHO MADE THIS POSSIBLE,
MADE SURE SEVERAL OF YOU MADE IT
HERE WITHOUT STANDING IN LINES.
IF I CAN HAVE THE NEXT SLIDE.
MAYBE I CAN DO IT.
YES.
THESE ARE THE PEOPLE WHO HELPED
ORGANIZE THIS SYMPOSIUM, ADMIN
STAFF FROM MY OFFICE, I SHOULD
SAY I'M THE SCIENTIFIC DIRECTOR,
NATIONAL EYE INSTITUTE.
PEOPLE FROM MY OFFICE, MIKA,
CHARLES
PRINCESS HAVE HELPED, STILL
OUTSIDE THE FRONT DESK, IF YOU
NEED HELP, NATHAN, CINDY, WITH
MY STAFF HELPING THEM ORGANIZE
THE SYMPOSIUM.
A BIG THANKS TO THE PLANNING
COMMITTEE TO IN A VERY SHORT
TIME FROM THE TIME OF OUR
CONCEPTION SINCE THE LASKER
AWARD TO PUTTING THIS TOGETHER
MAKING THIS HAPPEN, A WONDERFUL
AGENDA, FULL DAY AND A HALF FOR
ALL OF YOU STARTING WITH JOHNNY
TAM, TIERNAN KEENAN, TONY
DRIVER, AND PAEK LEE, AND DAVID
SCHNEEWEIS.
I THANK THEM ALL.
LAST BUT NOT LEAST THE IMPORTANT
PIECES, AMY AND HER CONSULTING
COMPANY, WHO YOU'VE GOTTEN
MULTIPLE E-MAILS FROM AMY.
I THANK THEM ALL FOR MAKING THIS
EVENT POSSIBLE.
WITH THAT, I'LL MOVE TO
INTRODUCING THE NEI DIRECTOR,
DR. MICHAEL CHANG, TO SAY A FEW
WORDS AS OPENING REMARKS FOR THE
SYMPOSIUM.
[APPLAUSE]
>> WELL, GOOD MORNING TO ALL OF
YOU.
WE'RE REALLY EXCITED ABOUT THESE
NEXT COUPLE DAYS HERE.
AND I JUST WANT TO THANK YOU FOR
COMING HERE TO BETHESDA.
WHAT WE DID IS PUT THIS ON IN
FAIRLY SHORT NOTICE.
WHAT REALLY SPURRED THIS WAS THE
LASKER AWARD AND NATIONAL MEDAL
OF TECHNOLOGY.
WE WANTED TO GET THIS DONE AT A
TIME THAT WAS -- WHILE IT WAS
STILL FRESH.
BECAUSE OF THAT, THIS WHOLE
GROUP THAT WAS TALKED ABOUT DID
A LOT OF WORK TO PUT THIS
TOGETHER ON SHORT NOTICE.
JUST ANOTHER WORD OF THANKS TO
THEM.
AND TO ALL OF YOU FOR MAKING IT
HERE TO BETHESDA.
IN ADDITION TO THE FOLKS, I WANT
TO CREDIT KAPIL, WHOSE IDEA IT
WAS TO PUT THIS TOGETHER.
HE WAS THE ONE THAT ASSEMBLED
THIS PLANNING GROUP.
THERE WERE SOME FOLKS FROM NIBIB
WHO HELPED US OUT AS WELL, JUST
ANOTHER WORD OF THANKS TO AMY
FOR REALLY BEING THE ONE IN
CAPITOL CONSULTING GROUP TO DO
THE LOGISTICS.
WHAT WE WANT TO DO IS LOOK BACK
AND CELEBRATE THIS TECHNOLOGY
AND LOOK FORWARD.
WHERE DO WE GO FROM HERE?
AND I JUST WANT TO SAY A FEW
REMARKS TO PUT THIS INTO
PERSPECTIVE BECAUSE I THINK THAT
OCT IMAGING HAS BEEN
TRANSFORMATIVE TO THE WAY WE
TAKE CARE OF PATIENTS AND THE
WAY WE THINK OF RESEARCH IN
VISION SCIENCE.
AND THE WAY THAT I LOOK AT THIS
IS THAT WHEN I WAS A RESIDENT,
SO I FINISHED IN 2001, SEE DAVE
GITEN, ONE OF MY FELLOWSHIP
MEANTORIES.
I HAD TO LEARN TO USE THIS
DEVICE.
CONTACT LENS.
TO EXAMINE ALL THE NUANCE OF THE
OPTIC NERVE HEAD AND MACULA.
I ALWAYS THOUGHT THAT WAS MY
ADDED VALUE AS AN
OPHTHALMOLOGIST.
BUT BECAUSE OF THESE
TECHNOLOGIES, PEOPLE DON'T DO
THIS ANYMORE.
THEY GET IMAGES.
AND, YOU KNOW, IN A WAY THAT'S
BEEN COMPLETELY TRANSFORMATIVE
IN WAYS THAT I THINK NOT
EVERYBODY TOTALLY APPRECIATES.
IT'S BECAUSE OF THAT, DAVID,
JIM, AND ERIC RECEIVED THE
LASKER AWARD.
A FEW WEEKS LATER THEY FOUND
THEMSELVES IN THE WHITE HOUSE
RECEIVING A NATIONAL MEDAL OF
TECHNOLOGY AND INNOVATION FROM
THE PRESIDENT, A REALLY BIG WIN
FOR THE VISION COMMUNITY.
AND JUST REALLY EXCITED THAT
DAVID AND JIM ARE HERE IN
PERSON.
ERIC UNFORTUNATELY COULDN'T MAKE
IT BUT I WANTED TO CONGRATULATE
BOTH OF YOU FOR THAT
ACCOMPLISHMENT.
[APPLAUSE]
SO, JUST TO SAY THE OBVIOUS.
IT'S BEEN -- THESE TECHNOLOGIES,
OCT, OTHER IMAGING TECHNOLOGIES,
THAT HAVE REALLY DRIVEN ALL THIS
ADVANCE IN DATA SCIENCE AND A.I.
THAT WE'VE SEEN IN THE VISION
FIELD.
AND NOW WHAT WE'RE HEARING ABOUT
IS GROWTH IN THE FIELD THAT IS
NOW WELCOMING KNOWN AS
OCULOMICS, WHERE THERE'S BEEN
IMPRESSIVE WORK YOU'VE READ
ABOUT AND YOU'LL HEAR ABOUT OVER
THE NEXT COUPLE DAYS, INVOLVING
A.I. MODELS TRAINED USING THESE
TECHNOLOGIES TO LOOK AT
DIAGNOSIS, PREDICTION OF
SYSTEMIC DISEASE,
NEURODEGENERATIVE DISEASE,
PARKINSON'S, ALZHEIMER'S,
PSYCHIATRIC DISEASE, CARDIAC
DISEASE.
THE QUESTION IS OBVIOUSLY WE'VE
GOT THESE TECHNOLOGIES, HOW ARE
WE GOING TO BUILD ON THEM.
FOUR THINGS WE'RE INTERESTED IN
HOW WE CAN TRY TO PROVIDE
FRAMEWORK TO HELP THE COMMUNITY
IN THESE AREAS.
NUMBER ONE IS THAT I THINK ONE
THING THAT'S OBVIOUS IS THAT
WE'RE GOING TO NEED LARGE
DATASETS OF IMAGES.
A.I.-READY DATASETS THAT AVOID
BIAS.
DIFFERENT IMAGING DEVICE,
DIFFERENT RACES, DIFFERENT
POPULATIONS.
AND AT THE NIH, ONE OF THE
THINGS THAT WE REALLY GOT
INTERESTED IN IS TRYING TO
ADDRESS THIS.
ONE PROJECT I WANT TO MAKE SURE
YOU'RE AWARE OF IS AN NIH COMMON
FUND PROJECT.
SO ANY AREA OF SCIENCE, ANY AREA
OF MEDICINE CALLED BRIDGE TO
A.I., IT WAS A PROJECT THAT
BEGAN IN 2021.
AND SO THE FIRST PHASE OF THAT
PROJECT COMMITS $130 MILLION
OVER FOUR YEARS TO BUILD
DATASETS.
AT NIH, MANY OF YOU KNOW NIH
EXTREMELY WELL.
WE'VE GOT THIS MANTRA,
HYPOTHESIS-DRIVEN RESEARCH.
THIS IS $130 MILLION FOR
BUILDING DATASETS, MORE OF A
HYPOTHESIS-GENERATING FRAMEWORK.
IN ADDITION TO BUILDING
MULTI-MODAL DATASETS, WE'VE
GOTTEN ETHICS COMPONENTS
INTEGRATED UP FRONT TO REDUCE
BIAS AND DEAL WITH PRIVACY.
AND IT'S MANAGED, ALTHOUGH IT'S
TRANS-NIH, IT'S MANAGED BY FIVE
INSTITUTES.
BIOMEDICAL, NIBIB, NATIONAL
LIBRARY OF MEDICINE,
COMPLEMENTARY MEDICINE AND
HEALTH, GENOME AND US.
THERE ARE FOUR DATA GENERATION
PROJECT AND ONE AWARDS FOR
SO-CALLED BRIDGE CENTER TO UNIFY
ALL OF THAT.
AND ONE THING THAT WE WERE
EXCITED ABOUT, ONE OF THOSE FOUR
DATA GENERATION TEAMS IS LED BY
A GROUP OF OPHTHALMOLOGISTS,
CECILIA LEE AND AARON LEE.
AARON LEE IS ONE OF THE SPEAKERS
HERE.
BIG DATA, LARGE DATASETS,
AVOIDING BIAS IS NUMBER ONE.
NUMBER TWO IS DATA SHARING AND
HARMONIZATION.
CLEARLY MODERN RESEARCH RELIES
ON BIG DATA, REGARDLESS OF
IMAGING OR ANY TYPE OF DATA.
WE NEED DATA SHARING, DATA
HARMONIZATION TO TAKE ADVANTAGE
OF THAT.
TO REALLY JUST DIVE INTO THAT
MORE, WE'VE GOT THIS PARADIGM,
THERE ARE OFTEN MULTIPLE SMALL
STUDIES GOING ON AROUND THE
WORLD THAT ARE ESSENTIALLY
TRYING TO ANSWER THE SAME
QUESTION.
YET ARE INDIVIDUALLY
UNDERPOWERED TO BE ABLE TO FULLY
ANSWER THOSE QUESTIONS AND
ADVANCE THE FIELD.
IN MY OPINION ONE OF THE
CHALLENGES OUR ACADEMIC SYSTEM
IS OFTEN NOT SET UP TO PROVIDE
INCENTIVES FOR PEOPLE TO SHARE.
I'D ARGUE SOMETIMES THE SYSTEM
DISINCENTIVIZES PEOPLE TO SHARE.
ANOTHER PROBLEM THOUGH IS EVEN
IF PEOPLE DID WANT TO SHARE,
WHEN YOU REPRESENT AND COLLECT
YOUR DATA INCONSISTENTLY YOU
CANNOT JUST COMBINE DATASETS.
WE NEED METHODS OF STANDARDIZED
DATA REPRESENTATION.
IN TERMS OF SHARING PIECE MANY
OF YOU KNOW AT THE NIH AND WHITE
HOUSE THERE ARE DATA SHARING
POLICIES.
IF YOU DON'T COME UP WITH A PLAN
WE WON'T FUND YOUR RESEARCH.
AND THAT'S WHAT I WOULD CONSIDER
A STICK.
I FEEL STRONGLY THAT IN ADDITION
TO THOSE SO-CALLED STICKS WE
NEED INCENTIVES, CARROTS TO
MOTIVATE IF YOU WANT TO DO THAT.
I MEET WITH EDITORS IN CHIEF OF
SOME OF THE MAJOR VISION
JOURNALS A FEW TIMES A YEAR.
WHAT CAN WE DO TOGETHER TO
ADVANCE THE COMMUNITY?
ONE OF THE THINGS WE CAME UP
WITH WAS TO TRY TO CREATE A NEW
PUBLICATION TYPE, A DATASET OR
SOFTWARE LIBRARY WHERE YOU CAN
WRITE A PAPER JUST ABOUT YOUR
DATASETS.
AND THAT WAY WE'LL COULD GET
ACADEMIC CREDIT, YOU CAN CITE IT
USING PubMed.
A SHOUT OUT TO MARCO ZARBIN,
EDITOR OF CHIEF, PIERCE KEY AND
AARON LEE FOR WRITING A PAPER
THAT DEFINED THAT TYPE OF
PUBLICATION A FEW YEARS AGO.
EMILY CHEW IS HERE, THE SECOND
JOURNAL THAT'S IMPLEMENTED THAT.
I HOPE IT'S THINGS LIKE THAT
THAT SHIFT THE CULTURE TOWARD
INCENTIVIZING DATA SHARING AND
TEAM SCIENCE.
I THINK WE'RE GOING TO NEED THAT
AS A COMMUNITY.
WE'RE GOING TO NEED A COMMON
DATA MODEL FOR OPHTHALMOLOGY,
VISION SCIENCE, AND IMAGING.
AND AT THE NATIONAL EYE
INSTITUTE WE'VE BEEN WORKING
WITH THE AMERICAN ACADEMY OF
OPHTHALMOLOGY TO DEVELOP THAT
COMMON DATA MODEL, AND WHO IS
LEADING THAT.
SALLY BAXTER FROM SAN DIEGO,
KERRY GOETZ FROM THE NATIONAL
EYE INSTITUTE HERE TODAY AND
MICHELLE RIBAR DOING A
SABBATICAL AT NEI TWO YEARS,
BASED IN OREGON, THOSE ARE
IMPORTANT, DATA SHARING, DATA
HARMONIZATION FOR IMAGING IN THE
FUTURE.
NUMBER THREE, OCULAR EMISSION
STANDARDS.
TO DO THE BEST RESEARCH AND TAKE
THE BEST CARE OF PATIENTS THESE
IMAGING DEVICES WILL HAVE TO
TALK EACH OTHER AND TALK TO
EHRS, IMAGE MANAGEMENT SYSTEMS.
ONE OF THE CHALLENGES IN THE
RADIOLOGY WORLD, THEY HAVE DONE
THIS FOR DECADES, BASICALLY
EVERY DEVICE SOLD ADHERES TO
DICOM STANDARDS, PLUG AND PLAY.
IN THE VISION FIELD DICOM
COMPLIANCE, STANDARDS DEFINED
FOR ALMOST EVERY MAJOR IMAGING
DEVICE BUT COMPLIANCE CONTINUES
TO BE OPTIONAL AND FAIRLY LOW.
DEVICES MARKETED AS COMPLIANT
OFTEN DO NOT MEET FULL
FUNCTIONALITY, A BARRIER TO
DEVELOPING LARGE TRAINING SETS
FOR A.I. AND MACHINE LEARNING
AND JUST FOR CLINICAL CARE
OVERALL.
WHAT ARE WE TRYING TO DO ABOUT
THAT?
WHEN I STARTED THIS POSITION,
ABOUT THREE YEARS AGO, I REALLY
FELT LIKE WE HAVE TO SOLVE THIS.
SO, WE STARTED WORKING WITH THE
FDA AND THAT GROUP AT THE FDA
WAS LED BY MALPINA EDELMAN AND
THE OEC GROUP IS LED BY MICKEY
TRIPATHI, REGULATING ELECTRONIC
DATA EXCHANGE.
WHAT CAN WE DO WORKING TOGETHER
TO ADVANCE TOWARD MORE OF AN
INTRAOPERABLE WORLD.
WE SPENT NINE MONTHS PLANNING
THE WORKSHOP IN MAY 2022, OUR
LEAD WAS KERRY GOETZ WITH AMBER
REID, A GREAT WORKSHOP, HUNDREDS
ATTENDED.
SIX MONTHS AFTER THAT, TWO MAJOR
RESEARCH SOCIETIES PUBLISHED A
POSITION PAPER SAYING WE NEED
HAVE INTRAOPERABILITY OF
DEVICES.
AND A FEW MONTHS AGO WE
PUBLISHED POSITION PAPER
TOGETHER WITH THE FDA AND ONC
THAT LAYS OUT WHAT ARE THE
LEVERS WE WANT TO USE AS THESE
AGENCIES TO TRY TO ADVANCE THE
FIELD.
SO THE FDA HAS THEIR SO-CALLED
LEVERS, ONC HAS THEIRS TO LIMIT
INFORMATION BLOCKING.
FROM MY PERSPECTIVE I DON'T WANT
TO BE FUNDING GRANTS IN THE
FUTURE IF THEY USE DEVICES THAT
DON'T CONFORM TO STANDARDS LIKE
DICOM BECAUSE I JUST DON'T THINK
THAT'S HOW WE'RE GOING TO DO THE
BEST RESEARCH, OF THE SORT WE
SHOWED ON THE PREVIOUS SLIDES,
OR FRANKLY TAKE THE BEST CARE OF
PATIENTS.
REALLY IMPORTANT, OCULAR IMAGING
STANDARDS.
LASTLY WE'VE GOTTEN INTERESTED
IN TRYING TO ADVANCE OCULAR
IMAGING FOR OCULOMICS.
AND ABOUT A WEEK AGO, THE
OFFICIAL ROLLOUT, RESEARCH
OPPORTUNITY ANNOUNCEMENT WAS
PUBLISHED FOR A NEW COMMON FUND
VENTURE INITIATIVE CALLED
OCULOMICS.
AND THE GOAL OF THIS IS TO
DEVELOP NOVEL NON-INVASIVE
OCULAR EMISSION TECHNOLOGIES,
MACHINE LEARNING ALGORITHMS AND
OTHER TOOLS TO IDENTIFY
BIOMARKERS FOR SYSTEMIC DISEASE.
THIS IS SOMETHING WE'RE EXCITED
ABOUT.
I JUST WANT TO CALL OUT IT CAME
OUT OF DISCUSSIONS THAT STARTED
WITH OUR PROGRAM OFFICERS AND
NEI WITH NIBIB, BIOMEDICAL
ENGINEERING, BIOENGINEERING,
NINDS, NEUROSCIENCE, TOGETHER
WITH NHLBI, HEART LUNG, AND NIA
AGING.
TONY GOVER IS THE LEAD, TONY IS
HERE.
CAN YOU RAISE YOUR HAND?
UP IN THE FRONT THERE.
IF YOU'RE INTERESTED IN THIS,
TONY IS THE BEST CONTACT PERSON
FOR THIS.
SO SORRY TO DO THAT TO YOU.
THEY HAVE DONE A GREAT JOB IN
PUTTING THIS TOGETHER.
AND SO IT'S ON A FAIRLY
AGGRESSIVE TIME FRAME WHERE THE
LETTERS OF INTENT AND DEADLINES
ARE DUE WITHIN THE NEXT FEW
MONTHS.
BUT WE'RE REALLY EXCITED ABOUT
THIS, CONNECTING THE EYE WITH
THE REST OF THE BODY.
AND JUST WHERE ARE THESE IMAGING
TECHNOLOGIES GOING.
WITH THAT, THIS IS MY LAST
SLIDE.
I WANT TO JUST FINISH BY SAYING
THAT I'M REALLY EXCITED TO HAVE
ALL OF US HERE, I HOPE THERE'S A
LOT OF GOOD CONVERSATION, BOTH
UP HERE AT THE PODIUM, AT THE
MICROPHONES, JUST IN THE
HALLWAYS.
WELCOME TO BETHESDA.
AND KAPIL, I'M GOING TO HAVE YOU
COME UP ON STAGE TO INTRODUCE
JIM.
AND THANK YOU ALL VERY MUCH.
[APPLAUSE]
>> I REALIZED IF I GO TO
ACCOMPLISHMENTS AND AWARDS WE'LL
SPEND A GOOD PART OF THE MORNING
DOING THAT.
I'M GOING TO DO SNIPPETS OF HIS
RESEARCH AND AWARDS AND HOPE
IT'S ACCEPTABLE.
AS WE KNOW, HE'S A PROFESSOR OF
BIOMEDICAL ENGINEERING AND
ELECTRICAL ENGINEERING, M.I.T.,
CO-INVENTOR OF OCT, CO-RECIPIENT
OF LASKER AWARD AND NATIONAL
MEDAL OF TECHNOLOGY AND
INNOVATION IN 23 PRESENTED BY
PRESIDENT OBAMA.
PRESIDENT BIDEN.
HE'S A MEMBER OF -- I LEARNED
DETAILS OF HIS LIFE I THOUGHT I
WAS SHARING WITH ALL OF YOU.
AND THERE ARE A FEW KEY WORDS IN
HIS LIFE, IN HIS SPEECH HE USED
AND SOME OF THESE ARE PASSION,
DEDICATION, TENACITY FOR HIS
RESEARCH.
AND PAYING ATTENTION OR DOING
TEAM SCIENCE AND TRANSLATION
RESEARCH, AS YOU HEARD FROM
MIKE'S OPENING REMARKS IS A KEY
ELEMENT FOR US, AND WE'LL SEE
THAT TEAM FOR THE NEXT DAY AND A
HALF THROUGHOUT MANY TALKS AND
MANY WAYS.
AND THE LAST THING I LEARNED
FROM HIS SPEECH WAS HIS
ATTENTION TO LISTENING TO HIS
TEACHERS AND MENTORS AND I HOPE
TRAINEES IN THE AUDIENCE ARE
LISTENING TO THAT AS HE REALLY
HAS AN EAR FOR WHAT HIS TEACHERS
ADVISE HIM.
I'LL TELL YOU WHY THAT'S
IMPORTANT FOR ALL OF US.
HE WAS SO PASSIONATE ABOUT
ELECTRONICS, AS A TEEN USING A
KIT DEVELOPED A TELEVISION BY
HIMSELF, I WAS TELLING MY SON
LAST NIGHT, HE WAS EXCITED TO
HEAR THAT.
HIS SECOND TALENT WAS HE WAS
GOOD AT MUSIC, AND SO GOOD AT
SOME POINT HE THOUGHT HE WANTED
TO BE A PROFESSIONAL MUSICIAN.
SO A GOOD FORTUNE ALL OF US HE
LISTENED TO HIS TEACHERS' ADVICE
AND DIDN'T GO INTO MUSIC AS A
CAREER.
LASTLY, I LEARNED FROM ERIC
SWANSON'S SPEECH TESTAMENT TO
DEDICATION FOR HIS WORK WHEN HE,
DAVID, ERIC, ALL OF THEM, WERE
DISCUSSING WHO WILL BE THE FIRST
VOLUNTEER TO TEST THE OCT, AND
VOLUNTEERED HAVE A LASER BEAM
SWEPT ACROSS THEIR RETINA, YOU
CAN IMAGINE AT THE TIME WAS
POTENTIALLY UNSAFE AND THERE WAS
ANXIETY AROUND IT, HE WAS THE
FIRST TO PUT HIS CLINTON --
CHIN ON THE STAND.
THAT'S JAMES FUJIMOTO, AND
WITHOUT FURTHER ADO I WOULD LIKE
TO WELCOME HIM.
[APPLAUSE]
>> THANK YOU.
IT'S A PRIVILEGE TO SPEAK TO YOU
SPECIFICALLY BECAUSE IN THE
AUDIENCE ARE MANY OF THE KEY
THOUGHT LEADERS IN CLINICAL
MEDICINE, FUNDAMENTAL RESEARCH
THAT DROVE DEVELOPMENT OF THIS
TECHNOLOGY, BOTH IN FUNDAMENTAL
SCIENCE AS WELL AS CLINICAL
TRANSLATION.
THIS PRESENTATION IS GOING TO
DESCRIBE HISTORY, EVOLUTION,
FUTURE PROSPECTS OF OCT.
AND BEFORE I BEGIN I WANTED TO
ACKNOWLEDGE OUR COLLABORATORS.
WE WERE FORTUNATE TO WORK WITH
OUTSTANDING CLINICAL SHOT
LEADERS.
A LONGTIME COLLABORATION.
IN THE AREA COMPUTATION, AND
INDUSTRY AS WELL.
IT HAS MULTIPLE APPLICATIONS, IN
OPHTHALMOLOGY, ALSO IN
CARDIOLOGY, HAS MANY FUNDAMENTAL
RESEARCH APPLICATIONS, USED IN
DIVERSE APPLICATIONS SUCH AS
ENDOSCOPY AND OTHER TYPES OF
ENDOSCOPIC IMAGING.
SO THE THEMES OF THIS
PRESENTATION ARE -- WE'LL
DISCUSS HISTORY OF OCT, AND TO
USE A PHRASE DEVELOPED BY ERIC
SWANSON THERE'S AN ECOSYSTEM OF
TECHNOLOGY TRANSLATION THAT
REQUIRES BASIC SCIENCE AND
TECHNOLOGY, APPLIED SCIENCE AND
MEDICINE.
WE'LL DESCRIBE ADVANCES THAT
ENABLED ENHANCED FUNCTIONALITY,
SPECTRAL DOMAIN, AND FINALLY
WE'LL LOOK AT SCIENTIFIC
CLINICAL AND ECONOMIC IMPACT.
SO, ONE OF THE THEMES IS CONCEPT
THAT THERE'S AN ECOSYSTEM.
GOVERNMENT FUNDING SUPPORTS
BASIC SCIENCE AND TECHNOLOGY
WHICH CAN THEN BE DEVELOPED INTO
APPLIED SCIENCE AND ENGINEERING.
IN CLINICAL APPLICATIONS,
CLINICAL STUDIES IN MEDICINE BY
THOUGHT LEADERS ARE CRITICAL
COMPONENT, INDUSTRY
PARTICIPATION, INVESTMENT,
DEVELOPMENT, ROLE OF
ENTREPRENEURSHIP ARE ALSO
IMPORTANT.
ALL OF THESE ARE SYNERGISTIC TO
IMPROVE PATIENT CARE AND
OUTCOMES.
WE ALSO HAVE ADVANCES FROM
INNOVATION TRANSFERRED FROM
OTHER OTHERS, AS WELL AS
ECONOMIC COMPONENT TO ALL OF
THIS.
I WAS FORTUNATE TO WORK WITH
ERIC IPPEN, ONE OF THE FOUNDERS,
I DID MY DOCTORAL STUDIES WITH
HIM AND MOUNTAIN -- AT M.I.T.
IN THE 1980s, THIS IS THE
TECHNOLOGY AT THE TIME,
OSCILLATORS AND AMPLIFIERS,
USING THIS WE BECAME INTERESTED
IN THERAPEUTICS, APPROACHED BY
CARMEN AND DID SOME OF THE FIRST
LASER RETINAL INJURY STUDIES
WHICH LED TO STUDIES THAT
EXPANDED THE STANDARD TO SHORT
PULSES.
I'LL MENTION WE WERE FORTUNATE
TO WORK WITH REGINALD, WHO
BECAME DIRECTOR OF A MEDICAL
CENTER IN GERMANY, AND YOU MAY
NOTICE ATUL WHO BECAME A
RESEARCHER, A VERY UNUSUAL GROUP
OF CO-AUTHORS, OUTSTANDING
COLLEAGUES.
WE FIRST BECAME INTERESTED IN
THE CONCEPT OF IMAGING BECAUSE
OF WORK DONE BY MICHELLE AT AT&T
BELL LABORATORIES IN 1971 AND
HAD THE CONCEPT OF AN OPTICAL
SHUTTER, A PICO SECOND, TO
PHOTOGRAPH A PULSE OF LIGHT
TRAVELING THROUGH MILK.
HERE YOU SEE THE PHOTOGRAPH.
THIS IS AN ULTIMATE HIGH SPEED
PHOTOGRAPH ON THE PICO SECOND
TIME SCALE.
IN HIS PUBLICATION, DUGUAAY
DEVELOPED PICTURE RANGING, IF
YOU PLACE AN OBJECT BEHIND A
SCATTERING MATERIAL AND YOU
COULD THEN DO A HIGH SPEED
PHOTOGRAPH, PHOTOGRAPHING ONLY
THE LIGHT THAT COMES FROM THE
OBJECT, ESSENTIALLY YOU COULD
SEE BEHIND THE SCATTERING
MATERIAL.
HE PARTIALLY RECOVERED THE ATT
LOGO.
HE ALSO SAID ONE POSSIBILITY OF
GATED PICTURE RANGING IS
POTENTIAL TO SEE THROUGH HUMAN
SKIN.
CONCEPT OF INTERNAL BODY
IMAGING.
WE APPLIED TECHNOLOGIES FOR
IMAGING AND INTERNAL BODY
APPLICATIONS.
SO, IT WAS POSSIBLE TO USE
TECHNIQUE WHICH ESSENTIALLY
MEASURED REFLECTIONS OR BACK
SCATTER BY COMPARING TO
REFERENCE PULSE, AND WITH THIS
IT WAS -- WE WERE ABLE TO
MEASURE CORNEAL THICKNESS,
CORNEA TO AQUEOUS, AND THIS WAS
POSSIBLE AND REQUIRED SHORT
PULSE LASERS.
IT WAS POSSIBLE TO AN OLD
TECHNIQUE DATING BACK TO SIR
ISAAC NEWTON, TO COMPARE LIGHT
BEAM TO REFERENCE PATH, IF --
IT WAS POSSIBLE TO MEASURE, AND
MEASURED ANTERIOR CHAMBER,
MEASURING DISTANCE TO IRIS, BY
DAVID HUANG, A MD/PHD STUDENT IN
OUR GROUP.
DAVID RECOGNIZED IT WAS POSSIBLE
TO GO BEYOND THIS AND EXTEND THE
CONCEPT TO IMAGING BY SCANNING
THE BEAM IN THE TRANSVERSE
DIRECTION.
SO THIS REPRESENTS EARLY OCT
IMAGE EX VIVO, THE BEAM IS
INCIDENT, DISPLAYED AS A FALSE
COLOR SCALE, BONDING HISTOLOGY
FROM EX VIVO EYE.
AND I APOLOGIZE FOR SHOWING
THIS, DAVID.
IT'S A GREAT PHOTO.
OKAY.
SO THIS IS A PHOTO OF DR. HUANG
WHEN HE WAS A Ph.D. STUDENT IN
OUR GROUP AT THE INTERNATIONAL
QUANTUM ELECTRONICS CONFERENCE
IN VIENNA, 1992.
AND DAVID LATER WENT ON TO
BECOME PROFESSOR OF
OPHTHALMOLOGY AND BIOENGINEERING
AT OREGON HEALTH AND SCIENCES
UNIVERSITY AND HE'S MADE MANY
POWERFUL CONTRIBUTIONS IN THE
FIELD OF OPHTHALMOLOGY.
I SHOULD ALSO MENTION THE
CONCEPT OF GENERATING IMAGES
FROM REFLECTED LIGHT WAVE WAS
INDEPENDENTLY DESCRIBED BY
PROFESSOR HIROTANO IN JAPAN AT
AROUND THE SAME TIME.
WE WERE FORTUNATE TO WORK WITH
ERIC SWANSON.
UNFORTUNATELY ERIC COULD NOT
ATTEND TODAY.
HE HAD A BOARD MEETING PLANNED
SEVERAL MONTHS IN ADVANCE AND
COULD NOT MOVE.
AT THE TIME WE STARTED
COLLABORATION HE WAS AT M.I.T.
LINCOLN LABORATORIES, THIS SHOWS
EARLY OCT TECHNOLOGY, NOT REALLY
POSSIBLE TO USE FOR CLINICAL
IMAGING.
ERIC REDESIGNED THIS INTO A
COMPACT FORM AND PATIENT
INTERFACE THAT INCREASED IMAGING
SPEED, ALLOWING IMAGES TO BE
FORMED IN SECONDS, PATIENT
INTERFACE SOFTWARE CONTROL.
AND I SHOULD ALSO MENTION THAT
ERIC WENT ON TO BECOME
CO-FOUNDER OF THE FIRST OCT
COMPANIES, AND IT'S INTERESTING
HE CO-FOUNDED COMPANIES SIX MORE
NETWORKS, ACACIA, RECENTLY
ACQUIRED BY CISCO, WENT PUBLIC
WITH A MULTI-BILLION DOLLAR
MARKET CAP.
THIS IS A PHOTOGRAPH OF OUR
EARLY OCT RESEARCH TEAM.
JOE IZATT, A POSTDOC, WENT ON TO
BECOME PROFESSOR AT DUKE
UNIVERSITY, AND MICHAEL HE,
MD/PHD STUDENT IN PRIVATE
PRACTICE, WHEN WITH A US
DEVELOPED SOFTWARE PROTOCOLS AND
EXAMINATION METHODS IN USE FOR
10 OR 20 YEARS.
WE SEE AN EXAMPLE OF THE FIRST
OCT INSTRUMENT, EARLY 1980s,
USING A MAC COMPUTER, THE BEAM
SCANNING ON THE RETINA,
GENERATION OF OCT IMAGES ON
MacINTOSH.
WE WERE FORTUNATE TO WORK
CLOSELY WITH CLINICAL THOUGHT
LEADERS, CARMEN AT THE NEW
ENGLAND EYE CENTER, LED STUDIES
IN 5,000 PATIENTS, IN THE LATE
TO 1990s, THIS IS AN EXAMPLE
OF FIRST OCT IMAGING STUDY OF
MACULAR DISEASE SHOWING MACULAR
HOLES, ALSO STUDIES IN DIABETIC
RETINOPATHY AND MACULAR
DEGENERATION.
I WANTED TO ACKNOWLEDGE WORK OF
JOEL SCHUMAN WHO WILL BE
SPEAKING TODAY, JOEL DID THE
FIRST STUDIES IN OCT IN
OPHTHALMOLOGY, THIS INTRODUCED
THE CONCEPT OF QUANTITATIVE
MEASUREMENT OF THE NERVE FIBER
LAYER, MAPPING, GLAUCOMA
DETECTION, PROGRESSION, RESPONSE
TO THERAPY.
QUANTITATIVE MEASURES OF
SURROGATE MARKERS ARE EXTREMELY
IMPORTANT TODAY.
CARMEN AND JOEL LED DEVELOPMENT
OF FIRST OCT ATLAS, AN IMPORTANT
STEP IN FACILITATING CLINICAL
ADOPTION BECAUSE TECHNOLOGY AND
METHOD WAS RELATIVELY UNKNOWN AT
THE, GUIDING THE INTERPRETATION
OF OCT AS A NEW MODALITY, IN
IT'S FOURTH EDITION NOW LED BY
JOEL SCHUMAN, EXPANDED 500 PAGES
AT THIS POINT.
THERE'S ALSO IMPORTANT
INVESTMENT FROM INDUSTRY.
JOHN MOORE WAS THE PRESIDENT OF
HUMPHREY ZEISS AND MADE A
COURAGEOUS DECISION, THERE WAS
NO PRECEDENT FOR DEVELOPING OCT
AT THAT TIME, A TREMENDOUS
COMMERCIAL RISK.
JAY WEI DEVELOPED THE ZEIZZ
INSTRUMENT, BECAME FOUNDER OF
OPTI VIEW.
THERE ARE MULTIPLE GENERATIONS,
THE STRATUS IS WHERE WE STARTED
TO SEE LARGER SCALE CLINICAL
ACCEPTANCE, INTRODUCED IN 2002.
WE CAN SEE THAT THERE'S
REPRESENTATIVE IMAGES, INITIAL
PROTOTYPE IMAGES, RELATIVELY LOW
PIXEL RESOLUTION, THE STRATUS
HAD HIGHER IMAGING SPEED.
RESOLUTION AND AXIAL DIRECTION
WAS THE SAME.
BUT THE HIGHER SPEED ALLOWED
HIGHER DEFINITION IMAGE.
THAT WAS AN IMPORTANT FACTOR IN
ACCELERATING CLINICAL
ACCEPTANCE.
SO IF YOU LOOK AT THE HISTORY OF
OCT, WELL, THERE'S A RELATIVELY
LONG HISTORY, UNTIL WE STARTED
TO SEE APPRECIABLE CLINICAL
UPTAKE.
I WANTED TO MENTION THAT
1999-2001, THESE ARE EXTREMELY
BAD FAILS COMPARED TO WHAT YOU
WOULD EXPECT IN OTHER AREAS.
AND ONLY WITH THE DEVELOPMENT OF
THERAPY, ANTI-VEGF, PIONEERED BY
PHIL ROSENFELD, DID WE SEE
APPRECIATABLE UPTAKE OF OCT IN
OPHTHALMOLOGY.
I WANTED TO ACKNOWLEDGE PHIL
ROSENFELD, AND ACCELERATED
ACCEPTANCE OF IMAGING TECHNOLOGY
BECAUSE PERSONALIZATION OF THE
TREATMENT WAS NEEDED, AND THIS
DROVE THE ADOPTION BUT ALSO
SAVED HEALTH CARE COST.
SO THE ACADEMY OF OPHTHALMOLOGY
IN 2006, WE STARTED TO SEE WIDER
SPREAD APPLICATION OF OCT,
MULTIPLE COMPANIES THAT WERE
MARKETING OCT TECHNOLOGY.
AND THEN IN PARALLEL WITH THIS
THERE WAS DEVELOPMENT OF
SPECTRAL DOMAIN, THIS DATES BACK
TO 1995.
BUT WITH THE DEVELOPMENT OF
HIGHER SPEED, IT BECAME POSSIBLE
TO INCREASE FUNCTIONALITY.
I WANTED TO MENTION THAT THIS
REALLY WAS AN INTERNATIONAL
EFFORT PIONEERING WORK AT THE
MEDICAL UNIVERSITY OF VIENNA,
PROFESSOR FERCHER, COPERNICUS
UNIVERSITY AND MULTIPLE GROUPS
DEMONSTRATED SPEED AND
ADVANTAGES.
IT BECAME POSSIBLE DO VIDEO RATE
FRAME ACQUISITION, LIKE YOU SEE
HER, OPTIC DISK, FIBER LAYER,
FLOOD FLOW IN RETINAL
VASCULATURE.
THIS ENABLED VOLUMETRIC OCT,
SCANNING SEQUENTIAL FRAMES
ALLOWS PROJECTION, ENABLES
LONGITUDINAL STUDIES, WORK BY
GREGORI AND PHIL ROSENFELD AT
BASKIN PALMER DEMONSTRATING ONE
COULD TAKE VOLUMETRIC IMAGES,
PROCESS TO EXTRACT FEATURES, DO
LONGITUDINAL FOLLOW-UP ON
SEQUENTIAL PATIENT VISITS TO
EXAMINE TREATMENT RESPONSE OR
PROGRESSION.
IT'S POSSIBLE TO EXTEND SPECTRAL
DOMAIN TO HIGH RESOLUTION, HERE
REWEI SEE TRADITIONAL
LOGARITHMIC DISPLAY SCALE, TO
HAVE HIGH RESOLUTION WE NEED TO
USE LINEAR SCALE.
WE CAN SEE DETAILS IN OUTER
RETINA APPROACHING WHAT ONE CAN
SEE IN HISTOLOGY IN TERMS OF
MEASURING THICKNESSES OF
STRUCTURES WHICH COULD BE
POTENTIAL SURROGATE MARKERS.
IT'S POSSIBLE TO TAKE VOLUME
MEASUREMENTS TO PERFORM MOTION
CORRECTION AND VOLUME AVERAGING,
THIS IS A VOLUME AVERAGE IMAGE
THAT'S CUT-AWAY VIEWS,
TREMENDOUS AMOUNT OF INFORMATION
FROM FEATURES IN THE OUTER
RETINA TO DRUSEN, ABILITY TO
IDENTIFY DIFFERENT TYPES AND MAP
OVER WIDE FIELDS OF VIEW,
REQUIRING A.I. METHODS.
OKAY.
NOBODY MAJOR DEVELOPMENT WITH
OCT ANGIOGRAPHY ENABLED BY HIGH
SPEED, ENABLED REPEATED SCANNING
TO DETECT MOTION CONTRAST FROM
BLOOD FLOW.
THIS ENABLED THREE DIMENSIONAL
IMAGING, IMAGES WERE SHARP, NOT
OBSCURED BY DYE LEAKAGE AS YOU
SEE WITH FLUORINE, THIS COULD BE
PERFORMED ON EVERY PATIENT VISIT
ENABLING LONGITUDINAL STUDIES.
THIS HAD SOME CHALLENGES.
THERE WERE LONG ACQUISITION
TIMES, GENERATING LARGE
DATASETS, STILL LIMITATIONS IN
ABILITY TO DIFFERENTIATE FLOW
SPEED, AND ALSO THIS REQUIRES
CAREFUL EXAMINATION, CAREFUL
MANAGEMENT OF DATA, BECAUSE
THERE'S POTENTIAL FOR ARTIFACTS.
OCT ANGIOGRAPHY DATES BACK TO
BEFORE 2006, A GROUP IN JAPAN.
ONE OF THE SEMINAL CONTRIBUTIONS
WAS THE WORK BY OHSU, WHO IS
ALSO ON THIS PROGRAM, SPECTRUM
AMPLITUDE CORRELATION AND
GEOGRAPHY, ACCELERATING ADOPTION
OF ANGIOGRAPHY INTO COMMERCIAL
APPLICATION.
SO, ESSENTIALLY OCT ANGIOGRAPHY
WORKS BY REPEATING SCANS AT SAME
LOCATION MULTIPLE TIMES,
GENERATING DECORRELATION IMAGE,
DATA INTENSIVE BUT GENERATES
VASCULAR CONTRAST, DEPTH
RESOLVED.
YOU CAN SEE EXAMPLE OF THIS
CIRCA 2010 GOING THROUGH THE
RETINAL VASCULATURE, INTO THE
SUBRETINAL SPACE.
YOU CAN ALSO SEE THE CHOROIDAL
VASCULATURE.
THERE'S BEEN TREMENDOUS INTEREST
ACADEMICALLY AND THIS ALSO
STIMULATED COMMERCIAL
DEVELOPMENT, MULTIPLE COMPANIES
INTRODUCED OCT ANGIOGRAPHY,
ACCELERATING OUR UNDERSTAND OF
DISEASE PATHOGENESIS AND
PROVIDES NEW MARKERS FOR
MEASURING PROGRESSION AND
TREATMENT RESPONSE.
THERE'S AN ALTERNATE METHOD OF
IMAGING WHICH IS THE DOMINANT
METHOD THAT'S USED IN ALMOST ALL
OTHER APPLICATIONS FOR INTERNAL
MEDICINE, DATES BACK TO 1992,
THERE WERE MULTIPLE
DEMONSTRATIONS, AND LATER
RECOGNIZED THIS HAD A TREMENDOUS
SPEED ADVANTAGE.
I ESPECIALLY WANTED TO MENTION
THAT THE LASER LIGHT SOURCE IS A
CHALLENGE FOR SWEPT SOURCE.
HERE WE SEE EXAMPLE OF SO-CALLED
VERTICAL CAVITY EMITTING LASER,
ASPIRING INNOVATION FROM OPTICAL
COMMUNICATIONS, THIS IS AN
ENABLING TECHNOLOGY FOR
VIRTUALLY ALL OF WIDE FIELD OCT
AND OCT ANGIOGRAPHY WE SEE
TODAY, SWEEP RATES INTO
MEGAHERTZ, SO HERE WE SEE
EXAMPLE OF WIDE FIELD OF VIEW
FLY-THROUGH, 600 KILOHERTZ SCAN
RATE, 23 MILLIMETER FIELD OF
VIEW, EXACTING A SINGLE B SCAN
WHICH SCANS OPTIC NERVE HEAD,
MACULA, MORE INTO THE PERIPHERY.
WE CAN GENERATE WIDE FIELD
IMAGES THAT SPAN FIELDS OF VIEW
WITH SCANNING LASER
OPHTHALMOLOGY.
WE CAN LOOK AT THE DIFFERENT
RETINAL LAYERS THROUGH
HIGHLIGHTING THE NERVE FIBER
LAYER, SECTION DEEPER INTO
SUBRETINAL SPACE, VORTEX VEIN
SPES.
THIS IS CAPTURED ACROSS FIELD OF
VIEW, POSSIBLE TO ZOOM ON
DIFFERENT REGIONS AND PERFORM
HIGHER RESOLUTION SCAN, IN THE
FULL VIEW REGION OR DIRECTING TO
MORE PERIPHERAL REGION HERE.
WE CAN START TO SEE INDIVIDUAL
CAPILLARIES.
WE CAN USE LONG RANGE PROVIDED
BY SWEPT SOURCE TO ANTERIOR EYE
BIOMETRY, 25 KILOHERTZ, THIS CAN
SPAN THE INTERIOR CHAMBER, TO
THE BACK OF THE LENS.
ONE CAN DO WIDE FIELD OF VIEW,
THIS IS 25-MILLIMETER SQUARE
FIELD OF VIEW, RENDERING THE
EYE.
AND THE EYELIDS.
YOU CAN TAKE THIS TO EXTREMELY
SEVERE DISTANCES.
THIS IS A CUBIC MILLIMETER FIELD
OF VIEW, LIFE SIZE REPLICA OF A
PERSON AND CHESS BOARD.
OKAY.
BUT I THINK MORE INTERESTING IN
RETINA IS ABILITY TO TAKE THIS
TO EXTREMELY SMALL SCALE, HIGH
DEFINITION SCANNING.
WITH HIGH SAMPLE DENSITY HERE WE
CAN START TO RESOLVE THE
CAPILLARIES AND SEE CAPILLARY
CONNECTIVITY, SKELETONIZED, WE
CAN LOOK AT THE THREE
DIMENSIONAL STRUCTURE.
SO REPRESENTING THIS AS A GRAPH,
THIS COULD BE POTENTIALLY QUITE
IMPORTANT FOR DIABETIC
RETINOPATHY, WHERE WE COULD
IDENTIFY NON-PERFUSION AT THE
CAPILLARY LEVEL AND TRACK ITS
PROGRESSION AND RESPONSE.
THERE'S INTEREST IN RESOLVING
BLOOD FLOW SPEED AT CAPILLARY
LEVEL USING SCAN TIME ANALYSIS,
WE CAN ASSESS THE SATURATION OF
THE OCT-A SIGNAL WITH TIME,
REPORTED TIME, REPEATED TIME
MEASUREMENTS.
AND BY DOING FOUR TO FIVE
REPEATED B SCANS AND COMPARING
OCT ANGIOGRAPHY AND DIFFERENT
TIME INTERVALS CAN EXTRACT
SURROGATE MARKETER FOR BLOOD
FLOW SPEED, CAN BE EVALUATED,
DATA INTENSIVE, CAN CLASSIFY BY
SURROGATE MARKER FOREBLOOD FLOW
SPEED, DISPLAYED, SO HERE YOU
SEE RETINAL NERVE FIBER LAYER,
SLOWER SPEED, VERSUS DEEP
CAPILLARY PLEXUS, SLOWER SPEED
AND DCP.
WE CAN LOOK AT EXAMPLES IN
DIABETIC RETINOPATHY VERSUS
HEALTHY, MILD PDR, VERSE U.S.
SEVERE NPDR, YOU SEE CAPILLARY
DROPOUT BUT WE SEE ALTERATIONS
IN BLOOD FLOW SPEED IN DIFFERENT
CAPILLARY PLEXUS, BY ASSESSING
FLOW IMPAIRMENT THE HOPE IS THIS
MIGHT BE A REVERSIBLE MARKER
THAT PRECEDES CAPILLARY
NON-PERFUSION.
WE CAN LOOK AT THE INDIVIDUAL
CAPILLARY LEVEL, HERE YOU SEE
ENLARGEMENT, STANDARD OCT
ANGIOGRAPHY, VERSUS SCAN TIME
ANALYSIS.
WE CAN START TO SEE DIFFERENCES
IN FLOW WHICH ARE NOT
NECESSARILY REFLECTED IN THE
GRAYSCALE IMAGE.
SO WE THINK THIS IS POTENTIALLY
QUITE AN EXCITING TECHNIQUE.
THIS CAN ALSO BE APPLIED TO THE
CHORIOCAPILLARIS, COMPARING
HEALTHY NORMAL VERSUS
DIABETIC-TREATED PDR,
ALTERATIONS OF COURSE IN THE
CHORIOCAPILLARIS AREAS OF
NON-PERFUSION, BUT ALSO AREAS OF
FLOW IMPAIRMENT.
AGAIN, THIS MIGHT BE A
REVERSIBLE MARKER, NOT ONLY IN
DIABETIC RETINOPATHY BUT IN AMD.
OKAY.
LET'S CONSIDER THE SCIENTIFIC
CLINICAL AND ECONOMIC IMPACT.
I WANT TO EMPHASIZE THE
INTERNATIONAL COMMUNITY.
THERE'S MULTIPLE RESEARCHERS,
OVER 500 ORGANIZATIONS
PERFORMING OCT RESEARCH.
THIS WAS A SURVEY BACK IN 2015,
YOU SEE THE LINES REPRESENT
COLLABORATIVE CONNECTIONS
BETWEEN DIFFERENT RESEARCH
GROUPS.
THIS WAS REALLY CRITICAL
COMPONENT IN ADVANCING THE
TECHNOLOGY AND IN ADVANCING
HEALTH CARE.
THIS IS ALSO AN EXAMINATION OF
PUBLICATIONS, AND WE CAN NOTICE
THAT PUBLICATIONS TRACK THE
COMMERCIALIZATION.
SO DEVELOPMENT OF OCT AND
OPHTHALMOLOGY LED TO
AVAILABILITY OF TECHNOLOGY FOR
FUNDAMENTAL RESEARCH AS WELL AS
CLINICAL STUDIES, INTRODUCTION
OF OCT COMMERCIALLY IN
CARDIOVASCULAR ALSO ENABLED
WIDER SPREAD STUDIES, AND
THERE'S MULTIPLE COMPANIES
DEVELOPING PRODUCTS IN THIS
AREA.
OPHTHALMOLOGY, I'M SO SORRY.
UH-OH.
THE COMPUTER HAS FROZEN.
IT'S NONRESPONSIVE.
CAN I GET ASSISTANCE?
>> WE'RE GETTING IT.
>> OKAY.
LET ME TRY TO ADVANCE.
STILL NONRESPONSIVE.
THE KEYBOARD IS NONRESPONSIVE
TOO.
OKAY.
CAN YOU CLICK FORWARD FOR ME?
FORTUNATELY WE'RE NEAR THE END.
OKAY.
CAN YOU CLICK.
MAYBE IT'S WORKING.
SO OPHTHALMOLOGY IS THE LARGEST
AREA WE SEE PUBLICATION,
REPRESENTED BY THE GREEN BAR
HERE.
IT IS STILL NONRESPONSIVE.
LET ME GO BACK.
CARDIOLOGY, THE BLUE BAR, THE
SECOND AREA.
AND THERE'S MULTIPLE OTHER AREAS
THAT ARE BEING DEVELOPED.
THE SECOND LARGEST CLINICAL
APPLICATION IS IN CARDIOLOGY.
I SHOULD MENTION THAT THIS WAS
LED BY A GROUP AT MASSACHUSETTS
GENERAL HOSPITAL.
THEY PERFORMED THE FIRST IN-MAN
STUDIES USING OCT.
THIS HAS BEEN A POWERFUL
TECHNOLOGY FOR UNDERSTANDING
PATHOGENESIS OF CARDIOVASCULAR
DISEASE.
THERE'S MULTIPLE CLINICAL
STUDIES UNDERWAY.
STILL RELATIVELY EARLY IN TERMS
OF STANDARD OF CARE.
OCT IS BEING DEVELOPED IN MANY
OTHER CLINICAL SPECIALTIESN
GASTROENTEROLOGY AND DETERMINE
NOTHING AND PULMONOLOGY.
IF WE COME BACK TO OPHTHALMOLOGY
THIS HAS A VERY, VERY LONG
HISTORY, REQUIRED A LONG TIME TO
DEVELOP, SINCE THE INITIAL
DEMONSTRATION.
THIS TRACKS THE DEVELOPMENT TO
THE COMMERCIAL INTRODUCTION OF
OCT ANGIOGRAPHY BY OPTIVIEW IN
2014.
AND IN GENERAL, CLINICAL
INSTRUMENTATION IS A VERY LONG
PROCESS.
MULTIPLE YEARS, LABORATORY
STUDIES, APPROVAL, MULTI-CENTER
STUDIES, EFFICACY, REIMBURSEMENT
TO THE POINT THERE'S RETURN ON
VERY KNEW, AND THE MARKET IS
LIMITED COMPARED TO
PHARMACEUTICAL.
WE'VE SEEN TREMENDOUS ECONOMIC
IMPACT, SO WITH THE DEVELOPMENT
OF ANTI-VEGF AND USE OF OCT TO
PERSONALIZE ANTI-VEGF, THERE WAS
A STUDY IN 2018 THAT
DEMONSTRATED THAT IT WAS
POSSIBLE TO SAVE OVER $10
MILLION TO THE GOVERNMENT AND TO
PATIENTS BY USING OCT.
THIS OF COURSE IS JUST ONE
MEASUREMENT.
I THINK THE MAJOR IMPACT IS ON
PATIENT CARE.
EARLY DIAGNOSIS PREVENTING LOSS
OF VISION, MANAGING TREATMENT,
THIS IS REALLY THE MAJOR IMPACT
LED BY CLINICAL THOUGHT LEADERS,
AND CLINICIANS WHO ARE ON THE
FRONT LINES OF CLINICAL CARE.
THIS IS VERY HARD TO MEASURE BUT
I THINK IT'S THE PRIMARY
OBJECTIVE FOR WHAT ALL OF US ARE
DOING.
THE TAKEHOME MESSAGES ARE THE
DEVELOPMENT OF OCT IS AN
EXAMPLE, ONE EXAMPLE OF
TRANSLATION OF RESEARCH TO
CLINICAL IMPACT.
I THINK THERE ARE MANY POTENTIAL
TECHNOLOGIES, METHODS, THAT CAN
BE TRANSLATED OF COURSE.
DOCTORAL TRAINEES AND EARLY
CAREER PROFESSIONALS MADE MAJOR
ADVANCES, THIS IS POSSIBLE AT
EARLY CAREER STAGE.
INTERNATIONAL COMMUNITY PLAYED A
CRITICAL ROLE IN THE DEVELOPMENT
OF OCT.
ADVANCES IN TECHNOLOGY, OPTICAL
COMMUNICATIONS, COMPUTATION,
IMAGING PROCESSING IN PARTICULAR
COULD BE TRANSLATED TO ENABLE
ADVANCES IN MEDICINE AND
WIDESPREAD IMPACT REQUIRES
ECOSYSTEM OF GOVERNMENT FUNDING,
FUNDAMENTAL RESEARCH,
ENGINEERING, CLINICAL STUDIES BY
CLINICIANS, SCIENTISTS, INDUSTRY
INVESTMENT AND MANY OTHER
COMPONENTS.
AGAIN, I WANTED TO ACKNOWLEDGE
ALL OF OUR COLLABORATORS, AND
THEN ESPECIALLY ACKNOWLEDGE THE
NATIONAL INSTITUTES OF HEALTH.
WE WERE FORTUNATE TO HAVE
LONG-RUNNING GRANT FROM NEI, AND
AIR FORCE OFFICE OF SCIENTIFIC
RESEARCH INSTRUMENTAL IN FUNDING
TECHNOLOGY DEVELOPMENT, INDUSTRY
AND FOUNDATION SUPPORT.
I HOPE THIS GIVES A SENSE FOR
THE DEVELOPMENT OF OCT
TECHNOLOGY, AND THE COMMUNITY
REALLY THAT DEVELOPED THIS.
SO THANK YOU VERY MUCH FOR YOUR
ATTENTION.
[APPLAUSE]
>> TIME FOR QUESTIONS?
>> CONGRATULATIONS FOR
COMPREHENSIVE REVIEW,
OUTSTANDING CONTRIBUTION FOR
GIVING US VISIONS OF THE FUTURE.
SO, I WAS LOOKING AT THE
OUTSTANDING DEMONSTRATION OF THE
PHOTOGRAPHS AT THE HIGH
RESOLUTION.
WHAT ULTIMATELY IN TISSUE
ISCHEMIA PLAYS CRITICAL FROM
CARDIOVASCULAR DISEASE, ISCHEMIC
DEATH OF PHOTO, SPECULATION, IS
THERE A WAY TO COME UP WITH
PHOTOGRAPHS?
>> YOU'RE ASKING ABOUT ISCHEMIA
IN CONTEXT OF RETINA?
>> YES.
>> THIS IS A GENERAL ISSUE.
>> IN THE BLOOD FLOW PARAMETERS.
>> YEAH.
SO THAT'S AN IMPORTANT AND
INTERESTING QUESTION.
OCT ANGIOGRAPHY CAN MEASURE
VASCULAR STRUCTURE, NOW WE'RE
STARTING TO GET TO THE POINT WE
CAN ASSESS FLOW.
TO THE EXTENT THAT THAT'S
RELATED, RIGHT?
ONE CAN ASSESS IT.
HOWEVER, IF YOU'RE ASKING ABOUT
SO-2 OR PO-2 THAT IS VERY HARD.
IDEALLY ONE WOULD LIKE TO ASSESS
THIS.
BUT THAT'S METABOLIC.
SO THE TRANSS FROM STRUCTURAL TO
FUNCTIONAL TO METABOLIC IS VERY
HARD.
>> THANK YOU FOR THE FASCINATING
TALK AND CONGRATULATIONS.
I HAD A QUESTION ABOUT THE GRID,
WHICH IS THE MOST IMPORTANT
THING THAT ALL OF US USE,
CENTRAL FIELD THICKNESS, NINE
SUBFIELDS.
AND, YOU KNOW, THIS WAS MACULAR
GRID, CIRCULAR CONCENTRIC ONE,
FROM THE '70s.
WONDERING WHAT'S THE STORY
BEHIND HOW IT CAME TO OCT, WAS
THAT YOUR TEAM, HOW DID IT GET
ADOPTED INTO OCT IMAGING WITH
THE CIRCULAR GRID ON SQUARE
IMAGING VIEW?
>> I'M SORRY, THE SOUND QUALITY
IS NOT VERY GOOD UP HERE.
>> THE GRID.
>> THE ADAPTION TO --
>> OCT OF CIRCULAR GRID WITH
CENTRAL SUBFIELD THICKNESS, ALL
THE NINE SUBFIELDS THAT ARE
THERE?
>> OH, OKAY.
YOU'RE ASKING ABOUT ETTRS?
>> YES.
>> OKAY.
WITH THE RATIONALE, THE EARLY
INSTRUMENTS HAD LIMITED
ACQUISITION SPEED.
SO THE CONCEPT IN THOSE
INSTRUMENTS, THIS IS VERY
SPECIFIC, TO SCAN RADIALLY, TO
MAP THICKNESS AND SUPERIMPOSE ON
ETTDRS.
WITH THE DEVELOPMENT OF HIGH
SPEED STANDARD IS VOLUMETRIC
ACQUISITION, THIS GENERATES
COMPREHENSIVE DATA, THINGS HAVE
EVOLVED SINCE THE EARLIER
COMMERCIALIZATION.
>> THANK YOU.
>> PROFESSOR, I'D LIKE TO ADD MY
CONGRATULATIONS.
YOU ARE CERTAINLY HAVE SHOWN US
A NEW WORLD CLINICALLY.
I THINK THE IMPACT IS
TREMENDOUS, AS A CLINICIAN I CAN
APPRECIATE THE -- THE TIME I WAS
IN TRAINING.
MY QUESTION IS, SO WHERE DO YOU
THINK WE'RE GOING TO GO FROM
HERE IN THE NEXT TEN YEARS WITH
THIS TECHNOLOGY?
I'M SURE YOU HAVE SOME IDEAS
THAT YOU'RE HOLDING OUT.
I KNOW EVERY TIME I ASK YOU
QUESTIONS LIKE THIS, YOU HAVE A
FEW THINGS IN YOUR POCKET.
>> WOW!
OKAY.
SO, I THINK IT WOULD BE
INTERESTING TO SEE THE
APPLICATIONS IN OTHER AREAS,
RIGHT?
SO INTERNAL MEDICINE, SURGICAL
GUIDANCE, THESE ARE POTENTIALLY
VERY INTERESTING, POWERFUL
AREAS.
EACH OF THESE INDICATIONS
REQUIRES A SEPARATE DEVELOPMENT.
THIS IS AMAZINGLY CHALLENGING.
IT TOOK A LONG TIME TO GET OCT
ESTABLISHED IN OPHTHALMOLOGY.
I THINK IN OPHTHALMOLOGY WE'RE
STARTING TO SEE INTEGRATION OF
FUNCTIONAL IMAGING, RIGHT?
WITH STRUCTURAL IMAGING.
IN THE PROGRAM YOU'LL HEAR MANY
PRESENTATIONS THAT HAVE --
LOOKING AT FUNDAMENTAL RESEARCH,
CLINICAL APPLICATIONS, VISIBLE
OCT, ALL OF THESE TECHNIQUES ARE
STARTING TO EXTEND INTO
FUNCTIONAL AND POSSIBLY INTO
METABOLIC, SO I THINK THAT'S
VERY INTERESTING.
ALSO OF COURSE LOW COST
EXTENDING POINT OF CARE TO THE
PHARMACY, TO THE PRIMARY CARE,
MAYBE PRIMARY CARE, THAT WOULD
HAVE TREMENDOUS IMPACT ON VISION
LOSS, EARLY DETECTION OF OCCULT
DISEASE.
>> THANK YOU.
>> I'D LIKE TO THANK DR.
FUJIMOTO FOR THE TALK.
[APPLAUSE]
>> GOOD MORNING, I'M DEPUTY
SCIENTIFIC DIRECTOR IN NEI.
MY JOB IS TO GIVE A FEW
HOUSEKEEPING ITEMS, ALSO GET
FIRST SESSION UNDERWAY.
WHILE I DO HOUSEKEEPING MAYBE
THE SPEAKERS FOR FIRST SESSION
CAN COME UP SO WE CAN GET MOVING
RAPIDLY.
FIRST OF ALL, I'M SUPPOSED TO
MAKE EVERYBODY AWARE OF THE FACT
THAT THIS MEETING IS BEING
RECORDED AND ALSO LIVECAST.
THERE'S AN AUDIENCE, WE DON'T
KNOW HOW LARGE IT IS AT THIS
POINT BUT ABOUT OVER 100 PEOPLE
HAVE REGISTERED.
LOOKING FORWARD TO NEXT AND
SUBSEQUENT SESSIONS.
SPEAKERS ARE ASKED TO PLEASE
PROVIDE PRESENTATIONS TO A.V.
FOLKS AT THE BACK OF THE ROOM IF
YOU HAVEN'T ALREADY, AND MEET AT
THE PODIUM A FEW MINUTES BEFORE
THE SESSION.
LOOKING FORWARD TO THE BREAK
AFTER THIS SESSION.
IF YOU HAVE A GREEN DOT ON YOUR
BADGE IT MEANS YOU PAID FOR
LUNCH WHICH GETS YOU COFFEE
DURING THE BREAK.
SO THAT WILL BE OUTSIDE, AROUND
TO THE RIGHT IN THE FAES
TERRACE.
IF YOU DID NOT PAY FOR LUNCH THE
COFFEE SHOP IS 20 YARDS DOWN THE
HALLWAY NEAR THE BOOK STORE.
I THINK YOU HAVE DISCOVERED
ALREADY YOU'RE NOT ALLOWED TO
HAVE FOOD OR DRINK IN THE
AUDITORIUM.
AND SO YOU NEED TO KEEP THAT
OUTSIDE, RESTROOMS ARE JUST
OUTSIDE OF THE AUDITORIUM,
RESTROOMS ARE OUTSIDE THE
AUDITORIUM.
I THINK WE CAN PROBABLY MOVE ON.
THE FIRST SESSION IS TRADITIONAL
STRUCTURES/BIOMECHANICAL OCT,
AND EACH SESSION IS GOING TO
BE -- GOING TO HAVE SEVERAL
SPEAKERS AND A MODERATOR, AND WE
ASK THAT YOU HOLD YOUR QUESTIONS
TO THE END OF EACH SESSION.
GETTING THE FIRST SESSION,
MODERATING THE FIRST IS DR.
KIRILL LARIN, THE CULLEN COLLEGE
OF ENGINEERING DISTINGUISHED
PROFESSOR OF BIOMEDICAL
ENGINEERING, UNIVERSITY OF
HOUSTON.
I INVITE DR. LARIN UP TO LEAD
THE SESSION.
>> THANK YOU VERY MUCH.
>> WELCOME TO THE SESSION.
TO CELEBRATE OCT MADE PROGRESS
FOR CLINICAL RESEARCH OVER THE
YEARS.
I'M PLEASED REMIND EVERY SPEAKER
PRESENTING DATA, HOLD THE
QUESTIONS.
I'VE BEEN ASKED TO PUT DOWN THIS
PAGE.
YOU DON'T NEED TO SIT HERE, YOU
CAN ENJOY FROM AUDIENCE.
LET ME INTRODUCE DR. XU, M.D.
PhD from Columbia University,
residency, University of
California San Diego, and
currently assistant professor
University of Southern
California.
>> THANK YOU FOR THE
INTRODUCTION.
I'D LIKE TO THANK THE ORGANIZERS
FOR INVITATION TO SPEAK TODAY.
IT'S A GREAT HONOR TO BE HERE
AND CELEBRATE ACHIEVEMENTS OF
THE THREE, AND I'M EXCITED TO
SHARE WORK OCT ENABLED FOR US IN
OUR LAB.
I'D LIKE TO ACKNOWLEDGE FUNDING
SOURCES, I DO RECEIVE RESEARCH
SUPPORT FROM HEIDELBERG
ENGINEERING, I'LL BE TALKING
ABOUT THEIR SYSTEM TODAY.
PRIME PACG IS A COMMON CAUSE OF
PERMANENT VISION LOSS WORLDWIDE,
AFFECTING 24 MILLION PEOPLE,
THREE-QUARTERS IN ASIAN REGIONS,
EXPECTED TO RISE DUE TO AGING OF
WORLD'S POPULATION, CONCERNING
AS PACG IS MORE VISUALLY
DAMAGING CONFERRING 2.4 TIMES
HIGHER ODDS OF BLINDLESS.
THERE'S CONTACT BETWEEN THE MESH
WORK AND EYE WORK, IN SEVERE
CASES CAN LEAD TO ELEVATED
INTRAOCULAR PRESSURE AND
NEUROPATHY.
CURRENT CLINICAL STANDARD TO
DETECT ANGLE CLOSURE IS
GONEOSCOPEY, WHEN WE CAN'T SEE
THIS STRUCTURE WE TELL PATIENTS
THEY HAVE ANGLE CLOSURE AND MAY
BE AT RISK FOR PACG.
ANGLE CLOSURE FORMS THE BASIS OF
CURRENT DEFINITION OF PRIMARY
ANGLE CLOSURE DISEASE, MILDEST
FORM, THERE ARE TWO OR MORE
QUADRANTS.
PACG IS DIAGNOSED IN THE
PRESENCE OF GLAUCOMA OPTIC NERVE
DAMAGE WITH OR WITHOUT VISUAL
FIELD DEFECTS.
IT HAS A NUMBER OF LIMITATIONS,
SUBJECTIVE, EXPERTISE DEPEND,
MODERATE REPRODUCIBILITY.
THE CONTACT METHOD CAN BE
UNCOMFORTABLE AND TIME CONSUMING
FOR SOME PATIENTS, THESE
LIMITATIONS LEAD THIS TO BE
UNDERPERFORMED BY PHYSICIANS AT
LEAST IN THE UNITED STATES.
A STUDY FOUND PATIENTS
UNDERGOING FIRST-TIME GLAUCOMA
EVALUATIONS, ONLY 30% ARE
RECEIVING GONIOSCOPY.
LIMITATIONS CONTRIBUTE TO MAKE
ISSUE IN ANGLE CLOSURE, REMAINS
UNDIAGNOSED AND UNTREATED UNTIL
AFTER VISION LOSS OCCURS.
WE CAN SEE HERE THIS PREVALENCE
OFTEN EXCEEDS 25%, EXCEPTION
BEING IN COUNTRIES IN SINGAPORE
AND JAPAN WITH BETTER EYE CARE.
OUR LAB USED DATA FROM THE IRIS
REGISTRY, ELECTRONIC HEALTH CARE
DATABASE ADMINISTERED BY
AMERICAN ACADEMY OF
OPHTHALMOLOGY.
IN THE IRIS REGISTRY WE
IDENTIFIED 49,000 PATIENTS WITH
NEWLY DIAGNOSED PACG, FOUND THAT
12.4%, 1 OUT OF 8 BLIND IN ONE
EYE AT THE TIME OF DIAGNOSIS,
HIGHER AMONG BLACK AND HISPANIC
AMERICANS.
WE FOUND THAT LATE DETECTION
WHICH WE DEFINE AS ONSET OF
GLAUCOMA WITHOUT PRIOR DETECTION
OF ANGLE CLOSURE CONFERRED A
HIGHER RISK OF BLINDNESS NEARLY
DOUBLING THE ODDS.
THESE DATA CONVEY URGENT NEED IN
THE FIELD OF ANGLE CLOSURE FOR A
METHOD TO DETECT PATIENTS AT
RISK FOR PACG.
THANKS TO OUR HONORREERS WE LIVE
IN GENERATION OF OCT PROVIDING
ALTERNATIVE FOR EVALUATING
ANTERIOR SEGMENTS.
THERE'S RAPID EVOLUTION OF
TECHNOLOGY TO MORE MODERN DOMAIN
AND SWEPT SOURCE SYSTEMS.
IT PRODUCES BEAUTIFUL IMAGES OF
THE ANTERIOR SEGMENT AND
ANATOMICAL STRUCTURES.
WE CAN SEE THE CORNEA, IRIS,
LENS, ANGLE RECESS.
A FEW YEARS AGO MY LAB ASKED THE
QUESTION, CAN ANALYSIS OF AS-OCT
DETECT GONIOSCOPYIC ANGLE
CLOSURE?
WE LIVE IN THE ERA OF A.I., WHEN
COMPUTERS ARE TAUGHT COGNITIVE
FUNCTION, ANALYZING IMAGES,
HOLDS POTENTIAL TO REVOLUTIONIZE
HEALTH CARE BY INCREASING ACCESS
TO CARE AND DECREASING COSTS.
IN 2019 WE PUBLISHED THIS PAPER,
DEVELOPED A.I. ALGORITHM TO
AUTOMATE DETECTION USING DATA
FROM CHINESE-AMERICAN EYE STUDY
FUNDED BY NATIONAL EYE
INSTITUTE, CONDUCTED IN LOS
ANGELES BY USC INVESTIGATORS.
OVER 4500 CHINESE AMERICANS WERE
RECRUITED, ALL RECEIVED
GONIOSCOPY AND OCT IMAGING.
IN ORDER TO DEVELOP OUR
ALGORITHM WE USED 4,000 IMAGES,
PAIRED WITH A GRADE PROVIDED BY
A TRAINED OPHTHALMOLOGIST
PERFORMING MANUAL GONIOSCOPY ON
EACH PARTICIPANT.
THESE ARE RECEIVING OPERATING
CHARACTERISTICS CURVES THAT SHOW
PERFORMANCE OF THIS ALGORITHM,
IN THE RED CURVE WE CAN SEE
ABILITY OF THE ALGORITHM TO
DETECT ANGLE CLOSURE BASED ON A
SINGLE IMAGE.
HERE THE PERFORMANCE WAS GOOD
WITH AREA UNDER THE CURVE OF 0.
93.
FOR DETECTING ANGLE CLOSURE IN
MULTIPLE QUADRANTS IT'S EVEN
BETTER.
RECENTLY WE'VE PERFORMED WORK TO
DEMONSTRATE GENERALIZABILITY IN
COMMUNITY-BASE AND
HOSPITAL-BASED CLINICS.
WE RUN INTO ANOTHER ISSUE WHICH
IS THAT GONIOSCOPY IS WEAKLY
PREDICTIVE OF WHICH PATIENTS
WILL DEVELOP PACG, THE TOPIC OF
A LANDMARK STUDY IN THE FIELD OF
ANGLE CLOSURE AND GLAUCOMA, THE
ZAP TRIAL IN "LANCET" IN 2019,
TO LOOK AT BENEFIT OF LASER
PERIPHERAL IRIDOTOMY, FOR THE
PREVENTION OF ANGLE CLOSURE.
THIS CREATES COMMUNICATION
BETWEEN THE ANTERIOR AND
POSTERIOR CHAMBERS, EQUALIZATION
ALLOWS FOR MORE FACILE AQUEOUS
FLOW, LEADS TO FLATTENING OF THE
IRIS CURVATURE, WIDENING OF
ANGLE WIDTH AND IN SEVERE
CLOSURE REDUCTION IN INTRAOCULAR
PRESSURE.
THE TRIAL RECRUITED 889
PARTICIPANTS, BETWEEN 50-70,
MAINLY CHINESE, RANDOMIZED TO
LPI IN ONE EYE, MONITORING OF
OTHER EYE, FOLLOWED FOR SIX
YEARS.
ENDPOINT WAS PROGRESSION TO
PRIMARY ANGLE CLOSURE MARKED BY
FORMATION OF PAS, ELEVATED IOP,
ACUTE ANGLE CLOSURE ATTACK.
THE ZAP TRIAL FIELDED TWO
FINDINGS, LPI WORKS, REDUCING
RISK OF PROGRESSION BY 50%.
HOWEVER, THE OTHER FINDING WAS
THAT EVEN IN UNTREATED EYES RISK
OF PROGRESSION WAS VERY LOW AT
ONLY 0.8% PER EYE YEAR.
THIS LED ZAP TRIAL TO CONCLUDE
IT'S NOT THE BEST USE OF
RESOURCES.
MORE RECENTLY WE USED DATA FROM
DATABASE, HEALTH CARE CLAIMS
DATABASE, TO ASSESS LPI
UTILIZATION IN THE REAL WORLD.
HERE IN OVER 52,000 PATIENTS
NEWLY DIAGNOSED WITH ANATOMICAL
NARROW ANGLES WE FOUND OVER A
QUARTER OF PATIENTS RECEIVED LPI
WHICH IS OVERUTILIZATION BASED
ON FINDINGS BY THE ZAP TRIAL.
WE ALSO FOUND THAT THE ODDS OF
TREATMENT WAS HIGHER AMONGST
ASIANS AND HISPANIC AMERICANS,
WHICH SUGGESTS PERHAPS DISEASE
SEVERITY MAY BE HIGHER IN
CERTAIN RACIAL POPULATIONS A
SECOND URGENT NEED, TO RISK
STRATIFY FOR ANGLE CLOSURE
PROGRESSION.
FORTUNATELY, AS-OCT IMAGED CAN
BE ASSESSED QUANTITATIVELY, ABLE
TO OBTAIN MEASUREMENTS OF
BIOMETRIC PARAMETERS THAT
DESCRIBE SIZE, SHAPE,
CONFIGURATION OF THE ANTERIOR
SEGMENT AND ITS ANATOMICAL
STRUCTURES.
OVER THE PAST FOUR YEARS OR SO
MY LAB HAS BEEN ASKING THIS
QUESTION, ARE AS-OCT
MEASUREMENTS PREDICTIVE OF ANGLE
CLOSURE OUTCOMES?
IN 2020 COLLABORATED WITH
AUTHORS OF THE ZAP TRIAL IN
ORDER TO CONDUCT STUDY,
ASSESSING RISK FACTORS FOR
PROGRESSION.
IN THIS STUDY WE TOOK DATA FROM
643 UNTREATED EYES, ALL RECEIVED
BASELINE GONIOSCOPY USING AN
OLDER DEVICE, OUTCOME MEASURE
WAS PROGRESSION FROM PACS TO
PAC.
THIS SHOWS MULTI-VARIABLE MODEL,
ASSESSING PREDICTORS OF
PROGRESSION.
OUR MEASURE OF ANGLE WIDTH WAS
AOD, ANGLE OPENING DISTANCE.
THIS MODEL IS ADJUSTED FOR IRIS
CURVATURE, AGE, ANTERIOR CHAMBER
DEPTH.
WE CAN SEE SMALLER AOD, EACH 10
MICRONS SMALLER CONFERS 10%
HIGHER ODDS TO PROGRESSION.
WHEN WE REPLACED WITH GONIOSCOPY
SCORE, THE SUM OF THE GONIOSCOPY
GRADES BETWEEN FOUR QUADRANTS,
GONIOSCOPY IS NOT PREDICTIVE OF
ANGLE CLOSURE PROGRESSION.
THIS EVIDENCE PROVIDES EVIDENCE
THAT AS-OCT PROVIDES CLINICAL
INFORMATION NOT AVAILABLE USING
CONVENTIONAL ASSESSMENT METHODS.
MORE RECENTLY WE'VE PUBLISHED
OTHER PAPERS DEMONSTRATING THE
UTILITY OF AS-OCT IN TERMS OF
PREDICTING OUTCOMES IN ANGLE
CLOSURE EYES, BOTH IN RESPONSE
TO TREATMENT, AFTER LPI, AS WELL
AS RISK OF PROGRESSION IN
LPI-TREATED PACS EYES.
LOOKING AHEAD IT'S CLEAR AT THIS
POINT THAT AS-OCT HOLDS
POTENTIAL WORLDWIDE, HAS NOT
BEEN WIDELY ADOPTED INTO ROUTINE
CLINICAL CARE.
IT'S IMPORTANT TO CONSIDER
CERTAIN BARRIERS TO CLINICAL
IMPLEMENTATION THAT MIGHT LIMIT
ULTIMATE CLINICAL BENEFIT OF
AS-OCT IMAGING.
FIRST BARRIER MOST PROVIDERS
DON'T HAVE TIME OR EXPERTISE TO
MANUALLY ANALYZE AS-OCT IMAGES.
THIS LED OUR LAB TO COLLABORATE
WITH HEIDELBERG ENGINEERING TO
PROVIDE EXPERT LEVEL DETECTION
AS WELL AS QUANTITATIVE
BIOMETRIC ANALYSIS.
HERE WE DEVELOPED ALGORITHM THAT
COULD PREDICT COORDINATES OF THE
SPUR TO TRAIN THIS ALGORITHM WE
USED JUST OVER 4,000 IMAGES, AND
IT'S IMPORTANT TO MENTION THE
SCLERAL PURCHASE IS POSTERIOR TO
MESHWORK, AND TRABECULAR
MESHWORK CANNOT BE VISUALIZED,
CANNOT PROCEED UNTIL THE SCLERAL
SPUR HAS BEEN MARKED.
WE TESTED THE ALGORITHM BETWEEN
TWO HUMAN GRADERS IDENTIFYING
2600 SCLERAL SPURS, THE ERROR OF
SECOND HUMAN WAS CALCULATED AS
REFERENCE MINUS PREDICTED
COORDINATES, MEDIAN ERROR 60
MICRONS, THIS SHOWS AGREEMENT
BETWEEN HUMAN AND MACHINE, WE
SEE SCATTER PLOT LOOKS SIMILAR,
MEDIAN ERROR IS 56 MICRONS.
THIS TABLE THE SHOWS INTEGRATOR
REPRODUCIBILITY OF MEASUREMENTS
ASSOCIATED WITH PREDICTED
LOCATIONS.
BETWEEN THE TWO WE SEE AGREEMENT
WAS EXCELLENT WITH INTRACLASS
CORRELATION EXCEEDING 0.96 FOR
ALL BIOMETRIC PARAMETERS,
MATCHED BY THE DEEP LEARNING
ALGORITHM WHICH PRODUCED
SIMILARLY HIGH ICC VALUES, WHEN
COMPARED WITH REFERENCE GRADER.
A SECOND BARRIER TO THE
IMPLEMENTATION IS THE FACT THAT
AS-OCT DEVICES ARE STILL
RELATIVELY UNCOMMON AND
EXPENSIVE.
FORTUNATELY MODERN BIOMETERS
USED TO PERFORM CALCULATIONS FOR
CATARACT SURGERY ARE BUILT ON
SWEPT SOURCE AS-OCT DEVICE WHICH
PROVIDES TROJAN HORSE FOR
GETTING TECHNOLOGY INTO CLINICS.
THESE SYSTEMS INCLUDE
HEIDELBERG, ALCON AND TOMEY,
WITH POTENTIAL TO USE THEM FOR
ANGLE CARE PATIENTS, IMPORTANT
TO EMPHASIZE THESE DEVICES ARE
ALL VERY EXPENSIVE AND LOW COST
OCT TECHNOLOGY IS NEEDED FOR
MORE RESOURCE-LIMITED SETTINGS.
A THIRD BARRIER TO
IMPLEMENTATION IS THE FACT THERE
IS A LACK OF STANDARDIZATION
BETWEEN AS-OCT SYSTEM AND
IMAGES.
HERE ARE REPRESENTATIVE IMAGES
FROM VARIOUS DEDICATED AS-OCT
SYSTEMS OR TRADITIONAL SPECIAL
DOMAIN AS-OCT SYSTEMS WITH
CUSTOM LENSES.
THE IMAGE APPEARANCE DIFFERS
BETWEEN DIFFERENT DEVICES,
PARTLY BECAUSE REFRACTION
CORRECTION ALGORITHMS APPLIED
DIFFERS FROM COMPANY TO
COMPANY.
THEREFORE IT'S IMPORTANT TO
CONSIDER INTRAOPERABILITY OF
DEVICES AND MEASUREMENTS.
IN THIS STUDY WHEN I WAS A
FELLOW WE COMPARED MEASUREMENTS,
FOR THE MEASUREMENT OF ANGLE
OPENING DISTANCE WHILE
MEASUREMENTS CAN CORRELATED THEY
ARE NOT INTERCHANGEABLE BETWEEN
THE TWO DEVICES.
HOWEVER, MORE RECENTLY WE
PERFORMED COMPARISON BETWEEN TWO
SWEPT SOURCE DEVICES, RESULTS
WERE MORE ENCOURAGING ESPECIALLY
AFTER COLLECTING FOR PUPILLARY
DIAMETER.
HERE THERE'S EXCELLENT
CORRELATION AND WE CONCLUDED IN
FACT THESE MEASUREMENTS COULD BE
USED INTERCHANGEABLY BETWEEN THE
TWO DEVICES.
THE FINAL BARRIER THAT I'LL TALK
ABOUT IS THAT LITTLE IS KNOWN
ABOUT THE RACIAL DIFFERENCES IN
PATHOGENESIS, MOST OF THE DATA
THAT I PRESENTED TODAY WAS
DERIVED FROM MOSTLY ASIAN
POPULATIONS, AND AS YOU HEARD
EARLIER ON, THE DISEASE TENDS TO
DISPROPORTIONATELY AFFECT RACIAL
MINORITIES IN THE UNITED STATES.
I'M EXCITED TO SHARE THE
OBJECTIVES OF OUR MULTI-RACIAL
ANGLE CLOSURE STUDY, A STUDY
WE'LL BE CONDUCTING IN LOS
ANGELES COUNTY USING OUR ACCESS,
UNIQUE ACCESS TO A MULTI-RACIAL
POPULATION, WITH THESE GOALS IN
MIND.
FIRST WE WANT TO ANSWER
FUNDAMENTAL QUESTIONS, WHY ARE
SOME GROUPS AT HIGH RECOLLECT OF
PACZ G, THIS PROVIDES A
POTENTIAL SOLUTION TO THE
PROBLEM.
WE WOULD LIKE TO ESTABLISH
DEFINITIONS OF NARROW ANGLES TO
ENTRENCH THIS TECHNOLOGY INTO
CLINICAL USE, AND FINALLY WANT
TO IDENTIFY NOVEL OCT-BASED RISK
FACTORS BASED ON DYNAMIC LIGHT
TO DARK IMAGING, HIGH RESOLUTION
HIGH DENSITY OCT IMAGEEL.
PACG IS A DEVASTATING DISEASE
AFFECTING MILLIONS OF PEOPLE
WORLDWIDE, ANGLE CLOSURE
DETECTION CAN BE AUTOMATED USING
AS-OCT COMBINED WITH A.I.,
PROVIDES UNIQUE CLINICAL
INFORMATION THAT GONIOSCOPY DOES
NOT.
MORE WORK IS NEEDED TO OVERCOME
IMPLEMENTATION BARRIERS, TO
HARNESS AS-OCT TECHNOLOGY FOR
ANGLE CLOSURE CARE.
I'D LIKE TO THANK YOU FOR YOUR
ATTENTION TODAY.
AND CONGRATULATIONS AGAIN TO OUR
HONOREES.
>> THANK YOU VERY MUCH.
[APPLAUSE]
PLEASE HOLD YOUR QUESTIONS TO
DISCUSSION LATER ON.
LET ME INTRODUCE THE SECOND
SPEAKER, KRISTINA IRSCH, WHILE
WORKING ON HER Ph.D. SHE WAS
SPENDING SOME TIME IN WILMER EYE
INSTITUTE IN BALTIMORE, REMAINED
AT POSTDOC, RECEIVED FELLOWSHIP.
SHE REMAINED AT JOHNS HOPKINS
UNIVERSITY SCHOOL OF MEDICINE
AND CURRENTLY ASSISTANT
PROFESSOR.
WELCOME.
>> THANK YOU.
MY INTERESTS HAVE BEEN IN USING
THE EYE AS A PORTAL TO PERFORM
IN VIVO HUMAN.
IT HAS POTENTIAL TO SERVE AS
WINDOW INTO THE BODY INCLUDING
THE BRAIN TO STUDY BASIC
SYSTEMIC PATHOPHYSIOLOGY.
MUCH OF THIS PROMISE, HOWEVER,
REMAINED UNFULFILLED BECAUSE WE
STILL HAVE NOT TAKEN INTO
ACCOUNT THE HUMAN FACTOR.
MAXIMUM RESOLUTION
STATE-OF-THE-ART RETINAL IMAGE
THAT CAN BE OBTAINED FROM A
HEALTHY YOUNG VOLUNTEER WITH A
PERFECTLY TRANSPARENT EYE HAS
VERY LITTLE TO DO WITH THE REAL
LIFE PATIENTS.
WITH EYES THAT MOVE, OR OLDER
EYES THAT ARE NOT SO TRANSPARENT
ANYMORE.
PATIENTS BY DEFINITION HAVE
PATHOLOGY AND ARE NOT IDEAL
SUBJECTS.
SO, OUR RESEARCH IS AIMED AT
SOLVING FUNDAMENTAL PROBLEMS,
SUCH AS MOTION ARTIFACTS AND
OCULAR SCATTERING TO USE THE EYE
AS IN VIVO MICROSCOPE.
CURRENT WORK IS MAINLY DIRECTED
TO TACKLING ISSUES WITH
IMPERFECT OCULAR MEDIA
TRANSPARENCY, STARTING WITH THE
CORNEA, THAT IS OUR WINDOW INTO
THE EYE AND TO THE RETINA, AND
IF THIS WINDOW BECOMES CLOUDY,
SUCH AS WITH AGE OR MANY CORNEAL
DISEASES, WE NOR THE PATIENT
WILL BE ABLE TO SEE THROUGH IT.
CORNEA TRANSPARENCY RELATES TO
STROMAL STRUCTURE, INTERACTION
BETWEEN LIGHT AND REGULAR
ARRANGEMENT OF COLLAGEN FIBRILS
RESPONSIBLE FOR THE TRANSPARENCY
OF THE CORNEA.
CHANGES IN COLLAGEN FIBER
ARRANGEMENT CAUSED BY AGING,
INFECTION, INHERIT PATHOLOGY,
TRAUMA, SURGERY, CAUSES
INCREASED LIGHT SCATTERING WHICH
THEN CAUSES A LOSS OF
TRANSPARENCY.
DESPITE ITS SIGNIFICANCE,
CURRENT MEANS TO ASSESS CORNEA
TRANSPARENCY EXTREMELY LIMITED.
NORMALLY CONSISTING OF
UNDETAILED AND GROSS OBSERVATION
OF VISIBLE OPACITIES, USING
MICROSCOPE WITH HUMAN OBSERVER.
DUE TO SUBJECTIVE AND ONLY
QUALITATIVE NATURE RESULTS
OBSERVER DEPENDENT, DIFFICULT TO
STANDARDIZE OR FOLLOW, LACK
REPRODUCIBILITY, IT'S NEBULOUS
AND DIFFICULT OF DESCRIBING
CLOUDS AND CHANGES IN THE
ATMOSPHERE, SO THERE IS A CLEAR
NEED FOR AN OBJECTIVE AND
QUANTITATIVE ABILITY TO ASSESS
CORNEAL FINDINGS LEADING US TO
OUR FIRST GOAL.
NONE OF THE AVAILABLE CLINICAL
IMAGING MODALITIES PROVIDES HIGH
RESOLUTION IN ALL THREE
DIMENSIONS.
WHAT CLINICAL OCT SYSTEMS ENABLE
CROSS-SECTIONAL VIEWS OF THE
CORNEA, AND DETECTION OF STROMAL
OPACITIES, AT AXIAL RESOLUTION
SUPERIOR OF COURSE THAN SPLIT
LENS BIOMICROSCOPY, LATERAL
RESOLUTION IS LIMITED.
CONFOCAL MICROSCOPY IS LIMITED
AXIALLY.
WITH SO-CALLED FULL-FIT OCT OR
OCM DEVELOPED IN PARIS, BOTH
HIGH RESOLUTION CROSS-SECTIONS
AND EN FACE USE CANNING ACHIEVED
COMBINING ELEMENTS OF BOTH.
IT HAD REMAINED LIMITED TO ONLY
EX VIVO APPLICATIONS, ALSO
REQUIRING CONTACT ONTO
STATIONARY TISSUE SAMPLES.
SPECIFIC AIMS HAVE BEEN TO MAKE
FULL FIT OCT IN VIVO MICROSCOPE
TAILORED TO NEEDS OF
QUANTITATIVE ASSESSMENT.
LET ME SHOW YOU PRELIMINARY
RESULTS ON QUANTITATIVE
ASSESSMENT.
WE DEVELOPED AN IMAGE
ANALYSIS-BASED APPROACH BASED ON
A PHYSICAL MODEL THAT USES
STROMAL LIGHT SCATTERING AS
OBJECTIVE INDICATOR.
ON THE LEFT YOU SEE A TYPICAL
CROSS-SECTION OF FULL FIT OCT
IMAGE EX VIVO OF NORMAL CORNEA.
NOTE IN THE STROMA THE SIGNAL
DECREASES WITH DEPTH.
IN FACT IT'S EXPECTED TO FOLLOW
EXPONENTIAL DECAY BECAUSE LIGHT
IS EXPECTED TO BE ATTENUATED BY
SCATTERING PROCESSES IN THE
STROMA.
FROM THE RATE OF EXPONENTIAL
DECAY WE CAN CALCULATE THE
SCATTERING OF PHOTON PATH OF
QUANTITATIVE MEASURE OF GRADE OF
TRANSPARENCY.
SO IT REPRESENTS THE AVERAGE
DISTANCE THAT THE LIGHT PHOTONS
CAN TRAVEL UNIMPEDED WITHOUT
BEING SCATTERED.
SO THE HIGHER THE VALUE, THE
MORE TRANSPARENT THE CORNEA.
ANY SITUATION CAN'T DEVIATION
FROM EXPONENTIAL DECAY WHICH WE
ESTIMATE BY REDUCED CHI-SQUARE
STATISTICS, LET'S HAVE A LOOK AT
EXAMPLES.
ON TOP WE HAVE A NORMAL CORNEA
WITH INTACT TRANSPARENCY, NORMAL
EXPONENTIAL DECAY CONFIRMED BY
RATIO CLOSE TO ONE.
THIS, NOTE WE'RE NOT RESOLVING
FINAL ENDOTHELIAL LAYER HERE,
SHOWS FASTER DECAYING
EXPONENTIAL PROFILE CON
CONFIRMED BY LOWER VALUE.
THIS PATHOLOGICAL CORNEA WITH
SOME STROMAL SCARRING SHOWS
NON-EXPONENTIAL PROFILE, AND
THAT'S CONFIRMED BY RATIO FAR
GREATER THAN ONE.
HERE THE FIT BY STANDARD DECLAY
MODEL WHERE WE HAVE THE DEPTH,
THE SCATTERING DEPTH DEPENDENT
CONFIRMS THERE IS SIGNIFICANT
DEVIATION FROM THE MONO
EXPONENTIAL FIT BELOW 150
MICRONS, ASSOCIATED WITH STROMAL
HETEROGENEITY IN THAT AREA.
WHILE DEVELOPMENT OF FULL FIT
OCT HAS BEEN ONGOING FOR USE IN
VIVO WHICH I'M GOING TO TALK
ABOUT IN A LITTLE BIT, THE SAME
METHOD MAY ALREADY BE APPLIED TO
CURRENT CLINICAL IMAGING
MODALITIES, INCLUDING STANDARD
SPECTRAL DOMAIN OCT, AND ENABLE
OBJECTIVE QUANTITATIVE
ASSESSMENT OF CORNEA
TRANSPARENCY IN THE CLINICAL
SETTING.
A SPECIFIC EXAMPLE OF
APPLICATION IN OPHTHALMOLOGY
PRACTICE, ASIDE FROM
STANDARDIZED DIAGNOSIS, IT CAN
BE USED FOR STANDARDIZED
TREATMENT FOLLOW-UP.
SO FOR EXAMPLE, IN THIS PILOT
STUDY INCLUDING 21 PATIENTS WITH
FUCHS DYSTROPHY WHO RECEIVED
CORNEA CRAFT WE MONITORED CORNEA
TRANSPARENCY IN INTERVAL OF AT
LEAST THREE MONTHS.
ON THE Y-AXIS HERE WE PLOT THE
DEGREE OF TRANSPARENCY IN TERMS
OF FRACTION OF TRANSMITTED
LIGHT, WHAT WE TERM COHERENT
TRANSMITTANCE, THAT ALSO
EXPRESSES THE PHOTON OF
SCATTERING MEAN-FREE PATH IN
RELATION TO ACTUAL THICKNESS OF
THE CORNEA.
SO WHAT IS SHOWN HERE IS CORNEA
TRANSPARENCY IMPROVES AND
STABILIZES AROUND SIX MONTHS
WHICH IN FACT APPEARS TO
CORRELATE WITH STABILIZATION OF
VISUAL ACUITY.
IN COLLABORATION WORK HAS BEEN
ONGOING TO MAKE FULL FIT OCT
SUIT SUITABLE FOR IN VIVO
EXAMINATION.
ON THE RESULT ANTERIOR AND
POSTERIOR LAYERS OF CORNEA, AND
NOTE BECAUSE OF THE CURVATURE OF
THE CORNEA SINGLE LAYER MAY CUT
AND CONTAIN SEVERAL CORNEA
LAYERS AT A TIME.
GOING THROUGH INDIVIDUAL LAYERS,
STARTING WITH THE EPITHELIUM,
AND ALSO SHOWING THIS ZOOMED
AREA WITH NON-CONTACT FULL FIT
OCT SYSTEM, IN COMPARISON WITH
CLINICAL CONTACT CONFOCAL
MICROSCOPY.
SUBBASAL NERVE PLEXUS SHOWING
INDIVIDUAL NERVES, HERE STROMA,
MIDDLE STROMA, YOU SEE THICKER
NERVES THAN IN THE SUBBASAL
NERVE PLEXUS.
POSTERIOR.
TO ACCOUNT FOR CURVATURE WE
RECENTLY REDESIGNED IN VIVO
SETUP BY REPLACING THE FLAT
MIRROR IN THE REFERENCE ARM WITH
CURVED REFERENCE MIRROR TO MIMIC
CORNEA CURVATURE IN WHAT WE
TERMED CURVED FIELD OCT TO
CAPTURE LARGER FIELDS OF
INDIVIDUAL LAYERS SUCH AS FINE
SUBBASAL NERVE PLEXUS, IN
COMPARISON TO FULL FIELD OCT.
TO FURTHER ENHANCE FULL FIELD
OCT TECHNOLOGY WE'RE EXPLORING
MOTION COMPENSATION TECHNIQUES,
IN COLLABORATION WITH THE GROUP
AT JOHNS HOPKINS.
I ONLY SHOWED YOU SLICES OF THE
CORNEA WITH OUR IN VIVO FULL
FIELD OCT SETUP, NO
CROSS-SECTIONAL VIEWS OF THE
ENTIRE CORNEA, AND THIS IS
BECAUSE OUR EYE IS CONSTANTLY IN
MOTION, EVEN DURING SO-CALLED
STEADY FIXATION, AND MAJOR
SOURCE OF INVOLUNTARY MOTION IS
ACTUALLY FROM VASCULAR PULSATION
RESPIRATION THAT MANIFESTS IN
AXIAL DIRECTION.
SIMPLY THE INTEGRATION OF
SPECTRAL DOMAIN OCT WITHIN FULL
FIELD OCT TO LOCATE AND TRACK
CORNEA SURFACE WHICH HELPS US TO
GUIDE FULLFIELD OCT IMAGING HAS
ALREADY ALLOWED US TO IMAGE THE
TRABECULAR MESHWORK WITH
IMPLICATIONS AS YOU HEARD FOR
GLAUCOMA RESEARCH AND DIAGNOSIS.
RECENT ADVANCES IN PHYSICS OF
TURBID MEDIA ALLOW US TO GO A
STEP FURTHER TO CONCEIVE
DEVELOPMENT OF SYSTEMS THAT
BEYOND CHARACTERIZE WILL ALSO
ENABLE COMPENSATION FOR LOSS OF
TRANSPARENCY.
LIGHT CAN BE FOCUSED BY SHAPING
LIGHT WITH THE SPATIAL LIGHT
MODULATOR, SLM, AND THIS HAS
OPENED A NEW ROUTE TOWARDS
MATRIX APPROACH OF LIGHT
PROPAGATION THROUGH COMPLEX
MEDIA RELATING THE INPUT MODES
SUCH AS GENERATED SLM TO OUTPUT
MODES DETECTED BY CCD CAMERA.
FOR EXAMPLE, BIOILLUMINATING
CLOUDY MEDIUM WITH ARRAY OF
INDIVIDUALLY MODIFIABLE
ILLILLUMINATORS, DETECTING
RESPONSES, IT'S POSSIBLE TO
CONSTRUCT A MATRIX THAT
CHARACTERIZES THE SCATTERED
MEDIUM ITSELF.
AND THEN WITH THIS INFORMATION
WE CAN THEN MANIPULATE THE ARRAY
OF ILLILLUMINATORS TO OPTIMIZE
LIGHT TRANSMISSION AND FOCUS
IMAGE THROUGH A CLOUDY MEDIUM
SUCH AS EGG SHELL IN THIS
EXAMPLE.
IN COLLABORATION WE'VE BEEN
INVESTIGATING SUCH A NOVEL ARRAY
ILLILLUMINATOR OR MATRIX
APPROACH TO OCT WITH THE AIM OF
EVENTUALLY PERFORMING RETINAL
IMAGING THROUGH CLOUDY CORNEA OR
CRYSTALLINE LENS SUCH AS EYES
WITH CATARACTS.
COULD DEMONSTRATE
PROOF-OF-CONCEPT WITH
DETERIORATED TRANSPARENCY.
FOR EXAMPLE, SHOWING RESOLUTION
TARGET UNDER CLOUDY EX VIVO
CORNEA IMAGED OUT CORRECTION,
THIS IS WITH ADAPTIVE OPTICS
LIGHT CORRECTION OF ABERRATIONS,
THIS IS WITH MATRIX APPROACH
CORRECTION OF SCATTERING
INCLUDING ABERRATIONS.
SO NOTE THAT UNLIKE MORE
CONVENTIONAL ADAPTIVE OPTICS,
THAT ALLOWS TO CORRECT FOR ONE
PART OF THE IMAGE, MATRIX
APPROACH YIELDS HIGH QUALITY
IMAGE OF THE RESOLUTION TARGET
OVER THE ENTIRE FIELD OF HAVE
YOU.
FULL FIELD OCT SHOWS PROMISE FOR
CORNEA CHARACTERIZATION AND
QUANTITATIVE ASSESSMENT,
CELLULAR RESOLUTION BEYOND
CAPABILITIES OF STANDARD OCT.
ASSESSMENT OF STROMAL LIGHT BACK
SCATTERING WITH FULL FIELD OCTS
SHOWS PROMISE AS OBJECTIVE MEANS
TO QUANTIFY TRANSPARENCY.
WE CAN DIFFERENTIATE
HETEROGENEOUS PATHOLOGIC TISSUES
FROM HOMOGENOUS ONES, ALLOWING
US TO QUANTIFY THE DEGREE OF
TRANSPARENCY IN HOMOGENOUS
TISSUES.
MOTION COMPENSATION AND ARRAY
ILLUMINATION, MATRIX APPROACHES,
MAY FURTHER ENHANCE OCT
TECHNOLOGY AND ENABLE DEEPER
PARENTHESES TRYINGS --
PENETRATION.
I'D LIKE TO THANK MY PRIMARY
MENTORS, WHO IS SITTING RIGHT IN
THE FRONT IN THE AUDIENCE, I'VE
WORKED WITH THEM SENSE GITTING
MY Ph.D. END JOSEF BILLE WHO
INTRODUCED ADAPTIVE OPTICS TO
OPHTHALMOLOGY AND A FRIEND OF
HIDE ELBERG ENGINEERING, WHO
PASSED AWAY A FEW MONTHS AGO.
THIS ENTIRE GROUP SHOWN HERE,
LISTED, HAS BEEN WORKING
TOGETHER TO CONTINUE TO ADVANCE
TOWARDS THE GOAL OF IMPROVING
OCULAR IMAGING WITH POTENTIAL
RAMIFICATION FOR IMPROVING
OVERALL HEALTH.
THANK YOU.
[APPLAUSE]
>> NEXT TALK, CRISTINA
CANAVESI, SHE'S FOUNDER AND
PRESIDENT OF LIGHTOP
CORPORATION.
>> GOOD MORNING.
MANY THANKS TO THE ORGANIZERS
FOR INCLUDING ME IN THIS
WONDERFUL AND MUCH DESERVED
CELEBRATION OF THE INVENTORS OF
OCT.
BEFORE I START, I WANTED TO
PROVIDE A SHORT BACKGROUND OF MY
COMPANY, STARTED IN 2013, A
WOMEN-OWNED BUSINESS.
WE'RE GRADUATE OF THE I-CORPS
PROGRAM AND ILLUMINATE.
FUNDED BY NATIONAL SCIENCE
FOUNDATION AND NATIONAL
INSTITUTES OF HEALTH VIA SBIR
PROGRAMS AND PROGRAMS IN NEW
YORK STATE AND ROCHESTER WHERE
WE'RE BASED.
OCX IS A NEW TYPE OF INSTRUMENT
THAT OPERATES AT DIFFERENT
SCALES STARRING FROM OCT ON THE
CORNEA IN THIS EXAMPLE WITH WIDE
FIELD OF VIEW AND THEN MOVING
SEAMLESSLY TO MICROSCOPIC SCALE
TO CELLULAR LEVEL WHERE WE CAN
SEE THE INDIVIDUAL ENDOTHELIAL
CELLS LINING THE POSTERIOR
SURFACE OF THE CORNEA.
THIS IS ONE OF SEVERAL EXAMPLES
BRINGING BETTER IMAGES FOR
BETTER RESEARCH.
WHAT IS OCX AND WHY IS IT
DIFFERENT?
IT IS A NOVEL CLASS OF IMAGING
THAT COMBINES FOR THE FIRST TIME
IN A SINGLE INSTRUMENT OPTICAL
CORNEA GDOCM, CALLING THIS OCX.
I'M SHOWING HOW THE SYSTEM IS
ABLE TO SURVEY THE REGION OF
INTEREST WITH OCT FIRST, OVER
LARGE FIELD OF VIEW AND THEN
ZERO IN WITH HIGH MAGNIFICATION
TO CAPTURE TARGETED IMAGE WITH
OUR PATENTED GDOCM TECHNOLOGY,
PROVIDING AN IMAGE WITH 16 TIMES
HIGHER LATERAL RESOLUTION THAN
TRADITIONAL OCT LEADING TO
BETTER IMAGES AND BETTER DATA.
GDOCM THEY ARE INTEGRATED WITH
EASY TO USE INTERFACE THAT LETS
RESEARCHERS FOCUS ON THE SCIENCE
RATHER THAN ON THE INSTRUMENT
ITSELF.
THESE CAPABILITIES RESULT IN
NON-INVASIVE IMAGES OF TISSUE
WITH CELLULAR RESOLUTION
COMPARABLE TO HISTOLOGY.
SINCE THE HIGH RESOLUTION
DATASETS THAT RESULT IT'S
DESIRABLE TO COMBINE THEM WITH
MACHINE LEARNING APPROACHES FOR
AUTOMATED ASSESSMENT OF CELLULAR
FEATURES.
FUNCTIONAL ASSESSMENT CAN BE
ACHIEVED BY COMBINING OCX WITH
OTHER MODALITIES, ONE EXAMPLE IS
ANGIOGRAPHY, A TOPIC OF A LATER
SESSION, AND IN OUR CASE WE
ASSESS VASCULATURE WITH NOVEL
EFFECTOR ANNUAL APPROACH FOR
OCT-A.
SO, YOU HAVE SEEN A VERSION OF
THIS CHART BEFORE, COMPARING OCT
WITH OTHER NON-INVASIVE
MODALITIES.
THIS ONE IS DIFFERENT BECAUSE ON
THE VERTICAL AXIS WE HAVE
LATERAL RESOLUTION, WHICH IS THE
PARAMETER THAT IS KEY IF YOU'RE
INTERESTED IN CELLULAR LEVEL.
WE HAVE PENETRATION INTO TISSUE,
NATURAL TRADEOFF BETWEEN
PARAMETERS, DIFFERENT METHODS
FALL ALONG THE DIAGONAL.
SO THE GOAL FOR VISUALIZING
PROCESSES AT THE CELLULAR LEVEL
TO OBTAIN RESOLUTION AND
MICROMETER SCALE OVER
PENETRATION DEPTH OF THE
MILLIMETER SCALE.
SO IN THE UPPER PART OF THE
CHART THERE ARE METHODS THAT
HAVE INADEQUATE RESOLUTION TO
IMAGE INDIVIDUAL CELLS.
ULTRASOUND AS AN EXAMPLE HAS
EXCELLENT PENETRATION INSIDE THE
BODY BUT RESOLUTION IS GENERALLY
LIMITED.
AND THIS IS CROSS-SECTIONAL
PRESENTATION OF ULTRASOUND.
OCT WHICH WE ALL KNOW AND LOVE
HAS THE EXQUISITE CAPABILITY TO
RESOLVE LAYERS IN THE
CROSS-SECTIONAL VIEW DOWN TO THE
MICROMETER SCALE.
BUT IT DOESN'T HAVE ENOUGH
RESOLUTION IN THE ORTHOGONAL OR
LATERAL DIMENSION.
OPPOSITE SIDE WE HAVE MICROSCOPY
TECHNIQUES WHICH ARE CAPABLE OF
RESOLVING DOWN TO THE CELLULAR
AND SUBCELLULAR LEVEL BUT SUFFER
FROM LIMITED PENETRATION INSIDE
OF THE TISSUE.
SO WE HAVE CONFOCAL MICROSCOPY.
HERE IS SHOWING ENDOTHELIUM, AND
THIS VIEW IS PARALLEL TO THE
SURFACE OF THE TISSUE.
AND THIS IS A TYPICAL VIEW OF
MICROSCOPY, AS WAS DISCUSSED IN
PREVIOUS TALK THIS IS A
BEAUTIFUL PRESENTATION BUT
SUFFERS FROM PENETRATION AND
ALSO GREATLY SUFFERS IN FIELD OF
VIEW WHICH IS TYPICALLY LESS
THAN HALF A MILLIMETER.
SO, THIS WAS INTRODUCED, OPTICAL
CURRENT MICROSCOPY OCM BY
INCREASING NUMERICAL APERTURE,
ACHIEVES EXCELLENT LATERAL
RESOLUTION AGAIN WITH
LIMITATIONS AT THE DEPTH OF
FOCUS BECOME SHALLOW DOWN TO
TENS OF MICRONS.
SO, GDOCM WAS INTRODUCED TO
BRIDGE THE GAP BETWEEN THESE TWO
SETS OF TECHNIQUES.
ACHIEVED MICROMETER SCALE
RESOLUTION OVER CLINICALLY
RELEVANT DEPTH.
BY INTEGRATING LIQUID LENS TO
DYNAMICALLY REFOCUS HIGH
NUMERICAL APERTURE BEAM OF LIGHT
IN THE TISSUE, GDOCM MAINTAINS
HIGH LATERAL RESOLUTION
THROUGHOUT THE DEPTH OF IMAGING.
ON THE RIGHT IS AN EXAMPLE OF A
HUMAN CORNEA IMAGE WITH GDOCM.
AND SINCE GDOCM IMAGING ACQUIRES
3D IMAGES, TWO MICRON
RESOLUTION, WE HAVE VISUALIZE
THE CROSS-SECTIONAL B SCANS AT
THE TOP AS WELL AS VIEWS TYPICAL
OF MICROSCOPY SHOWN AT THE
BOTTOM.
AND THIS VIEW HIGHLIGHTS THE
CELLULAR RESOLUTION CAPABILITY
IN THE LATERAL PLANE.
SO, BY COMBINING OCT AND GDOCM
IN A SINGLE INSTRUMENT, OCX
ALLOWS WIDE FIELD OF VIEW TO
CELLULAR LEVEL.
OUR VISION WITH DUAL MODALITY
OCX IMAGING IS TO SUPPORT ENTIRE
OCULOMICS PIPELINE FROM DRUG
DISCOVERY AND DISEASE
INVESTIGATIONS IN VITRO AND EX
VIVO, AND TO TESTING FOR
MANUFACTURING OF CONTACT LENSES
AND INTRAOCULAR DEVICES INTO
PRE-CLINICAL AND CLINICAL
STUDIES.
WE BRING DUAL MODALITY IMAGING
CAPABILITY, AND 3D WITH CELLULAR
RESOLUTION, ASSOCIATED ANALYSIS
BASED ON A.I. AND MACHINE
LEARNING.
I WILL HIGHLIGHT A FEW
APPLICATIONS INCLUDING CORNEA
AND RETINAL IMAGING AND
REGENERATIVE MEDICINE.
SO HERE ARE SOME HIGHLIGHTS ON
OUR WORK ON CORNEAL IMAGING TO
GET BETTER RESULTS FASTER, WE
CAN PERFORM TRADITIONAL
MEASUREMENTS AND TASKS, OCT IS
CURRENTLY EMPLOYED SUCH AS
MEASURING THICKNESSES OF THE
DIFFERENT LAYERS OF THE CORNEA.
AND WE CAN DO THIS, FOR EXAMPLE,
AT EYE BANKS.
HERE IS A PICTURE SHOWING
IMAGING OF DONOR TISSUE, DONOR
CORNEAL TISSUE, STORED IN
VIEWING CHAMBER WITHOUT
CONTACTING TISSUE OR EXPOSING IT
TO THE OUTSIDE ENVIRONMENT.
AND WE CAN ALSO PERFORM DETAILED
CELLULAR EXAMINATION BY
AUTOMATICALLY SEGMENTS
ENDOTHELIUM AND NUMERICALLY
FLATTENING SO WE CAN PRESENT
ENDOTHELIAL CELLS IN A SINGLE
PLANE.
AND USING MACHINE LEARNING TO
AUTOMATICALLY COUNT THE CELLS
AND PROVIDE UNBIASED ESTIMATION
OF ENDOTHELIAL CELL DENSITY.
SO HERE'S AN EXAMPLE, I
APOLOGIZE FOR THE FORMATTING.
SO, THIS IS AN EXAMPLE OF OCX
IMAGING IN MICE.
WE HAVE ON THE LEFT OCT OR WIDE
FIELD OF VIEW AND GDOCM ON THE
RIGHT.
WE'RE ABLE IN VIVO TO VISUALIZE
EPITHELIAL CELLS, ENDOTHELIAL,
CORNEAL NERVES.
WHEN IMAGING EXCISED HUMAN
RETINA WE CAN START WITH THE OCT
IMAGING OF THE LARGER FIELD OF
VIEW AND DETAILED EXAMINATION OF
RETINA WITH GDOCM AND HIGH
RESOLUTION.
SO MOVING TO REGENERATIVE
MEDICINE, THIS MULTI-SCALE
APPROACH OF OCX IS SUITED TO
IMAGE ORGANOIDS, HERE'S AN
EXAMPLE OF THE SAME RETINAL
ORGANOIDS IMAGED ON THE LEFT
WITH LEICA BIOOPTIGEN SYSTEM,
YOU CAN APPRECIATE THE ADVANTAGE
BY HIGH LATERAL RESOLUTION.
LEVEL OF DETAIL IN OCX IMAGE
SHOWS DIFFERENTIATION IN LAYER
OF THE ORGANOIDS, INCLUDING
OUTER LAYER, AND THIS
COMBINATION OF OCT AND GDOCM IS
SUITED TO HIGH-THROUGHPUT
SCREENING OF ORGANIZE AND OTHER
3D CELL TISSUE CULTURES WITHOUT
NEED FOR SPECIALIZED
PREPARATION.
OCX IS NON-INVASIVE,
NON-CONTACT, ENABLES
LONGITUDINAL STUDIES ON THE SAME
SAMPLE OVER TIME.
SO, BEFORE I CONCLUDE, I WAS
ASKED TO INCLUDE A FEW WORDS
ABOUT STANDARDIZATION OF DATA
ACROSS PLATFORMS.
I WANTED TO HIGHLIGHT THE WORK
WE'VE DONE TO DEVELOP AND
COMMERCIALIZE TOOLS TO EXTRACT
RELEVANT BIOMARKERS FROM OCT
DATA.
IN THIS CONTEXT, WE HAVE
DEVELOPED SOOLS THAT WORK FOR
DATA SETS ON MULTIPLE
INSTRUMENTS, THE GOAL TO ADVANCE
THE PACE OF DISCOVERIES WITHOUT
DUPLICATING WORK SO A BIG PART
OF OUR EFFORT GOES INTO
DEVELOPING TOOLS EASY TO USE AND
PROVIDE NEW CAPABILITIES, SUCH
AS OCT ANGIOGRAPHY.
HERE IS THE EXAMPLE OF THE WORK
FLOW INTEGRATING SOFTWARE TOOLS
WITH THIRD PARTY INSTRUMENTS, IN
THIS CASE IMAGE ACQUISITION IS
PERFORMED WITH LEICA OCT SYSTEM,
TO EXTRACT THE DYNAMIC COMPONENT
OF THE FLOWING BLOOD CELLS FOR
REPEATED ACQUISITION, THESE
SCANS REPEATED AT EACH LOCATION.
OVER TIME.
FIRST SOFTWARE TOOL IS FRAME
ALIGN, PROPRIETARY ALGORITHM FOR
VOLUME REGISTRATION THAT
MINIMIZES DISTORTIONS, THIS IS
NEEDED TO CORRECT FOR MOTION
ARTIFACTS FROM IN VIVO IMAGING.
OCTA SIGNATURES ARE EXTRACTED
USING NOVEL FACTOR ANALYSIS
APPROACH.
OCTA TOOL OUTPUTS TWO FILES, ONE
CONTAINS STRUCTURAL SIGNAL, THE
OTHER DYNAMIC VASCULAR
SIGNATURES, BOTH, FRAME ALIGN
AND OCTA TOOL WERE DESIGNED SO
THEY ARE EASY TO USE, DEVELOPED
SO RESEARCHERS CAN FOCUS ON THE
IMAGING AND BIOLOGY WITHOUT
HAVING TO TWEAK PARAMETERS
ENDLESSLY TO GET A DECENT
RESULT.
THE 3D IMAGES ARE DISPLAYED IN
THE VIEWER WHICH YOU'VE BEEN
SEEING IN ACTION THROUGHOUT THE
PRESENTATION.
SO HERE IS AN EXAMPLE OF THE
OCTA RESULT FOR MICE RETINA.
THESE ARE ALL PROJECTION OF
RETINAL NERVE FIBER LAYER, ALL
THREE OF THESE IMAGES ORIGINATE
FROM THE SAME DATASET, PROCESSED
IN DIFFERENT WAYS.
THE FIRST TWO IMAGES AT THE LEFT
AND CENTER ARE THE STRUCTURAL
OCT DATA, WHILE THE RIGHT MOST
IMAGE IS FUNCTIONAL OCTA DATA.
YOU CAN APPRECIATE INTERNAL
STRICTURES AND FIBERS ARE NO
LONGER PRESENT, THIS IS THE
WALLS OF THE VASCULATURE.
TO CONCLUDE I WANT TO SHARE OUR
EXCITEMENT TO BE WORKING AT
BASKIN PALMER EYE INSTITUTE TO
INVESTIGATE OCX CAPABILITIES ON
FOUR PATIENT GROUPS IN AN
IRB-APPROVED STUDY FOR CORNEAL
INFECTION, DRY EYE, OCULAR
SURFACE, NEOPLASIA, FUCHS
DYSTROPHY.
HERE IS A PICTURE OF THE
INSTRUMENT SETUP.
WATCH FOR UPDATES IN THE COMING
MONTHS.
MANY TALENTED INDIVIDUALS HAVE
CONTRIBUTED TO THE DEVELOPMENT
OF THIS TECHNOLOGY, SHOWN HERE.
A LOT OF THEM, IN NO PARTICULAR
ORDER, FROM SCIENTIFIC
COLLABORATORS, MANUFACTURING,
PRE-CLINICAL, CLINICAL
DEVELOPMENTS AND EVERYTHING IN
BETWEEN.
AND WITH THAT IF YOU'D LIKE TO
DISCUSS HOW OCX CAN BENEFIT YOUR
RESEARCH PLEASE COME FIND ME IN
PERSON TODAY, TOMORROW, OR REACH
OUT TO ME VIA E-MAIL, I'D BE
HAPPY TO TALK MORE.
THANKS.
[APPLAUSE]
>> THE FLOOR IS OPEN FOR
QUESTIONS FOR ALL THE SPEAKERS.
>> WONDERFUL PANEL.
GREAT DISCUSSION.
GREAT TALKS.
SO, QUESTIONS, YOU SHOWED HIGH
RESOLUTION WAYS OF LOOKING AT
CORNEA.
CRISTY SHOWED IN
POST-TRANSPLANTER PATIENTS
LOOKING AT CLARITY BUT
TECHNIQUES MIGHT BE USEFUL FOR
LOOKING AT -- AS A BIOMARKER FOR
ENDOTHELIAL CELL FUNCTION, EVEN
EARLY STAGES OF CORNEAL
DECOMPENSATION.
HAVE YOU THOUGHT ABOUT USING IT
IN THOSE SETTINGS?
>> DO YOU WANT ME TO ANSWER?
YOUR CLINICAL STUDY IS STILL
UNDERWAY.
YEAH, NO, GOOD QUESTION.
SO THE RESULTS ARE SHOWN ON THE
CORNEA TRANSPARENCY,
STANDARDIZED TREATMENT FOLLOW-UP
WHICH USES STANDARD OCT, OPTOVUE
DEVICE.
I FEAR MOTION COMPENSATION
STRATEGIES TO COMPENSATE FOR THE
ACTION MOTION REALLY IS NEEDED
BECAUSE IT'S NOT SO EASY TO USE
ON PATIENTS.
MOST OF THE IMAGES I SHOWED WAS
MY EYE.
I'M VERY TRAINED FROM DAVID
GITEN'S LAB TO FIXATE ON A
TARGET.
I'M VERY STILL.
THESE ARE ALL GOOD COMMENTS, AND
TO LOOK AT.
IT'S STILL A TIME DOMAIN
TECHNIQUE, FULLFIELD OCT
SYSTEMS.
TO GET THE VOLUME WHICH WE
HAVEN'T SUCCEEDED GETTING IN
VIVO IMAGES, YOU DO TIME DOMAIN
SCANNING.
>> IN OUR CASE, WE GET ENTIRE
DEPTH PROFILE, DEFINITELY WILL
BE INTERESTING TO INVESTIGATE
THAT.
THANKS.
>> MY QUESTION IS TO KRISTINA
WITH A K.
AS YOU'RE PLOTTING INTENSITY OF
LIGHT FROM CORNEA, WHAT YOU
PLOTTED IS PROBABLY A
(INDISCERNIBLE), JUST FROM THE
NATURE OF THE PLOTTING, SO YOU
COULD PROBABLY SUBTRACT LOWER
LEVEL TO GET THE MAJOR
COMPONENT, WHICH MIGHT ACCOUNT
FOR MAYBE 10 TO 15% OF THE
INTENSITY SO THAT MIGHT GIVE YOU
A NUMBER PROBABLY YOU'RE LOOKING
FOR.
>> THE ECHO IS SO BAD, I ONLY
GOT BITS AND PIECES.
YOU'RE SAYING OUR ANALYSIS, HOW
IT'S AFFECTED BY THE SURFACE OR
SOMETHING?
>> YES, YES.
SPECTROSCOPY, WE USED TO DO
STRIPPING, IT APPEARS
BIEXPONENTIAL, YOU MIGHT HAVE A
MINOR COMPONENT AT LOWER LEVEL,
BY SUBTRACTING ONE YOU GET THE
MAJOR COMPONENT WITH PROBABLY
HIGHER LEVEL OF ACCURACY.
>> I APOLOGIZE, IT'S A LOT OF
ECHO FOR US HERE, NOT AT THE
PODIUM.
MAYBE WE CAN DISCUSS MORE IN THE
BREAK.
I WANT TO POINT OUT ONE THING, I
DIDN'T GET ALL THE POINTS,
SORRY.
FOR THAT ANALYSIS, I'M SO HAPPY
ABOUT THE STANDARD, THE MEASURES
FOR PUTTING STANDARDIZATION IN
IMAGING.
WE WORK WITH A BLACK BOX
CLINICAL SYSTEM, WE DID ANALYSIS
IN J PEG IMAGES BECAUSE WE
DIDN'T HAVE ACCESS TO RAW DATA.
WE DO STANDARDIZATION OF IMAGES,
SO WITH THE EPITHELIAL SURFACE,
AND I DIDN'T HAVE TIME TO GET
INTO THIS.
THERE'S A LOT OF ARTIFACT,
REFLECTION, THAT WE COMPENSATE
FOR AND POSTERIOR STROMAL
ARTIFACT, PCA ANALYSIS TO
STANDARDIZE ALL THE IMAGES SO
WE'RE STARTING FROM THE SAME
BASELINE.
>> CONGRATULATIONS.
>> WE CAN DISCUSS MORE LATER.
VERY INTERESTING.
THANK YOU.
>> EXCELLENT WORK.
THANK YOU.
>> DAVID?
>> THANK YOU.
I HAVE A COMMENT FOR BEN.
I'M VERY HAPPY TO HEAR THAT
ANTERIOR SEGMENT OCT IMAGES OF
THE ANGLE, ANGLE PARAMETER, AOD,
ET CETERA, CONTAIN INFORMATION
THAT'S AVAILABLE IN GONIOSCOPY,
LONGITUDINAL TRIAL, WE WERE
INVOLVED IN DEVELOPMENT OF THOSE
METRICS, WITH OCT, AND IT WAS
QUESTIONABLE BACK THEN WHETHER
THEY WERE OF ADDITIONAL VALUE.
OFTEN IT'S HARD TO PUBLISH THESE
OCT METRICS OR MEASUREMENTS
BECAUSE A LOT OF REVIEWERS HAVE
QUESTIONS, YOU'RE NOT SHOWING
ANYTHING DIFFERENT.
THERE ARE NO ADDITIONAL VALUE.
IT OFTEN TAKES DECADES FOR IT TO
SHOW UP WITH LONGITUDINAL DATA,
SO ANYWAY, WHEN YOU REVIEW A
PAPER, WITH SOME NEW METRIC,
JUST KEEP THAT IN MIND.
DON'T REQUIRE THAT THE AUTHOR
HAVE TO SHOW THEY ACTUALLY HAVE
CLINICAL SIGNIFICANCE IN THE
FIRST PUBLICATION.
THAT'S ONE OF MY PET PEEVES.
AND I HAVE QUESTION FOR CHRISTY
AND CHRISTINA, I'M INTERESTED IN
OPTICAL COHERENCE MICROSCOPY OF
THE CORNEA.
I NOTICE IN OUR OWN WORK, ALSO
IN PUBLICATIONS THAT THE
CONTRAST FOR ESPECIALLY FOR
NERVE AND COLLAGEN FIBERS ARE
DIFFERENT AT DIFFERENT
WAVELENGTHS.
I DON'T THINK THERE HAS BEEN
SYSTEMATIC COMPARISON.
BUT I LIKE TO KNOW IN YOUR WORK
HAVE YOU NOTICED DIFFERENT
APPEARANCES AT DIFFERENT
WAVELENGTHS?
>> WE OPERATE AROUND 850
NANOMETERS, WE HAVEN'T LOOKED AT
OTHER WAVELENGTHS.
>> IT'S A GOOD POINT.
WE'VE ALSO LOOKED WITH 850, SO,
YEAH, NOT MUCH EXPERIENCE THERE.
GOOD POINT TO EXPLORE.
>> THANK YOU.
>> I JUST WANTED TO COMMENT ON
DAVID'S POINT.
FIRST, THANK YOU FOR SHARING THE
STORY OF WHERE THESE BIOMETRIC
PARAMETERS CAME FROM.
IT WAS VERY CRUCIAL TO HAVE
HANDCRAFTED FEATURES EARLY ON SO
WE COULD UNDERSTAND EXACTLY HOW
THE DISEASE PROCESS WORKED.
NOWADAYS, THE MOST LIKELY
APPROACH IS JUST TO USE A.I. BY
STICKING IMAGES IN DIRECTLY,
OBVIOUSLY THERE'S LACKS OF
EXPLAINABILITY AND
INTERPRETABILITY, TO TAKE THE
TIME TO CRAFT FEATURES HELPED
ESTABLISH THE FIELD AND THE WORK
I DO.
>> THANK YOU.
>> A FEW QUICK QUESTIONS AND FEW
QUICK ANSWER IN THE INTEREST OF
TIME.
>> THANKS FOR THE EXCELLENT
TALKS, I HAVE A QUESTION FOR
BEN.
LOOKING AT THOSE ANTERIOR IMAGES
FROM DIFFERENT DEVICES, IT WAS
JUST A LITTLE BIT, YOU KNOW, ODD
TO SEE SO MUCH VARIATION IN THE
WAY THAT THE FEATURES ARE
PRESENTED.
SO, I WAS WONDERING WHEN WE GO
TOWARDS MORE OBJECTIVE MEASURES,
ANTERIOR SEGMENT QUANTITATIVE
PARAMETERS, SO WHAT ARE YOUR
SUGGESTIONS LIKE TRYING TO
COMPARE DIFFERENT CLINICAL
NUMBERS THAT YOU'RE GETTING FROM
DIFFERENT SYSTEMS TO GET
OBJECTIVE SENSE OF PARAMETERS OF
INTEREST.
WE HAVE DIFFERENT DEVICES
DIVERSITYING DIFFERENT IMAGES,
MAYBE THE PARAMETERS ARE NOT
CONSISTENT BETWEEN DEVICES.
>> THAT'S A VERY IMPORTANT
POINT.
WE'RE INVESTING TIME, RESOURCE,
HARD WORK TO ESTABLISH CUTOFFS
TO REDEFINE NARROW ANGLES BUT
LOCKED INTO A SINGLE SYSTEM,
THAT WE USE TO COLLECT THE DATA.
AND SO WITHOUT THE ABILITY TO
TRANSLATE THESE FINDINGS BETWEEN
DIFFERENT DEVICES HAVE TRUE
INTEROPERABILITY IT LIMITS TO A
SINGLE SYSTEM, THIS IS AN
IMPORTANT CONVERSATION WE NEED
TO CONTINUE TO HAVE, DEVELOP
TECHNIQUES FOR INTEROPERABILITY
AND ABILITY TO TRANSLATE
FINDINGS BETWEEN DIFFERENT
DEVICES.
THANK YOU VERY MUCH.
>> ONE MORE QUESTION.
>> IN THE INTEREST OF TIME I'M
GOING TO SAVE MY COMMENT FOR
LATER AND JUST THANK THE
PANELIST S FOR THREE AWESOME
TALKS.
[APPLAUSE]
>> WE'RE MOVING TO A BREAK.
WE HAVE HOUSEKEEPING.
>> YEAH, THAT CONCLUDES THE
SESSION.
LET'S TAKE A 15-MINUTE BREAK
NOW.
RETURN AT -- LET'S SAY 11:05 TO
KEEP IT EASY.
TRY TO BE HERE ON TIME SO WE CAN
GET AN ON-TIME START.
>> WE THOUGHT IT WOULD BE
IMPORTANT TO IMPROVE THE VISUAL
EXPERIENCE OF EVERYBODY, SO
WE'RE HAVING THE SPEAKERS SIT IN
THE FRONT ROW SO THEY CAN SEE
THE SCREEN.
AND WE'RE HOPING THAT THE BOTTOM
20% OF THE SCREEN WILL NOW BE
VISIBLE TO EVERYBODY ELSE IN THE
AUDIENCE.
SO, WITH THAT, I WILL INTRODUCE
THE NEXT SESSION, WHICH IS HIGH
RESOLUTION AND AO-OCT, MODERATED
BY AUSTIN RORDA FROM UNIVERSITY
OF -- WELL, BERKELEY, UNIVERSITY
OF CALIFORNIA AT BERKELEY.
I THINK, DR. RORDA, YOU'RE GOING
TO SPEAK FROM DOWN THERE, OR
MOVE OVER AND TURN AROUND?
>> YES.
>> GREAT.
>> WELCOME TO THE NEXT SESSION,
HIGH RESOLUTION AND AO OCT.
I'LL KEEP THE INTRO SHORT IN THE
INTEREST OF TIME.
THE FIRST SPEAKER IN THE SESSION
IS DON MILLER, PROFESSOR AT THE
SCHOOL OF OPTOMETRY, INDIANA
UNIVERSITY, THE TITLE IS RECENT
ADVANCES IN ADAPTIVE OPTICS OCT
TECHNOLOGY AND USE.
>> I WANT TO THANK THE
ORGANIZERS FOR THE INVITE, TO
COMMENT IN A COUPLE AREAS,
RECENT ADVANCES IN MY LAB,
INDIANA UNIVERSITY.
I HOPE YOU'LL LEARN OUR
MOTIVATION FOR IMAGING RETINA
WITH THIS COMBINATION OF AO AND
OCT, DEVELOPING HIGH SPEED AO
SYSTEM AND BENEFIT THAT MAY
ACCRUE, AND A SPECIFIC
APPLICATION OF USING THIS TECH
NOTHING TO LOOK AT PHOTORECEPTOR
CELLS.
TECHNOLOGY TO LOOK AT
PHOTORECEPTOR CELLS.
THIS USES A SENSOR TO MEASURE
ABERRATIONS OF THE EYE AND
INFORMATION IS FED VIA COMPUTER
TO TAKE THOSE ABERRATIONS OUT.
DOING THAT GETS US DOWN TO ABOUT
A 2-MICRON LATERAL RESOLUTION IN
RETINA.
TAKE AN AO, PUT IT INTO THE
SAMPLE ARM, YOU END UP WITH 3D
RESOLUTION DOWN TO THE IMPORTANT
SPATIAL SCALE, RESPONDING TO
DIMENSIONS OF SINGLE CELLS.
HERE'S AN EXAMPLE THAT
ILLUSTRATES THE CELLULAR DETAILS
WE CAN SEE IN THE RETINA WITH
THIS COMBINATION, IN ADDITION TO
POST-PROCESSING, A COMPOSITE
IMAGE WHERE WE COLLECT IMAGES,
IN THIS CASE THE SAME PATCH, A
LITTLE OFF FROM THE FOVEA.
THIS IS A FLY-THROUGH OF THE
VOLUME.
NERVE FIBER LAYERS ON TOP.
YELLOW LINE CORRESPONDS TO
CROSS-SECTION OVER HERE ON THE
RIGHT.
SO WE'RE JUST GETTING INTO THE
GANGLION CELL LAYER, YOU CAN SEE
THE STACKS ON TOP OF THE OTHER,
THE SOMA, FIRST PLEXUS,
INTERPLEXIFORMILAYER, INNER
NUCLEAR LAYER, BRIGHT SOMAS HERE
WE BELIEVE ARE THE DISPLACED
RETINAL GANGLIA CELLS BUT THAT
REMAINS IN DEBATE ABOUT THAT.
INTO THE OUTER PLEXIFORM LAYER,
ANOTHER PLEXUS, INTO THE DARK
OUTER NUCLEAR LAYER, YOU SEE
STRIATIONS WHICH MAY BE
INDIVIDUAL AXONS, AND THE OUTER
LAYERS, CONE CELL, FINALLY RPE
MOSAIC.
EACH BLEMISH IS INDIVIDUAL RPE
CELL.
THAT'S THE TYPE OF IMAGE WE CAN
GET.
AND WITH A BIT OF WORK, SO THIS
TYPE OF VOLUME CONTAINS
THOUSANDS OF CELLS, DIFFERENT
TYPES, THAT WE CAN NOW STUDY
USING THIS TECHNOLOGY.
IT DIDN'T HAPPEN OVERNIGHT.
IF YOU LOOK AT THE HISTORY OF
IT, IT GOES WAY BACK 25 YEARS,
AND I THINK KIND OF A NICE
REFLECTION OF THE DEVELOPMENTS
OVER TIME HAS BEEN INCREASE IN
SPEED OF THESE SYSTEMS,
ILLUSTRATED IN TERMS HERE.
THERE'S IMPROVEMENT OF 500 TIMES
IN SPEED, BIG JUMP FROM TIME
DOMAIN WITH UP TO SPECTER
DOMAIN, TIME DOMAIN WAS HARD TO
DO WITH AO.
THE LAST DECADE ANOTHER 40 TIMES
INCREASE, THAT GOT US UP INTO
THE MEGAHERTZ RANGE, POINT
SCANNING, LINE SCANNING, FULL
FIELD, BROKEN INTO SPECTER
DOMAIN, SWEPT SOURCE.
MANY IF NOT MOST USE MEGAHERTZ
SPEEDS.
AS GREAT AS TECHNOLOGIES ARE
OVER HERE, I DON'T THINK ANY OF
THESE MEGAHERTZ SYSTEMS ARE
COMMERCIALLY VIABLE, BASED ON
OPTICAL TECHNOLOGIES OVERLY
BULKY, COMPLEX, EXPENSIVE, AND
NON-SCALABLE.
WORK INTO DEVELOPING HIGH SPEED
AO SYSTEM, BY A POSTDOC IN MY
LAB.
WE NEEDS TO GO TO HIGH ENOUGH
LOOP RATE TO KEEP RESIDUAL
ABERRATIONS LOW, MOST CORRECT UP
TO A COUPLE HERTZ.
THIS IS BASED ON MEASUREMENTS
ACQUIRED IN HEALTHY SUBJECTS,
IDEAL CONDITIONS.
THERE MAY BE ADDITIONAL MORE
ELEVATED ABERRATIONS.
OUR GOAL WAS TO SEE HOW FAST WE
COULD GO, WE GOT UP TO 33 HERTZ,
40 HERTZ CUTOFF FREQUENCY, ABOUT
20 TO 40 TIMES HIGHER THAN THE
CUTOFF OF CURRENT SYSTEMS.
OBVIOUSLY THE QUESTION IS, IS
THERE ANY BENEFIT IN GOING
FASTER.
SO, WE LOOKED AT A NUMBER OF
CLINICAL CONDITIONS WHERE WE
THOUGHT INCREASED TEMPORAL
ABERRATIONS MAY OCCUR.
AND THERE'S A LIST OF SOME OF
THESE OUGHT OFFICIAL TEARS,
PEOPLE USE THOSE A LOT, THEY
CREATE IRREGULAR TEAR FIRM,
EXCESSIVE BLINKING, AN ISSUE
WITH AO.
WE LOOK AT INCREASE THE
NYSTAGMUS, INCREASED EYE MOTION,
NON-CYCLED PLEGED EYES, IF YOU
HAVE A LARGE ENOUGH PUPIL MORE
CLINICALLY PEEPEL WITH NARROW
ANSWER ALSO, AND PEOPLE WITH
CONTACT LENSES MOVE ON THE
RETINA, HIGH -- SOMEONE WITH
HIGH MYOPIA WHO GOES OUTSIDE
DYNAMIC RANGE OR CLINICALLY WITH
KERATACONUS, MANY EXACERBATED IN
OLDER PATIENTS, AND PATIENTS
WITH DISEASE.
THIS IS LOOKING AT ABERRATIONS,
TYPICALLY CHARACTERIZED IN TERMS
OF POWER SPECTRA, WHICH IS IN
THIS CASE DECREASE AS EXPECTED
MYOTONICALLY WITH TEMPORAL
FREQUENCY.
IMPORTANT IS THIS LINE, THIS IS
THE DIFFRACTION LIMIT LINE,
ANYTHING BELOW THAT MEANS THE AO
IS PROVIDING DIFFRACTION-LIMITED
IMAGE.
THAT'S THE NORMAL SUBJECT.
IF WE LOOK AT CASES I HAD A LIST
OF ON THE PREVIOUS SLIDE,
CLINICAL ONES, WE GET WAY UP
HERE.
THIS IS TYPICALLY 1 TO -- IT
FROZE UP.
HERE WE GO.
OH, TOO FAR.
GOES UP 1 TO 2 ORDERS OF
MAGNITUDE.
HIGHER.
AND SO THESE AREN'T GOING TO BE
CORRECTED WITH CONVENTIONAL
SYSTEM.
THIS FOR REFERENCE IS OUR LINE,
AT OUR HIGH SPEED SYSTEM.
AND SO THEY DO FALL BELOW THAT.
AND SO, A LITTLE BIT OF TROUBLE
WITH THE -- HERE WE GO.
AND SO THE ANSWER THEN TO THAT
QUESTION ON THE PREVIOUS SLIDE
IS, YEAH, THE FASTER AO IS
REQUIRED TO REACH DIFFRACTION
LIMITED PERFORMANCE, FOR OTHER
CASES THAT -- OR ALL THESE OTHER
CASES THAT WE HAD LOOKED AT.
TWO EXAMPLES GOING HIGH SPEED,
YOU GET A FEEL FOR WHAT WE SEE,
THIS IS THE CASE WITH SOMEONE
WITH HIGH VISCOUS ARTIFICIAL
TEARS.
THIS IS RIGHT AFTER THEY OPEN
THEIR EYE AFTER A BLINK, WITHOUT
AO, MATCHES UP HERE, NO CHANGE.
THIS IS WHAT IT EVOLVES DOWN TO,
TAKES A SECOND TO CONVERGE TO
DIFFRACTION LIMIT, AN AVERAGE
EVER 12 TRACES, ULTRA FAST, DOWN
TO 63 SECONDS.
AND THIS DIFFERENCE YOU CAN SEE
IN OUR AS-OCT, THE CONE MOSAIC,
CONSECUTIVE FRAMES AFTER THE
BLINK, 60 MILLISECONDS, SHARP
IMAGES OF CONE MOSAIC,
CORRECTION IS STABLE.
CONVENTIONAL TAKES LONGER TO
CONVERGE, THERE'S OSCILLATIONS
AS WELL.
HERE IS ANOTHER EXAMPLE, THIS IS
A SUBJECT WITH NYSTAGMUS, A
FRACTION OF A MILLIMETER.
THIS IS CONVENTIONAL, ULTRA FAST
DOES A BIT BETTER.
IN TERMS OF AVERAGE RATIO WITH
ULTRA FAST DOWN TO ALMOST GET TO
DIFFRACTION LIMIT OF .8,
CONVENTIONAL IS A BIT LOWER.
AND HERE'S SOME EXAMPLES OF
IMAGING IN THAT NYSTAGMUS EYE,
WITH CONVENTIONAL FRAMES DON'T
EACH GOOD ENOUGH IMAGE QUALITY
TO SEE THE CONES, LIKE DOWN IN
HERE, THIS LOCATION.
IN CONTRAST WITH HIGH SPEED AO,
WE'RE ABLE TO GET CONSISTENTLY
GOOD IMAGE QUALITY ACROSS IT.
IN BOTH CASES, THE MOTION OF THE
RETINA WE'RE NOT ABLE TO CORRECT
WITH AO, IT'S GOING TO BE IN THE
DATA.
TEMPORAL ABERRATIONS NOTABLY
ELEVATED IN THE NUMEROUS
CLINICALLY MORE RELEVANT
SCENARIOS, BUT IT'S ALL KIND OF
A GRAY CONTINUUM THERE.
IN THESE SCENARIOS ULTRA FAST
AO, ALPHA FORMS, CONVENTIONAL
AO, WE HAVEN'T FOUND ANY
PERFORMANCE PENALTY IN
INCREASING THE AO SPEED.
SO THAT GETS US TO THE LAST
PROJECT WHICH IS A SPECIFIC USE
OF AS-OCT, AND THIS ONE IS
GETTING DOWN TO THE CONE OUTER
SEGMENT LENGTH, LED BY A Ph.D.
STUDENT IN MY GROUP, GIVING A
DETAILED PRESENTATION AT ARVO,
FOR THOSE INTERESTED.
SO LET'S START WITH THIS.
IN MANY AS-OCT STUDIES WE USE
THE SAME CONE REFLECTIONS, AS
YOU FIND IN CLINICAL IMAGES,
CONE OUTER SEGMENT TIP BAND, WE
CAN ZOOM IN, THEY GET BLURRY BUT
STRADDLE THE OUTER SEGMENT.
AND IF WE MEASURE DISTANCE
BETWEEN THE TWO BANDS,
CORRESPONDS TO CONE OUTER
SEGMENT LENGTH.
WITH AS-OCT THAT AFFORDS HIGHER
RESOLUTION, BANDS TURN INTO ROWS
MUCH PUNCTATED REFLECTIONS, EACH
IS LIGHT REFLECTING FROM
INDIVIDUAL CELLS, IN AGGREGATE
THE LENGTH SHOULD BE SIMILAR TO
OVER HERE WITH CLINICAL OCT.
NOW LET'S GO TO A DISEASED EYE,
RETINITIS PIGMENTOSA, A DISEASE
WE'VE BEEN STUDYING IN MY LAB.
CHARACTERIZED BY HEALTHY CENTRAL
ISLAND SEPARATED FROM THE
ATROPIC ZONE BY THIS TRANSITION
ZONE IN BETWEEN.
AND THAT TRANSITION ZONE IS
OFTEN OPERATIONALLY DEFINED BY
WHERE THE COST BAND HERE ENDS.
AND THEN WHERE THE ISO S BAND
ENDS OVER HERE.
THIS NATURALLY BRINGS UP THIS
QUESTION, WHAT IS THE OUTER
SEGMENT OF LENGTH OF CONES IN
THIS TRANSITION ZONE GIVEN THERE
IS NO COST BAND IN HERE FROM
CLINICAL OCT.
AND SO WE THOUGHT MAYBE AS-OCT
WOULD PROVIDE CLUES TO WHAT'S
GOING ON.
HERE IS AN EXAMPLE OF ANOTHER RP
PATIENT, IMAGED AT THESE THREE
LOCATIONS, CRITICAL IS JUST
REALLY THAT THE 6-DEGREE
LOCATION IN THE TRANSITION ZONE,
IF THIS WAS A NORMAL HEALTHY
RETINA AT 6 DEGREES WE WOULD SEE
THESE TWO ROWS OF PUNCTATED
REFLECTIONS, AND GIVEN THIS IS
AN RP PATIENT, CLINICAL OCT,
REASONABLE GUESS WOULD BE WE
JUST DON'T SEE THIS BRIGHT BAND
OF REFLECTIONS.
WHEN WE LOOK INTO IT, THIS IS
WHAT WE GET.
WE DON'T GET LESS REFLECTIONS,
WE GET A WHOLE BUNCH MORE, ALL
OVER THE PLACE.
SO THERE'S REALLY NO OBVIOUS
VISUAL CORRELATION BETWEEN THIS
TYPE OF IMAGE AND WHAT YOU GET
CLINICALLY OVER HERE.
SO OUR GOAL WAS -- OR REALLY
QUESTION, CAN WE DEVELOP A
METHOD THAT WILL ALLOW US TO
DECIPHER THIS MESS, WHICH BOILS
DOWN TO WHICH OVER HERE, WHICH
REFLECTIONS OVER HERE ARE THAT
THE COST REFLECTION OF EACH
CELL, AND SO GEORGE JI CAME UP
WITH THIS METHOD, BASED ON THE
OPTORETINOGRAM, A WHOLE SESSION
THIS AFTERNOON.
I'LL GIVE TWO SENTENCES.
FIRST IS JUST DEFINITION, AS I
THINK OF IT, OPTICAL MEASUREMENT
OF CHANGE IN CONE CELL IN
RESPONSE TO LIGHT STIMULATION,
AND THAT'S ALMOST ALWAYS USED IN
TERMS OF THE CONES LOOKING AT
THE DIFFERENCE IN PHASE BETWEEN
THE IS/OS AND COST REFLECTION OF
THE SAME CELL.
GEORGE WENT IN AND LOOKED AT ALL
THE REFLECTIONS BEHIND HERE, AND
LOOKED AT ORG SIGNAL.
SO BASED ON THAT HE WAS ABLE TO
INFER IF A REFLECTION OCCURRED
INSIDE OF THE OUTER SEGMENT AT
THE TIP OF THE OUTER SEGMENT, OR
DOWN BENEATH.
AND HE HAD A COMPLICATED METHOD,
I WON'T GO THROUGH IT HERE.
BUT HAPPY TO ANSWER YOUR
QUESTIONS AT ARVO ABOUT IT.
I'M JUST GOING TO JUMP TO
RESULTS WITH THIS IS METHOD.
AND SO WE CAN READILY FIND THE
IS/OS REFLECTION, NORMAL OR
DISEASE, BY YELLOW STARS.
USING GEORGE'S METHOD, THE RED
SPOTS CORRESPOND TO WHERE COST
IS.
SO NOW WE'RE IN A POSITION TO
MEASURE OUTER SEGMENT LENGTH
EVEN IN THE DISEASED PATCH AND
FIGURE OUT WHICH CONES HAVE
ADDITIONAL REFLECTION.
LAST SLIDE, THE CONTROL SUBJECT,
WE HAVE A NUMBER OF THEM BUT
IMAGING AT TWO, FOUR, SIX
DEGREES, THIS IS THE
DISTRIBUTION OF CONE OUTER
SEGMENT LENGTH, FAIRLY
HOMOGENOUS IN OUTER SEGMENT
LENGTH HERE.
WE CAN GO IN NOW AND MEASURE
WHICH ONES HAVE EXTRA
REFLECTIONS HERE, AND THIS IS
THE PERCENTAGE OF THEM.
THEY VARY BETWEEN 6 TO 10%.
SO VERY SMALL PERCENTAGE OF THEM
HAVE THESE EXTRA REFLECTIONS.
WE NOW GO INTO A DISEASE PATCH,
TWO EXAMPLES HERE, TWO SUBJECTS.
TWO, FOUR, SIX, CENTRAL HEALTHY
ISLAND 2 AND 4 GET CONES OF SAME
LENGTH BUT EXTRA REFLECTIONS,
MORE IN THIS PARTICULAR ONE,
LIKE 33%.
THEN THE TRANSITION ZONE,
BECOMES BIMODAL, A LOT OF SHORT
LENGTH CONES.
FOR THE LONGER LENGTH CONES
STILL NORMAL IN LENGTH, HALF OF
THEM HAVE THESE EXTRA
REFLECTIONS.
WE HAVE A SIMILAR STORY FOR THE
SECOND RP.
KIND OF KEY FINDINGS AT THIS
POINT IN OUR PROJECT IS THAT IN
THE TRANSITION ZONE WE TEND TO
GET THIS BIMODAL DISUSING, A LOT
OF DIFFERENT LENGTHS, AND THAT
THESE NORMAL LENGTH CONES HERE
ON THIS MODE AND THIS MODE DOWN
HERE WHICH IS SMALLER LIKELY TO
HAVE EXTRA REFLECTIONS, FIVE TO
SEVEN TIMES MORE.
MAYBE NORMAL LENGTH CONES MAY
ALREADY BE COMPROMISED.
WE TESTED BY LONGITUDINALLY
TRACKING THESE CONES OVER TIME.
SO IN CONCLUSION I GAVE A LITTLE
BIT OF INTRODUCTION TO AS-OCT
AND MOTIVATION FOR IT, USED ON
DEVELOPING HIGH SPEED, BENEFIT
THAT SEEMS TO ACCRUE FROM GOING
FASTER, AND INTO SPECIFIC
APPLICATION LOOKING AT CONE
PHOTORECEPTOR CELLS, OUTER
SEGMENT LENGTHS AND ADDITIONAL
REFLECTIONS.
THANK YOU.
[APPLAUSE]
THANKS
>> THANKS FOR THE GREAT START,
DON.
NEXT SPEAKER IS FROM NEI, ANDREW
BOWER, FROM NEI, SURFACING
RESOLUTION LIMIT OF ADAPTIVE
OPTICS OCT IMAGING.
>> THANKS FOR THE INTRODUCTION,
AUSTIN.
WE HEARD A GREAT TALK FROM DON
GIVING BACKGROUND IN AS-OCT, AND
EXCITING NEW DEVELOPMENTS IN THE
FIELD.
MY BACKGROUND IS MICROSCOPY,
RESOLUTION IS CENTRAL TO
EVERYTHING THAT WE THINK ABOUT.
AND REALLY DEFINES THE WAY WE
THINK ABOUT THE FIELD.
SUPER RESOLUTION TECHNIQUES
CHANGED THE WAY WE DO SCIENCE,
ALLOWING US TO ASK AND ANSWER
QUESTIONS WE NEVER IMAGINED IN
THE PAST.
RETINAL IMAGING FIELD, I'VE
FOUND THAT WE ARE AT THE
PRECIPICE OF A SIMILAR KIND OF
REVOLUTION, TODAY I'D LIKE TO
SHARE PART OF THAT JOURNEY HOW
WE'VE BEEN PUSHING RESOLUTION
LIMITS BEYOND WHAT WE MAY BE
ABLE TO ACHIEVE WITH ADAPTIVE
OPTICS ALONE SPECIFICALLY FOR
AS-OCT IMAGE.
AN EXAMPLE WHERE I'M COMING FROM
HERE LET ME START WITH A
CLINICAL INFRARED REFLECTANCE
IMAGING A HEALTHY SUBJECT WE
IMAGED UPSTAIRS IN THE EYE
CLINIC.
YOU CAN SEE THE DISC HERE,
CENTERED AT THE FOVEA HERE.
IF WE ZOOM IN ON A REGION OF
RETINA 2 OR 3 MILLIMETERS FROM
THE FOVEA WE CAN GET A NICE
IMAGE OF PHOTORECEPTORS LIKE DON
SHOWED EARLIER.
BECAUSE THIS IS THREE
DIMENSIONAL, WE GET NOT ONLY A
VIEW OF THE PHOTORECEPTOR LAYER
SHOWING US BRIGHT SPOTS AND
DISKS CORRESPONDING TO
PHOTORECEPTOR OUTER SEGMENTS,
THREE DIMENSIONAL VIEW, YOU CAN
SEE PHOTORECEPTOR REFLECTIONS
HERE AND THE RPE CELLS
UNDERNEATH.
HOWEVER, IF WE MOVE A FEW
MILLIMETERS CLOSER TO THE FOVEA,
CAPTURE THE EDGE, YOU SEE THE
DARK IMAGE AND DOME SHAPE,
IMAGES LOOK DIFFERENT IN OUR
SYSTEM.
YOU CAN SEE THESE CONES ARE MUCH
SMALLER, MUCH CLOSER SPACED
TOGETHER AS WE EXPECT, PUSHING
THE LIMITS OF WHAT WE ACHIEVE
DUE TO RESOLUTION CAPABILITIES
OF OUR INSTRUMENT.
AT THE TOP LEFT YOU CAN
DISTINGUISH PHOTORECEPTORS.
CLOSER YOU SEE IMAGES BLURRY,
HAZY, A SPECKLED APPEARANCE.
IT BECOMES DIFFICULT TO
DISTINGUISH PHOTORECEPTORS AND
UNDERSTAND WHAT WE'RE REALLY
SEEING.
THIS IS UNFORTUNATE BECAUSE THIS
IS A VERY IMPORTANT AND CRITICAL
PART OF OUR VISUAL SYSTEM.
IT'S UNIQUE TO THE HUMAN VISUAL
SYSTEM, A MISSED OPPORTUNITY TO
SHOW YOU CELLS IN MORE DETAIL.
SO FOR US IT LED TO THE QUESTION
THAT SPAWNED THIS, HOW CAN WE
IMPROVE LATERAL RESOLUTION
BEYOND DIFFRACTION LIMIT THAT
AS-OCT ALLOWS.
WE TOOK A STEP BACK, LOOKING AT
WHAT WE LEARNED FROM THE
SCANNING FIELD, 2D ANALOG TO 3D
IMAGES.
THIS IS A 790-NANOMETER, LOWER
WAVELENGTH, HIGHER RESOLUTION,
FOVEA OF HEALTHY SUBJECT, AND
YOU CAN SEE THESE ARE GOOD
IMAGES.
WE CAN DELINEATE PHOTORECEPTORS
QUITE WELL.
IF WE ZOOM IN ON A REGION VERY
CLOSE TO THE FOVEA CENTER
THERE'S BLURRINESS, HAZINESS,
AND WE CAN GET BEYOND THIS NICE
IMAGE AND PUSH FURTHER.
FIRST THING WE CAN DO IS BRING
IN SUBAREA DETECTION SIGNAL, A
SMALL PIN HOLE ALLOWING US TO
REFLECT SLIGHT COMING BACK TO A
SMALL PATCH, ELIMINATING BLURRY,
HAZY LIGHT.
WE CAN MODIFY ILLUMINATION, WHAT
WE SENDING TO THE RETINA.
INSTEAD OF ILLUMINATING WITH
CIRCULAR BEAN WITH ILLUMINATE
WITH A RING-SHAPED BEAM.
COMBINING THE TWO APPROACHES,
RING ILLUMINATION, AND SUBAREA
DETECTION, WE GET BY FAR BEST
RESULTS WITH OUR AO-SLO.
WE GO FROM SOMETHING THAT IS
VERY GOOD WITH AO ALONE AND PUSH
BEYOND THAT RESOLUTION LIMIT TO
GET SOMETHING THAT'S EVEN
BETTER.
SO, THE IDEA KIND OF CAN WE
THROW IT IN AND USE IT IN OUR
AS-OCT SYSTEM?
THE ANSWER IS NOT EXACTLY, NOT
RIGHT AWAY.
THE CHALLENGE HERE IS THAT IN
OUR AS-OCT SYSTEM AND IN SEVERAL
WE HAVE THIS ARCHITECTURE THAT
HAS A SHARED ILLUMINATION AND
DETECTION PATH.
BASIC SETUP, 3 MEGAHERTZ, LIGHT
SOURCE, SEND IT THROUGH
SCANNERS, SCANS THE PATTERN ON
THE RETINA, THAT LIGHT THAT
RETURNS TAKES THE SAME PATH BACK
AND SENT TO DETECTION CHANNELS.
YOU CAN IMAGINE IF WE WANTED TO
PUT A RING ILLUMINATION, LIGHT
COMING BACK WOULD ALSO HIT THAT
RING PATTERN AND WOULD AFFECT
OUR DETECTION SIDE.
SAME WITH THE SUBAREA DETECTION
SIGNALS.
THEY ARE AFFECTING EACH OTHER,
NOT INDEPENDENTLY CONTROLLING
WHERE WE NEED TO BE.
AO IS HAPPENING IN THE
BACKGROUND THE WHOLE TIME SO
WE'RE USING AO TO KEEP
OURSELVES AT DIVERSITY FRACTION
LIMIT.
WE TAKE A DIFFERENT APPROACH,
SEPARATE THESE TWO, NOW WE HAVE
TWO INDEPENDENT PATHS.
RING ILLUMINATION MASK, SEND
BEAM TO SCANNERS, SCAN ACROSS
THE RHETT -- RETINA.
LIGHT GOES TO SEPARATE DETECTION
PATH, PUT THE SUBAREA DETECTION
IN.
DETECT IN TYPICAL OCT SETUP.
WE HAVE INDEPENDENT CONTROL OF
ILLUMINATION AND DETECTION.
WE CAN SEE HOW WELL THIS WORKS.
TO START WE DID THIS OUTSIDE THE
EYE, JUST TO VALIDATE THE
RESOLUTION IMPROVEMENT WE EXPECT
TO SEE BASED ON AO-SLO.
BAR TARGET, AS SIZES GET SMALLER
WE WANT TO DISTINGUISH THREE
BARS FOR EACH PATTERN.
IF WE SHOW IMPROVEMENT BETWEEN
CONVENTIONAL TYPICAL CASE AND
OUR RING ILLUMINATION AND
SUBAREA DETECTION CASE, WE'LL BE
MORE CONVINCED THIS IS WORKING.
ZOOM IN ON A SMALL PATCH AND USE
CONVENTIONAL CASE, THE ACCEPTUP
WE CAN TELL MAYBE THERE'S A FEW
AREAS WHERE WE CAN DISTINGUISH
THIS BAR, BAR PATTERNS, BUT IT'S
VERY BLURRY AND RIGHT AT THE
LIMITS OF WHAT OUR SYSTEM CAN
RESOLVE.
BRINGING IN SUBAREA DETECTION
PIN HOLE WE SEE IMPROVEMENT.
ESPECIALLY TOWARDS THE TOP LEFT
PORTIONS, COMPARING THEM YOU CAN
SEE A SMALL IMPROVEMENT IN
ABILITY TO RESOLVE FINER
FEATURES BUT BY FAR THE BEST
RESULTS ARE COMBINING THESE AS
WE EXPECT FROM OUR AO-SLO
RESULTS, MAKING OUT MORE
PATTERNS, DOWN TO FINE PATTERNS
THAT ARE BASICALLY NOT ABLE TO
BE RESOLVED IN CONVENTIONAL
APPROACH.
DRAWING A LINE, WE CAN SEE FOR
THIS BAR PATTERN CONVENTIONAL
CASE WE DON'T SEE CLEAR CONTRAST
BETWEEN BARS, BRINGING IN
SUBAREA DETECTION SCHEME WE SEE
A LITTLE BIT OF CONTRAST THERE
BUT, AGAIN, AGREEING WITH WHAT
WE SEE BEST IS COMBINING IN
ADDITION TO ADAPTIVE OPTICS.
THIS LOOKS LIKE IT'S WORKING
OUTSIDE THE EYE BUT THE REAL
IMPORTANCE HERE IS HOW WELL IT
WORKS INSIDE THE HIGH.
WE STARTED FIRST BY LOOKING AT
FOVEAL SCANS, CONVENTIONAL
FIRST.
ASTERISK AGAIN, THE SMALL
PHOTORECEPTORS, TIGHTLY SPACED
IN THE HUMAN EYE.
YOU CAN SEE A BIT OF CHALLENGES
WE'RE FACING RIGHT AWAY AT THE
FIRST REFLECTIVE LAYER.
YOU START TO SEE SMEARING ALONG
THIS PHOTORECEPTOR BAND,
INDICATING WE'RE AGAIN AT THE
LIMIT OF RESOLUTION, WHAT WE CAN
SEE IN THE CONES.
REALLY EXCITING WHEN WE BRING IN
THE SUBAREA DETECTION CASE WE
CAN START TO SEE WHAT DON WAS
DESCRIBING EARLIER, PUNCTATE IN
THE RECEPTOR RECEPTOR BANS NOW
SEEN IN INDIVIDUAL CONES.
WE CAN SEE PUNCTATE GETTING
CLOSER TO FOVEAL CENTER, A BIG
IMPROVEMENT, EXCITING TO SEE.
THE BEST WAY IS ZOOMING IN, YOU
CAN SEE INDIVIDUAL REFLECTIONS
BECOMING MUCH MORE CLEAR AS THEY
ADD RESOLUTION-ENHANCING
CONDITIONS.
THIS IS A 2D IMAGES, SPEED
INCREASES OVER THE COURSE IS
BEING ABLE TO DO TRUE VOLUMETRIC
IMAGING WITH DENSE SAMPLING.
WE WERE EXCITED TO GO AFTER THAT
NEXT, LOOKING AT THE FIRST
PHOTORECEPTOR AT THE FOVEAL
SECTION, A DIFFERENT SUBJECT,
LOOKING CENTERED AT THE FOVEAL
CENTER.
WE TAKE A SLAB THROUGH THAT
PHOTORECEPTOR REFLECTION, TURN
IT ON ITS SIDE AT THE LOOK AT
THE PROJECTION.
CONVENTIONAL IMAGE LOOKS LIKE
THIS, DUE TO THE DOME SHAPE OF
THE PHOTORECEPTORS AS WE MIGHT
EXPECT.
TOWARDS THE EDGES MAYBE YOU CAN
RESOLVE A FEW BUT VERY HAZY
SPECKLED IMAGE DIFFICULT TO
DETERMINE CELLULAR STRUCTURE OF.
WHEN WE BRING IN THE SUBAREA
DETECTION CASE WE IMMEDIATELY
SEE IMPROVEMENT, ESPECIALLY ON
EDGES OF IMAGES WHERE THE CONES
AT THE EDGES ARE NOW EASY TO
DISTINGUISH.
WE SEE A BIT OF A HAZY PATTERN
AS WE GET CLOSER TO THE CENTER
OF THE FOVEA.
A BIG IMPROVEMENT.
WHEN WE BRING IN COMBINED
APPROACH WITH RING ILLUMINATION
AND SUBAREA DETECTION ALL EDGES
ARE VISIBLE, SPECKLED APPEARANCE
STARTS TO DIMINISH, WE START TO
GET CLOSE TO THE FOVEAL CENTER
IN ABILITY TO REDUCE THESE
CELLS.
I'M GOING TO LET THIS PLAY SO
YOU CAN SEE THE IMPROVEMENT SIDE
LIE SIDE.
IT LOOKS LIKE A BIG IMPROVEMENT,
VERY EXCITING, BUT PUTTING
EVERYTHING SIDE BY SIDE WE WANT
TO KNOW HOW MUCH WE CAN EXPECT
TO ACHIEVE IN DOING THIS,
BRINGING THESE MODULES IN.
A SMALL REGION, VISUALLY WE
CAN'T RESOLVE MUCH TO SOMETHING
THAT'S A LITTLE BETTER WITH
SUBAREA DETECTION TO SOME IMAGES
WHERE WE CAN SEE EVERY CONE
PHOTORECEPTOR WITH COMBINED RING
AND SUBAREA MODULES.
TO QUANTIFY THIS, ONE OF THE
TOOLS WE USE IS POWER SPECTRUM
DENSITY, SIMILAR TO WHAT DON WAS
DOING IN A MORE SPATIAL SENSE.
WE WANT TO LOOK AT SOME KIND OF
RESOLUTION OR CONTRAST METRIC
THAT RANGES ACROSS FEATURE SIZE
SO ON THE Y-AXIS YOU'RE LOOKING
AT CONTRAST RESOLUTION TYPE
METRIC, X-AXIS WE'RE LOOKING AT
SPATIAL FEATURE SIZE AND
SPACING, SO TOWARDS THE LEFT
LARGE FEATURES THAT ARE SPACED
FAR APART, TOWARDS THE RIGHT
SMALLER OBJECTS MORE CLOSELY
SPACED TOGETHER.
YOU CAN IMAGINE FOVEAL CONE
SPACING LIES IN THE MIDDLE HERE,
AND WHAT WE'D EXPECT TO SEE WITH
IMPROVEMENT IN RESOLUTION IS A
PEAK TO OCCUR ABOVE BASELINE
PROVIDED TO THE CONVENTIONAL
CASE.
EVERYTHING IS IN REFERENCE TO
CONVENTIONAL CASE.
SUBAREA, WE DO THE PEAK
CORRESPONDING TO THE SPACING
WE'D EXPECT TO SEE FOVEA
PHOTORECEPTORS AT.
AND BRINGING IN THE RING AREA WE
SEE DRAMATIC INCREASE THAT WE
SEE VISUALLY SHOWING 20X
IMPROVEMENT IN THIS PSC METRIC
RELATIVE TO CONVENTIONAL CASE,
DRAMATIC IMPROVEMENT IN
RESOLUTION FOR AO-OCT SYSTEM.
COMING BACK TO THE WHOLE
APPROACH, WE STARTED WITH OUR
AO-SLO, WE START WITH NICE
IMAGES WITH CONVENTIONAL
ADAPTIVE OPTICS.
WE FOUND WITH ENHANCING USING
RESOLUTION-ENHANCING MODULES CAN
TAKE A NICE IMAGE AND PUSH
BOUNDARIES FURTHER TO GET IMAGES
EVEN SHARPER, EVEN CLEARER.
WE'VE TAKEN THESE IDEAS AND
TRIED TO MOVE TO THREE
DIMENSIONAL AO-OCT, LOWER
RESOLUTION BECAUSE OF LOWER
WAIVE LENGTH BUT STILL QUITE
NICE, TO WHERE WE CAN NOW REVEAL
UNDERLYING CELLULAR STRUCTURE WE
WEREN'T ABLE TO DELINEATE, AN
EXCITING OPPORTUNITY HERE.
I'M EXCITED TO SEE THIS AS WE
PUSH THIS CLOSER TOWARDS
CLINICAL SETTINGS AND TRY TO
UNDERSTAND A LOT OF THE
PROPERTIES FOVEAL CONE MOSAIC,
AND THIS IS ONLY THE BEGINNING.
OUR SYSTEM, THERE'S SOME THINGS
WE CAN DO TO IMPROVE RESOLUTION
FUNDAMENTALLY BY GOING TO LOWER
WAVELENGTHS, THERE'S A LOT OF
ROOM FOR IMPROVEMENT, WE'RE
EXCITED TO PUSH BOUNDARIES
FURTHER AND GET CLOSER TO
SOMETHING, FINDINGS RESOLUTION
COMMUNITIES OR MICROSCOPY
COMMUNITIES FOUND IN THE PAST
AND PUSHED BOUNDARIES OF WHAT
WE'RE ABLE TO DO.
WITH THAT I'D LIKE TO
ACKNOWLEDGE THE MEMBERS OF MIGHT
HAVE LAB INCLUDING P.I., DR.
JOHNNY TAM, COLLABORATORS WITH
NIH AND AS WELL AS STANFORD
UNIVERSITY AND THE FDA.
THANK YOU.
[APPLAUSE]
THANKS, ANDREW.
THE THIRD SPEAKER TODAY IS
ZHOULIN LIU, STAFF FELLOW,
OFFICE OF SCIENCE AND
ENGINEERING LABS, U.S. FOOD AND
DRUG ADMINISTRATION, THE TITLE
IS IMAGING HUMAN
CHORIOCAPILLARIS WITH ADAPTIVE
OPTICS-OCT.
>> THANK YOU VERY MUCH, FOR THE
INTRODUCTION.
IT IS AN HONOR TO BE HERE TO
SHARE HOUR RESEARCH AT THE FDA.
PREVIOUS SPEAKERS TALKED ABOUT
CLINICAL APPLICATIONS.
I'D LIKE TO START WITH THE
AO-OCT DEVICE.
THE COMPANIES WHO HAVE ACHIEVED
AO COMMERCIALIZATION HAVE AO
DEVICES IMPLEMENTED WITH
DIFFERENT IMAGE MODALITIES.
AND THOSE COMPANIES RECEIVED
COMMERCIALIZATION OUTSIDE OF THE
U.S.
WHY HAS AO-OCT NOT ACHIEVED FULL
CLINICAL TRANSLATION?
IN TERMS OF REGULATORY BURDEN
THERE'S PERFORMANCE ASSESSMENT
FOR STANDARDIZATION AND
REGULATORY EVALUATION, IN TERMS
OF DEVICE LIMITATIONS, SMALL
IMAGING TRANSLATING INTO
INCOMPLETE PICTURE.
NEW TECHNOLOGIES AUTOMATED
ALGORITHMS, AI AND BEST
PRACTICES HAVE NOT FULLY
IMPLEMENTED IN THAT SPACE.
THEY LACK VALIDATED BIOMARKERS,
WITH USE AO-OCT.
OF AO PROGRAM AT FDA ATTEMPTED
TO ADDRESS SOME HURDLES, AS WELL
AS BIOMARKER DEVELOPMENTS WHICH
I'M GOING TO TALK MORE IN THE
NEXT TWO SLIDES.
I LIKE TO THINK AS A PERSONAL
DEVICE THAT CREATES CHALLENGES
FOR THE DEVELOPERS AND REVIEWERS
IN TERMS OF STANDARDIZATION IN
ASSESSMENT.
NOTICE THERE ARE METRICS YOU CAN
TARGET.
WE DEVELOPED AO PHANTOM FOR
RESOLUTION ASSESSMENT.
WE CREATE THAT HOLLOW CONE AS
PHOTORECEPTOR PHANTOM.
YOU MAY SHOW ON THE RIGHT
HERE -- SORRY ABOUT THAT.
IMAGE ON THE RIGHT IS TAKEN WITH
OUR AO INSTRUMENT.
AO PHOTORECEPTOR PHANTOM IS USED
IN MULTI-SITE CLINICAL STUDY,
WILL BE SUBMITTED TO THE PHANTOM
LIBRARY.
WE DEVELOPED BIOMARKERS THAT
TARGET DIFFERENT DISEASES.
WE STUDY MORPHOLOGY.
ALSO WE DEVELOPED RETINAL
GANGLIA CELL BIOMARKERS.
THE DENSITY REDUCTION WITH CELL
BODY ENLARGEMENT IN GLAUCOMA
COMPARED WITH CONTROL SUBJECTS
TAKEN AT THE SAME.
BEYOND OPHTHALMOLOGY TO STUDY
NEUROLOGICAL DISEASE WHICH
CALLED MULTIPLE SCLEROSIS.
FOR OTHER DISEASE WE TARGET
RECEPTOR, PIGMENT EPITHELIUM
CELLS, BEGIN ESTABLISHING
NORMATIVE DATA FOR RPE AND
PHOTORECEPTOR MORPHOLOGY.
WE'RE REALLY DEVELOPING A
GROWING LIST OF AOCT
CAPABILITIES WE HOPE TO IMPACT
FOR CLINICAL TRANSLATION AS WELL
AS WELL AS REGULATORY SCIENCE.
THE TALK ALIGNS WITH PREVIOUS
EFFORT IN TERMS OF CELLULAR
BIOMARKER DEVELOPMENT, STEPPED
OUR CAPABILITY TO IMAGE HUMAN
CHORIOCAPILLARIS.
WE KNOW THE HUMAN
CHORIOCAPILLARIS APPLIES
METABOLIC NEEDS FOR
PHOTORECEPTOR RPE COMPLEX, AND
WE ALSO KNOW THAT THE CC PLAYS
ESSENTIAL RETINAL HEALTH.
VISUALIZING INDIVIDUAL
CHORIOCAPILLARIS SEGMENTS WITH
CURRENT AVAILABLE IMAGING
MODALITIES, IMPOSING OR LIMITS
UNDERSTANDING ON DISEASE
MECHANISM AND ABILITY TO MONITOR
DISEASE PROGRESSION.
PREVIOUS ATTEMPTS ON RESOLVING
CHORIOCAPILLARIS WITH AO-OCT HAS
LIMIT IMAGING FIELD OF VIEW, AND
REQUIRED EXTREMELY LONG
ACQUISITION TIME.
SO, OBJECTIVE HERE TODAY IS
REALLY TO DEVELOP AO-OCT TO MAP
HUMAN MORPHOLOGY.
WE USE OCT SYSTEM, HERE IS A
SCHEMATIC DIAGRAM OF THE LAYOUT.
I WON'T GO INTO DETAIL BUT
HIGHLIGHT A FEW KEY FEATURES,
THAT IS VERY IMPORTANT FOR THIS
STUDY.
THAT IS THE ACQUISITION SPEED
ALONG WITH RELATIVELY LARGE
IMAGE FIELD OF VIEW.
AND THEN WE DESIGN INTO TWO
PARTS.
FIRST PROTOCOL AIMED TO OPTIMIZE
EYE POSITION, WE STUDY HOW
REPEATED B SCAN AND NUMBER OF
VOLUME AVERAGING COULD AFFECT CC
IMAGING.
PROTOCOL 2, TO ESTABLISH
NORMATIVE DATA, HUMAN
CHORIOCAPILLARIS MORPHOLOGY.
CO-ALIGNING INFORMATION ARE
OBTAINED FROM THE SAME AO-OCT
VOLUME FOR VISUALIZATION.
AFTER SEGMENTATION WE CAN HAVE
MORPHOLOGICAL PARAMETERS TO SOME
RESULTS PRESENTED LATER.
SO, LET'S LOOK AT RESULTS.
HOW NUMBERS AFFECT SHOWING FROM
LEFT THROUGH RIGHT HERE IS THE
CHORIOCAPILLARIS VIEW FROM
SINGLE VOLUME ACQUISITION,
DIFFERENT B SCAN SETTINGS.
WE CAN SEE THE VESSEL CONTRAST
IMPROVED WITH INCREASING NUMBER
OF REPEAT B SCANS BUT LARGE
REPEAT B SCANS WILL RESULT IN
LONG VOLUME ACQUISITION TIMES
AND BECOME A PROBLEM.
REGARDLESS, IF WE LOOK AT ZOOMED
IN IMAGES FROM THE SAME LOCATION
WE CAN APPRECIATE THE BENEFIT
FROM INCREASING REPEAT NUMBER OF
B SCANS, QUANTIFIED BY TAKING
SEGMENTATION RESULTS, COMPARE
THE SIGNAL FROM THE VESSEL AREA
VERSUS SIGNAL AREA FROM THE
VOID.
THIS SHOWS INCREASE IN SIGNAL TO
NOISE WITH INCREASING NUMBER OF
REPEAT SCANS FROM FOUR TO
TWELVE.
WE WANT TO KNOW HOW SIGNAL NOISE
IS BENEFIT FROM VOLUME AVERAGE,
DEFINE TOTAL ACQUISITION TIME
TWO SECONDS, WHICH IS BEFORE OUR
PATIENTS HOLD THEIR EYE OPEN,
THAT WOULD BE THE TIME WHEN YOU
ASK THE SUBJECT TO OPEN YOUR
EYES, ONE TWO, TWO SECONDS LATER
YOU GET IMAGE, SIGNAL TO NOISE
IMPROVING WITH INCREASING VOLUME
AVERAGING THAT AGREES WITH OUR
VISUAL INSPECTION.
WE CAN DO THE SAME WITH OTHER
REPEATED SCAN SIGHTINGS.
HERE IS THE RESULTS WITH MAXIMUM
PERMISSIBLE VOLUME AVERAGE, AND
THIS IS FOR REPEAT, SCAN OF
FOUR, NUMBER SIX, UP TO 12.
WE CONCLUDE THE MOST BENEFIT ON
SIGNAL TO NOISE IS COMING FROM
NUMBER OF B SCANS, REPEAT B SCAN
USE, VOLUME AVERAGING.
WE THINK IMAGES WITH SIGNAL TO
NOISE ABOVE 20 DB ALLOWS
VISUALIZATION, AND THERE IS A
SWEET SPOT WHERE YOU GET A GOOD
BALANCE IN BETWEEN SIGNAL TO
NOISE AND EYE MOTION.
WE FINALIZE REPEAT SCANS AS
OPTIMAL SCAN PARAMETER FOR
SUFFICIENT SIGNAL TO NOISE, NO
NEED FOR VOLUME AVERAGING.
SO, WITH THAT SCAN PROTOCOL, WE
CAN MAP OUT PHOTORECEPTOR
COMPLEX.
HERE IS EXAMPLE FROM 38-YEAR-OLD
SUBJECT, HEALTHY VOLUNTEER, THIS
IS MONTAGE, GENERATED FROM
SINGLE VOLUMES, HERE SHOWS
CORRESPONDENTING
CHORIOCAPILLARIS REGION.
FOR GENERATING DATA TOOK PLACE
UNDER TWO MINUTES.
HOWEVER, THE TOTAL IMAGING TIME
LASTS ABOUT ONE HOUR.
BELIEVE IT OR NOT, WE FOUND THE
STREAMING THE DATA, FROM OUR
DIGITIZER TO THE COMPUTER TAKES
MOST OF THE TIME.
MORE THAN 90% OF THE TIME
SUBJECTS WERE WAITING, KEEP
THEIR EYE CLOSED.
JOHNNY TAM AND TEAM AT NEI HAVE
DEMONSTRATED SIMILAR DATA
STREAMING WITH DATA PIKING AND
ABERRANT STRATEGY, WE ESTIMATED
IMAGING, TOTAL TIME DURATION CAN
BE SHORTENED DOWN TO FIVE TO TEN
MINUTES TO GENERATE THE DATA
THAT CREATED SUCH A PICTURE.
NOW I'D LIKE TO GO BACK TO
IMAGES FOR A LITTLE BIT MORE
DETAILS, IN THE MONTAGE SHOWS
NOT ONLY WE CAN VISUALIZE
INDIVIDUAL CHORIOCAPILLARIS BUT
LOBULAR STRUCTURE AND
DISTRIBUTION, CONSIDERED AS A
VERY IMPORTANT ROLE IN TERMS OF
REGULAR FLOW OF CIRCULATION.
AND SHOWS SIMILARITY, COMPARED
WITH HUMAN CHORIOCAPILLARIS,
WHEN WE PUT SIDE BY SIDE AT THE
SAME SKILL PERSPECTIVE.
FURTHERMORE IF WE COMPARE AO-OCT
DATA WITH CONVENTIONAL IMAGE
FROM THE SAME SUBJECT, WE CAN
APPRECIATE LEVEL OF DETAILS AND
RESOLUTION FROM USING AO,
ALTHOUGH SOME COARSE FEATURES
CAN BE VISUALIZED IN BOTH IMAGES
INDICATED HERE.
WE ESTABLISH NORMATIVE DATA FOR
CHORIOCAPILLARIS QUANTIFICATION
FROM 21 HEALTHY SUBJECTS OR
VOLUNTEERS.
AND OUR RESULTS INDICATE THAT
HUMAN CHORIOCAPILLARIS SHOWS
DIFFERENCES IN VASODENSITY,
DIAMETER, AS WELL AS VOID
DIAMETER.
WITH THIS NORMATIVE DATA WE CAN
QUANTIFY HOW CHORIOCAPILLARIS
MORPHOLOGY DIFFER IN DISEASED
CONDITION.
HERE IS EXAMPLE OF 58 YEARS OLD
VOLUNTEER WHO HAD NO DIAGNOSIS
OF CURATIVE DISEASE, IMAGED
MACULAR ACROSS HORIZONTAL AND
VERTICAL MAIN LINE, IN AO-OCT
VOLUMES WE SEE MOST OF THE CONES
ARE GUIDING REGARDLESS OF
PRESENCE OF DRUSEN AT CENTRAL
MACULA.
AS AN RPE LAYER REVIEWS MORE
DRUSEN ACROSS IMAGING FIELD,
CORRESPONDING CHORIOCAPILLARY
MONTAGE AT SAME LOCATION.
THERE IS A CORRESPONDENCE
BETWEEN PRESENCE OF DRUSEN AND
FLOW SIGNAL, CONFIRMED WHEN WE
SEPARATE DRUSEN REGIONS.
WE OBSERVE A 13% DENSITY
REDUCTION IN DRUSEN REGION
COMPARED WITH NEIGHBORING
NON-DRUSEN REGIONS.
HERE IS ANOTHER EXAMPLE, A
SUBJECT WITH A CONE-ROD ATROPHY,
AO-OCT SCANS SHOW CENTRAL
MACULAR BEAM MOSTLY AFFECTED BY
DISEASE, ALONG WITH PRESENCE OF
DRUSEN.
HOWEVER CHORIOCAPILLARY AND
VESSELS ARE INTACT AS WE CAN SEE
HERE.
WE DID OBSERVE AROUND THE CENTER
FOVEA AND VESSELS ARE VISIBLE,
CLEARLY RESOLVED UNDER THE
DRUSEN REGION IF WE COMPARE.
THE ORGANIZATION IS DISRUPTED AT
THE CENTER MACULA INDICATING
THIS KIND OF REGIMEN AND
DISTRIBUTION CAN BE USED AS
POTENTIAL BIOMARKER FOR
CHORIOCAPILLARY NORMITY.
I'D LIKE TO GO BACK TO THE
PICTURE I SHOWED AT THE
BEGINNING, DEVICES OFFER
RESOLUTION AND SENSITIVITY FOR
LIVING HUMAN EYE, WITH
GEOGRAPHY, APPROACH PROVIDES
COMPLETE VIEW OF THE OUTER
RETINA.
WHICH OPENS TREMENDOUS
OPPORTUNITY TO STUDY
CHORIORETINAL DISEASE SUCH AS
MACULAR DEGENERATION AND HELP
IMPROVE OUR DISEASE MECHANISM,
TRACKING DISEASE PROGRESSION.
AND IMAGING WITH LARGE VIEW
MAKES THIS METHOD EXTREMELY
VALUABLE AND HELPFUL FOR EARLY
DISEASES, DISEASE PROGRESSION,
ASSESS TREATMENT OUTCOME.
THIS WORK COULD NOT BE
ACCOMPLISHED WITH SUPPORT.
THE LEAD OF THE OPHTHALMOLOGY
PROGRAM, AND OTHERS.
I'D LIKE TO ACKNOWLEDGE MY
COLLABORATORS.
THANKS FOR THE SUPPORTING,
FUNDING SUPPORT, AND THANK YOU
FOR YOUR ATTENTION.
[APPLAUSE]
>> THANKS.
NOW WE'LL TRANSITION, WE HEARD
THREE PRESENTATIONS THAT USED
ADAPTIVE OPTICS, THE SECOND,
LAST TWO TALKS, ABOUT BE
SWITCHING FROM INFRARED
WAVELENGTHS TO VISIBLE
WAVELENGTHS TO IMPROVE
RESOLUTION OF OCT.
FIRST IN THE SECOND HALF IS HAO
ZHANG.
>> I'LL FOCUS ON THE TECHNOLOGY
HISTORY, MY COLLABORATORS WILL
SHARE ON APPLICATIONS.
I ACKNOWLEDGE I RECEIVED
TREMENDOUS HELP FROM
HARD-WORKING TEAM AND
COLLABORATORS WHO PROVIDE ALL
SORTS OF SUPPORT AT DIFFERENT
STAINS OF TECHNOLOGY
DEVELOPMENT, ESPECIALLY FOR
HUMAN STUDY PROFESSOR SCHUMAN,
JUST STEPPED OUT, PROVIDING
SUPPORT IN INITIAL ADAPTATION ,
AND JEFF GOLDBERG, PUT THE
DEVICE IN A STRESS TEST THAT
DISCLOSED DESIGN IMPERFECTION
AND DEFECTS, LOTS OF WORK IS
CO-DEVELOPED WITH MY START-UP
COMPANY SO I HAVE TO DISCLOSE
HERE.
THESE ARE OUTLINES.
MICHAEL MENTIONED
STANDARDIZATION.
THIS IS OUR EFFORT TRYING TO DO
THAT.
FUTURE TECHNOLOGY DEVELOPMENT.
IN 2013, OUR LAB PUBLISHED THE
FIRST IN VIVO IMAGING FOR
VISUALIZED OCT TO ACHIEVE HIGHER
RESOLUTION, HIGHER CONTRAST.
WE MOVED TO 1330, TO 510 TO 610,
GREENISH TO YELLOW LIGHT.
THE BENEFIT, 1.3-MICRON, IF WE
NORMALIZE, WE HAVE TO BE VERY
CAUTIOUS OF THE POWER ON CORNEA
SO WE CONTROL LIGHT INTENSITY TO
BE WITHIN QUARTER OF A
MICROWATT, TYPICALLY
ILLUMINATION IS 1 TO 2
MILIWATTS.
WE DESIGN BECAUSE OF THE NATURAL
BANDWIDTH LIMIT
WE'RE TRYING TO MAXIMIZE ROLLOFF
TO OR MINIMIZE ROLLOFF IN OUR
DESIGN.
THE WHOLE WORLD HAS SEEN
TREMENDOUS GROWTH IN RESEARCH,
NOT ONLY FOR TECHNOLOGY
DEVELOPMENT BUT ALSO FOR
APPLICATIONS.
IN 2002 THE NAME CAME OUT FIRST,
PROFESSOR WOLFGANG PUT OUT
ABSTRACT AT A TIME UTILIZED,
GOING THROUGH A DOUBLE PRISM
ASSEMBLY TO SELECT DESIRED WAIVE
LENGTH AND QUANTIFY THE
RESOLUTION UP TO .7 MICRONS.
IN 2012 THE TEAM LED BY
PROFESSOR (INDISCERNIBLE) USED A
130 FEMTOSECOND LASER, THERE
COULD BE A NON-DOUBLED BEAM FOR
INFRARED, DOUBLE FOR VISIBLE
LIGHT.
GOES THROUGH THE TWO
SPECTROMETERS TO HAVE
NEAR-INFRARED AND VISIBLE LIGHT
OCT.
A TEAM FROM TAIWAN VERY MANY
STRAIGHT A CONCEPT, RECEIVED
NOBEL PRIZE FOR PHYSICS.
BLUE LIGHT TO PUMP, USING STRONG
BLUE LIGHT TO FOCUS AT THE
POWDER OF THE PHOSPHOR, AND
COLLECTING THE LIGHT, THEY WERE
ABLE TO DEMONSTRATE LED
PHOSPHOR, MORE PEOPLE CAN
ACHIEVE VISIBILITY, A DANISH
COMPANY START TO COMMERCIALIZE
THE LASER, THEY HAVE A DIFFERENT
RANGE OF LASER, PROVIDE
400-NANOMETER TO 20 TO
40-NANOMETER ILLUMINATION RANGE.
WE USE LASER FROM THE VERY
BEGINNING SO THIS TALK FOCUS ON
DATA ACQUIRED FROM NKT, THANKS
FOR THE SUPPORT FROM NIH WE'RE
WORKING ON THE NEXT GENERATION
SOURCE.
SO AT THE TIME WE WERE USING
85-NANOMETER BANDWIDTH.
WE CANNOT FIND FIBEROPTIC
COMPONENT FOR VISIBLE LIGHT.
IT WAS BUILT IN FREE SPACE.
A SIMPLE SEGMENTATION VISUALIZED
CAPILLARY, ANOTHER SEGMENTATION
OF THE PROJECTION VISUALIZED THE
FIBER BUNDLES AT THE TIME.
AS WE KEEP DEVELOPING TECHNOLOGY
WITH BETTER SPECTROMETRY DESIGN,
BETTER NOISE SUPPRESSION, WE
WERE ABLE TO ACQUIRE REALLY HIGH
QUALITY IMAGE FROM SMALL
ANIMALS, I WILL SHOW A FEW CASES
OF THE ANATOMIC IMAGE,
FUNCTIONAL IMAGING FOR ANIMAL
RESEARCH.
WE ALSO SPENT QUITE A FEW EFFORT
TRYING TO MAP OUT PATHWAY OF
CANAL AND VASCULAR HOPING IN THE
FUTURE WE CAN GUIDE MINIMAL
INVASIVE GLAUCOMA SURGERY.
I'LL USE OCT FIBRO GRAM AS
EXAMPLE.
FIRST STEP TO ACQUIRE VOLUME OF
OCT, THE VOLUME OF OCT USING
TEMPORAL AVERAGING, THIS IS
COMBINED FIBER BUNDLES WITH
CAPILLARY.
AT THE SAME TIME SCAN -- USING
SAME VOLUME, APPLIED THE
ANGIOGRAM ALGORITHM, FIBERS ARE
GONE, NO MOTION CONTRAST FROM
FIBERS, CAP LOWER CAPPED, TAKE
THE DIFFERENCE WE'LL BE ABLE TO
VISUALIZE ALL THE FIBERS AND ALL
THE CAPILLARIES.
IF WE MONTAGE, THERE WILL BE
FIBERS AND CAPILLARY.
HOW ARE WE GOING TO USE THAT?
ONE OF THE ANALYTICAL SHOW
ANALYSIS, CONSIDER A PHANTOM,
HERE IS THE OPTICAL DISC, WITH
ALL THE FIBERS STORMING A STAR
SHAPE WITH DIFFERENT FIBERS,
COUNT HOW MANY INTERSECTIONS,
AND PLOT RADIUS, EXPECTED A
NUMBER OF INTERSECTIONS, CALL
THAT A DECAY, INTERESTINGLY
CORRESPONDING TO DENSITY OF THE
FIBERS.
THIS ANALYSIS CAN ALSO PERFORM
BY FOUR QUADRANTS, WHICH MORE
ALIGN WITH CLINICAL STUDIES.
I MENTIONED TAKING ADVANTAGE OF
THE HIGH RESOLUTION, WE'RE
WORKING WITH COLLABORATORS, SCAN
ACROSS ANTERIOR SIGNAL OF THE
EYE.
WHAT'S THE BENEFIT?
WE'LL BE ABLE TO ACQUIRE
SO-CALLED DIGITAL TWIN, THIS HAS
BEEN WIDELY USED FOR ANY BRAIN
SURGERY THAT THERE'S A 3D
RECONSTRUCTION OF THE WHOLE
BRAIN AND HOW TO DO THE SURGICAL
PLANNING IS ALL RELYING ON THAT.
WE TRY TO DUPLICATE FOR
OPHTHALMOLOGY.
THIS IS THE WHOLE EYE DIGITAL
TWIN FROM THERE WE SEGMENT THE
CANAL, ANTERIOR AND POSTERIOR
CHAMBER.
IT PROVIDES CONTRAST TO
POTENTIALLY CONTRIBUTE TO
HEMODYNAMIC ANALYSIS.
THIS IS MD/PHD STUDENT
CONTRIBUTE ON THE STUDY.
TAKE A B SCAN, FROM THE B SCAN
IMAGE TAKE A VESSEL SCAN.
ACROSS THE WHOLE BANDWIDTH OF
THE NANOMETERS TAKE A SHORTER
BAND AND PERFORM TRANSFORM OF
SHORTER BANDWIDTH, THE DOWN SIDE
FOR THE SHORTER BANDWIDTH, THE
UPSIDE IS WE HAVE SPECTROSCOPY
INFORMATION.
BY ANALYZING WITH KNOWN SPECTRAL
INFORMATION OF HEMOGLOBIN WE'LL
BE ABLE TO MAP CAPILLARY --
OXYGEN CONCENTRATION IN BLOOD
INDIVIDUAL VESSELS.
SO, ONE OF THE KEY DEMONSTRATION
IS HOW WE VALIDATE THAT.
WE CAN SAY RANDOM NUMBER FOR
CAPILLARY, WHETHER TRUE OR NOT.
WE STUDY -- THIS STUDY HAS BEEN
PAINFULLY DRAGED FOR A NUMBER OF
YEARS BEFORE WE FOUND IT'S TRUE.
BOTTOM RIGHT FIGURE, HORIZONTAL
AXIS IS THE OXYGEN PRESSURE WE
CONTROL OF SMALL ANIMAL.
WE CONTROL THE INHALATION
CONCENTRATION OF OXYGEN TO THE
ANIMAL.
PRESSURE DROP.
WE PROVIDE LESS FROM LEFT TO
RIGHT.
IF WE READ THE CURVE CAREFULLY
WE PROVIDE LESS OXYGEN THE ICON
SUPERVISORS MORE.
IN THE VERY BEGINNING WE SAID
SOMETHING MUST BE WRONG.
WE PROVIDE LESS OXYGEN HOW COME
THE EYE CONSUMES MORE.
THROUGHOUT THE 30 YEARS OF A
CAREER HE MASTERED TECHNOLOGY
USING ELECTRODES TO MAP OUT
PARTIAL PRESSURE OF OXYGEN AT
DIFFERENT LAYERS OF THE RETINA.
USE FORM AN ANALYTICAL MODEL,
USING CHOROIDAL CONCENTRATION,
CHANGE BOUNDARY CONDITION, USING
THE MODEL, TO ESTIMATE WHETHER
THE OCT MEASURES OXYGEN
CONSUMPTION MAP WITH BIAS,
CALIBRATABLE BUT THE TREND SHOWS
THE SAME THING.
AT THE END IT WAS VERY EASY
EXPLAINABLE IS MEASURED IN
RETINAL CIRCULATION, SUPPORTED,
MAJORITY OF THE OXYGEN SUPPLY
COMES FROM CIRCULATION WITHOUT
ACTIVE VASOCONSTRICTION OR
VASODILATION FEEDBACK.
WHEN WE SUPPLY LESS OXYGEN, THE
SYSTEMIC SUPPLY BECAME LESS.
NOW, INNER RETINAL CIRCULATION
HAS TO COMPENSATE FOR THE OXYGEN
SUPPLY IN ORDER TO MAINTAIN
DEMAND.
ANOTHER STUDY WE CONDUCTED TOO
USE TYPE 1 DIABETIC MOUSE WITH
GENE KNOCKOUT.
BY WEEK 25 THIS GROUP OF MOUSE
WILL SHOW CAPILLARY DROPOUT
WHICH MEANS HAS A PHENOTYPICAL
ALTERATION CAUSED BY DIABETES.
WE IMAGED THEM AT 7, 9, 11, 13
WEEK, WE SHOW THE TWO GROUPS OF
ANIMALS GROW AS EXPECTED,
DIABETIC ANIMAL HAS HIGH GLUCOSE
CON TRYINGS, NO CAPILLARY CHANGE
AT ANY TIME.
THE CELL COUNTS ARE THE SAME
BETWEEN THE TWO GROUPS.
BUT THE METABOLIC DEMAND BECAME
SPECIFICALLY SIGNIFICANT BY WEEK
11.
SO WHICH MEANS IF WE TAKE THE
OCT ANGIOGRAM, OCT IMAGE OF THE
TWO GROUPS OF ANIMALS, THOSE ARE
BOTH HEALTHY.
USING METABOLIC IMAGING, WE SHOW
THAT THE INNER RETINAL
CIRCULATION IS ALREADY PROVIDING
MORE OXYGEN SUPPLY TO THE EYE,
MAY BENEFIT HYPOTHESIS TEST AS
THE ISCHEMIC DRIVEN PROCESS
START WAY EARLY THAN ANY
CAPILLARY DROPOUT.
SO, NOW, EVENTUALLY WE WANT TO
PUSH TO THE HUMAN STUDY.
WE HAVE TO MAKE SURE IT'S SAFE.
VELOCITY USED AROUND TEN, 100 TO
A QUARTER OF MILIWATTS,
MICROWATTS, MEASURED CLINICAL
DEVICE THAT ACCESSIBLE, IN THE
HOSPITAL, COMPARABLES.
WE'RE WELL WITHIN THE SAFETY
RANGE.
AND FDA PROVIDES NON-SIGNIFICANT
RISK WHEN WE PROVIDE ALL.
WE APPRECIATE THE HELP FROM NIH
THAT SUPPORTED TECHNICAL
ITERATION YEAR AFTER YEAR AFTER
YEAR.
LIKE PROFESSOR FUJIMOTO
MENTIONED, THIS IS A SLOW
PROCESS, TRANSLATING ANYBODY TO
THE LAB REQUIRES MULTIPLE YEARS
OF EFFORT AND CAN BE EXPENSIVE.
IN 2015 WE VIEWED THE FIRST
PROTOTYPE, ONLY LAB MEMBERS WERE
BRAVE ENOUGH TO BE SCANNED.
2016 MACHINES WERE BEING
PACKAGED TO A BIG CABINET SO CAN
BE MOVED TO HOSPITAL FOR PATIENT
SCANNING.
2017 MY START-UP COMPANY VIEWED
FIRST PROTOTYPE, 2018 THE SECOND
GENERATION WAS INSTALLED AT
PROFESSOR SCHUMAN'S LAB AT NEW
YORK.
AND YEAR AFTER YEAR WE KEEP
ITERATING.
WE ONLY HAVE SEVEN PEOPLE,
REINVENTING THE WHEEL THAT
OTHERS ARE DOING, I DON'T KNOW
HOW BIG THE TEAMS ARE.
SO G.E. CONTRIBUTED TREMENDOUSLY
TO THE SO JI CONTRIBUTED, NOW
AT HOPKINS, AND WE ALSO COMPARED
THE IMAGE UNDER THE SAME NUMBER
OF B SCAN AVERAGES.
THE DOWN SIDE CLEARLY IS WE
CANNOT GO BEYOND RPE BECAUSE
PIGMENTATION BLOCKS VISIBLE
LIGHT, ALMOST A HARD LIMIT FOR
VELOCITY.
THESE ARE FINE LAYERS NOT EASILY
DIFFERENTIATABLE BY INFRARED
LIED.
THIRD ONE, THE PROFESSOR ACQUIRE
THE SAME SUBJECT, WITHIN SAME
HOUR BY VELOCITY, AND FOR
LEADING CLINICAL DEVICES.
THE
AT THE TIME IT WAS NOT THE MOST
ADVANCED SIGNAL PROCESSING,
OPTICAL DESIGN FOR DEVELOPS ON
VELOCITY BUT BENEFIT FOR HIGH
CONTRAST AND RESOLUTION IS
OBVIOUS IN MY OPINION.
NOW HERE'S THE MAJOR TECHNICAL
BARRIER THAT WE FACE AT THE
TIME, WAS IF WE HAVE A SLOW
RATE, 20 KILOHERTZ, EVERYTHING
FINE.
THIS JUST TWO SLOW FOR ANY HUMAN
IMAGES.
PUSH TO HIGHER SPEED, SO 125 IS
COMMONLY USED FOR VELOCITY.
WHY THAT'S THE CASE, INTRINSIC
NOISE ASSOCIATED WITH NON-LINEAR
GENERATION OF BROADENING CAUSED
BY FEMTO SECOND, PICO SECOND
LASER, SIGNALING INTENSITY, WE
CANNOT PUMP MORE ENERGY WITH THE
HOPE OF SUPPRESSING THE NOISE.
THE MORE ENERGY WE APPLY, THE
MORE NOISE WE END UP WITH.
SO ONE TEAM MEMBER GENIUSLY
DESIGNED A BALANCE DETECTION OF
ARCHITECTURE.
IN OTHER WORDS, A TYPICAL IS
INTEGRATED.
IN OTHER WORDS, THE DELAY LINE
IS USED BY A TRANSMISSION, AND
RETURN LIGHT AND DELAY LINE GOES
THROUGH 50-50 INFLAMMATORY SO
SPECTROMETERS ACQUIRE OPPOSITE
PHASE INTERFERENCE WHICH HAS TO
BE THE CASE BECAUSE ENERGY
CALIBRATION, IF WE CALIBRATE TWO
CAREFULLY THE OPPOSITE PHASE
CANCEL THE NOISE.
I'LL SHOW HOW IT'S GOING TO
WORK.
THE BRIGHT BACKGROUND IS CAUSED
BY THE GREEN NOISE.
GREEN NOISE IS DOMINANTLY CLOSER
TO ZERO LINE POSITION.
SO IN OTHER WORDS, THE PERFECTLY
CALIBRATED SPECTROMETER AT THE
SUBPICO METER ACCURACY WILL
PROVIDE ALMOST PERFECT NOISE
CANCELLATION TO REACH A NOISE
LIMIT.
HERE IS ANOTHER CASE, WITH AND
WITHOUT DETECTION.
WHAT WE'VE DONE IS BY REDUCING
THE NOISE WE CAN AFFORD TO GO
HIGHER SPEED.
BY PUSHING THE SPEED TO A HIGHER
LEVEL, WE CAN AFFORD TO HAVE A
LARGER FIELD OF VIEW, MORE
SELECTABLE IN DESIGNING SCANNING
PROTOCOLS.
AND THIS IS A SCANNING-EM IMAGE
FROM A STANFORD TEAM OF A
MONKEY, IT SHOWS THE FIBER
BUNDLE MAP OF THE FUNDUS.
WE SHOW ALMOST IDENTICAL BUNDLES
IN HUMANS, IT PROVIDES
TREMENDOUS OPPORTUNITY TO
ANALYZE FIBER DENSITY, FIBER
ORIENTATION, POTENTIALLY
CORRELATE WITH VISUAL FIELD.
IN ORDER TO FACILITATE
COLLABORATION ACROSS THE
COUNTRY, OUR TEAM WITH SUPPORT
FROM NIH PUT TOGETHER SOFTWARE,
INTEGRATE ALL THE LATEST
TECHNOLOGY DEVELOPMENT WE HAVE
DONE IN THE LAB, IT TO
PYTHON-BASED FREEWARE.
THE RED DOT REPRESENT THE LABS
IN HOSPITALS ACQUIRED A FROM US,
MY START-UP COMPANY.
BLUE DOTS REPRESENT LABS AND
HOSPITALS DOING TECHNOLOGY
DEVELOPMENT.
THIS IS ONLY THE U.S.
I'M NOT INCLUDING ASIA AND
EUROPEAN COUNTRIES.
IT'S GROWING.
TRYING TO PROVIDE MORE
STANDARDIZED DATA PROCESSING
WILL HELP TECHNOLOGY TO BE
BETTER ADAPTED.
SO WHAT'S THE FUTURE TECHNOLOGY,
TECHNICAL AND CLINICAL
DEVELOPMENT?
WE HAVE TO WORK WITH -- WE AS
ENGINEERS HAVE TO WORK WITH
BIOLOGISTS AND CLINICIANS TO
IDENTIFY FUNCTIONAL BIOMARKERS
AGAINST ACTUAL DISEASE
MANAGEMENT.
WE WANT STANDARDIZED PROTOCOL SO
STABILITY WON'T BE AN ISSUE.
WE'LL TRY TO PROVIDE MORE ROBUST
USER-FRIENDLY DEVICES, AND WE
TRY TO -- WORKING WITH WHOEVER
WILL BE INTERESTED TO BROADEN
THE TECHNICAL IMPACT.
AGAIN, THIS IS THE BEGINNING.
WE TRY OUR BEST TO PUSH
TECHNOLOGY FORWARD WITH ALL THE
HELP FROM NIH AND MY
COLLABORATORS.
THANK YOU VERY MUCH.
[APPLAUSE]
>> LAST TALK IN THE SESSION IS
XIAORONG LIU, ASSOCIATE
PROFESSOR OF BIOLOGY AND
PSYCHOLOGY AT UNIVERSITY OF
VIRGINIA.
>> MY TALK IS A CONTINUATION.
WE'RE INTERESTED TO DEVELOP A
NOVEL BIOMARKER FOR RETINAL
GANGLION CELL DAMAGE.
YOU ALL KNOW RETINAL NEUROFIBER
LAYER CONTAINS THINGS IN
ADDITION TO AXON BUNDLES,
CELLULAR STRUCTURES, STARTING
IDEA WAS SIMPLE.
IF WE CAN VISUALIZE INDIVIDUAL
AXON BUNDLES MAYBE WE'LL HAVE A
BETTER IDEA WHAT'S GOING WITH
RGC.
WE STARTED IN MICE.
AS YOU KNOW, IN MICE IT'S MOST
WIDELY USED RESEARCH ANIMAL
MODELS, BECAUSE OF THE
AVAILABILITY OF GENETIC DISCERN
AND EYE DISEASE MODELS.
WE TAKE RETINA OUT, FLATTEN, CUT
TO FOUR LEAVES, STAIN TO EXAMINE
HOW GANGLION CELLS SURVIVE OR
DIE IN DIFFERENT CONDITIONS.
THEY ARE STAINED IN THIS CASE,
TRANSCRIPTION FACTOR, EACH DOT
REPRESENTS ONE SINGLE RETINAL
GANGLION CELL.
IF WE CHANGE THE FOCUS SLIGHTLY
TO THE MORE SUPERFICIAL LAYER,
THE RETINAL GANGLION CELL ON THE
TOP FACING UP, IF WE CHANGE THE
FOCUS A LITTLE BIT WE CAN SEE
NERVE FIBER LAYER IN MICE.
BLOOD VESSELS ARE STAINED IN
RED.
IN BETWEEN BLOOD VESSELS YOU CAN
SEE FIBER BUNDLES.
THESE ARE STAINED BY SMI-32,
MARKER FOR SMALL GROUP OF
RETINAL GANGLION CELLS.
WE CAN SEE THESE WELL IN EX VIVO
CONFOCAL IMAGES.
NOW CAN WE SEE IT IN VIVO?
WE USE A SYSTEM BUILT BY HAO
ZHANG'S COMPANY, RODENTS, MICE
NEED TO BE ANESTHETIZED, TAKE A
PICTURE, USE THE BLOOD VESSELS
AS LANDMARKS.
WE CAN ALIGN THEM, MUCH BIGGER
FIELD OF VIEW.
AS WE SCAN THROUGH THE EYE WE
COLLECTED B SCANS, FOCUS ON TOP
SUPERFICIAL THICKNESS LAYER.
YOU CAN SEE BLOOD VESSELS.
OPTIC NERVE HAT, AT THE CENTER
IN BETWEEN THE VESSELS YOU SEE
THE FIBERS.
SAME EYE, NOW WE PROCESS FOR
NERVE FIBERS.
THEN WE CAN USE AGAIN THE BLOOD
VESSELS, THIS IS ONE OF THE
FIRST GROUP OF IMAGES WE
COLLECTED FROM MICE IN 2019, AND
THIS GIVE US THE CONFIDENCE FOR
THE FIRST TIME, WE PROBABLY CAN
SEE THE INDIVIDUAL AXON BUNDLES
IN VIVO.
SO THIS IS JUST PUT IN A 3D
RENDERING, A MOUSE RETINA, AND
OPTIC NERVE HAT, AND STARTING
FROM THE BOTTOM THESE ARE THE
CHOROID RPE, MICE ARE NOCTURNAL,
THEY HAVE A LOT OF
PHOTORECEPTORS, THEY DON'T HAVE
MANY CONES, AND ROUGH LAYER OF
30 LAYERS, THEN GO UP.
I WANTED TO POINT OUT FOR MOUSE
RETINA THEY DON'T HAVE MANY
RETINAL GANGLION CELLS.
YOU BARELY SEE A REAL BAND OF
GCL.
BECAUSE THEY DON'T HAVE MANY,
DEPENDING ON SPECIES, SOME
VARIATIONS, COMPARED TO HUMAN
EYES WE HAVE A MILLION CELLS.
WHAT YOU SEE HERE IS THAT'S
PROBABLY JUST ONE SINGLE LAYER
OF SOMA, TIGHTLY SQUEEZED IN
FIBERS AND AXON BUNDLES.
BLOOD VESSELS AS YOU NOTICED
CAST DARK SHADOWS, IN BETWEEN
BLOOD VESSELS YOU CAN SEE
INDIVIDUAL AXON BUNDLES OVER
THERE.
AND SO WE DID A SCAN, WE CALL
THIS B SCAN, OPTIC NERVE HAT, AT
THE CENTER DO ADJUSTMENT TO MAKE
SURE WE SCAN ALL THE AXON
BUNDLES AT THE SAME ANGLE.
SO THIS IS MOUSE EYE, RADIUS
AROUND 350 MICRO METER.
YOU CAN SEE INDIVIDUAL AXON
BUNDLES RATHER THAN PIXELATED
LAYER.
THIS GIVE US THE -- MAKES US
FEEL WE CAN QUANTIFY ALL
DIFFERENT CHANGES.
THIS SHOWS EXAMPLE, DISTRIBUTION
OF THE AXON BUNDLE HEIGHT RATHER
THAN SPECIFICALLY IN C57 BLACK.
THEY ARE LOOSELY PACKED IN THE
RNFL, A SINGLE LAYER, ROUND
SHAPE, AND SO WE TRACKED THE
CHANGES OF INDIVIDUAL BUNDLES,
ALSO IN CHRONIC MODELS OF OCULAR
HYPERTENSION.
THE IDEA WE CAN QUANTIFY THE
NUMBERS, PATTERNING, THE SIZE OF
AXON BUNDLES, CORRELATED WITH
GANGLION CELL DENSITY, WHICH I'M
NOT GOING INTO DETAILS TODAY.
SO FAR, ALL THE IMAGES ARE IN
VIVO, AS YOU CAN IMAGINE PEOPLE
WILL ASK US FOR VALIDATION.
ESPECIALLY FOR FIBRO GRAMS,
HEAVILY PROCESSED IMAGES.
WHAT WE DID IS TAKE IN VIVO
IMAGE BY VISIBLE LIGHT,
SACRIFICE THE ANIMAL, TAKE THE
RETINA OUT, FLAT MOUNT, STAIN
FOR MARKER FOR AXONS.
AND IF WE ZOOM IN, WE CAN MATCH
EVERY SINGLE FIBER FROM IN VIVO
PICTURE TO CONFOCAL PICTURE, ONE
TO FOUR ARE AXON BUNDLES, FIVE
THROUGH SEVEN ARE BLOOD VESSELS.
ON THE RIGHT BLOOD VESSELS ARE
DARK BANDS IN BETWEEN.
YELLOW-- ORANGE ARROWS POINT TO
FIBERS.
FOR EXAMPLE, THE NUMBER 1 AT THE
BOTTOM WE CAN MATCH FIBER TO
FIBER, DIAMETER FOR THAT FIBER
IS ABOUT 8 MICROMETERS.
WE ALSO SHOW THIN LINE, NUMBER
3, 2.5 MICROMETER DIAMETER.
SO, SO FAR WE FEEL LIKE YES WE
ESTABLISHED ESPECIALLY TO IMAGE
THE FIBERS IN THE RNFL LAYER.
MOUSE EYES ARE SIMPLE.
THEY DON'T HAVE STRUCTURED OPTIC
NERVE HAT, AND THE AXON BUNDLES
ALSO PASS INNED RNFL, MANY
FEATURES WE'D LIKE TO STUDY MICE
DO NOT HAVE.
WE'RE LOOKING FOR ANIMAL MODEL
TO BRIDGE MOUSE RESEARCH WITH
CLINICAL RESEARCH.
SO, WE STARTED TO IMAGE THIS
MODEL, THREE SHREW.
SMALL NUMBER OF PAPERS PUBLISHED
TO STUDY NOT ONLY EYE
DEVELOPMENT, ALSO DISEASE, ALSO
VISUAL PATHWAYS FROM EYE TO
BRAIN, COMPARE MOUSE EYES, TREE
SHREW EYES ARE MUCH BIGGER,
8-MILLIMETER VERSUS 3.
IF WE FLAT MOUNT, SAME SCALE,
MOUSE EYES ARE REALLY SMALL.
AND BOTH ARE STAINED FOR 2G-1.
ON THE LEFT YOU CAN SEE FIBERS
ARE VERY LOOSE, CONVERGE TO THE
CENTER OF OPTIC NERVE HAT.
FOR TREE SHREW EYES MUCH BIGGER.
YOU CAN SEE FIBERS TIGHTLY
PACKED NEXT TO EACH OTHER.
LEFT SIDE IS OCT FIBROGRAM, SAME
EYE WE USED BLOOD VESSELS AS
MARKERS SO WE CAN ALIGN THEM IN
VIVO VERSUS EX VIVO.
AND THERE ARE MUCH MORE FIBER
BUNDLES.
AXON COUNTING WAS DONE.
TREE SHREW EYES HAVE 300,000
GANGLION CELLS, WE MUCH MORE
THAN MOUSE EYES.
WAY MUCH MORE THAN MOUSE EYES.
WE COMPARE B SCANS SIDE BY SIDE,
TREE SHREW EYES, MOUSE EYES ON
THE RIGHT.
YOU CAN SEE CLOSER TO OPTIC
NERVE HAT, AXON BUNDLES GOT
ELONGATED VERTICALLY, MUCH
THICKER COMPARED TO MOUSE EYES,
SIMPLE SHAPE AXON BUNDLES.
EVEN THOUGH THEY LOOK LIKE THERE
MIGHT BE LAYERS, I THINK IT'S
STILL ONE SINGLE LAYERED AXON
BUNDLES BECAUSE THIS IS A
DEVELOPMENTAL ISSUE AS THE AXONS
STARTED TO GROW.
THEY NEEDED TO FIND A PATH WHERE
TO GO INSTEAD OF CIRCLING AROUND
IN RETINA EARLIER BEFORE THEY
REACH TO OPTIC NERVE HAT.
THEY NEED TO CRAWL A INNER
SURFACE, AS MORE CELLS JOIN IN
TOWARDS THE CENTRAL AREAS, THEY
KEEP HOLDING NEW AXON ON TOP OF
EACH OTHER.
PERIPHERAL, YOU SEE BUNDLES ARE
GETTING MORE ROUND SHAPE, TAKING
UP MORE SPACE.
WE ALSO DID VALIDATION CONFOCAL
IMAGING, NOT EXACTLY THE SAME
LOCATION, THEY ARE THE SAME
EYES, ONE THING WE CANNOT DO
CIRCULAR SECTION FOR CONFOCAL
IMAGING.
ALSO FOR TREE SHREW EYES, THEY
ARE TOO BIG, HARD TO MATCH
IDENTICAL LOCATION FROM IN VIVO
TO EX VIVO.
GRAY SIGNAL FROM 2J-1,
VERTICALLY ELONGATED BUNDLES.
BLUE SIGNALS, NUCLEAR EYE.
FOR MOUSE A THICK LAYER, FOR
TREE SHREWS THEY ARE DIURNAL,
AND NOT AS THICK AS MOUSE EYES.
WE FOCUS ON INNER RETINA.
LEFT SIDE IN VIVO IMAGE, RIGHT
SIDE IS CONFOCAL.
ON THE LEFT SIDE YOU CAN SEE
INDIVIDUAL AXON BUNDLES
VERTICALLY ELONGATED.
NOW WE HAVE A GANGLION CELL
LAYER, DARK BANDS, THREE TO FIVE
SOMA LAYERS, TWO MARKERS.
AND NOW WE CAN SEE SUBLAYERS.
THIS COULD BE INTERESTING FOR
GLAUCOMA, EARLY INDICATOR FOR
GANGLION CELLS DEATH.
WHEN CELLS START TO DEGENERATE,
TREES WILL RESHAPE, START TO
MODEL, MAY CHANGE THE
SUBSTRUCTURE.
SO TISSUE WILL GIVE US POTENTIAL
TO MONITOR ALL THE SUBTLE
CHANGES, ESPECIALLY AT EARLIER
STAGE OF DISEASE.
WE WILL START TO DEVELOP TREE
SHREW OCULAR HYPERTENSION MODEL,
AND THEN WE CAN MONITOR ALL THE
DIFFERENT STRUCTURES IN THE RNFL
GANGLION LAYER AND IPL TO
QUANTIFY AND TRACK ALL THE
CHANGES WITH DISEASE
DEVELOPMENT.
WE SUBMITTED THIS MANUSCRIPT
LAST YEAR, I STATED TREE SHREW
REPRESENT MODEL BETTER TO HUMAN
EYES.
REVIEWERS ASK, YOU'VE GOT TO
SHOW THE HUMAN DATA.
WE STARTED IN COLLABORATION WITH
PETER NETLAND AT UVA.
THIS STARTED RIGHT AFTER COVID,
THAT'S OCT TRADITION FROM JAMES
FUJIMOTO, WHOEVER BUILD A SYSTEM
WILL BE TESTED FIRST.
OUR EYES ARE NOT GOOD.
OLD EYES WITH ALL KINDS OF
THINGS, MYOPIA, NOT EASY TO FIND
A FLATTENED AREA.
WE MOVED DOWN FROM THE P.I.s,
POSTDOCS, GRADUATE, JUST
GRADUATED FROM COLLEGE, GOT THIS
BUILT, THE DARK CENTER IS THE
FOVEA.
YOU CAN SEE FIBERS CURVE AROUND
THE FOVEA.
YOU PROBABLY HAVE SEEN THIS
PICTURE, FREE HAND DRAWING OF
THE HUMAN FOVEA FIBERS.
YOU MIGHT KNOW THIS.
AT THAT TIME I WAS RESEARCHING
TO FIGURE OUT WHO DID THIS
BEAUTIFUL PICTURE, AND I FOUND
ALL KIND OF REVIEWS, DIFFERENT
VARIATIONS, NOT SURE WHERE IT'S
FROM UNTIL I TALKED TO MY
POSTDOC, DAVE, UCSF.
HE GIVE ME THIS BOOK, HISTOLOGY
OF THE HUMAN EYE.
IN THE BOOK WE FOUND THIS
PICTURE.
DR. WILLIAM HOYT, WHO WE SEE HIS
COLLEAGUES, 1960 IT'S AND '70s
BASEED ON SUPER STAINING OF
POSTMORTEM HUMAN EYE DID THIS
FREE HAND DRAWING.
AND DAVE WAS GENEROUS ENOUGH TO
GIVE ME THE BOOK, BUT THAT BOOK
CONTAINS THIS INTERESTING NOTE.
HE TOOK IT, AND MATT RETIRED, IF
YOU SEE THIS, SORRY MATT, BUT
THANK YOU DAVE, THIS WORK IS
MINE NOW.
I WILL SUMMARIZE AND CONCLUDE.
WE STARTED OUT WORK FROM MICE.
IT'S BEEN WONDERFUL
COLLABORATION WITH HAO ZHANG AND
GROUP, WORK IN COLLABORATION
BETWEEN MY POSTDOC FELLOW MARTA
WHO DID ALL THE IMAGING,
INCLUDING MOUSE TISSUE AND
HUMAN, AND DAVE MILLER WHO
GRADUATED FROM ZHANG'S LAB, WHO
DID THE COATING, COLLABORATING
NOW WITH MY STUDENT, AND THE
BEAUTIFUL CONFOCAL IMAGES, AND
THE TREE SHREW COLONIES AT UVA,
THAT'S GRACE.
AND FINALLY TWO CLINICIANS, DR.
NETLAND AND DR. COSTE UVA
OPHTHALMOLOGY.
AND FINALLY THE FUNDING.
THANK YOU ALL.
[APPLAUSE]
THANKS TO ALL THE SPEAKERS.
YOU'RE ALL ON TIME.
NOW YOU HAVE A CHANCE TO SIT IN
FRONT OF THE ROOM AND STAKE
QUESTIONS FROM THE AUDIENCE.
I'M GOING TO BE A QUESTIONER SO
I'M GOING TO BE ON THIS SIDE.
ANY QUESTIONS FROM THE AUDIENCE?
IF NOT, THINK ABOUT SOME.
THERE'S A HARD STOP AT 1:00.
AND IF -- YOU CAN GO AHEAD.
>> WONDERFUL TALKS, REALLY
AMAZING TECHNOLOGY.
I'M BLOWN AWAY EVERY TIME.
I HAVE A QUESTION.
WHEN SHOWING TRANSITION ZONE, IN
YOUR RP PATIENTS, WHAT -- IS
THERE ANY CHANCE THOSE ARE
MIGRATING RP CELLS, ROD OUTER
SEGMENT, HOW DO YOU KNOW?
CAN YOU TELL US MORE ABOUT THAT?
>> YES, ABOUT THE TRANSITIONS,
CERTAINLY WITH THE RPE CELLS, WE
CAN FIND IF YOU -- IF YOU FIND
THOSE, IF YOU GO OUT FARTHER
BEYOND TRANSITION ZONE YOU START
TO SEE THEM LIFT OFF CLUMPS OF
RPE CELLS, COME INTO THE INNER
RETINA.
THOSE HAPPEN LATER IN THE
PROCESS, NOT WITHIN THE
TRANSITION ZONE THAT WE FIND.
WE DO SEE RODS IN THE --
>> (INAUDIBLE).
>> WE DO SEE RODS IN THERE.
WE DISCOUNT THEM, THE OUTER TIP
OF RODS, THEY GO ALL THE WAY
DOWN TO THE TOP OF THE RPE,
FURTHER DOWN THAN THE CONE OUTER
TIP, WE CAN SEPARATE THOSE OUT.
IF THEY MESS IN THERE, IT'S A
REAL MESS, YOU LIKE WORKING WITH
NORMAL RETINA, YOU GET TO THE
DISEASE AND YOUR HEART SINKS BUT
WE'RE WORKING THROUGH THAT.
THAT WAS A PROJECT THERE.
>> WE HAD SIMILAR OBSERVATION,
RELATIVELY HEALTHY, YOU CAN
SEGMENT OUT LAYERS FROM CONES
AND RPE AND DEEPER LAYERS AS
WELL BUT IN DISEASED CONDITIONS
SUPER HARD, YOU CAN SEE RPE
CELLS.
LAYERS STILL THERE.
OVER THE TIME, ESPECIALLY IN THE
LATE STAGE OF THE DISEASE
DEVELOPMENT, YOU CANNOT SEE RP
CELLS MIGRATE AND FORM A LAYER
WHETHER YOU CAN IDENTIFY THE
CELLS ABOVE THE NORMAL RPE
LAYER.
YOU CAN COUNT THEM AND MAP OUT
THEIR MORPHOLOGY.
WE BELIEVE THOSE ARE RPE ELSE
BUT BECAUSE THE RETINA IS SO
MESSED UP IT'S HARD.
>> YOU SHOULD MAKE COMMENT WE
USE ORG SIGNAL TO SEPARATE OUT
RODS FROM CONES, SO THE RODS
HAVE A SEPARATE DISTINCT ORG
SIGNAL.
THAT HELPS US, IF THERE'S A
SHORT ROD, --
>> IT IS DIFFICULT TO HEAR
QUESTIONS FROM THE MICROPHONE
BECAUSE OF THE ECHO.
IF THEY ASK YOU TO REPEAT,
REPEAT SLOWLY OR MAKE THE FIRST
QUESTION SLOW.
>> MY QUESTION FOLLOWS CLOSELY
ON AMIR'S.
CAN YOU HEAR ME OKAY?
I AM FOLLOWING UP ON AMIR'S
QUESTION.
I GUESS SINCE WE FIRST STARTED
OBSERVING THESE THINGS, IN YOUR
GROUP, DON, IT'S BEEN ISO COST,
YOU'RE SHOWING IMAGES EVEN IF
THE REFLECTIONS OVERLAP NO
GUARANTEE IT'S ISO OR COST.
CLINICIANS ARE GOOD AT LOOKING
AT IMAGE, THIS LOOKS SICK TO ME,
BUT FROM MY PERSPECTIVE, I HAVE
NO IDEA UNTIL WE PUT NUMBERS,
IT'S HARD TO SAY MUCH.
DO YOU THINK -- ARE THERE
PROSPECTS FOR QUANTIFICATION OF
ORG OR MORPHOLOGICAL
QUANTIFICATION AGNOSTIC TO THE
CHANGES OR, YOU KNOW, YEAH
MORPHOLOGICAL CHANGES SEEN IN
DISEASE?
DO YOU THINK IT'S A AN AVENUE,
YOU KNOW --
>> YEAH, A LONG QUESTION, RAVI.
THE ONE THING WE WERE MAYBE
RELATED TO THAT WAS THOSE CONES
THAT HAD EXTRA REFLECTIONS IN
THEM THAT HAD KIND OF NORMAL
LENGTH IN RP WE THOUGHT IF WE
MEASURE THEIR ORG THAT THEY
WOULD BE REDUCED RELATIVE TO
THOSE CONES OF SIMILAR LENGTH
THAT DIDN'T HAVE EXTRA
REFLECTIONS.
WHAT GEORGE FOUND THERE WASN'T
ANY STATISTICAL DIFFERENCE
BETWEEN THE TWO.
SO THAT'S THE EXTRA COMPLICATION
HOW WE RELATE THE FUNCTIONAL
PART TO ANATOMICALLY WITH EXTRA
REFLECTIONS.
WHAT GEORGE FINDS WITH ORG IF
IT'S INSIDE OF WHAT WE THINK OF,
INTERPRETED CORRECTLY, THE OUTER
SEGMENT, THEN THE DEEPER THAT
REFLECTION IS IN THE OUTER
SEGMENT, THE STRONGER THE ORG
SIGNAL IS.
IF IT'S A SHORTER LENGTH, IT
WILL BE CORRESPONDLY REDUCED ORG
WITH THE UNIQUE SIGNATURE TO
IDENTIFY AS S,M, OR L CONE.
>> JOEL?
>> JOEL SCHUMAN.
FIRST OF ALL, GREAT TALKS.
AND I'D LIKE TO TAKE YOU TO THE
INNER RETINA.
SO, YOU'VE PRESENTED REALLY
BEAUTIFUL IMAGES OF THE RETINAL
GANGLION CELLS, AND YOU
PRESENTED REALLY NICE IMAGES IN
HUMAN EYES, LOOKING AT THE
RETINAL GANGLION CELL AXONS.
AND HAO, I'M SORRY I MISSED
YOUR TALK.
I WANT TO FIND OUT WHAT YOU
LEARNED IN TERMS OF GLAUCOMA
LOOKING AT RETINAL GANGLION
CELLS, LOOKING AT CELLS DAMAGED
IN THE DISEASE.
YOU SHOWED YOU COULD VISUALIZE
THESE CELLS, OVER TIME WHAT
HAPPENS TO THESE CELLS?
AND WHAT HAPPENS TO THE NERVE
FIBER BUNDLES WHEN YOU LOOK AT
IT WITH VISIBLE LIGHT OCT?
>> HELLO?
OKAY.
SO, WE DID SHOW A LOT OF BASIC
RESEARCH DONE IN ANIMAL MODELS,
ESPECIALLY IN MICE, GLAUCOMA
MODELS.
PEOPLE NOW REALIZE AGAIN IN
CELLS, THERE'S A SUBTYPE
DEPENDENT MANNER, LOCATION
DEPENDENT DIFFERENCES, AND ALSO
WHEN THEY DIE THEY DON'T JUST
DIE RIGHT OVER THERE.
DENDRITIC STRUCTURE CHANGES IN
IPL, SO MUCH CHANGES, AXON
RETRACTION, THEY COULD BE LIKE
DEPARTMENTALIZED DAMAGE TO ONE
INDIVIDUAL CELL, AND THERE'S
STILL A LOT WE NEED TO LEARN HOW
BUNDLES BREAK DOWN AND THERE'S
ONE INTERESTING DETAIL WE
NOTICED, THE LARGE BUNDLES TEND
TO BREAK DOWN TO SMALLER ONES AT
EARLIER STAGE OF GLAUCOMA.
BUT WE DON'T KNOW WHY AND HOW
THIS HAPPENS.
AND EVEN FOR AXON BUNDLES WE
KNOW -- WE DON'T KNOW WHY THEY
JOIN THIS BUNDLE, NOT THE OTHER
BUNDLE.
IT'S NOT TYPE SPECIFIC.
MAYBE LOCATION DEPENDENT, MAYBE
THIS IS DEVELOPMENTAL ISSUE.
STILL A LOT OF QUESTIONS WE NEED
TO LOOK INTO.
>> HOW THAT GOES INTO THE CELL
BODIES?
>> I CANNOT HEAR YOU.
>> HOW IS THAT GOING TO THE CELL
BODIES?
>> RDC SOMAS?
>> RIGHT, TO YOUR RIGHT.
>> DON OR ZHOULIN?
>> SO, THAT WAS A SMALL STUDY,
WE RECRUIT GLAUCOMA SUBJECTS,
PATIENTS, WE COMPARED RDC
MORPHOLOGY, ALSO DEMONSTRATED
DEMONSTRATED AND SHOWN?
SLIDES WE FOUND DENSITY DECREASE
WERE REDUCTION AND SOMA IN LARGE
IS CORRELATED WITH HEMIFIELD
DEFECT.
THAT MEANS THE DISEASE WHERE
CELL BODY REFLECTS DIFFERENT
STAGE OF THE DISEASE DEVELOPMENT
BECAUSE WE LOOK AT THE PATIENTS
WITH DIFFERENT STAGE OF THEIR --
ON THEIR DISEASE DEVELOPMENT.
YOU MEASURE THE NERVE FIBER
BUNDLES AS WELL.
ON THAT SLIDE WE DIDN'T
EMPHASIZE.
FIVE YEARS OUT, WE FOLLOWED SOME
OF THE SUBJECTS OVER TIME, OVER
THE FIVE YEARS PERIOD OF TIME.
BUT BECAUSE THE DATASET IS SO
HUGE, JUST COUNTING THE CELLS IS
REALLY TAKING A LOT OF TIME.
IN ONE SINGLE AO-OCT VOLUME YOU
MAY HAVE THOUSANDS OF CELLS,
JUST SMALL REGION, REALLY HAVE
TO DO KILLER JOB COUNTING THOSE
CELLS.
BUT OVER THE YEARS WE
COLLABORATED WITH OUR
COLLABORATORS LIKE DUKE
UNIVERSITY, TRY TO DEVELOP
MACHINE LEARNING-BASED AUTOMATED
MACHINE LEARNING ALGORITHM TO
AID FOR CELL COUNTING.
SO WE'RE GOING TO FIND OUT.
WE COLLECT THOSE DATA BUT HAVE
NOT YET HAD THE TIME TO
FINALIZE, ANALYZE THOSE DATA
YET.
>> THANK YOU.
>> I'LL LET YOU KNOW.
>> MAY I ADD ONE MORE.
WE'RE DOING A LONGITUDINAL STUDY
LOOKING AT GLAUCOMA, AND WE HAVE
SOMEBODY PRESENTING AT ARCO,
MACK KELLER.
WE'RE TRACKING THE SAME CELLS,
THEY DROP OUT AT A MUCH HIGHER
RATE THAN WHAT WE'RE FINDING IN
JUST NORMAL AGING, IN OUR CASES
WE PICKED LOCATIONS IN THESE
DEFECTS GOING INTO THEM.
WHEE
WE HAD TO BE EXTRA WHERE WE
PICK.
IN THOSE CASES WE'RE PICKING WE
DO SEE NOTABLY HIGHER RATE OF
SOMA LOSS, SUBCLINICAL, AND
MAKES OUR CLINICAL COLLABORATOR
NERVOUS, WORKING WITH THESE
PATIENTS.
>> CHRISTINE?
>> CONGRATULATIONS TO EVERYONE.
REALLY WONDERFUL TALKS.
I'D OF I HAVE QUESTIONS ABOUT
OUTER RETINA.
ONE IS A COMMENT.
THE OTHER IS A QUESTION.
THE COMMENT IS THAT THERE WAS A
PAPER IN EXPERIMENTAL EYE
RESEARCH ON AGING MONKEYS, AND
THEY HAD WHAT THEY CALLED WHITE
DOTS, IN THAT PLACE BETWEEN WHAT
I CALL EZ AND IZ.
I'M WONDERING IF THEY ARE THE
SAME THINGS YOU'RE SEEING IN
YOUR RPE PATIENTS BECAUSE THEY
MIGHT BE THE SAME PHENOMENON,
GOOD IF THAT COULD BE FOUND
BECAUSE IT'S AN AGING
PHENOMENON.
THAT'S THE FIRST COMMENT.
THE QUESTION WAS, ARE YOU ABLE
TO DETERMINE IF SOME OF THESE
PHENOMENA YOU'RE SEEING IN RPE
PATIENTS I HEARD TWO OF YOU SAY
THE RPE IS LEAVING A LAYER.
I'VE BEEN TO MEETINGS WHERE
PEOPLE WILL INSIST THOSE ARE
MACROPHAGES OR MICROGLIA WHO
CAME AND ATE RPE.
SO MY E.M., MAYBE THAT COUNTS,
MAYBE IT DOESN'T BUT HOW DO YOU
DISTINGUISH BETWEEN RPE AND RPE
MASQUERADING AND HOW SOON CAN
YOU DO THAT IF YOU CAN DO IT?
>> THAT'S TOUGH.
>> [OFF MICROPHONE].
>> YEAH, THAT'S BETTER, YEAH.
YEAH, WE GO TO ARVO.
I SEE PRESENTATIONS WHERE
MICROGLIA GO TO THE
PHOTORECEPTOR LAYER IN RPE
PATIENTS.
WE WERE ANXIOUS TO SEE IF WE
COULD DO AO-OCT ANGIOGRAPHY TO
SEE THE MOTION OF MICROGLIAL
CELLS EATING PHOTORECEPTORS
BECAUSE ADJACENT PHOTORECEPTORS
SHOULDN'T BE MOVING AROUND LIKE
MYOGLIA, SHOULD BE ACTIVE.
WE HAVEN'T SEEN THAT.
WHATEVER WE'RE DOING, WE'RE
MISSING THE MICROGLIAL DOWN
THERE.
THEY NEED TO BE DOWN THERE BUT
WE JUST HAVEN'T BEEN ABLE TO
DETECT SOMETHING.
SO, YEAH, WE CAN'T DO IT.
MAYBE ZHOULIN CAN.
>> CAN YOU TRACK THE DIFFERENT
PHENOMENA FROM MICROGLIA COMING
DOWN?
>> YEAH, WE CAN TRACK THAT.
>> MY ARGUMENT IS ALWAYS YOU
HAVE TO RECREATE THE BEHAVIOR
WHICH MEANS SOME OTHER CELL TYPE
HAS TO GET INTO THE LAYER,
PRETEND TO BE RPE AND HEAD UP.
CAN YOU SHOW THAT ONE WAY OR THE
OTHER?
I'M HAPPY TO BE WRONG.
>> WE CAN CERTAINLY SHOW THE RPE
MIGRATING UP.
I DON'T KNOW IF WE WOULD BE ABLE
TO PUBLISH IT THOUGH.
>> RICHARD?
>> YEAH, TWO QUICK QUESTIONS.
ONE FOR ZHOULIN AND ONE FOR DON.
FIRST OF ALL, ALL THESE
PRESENTATIONS WERE FANTASTIC.
LOOKING AT THE CHORIOCAPILLARIS
ARE YOU ABLE TO SEE ANY DYNAMICS
OF THE CAPILLARIES CONTRACTING
OR EXPANDING IN YOUR IMAGING,
AND CAN YOU WITHOUT -- IT'S
DIFFICULT WHEN YOU HAVE TO DO
ALL THAT AVERAGING BUT --
>> THANK YOU FOR THE QUESTION.
THIS IS A REALLY LIKE THE
PRELIMINARY OUTLIER COLLECTED,
DATA WE COLLECTED RECENTLY.
I THINK THE TECHNOLOGY WILL
ALLOW YOU TO TRACK LIKE THE
SHRINKAGE OF THE VESSEL, IF YOU
MONITOR THEM OVER TIME.
WE HAVEN'T DONE THAT TYPE OF
STUDY.
>> I DON'T HAVE ANYTHING TO ADD.
WE'RE WORKING, IT DOESN'T
PENETRATE WELL BEHIND THE
CHORIOCAPILLARIS.
WITH THE 750, THAT'S A NICE
SYSTEM.
>> WE PUBLISHED.
>> BUT WE DIDN'T PUBLISH THAT
ABOUT THICKNESS CHANGES.
YEAH.
>> AND JUST BRIEFLY HOW, I MEAN,
I THINK OBVIOUSLY WE'RE ALL
EXCITED WITH VISIBLE OCT FOR ITS
CAPABILITY OF LOOKING AT
METABOLIC CHANGE BUT IT'S VERY
BRIGHT
WHAT ARE YOUR STRATEGIES MOVING
FORWARD TO INCREASE THE
USABILITY FOR HUMAN SUBJECTS?
>> YEAH, THANKS FOR THE
QUESTION.
FOR THE BRIGHTNESS CAUSE
POTENTIALLY TWO ISSUES.
A, PATIENT EYE GOT TIRED AFTER
ALIGNMENT.
B, FOR ALIGNMENT TAKING TOO
LONG, THEY MIGHT TRIGGER
NEUROVASCULAR CAPILLARY CAUSING
METABOLIC FEATURES TO BE
CHANGED.
SO, THE TWO POTENTIAL SOLUTIONS,
ONE IS MAKING FASTER, SO LOTS OF
EFFORT TRYING TO PUSH FROM 20
KILOHERTZ TO 200 KILOHERTZ,
WE'RE AT 100 KILOHERTZ AT THE
MOMENT, 200 KILOHERTZ NOT THERE
YET.
MIGHT REACH 200 KILOHERTZ OR
HIGHER, WE'RE NOT THERE YET.
ANOTHER COMPROMISE IS DON'T USE
VISIBILITY UNTIL IT'S ABSOLUTELY
NECESSARY.
WE THINK WITHIN THE LAST TWO
LATEST ITERATIONS, PREVIOUS
VELOCITY, EVERYTHING IS DONE BY
NEAR-INFRARED CELL, SWITCH TO
OCT.
DOWN SIDE WAS THE TWO MODALITIES
ARE PERFORMED INCONSEQUENTIAL.
THERE'S A TIME DELAY, THE EYE
MAY MOVE.
BY CONSULTING WITH COLLABORATORS
AROUND THE COUNTRY, THE BETTER
SOLUTION FROM THE COLLABORATORS
ARE HAVING ALWAYS ON, INFRARED
FUNDUS, DON'T TURN ON VISIBILITY
UNTIL ABSOLUTELY NECESSARY.
FINISH ALIGNMENT, SHUT AND SCAN.
THAT'S IT.
TRYING TO MINIMIZE EXPOSURE,
THAT'S THE CURRENT SOLUTION,
TECHNICAL SOLUTION.
>> WE HAVE TIME FOR ONE LAST
QUICK QUESTION.
>> SIPS WE HAVE THE -- SINCE WE
HAVE TIME TO USE A.I. ANALYSIS
WE'VE LEARNED SO MUCH.
ONE IS THE EASY LAYER SEEMS TO
THIN OUT INTO JUNCTION ACTIVE
ZONE OF A LESION GROWTH.
THIS IS WHAT WE SEEM TO TO SEE
IN OCT.
>> I'M HAVING A LITTLE HARD TIME
HEARING.
WE HAVE NOT FOLLOWED THE EASY
THICKNESS SO THAT'S NOT KIND OF
A BIOMARKER WE'VE BEEN LOOKING
AT FOR THES.
SO I CAN'T PROVIDE ANYTHING BUT
I THINK JOLI NHAS A LOT OF
INSIDE, SHE'LL BE ABLE TO
PROVIDE --
>> WE HAVE TO WRAP IT UP BECAUSE
WE'RE GOING TO HAVE SOME LUNCH.
I THINK WE CAN JUST TAKE THESE
CONVERSATIONS OFFLINE.
>> IS IT THE LAST PHRASE?
>> YOU CAN INTERRUPT DAVID IF
YOU WANT, BUT YOU CAN'T
INTERRUPT ME.
>> I THINK WE HAVE TO GET TO
LUNCH RIGHT NOW, SO THANKS TO
EVERYBODY IN THIS SESSION.
IN TERMS OF LUNCH OPTIONS, THOSE
OF YOU WHO DID NOT PURCHASE A
BOX LUNCH MIGHT WANT TO MAKE
YOUR WAY DOWN TO THE CAFETERIA
THAT'S ONE FLOOR DOWN ON THE
B1 LEVEL.
THERE'S ALSO THE COFFEE SHOP
RIGHT OUTSIDE IN THE -- NEAR THE
BOOK STORE.
THERE'S ALSO ANOTHER KIND OF A
FAKE STARBUCKS THAT'S IN THE
ATRIUM OF THE MEDICAL CENTER
THAT'S JUST ABOUT A THREE-MINUTE
WALK AWAY.
AND LET ME ALSO MENTION THAT WE
PUT A MAP OF THE CAMPUS INTO THE
AGENDA, SO IF YOU WANT TO GO
BACK TO THE WEBSITE FOR THE
MEETING, AND ARE INTERESTED IN
THAT, YOU CAN GRAB THAT.
AND WE WILL RECONVENE AT
2:00 P.M.
SO 10 MINUTES LATER THAN
INDICATED IN THE PROGRAM, SINCE
WE'RE ENDING A LITTLE BIT LATE,
SO 2:00 P.M., LET'S BE READY TO
GO IN HERE.
THANKS, EVERYBODY.
[APPLAUSE]
[SPEAKER NOT ON MIC]
[WAITING FOR AUDIO FEED]
[NO AUDIO]
KIND OF LIKE DIABETES.
SO WE WONDERED WHETHER WE CAN
USE OCTA TO TRY TO ASSESS
CHANGES THAT MIGHT PREDISPOSE TO
VASCULAR DEMENTIA, BECAUSE
DIABETES IS ACTUALLY ALSO A RISK
FACTOR FOR VASCULAR DEMENTIA.
AND THE REASON WE WANTED TO DO
THIS WAS BECAUSE SEVERAL
STUDIES, AND ONE I'M SHOWING
HERE, ON AN EPIDEMIOLOGIC LEVEL
HAD SHOWN THAT RETINOPATHY,
WHICH IS THE END STAGE OF
CAPILLARY DAMAGE, ACTUALLY
PREDICTS COGNITIVE IMPAIRMENT IN
A 10-YEAR STUDY.
SO IF YOU HAVE BASELINE LEVELS
OF RETINOPATHY, YOU'RE MORE
LIKELY TO HAVE SOME LEVEL OF
COGNITIVE IMPAIRMENT IN THE
SUBSEQUENT 10 YEARS AS MEASURED
BY YOUR ABILITY TO RECALL
CERTAIN WORDS OR TO MEMORIZE A
CERTAIN PATTERN.
AND SO THIS ALONG WITH THE IDEA
THAT WE CAN DETECT SUBCLINICAL
CHANGES IN THE RETINA, IN THE
RETINAL CAPILLARIES, MADE US
THINK THAT WE COULD ACTUALLY
GAIN SOME INSIGHT INTO VASCULAR
COGNITIVE IMPAIRMENT.
SO ONE OF MY POSTDOCS STARTED TO
LOOK AT A SMALL COHORT OF
PATIENTS WHO HAD BEEN WELL
CHARACTERIZED BY NEUROLOGISTS
AND NEUROPSYCHOLOGISTS FOR THEIR
COGNITIVE ABILITY, AND WE FOUND
THAT ACTUALLY WHEN WE LOOK HE AT
THESE COHORTS AND CDR SOME OF
THE BOXES HERE, THE ORANGE BOX
IS A MEASURE OF PEOPLE WHO
HAVE -- INDICATES PEOPLE WHO
HAVE SOME LEVEL OF COGNITIVE OR
BEHAVIORAL IMPAIRMENT.
AND BLUE REPRESENTS NORMAL.
AND WHAT YOU SEE IS THAT PEOPLE
WHO ARE ON THE LEFT SIDE OF THE
VESSEL SKELETON DENSITY SCUFER
THERE OR PLOT ARE THE ONES WHO
ARE ORANGE.
THE OTHER ONES WHO HAVE SOME
LEVEL OF COGNITIVE IMPAIRMENT.
AND IN FACT, THERE WAS A FOUR
FOLD INCREASED RISK OF HAVING
SOME LEVEL OF BEHAVIORAL OR
COGNITIVE IMPAIRMENT, THIS IS
SUBCLINICAL NOW, THESE ARE NOT
PEOPLE WHO ARE BEHAVIORALLY --
WHO ARE DIAGNOSED WITH A
CONDITION, BUT THEY'RE
COGNITIVELY IMPAIRED IN SUBTLE
WAYS, THOSE PEOPLE HAVE MUCH
LOWER VESSEL DENSITY.
THEY'RE IN THE LOWER TERTILE OF
THE CAPILLARY DENSITY.
THE DENSITY ACTUALLY CORRELATES
WITH COGNITION.
IT TOOK ME A LONG TIME TO WRAP
MY HEAD AROUND THAT.
BUT WE LOOKED IN LATIN
AMERICANS, WE'VE LOOKED IN BLACK
AMERICANS, WE HAVE A COHORT OF
CAUCASIAN AMERICANS NOW, AND
USING SEVERAL DIFFERENT MEASURES
OF COGNITION, INCLUDING NIH
TOOLBOX AND COGNITIVE
ASSESSMENT, WE'VE REPEATEDLY
DEMONSTRATED THAT THERE'S A
CORRELATION, SIGNIFICANT
CORRELATION BETWEEN CAPILLARY
DENSITY IN THE RETINA AND
COGNITIVE ABILITY.
IT'S NOT NECESSARILY DEMENTIA,
OR SEVERE COGNITIVE IMPAIRMENT,
BUT JUST COGNITIVE ABILITY.
AND SO THE IDEA THEN THAT WE ARE
ABLE TO DETECT PRE-CLINICAL
CHANGES IN TERMS OF WHAT'S
HAPPENING IN THE EYE AND WHAT'S
HAPPENING IN THE BRAIN SEEMS TO
REALLY HAVE TAKEN HOLD AT LEAST
IN MY MIND, AND SO I'M NOT GOING
TO TALK A LOT ABOUT THE
COGNITIVE WORK, BUT I'M GOING TO
TURN AND SAY -- SO WHAT IS THE
BIOLOGICAL SUBSTRATE BETWEEN
THINGS THAT ARE HAPPENING IN
RETINAL BLOOD VESSELS AND THINGS
THAT ARE HAPPENING IN THE BRAIN.
AND SO WHAT WE DID WAS
COLLABORATE WITH AN
EPIDEMIOLOGIST WHO'S WORKED A
LOT WITH LOS ANGELES LATINO EYE
STUDY AND AFRICAN AMERICAN EYE
DISEASE STUDY AND A POSTDOC TO
CORRELATE THE MEASURES OF
RETINAL CAPILLARY DENSITY WITH
INTRACRANIAL MEASURES OF
PERFUSION IN THE WHITE MATTER.
THESE ARE TWO SUCH MEASURES
PLOTTED HERE.
MEAN-FREE WATER IS A MEASURE
DERIVED FROM MRI SCANS AND
REFLECTS INTEGRITY OF WHITE
MATTER TRACKS, AND PEAK
SKELETONIZING DIFFUSIVITY IS
ANOTHER MEASURE OF WHITE MATTER
INTEGRITY.
AND THESE ARE USED KIND OF IN
THE NEUROLOGICAL WORLD TO ASSESS
WHITE MATTER DISEASE.
AND IN BOTH CASES, THOSE
MEASURES CORRELATED WITH BOTH
VESSEL SKELETON DENSITY IN THE
RETINA AS WELL AS VESSEL AREA
FLUX, OR THE FLUX MEASURES WHICH
I DESCRIBED TO YOU EARLIER, AND
THE REASON WHY I'M SHOWING YOU
THE FLUX MEASURES HERE IS
BECAUSE THEY WERE MORE
SIGNIFICANT AND MORE ROBUST THAN
THE SKELETON DENSITY MEASURES.
AND SO THE IDEA HERE I THAT THE
CHANGES THAT ARE OCCURRING IN
THE RETINAL KEAB LE CAPILLARIESE
OCCURRING IN THE BRAIN ACTUALLY
HAS A BIOLOGICAL SUBSTRATE IN
MEASURES OF WHITE MATTER
INTENSITY.
THE NEXT THING WE ACTUALLY
STARTED TO LOOK AT WAS TO SAY
WELL, WHAT ARE THE BIOLOGICAL
SUBSTRATES BEHIND THESE KINDS OF
CHANGES IN CAPILLARES, BOTH IN
THE BRAIN AND IN THE EYE, AND
THERE'S OBVIOUSLY MANY POTENTIAL
WAYS THAT THAT COULD WORK, BUT
ONE OF THE LEADING CONTENDERS TO
DRIVE SUCH CHANGES WOULD BE APOE
LIPOPROTEIN 4 WHICH IS A MAJOR
RISK FACTOR FOR VASCULAR
DEMENTIA, COGNITIVE IMPAIRMENT,
AS WELL AS FOR ALZHEIMER'S.
SO THE HYPOTHESIS IS THAT
PERHAPS PATIENTS WHO HAVE APOE
E4 ALLELES HAVE POSSIBILITY FOR
HAVING DECREASED OR ACCELERATED
CAPILLARY DENSITY LOSS OVER TI
TIME.
SO WE TEAMED UP WITH A NEWER
TOLL GIST AT UNIVERSITY OF
CALIFORNIA SAN FRANCISCO IN
THEIR MEMORY AND AGING CENTER
THERE AND RECRUITED ABOUT 100
SUBJECTS WHO WERE PARTICIPATING
IN A MEMORY AND AGING STUDY.
THESE ARE HEALTHY CAUCASIAN
ADULTS WHO HAVE JUST BEEN IN
THIS LONGITUDAL STUDY.
THEY GET MRI SCANS, THEY GET PET
SCANS, THEY HAVE COGNITIVE
EVALUATIONS, AND WHAT WE WANTED
TO DO WAS TO SEE IF THOSE
PATIENTS PERHAPS HAD DECREASED
CAPILLARY DENSITY BASED ON THEIR
APOE PHENOTYPE.
AND IT LOOKS LIKE AFTER
ADJUSTING FOR ALL THE THINGS
THAT ONE WOULD WANT TO ADJUST
FOR, WHICH IS, YOU KNOW, GENDER
AND HYPERTENSIVE STATUS AND
DIABETIC STATUS AND ALL THE
OTHER RISK FACTORS, PATIENTS WHO
HAD APOE4 -- AT LEAST ONE APOE R
CAPILLARY DENSITY THAN PATIENTS
WHO HAD NO ALLELES.
THESE ARE PATIENTS WHO ARE
HEALTHY, THEY HAVE NO COGNITIVE,
NO VISUAL COMPLAINTS, AND THEY
HAVE SOME COMORBIDITIES WHICH
WE'VE ADJUSTED FOR.
SO THAT IDEA WAS VERY
INTERESTING AND ACTUALLY
SURPRISED ME BECAUSE I DIDN'T
THINK WE WOULD ACTUALLY SEE SUCH
AN ASSOCIATION.
AND WE DID CONTROL FOR ALL KINDS
OF AMYLOID ON THE PET SCAN AND
FOR INTERCEREBRAL VOLUME,
DIFFERENT PARTS OF THE BRAIN
VOLUME AND WHOLE BRAIN VOLUME,
AND NONE OF THOSE THINGS MADE A
DIFFERENCE.
AND WHAT WAS MORE INTERESTING IS
WHEN WE LOOKED AT ACTUALLY THIS
POPULATION OF PATIENTS AND WE
LOOKED AT THE ASSOCIATION
BETWEEN RETINAL CAPILLARY
DENSITY AND AGE, THERE WAS A
SIGNIFICANT ASSOCIATION ONLY IN
PATIENTS WHO HAD AN APOE4
ALLELE, SUGGESTING THAT APOE4 IS
ACTUALLY DRIVING A DECREASE IN
CAPILLARY DENSITY IN AN
AGE-DEPENDENT MANNER, AND IF
YOU'LL REMEMBER IN OUR AFRICAN
AMERICAN EYE DISEASE STUDY, AGE
WAS INDEPENDENTLY A PREDICTOR OF
VESSEL SKELETON DENSITY THAN
DIABETES AND HYPERTENSION.
AND SO THIS ACTUALLY WAS A
REALLY EXCITING FINDING THAT
PERHAPS PROVIDED BIOLOGICAL
SUBSTRATE TO THE WAY IN WHICH
CAPILLARY DENSITY IS DECREASING
IN THE EYE AND REFLECTING
CHANGES IN THE BRAIN.
SO TAKE-HOME POINTS ARE THAT
OCTA IS ABLE TO DETECT
SUBCLINICAL CHANGES IN
CAPILLARY -- RETINAL CAPILLARY
DENSITY ACROSS A SPECTRUM OF NOT
ONLY RETINAL DISEASES BUT
SYSTEMIC DISEASES AND YOU'LL
HEAR A LOT MORE ABOUT RETINAL
DISEASES.
OCTA MEASURES CORRELATE WITH
COGNITIVE ABILITY.
EVEN IN PATIENTS WHO ARE
NEUROLOGICALLY INTACT AND HAVE
NO OPT K OPT KNOW LOGIC SYMPTOMR
COMPLAINTS.
IT SEEMS THAT THIS KIND OF
CHANGE IS ACTUALLY DRIVEN AT
LEAST IN PART BY APOE4 MEDIATING
CHANGES IN CAPILLARY INTEGRITY.
SO I'D LIKE TO THANK AGAIN ALL
MY COLLABORATORS.
I'VE TRIED TO MENTION THE PEOPLE
ALONG THE WAY THAT CONTRIBUTED
TO THE WORK THAT I SHOWED HERE,
AND ALWAYS SAY THAT WE'RE
INTERESTED IN POSTDOCTORAL
FELLOWS AND STUDENTS WHO ARE
INTERESTED IN PARTICIPATING IN
OUR WORK.
THANK YOU VERY MUCH, THANK YOU
TO THE NIH FOR YOUR FUNDING, AND
THANKS TO THE LASKER AWARD
WINNERS FOR ALL THEIR
CONTRIBUTIONS TO OUR WORK.
[APPLAUSE]
>> HI.
I'M RICHARD ROSEN.
TODAY I HAVE THE PLEASURE OF
INTRODUCING YALI JIA, JENNIE
WEEKS PROFESSOR OF OPHTHALMOLOGY
AT THE OREGON HEALTH AND SCIENCE
UNIVERSITY.
DR. JIA IS RENOWNED FOR HER
CONTRIBUTIONS TO THIS FIELD,
HAVING DEVELOPED THE SADA
ALGORITHM, PROBABLY ONE OF THE
MOST WIDELY USED OCTA ALGORITHM,
AND HAS ADDED TREMENDOUSLY TO
THIS FIELD.
SO YALI?
>> THANK YOU, DR. ROSENFELD, FOR
THE INTRODUCTION, AND ALSO IT'S
MY GREAT HONOR TO BE IN THIS
ROOM WITH SUCH A HIGH LEVEL OCT
CROWD.
TODAY I'M GOING TO TALK ABOUT
OUR RECENT WORK IN OUR LAB
FOCUSED ON TWO OF THE ADVANCES
ON OCT RESEARCH WE TRIED TO PUSH
FORWARD OCT INTO THE CLINIC.
TODAY'S TALK IS A FOCUS ON THE
DIABETIC RETINOPATHY.
WE ALREADY KNOW OCT IS A TYPE
OF -- ALGORITHM, IT HAS BEEN
PROVED VERY SUCCESSFUL.
IT'S A VERY SUCCESSFUL EXTENSION
OF OCT.
AND WE ALREADY SEE THIS KIND OF
A COMPARISON, OCTA COMPARES
FLUORESCING -- DUE TO THOSE
THREE-DIMENSIONAL NATURE, IT CAN
DEFINITIVELY DEFINE THOSE
RETINAL NEOVASCULARRIZATION AND
THE CAPILLARY DROPOUT.
SO THE QUESTION IS HOW ARE WE
GOING TO QUANTIFY THOSE TINY
NEOVASCULARRIZATION IN THE
DIFFERENT LOCATIONS.
ACTUALLY OCTA IS MO MORE
SUSCEPTIBLE TO -- THAN THE
CONVENTIONAL OCT, FOR EXAMPLE
THE MOTION ARTIFACTS IS VERY
PRONOUNCED, SIGNAL ATTENUATION
ARTIFACTS DUE TO THE SHADOW OR
DUE TO THE -- AND THE PROJECTION
ARTIFACTS DUE TO THE MULTIPLE
SCATTERING PHENOMENA.
SO ALL OF THOSE ARTIFACTS SHOULD
BE RESOLVED FOR FURTHER
MEASUREMENTS AND WE SHOULD TAKE
ADVANTAGE THE ADVANCE TRYING TO
USE THOSE CONCEPTUAL INFORMATION
AND MINIMIZE THE INTERFERENCE
FROM THE ARTIFACTS.
I'M GOING TO SHOW YOU A COUPLE
OF EXAMPLES TO SEE HOW A.I. CAN
HELP OCTA RESEARCH.
FIRST I START WITH
VISUALIZATION.
SO A.I. CAN HELP IMPROVE THE
OCTA IMAGE GENERATION,
CONSTRUCTION, AND ALSO IMPROVE
RESOLUTION.
FIRST OF ALL, THIS STEP IS QUITE
ESSENTIAL, BECAUSE FOR THE
LAMINAR STRUCTURE OF THOSE
CAPILLARY PLEXUS, WE SHOULD
PROJECT IT ON TO 2D FIRST,
RIGHT, BEFORE WE MOVE TO THE
BIOMARKER MEASUREMENT.
SO SLAB SEDIMENTATION IS VERY
SIGNIFICANT STEP.
WE HAVE TO MAKE SURE THIS STEP
IS VERY ACCURATE SO WE USE DEEP
LEARNING TO MAKE SURE THE FIRST
STEP CROSS SEDIMENTATION USE
THOSE SEMANTIC SEGMENTATION BY
THE FIRST STEP BY DEEP LEARNING,
THEN WE ADD THE GRAPH SEARCH TO
REFINE THE RESULTS.
THIS HAS BEEN DEMONSTRATED ON
THE VERY CHALLENGING
PARAPAPILLARY SCANS.
THEN AFTER WE PROJECT THE OCT
SIGNAL ON TO THE 2D MAP, FOR
SOME SCANS ACTUALLY WE DON'T
HAVE ENOUGH RESOLUTION BECAUSE
WE HAVE TO -- MAKE SURE WE CAN
CATCH THE SCAN'S REASONABLE
AREA.
SO LOW DEFINITION IMAGE, IN OUR
LAB WE TRIED TO USE THOSE SMALL
AREA SCAN WITH HIGH DEFINITION,
HIGH-DENSITY SCANS USED AS -- TO
TRY TO BORROW THE
SUPERRESOLUTION CONSTRUCTION
FROM THE MICROSCOPY AREA, AND WE
TRIED TO LEARN THOSE DEEPER
FEATURES FROM THE CAPILLARY
DETAILS AND RECONSTRUCT THE
CAPILLARY DETAILS FROM THE LOW
RESOLUTION IMAGE.
IN THIS WAY, WE CAN IMPROVE
THOSE VISUAL -- AND THE
APPEARANCE FOR THOSE PATHOLOGIES
ON THE ANGIOGRAMS CAN HELP US TO
DO THE DIAGNOSIS AND THE
STAGING.
I HOPE YOU CAN PERCEIVE THE
DIFFERENCE BEFORE AND AFTER THIS
STEP.
ALSO THAT'S ALSO HELP FOR OTHER
BIOMARKER DETECTION.
YOU KNOW, WE COULD FIRST IMPROVE
THE CAPILLARY RESOLUTION AND
THEY MOVE TO ANOTHER NEURAL
NETWORK AND WE'RE ABLE TO
CLASSIFY ARTERIES AND VEINS TWO
TYPE OF VESSELS FROM THE SINGLE
MAP.
ACTUALLY DEEP LEARNING DID A
VERY GOOD JOB EVEN OVER AUTO
PERFORM THE HUMAN -- SO THE
DETAIL -- SO THEY CAN SEPARATE
THOSE TWO TYPE OF VESSELS AND
THEN LATER WE CAN GO TO THE
CAPILLARY MAP GENERATOR,
CAPILLARY MAP AND ALSO CAN
QUANTIFY THE TORE TEU TORTUOSITR
FURTHER ANALYSIS.
AFTER WE DO THE RECONSTRUCTION,
WE CAN IMPROVE THOSE OCT
SIGNALS, AFTER WE OVERLAY OCT
ONTO THE MAP, WE'RE ABLE TO
DIFFERENTIATE THE PERFUSION
CENTERS OF THE -- WE MICRO ANEU,
SO THOSE DIFFERENT TYPES
CORRELATED WITH THE LOCATION TO
THE RETINAL FLUID.
IN OUR STUDY, WE FIND THOSE
PERFUSED THE MICRO ANEURYSMS
MORE COLOCATED WITH RETINAL
FLUID, PROBABLY EARLIER
BIOMARKER THAN WHEN WE -- BEFORE
WE DETECT THE RETINAL FLUID IN
CLINIC.
NEXT WE'LL MOVE TO SEE HOW A.I.
IMPROVES THE BIOMARKER
MEASUREMENT.
AND AS I ALREADY INDICATED, YOU
KNOW, OCT MERELY PROVIDED TWO
TYPE OF BIOMARKER FOR THE
CURRENT D.R. RESEARCH.
FIRST OF ALL IT'S THE CAPILLARY
NON-PERFUSION AREA.
HERE WE MEASURE THE AVASCULAR
AREA INSTEAD OF THE VESSEL
DENSITY.
SO IN OUR EARLIER WORK, WE
ALREADY -- OCT AND
FLUORESCING -- THE RESULT IS NOT
EQUIVALENT BUT THEY ALREADY SHOW
MAJORITY AGREEMENT.
AND THEN ALSO WHEN WE SPLIT INTO
THE THREE SLAB SUPERFICIAL
INTERMEDIATE -- THE DEEP FLEX
US, NON-PERFUSION AREA CAN BE
BETTER VISUALIZED.
AND YOU CAN APPRECIATE THOSE
ENLARGE THE CAPILLARY SPACE NEAR
THE -- THE DIABETES GROUP
WITHOUT D.R. EVEN.
SO THAT'S KIND OF AN EARLIER
BIOMARKER WE CAN CONSIDER FOR
THE FUTURE RESEARCH.
MOTIVATED BY THE NON-PERFUSION
AREA'S FUNCTION, SO IN OUR
GROUP, WE INTELLIGENTLY PUT --
CT AND OCT MAP TOGETHER ALSO
COMBINED WITH THE INNER RETINAL
SIGNALINGS AND TOGETHER WE ARE
ABLE TO DIFFERENTIATE THE TWO
AVASCTRUEAVASCULAR AREA, WE CANR
FROM SIGNAL LOSS.
WE ALSO KNOW THE IPT IMMEDIATE
AND DEEP LAYERS MORE FREQUENTLY
CONFOUNDED BY MOTION AND SOME
RESIDUAL PROJECTION ARTIFACTS
SO -- WORK ON THOSE AI MODEL TO
IMPROVE THE NON-PERFUSION AREA
ON THREE LAYERS.
AND A GOOD DEEP LEARNING
ALGORITHM ALSO SHOULD BE APPLIED
ON THE DIFFERENT, YOU KNOW,
VARIOUS REGIONS OF THE OCTA.
THIS SHOWS AN EXAMPLE FOR OUR
RESEARCH.
IN OUR OHSU COHORT, WE ALSO USED
THIS DEEP LEARNING, W WHICH SHOS
IN THE SUPERFICIAL VASCULAR --
AVASCULAR AREA ACTUALLY IT'S
ASSOCIATED WITH DISEASE
PROGRESSION IN ONE YEAR, AND THE
DCP AVASCULAR AREA AT BASELINE
CAN PREDICT THE TREATMENT
REQUIREMENT IN ONE YEAR.
AND THE RESULT CORRESPONDS TO
THE PREVIOUS STUDY VERY SMALLER
COHORT FROM OTHER GROUP.
WE ARE ABLE TO USE THE OCT
SIGNAL FROM THE OCT VOLUME WE
DON'T WANT TO GET READ OF THOSE
HIGH-DENSITY, HIGH DEFINITION --
VOLUME THAT ALSO PROVIDE VERY
RICH INFORMATION, AND THAT'S
INTRINSIC HIGH ASSEMBLING
VOLUME, AND IN OUR STUDY WE
TESTED A UNIT LIKE A CONVOLUTION
NEURAL NETWORK AND THE
INTERRETINAL -- FLUID AND
SUBRETINAL FLUID CAN BE
EXTRACTED AND BY ADDING THOSE
OCTA SIGNAL -- SO CAN FURTHER
ENHANCE THE ROBUSTNESS OF THE
NETWORK.
THAT SHOWS HOW THOSE CAN BE
SIMULTANEOUSLY -- TOGETHER SO ON
ONE HAND WE COULD FIGURE OUT THE
RETINAL FLUID ON THE OTHER HAND,
WE COULD FIGURE OUT THE ISCHEMIA
STATUS.
THIS SHOWS YOU AN EXAMPLE BEFORE
AND AFTER THE TREATMENT, SO WE
COULD CHECK THOSE NEW FLUID AND
CHANGE -- THE FLUID AND ALSO WE
CAN COMPARE TO THE OCTA CHANGE
WITHIN THOSE TWO TIME POINTS.
IN OUR STUDY, WE ALSO CHOSE A
DEEP LEARNING BASE THAT FLUID
VOLUME IS MORE ACCURATE THAN THE
CONVENTIONAL SUBFIELD SIGNALS IN
MACULAR EDEMA STUDY.
THIS SHOWS THAT'S NOT RED FLAG
TO -- THE CONVENTIONAL -- OCT
BUT ALREADY SHOWS VERY DRAMATIC
FLUID INSIDE OF THE VOLUME.
AND WE ALSO DID ANOTHER STUDY IN
DME, WE FOUND THAT FLUID
ACTUALLY -- THAT'S RESOLVED IF
WE -- THE FLUID IN THE INNER
NUCLEAR LAYER, IT'S A VERY
SUPERFICIAL INNER FLUID THAT'S
HIGHLY CORRELATED WITH VISUAL
ACUITY.
EVEN WHEN WE DO THE MULTIVARIATE
ANALYSIS, INCLUDE OTHER
OCT-BASED BIOMARKER OR OTHER
STRUCTURE SIGNALING MEASUREMENT.
THIS IS STILL THE STRONGEST
FACTOR FOR THE VISUAL ACUITY.
NOW I WANT TO SWITCH THE GEAR TO
THE DIRECT DIAGNOSIS.
THINK ABOUT THINGS WE PUT A LOT
OF EFFORT FOR EXTRACTING THE
BIOMARKER.
HOW ABOUT WE JUST INPUT TO THE
OCT AND OCTA PICTURES OR
VOLUMES, RIGHT, LET THE MACHINE
TO DO ALL THE WORK.
WE JUST WANT TO KNOW IF THIS
CASE ARE REFERABLE OR
NON-REFERABLE.
IT REALLY BASED ON THE CLINICAL
NEEDS, AND SOMETIMES WE WANT TO
DO THOSE TWO CLASS SEPARATION,
FIGURE OUT THE NON-PRODUCTIVE
AND PRODUCTIVE AND ALSO WE WANT
TO HAVE A NARROWER
CLASSIFICATION.
SO WE TEST IT USING EPBRS, AND
WE FOUND OUR RESULT IS NOT
PERFECT FOR THE -- BECAUSE IT'S
VERY -- SHOWS VERY CLOSE SCORE
TO THE MODERATE NBPR BUT FOR THE
2-CLASS, WE ARE ABLE TO PROVIDE
THE EQUIVALENT SENSITIVITY OR
DIAGNOSIS POWER FOR
DIFFERENTIATING THE REFERABLE
D.R., WHICH CAN REDUCE THE
BURDEN FOR THE REFERRAL.
THIS DIRECT DIAGNOSIS CAN BE
DONE ON THE 6 -- IMAGE WHICH
REQUIRES SEGMENTATION OR WE
COULD BE DONE ON THE 2 VOLUME
DIRECTLY, THE BENEFIT IS VERY
APPARENT AND NO SEGMENTATION
REQUIRED.
AFTER THE DIAGNOSIS STEP, WE
FREQUENTLY HEAR ABOUT THIS TERM,
HEAT MAP, AND THEN GENERATED
THIS COLORFUL MAP.
IT BARELY GIVES US USEFUL
INFORMATION, WE DON'T KNOW WHICH
AREA IN DECISION-MAKING.
SO IN OUR GROUP, WE WORK ON TO
GENERATE ACTIVATION MAP TO TRY
TO IMPROVE THE RESOLUTION, TRY
TO GIVE YOU BIOMARKER ACTIVATION
MAP TO SHOW WHERE OR WHICH
PATHOLOGIES REALLY CONTRIBUTE TO
THE DISEASE.
THIS INCLUDED TWO STEP OF DEEP
LEARNING.
FIRST OF ALL, WE NEED TO HAVE A
DEEP LEARNING D.R. CLASSIFIER.
IN THIS CASE, WE SHOULD CLASSIFY
NON-REFERABLE FROM REFERABLE,
AND IN THOSE CLASSIFIER MOVE TO
THE BIOMARKER ACTIVATION MAP
GENERATION FRAMEWORK HERE, WE
USE THE -- NETWORK.
I SHOW YOU HOW.
AND BASICALLY NOT TO JUST TELL
US YES OR NO DECISION AND ALSO
PROVIDE US A MAP TO TELL US
WHERE THE NETWORK MAKES THIS
DECISION FROM THE OCT AND THE --
OCT.
SO BASICALLY THIS AGAIN IS
GENERATIVE LEARNING NETWORK,
THEY TRY TO KEEP CHANGING USING
THE -- STEP, KEEP CHANGING THE
PIXEL BRIGHTENINGS, THEY MAKE
SURE THOSE POSITIVE GROUP HERE
IS REFERABLE GROUP.
THEY TRY TO CREATE THE FORGED,
THE IMAGE, AND TRY TO FOOL THE
NETWORK TO BE CONSIDERED AS A
HEALTHY CONTROL.
SO ONCE THEY PASS THIS TEST, AND
THE DIFFERENCE BETWEEN THOSE
PIXELS AND THE ORIGINAL PICTURES
CAN BE FIGURED OUT IS THAT THE
PIXELS WE CONSIDER FOR THE BAM.
AND FOR THE BAM PIXEL GROUP, WE
COMPARE TO THOSE BIOMARKER BASED
SEGMENTATION NON-PERFUSION AREAS
AND THE FLUID -- THEY EXACTLY
MATCH EACH OTHER.
SO THAT'S KIND OF INDIRECTLY CAN
VALIDATE BAM, GIVE US THE
REASONABLE INFORMATION.
SO USING THIS BIOMARKER
ACTIVATION MAP, WE DON'T HAVE TO
DO THE DEEP LEARNING BIOMARKER
EXTRACTION, YOU KNOW, -- TO PULL
OUT OF THOSE PIXEL GROUPS
WHERE -- PATHOLOGIES THEY MAY BE
NON-PERFUSION, THEY MAY BE FLUID
OR THEY MAY BE MICRO ANEURYSM.
SO THE SUMMARY FOR THIS SECTION
IS DEEP LEARNING DO PROVE VERY
POWERFUL FOR STUDYING OCT IN
D.R., AND WE HAVE THE REVIEW
PAPER PUBLISHED A FEW YEARS AGO
IF YOU HAVE INTEREST, YOU CAN
CHECK OUT THE DETAILS, ALSO
INCLUDE A LOT OF WORK FROM OTHER
GROUPS.
I WANT TO SWITCH TO ANOTHER
ADVANCE WHICH ALSO HELPS FOR THE
DIAGNOSIS OF D.R.
WE HAVE BEEN PUT TO OUR
STUDENT -- TOGETHER -- HIGH
RESOLUTION PROTOTYPE, BUILD UP
THIS HIGH PERFORMANCE IMAGING
PLATFORM, ACTUALLY IT'S JUST
LIKE BUILD A FANCY CAMERA.
WE HAVE TO FIGURE OUT THOSE SIX
COMPONENTS, LENS, LASER, HOW TO
STABILIZE, HOW TO MAKE THE
ALGORITHM EFFICIENT.
SO WE VERY DILIGENTLY STARTED
ABOUT 10 YEARS AGO FROM OUR
FIRST GENERATION AND -- EVERY
PAPER WE MAKE A SINGLE STEP,
TRIED TO CONQUER A SINGLE
PROBLEM AND FINALLY WE ARE ABLE
TO GENERATE THOSE SINGLE SHOT
AND THEN -- SCANS, THIS SHOWS
NON-PRO LIVE TIP DRIs, WE'RE
ABLE TO VISUALIZE THIS -- IN A
SINGLE SYSTEM, AND ALSO WE ARE
ABLE TO SEE THOSE VERY EARLY
SPROUTS OF THE
NEOVASCULARRIZATION.
I THINK YOU HAVE TO BE VERY
CLOSELY MAYBE I SHOULD MAGNIFY
THOSE AREAS.
ALL THOSE ADVANCED -- OTHER
GROUP OF FOLKS WIDE FIELD OCT
AND IT'S GREAT NEWS THAT HAS
BEEN -- INHERITED BY SOME
COMMERCIAL OCT COMPANY.
THEY ALREADY MAKE IT
COMMERCIALIZED, 18 BY 18, AND
EVEN LARGER SCANS FROM THE
SINGLE EYE.
ACTUALLY THE SOURCE IS NOT
THE -- LASER, THAT'S JUST THE
200-KILOHERTZ 16-NANOMETER.
AND IN THE MILD D.R., WE CAN SEE
THE -- AND WE ALSO COULD SEE
CORRESPONDED TO THE
CROSS-SECTIONALS TO WIDE FIELD
OF VIEW AND THE MODERATOR MPBR,
WE PROBABLY WANT TO LOOK AT
WHERE IS THE MPA AND THE
NEOVASCULARIZATION IS.
I'M NOT SURE IF YOU CAN SEARCH,
YOU CAN FIND OUT THIS KNEW OWE
VASCULARIZATION SPROUT FROM THIS
ENTIRE IMAGE.
IF I CHANGE THE COLOR YOU'RE
PROBABLY ABLE TO SEE IN THE
BOTTOM, THOSE TWO DOTS, YELLOW
DOTS, THAT'S NEW VESSELS.
SO IT'S JUST A SUBCLINICAL
INFORMATION CAUGHT BY THAT
SINGLE SHOT.
I DO HAVE A DISCLOSURE HERE,
INTALIGHT PROVIDED THE
SOFTWARE -- I SHOW YOU A CASE
FOR THE PROLIFERATIVE D.R. AND
USING THIS SINGLE 12 BY 12, YOU
CAN RESOLVE THIS TYPE OF LARGE
VESSELS, AND WHEN WE EXTE EXTEND
THE FIELD OF VIEW, YOU CAN SEE
MORE, AND THIS CAN BE EASY TO
IGNORE FROM A CLINICAL.
AND ALL THOSE SPROWDZ ARE
CORRESPONDING TO THE
CROSS-SHEX-SECTIONAL SCANS, WE N
VALIDATE NEOVASCULARIZATION.
SO THE INNER RETINAL SLAB, ALSO
WE COULD OVERLAID -- BETTER
IDEA.
AND COMPARED TO THE
FLUORESCING -- YOU PROBABLY CAN
SEE EVEN SOME AREAS ALREADY SHOW
BY THIS VERY DEFINITIVE OCTA
SCANS.
AND THE -- VOLUME -- AND DEEP
LEARNING RESOLVED FROM THIS
MODERATE NPBR SCANS VERY TINY
AREAS, AND THAT'S ACTUALLY -- WE
JUST APPLIED OUR PREVIOUS DEEP
LEARNING ALGORITHM ON THOSE WILD
FIELD SCANS.
WE DL NOT DO ANY CHANGE JUST
BECAUSE THOSE WIDE FIELD SCANS
PROVIDED SUFFICIENT RESOLUTION,
AND THE RETINAL SIGNALING GAVE
US A BETTER IDEA ON THE SIGNALS
CHANGE ON THE WIDE ANGLE
COMPARED TO THE CONVENTIONAL
AREAS WE CAN SEE FROM THE
CLINIC.
FOR THE -- DEFECT WE ALSO CAN
REVIEW THOSE -- WE ALSO CAN
REVIEW THOSE PHOTORECEPTOR LOSS
FROM THE -- AREAS AND WE ALSO
BENEFIT FROM THOSE
CROSS-SECTIONAL, YOU'RE ABLE TO
SEE PHOTORECEPTOR LOSS.
CHOROIDAL VASCULATURE ALSO CAN
BE VISUALIZED DUE TO THE DEEPER
HIGH PEN TAITION O PENETRATION.
I WANT TO USE SOME SPECULATION
ON THE FUTURE TO CONCLUDE MY
TALK.
WE ALREADY KNOW THERE IS TWO
TYPE OF SOFTWARE, VERY
SUCCESSFUL FOR D.R. SEGMENTATION
BASED ON THE PHOTO.
WE REALLY HOPE THOSE WHO ADVANCE
TO OCT AND OCT CAN DO SOMETHING
TO HELP, COMBINE WITH AI TO
HELP, ALSO FOR OTHER TYPE OF --
DISEASE, AND THE WIDE FIELD OF
VIEW MAY GIVE US BETTER
INFORMATION AND FURTHER COMBINE
AND INTEGRATE I.
I WANT TO ACKNOWLEDGE, WE HAVE A
WONDERFUL COLLABORATOR TEAM FROM
RETINAL SERVICE AND MENTORS,
ALSO THE NIH FUNDING SUPPORT AND
THE BRIGHT FOCUS FOUNDATION
SUPPORT, AND THE MATERIAL
SUPPORT, AND THERE IS A
WONDERFUL SUPPORT FROM OUR TEAM,
THE LAB.
I WANT TO STOP OVER HERE.
THANK YOU SO MUCH.
[APPLAUSE]
>> KNE THANK YOU, YALI, FOR THAT
TOUR DEFORCE.
IT IS NOW MY PLEASURE TO
INTRODUCE DR. TOCO CHUI.
SHE ALSO CODIRECTS THE ADVANCED
RETINAL IMAGING LABORATORY WITH
PROFESSOR RICH ROSEN, SO TWO
GIANTS IN ONE SPACE.
TOCO?
COME ON OVER.
>> HELLO, EVERYONE.
HOW ARE YOU?
IT IS A GREAT HONOR AND A
PRIVILEGE TO PARTICIPATE IN
TODAY'S SYMPOSIUM.
I WOULD LIKE TO CONGRATULATE
JIM, DAVID AND ERIC FOR THEIR
VERY WELL-DESERVED SUCCESS OF
THE INVENTION OF OCT.
IT IS TRULY REVOLUTIONARY IN THE
FIELD OF OCULAR HEALTHCARE AND
CLINICAL RESEARCH.
AND TODAY, I WILL BE SHOWING YOU
HOW OUR LAB USES O.C.T. ANG
YOGRAPHY TO EVALUATE
VASO-OCCLUSION DYNAMICS IN
PATIENTS WITH SICKLE CELL
DISEASE.
I WOULD LIKE TO ACKNOWLEDGE THE
MANY MEMBERS OF MY TEAM AND
COLLABORATORS WHO MADE THIS
PRESENTATION POSSIBLE.
I WOULD ALSO LIKE TO THANK THE
VERY GENEROUS SUPPORT FROM THESE
FUNDING SOURCES, ESPECIALLY THE
NATIONAL EYE INSTITUTE AND THE
NATIONAL HEART, LUNG AND BLOOD
INSTITUTE FOR THE MAJOR SUPPORT
OF OUR SICKLE CELL DISEASE
RESEARCH.
OKAY.
SO A VERY SHORT INTRODUCTION
ABOUT SICKLE CELL DISEASE, SCD.
IT IS THE MOST COMMON INHERITED
BLOOD DISORDER.
ABNORMAL HEMOGLOBIN IN SICKLE
CELLS BECOME VERY HARD AND LOOK
LIKE A SICKLE.
TODAY I WILL SHOW YOU HOW WE
VALIDATE CROSS-SECTIONALLY -- IN
SICKLE CELL DISEASE PATIENTS AND
TO MONITOR THE TREATMENT EFFECT
OF HYDROXYUREA AND CRISPR BASED
GENE EDITING USING CLINICAL
OCTA.
SO SICKLE HEMOGLOBIN FIBER
FORMATION WITHIN RED BLOOD CELLS
LEADS TO AN INCREASE IN CELL
STIFFNESS AND BLOOD VISCOSITY.
AND THE FORMATION OF THESE
FIBERS STIFFEN AND CAN CHANGE
THE CELL'S MORPHOLOGY TO SICKLE
SHAPE.
THE FORMED CELLS CAN INJURE
BLOOD VESSELS IN THE EYE.
AS SEEN IN THIS ANIMATION ON THE
LEFT, BLOOD VESSELS CAN GET
BLUNTED BY SICKLE CELLS, CAUSING
INTERMITTENT PERFUSION OR
PERMANENT OCCLUSION.
AND WE HYPOTHESIZE THAT PRIOR TO
PERMANENT OCCLUSION, MONITORING
THE FREQUENCY OF INTERMITTENT
PERFUSION MAY HAVE PROGNOSTIC
VALUE FOR ASSESSING SICKLE CELL
DISEASE ACTIVITY.
AND I WOULD LIKE TO DRAWL YOUR
ATTENTION TO THE BACKGROUND
IMAGE HERE, WHICH IS A WILD
FIELD OCTA IMAGE THAT WE
OBTAINED RECENTLY ON A PATIENT
WITH SICKLE CELL RETINOPATHY AND
NEOVASCULARIZATION IN THE
PERIPHERY.
SO BY NOW, WE ALL -- WE SHOULD
ALL KNOW THAT O.C.T. IS A
NONINVASIVE AND DYE-FREE IMAGING
TECHNIQUE.
ON THE RIGHT IT'S A FULL
VASCULAR OCT ANG YOGRAPHY. AND
IN HERE IT'S A COLOR-CODED OCTA,
WHICH SHOWS THE FLEE DIFFERENT
RETINAL CAPILLARY LAYERS.
AND THIS IS A 3D RENDER OF MICRO
VASCULATURE OF THE SAME CONTROL
SUBJECT, AND THE CENTER SHOWS
THE -- WITH SURROUNDING VASCULAR
NETWORK GOING FROM THE
SUPERFICIAL LAYER TO THE DEEP
LAYER.
I HOPE YOU CAN TELL THAT THESE
ARE NOT O.C.T. IMAGES.
THIS IS A SCREENSHOT FROM THE
LASKER DEBAKEY AWARD YOUTUBE
VIDEO WHICH I EDITED TO MAKE TWO
SLIGHTLY DIFFERENT IMAGES.
BY THE WAY, PLEASE GO WATCH THIS
YOUTUBE VIDEO WHEN YOU HAVE
TIME.
THE PRODUCTION IS EXCELLENT.
BUT DON'T WATCH IT RIGHT NOW.
JUST STAY WITH US.
OKAY?
[LAUGHTER ?CHT TRUST ME, THE
VIDEO IS GREAT.
SO INTERMITTENT PERFUSION
IMAGING AND QUANTIFICATION
APPROACH THAT I'M GOING TO TALK
ABOUT WILL ACTUALLY -- WERE
ACTUALLY INSPIRED BY MY FAVORITE
CHILDHOOD GAME, SPOT THE
DIFFERENCE.
TO YOU GUYS KNOW ABOUT THIS
GAME?
YES?
EXCELLENT.
IN ORDER TO SPOT THE DIFFERENCES
WE NEED TO GO BACK AND FORTH
BETWEEN THESE TWO IMAGES, RIGHT?
CAN YOU TELL ME THE THREE
DIFFERENCES ON DAVID, JIM AND
ERIC CARTOON CHARACTERS?
YOU CAN JUST SHOUT OUT THE
ANSWER.
YES, EXCELLENT!
CONGRATULATIONS.
LEVEL UP.
SO I'M -- REVIEW THE DIFFERENCES
LIKE THIS.
TO FURTHER CHARACTERIZE THE
DIFFERENCES OF FEATURES THAT
ONLY APPEARED IN IMAGE ONE ARE
COLORED IN RED AND FEATURES
APPEAR ONLY IN IMAGE TWO ARE
COLORED IN CYAN.
SO HERE ARE TWO AVERAGE OCTA
SCANS OBTAINED AT BASELINE IN
ONE HOUR FOLLOW-UP IN A SICKLE
CELL PATIENT WITH HBSS GENOTYPE.
NOW, LET'S SPOT THE DIFFERENCES
IN THESE TWO AVERAGE OCTAs.
NEAR-INFRARED ONE WOULD LIKE TO
GIVE IT A TRY?
I CAN SEE SOME OF YOU ARE
ACTUALLY SHAKING YOUR HEADS.
YES, I DON'T BLAME YOU.
IT'S NOT EASY, RIGHT?
OKAY.
SO TO OBJECTIVELY IDENTIFY
PERFUSION DIFFERENCES OVER ONE
HOUR, WE FIRST COMPUTED THE
NORMAL VAIR YAI VARIATION IN PIL
INTENSITY DIFFERENCE --
UNAFFECTED CONTROLS.
AND THEN DETERMINE THE -- FOR
NON-PERFUSION AND REPERFUSION
OVER ONE HOUR.
AND WE THEN USED THE CUTOFFS TO
IDENTIFY CAPILLARY -- AT NORMAL
PERFUSION IN SICKLE CELL DISEASE
PATIENTS.
CAPILLARY SEDIMENTS APPEARED
ONLY AT THE BASELINE WERE
IDENTIFIED AS NON-PERFUSION AND
CAPILLARY SEDIMENTS APPEARED
ONLY AT THE FOLLOW-UP VISIT OR
FOLLOW UP SECTION, WERE DEFINED
AS REPERFUSION.
SO ON THE RIGHT NOW, IT'S AN
INTERMITTENT PERFUSION MAP WHICH
SHOWS CAPILLARY NON-PERFUSION IN
RED, AND REPERFUSION IN CYA FL
COLOR.
OKAY.
SO HERE IT ANOTHER EXAMPLE WE
SHOWED -- WHICH SHOWS BOTH THE
MACULA AND THE -- RETINA.
SO ACTUALLY TOGGLING BACK AND
FORTH WITH AN INTERMITTENT -- AT
THE END OF THE VIDEO, AGAIN, THE
INTERMITTENT PERFUSION MAP SHOWS
REPERFUSION IN CYAN.
THIS MAP PROVIDES INSTANT
QUALITATIVE INTERPRETATION OF
THE PERFUSION STATUS OVER ONE
HOUR.
HERE WE CAN SEE THE INCREASING
INTERMITTENT PERFUSION WITH
INCREASING DISEASE ACTIVITY WITH
THE HIGHEST LEVEL OF
INTERMITTENT PERFUSION FOUND IN
HBSS GENOTYPE.
OKAY.
SO TO QUANTIFY THE INTERMITTENT
PERFUSION CHANGES, WE CALCULATED
THE PERCENT OF PIXELS WITH
NON-PERFUSION AND WREE PERFUSION
OVER ONE HOUR.
INTERMITTENT PERFUSION INDEX WAS
DEFINED AS THE TOTAL PERCENTAGE
OF NON-PERFUSION AND REPERFUSION
AREAS IDENTIFIED USING OUR
NORMATIVE BASE IMAGE PROCESSING
APPROACH.
SIGNIFICANT DIFFERENCES WERE
OBSERVED BETWEEN CONTROLS AND
PATIENT WITH HBSC AND HBSS
GENOTYPES.
WE ALSO FOLLOWED THREE SICKLE
CELL PATIENTS BEFORE AND AFTER
TREATMENT.
AS YOU CAN SEE ON THE RIGHT SIDE
OF THIS BOX PLOT, INTERMITTENT
PERFUSION INDEX WAS OBVIOUSLY
LOWER AFTER TREATMENT.
AND HERE IS A TREATMENT-NAIVE
HBSS PATIENTS IMAGE PRIOR TO THE
INITIATION OF HYDROXYUREA.
AGAIN THE TWO MACULAR OCTA
TOGGLING BACK AND FORTH WITH THE
INTERMITTENT PERFUSION MAP
SHOWING AT THE END OF THE VIDEO,
AND INTER MITT ENT PERFUSION
INDEX WAS ABOUT 3% BEFORE
TREATMENT.
ON THE RIGHT NOW YOU CAN SEE THE
EFFECT OF HYDROXYUREA TWO MONTHS
AFTER TREATMENT.
IT WORKS BY MAKING THE RETINAL
CELL MORE FLEXIBLE, THEREFORE
IMPROVING BLOOD FLOW.
THERE'S A SIX-TIME REDUCTION IN
INTERMITTENT PERFUSION EVENT
SINCE WITH THIS NORMATIVE BASE
IMAGE PROCESSING APPROACH.
AND NALD IN ADDITION TO OCTA IG
WE ALSO IMPLEDGE OF ALLEGIANCED
THIS -- ONE THING WE'RE NOT ABLE
TO SEE IN OCTA IS THE ACTUAL
BLOOD CELL MOTION.
AND ADAPTIVE OPTICS -- OF BLOOD
CELLS AND REVIEW BLOOD FREL
DYNAMICS, UNAVAILABLE FROM OCTA.
AND IN PARTICULAR, ADAPTIVE
OPTICS IMAGING CAN PROVIDE
VISUALIZATION OF RETINAL CELLS
IN PERFUSED AND NON-PERFUSED
BLOOD VESSEL.
SO BASELINE ADAPTIVE OPTICS IS
SHOWN TWOP MONTHS AFTER
HYDROXYUREA IT ON THE RIGHT.
-- REVIEWED TWO OCCLUDED
CAPILLARIES WITH -- AND
SLUDGING.
AND THESE WERE REPERFUSED TWO
MONTHS AFTER HYDROXYUREA
TREATMENT.
INTERESTINGLY -- WAS OBSERVED AT
A PREVIOUSLY OBSERVED VO
CAPILLARY -- ADAPTIVE --
IMPROVED BLOOD FLOW AFTER
TREATMENT.
THIS IS A SICKLE CELL PATIENT
IMAGE BEFORE CRISPR.
-- INDEX WAS ABOUT 3%.
IN SIX MONTHS AFTER CRISPR, OCTA
SHOWS FOUR TIMES REDUCTION IN
INTERMITTENT PERFUSION INDEX.
AND THIS CASE SUGGESTS THAT
CRISPR BASE GENE EDITING IN
SICKLE CELL DISEASE WHILE
SUBSTANTIALLY EFFECTIVE MAY NOT
COMPLETELY ELIMINATE
VASO-OCCLUSIVE ACTIVITY.
OKAY.
SO TO VALIDATE INTERMITTENT
PERFUSION INDEX AS OBJECTIVE
INDICATOR OF DISEASE ACTIVITY
AND TREATMENT SUCCESS, WE WILL
MONITOR OUR PATIENTS FOR FIVE
YEARS USING OCTA.
WE JUST FINISHED OUR FIRST YEAR
TIME POINT AND HERE IT'S AN
EXAMPLE OF INTERMITTENT
PERFUSION OVER ONE YEAR IN A
PATIENT WITH HBSS GENOTYPE.
OUR HYPOTHESIS IS THAT
INTERMITTENT PERFUSION INDEX
WILL CORRELATE MORE STRONGLY
WITH SICKLE CELL DISEASE
SEVERITY.
THEN ANY OTHER CURRENTLY
AVAILABLE BIOMARKER.
THESO HOPEFULLY I WILL HAVE MORE
PRELIMINARY DATA TO SHOW YOU
NEXT YEAR.
THIS IS A 3D RETINAL PERFUSION
OVER ONE YEAR OF THE SAME
PATIENT.
HERE YOU CAN SEE MORE CLEARLY
THE PRESENCE OF INTERMITTENT
PERFUSION AT DIFFERENT CAPILLARY
LAYERS.
ARE YOU ABLE TO SEE IT OKAY?
OKAY.
SO THIS IS A MOVIE OF SHOWING
RETINAL INTERMITTENT PERFUSION
ONE YEAR -- OVER ONE YEAR IN A
PATIENT WITH HBSC GENOTYPE.
WE CAN SEE MULTIPLE CAPILLARY
SEDIMENT WITH INTERMITTENT
PERFUSION.
ON THE RIGHT, IT THE
CORRESPONDING CHORIOCAPILLARIS
LAYER.
I'M A LITTLE EMBARRASSED TO SHOW
YOU RIGHT NOW AFTER SEEING
JOLIN'S AOCT CHORIOCAPILLARIS
IMAGE, BUT THAT'S WHY I WANT TO
EMPHASIZE THAT THIS IS DONE
USING CLINICAL OCTA, SO IT'S
NOT -- IT'S NOT ADAPTABLE --
IT'S CLINICAL OCTA.
OKAY.
SO ON THE RIGHT, IT'S A
CORRESPONDING CHORIOCAPILLARIS
LAYER, SO OVERALL, THE PERFUSION
STATUS WAS QUITE CONSISTENT OVER
ONE YEAR.
EXCEPT WITH SEVERAL LOCATIONS
YOU CAN SEE SOME MINOR
INTERMITTENT PERFUSION AS
INDICATED BY THE YELLOW ARROWS
HERE.
AND THIS IS A MORE CONVINCING
EXAMPLE OF CHORIOCAPILLARIS
INTERMITTENT PERFUSION OVER ONE
YEAR.
DO YOU SEE THOSE DARK REGIONS
FLICKERING.
THOSE ARE -- AT THE
CHORIOCAPILLARIS LAYER.
SO TO MAKE SURE THAT THESE
CHORIOCAPILLARIS INTERMITTENT
PERFUSION AREAS ARE REAL, NOT
DUE TO SOME OCT'S SEDIMENTATION
ERROR, WE ALSO REVIEWED THE
STRUCTURE O.C.T. LOCATED RIGHT
BELOW THE -- BRAIN SHOWN ON THE
LEFT PANEL HERE.
SO AS YOU CAN SEE, OVER ONE
YEAR, SUGGESTING THE
INTERMITTENT PERFUSION
VISUALIZED ON THE OCTA VIEW NOT
DUE TO SOME SEGMENTATION ERROR.
DOES IT MAKE SENSE?
OKAY.
HERE IT'S ANOTHER EXAMPLE WITH
EVEN MORE SEVERE INTER -- QK
DROPOUTS, I LOVE THIS VIDEO SO I
WILL JUST KEEP STALLING.
ARE YOU ABLE TO SEE INTERMITTENT
PERFUSION?
THIS IS ONE YEAR.
LGBT.
IN ADDITION TO THE INTERMITTENT
PERFUSION INDEX, WE ALSO
MEASURED PERIVASCULAR DENSITY.
COLORED IN RED AND CYAN
RESPECTIVELY.
SO ONE CONTROVERSY IN SICKLE
CELL DISEASE HAS BEEN THE ACTUAL
SITE OF OCCLUSION.
IN SOME ANIMAL STUDIES -- VENUES
MAY BE THE PREFERENTIAL SITE OF
OCCLUSION DUE TO THE ADHESION OF
SITES IN SICKLE CELLS.
OUR PRELIMINARY O.C.T. FINDINGS,
HOWEVER, WOULD SUGGEST THE SITE
WITH HIGH RISK OF VASO-OCCLUSION
IS ACTUALLY LOCATED IN THE
CAPILLARY -- RATIO IN PATIENTS
WITH SICKLE CELL DISEASE.
HERE WE ARE LOOKING AT 22 OCTA
MONTAGES COLLECTED OVER ONE
HOUR.
SO THIS IS ONE OUR, NOT ONE
YEAR.
SO 11 IMAGES AT THE BASELINE
SECTION AND 11 IMAGES AT THE ONE
HOUR FOLLOW-UP.
SO AT BASELINE, WE CAN SEE
MULTIPLE REGIONS WITH OWE
CLEUPTION NEAR -- AND THE
TEMPORO RETINA.
THESE REGIONS ARE SLOWLY
REPERFUSED OVER TIME AND WOULD
COMPLETELY REPERFUSE AFTER ONE
HOUR.
AND HERE I TINTED THE ARTERIOLES
IN RED AND THE VENULES IN
PURPLE.
DID YOU NOTICE ANYTHING IN
COMMON FOR THESE OCCLUDED
RENALES?
THEY ARE ALL ASSOCIATED WITH
ARTERIOLES RATHER THAN VENULES.
SUGGESTING THAT ARTERIOLE
CAPILLARY JUNCTION AS THE
PREFERENTIAL SITE OF
VASO-OCCLUSIONS.
SO IN CONCLUSION, OCTA
ANGIOGRAPHY PRESENTS A PROMISING
AVENUE IN THE MANAGEMENT OF
SICKLE CELL DISEASE THROUGH THE
DEVELOPMENT OF NONINVASIVE
BIOMARKERS TO PROGNOSTICATE
PROGRESSION AND MEASURE THE
RESPONSE TO TREATMENT.
THANK YOU FOR YOUR ATTENTION.
[APPLAUSE]
>> OKAY.
SO -- AND NOW FOR THE FINAL
PRESENTATION FROM THIS SESSION,
I HAVE MYCO-MODERATOR, NADIA
WAHID, PROFESSOR OF
OPHTHALMOLOGY AT TUFTS
UNIVERSITY.
SHE ALSO IS THE DIRECTOR OF THE
O.C.T. READING CENTER AND SHE'S
GOING TO SHARE WITH US OCTA,
UNDERSTANDING PATHOGENESIS AND
PROGRESSION OF RETINAL DISEASE,
FOCUSING ON A.M.D.
THANK YOU RICH, THANK YOU, MIKE
AND TO THE NIH FOR ORGANIZING
THIS.
I'M STUCK.
SLIDES NOT FORWARDING.
THEY ARE NOW.
HERE ARE MY DISCLOSURES.
OF NOTE, MY INSTITUTION RECEIVES
RESEARCH SUPPORT FROM PRETTY
MUCH, YOU KNOW, AND DEVICES FROM
PRETTY MUCH ALL OF THE O.C.T.
DEVICE COMPANIES.
WE HELP GIVE THEM FEEDBACK THAT
AIDS IN THE DEVELOPMENT OF THESE
DEVICES.
OKAY.
SO I'D JUST LIKE TO START WITH
MY ACKNOWLEDGMENTS.
IT HAS REALLY BEEN A GREAT
PRIVILEGE TO WORK OVER THE PAST
DECADE AND A HALF IN
COLLABORATION WITH PROFESSOR JIM
FUJ IMOTO'S LAB AT MIT, IT'S
VERY RARE TO FIND A COLLEAGUE
LIKE THIS WHO IS BOTH INCREDIBLY
BRILLIANT, VERY, VERY CAREFUL
AND INTELLECTUALLY HONEST AND,
AT THE SAME TIME, AS COLLEGIAL
AND AS WONDERFUL A PERSON TO
WORK WITH AS JIM, SO IT REALLY
HAS BEEN BOTH A PLEASURE AS WELL
AS A GREAT LEARNING EXPERIENCE
FOR ME.
I ALSO WANT TO ACKNOWLEDGE JAY
DUKER.
HE HAD STARTED OR WAS INITIALLY
INVOLVED IN THE COLLABORATION
WITH JIM AND VERY LIKELY WHEN HE
BECAME CHAIRPERSON, PASSED THE
LAB OVER TO ME, PROFESSOR
ROSENFELD, WHO WE'VE HAD A
PROFESSIONAL -- ALL OF THESE
STUDIES I'M GOING TO PRESENT
TODAY AS WELL AS THE CLINICAL
GROUP AT THE NEW ENGLAND EYE
CENTER, AND VERY IMPORTANTLY, I
WANT TO ACKNOWLEDGE THE NIH NEI
SUPPORT WITHOUT THIS WHICH IT
WOULDN'T HAVE BEEN POSSIBLE THAT
HAS ENABLED US TO CONTINUE THIS
JOURNEY OVER THE PAST LIKE I
MENTIONED DECADE AND A HALF TO
BETTER UNDERSTAND DISEASE
PATHOGENESIS, AND VERY
IMPORTANTLY HAS LED TO THE NEXT
GENERATION OF THERAPEUTICS AND
IS LEADING TO THE DEVELOPMENT OF
THE FIRST GENERATION OF
THERAPEUTICS FOR DRY M.D. THAT
YOU ARE STARTING TO SEE, TWO IN
CLINIC AT THIS POINT, SO JUST
REALLY WANT TO CALL THAT OUT,
THIS HAS BEEN ONE OF THE FASTEST
TRANSLATIONS FROM BASIC SCIENCE
INTO THE CLINIC THAT I THINK HAS
COME OUT IN MEDICINE AND REALLY
WANT TO ACKNOWLEDGE THE SUPPORT
THAT WE AND OTHER GROUPS HAVE
RECEIVED FROM THE NIH, NEI.
SO TALKING A LITTLE BIT ABOUT
A.M.D., I'M PRIMARILY GOING
FOCUS ON OCTA TODAY BECAUSE I
KNOW YOU'VE HAD TALKS AND ARE
GOING TO HAVE TALKS ON O.C.T.,
BUT WHEN WE TALK ABOUT GRADING
OF A.M.D. THERE'S SYSTEMS TO
GRADE SEVERITY, EARLY,
INTERMEDIATE, LATE, THERE'S THE
AREDS CLASSIFICATION AND THE CAM
GROUP THAT'S PRIMARILY
O.C.T.-BASED.
THERE ARE ALSO ONES THAT ASSESS
PROGRESSION RISK, ON -- SO ONE
OF THE BIG FOCUSES IN OUR LAB
WHEN WE'RE TALKING ABOUT OCTA
HAS BEEN LOOKING TO SEE -- ADD
OCTA AS PART OF THESE GRADING
SYSTEMS AND ESPECIALLY TO ASSESS
THE PROGRESSION OF DISEASE.
ONE CAME OUT EARLY ON IN THE
DAYS OF O.C.T. AS WE AND OTHER
GROUPS WERE LOOKING AT?
-- AND IN THING CHANGES IN THE
CHORIOCAPILLARIS AND HERE ARE
SOME OF THE MAJOR GROUPS THAT
HAVE BEEN WORKING SPECIFICALLY
ON THE CHORIOCAPILLARIS IN
AGE-RELATED MACULAR
DEGENERATION.
WE'VE KNOWN FOR A WHILE,
ALTERATIONS IN THE
CHORIOCAPILLARIS ARE ASSOCIATED
WITH AGE-RELATED MACULAR
DEGENERATION.
SCOTT MA CLOUD SHOWED THAT WAY
BACK.
ROB MULLINS HAS DONE A LOT OF
WORK ON THIS AS WELL, AND WE
KNOW THAT THESE CHORIOCAPILLARIS
CHANGES, SPECIFICALLY LOSS OF
THE CHORIOCAPILLARIS STARTS VERY
EARLY IN THESE PISHTS.
VPATIENTS, VERYEARLY ON, IN FACT
WITH THE NORMAL AGING PROCESS
AND THERE IS SOME DEBATE ABOUT
WHETHER THE CHORIOCAPILLARIS
LOSS PERCEIVES -- BUT I THINK
IT'S RECOGNIZED THAT
CHORIOCAPILLARIS AND RPE START
VERY, VERY EARLY ON IN DISEASE.
NOW ONE OF THE NICE PARTS ABOUT
OCD IN GEOGRAPHY IS YOU CAN
FOLLOW PATIENTS LONGITUDALLY,
UNLIKE IN PATHOLOGY, YOU CAN
ACTUALLY LOOK AT A PATIENT AND
FOLLOW THEM UP A YEAR LATER AND
FOUR YEARS AND FIVE YEARS LATER,
AND SEE HOW THEY HAVE BEEN
PROGRESSING.
SO THE QUESTIONS FOR US THAT OUR
LAB HAS BEEN TRYING TO ASSESS
OVER THE PAST 15 YEARS, 10, 15
YEARS IS, DOES CHORIOCAPILLARIS
LOSS HAPPEN?
IN EARLY AND
INTERMEDIATE A.M.D.?
IS IT WORSE AS A.M.D.
PROGRESSES?
WHAT ARE THE CONFOUNDERS, IS
IT -- THINGS THAT ARE ASSOCIATED
WITH BOTH THE STAGE OF A.M.D. AS
WELL AS ASSOCIATED WITH
PROGRESSION AND THEREFORE CAN
CONFOUND OUR RESULTS, AND THEN
WHAT KIND OF LONGITUDAL STUDIES
CAN WE DO TO BETTER ASSESS THESE
RELATIONSHIPS.
SO MOST OF THE WORK THAT I'M
PRESENTING NOW HAS BEEN DONE ON
USING JIM FUJIMOTO'S PROTOTYPE,
THESE PATIENTS ARE ALSO LOOKED
AT STRUCTURAL O.C.T. USING THE
ULTRA-HIGH RESOLUTION PROTOTYPE
DEVICE DEVELOPED BY PROFESSOR
FEW JFUJIMOTO'S GROUP AGAIN.
WE USE BOTH OF THESE DEVICES TO
KIND OF STUDY AND UNDERSTAND
DISEASE PATHOGENESIS AS WELL AS
PROGRESSION.
IN THIS STUDY WE PROSPECTIVELY
ENROLLED NORMAL VOLUNTEERS IN
PATIENTS WITH VARYING STAGES OF
DRY A.M.D.
ONE OF THE THINGS THAT WE'VE
ALSO STARTED DOING IN
COLLABORATION WITH PROFESSOR
FUJI KNOW TOE'S LAB IS ALSO
STARTING TO ENROLL THESE
PATIENTS ON TO COMMERCIAL
DEVICES TO TRY AND SEE IF WE CAN
TRANSLATES THE RUTLE WE'RE
SEEING IN THIS VERY HIGH-TECH
PROTOTYPE DEVICE INTO THE
COMMERCIAL DEVICES AS THESE GET
ROLLED INTO CLINICS.
AND THE REASON WE LIKE USING
SWEAT SOURCE, THE LONGER
WAVELENGTHS HAVE BETTERTER
PENETRANCE INTO THE
CHORIOCAPILLARIS AN AND AS WELLS
THE OUTER CHANGES SUCH AS DRUSEN
THAT HAPPEN IN PATIENTS WITH
MACULAR DEGENERATION THAT MAKE
EVALUATION OF THE COROLLARY
CAPILLARIS IF YOU'RE USING A
STANDARD SPECTRAL DOMAIN SYSTEM.
SO SOME OF THE FIRST THINGS THAT
WE STARTED OUT WITH, WHEN WE
STARTED STUDYING THE
CHORIOCAPILLARIS IN THE MACULAR
REGION OF NORMAL SUBJECTS, WE
NOTICED THAT THIS WAS GENERALLY
DENSE AND H HOMOGENEOUS, THAT
THERE WAS LOSS OF
CHORIOCAPILLARIS WITH AGE, AND
THIS WAS MORE PRONOUNCED IN THE
CENTRAL FOVEAL REGION, AND THESE
RESULTS AGAIN HAVE BEEN
VALIDATED ACROSS MULTIPLE
DIFFERENT GROUPS THAT HAVE
LOOKED AT -- IN NORMAL AGING.
SO WHAT DO WE START SEEING IN
PATIENTS WITH A.M.D.?
AS I MENTIONED WE KNOW FROM
HISTOPATHOLOGIC STUDIES HAVE A
PRETTY ENLARGED -- WE STARTED
ENROLLING THESE PATIENTS IN
CROSS-SECTIONAL STUDIES USING
THE DEVICES THAT I SPOKE ABOUT,
AND YOU KNOW, WE KNOW BASED ON
DATA FROM ROBYN GUYMER'S GROUP
AND VARIOUS INVESTIGATORS THAT
STRUCTURAL CHANGES CAN BE SEEN
VERY EARLY AND PRECEDE THE
DEVELOPMENT OF COMPLETE
GEOGRAPHIC -- AND WHETHER THESE
PATIENTS -- WE STARTED ENROLLING
PATIENTS WHO ARE AT A HIGH RISK
OF DEVELOPING ATROPHY PATIENTS
WITH SAY NASCENT ATROPHY OR LOSS
OF THE OUTER RETINA, ALONG WITH
INTERMEDIATE A.M.D. PRIOR TO
DEVELOPMENT AND WE STARTED
LOOKING AT THE CHORIOCAPILLARIS
IN THESE PATIENTS.
AND WHAT WE FOUND WAS THAT THEY
WERE CHORIOCAPILLARIS
ALTERATIONS IN EYES WITH NASCENT
ATROPHY AND DRUSEN -- WHICH WERE
THE TERMS THAT WERE PREVIOUSLY
USED FOR WHAT'S NOW CLASSIFIED
AS IRORA FOR THE --
PREDICTICALLY UNDER THESE AREAS
WE STARTED FINDING THERE WERE
AREAS OF CHORIOCAPILLARIS LOSS.
SO IF YOU WALK THAT BACK A
LITTLE BIT AND START LOOKING AT
PATIENTS WITH DR USEN TO SEE
WHERE THESE CHANGES START
HAPPENING UNDERNEATH THESE AREAS
OF DRUSEN, WE NOTICED THERE WAS
LOSS OF CHORIOCAPILLARIS AND
EVEN UNDER AREAS OF DRUSEN THAT
DON'T YET HAVE ANY ATROPHY
ASSOCIATED WITH THEM.
ON THE OTHER HAND, THERE WERE
ALSO DRUSEN THAT DID NOT SHOW
CHORIOCAPILLARIS LOSS, AND THIS
WAS REPLICATED BY AGAIN AS I
MENTIONED ACROSS VARIOUS
MULTIPLE GROUPS SINCE WE
INITIALLY PUBLISHED THOSE
RESULTS.
HOWEVER, DOING A DRUSEN BY
DRUSEN EVALUATION IS CHALLENGING
IN A CLINICAL TRIAL SETTING,
IT'S QUALITATIVE, IT VERY
TIME-CONSUMING, SO CAN WE NOW DO
THIS AT A LARGER LEVEL AND LOOK
AT IT IN A MORE QUANTITATIVE
SCWAIL?
SCALE?
SO QAWPT TAITIVE SCALES ARE ONE
OF THE THINGS WE TRIED TO
ESTABLISH BECAUSE THEY'RE
SOMETHING YOU CAN MOVE FORWARD
INTO CLINIC AND SOMETHING YOU
CAN MOVE FORWARD INTO CLINICAL
TRIALS THAT LOOK AT DRUG
DEVELOPMENT.
WELL LOOKED AT THIS METRIC FOR
QUANTIFYING CHORIOCAPILLARIS
FLOW VOIDS AND WE USED A
MULTI-SCALE FLOW VOID MAPPING,
VARIOUS FORMS HAVE BEEN USED
SINCE THAT, AND ALL OF THESE
ESSENTIALLY LOOK FOR -- IN THE
CHORIOCACAPILLARIS IN VARYING
LEVELS OF A.M.D.
NOT ONLY WAS THE AREA OF
CHORIOCAPILLARIS LOSS IMPORTANT
BUT THE CLUSTERING OF THESE
AREAS TOGETHER ALSO PREDICATED
MORE ADVANCED DEVELOPMENT OF
DISEASE.
SO WHEN WE STRATIFIED PATIENTS
BY SEVERITY OF A.M.D., WE FOUND
THAT NOT ONLY WAS THERE
INCREASED CHORIOCAPILLARIS
ALTERATION BY AGE, BUT THERE WAS
ALSO INCREASING CHORIOCAPILLARIS
ALTERATION WITH MORE ADVANCED
DISEASE STATE.
SO WHEN YOU LOOK
CROSS-SECTIONALLY AS YOU GET
MORE ADVANCED DISEASE STATE, YOU
GET WORSE AND WORSE AND WORSE
CHORIOCAPILLARIS.
SO ALL OF THIS IS WELL AND GOOD
IF YOU'RE DOING IT IN A
PROTOTYPE SYSTEM, THERE'S ONLY
ONE OF THAT PROAT SIDE SYSTEM OR
IT MAY BE TWO IN THE WORLD,
THEY'RE ALL DEPLOYED IN OUR LAB
AT THE NEW ENGLAND EYE CENTER,
HOW DO YOU THEN TAKE WHAT JIM IS
DEVELOPING IN HIS MACHINES AND
APPLY IT ON A MORE BROAD SCALE
ACROSS CLINICAL TRIALS AND IN
PATIENTS.
SO PHIL BRAUN, POST-DOCTORAL
FELLOW WITH US, THEN TOOK THIS
ON TO THE SLAB SOURCE O.C.T. AN-
HE LOOKED AT THESE FLOW VOIDS.
OF COURSE ONE OF THE ISSUES WITH
COMMERCIAL MACHINES IS THAT YOU
GET THE DATA IS MUCH LESS
FLEXIBLE, IT'S A LITTLE BIT OF A
BLACK BOX, YOU GET THE DATA THAT
YOU GET, AND YOU ARE NOT ABLE TO
RUN VERY MANY VARIATIONS ON THE
O.C.T. IN GEOGRAPHY RAW DATA.
SO WE USE THIS TECHNOLOGY
DEVELOPED BY ZHANG IN THE LAB
OVER IN RICKEY WANG'S LAB IN
WASHINGTON, AS WELL AS THE
O.C.T. -- AND ADJUST FOR AREAS
OF SHADOWING TO MAKE SURE WE
WERE NOT PICKING UP AREAS JUST
OF SHADOWING, AND TO DEVELOP
THESE OCTA AND GEOGRAPHY MAPS,
AND THEN WE LOOKED AT THE
CENTRAL 1-MILLIMETER,
3-MILLIMETER AND 5-MILLIMETER
CIRCLES AND WHAT WE FOUND WAS
THAT AS YOU LOOKED AT THESE
SERVICES, THAT THE CENTRAL AREAS
BECAME VERY QUICKLY AFFECTED BY
AGING.
SO THE CENTRAL 1 AND
3-MILLIMETER CIRCLES WERE VERY
EASILY AFFECTED THEREFORE WERE
NOT VERY SENSITIVE TO STAGE OF
DISEASE BECAUSE ALMOST EVERYONE
WAS AGED TEND TO HAVE MORE FLOW
VOIDS, HOWEVER WHEN YOU MOVED
OUT OF THOSE CENTRAL CIRCLES AND
LOOKED AT LIKE THE 5-MILLIMETER
AREA OR LOOKED AT THE ENTIRE
SLAB, YOU GOT A VERY HIGH
SENSITIVITY FOR STAGE OF DISE
DISEASE, AND THAT WAS INITIALLY
DONE AT THE NEW ENGLAND EYE
CENTER, WE THEN COLLABORATED
ACROSS A LARGE DATASET THAT SHE
HAD COLLECTED AS PART OF HER
RESEARCH, SUGGESTING LOCALIZED
IMPAIRMENT AND REDUCED BLOOD
FLOW PRECEDING THE DEVELOPMENT
OF ATROPHIC A.M.D. LESIONS IN
HER COHORT OF PATIENTS AS WELL.
SO NOW WHAT ABOUT GEOGRAPHIC
ATROPHY?
WE ACTUALLY STARTED WITH G.A.
BECAUSE THIS WAS ONE OF THE
EASIEST THINGS TO SEE.
SO THIS IS ONE OF OUR VERY FIRST
PUBLICATIONS THAT WE DID LOOKING
AT CHORIOCAPILLARIS BLOOD FLOW
UNDER GEOGRAPHIC ATROPHY.
WE FOUND NOT ONLY WAS THERE LOSS
OF CHORIOCAPILLARIS BLOOD FLOW
UNDER THE AREA OF GEOGRAPHIC
ATROPHY BUT YOU SEE THERE ALSO
APPEARS TO BE LOSS OF
CHORIOCAPILLARIS OUTSIDE OF THE
IMMEDIATE AREAS OF GEOGRAPHIC
ATROPHY.
I'M GOING TO TALK ABOUT VISTA
THAT WAS DEVELOPED AGAIN BY
JIM'S GROUP AT THE MIT LAB, AND
THIS UTILIZES VARIATIONS IN THE
TIME INTERVALS BETWEEN
CONSECUTIVE OCTA SCANS TO ASSESS
NOT JUST THE BINARY PRESENT FLOW
OR ABSENT BUT ALSO SPEED OF FLOW
IN THE RETINA.
THESE ARE NOW GETTING ROLLED TO
COMMERCIAL DEVICES FINALLY AFTER
ALMOST EIGHT OR NINE YEARS OF
THE INITIAL PUBLICATIONS AND
WE'RE REALLY EXCITED ABOUT THE
CAPABILITIES THAT THIS WILL
BRING TO THOSE COMMERCIAL
DEVICES.
SO WE LOOKED AT THE VISTA IN
THESE PATIENTS WITH GEOGRAPHIC
ATROPHY AND WHAT WE SAW WAS THAT
THERE WAS AN ALMOST TOTAL LOSS
OF CHORIOCAPILLARIS UNDER LYING
THE AREAS BUT WHEN YOU LOOKED IT
THE AREA AROUND THE GEOGRAPHIC
ATROPHY, THERE WAS SOME LOSS OF
CHORIOCAPILLARIS BUT THERE WAS
ALSO A LOT OF SLOWING DOWN OF
THE BLOOD FLOW.
NOTE VERY NICELY OVER HERE THAT
THERE IS SLOW BUT PRESERVED
BLOOD FLOW IN THAT SMALL AREA
THAT HAS MACULAR SPARING, THE
FOVEAL SPARING IN THIS PATIENT.
SO REALLY TO HAVE VIABLE RETINA,
EVEN IF YOU HAD SLOW BLOOD FLOW,
YOU NEEDED TO HAVE BLOOD FLOW
DOWN THERE.
SO ONE OF THE QUESTIONS WAS, IS
GLOBAL CHORIOCAPILLARIS
IMPAIRMENT CORRELATED WITH G.A.
GROWTH RATE.
SO NOW THIS IS TAKING ALL THE
DATA THAT WE ACQUIRED
CROSS-SECTIONALLY AND TRYING TO
SEE HOW WE CAN TRANSLATE THIS
INTO A RISK ASSESSMENT FOR
PATIENTS.
SO GLOBAL CHORIOCAPILLARIS
IMPAIRMENT IS CORRELATED WITH
G.A. GROWTH RATE, THEY DID THIS
REALLY NICE SMALL LONGITUDAL
STUDY WHERE WE LOOKED AT SOME
PATIENTS AT THE NEW ENGLAND EYE
CENTER AND FOLLOWED THEM UP OVER
TIME, AND WE INDEED DID FIND, IF
YOU SEPARATE OUT THE UNIFOCAL
PATIENTS THAT GLOBAL
CHORIOCAPILLARIS IMPAIRMENT WAS
CORRELATED WITH G.A. GROWTH
RATE.
OUR NEXT QUESTION WAS IS
CHORIOCAPILLARIS IMPAIRMENT
ADJACENT MORE CORRELATED WITH
G.A. GROWTH RATE FURTHER FROM
THE G.A. MARGINS AND WHEN WE
LOOKED AT THAT, IT DIDN'T REALLY
LOOK LIKE IT, AT LEAST NOT IN
OUR COHORT OF PATIENTS.
SO THERE IS SOME VARIABLE DATA
ON THIS DEPENDING ON WHICH YOU
LOOK AT BUT OUR DAY IT DID NOT
SUPPORT THE HYPOTHESIS THAT
IMPAIRMENT IN REGIONS CLOSER TO
THE MARGIN WAS MORE STRONGLY
CORRELATED WITH LESION GROWTH
RATE THAN IN REGIONS FURTHER
AWAY FROM THE MARGIN, THAT'S
ACTUALLY GOOD NEWS BECAUSE YOU
CAN DO A MORE SIMPLER GLOBAL
ANALYSIS TO ACTUALLY ASSESS RI
RISK.
THEN THE FINAL QUESTION WAS DO
G.A. LESIONS PREEF RENGSLY GROW
INTO REGIONS OF CHORIOCAPILLARIS
IMPAIRMENT?
I WON'T GO INTO THIS DETAILED
ANALYSIS BUT AS YOU CAN SEE WE
DID VERY LOCAL ANALYSES OF
CHORIOCAPILLARIS IMPAIRMENT AT
EACH SPOT ALONG THE G.A. MARGIN
AND THEN MAPPED OUT THE GROWTH
RATE OF EACH SIDE OF THE G.A.
LESION AND WHAT WE DID FIND WAS
THAT ACTUALLY PROBABLY NOT, THEY
PROBABLY DON'T GROW IN REGIONS
OF CHORIOCAPILLARIS IMPAIRMENT
BUT IT'S OVERALL THESE SCHEMA
THAT'S DRIVING GROWTH AND NOT
NECESSARILY DRIVING DIRECTIONAL
GROWTH.
SO IS CHORIOCAPILLARIS LOSS IN
INIMMEDIATE A.M.D. A MARKER FOR
PROGRESSION?
IT HAPPENS EARLY, IT'S WORSE AS
DISEASE ADVANCES.
AGE IS A DOMINANT CONFOUNDER,
AND THE EFFECT IS SEEN IN THE
OUTER RINGS BUT ALSO IN THE
WHOLE SLAB ANALYSIS.
AND ARE THERE LONGITUDAL
ANALYSES?
AT THAT POINT WE STARTED A
COUPLE OF LARGE LONGITUDINAL
STUDIES WHICH ARE THE IMPACT AND
SWAGGER STUDDIES.
WE HAVE MOSH TWO YEARS OF
FOLLOW-UP IN THESE PATIENTS NOW,
AND THE ANALYSIS ARE CURRENTLY
OP GOINGONGOING SO YOU SHOULD SE
RESULTS COMING OUT SOON.
IT MAY BE A USEFUL MARKER FOR
THE STAGE OF A.M.D. AND MAY HELP
US DETERMINE WHAT PATIENTS ARE
LIKELY TO BE FAST PROGRESSERS
VERSUS WHAT PATIENTS ARE LIKELY
TO BE SLOW PROGRESSERS IN
COLLABORATION WITH THE OTHER
STRUCTURAL BIOMARKERS THAT WE
KNOW NOW.
THE CAVEAT OVER HERE IS, THERE
WAS THIS REALLY NICE ANALYSIS
THAT SHOWED THAT THE TECHNIQUES
THAT HE USED TO BINARRIZE AND
THRESHOLD CAN INTRODUCE AS OR
AND THEREFORE YOU HAVE TO BE
VERY CAREFUL ABOUT BINARIZATION
AND THRESHOLD IN THE
CHORIOCAPILLARIS, AND THERE DOES
HAVE TO BE CONSENSUS AROUND THE
BEST WAY OF ANALYZING COMMERCIAL
IMAGES ESPECIALLY FOR THE BLACK
BOX THAT IS COMMERCIAL IMAGES,
AS WELL AS TRANSPARENCY FROM THE
DEVICE MANUFACTURERS ON THE WAY
THESE IMAGES ARE ENHANCED AND
THE WAYS IN WHICH THEY'RE
ANALYZED IN THESE COMMERCIAL
DEVICES.
SO WHAT ARE THE IMPLICATIONS?
A LOT OF DEATH AND DESTRUCTION
GOING ON IN THE
CHORIOCAPILLARIS.
AS WE AGE, WE ALL LOSE
CHORIOCAPILLARIS BUT METRICS CAN
ALSO BE A MARKER FOR THE
SEVERITY OF A.M.D. AND MAY BE
USEFUL IN STRATIFYING PATIENTS
FOR CLINICAL TRIALS OF EARLY AND
INTERMEDIATE A.M.D. AND THEY DO
CORRELATE ARE THE RATE OF
PROGRESSION IN G.A. BUT
ASSESSING CHORIOCAPILLARIS
METRICS IS DIFFICULT AND
REQUIRES VERY COMPLEX ANALYSES
AND RIGOROUS QUALITY CONTROL AND
THERE DOES NEED TO BE RIS RUSS
STANDARDIZATION OF THESE
METRICS.
I WANT TO END OVER HERE, THANK
EVERYONE INVOLVED IN THIS
RESEARCH AND THANK YOU FOR YOUR
ATTENTION TODAY.
[APPLAUSE]
>> SO ACTUALLY I THINK TIME FOR
THE PANEL DISCUSSION, SO RICH,
IF YOU WANT TO COME UP AND IF
ALL THE PRESENTERS WILL PLEASE
MAKE THEIR WAY UP ON STAGE.
IF THERE ARE ANY QUESTIONS,
PLEASE FEEL FREE TO COME TO THE
MICS AND GO AHEAD AND START WITH
ASKING.
>> SO I HAVE A QUESTION FOR YOU,
NADIA.
BEAUTIFUL WORK, VERY NICE
PRESENTATION.
SO DID YOU LOOK AT ANY PATIENTS
WHO HAD EARLY INTERMEDIATE
A.M.D., AND WHAT WAS THE
INCIDENCE OF CHORIOCAPILLARIS
DROPOUT IN THOSE PATIENTS THAT
HAVE NO EVIDENCE OF ATROPHY?
>> SO WE DID FIND THAT IT'S
REALLY INTERESTING BECAUSE YOU
CAN'T DEFINE A BINARY OF
CHORIOCAPILLARIS DROPOUT YES
VERSUS NO ABOVE AND BEYOND AGESG
SO WE'RE LOOKING AT AVERAGES.
BUT WHEN YOU LOOK AT THE
AVERAGES, THE VAST MAJORITY OF
PATIENTS WHO HAVE EARLY A.M.D.
AT LEAST IN OUR STUDIES, I THINK
IT'S BEEN REPLICATED ACROSS MANY
DIFFERENT GROUPS, DO SEEM TO ON
AVERAGE HAVE MUCH MORE
CHORIOCAPILLARIS DROPOUT
COMPARED TO NORMAL AGING.
AND I THINK IT'S ESPECIALLY
VISIBLE WHEN YOU MOVE OUTSIDE OF
THE IMMEDIATE CENTRAL REGION AND
INTO THE VERY CENTRAL REGION.
BUT OF COURSE PATIENTS WHO TEND
TO PROGRESS TEND TO HAVE MORE
THAN PATIENTS OR AT LEAST WHAT
WE'VE SEEN THAN PATIENTS WHO
DON'T TEND TO PROGRESS AS FAST.
>> IT'S VERY EXCITING THAT HE YU
SHOWED IT WASN'T LOCALIZED WHICH
REALLY BACKS UP THE WORK THAT
PEOPLE HAVE FAILED TO SHOW FOR A
LONG TIME.
I KNOW VLAS WAS WORKING ON THIS
FOR A LONG TIME AND IT NEVER
SEEMED TO PAN OUT.
>> I THINK IT'S A MORE
GENERALIZED ISCHEMIC PHENOMENON
THAN IT IS A LOCAL PHENOMENON.
SO IF WE HAVE SOME PEOPLE HERE
TO ASK QUESTIONS?
>> HI, NADIA.
PAT DEMORI FROM MOUNT ZION.
THIS MAY BE A PREMATURE QUESTION
BUT, IS IT POSSIBLE NOW OR EVER
TO CORRELATE THE DEGREE OF
CHORIOCAPILLARIS DROPOUT WITH
THE SIZE OF THE DRUSEN, EITHER
TOTAL SIZE OR HEIGHT?
I'VE ALWAYS THOUGHT HEIGHT OF
DRUSEN WAS GOING TO BE REALLY
LIKE A -- IT'S ISCHEMIA, BUT IN
MY OPINION, IT'S ALSO A BARRIER
FOR THE VEGF COMING FROM RPE
THAT THE CHORIOCAPILLARIS NEEDS
TO SURVIVE.
SO THAT'S A BARRIER NOT ONLY OF
OXYGEN BUT OF OTHER DIFFUSION.
AND TET, BROO BROOKS IS THICKENR
AT LEAST BECOMING MORE
PERMEABLE.
>> I THINK THAT WOULD ALSO
EXPLAIN WHY YOU HAVE
CHORIOCAPILLARIS DROPOUT JUST
WITH AGING.
I THINK GROUPS HAVE CORRELATED
CHORIOCAPILLARIS DROPOUT
WITHDRDROPOUT WITHDRUSEN VOLUME.
I DON'T KNOW IF NEAR-INFRARED
ONE HAS LOOKED SPECIFICALLY AT
HEIGHT BUT THAT'S AN INTERESTING
QUESTION AND THE DATA IS
DEFINITELY THERE, SO WE SHOULD
BE ABLE TO GO BACK AND HAVE A
LOOK AT THAT SO LET'S CHAT.
>> OKAY, GREAT.
DAVID.
>> HI, I HAVE A QUESTION FOR
TOCO.
YOU HAVE EXPLORED INTERMITTENT
FLOW AND SERVE -- SO MY QUESTION
IS ABOUT THAT, WHETHER IT USEFUL
TO LOOK AT TIME WITHIN A CARDIAC
CYCLE AND BEYOND A CARDIAC
CYCLE, THERE ARE MINUTES, HOURS
AND DAYS.
I WOULD ASSUME THERE -- DO YOU N
IDEA WHICH ONE IS CLINICALLY
USEFUL IN THE DISEASE SETTING?
>> I DON'T HAVE A VERY CLEAR
IDEA ABOUT THAT RIGHT NOW.
BUT BASED ON OUR PRELIMINARY
DATA, THE INTERMITTENT
PROFICIENT INDEX THAT WE MEASURE
IN SICKLE CELL DISEASE, IT WORKS
BECAUSE IT HAS A VERY CLEAR
SEPARATION BETWEEN THE TWO
SECTIONS.
HAVING SAID THAT, WE ALSO NOTICE
IPT MITT ENT PERFUSION WITHIN
ONE SECTION.
BUT WE WERE NOT ABLE TO QUANTIFY
THAT INTERMITTENT PERFUSION
WITHIN SECTION BECAUSE WE ARE
LIMITED BY THE LOWER
SIGNAL-TO-NOISE RATIO.
BUT I DO SEE IF WE HAVE A FASTER
SCANNER, BETTER IMAGE QUALITY,
WE SHOULD BE ABLE TO MEASURE
INTERMITTENT PERFUSION --
QUANTIFY INTERMITTENT PERFUSION
JUST WITHIN THE FIRST SECTION
WHICH IS LESS THAN 10 MINUTES.
OR IF WE EVEN HAVE A FASTER
SCANNER OR THE VISTA MACHINE, WE
SHOULD BE ABLE TO DO IT WITHIN
ONE SCAN.
>> SO IT DOESN'T HAVE TO TAKE A
LOT OF TIME IN CLINIC?
>> IT DOESN'T NEED TO TAKE A LOT
OF TIME.
TAKE MY STUDY AS PROOF OF
CONCEPT STUDY.
I JUST WANT TO SHOW PEOPLE THAT,
YES, WE'RE ABLE TO SEE THIS
INTERMITTENT PERFUSION.
BUT I'M VERY HOPEFUL THAT WE
COULD SHORTEN THE ENTIRE IMAGING
TIME INTO MAYBE LESS THAN A
MINUTE OR EVEN WITHIN SECONDS.
>> BY THE WAY, I NEVER WEAR A
WATCH AND ERIC SWANSON NEVER
WEARS A MUSTACHE, SO -- THOSE
CARTOON VIDEOS ARE TAKING A LOT
OF LIBERTY WITH OUR APPEARANCE,
BUT IT ALL IN THE SPIRIT OF FUN.
>> I HOPE YOU RECOGNIZE YOURSELF
IN THAT CARTOON CHARACTER.
YOU DON'T?
[LAUGHTER]
>> QUESTION TO THE SICKLE CELL
EXPERT.
SO AS THE SICKLE CELLS ARE
CLUSTERING AND ULTIMATELY THE
VESSEL LETS THEM GO, IS THERE A
CHANGE IN THE ARTERIAL
PLASTICITY IN THE SICKLE CELL
DISEASE?
>> SORRY, I'M NOT ABLE TO HEAR
VERY WELL FROM HERE.
YOU WERE ASKING --
>> THERE IS TEMPORARY BLOCKAGE,
BUT THEN THE CELLS -- SICKLE
CELLS WERE ABLE TO GO THROUGH.
SO IS THERE A CHANGE IN THE
ARTERIAL PLASTICITY IN SICKLE
CELL DISEASE?
OBVIOUSLY ALL OF THE -- CENTRAL
IN THE ARTERY.
>> I SEE.
SO THERE ARE MULTIPLE FACTORS,
SO THE INTERMITTENT PERFUSION
EVENT OR THE INDEX IS AFFECTED
BY THE NUMBERS OF SICKLE CELLS
THAT ARE FLOWING INSIDE THE
BLOODSTREAM, AND ALSO THE
ELASTICITY OF THE VASCULATURE,
OF THE BLOOD VESSEL WALL, YES,
SO THAT'S MORE THAN -- IT'S NOT
JUST THE BLOOD CELL ISSUE, IT'S
ALSO THE VASCULAR WALL ISSUE.
>> SO IT WOULD BE MORE
INTERESTING TO SEE ULTRASOUND
TECHNIQUE -- IN THE PERIPHERAL
ARTERY, WHERE IT MIGHT BE EASIER
TO MEASURE THE ARTERIAL
PLASTICITY.
>> I'M NOT -- DR. ROSEN, ARE YOU
ABLE TO GET THAT QUESTION?
>> I DIDN'T HEAR.
>> IT APPEARS YOU'RE THE
MODERATOR HERE SO YOU CAN HELP
ME WITH THIS.
I WORK WITH DR. ROSEN, SO HE
MIGHT BE ABLE TO --
>> SO ONE MORE QUESTION TO
DR. KASANI.
EXCELLENT WORK AND EXCELLENT
PRESENTATION.
SOLACE YOU ARE FOLLOWING UP THE
VASCULAR DENSITY, SO INSTEAD OF
MAPPING A FEW AREAS, YOU MUST DO
THE COMPLETE MAPPING, SO THAT
WAY YOU GET AN INTEGRAL VIEW.
AND THEN YOU COULD FOLLOW UP HOW
IT IS CHANGING WITH AGE, WITH
DEGENERATION, WITH TREATMENT AND
EVERYTHING ELSE.
SO WHAT ARE YOU MEASURING IN
CAPILLARY DENSITY?
IS IT THE NUMBER OF CAPILLARIES
FOR A UNIT AREA, THEIR DIVERSITY
BECAUSE CA THEY HAVE DIFFERENT
SIZES AND FUNCTION.
SO IS THERE SOMETHING YOU COULD
ULTIMATELY RELATE TO THE BLOOD
FLOW?
>> SO THAT'S A GOOD QUESTION.
SO THERE'S MANY DIFFERENT WAYS
OF QUANTIFYING THOSE OCTA MAPS.
AND THE METRIC THAT WE USE MOST
FREQUENTLY IS CALLED VESSEL
SKELETON DENSITY, SO BASICALLY
WHAT YOU DO IS YOU TAKE THE OCTA
IMAGE THAT IS GENERATED BY THE
DEVICE AND THEN YOU ACTUALLY
JUST LOOK AT EITHER THE AREA OF
THE IMAGE THAT'S COVERED BY
BINARIZED PIXELS, VESSEL AREA
DENSITY, OR YOU SKELETONIZE
THOSE CAPILLARES PROFILES AND
YOU LOOK AT THE ABSOLUTE LENGTH
OF CAPILLARES.
CAPILLARIES, SO IT'S EITHER
LENGTH OR UNITS IN AN IMAGE.
THERE'S MULTIPLE OTHER METRICS
THAT YOU CAN USE, BUT IN THAT
AREA, IT IS A GLOBAL MAP AND YOU
CAN LOOK AT DIFFERENT LAYERS,
RIGHT, YOU CAN LOOK AT THE
SUPERFICIAL LAYER OR THE
INTERMEDIATE LAYER OR THE DEEP
LAYER OR THE FULL THICKNESS.
AND WE'VE DONE IT EVERY WHICH
WAY, AND THE FINDINGS ARE
USUALLY MUST ROB MORE ROBUST FOE
SUPERFICIAL LAYER AND DEEP --
PROJECTION ARTIFACT ALGORITHMS
ARE PRETTY GOODENOW TOO, BUT
LARGER FIELDS OF VIEW, WHEN WE
WERE DOING A LOT OF THOSE
STUDIES, LARGER FIELDS OF VEUL
WERE DEFINITELY NOT COMMERCIALLY
AVAILABLE OR AVAILABLE AT ALL.
AND IT WOULD BE GREAT TO DO
LARGER FIELDS OF VEUL BUT
RESOLUTION FALLS OFF AND SOME OF
THE GREAT TALKS YOU HEARD ABOUT
TODAY LIKE YALI'S TALK ARE
DESIGNED TO GET WIDER FIELDS OF
VIEW AND MAINTAIN THE SAME
RESOLUTION AS YOU GET IN A THREE
BY THREE OR A SIX BY SIX.
SO THAT'S CHALLENGING, BUT
THERE'S PEOPLE WORKING ON IT AND
I'M SURE IT WILL BE AROUND SOON.
>> KEEP DOING THE MEASUREMENTS.
THAT'S WHERE THE GOOD SCIENCE IS
ALL ABOUT.
>> THANK YOU.
THANKS A LOT.
I HAVE A QUESTION ACTUALLY FOR
TOCO IF I CAN.
AND YALI.
WHEN YOU SAY 3%, YOU WENT FROM
3% REPERFUSION INDEX OR
PERFUSION INDEX TO LIKE 0.5,
DOES THAT MEAN THAT IT'S 3% OF
THE PIXELS OR 3% OF THE
CAPILLARY SEGMENTS?
>> 3% OF THE PIXELS.
YOU A. SO GREAT.
>> AND I THINK LAST QUESTION
FROM DAVID.
>> I HAVE SO THE COMMENT AND
QUESTION FOR AMIR.
I FIND YOUR PRESENTATION OF THE
FLUX DENSITY INTERESTING BUT
SOMEWHAT PROBLEMATIC.
YOU KNOW, WE ALSO LOOKED AT
SOMETHING SIMILAR CALLED FLOW
INDEX AND I AGREE THAT IT IS A
MORE ROBUST REFLECTION OF
DISEASE IN SOME WAY BECAUSE IT
REFLECTS BOTH THE SKELETAL
DENSITY AND VELOCITY AND VESSEL
CALIBER.
BUT I'VE ALWAYS BEEN BOTHERED BY
YOUR USE OF THE INTERLIPID
EXPERIMENT TO MOTIVATE IT
BECAUSE I DON'T THINK THAT SCALE
IS TO A CLINICAL SITUATION.
THE EXPERIMENTS ARE DONE AT
CONCENTRATION OF 1, 2, 3, 4%,
LOW PERCENTAGE, BUT IT DOESN'T
REALLY SCALE TO HIGHER
PERCENTAGES BECAUSE IF YOU THINK
OF 100% LIPID, THERE WOULD BE NO
FLOW SIGNAL.
100% WATER, NO FLOW SIGNAL.
IT MAXIMIZES AT 50%.
AND THAT'S WHERE RED BLOOD CELL
DENSITY SITS.
SO IT DOESN'T REALLY REFLECT RED
BLOOD CELL DENSITY THAT MUCH.
THAT LAST JUST DOESN'T FOLLOW.
THAT'S MY OPINION.
BUT MY QUESTION IS, WE FOUND
FLOW INDEX FLUX DENSITY MAY
PROBLEMATIC IN THAT IT WOULD BE
HIGH LEER SUSCEPTIBLE TO SIGNAL
STRENGTH VARIATION.
DO YOU FIND THAT AS WELL IN YOUR
FLUX WORK?
>> GREAT POINT INITIALLY.
SO WE DON'T HAVE IN VITRO FLUID
IK MODEL USING RBCs AND
CERTAINLY IN VIVO, IT IS VERY
DIFFERENT, THERE'S LOTS OF
DIFFERENT THINGS GOING ON.
HOWEVER, THE CORRELATIONS EXIST,
RIGHT?
AND SO THAT'S WHY WE DID THE
EXPERIMENTS THAT I SHOWED YOU IN
HUMAN SUBJECTS.
WE ACTUALLY LOOKED AT HUMAN
SUBJECTS ACROSS A NORMAL
HEMATOCRIT SO THE CORRELATIONS
EXIST AND THEY'RE VERY
SIGNIFICANT AND THEY'RE
REPRODUCIBLE AND WE'RE ACTUALLY
DOING IT ON A VERY LARGE SCALE.
SO I AGREE IT PROBABLY DOESN'T
TRANSLATE 100% BETWEEN MICRO
SPHERES OR LIPID SPHERES OR
WHATEVER YOU USE IN VITRO, BUT
IT DOES TRANSLATE ENOUGH FOR US
TO GET A SIGNAL THAT IS
SOMETHING MORE THAN JUST
THRESHOLDING AN IMAGE AND
BINARIZING IT.
SO WHAT EXACTLY THAT IS WILL
PROBABLY TAKE A LOT MORE IN
VITRO WORK.
WHICH I'D LOVE TO DO WITH
SOMEBODY.
THE SECOND PART OF YOUR QUESTION
WAS?
SORRY, I FOR FORGOT THE SECOND.
WHAT WAS THE SECOND?
OH, SIGNAL STRENGTH.
IT IS HIGHLY SENSITIVE TO SIGNAL
STRENGTH.
EXTRAORDINARILY SENSITIVE TO
SIGNAL STRENGTH.
SO THAT'S ONE OF THE REASONS WHY
WE STILL LOOK AT VESSEL SKELETON
DENSITY IN ALMOST EVERY MEASURE.
SO YOU CAN ONLY TAKE THE BEST OF
THE BEST OCTA IMAGES AND USE
FLUX.
AND IN FACT WE ONLY DO IT WITH
THE SWEAT SOURCE DEVICE WHICH IS
WHY I DON'T PRESENT IT ON EVERY
SINGLE DATASET.
SO IT TAKES, AS NADIA SAID, A
LOT OF QC, A LOT OF EFFORT TO
ACQUIRE THOSE IMAGES AND SO YOU
JUST CAN'T THROW SOMEBODY BEHIND
A SCANNER AND GET FLUX MEASURES.
BUT THAT IS ONE OF THE DRAWBACKS
FOR SURE.
>> I HAVE A QUESTION FOR YALI.
SO I REALLY LIKED THE
COMBINATION OF STRUCTURAL AND
OCTA, IT'S SO MUCH MORE POWERFUL
IN TERMS OF SHOWING WHAT'S
REALLY GOING ON.
SO IN TERMS OF A.I., IS IT
CONCEIVABLE THAT TOOLS WOULD BE
DEVELOPED THAT WOULD
SPECIFICALLY -- FOR MOST
CLINICIANS, THEY DON'T HAVE TIME
TO GO THROUGH ALL THESE GREAT
IMAGES, BECAUSE WE HAVE ONLY
MICRO SECONDS TO SEE PATIENTS.
AND SO THE QUESTION IS, CAN
THE -- DO YOU THINK THAT THE
SOFTWARE IN THE CONCEIVABLE
FUTURE WILL BE AVAILABLE THAT
BASICALLY WOULD BE ABLE TO PICK
UP, SAY, NEOVASCULAR VESSELS
RIGHT ON THE SURFACE AND GIVE A
READING BASED ON YOUR A.I.
SEGMENTATION?
YOU KNOW, SOME OF THESE FEATU
FEATURES -- AUTOMATED IN A WAY
THAT WOULD BE USEFUL.
>> THANKS FOR THE QUESTION, BY
THE WAY.
I REALLY HOPE TH SOMEONE IN THE
O.C.T. INDUSTRY IN THE AUDIENCE,
I REALLY WANT TO LET THEM KNOW,
WE DO NEED A.I. BASED
AUTOMATION, YOU KNOW, WHATEVER
YOU CAN MAKE FOR USE A.I. POWER
TO IMPROVE THE VISUALIZATION,
YOU KNOW, YOU CAN GATHER NOISE,
BACKGROUND NOISE AND A LOT OF
ARTIFACT.
SO HELP OUR DOCTORS TO -- TO SEE
THE IMAGE, THAT'S NUMBER ONE,
RIGHT?
AND BIOMARKER MEASUREMENT, THEN
A.I. CAN PROVIDE THE VALUE,
RELIABLE VALUE, THEN OUR
CLINICIANS CAN EASILY TO SEE THE
FOLLOW-UP COMPARED TO THE
BASELINE, THEN, YOU KNOW, THAT'S
GOING TO SAVE YOU TIME.
SO THE IDEA OF THE A.I., JUST
TRY TO SAVE USER'S TIME, THAT
SHOULD BE IMPLEMENTED IN THE
DEVICE.
HOPEFULLY IN NEAR FUTURE.
BUT I THINK THE VISUALIZATION
PART, THIS HAS BEEN SUCCESSFULLY
BEEN IMPLEMENTED BY SOME OF THE
OCTA DEVICE ALREADY.
I THINK THAT'S A FIRST STEP.
I'M NOT SURE WHY THEY ARE KIND
OF HESITANT TO USE THE
A.I.-BASED MEASUREMENT.
MAYBE THE -- THIS IS A HUGE STEP
FOR THEM TO MOVE FORWARD, OR
MAYBE THEY'RE WAITING ON SOME
LARGE DATASET, YOU KNOW, THAT'S
THE WHOLE COMMUNITY SHOULD GET A
LOT OF DATASETS TO VALIDATE.
>> I THINK THE VALIDATION SORT
OF HOLDS BEFORE PEOPLE READILY
EMBRACE IT.
BEAUTIFUL.
THANK YOU.
>> THANKS FOR THE QUESTION.
>> OKAY.
I THINK WE'RE DONE IF THERE ARE
NO OTHER QUESTIONS.
WANT TO GIVE US THE NEW TIME
SCHEDULE?
I THINK WE'RE ON SOME DIFFERENT
TIMES.
>> I'D LIKE TO THANK THE
SPEAKERS AGAIN.
[APPLAUSE]
AND LET'S RECONVENE AT 4:00 FOR
THE FINAL SESSION OF THE DAY.
I'D LIKE TO GET GOING WITH THE
FINAL SESSION OF THE AFTERNOON.
I'M PLEASED TO INTRODUCE JESSICA
MORGAN FROM THE UNIVERSITY OF
PENNSYLVANIA, AND JESSICA WILL
BE MODERATING THE SESSION ON
OPTORET NOGRAPHY.
ON OPTORETINOGRAPHY.
>> THANK YOU ALL SO MUCH.
IT TRULY IS AN HONOR TO BE PART
OF THIS REALLY SPECTACULAR
PROGRAM.
I'VE REALLY ENJOYED ALL OF THE
SESSIONS SO FAR TODAY, AND IT IS
MY HONOR TO MODERATE THIS FINAL
SESSION OF THE AFTERNOON ON OP
KNOW RETINOGRAPHY.
OUR FIRST SPEAKER IS RAM SABE
SABESAN, HE'S GOING TO BE
SPEAKING ON THE MECHANISMS AND M
ACATIONS OF OPTORETINOGRAPHY.
RAM, IT'S ALL YOURS.
>> ALL RIGHT.
THANK YOU TO THE ORGANIZERS FOR
INVITING ME.
IT IS MY PRIVILEGE AND HONOR TO
BE HERE.
AS FAR AS THE HI HISTORY OF O.C.
GOES, I'M A TOTAL NWEBIE OR AS
THE KIDS CALL IT NEWB, ONLY
DOING IT IN THE LAST SEVEN OR
EIGHT YEARS, SO I HAVE BEEN A
DIRECT BENEFICIARY OF ALL THE
WORK THAT THE LASKER AWARDEES
HAVE DONE OVER THE PAST VERY
MANY YEARS TO PROMOTE THE FIELD
OF O.C.T.
SO I WILL BE TELLING YOU ABOUT A
NEW AND EMERGING APPLICATION OF
O.C.T. THAT WE LIKE TO CALL
OPTORETINOGRAPHY AND I'LL TAKE
YOU INTO A LITTLE JOURNEY ON
STUDYING ITS MECHANISMS AND ITS
APPLICATIONS.
SO JUST AS A 30,000-FOOT VIEW,
WE CAN THINK ABOUT THE VARIOUS
METHODS THAT ARE USED TO ASSESS
THE HUMAN RETINA IN HEALTH AND
DISEASE IN THIS 2 BY 2 GRID,
WHERE STRUCTURE AND FUNCTION IN
THE COLUMBUS AND SUBJECTIVE AND
ON JEKTIVE ASSAYS ARE ON THE
ROWS.
RETINAL CAMERAS PROVIDING US
OBJECTIVE AND SUBJECTIVE
STRUCTURE.
PROVIDING SUBJECTIVE ASSAYS OF
FUNCTION AND AS FAR AS OBJECTIVE
ASSAYS OF FUNCTION GO, THERE ARE
NOT VERY MANY AVAILABLE OUT
THERE, AND ELECTRORETINOGRAPHY
IS PERHAPS THE MOST COMMON
PREVALENT ONE, AND THIS IS
PERHAPS AS THRILLED AS I CAN
APPEAR GETTING ONE OF THESE DONE
WITH TAPE ON MY FOREHEAD AND
LITTLE ELECTRODES RUNNING DOWN
MY LOWER EYELID, AND OF COURSE
THERE ARE VARIETY OF DIFFERENT
DISADVANTAGES OF USING ERG,
PRIMARILY THAT ITS RESOLUTION IS
TOO COARSE TO BE ABLE TO MEASURE
SCALE LAR CELL ACTIVITY IN THE
RETINA.
SO THE TERMINOLOGY OF THE OR
GWAS REALLY PROPOSED BY DON MA
CLOUD, DAVID WILLIAMS, HIS PH.D.
SUPERVISOR IN THE EARLY 80s.
AT THE TIME THEY DID NOT MEASURE
ANY VISUALLY EVOKED CHANGES.
AND I WAS NOT AWARE OF IT UNTIL
WE ATTENDED THE FESH -- WHEN ONE
OF HIS STUDENTS TOLD US AS EARLY
AS 1980, DON HAD COINED THIS
TERM TO DESCRIBE A CHANGE IN THE
NEAR INFRARED FOLLOWING VISUAL
STIMULATION AND WHEN THEY WERE
STUDYING THESE PAPERS ON TOAD
RETINA.
THIS RESONATED WITH US AND WE
BEGAN TO USE IT IN ABOUT THE
2019 TIME FRAME.
THESE ARE ALL THE PAPERS AROUND
THAT TIME WHO HAVE USED THE SAME
TERMINOLOGY, IT'S NOT TO SAY
THAT WE'RE THE PIONEERS OF THIS
FIELD NECESSARILY.
JUST THAT WE BEGAN TO USE IT
FIRST.
BUT THESE GUYS HAVE BEEN DOING
THESE KINDS OF MEASUREMENTS OF
NEAR-INFRARED CHANGES FOLLOWING
A VISUAL STIMULUS FOR ABOUT THE
LAST 20 YEARS OR 15 TO 20 YEARS
OR SO.
SO I DON'T HAVE TIME TO REALLY
GET INTO THE HISTORY OF
OPTORETINOGRAPHY BUT I'LL POINT
YOU TO THIS LITTLE WEBINAR I DID
A FEW YEARS AGO.
SO THE GENERAL PARADIGM IS THE
FOLLOWING.
THINK OF THIS AS THE
CROSS-SECTION SIGNAL OF THE
RETINA AND WE CAN STATION AN
IMAGING BEAM SO, AND WHAT WE
REALLY WACHT WAN WANT TO DO IS W
THE ACTIVITY IN DIFFERENT RAYS
OF THE RETINA FOLLOWING A VISUAL
STIMULUS STARTING FROM THE PHOTO
RECEPTORS DOWN TO THE GANGLION
CELLS.
SO THIS IS REALLY THE DREAM AND
A THE DREAM IS TO CREATE AN
ALL-OPTICAL ANALOG OF THE
ELECTRODE TO BE ABLE TO USE IT
IN A NONINVASIVE WAY IN A LIVING
EYE.
BUT THE STUDY OF THE DEFORMATION
CHANGES ARE NOT NEW.
THIS PAPER IS FROM THE 1970s,
ABOUT 10 OR 12 YEARS AFTER
INVENTION OF THE LASER WHERE
THEY USE A LASER TO MEASURE
CHANGES IN THE SHAPE OF A
CRAYFISH AXON WHERE THEY HOLD IT
UNDER THESE ELECTRODES AND
MONITOR THE OPTICAL CHANGE IN
THE -- AMOUNT OF THE OPTICAL
CHANGE IN THE AXON ALONG WITH
ITS ELECTRICAL ACTIVITY.
THE KEY POINT HERE IS THAT THEY
MEASURE CHANGES ON THE ORDER OF
ABOUT 10 ANGST TROMS IN ABOUT
1 MILLISECOND IN THIS AXON WHICH
ACCOMPANIES THE ACTION
POTENTIAL.
SO FAST FORWARD ABOUT 35 YEARS
LATER, OPTICAL -- WAS USED IN
PHASE RESULT CONFIGURATION BY
THESE GUYS OVER HERE MEASURING
THE SQUID GIANT AXON WHERE THEY
MEASURED SIMILAR KINDS OF
CHANGES ON THE SCALE OF ABOUT 1T
1 MILLISECOND.
NOW LET'S FAST FORWARD ABOUT 15
YEARS SINCE THEN, OUR
COLLABORATORS AT STANFORD AN NTU
HAVE USED QUANTITATIVE PHASED
IMAGING TECHNIQUE TO MEASURE
CHANGES IN THE SHAPE OF A
CORTICAL NEURON WHERE THE
MEMBRANE TENSION DURING DEEP
POLARIZATION OF A NEURON CAUSES
A REDISTRIBUTION OF CHARGES ON
THE SURFACE OF THE NEURON, WHICH
CAUSES TO BECOME MORE SPHE SPHE,
AND THEY DESCRIBE A VOLTAGE
DEPENDENT MEMBRANE CHANGE MODEL
SO LET'S MAKE A MENTAL NOTE OF
THAT AND A WE'LL COME BACK TO
THAT IN A SECOND AS TO HOW IT
RELATES TO CHANGES IN
PHOTORECEPTORS.
PHOTORECEPTORS SEEM TO HAVE A
BIT OF A BONANZA, IF YOU WILL,
WHEN IT COMES TO MEASURING THEIR
NEURAL ACTIVITY BUT BEFORE WE GO
THERE I'LL GIVE YOU A PRIMER ON
OSMOSIS OR OSMOTIC PRESSURE.
HI TO TURN TO HIGH SCHOOL
PHYSICS AND CHEMISTRY TO
REMEMBER WHAT THIS WAS.
OSMOSIS IS REALLY THE MOVEMENT
OF SOLVENT FROM HIGH KOL VENT
CONCENTRATION SUCH AS OVER HERE
TO LOW CONCENTRATION ACROSS A
PERMEABLE MEMBRANE.
SO THEY SUSPENDED ISOLATED --
SEGMENTS -- WHAT THEY FOUND WAS
THE ROD OUTER SEGMENTS CHANGE IN
THEIR WIDTH, LENGTH AND VOLUME,
THE ENTIRE SHAPE OF THE ROD
OUTER SEGMENT CHANGES WHEN
THEY'RE IN A DISH OF DIFFERENT
CONCENTRATION.
THEY ALSO CHANGE WHEN THEY ARE
HIT WITH SOME LIGHT.
AND SO THE ARGUMENT THERE IS
THAT PHOTO TRANSDUCTION PRODUCTS
ALTER THE OUTER SEGMENT VOLUME
DUE TO OSMOSIS.
THIS WAS REFURBISHED BY
PROFESSOR ED PU AT UC DAVIS WHO
PROPOSED WHEN LIGHT HITS A ROD
OUTER SEGMENT, THEY GET SUSPEND
SUSPENDED INTO THE CYTOSOL
CREATING A SITUATION LIKE SO AND
WATER ENTERS FROM THE CHOROID
SIDE TO BALANCE THE OSMOTIC
PRESSURE.
THEY SHOWED A DIRECT CORRELATION
OF THIS CHANGE WITH PHOTO
TRANSDUCTION, SHOWING THAT MICE
THAT LACKED -- DO NOT SHOW SUCH
A CHANGE WHEREAS WILD TYPE MICE
DO.
AND THEY WERE ABLE TO ESTABLISH
AN OSMOELASTIC MODEL WHEREBY THE
BYPRODUCTS OF PHOTO TRANSDUCTION
GENERATE SUFFICIENT OSMOTIC
PRESSURE LEADING TO WHATTER IT
ENTRY INTO THE OUTER SEGMENT AND
CHANGE ITS SHAPE.
SO WITH THAT BACKGROUND I WANTED
TO GIVE YOU A LITTLE OVERVIEW OF
WHERE WE COME IN INTO
OPTORETINOGRAPHY.
WE ARE INVOLVED IN DEVELOPING
TECHNOLOGY TO STUDY THE ORG.
WE ARE USING TO STUDY THE
VARIOUS MECHANISMS OF ULTRA
RETINAL FUNCTION AND TO USE IT
FOR RETINAL DISEASE.
SO I'LL TELL BUT OUR TOOLS, TELL
YOU ABOUT THE MECHANISMS,
LEACHING PHOTO TRANSDUCTION OF
THE VISUAL CYCLE AND HOW WE'RE
ESTABLISHING A NORMATIVE DATASET
FOR THE CONE ORG SPECIFICALLY
AND HOW WE'RE USING IT FOR
DISEASES.
SO WHEN THE TIME CAME FOR US TO
ENTER THIS FIELD, REALLY WE WERE
LEFT WITH THE CHOICE OF WHICH
PARADIGM TO GO AND WE ENDED UP
CHOOSING A -- PARADIGM IN ORDER
TO OBTAIN THE TRADEOFF BETWEEN
RESOLUTION, FIELD OF VIEW AND
SPEED.
SO SCANNING FULL FIELD SYSTEM,
STARTS WITH CREATING A LINE
ELIMINATION IN THE RETINA
TYPICALLY MADE WITH A
CYLINDRICAL LENS, BACK SCATTERED
FROM THE RETINA, DEFRACTURED VIA
A DIFFRACTION RATING AND
CAPTURED IN A 2D TYPICALLY HIGH
SPEED CAMERA AND WITH A SIMPLE
TRANSFORM GIVES THE B SCAN -- A
B SCAN CROSS-SECTIONAL IMAGE.
THEN YOU CAN TAKE A SCANNER AND
SCAN THAT LINEAR ILLUMINATION
ACROSS THE RETINA AND IN A
SINGLE SNAPSHOT, YOU CAN OBTAIN
THAT B SCAN AND BY SCANNING THE
SCANNER IN ONE DIMENSION, CREATE
THESE VOLUMES AT EXTREMELY HIGH
SPEED.
SO WE CAN THEN TAKE -- BRING THE
FOCUS UP TO THE INNER RETINA,
AND SEE THE VARIOUS CELLS AND
STRUCTURES INSIDE THE INNER
RETINA STARTING FROM THE
MACROPHAGES, THE GANGLION CELLS,
THE -- VESSELS AND SO ON.
THE OUTER RETINA, WE CAN SEE
CONES, INNER SEGMENT, OUTER
SEGMENT JUNCTION, AND THE RPE.
BUT REALLY THIS IS ENCOURAGING
FROM OUR STANDPOINT BECAUSE IF
YOU CAN VISUALIZE THE CELLS AND
THE STRUCTURE OF THE CELLS, THEN
IF YOU DEVELOP TECHNIQUES TO
IMAGE THEIR ACTIVITY WE CAN
CORRELATE THE TWO TOGETHER.
THE REASON THAT WE UNDERTOOK
THIS PROJECT WAS REALLY TO BE
ABLE TO PERFORM FUNCTIONAL
MEASUREMENTS SO HERE WHAT WE DO
IS WE TAKE THE OUTER RETINA
SPECIFICALLY AND SECTION OUT
THE -- AND THE COST, SHINE A
30-NANOMETER LIGHT AND LET'S SAY
THIS PATTERN LIKE SO INTEGRATING
LIKE PATTERN AND IF YOU WERE
DOING OUR JOB CORRECTLY, THEN WE
WOULD BE SEEING A CONE
FUNCTIONAL MAP OF THE SAME KIND
THROWSHOWING THE THREE-BAR PATTN
THE SAME WAY THIS EYE
ILLUMINATION IS SHINING ON THE
RETINA.
SO REALLY WE'RE MORE INTERESTED
IN THE -- HOW DOES THE ORG
CHANGE WITH THOSE FACTORS, SO WE
SEE THE OPTICAL -- FIRST
UNDERGOES A SHARP DECLINE OR
SHARP SHRINKAGE AND THEN RISES
AND FINALLY SATURATES, AND IT
HAS A BLEACHED DEPENDENCE -- THE
KINETICS AND AMPLITUDE OF THE
RESPONSE STEADILY INCREASES AS
YOU INCREASE THE BLEACH.
SO WE HAVE IMPLEMENTED THIS OR
DORGPARADIGM, REALIZING IT HAS A
BLEACH DEPENDENCE, WE CAN PICK A
WAVE LENGTH WHICH HAS A
DIFFERENTIAL -- WHEN WE DO THIS,
WHAT WE CAN FIND, WHAT WE FIND
IS THAT EACH CONE CHARACTERISTIC
OF ITS SPECTROTYPE IS SEGREGATED
IN THE SHORT WAVE OF THE CONE
WHICH IS PROPORTIONAL AND IT
SHOWS THE PROPORTIONAL OPTICAL
PATH LENGTH, WHICH LETS US
DESIGNATE ITS TYPE.
WE CAN SACRIFICE FIELD OF VIEW
OR SACRIFICE RESOLUTION FOR
FIELD OF VEUL WHEREIN VIEW WHERE
CAN INCREASE THE FIELD AND IN
THIS SCENARIO, WE SEE GREATER
CHANGE STARTING FROM THE FOVEA
WHERE THE OPTICAL PATH LENGTH IS
THE HIGHEST, DECREASING AS WE GO
FURTHER OUT IN ECCENTRICITY IT.
SO WHAT I'VE SHOWN YOU SO FAR
ARE CONE SO CALLED CONE
PHOTORECEPTOR ORGs, THERE ARE
OTHER PHOTORECEPTOR TYPES IN THE
RETINA.
THIS IS JUST TO SHOW THAT IN THE
SAME PARADIGM WE CAN ALSO
MEASURE CONE AND ROD FOR
RECEPTOR ORGs IN THE CORE
SCALE PARADIGM AND THE ROD PHOTO
RECEPTORS HAVE A LOWER
SENSITIVITY AND AMPLITUDE
COMPARED TO THE CONE WHEREAS IN
THE AO O.C.T. MODE, WE CAN ZOOM
IN AND LOCALIZE INDIVIDUAL CELLS
AND ASSIGN THE OR TB.s TO
INDIVIDUALS, OR TO INDIVIDUAL
RODS.
SO REALLY OUR GOAL HERE IS TO
STUDY THE MECHANISMS OF THE
ORGs.
IN OUR HANDS WE'VE NOTICED THE
EARLY SHRINKAGE AND THE TWO
RISING COMPONENTS, THE ONE THAT
FLATTENS OUT AND THEN ONE THAT
HAS A SLOWER RISE LIKE SO.
COMP 1 AND COMP 2.
FIRST LOOKING AT THIS EARLY
SHRINKAGE COMPONENT, AS WE
INCREASE THE BLEACH LEVEL THE
OPTICAL PATH LENGTH INCREASES
AND THEN FINALLY SATURATES, AND
THIS RANGES ABOUT BETWEEN 5 TO
ABOUT 15-NANOMETERS OR SO.
TURNS OUT THAT THIS LOW LATENCY
FAST KINETICS RESPONSE THAT IS
SEEN IN THE CONE OUTER SEGMENT
IS LINKED TO PHOTOISOMERIZ AI
TION DENOTED AS THE EARLY
RECEPTOR POTENTIAL AND IS
DIFFERENT FOR THE AMPLIFICATION
CASCADE THAT WE KNOW OFF IN
CONES.
HERE THE GOAL IS TO CHARACTERIZE
THE SENSITIVITY OF THE LIED
DPENT DENSE OF THE RESPONSES,
AND TO CHARACTERIZE THEIR
KINETICS AND THEN USE THE SAME
MODEL OF TRANSDUCTION, THAT
PROFESSOR ED PEW HAD USED TO
PREDICT THE SENSITIVITY OF
KINETICS.
HE'S A CLOSE COLLABORATOR OF
OURS ON THIS PROJECT.
THE WAY WE GO ABOUT DOING THIS
IS TO TAKE THE SATURATED
RESPONSE AND DIVIDE THEM UP INTO
EXPONENTIALS AND THEN SEE ITS
ENERGY DEEP DEPENDENCE.
SO WHEN WE MEASURE ITS
SENSITIVITY WE FIND COMPONENT
ONE IS MUCH FASTER KINETICS AND
MUCH GREATER SENSITIVITY THAN
COMP 2, WHICH LEADS US TO
HYPOTHESIZE THAT COMP 1 ARISES
FROM AN AMPLIFIED BYPRODUCT OF
PHOTO TRANSDUCTION, WHEREAS
COMPONENT 2 ARISES DUE TO A
MECHANISM LINKED TO BLEACHING.
SO I WILL NOW GIVE YOU TWO
EXAMPLES OF SCENARIOS WHICH HAVE
LED TO PREDICTIONS WHICH HAS LED
TO TEST THE PREDICTIONS OF
HYPOTHESES FOR THE DIFFERENT
COMPONENTS.
THE FIRST ONE IS A PATIENT WITH
MICROSCOTOMA, WE CAN FIND
REGIONS OF THE RETINA WHERE THEY
DID NOT SEE A VISUAL STIMULUS
WHEREAS OTHERS RIGHT IN THE
CENTER OF THE FOVEA HERE WHERE
THEY DO SEE A VISUAL STIMULUS.
AND WE CAN THEN GO ON AND
MEASURE ORGs IN THESE
DIFFERENT REGIONS.
SO IN THE AREA WHERE THE PERSON
HAD NORMAL MICRO PRIM TRI,
NORMAL VISION, THE ORGs LOOK
FAIRLY OKAY BUT IF WE LOOK AT
REGIONS WHERE THEY DID NOT SEE
THE STIMULUS, WE SEE THAT
INITIAL SHRINKAGE WHICH IS
CORRESPONDING TO THE
PHOTOISOMERIZATION RESPONSE BUT
WE DON'T SEE THE LATER SLOW RISE
OF THE RESPONSE WHICH WAS LINKED
TO PHOTO TRANSDUCTION, LEADING
US TO CONCLUDE THAT THE LOCAL --
WAS REALLY LOCALIZED TO THE
PHOTO RECEPTORS AND WAS NOT
CAUSED DUE TO CHANGES DOWNSTREAM
OF THE PHOTO RECEPTORS.
THE SECOND EXPERIMENT TO TEST
THE HYPOTHESIS WAS DONE IN
PATIENTS WITH A MUTATION CAUSED
IN THE GENE CODING FOR RGS9.
THIS IS AN ENZYME THAT IS
ESSENTIAL FOR THE DEACTIVATION
OF THE PHOTO TRANSDUCTION
CASCADE, AND CATALYZES THE
HYDROLYSIS OF QUANTITY SEEN
TRIPHOSPHATE.
THERE'S A SUBJECT GROUP IN
BRADYO PSI A IN THE EARLY
2000s THAT -- IF YOU DID
ORGs IN THESE PATIENTS, THE
HYPOTHESIS IS WE WOULD NOTICE
SLOWER RECOVERY OF THE CONE ORG
IN BRADYOPSIA.
OF COURSE THE NEXT STEP HERE IS
TO LINK THE FINDINGS THAT WE
HAVE HERE IN ORG TO ACTUAL
BIOPHYSICAL AND BIOCHEMICAL
MODELS OF PHOTO TRANSDUCTION AND
SEE -- AND TEST FURTHER HOW OUR
MODELS CAN BE REFINED TO FURTHER
GENERATE NEW HYPOTHESIS THAT CAN
BE TESTED IN THE FUTURE.
SO CHANGING GEARS NOW, THIS IS
THE LAST CHAPTER OF THE STORY,
IS TO APPLY ROENTGENOGRAMS TO
THOSE WITH DISEASE BUT -- WHAT
FACTORS AFFECT THE NORMATIVE
VARIATION IN THE CONE ORG.
AND SECOND WE WANT TO UNDERSTAND
HOW THE ORG IS DISRUPTED IN
RETINITIS PIGMENTOSA AS WE HEARD
FROM DON THIS MORNING, IT
CONSISTS OF A HEALTHY ZONE, A
ZONE OF ACTIVE DEGRADATION, AND
DISEASE ZONE WHEN BOTH THE
REFLECTIONS HAVE DISAPPEARED AND
THIS IS THE HALLMARK SIGN OF RP
SHOWING THIS KIND OF BULL'S-EYE
PATTERN WHERE THE RETINA IS,
QUOTE-UNQUOTE, HEALTHY OR NORMAL
IN THE CENTER.
AND OF COURSE WE WANT TO
UNDERSTAND HERE -- NORMAL
RETINAL STRUCTURE, NORMAL
FUNCTION WHEREAS IN THE CASE OF
BRADY OPS YA, WE'RE INTERESTED
IN STUDYING THE CORRELATION
BETWEEN BOTH.
WE CAN THINK OF TWO DIFFERENT
FACTORS, ONE IS PRERECEPTOR,
WHICH IS DICTATED BY THE
STIMULUS TREND, I TOLD YOU AS WE
INCREASE THE BLEACH LEVEL IN THE
RETINA, THE ORG AMPLITUDE AND
KINETICS INCREASES AND OF COURSE
ALSO FACTORS PERTINENT TO THE
ANTERIOR EYE, THINGS SUCH AS
CATARACT, AGE, LENS MEDIA, AND
OTHER OPACITIES.
AND THE RECEPTOR-CONE, SPECIFIC
PROPERTY SUCH AS THE INNER
SEGMENT DIAMETER, OUTER SEGMENT
LENGTH, ET CETERA, WHICH ALSO
GOVERN THE NORMATIVE VARIATION
IN THE CONE ORG.
SO IN ORDER TO CHARACTERIZE THE
CONE ORG, WE HAVE ESTABLISHED
THE CORE I TOLD YOU ABOUT A
LITTLE BIT AGO.
THIS MEASUREMENT TAKES ABOUT 10
MINUTES TO COMPLETE AND CAN BE
DONE ACROSS A LARGE AGE RANGE, A
LARGE SUBJECT GROUP.
IT'S MORE EXTENDED FIELD,
5 DEGREES AS OPPOSED TO 1 DEGREE
WE WERE DOING WITH ADAPTIVE
OPTICS, AND THIS IS THE GENERAL
TREND OF RESPONSES THAT WE SEE
THAT CLOSE TO THE FOVEA, THE
RESPONSES ARE THE LARGEST, AND
THEY DECREASE AS WE GO FURTHER
AWAY FROM THE FOVEA.
SO WHEN WE THEN BRING THESE
OPTICAL PATH LENGTH MEASUREMENTS
TOGETHER WITH THE OUTER SEGMENT
LENGTH, WE SEE THE PATH LENGTHS
OBEY THIS REALLY NICE
RELATIONSHIP BETWEEN THE OPTICAL
PATH LENGTH AND OUTER SEGMENT
LENGTH, AND THEN IF YOU DO THIS
FOR DIFFERENT BLEACHING
CONDITIONS OR BLEACHING LEVELS,
WE SEE THAT THE SLOPE OF THIS
CURVE UNDERGOES THE STEEPENING.
SO THE GOAL HERE IS GENERALLY TO
GENERATE A NORMAL GRAM LET'S SAY
WHERE WE CAN TAKE A SUBJECT AND
ACCORDING TO THE OUTER SEGMENT
LENGTH, ACCORDING TO THE BLEACH
SCALE, ACCORDING TO DIFFERENT
PROGRAM TE THE SUBJECT BE ABLE
TO PREDICT WITHIN A
CERTAIN DEGREE OF CERTAINTY WHAT
THEIR CONE ORGANIZE IN A NORMAL
CIRCUMSTANCE MAY BE, AND TRY TO
DOCUMENT THE DIFFERENT FACTORS
THAT AFFECT THE VARIATION OF THE
CONE ORG.
OKAY.
OF COURSE NOW WE'VE ESTABLISHED
THAT, WE WANT TO STUDY HOW THIS
IS AFFECTED IN RETINITIS
PIGMENTOSA.
AGAIN THIS IS OUR KIND OF
BULL'S-EYE PATTERN IN RP.
SO THIS OVERLAYING NOW THE
FUNCTIONAL MAP OF THE ORG ACROSS
THE STRUCTURAL MAP WE SEE HOW
THE ORG RESPONDS, AMPLITUDE IS
HIGHER IN THE FOVEA AND DEGRADES
AS YOU GO FURTHER OUT.
BUT IN THE CASE OF RP, I THINK
IT'S FROZEN, SORRY.
I GUESS THE POINT IS VERY CLEAR
HERE THAT IN THE CASE OF RP,
EVEN IN THE SO-CALLED HEALTHY
ZONE OR HEALTHY ZONE TRANSITION
ZONE, THE OPTICAL PATH LENGTH IS
FAR REDUCED COMPARED TO THE
NORMAL SCENARIO, AND ON THE LEFT
HERE IS SHOWN THE SUMMARY OF ALL
THIS DATA PUT TOGETHER ACROSS
PATIENTS WITH VERY DIFFERENT
GENOTYPES.
THE IDEA HERE IS -- I SHOULD
POINT YOUR ATTENTION TO THIS
PARTICULAR PATIENT WITH AN
IMPDH1 MUTATION WHERE EVEN
THOUGH THIS PATIENT'S TRANSITION
ZONE STARTS OUT HERE AT ABOUT
3 1/2 DEGREES, EVEN AT THOSE
SCALES, THEIR OPTICAL PATH
LENGTH IS FAR REDUCED COMPARED
TO WHAT YOU WOULD -- COMPARED TO
NORMAL, SO THIS IS CLEARLY A
SUBCLINICAL CHANGE THAT WOULD
NOT HAVE BEEN PICKED UP WITH
O.C.T.
OKAY.
AND REALLY IT'S NOT SO THAT THE
CORE SCALE ANALOG OF OUR ORG
REALLY ANSWERS ALL OUR
QUESTIONS, OF COURSE WE ARE
INTERESTED IN CELLULAR SCALE
PHENOTYPIC FEATURES IN PATIENTS
WITH DIFFERENT MUTATIONS, AND
HERE JUST SHOWING DIFFERENT
MUTATIONS FROM SNRNP, RHO, WE
CAN SEE HOW EVEN THE CONE MOSAIC
OF THESE PATIENTS OR THE
DIFFERENT ORG PHENOTYPES, FOR
EXAMPLE, SHOWING THREE CLUSTERS
HERE ARE VERY DIFFERENT BETWEEN
THE DIFFERENT GENES AND WE'RE
COLLECTING MORE DATA HERE TO
REALLY ESTABLISH A MORE GENOTYPE
PHENOTYPE CORRELATION DATABASE
WITH WHICH TO DRAW MORE
CONCLUSIONS.
SO WITH THAT, I'D LEAVE WITH YOU
A SUMMARY WHICH IS BASICALLY
THAT ORG IS REALLY A POWERFUL
TOOL TO REVEAL EARLY STEPS OF
TRANSDUCTION IN HUMAN RODS AND
CONES, A STORY THAT I DIDN'T
TELL YOU TODAY IS TO -- THAT IT
REVEALS THE TOPOGRAPHY OF THE
CONE MOSAIC IN THE HUMAN RETINA,
AND IT PROVIDES AN INSIGHT INTO
EARLY DYSFUNCTION IN PHENOTYPIC
VARIATION, RETINAL DISEASE.
I WOULD TAKE THIS OPPORTUNITY TO
THANK ALL MY COLLABORATORS, ALL
MY FUNDING SOURCES, AND THE
FOLKS IN THE LAB THAT DO ALL THE
WORK.
THANK YOU SO MUCH.
[APPLAUSE]
>> ALL RIGHT.
OUR SECOND SPEAKER FOR THIS
SESSION IS ROBERT ZAWADZKI.
HIS TALK IS TITLED OPTICAL
COHERENCE TECHNOLOGY BEHIND ORG.
ROBERT?
>> THANK YOU VERY MUCH THE
ORGANIZERS FOR INVITING ME AND
FOR GIVING ME THIS OPPORTUNITY
TO SPEAK TODAY.
I ALSO WANT TO CONGRATULATE JIM,
DAVID, AND ERIC FOR THIS GREAT
AWARD.
WHEN I WAS ASKED TO GIVE THIS
TALK, I FIND OUT I'M GOING TO BE
SANDWICHED BETWEEN RAVI AND RAM
SO I DECIDED TO KIND OF DO
SOMETHING DIFFERENT.
SO I'LL GIVE YOU A LITTLE BIT
MORE PERSPECTIVE ON ORG WITH
RESPECT TO O.C.T.
AND BEFORE I START, I WANT TO
ACKNOWLEDGE ALL OF THE
CONTRIBUTIONS FROM OUR
COLLABORATORS FROM THE LAB THAT
DID THE ANIMAL WORK.
FROM ED PU TB. H AND THEN RAVI
JONNAL FOR THE CLINICAL WORK AND
ALSO ALL THE COLLABORATORS THAT
WORKED WITH US THROUGHOUT THE
YEARS AND ALSO ALL OF THE
FUNDING SOURCES.
SO WHAT I WAS GOING TO START
WITH FIRST IS TALKING ABOUT THE
TECHNOLOGY IN GENERAL, AND THEN
I WANT TO USE THIS OPPORTUNITY
TO ALSO BRING KIND OF MEMORY OF
MY LATE ADVISER AND HIS
CONTRIBUTION TO THE FIELD AND
HOW -- KIND OF WORK HE DID THAT
REALLY RELATES TO THAT.
SO FIRST YOU CAN SEE HERE HE WAS
ONE OF THE PIONEERS OF USING
INTERFEROMETRY FOR MEASURING THE
EYE.
THIS IS VERY SIMILAR TO THE WORK
DONE BY RAVI JANNAL, USING THE
SIGNAL FROM THE -- AND RETINA
AND THIS IS USED TO LOOK AT
THE -- OF THE EYE AND LATER ON
IN MODERN ORGs, WITHOUT -- THE
SAME METHOD IS USED TO LOOK AT
THE SCINTILLATIONS OF THE PHOTO
RECEPTORS -- SEGMENT LENGTH
CHANGE.
SO LATER ON, THIS WAS ALSO THAT
KIND OF INITIAL WORK OF MEASURE
USING -- TO MEASURE THE EYE
LENGTH, OR MEASURE THE RETINAL
PROFILE WHICH IS EXACTLY WHAT
WE'RE DOING IN ORG,, WE'RE USING
O.C.T. AS A TOOL TO MEASURE
PRECISELY CHANGING LENGTH WITHIN
THE RETINA.
SO WE ARE HERE BECAUSE OF THE
INVENTION OF O.C.T. WITH THIS
GREAT, GREAT PAPER BY DAVID WANG
SHOWN HERE, THIS IS 1991, THAT
THE GROUP, COLLABORATION OF --
TWO YEARS LATER ARE ABLE TO SHOW
THE FIRST IN VIVO IMAGE OF THE
RETINA FROM AMERICAN JOURNAL OF
OPHTHALMOLOGY, AND THEN KIND OF
LATER ON, PROFESSOR FERCHER PUT
ON THIS GREAT WORK KIND OF
LINKING SCATTERING THERAPY AND
THE INFORMATION IN O.C.T. AND
YOU CAN SEE HERE THERE'S -- HOW
THE FIELD IS GENERATED BY THE
OBJECT.
HE THEN PUT IN THIS -- LIGHT --
POTENTIAL AND THEN LINKED THIS
WITH GENERATION OF THE REFERENCE
ARM SIGNAL AND THEN THE SAMPLE
ARM SIGNAL, SORRY, AND THEN
LATER ON WITH -- SEE THIS KIND
OF COMMON DESCRIPTION OF THE
INTERFERONS BEING -- OF THE
SAMPLE REFERENCE ARM AND THEN
INTERFERONS USING THIS FIRST --
FUNCTION DESCRIBED LATER IN
DETAIL, BUT THIS ALREADY, HERE
YOU HAVE HERE YOUR ENVELOPE OF
THE O.C.T. SIGNAL AND FRINGE
PATTERN.
FOR ALL THESE KR CONTRIBUTIONS
TOGETHER WITH JIM, DAVID AND
ERIC, HE WAS AWARDED THIS PRIZE
IN 2017, RIGHT BEFORE HE PASSED
AWAY.
SO NOW LET'S KIND OF MOVE ON AND
TALK MORE IN DETAIL ABOUT THE --
BEHIND THESE HIGH PREVISION
MEASUREMENTS NEEDED FOR ORG.
SO FIRST WE KNOW THAT O.C.T. IS
MEASURING THE EXACT POSITION OF
THE SCATTERING -- SCATTERED TO
GENERATE O.C.T., WE'RE BUILDING
UP THIS IMAGE FROM THE A SCANS
FOR THE FRONT OR BACK OF THE
EYE.
AND THEN THE FIRST MEASUREMENTS
PERFORMED WERE DONE USING TIME
DOMAIN O.C.T., SO IN TIME DOMAIN
O.C.T., YOU SEE THE REFERENCE
ARM MOVING -- I GUESS IT'S NOT
MOVING HERE, MOVING BACK AND
FORTH CREATING THIS WELL-KNOWN
SIGNAL THAT CREATE -- SO THIS
WAS KIND OF OLD DAYS WHERE WE
NEEDED TO HAVE TO SPEND SECONDS
OR MAYBE HUNDREDS OF HERTZ --
BUT THEN DEVELOPED INTO THE --
DOMAIN, HERE'S THIS COMBINATION
OF THE SPECTRAL O.C.T. AND --
O.C.T. SHOWING YOU THE GREAT
ADVANTAGE OF THE ABILITY TO
MEASURE THE SIMULTANEOUS A SCANS
WITHOUT THE NEED FOR SCANNING.
AND THIS CAN BE DONE BY
COMBINATION OF THIS FACT THAT IF
YOU'RE MEASURING THE SPECTRAL
INTERFERON -- DOMAIN, YOU CAN
THEN FULLY TRANSFORM DATA TO GET
YOUR INTENSITY AND TIME DOMAIN
SIGNAL SO YOU CAN GET ALL THE --
AT ONCE.
SO THIS WAS KIND OF REALLY PROOF
IN EARLY 2000s BY -- AND THE
MAIN ADVANTAGE HERE IS -- OR
SPECTRAL DOMAIN O.C.T. IS
ROUGHLY AMPLIFIED BY THE HANOVER
TOOL COMPARED TO TIME DOMAIN.
SO WITHOUT THIS, THERE WILL BE
REALLY KNOW REVOLUTION IN O.C.T.
IN THE EARLY 2000s, YOU CAN
SEE HERE FROM THE PAPER INCREASE
IN ACQUISITION -- OR THE -- RATE
OF THE -- YOU CAN SEE TIME
DOMAINS GOT STUCK AT ABOUT
THOUSANDS OF -- PER SECOND
VERSUS -- AND THE SPECTRAL
O.C.T. BACK IN 2002 AND UP TO
THE THREE HUNDREDS OF THOUSANDS
OF HERT AND -- MEGAHERTZ.
BUT WHAT IS REALLY KIND OF
NEEDED TO USE O.C.T. FOR SIGNAL
DETECTION IS THIS COHERENCE
FUNCTION THAT DESCRIBES THE
ENVELOPE, THE RED SIGNAL HERE
AND THE YELLOW IS THE FRINGE
PATTERN UNDERNEATH.
THE SHAPE OF THE FRINGE PATTERN
IS REDEFINED BY THE SPECTRAL
SHAPE OF THE LIGHT SOURCE.
AND THIS IS WHAT DEFINES OUR
COHERENCE LENGTH OR YOUR --
RESOLUTION IN THIS CASE.
SO IN THIS EQUATION, THIS IS
THIS ENVELOPE AND THEN THIS IS
OUR UNDERLYING FRINGE PATTERN,
SO THROUGH THIS THEORY, WE CAN
NOW LINK THE SPECTRUM, SPECTRAL
SHAPE OF THE LIGHT SOURCE WITH
THE COHERENCE LENGTH OF THE
O.C.T., AND HERE YOU CAN SEE
THAT FOR THE RED SHAPE OF THE
SPECTRUM, WHEN WE -- WE GET THIS
OUT CORRELATION FUNCTION OR
COHERENCE FUNCTION.
THE RED SIGNAL, THE RED ENVELOPE
IS DESCRIBED BY THE SPECTRAL
SHAPE OF THE SOURCE AND FRINGE
PATTERN, THE YELLOW PATTERN IS
DEFINED BY THE KIND OF POSITION
OF THE CENTRAL WAVELENGTHS OR
CENTRAL FREQUENCY OF THE
SPECTRUM.
SO IN RESPECT TO THE ORG
TECHNOLOGY WHAT'S REALLY NEEDED
IS TO -- THE ABILITY TO MEASURE
THE POSITION OF THE SCATTER --
THE OBJECTS THAT WE'RE
MEASURING, SO TO DO IT WE CAN DO
IT EITHER USING THE KIND OF
POSITION OF THE ENVELOPE, THE
RED FUNCTION OR WE CAN USE IT BY
EXTRACTING PHASE FROM THE
UNDERLYING FRINGE PATTERN.
SO IN CASE OF THE -- OF GETTING
THE POSITION OF THE ENVELOPE
HERE, WE WOULD SIMPLY USE THE
KIND OF -- TRY TO ESTIMATE WHAT
THE PRECISION OF GETTING THE
POSITION AND HERE WHAT'S
INTERESTING IS THAT THIS IS
REALLY FOLLOWING UP THE -- LIMIT
COMING FROM THE SUPERRESOLUTION
MICROSCOPY FROM -- OR STORM SO
BASICALLY THE PRECISION OF
ESTIMATION POSITION OF THE PEAK
USING ENVELOPE IS JUST GIVEN BY
THE COHERENCE LENGTH IN THIS
CASE THE BANDWIDTH OF THIS
PROFILE DEFINED BY -- INDEX AND
IN CASE OF THE PHASE INFORMATION
YOU CAN SEE THAT THIS IS ALSO
DEPENDING ON THE -- RATIO,
HOWEVER, NOW WE HAVE VALUES THAT
ARE LINKED WITH THE -- DEFINED
BY THE SCENARIO IN A WAY -- OF
THE WAVELENGTHS.
SO THIS IS THE ABSOLUTE POSITION
IN CASE OF ORG WE'RE ALWAYS
MEASURING THE CHANGES IN LENGTH
BETWEEN TWO STRUCTURES COULD B
BE -- SO FOR THAT, IF WE GET --
NOW THIS DIFFERENCE, THIS
RELATIVE DIFFERENCE, WE WOULD
USE THE FOLLOWING EQUATION, AND
HERE I CALCULATED THE VALUES OF
THE -- OF EXTRACTING PRECISION
OF THESE LENGTH MEASUREMENTS FOR
THREE DIFFERENT VALUES OF SNR
BEING 10, 100 AND A THOUSAND.
AND THE SOURCE WAS 850, ABOUT
6.4 MICRO METERS -- RESOLUTION
AND THEN USING THIS COHERENCE
FUNCTION PHASE, WE GET THE
VALUES THAT ARE ABOUT FACTOR OF
TWO SO 100 TIMES BETTER SO WE
HAVE THE SAME PARAMETERS -- SO
GENERALLY THE PHASE IS MUCH MORE
STABLE OR MUCH MORE SENSITIVE
THAN THE INTENSITY BASE
MEASUREMENTS, HOWEVER, THERE'S
ADVANTAGE IN USING INTENSIVE
BASED MEASUREMENTS BECAUSE THEY
CAN BE EASILY AVERAGED AND IT'S
ACTUALLY VERY EASY TO GET SNRs
IN THE RAKE OF THOUSANDS IF
NEEDED BY SPATIAL AND TEMPORAL
AVERAGING.
AS AN EXAMPLE I SHOW YOU HERE,
THIS IS AN EXAMPLE OF THE SINGLE
ON TOP AND -- BY AVERAGING 50 OR
ONE 50 VOLUMES WE GET HUGE
IMPROVEMENT IN SNR.
THIS IS JUST AGAIN SOME GRAPHS
HERE SHOWING YOU THAT INDEED WE
ARE -- THAT GOES WITH THE SQUARE
ROOT OF NUMBER OF AVERAGE
MEASUREMENTS, SO TO INCREASE BY
FACTOR OF 10 WE NEED TO
BASICALLY AVERAGE ABOUT 100, 100
MEASUREMENTS.
SO THIS CAN BE DONE IN THIS CASE
OVER TIME.
OR WE CAN DO IT ALSO HERE AS A
FUNCTION OF SPACE, SO OFTEN THIS
IS THE VIDEO SHOWING YOU THE
EVOLUTION OF THE PHASE IN A
MOUSE LIFE ON THE STAGE, WE
BASICALLY ARE LOOKING AT THE
PHASE DIFFERENCE BETWEEN THE
INITIAL POSITION AND THEN
CONSECUTIVE B SCANS SO THIS YOU
CAN SE SEE THE HEARTBEATING OF E
MOUSE AND EVENTUALLY IF YOU NOW
PROCESS THIS, WE CAN PERFORM NOW
THE SPATIAL AVERAGING AND YOU
CAN SEE HERE ON THE GRAPH
ACTUALLY E COMPARISON OF THE
INTENSITY BASE AND THE PHASE
BASE PRECISION OF THE INNER
SEGMENT, OUTER SEGMENT, YOU CAN
SEE THOSE ARE VERY SIMILAR SO
THE PHASE IS NOT MUCH HIGHER IN
THIS CASE.
SO NOW LET ME GO AND SWITCH
GEARS.
AS RAM SAID, THERE'S A LONG
HISTORY OF USING -- OR MEASURING
THIS -- IN THE RETINA.
YOU CAN SEE EXAMPLES OF THE
CHANGES IN THE SCATTERING AFTER
LIGHT STIMULATION IN THE RETINA.
AT THE BOTTOM, WE SEE CHANGES IN
THE SWELLING OF THE OUTER
SEGMENT PHOTO RECEPTORS.
YOU CAN SEE HERE THE DATES AND
THE NAMES OF THE -- SO THIS
PAPER IN 2007 IS REALLY THE EE
EQUIVALENT OF WHAT I WAS SHOWING
YOU EARLIER ON, WHICH IS THIS
COMMON PATH INTERFERON -- THAT
USES THE INTERFERENCE WITHIN THE
PHOTORECEPTORS OUTER SEGMENT AND
WHAT YOU SEE SCINTILLATIONS ARE
JUST A FACT OF THE -- OF THE
PHOTO RECEPTORS.
SO THIS WAS KIND OF EARLY WORK.
AND THEN THERE ARE MANY MORE
FOLLOW-UP STUDIES OVER YEARS,
USING DIFFERENT ASPECT OF
THIS -- SIGNALS BUT THE WORK WAS
SOMEHOW KIND OF NOT REALLY WELL
DESCRIBED NR THAT KIND OF
COHESIVE MANNER.
WHAT'S REALLY CHANGED IS THAT
WHEN PEOPLE START LOOKING JUST
AT PHOTO RECEPTORS, AND JUST AT
THE CHANGES LOCALLY WITHIN THE
OUTER SEGMENT AND THEN CAME THIS
IDEA OF REALLY USING THE PRECISE
PHASE MEASUREMENT WITHIN THE
OUTHEOUTER SEGMENT.
AND THEN SO THIS IS THE WORK YOU
CAN SEE HERE.
THERE WAS ALSO WORK ON USING
O.C.T. INTENSITY AS A WAY TO
MEASURE -- IN ANIMALS AND ALSO
CHANGES IN O.C.T. SCATTERING AS
WELL AS SOME WORK FROM JESSICA
MORGAN ON SOME KIND OF LINKING
OF THIS WORK OF FERCHER, BUT IN
THIS CASE THIS IS THE
INTERFERENCE FROM THE OUTER
SEGMENT ITSELF.
SO WITH THIS KIND OF -- IN MIND
IN THE LAB WE'VE BEEN WORKING ON
THE CLINICAL AND BASIC SCIENCE
WORK.
SO HERE ARE EXAMPLES OF THE
CLINICAL SYSTEMS DEVELOPED OVER
THE YEARS.
IN CHOIR LAB, RAVI JANNEL WILL
FOLLOW ME, INCLUDING THE TYPE OF
SIGNALS EXTRACTED FROM EACH OF
THE SYSTEMS USING EITHER
SCANNING AO-O.C.T., FULL FIELD
AO-O.C.T. OR SOME OTHER PROTO
CLINICAL SYSTEMS, HOWEVER I WANT
TO MOVE ON AND SHOW YOU SOME OF
THE WORK THAT WAS DONE WITH ED
PUGH IN RESPECT TO THE MOUSE.
IMAGES MICE AND SOME LATEST
RESULTS LINKING THE ORGs WITH
THE WATER FLUXES IN THE RETINA.
SO IN MICE WE WOULD -- THE
ANIMAL FOR ABOUT TWO HOURS, THE
MICE WERE POSITIONED -- INCLUDES
THE FIVE MINUTE FULL -- IMAGING
OF DARK ADAPTATION AND THEN
THERE'S A 10% BLEACH HAPPENING
ROUGHLY AT THE BEGINNING OF THE
SEDAN SO THSCAN, AND WE ALSO OBE
RETINA AFTER THAT FOR ABOUT FIVE
MINUTES.
AND SO HERE YOU CAN SEE THE
IMAGE OF THE RETINA AND THE AREA
THAT WAS BLEACHED AND THE AREA
OF THE B SCANS WE ARE ACTUALLY
EXTRACTING FROM THE MOUSE.
SO WE ONLY ARE ACQUIRING THE W B
SCANS BACK THEN ABOUT 1 HERTZ
RATE SO OUR DATA ARE FAIRLY SLOW
AND WE CAN FOLLOW ANIMALS FOR
SUCH A LONG TIME.
SO WHAT'S HAPPENING AGAIN, THE
IMAGE OF THE MOUSE RETINA HERE,
YOU SEE IT RESPONDING
PHOTORECEPTOR -- IN MOUSE YOU
CAN SEE THE SYNAPTIC BODY,
NUCLEI, AND AFTER SEGMENT AND
OUTER SEGMENT, THE PART OF
PHOTORECEPTOR THAT WE THINK IS
LINKED WITH THE SWELLING, SO IF
YOU LOOK AT THIS LENGTH OF
RESPONSE OF MOUSE RETINA, YOU
CAN SEE HERE THAT ON THIS
PROFILE WE'RE STARTING WITH THE
BLACK PROFILE BEING PROFILE
WITHOUT LIGHT STIMULATION, THEN
THE RED IS DURING LIGHT
STIMULATION.
SO HERE WE CAN ALSO TRY TO --
INSTEAD OF SHOWING THIS VIDEO WE
CAN HAVE IT COLOR-CODED -- THE
COLOR CODES THE TIME AFTER
STIMULATION, GOING FROM BEFORE
STIMULATION IS THE BLUE AND ALL
THE WAY TO THE POST STIMULATION
ON THE RIGHT.
YOU CAN HOPEFULLY SEE IN THE
CASE OF HIGH SOS, THE DIPS, YOU
HAVE THE STRONGEST EFFECTS IN
CHANGES OF SCATTERING AND
CHANGES IN THE POSITION OF THE
BENDS.
SO THIS WAS DESCRIBED FROM -- IN
2017 BY SANG ZHANG, INCREASED
THICKNESS OF THE BANDS.
SO THEN WE CREATED -- ED CAME UP
WITH THE STORY DESCRIBING THIS
AS A OSMOTIC MOVEMENTS.
SO WHAT WE DID LATER TO TRY TO
COLONIZE IT, WE NOW KIND OF SET
UP THE MODEL IN WHICH INSTEAD OF
USING THE LIGHT AS A STIMULATION
FOR RETINAL SWELLING, WE'RE NOW
USING RETINAL EDEMA, SO IN THIS
CASE WE'RE INJECTING MICE WITH A
SMALL AMOUNT OF WATER INTO THEIR
BODIES AND THIS CHANGES THE
OSMOLARITY OF THE BLOOD PLASMA
WHICH IS CAUSING THE SWELLING OF
OVERALL NEURAL TISSUE IN THE
BRAIN AND IN THE EYE.
SO WHAT WE'RE DOING NOW, WE HAVE
THE SAME KIND OF -- FOR -- BEING
THE WATER INJECTION VERSUS THE
FLASH OF LIGHT.
THE ONLY DIFFERENCE BETWEEN
THESE TWO EXPERIMENTS IS ORG AND
THE WATER INJECTION IS THAT THE
WATER INJECTION CHANGE IS
HAPPENING AT ABOUT FOUR TIMES
SLOWER RATE, SO THAT'S WHY WE
HAVE TO PERFORM THESE
MEASUREMENTS OVER 20 MINUTES,
AND THOSE WERE FIVE DIFFERENT
MEASUREMENTS THAT WE HAVE A
CONTROL, WITHOUT INJECTION,
WATER INJECTION, AND THEN A
FLASH WITH LIGHT, WITHOUT WATER
INJECTION.
THE DATA IS NOW ANALYZED IN A
WAY THAT FOR EACH OF THESE
BANDS, FOR EACH OF THIS PEAK
PROFILE, WE ARE MAPPING -- TH
THE -- WE CAN GET THE INTENSITY,
THE WIDTH OF THE PEAK AND ALSO
THE CHYMO GRAPH ON THE IMAGE C
THAT SHOWS YOU HOW THE RETINA
SWELLING OVER TIME AFTER WATER
INJECTION, SORE W SO WITH THIS,N
NOW KIND OF LOOK AND ANALYZE THE
SWELLING AND THE CHIMOGRAPHS FOR
THE LIGHT STIMULATION AND
THEN -- SO THIS IS SHOWING YOU
THREE DIFFERENT CASES.
THE ORG AFTER WATER INJECTION
AND ORG IN DEHIGH D DEHYDRATIOND
THE SAME FOR WATER INJECTION.
THERE'S NOT ENOUGH TIME TO GO
OVER DETAILS BUT IT LOOKS LIKE
THE OBSERVATION THAT WE HAVE IS
THAT THE SAME KIND OF SWELLING,
CHANGES IN SCATTERING THAT WERE
OBSERVED WITH THE LIGHT EVOKED
SIGNALS CAN BE OBSERVED WITH
THIS █WATER INJECTION, WHICH
FURTHER VALIDATES THE POINT THAT
THIS IS DUE TO THE WATER
INJECTION INITIALLY.
SO I WANT TO JUST LEAVE YOU NOW
WITH SOME CONCLUSIONS AND THANK
YOU VERY MUCH FOR YOUR
INTENTION.
[APPLAUSE]
>> ALL RIGHT.
OUR THIRD SPEAKER OF THE SESSION
IS RAVI JONNAL, ASSOCIATE
PROFESSOR OF OPHTHALMOLOGY AT
UNIVERSITY OF CALIFORNIA DAVIS
AND HE'LL BE TALKING TO US ABOUT
OPTORETINOGRAPHY, BASIC AND
TRANSLATIONAL APPLICATIONS.
RAVI.
>> HI, EVERYONE.
I WANT TO FIRST CONGRATULATE JIM
AND DAVID AND ERIC ALSO ON THEIR
PRESTIGIOUS AWARDS AND JUST SAY
HOW GRATEFUL I AM TO BE HERE AND
HAVE AN OPPORTUNITY TO PRESENT
TO SUCH AN ESTEEMED GROUP OF
PEOPLE.
SO I'M GOING TO TALK MORE ABOUT
OPTORETINOGRAPHY AFTER THE
EXCELLENT TALKS I DON'T HAVE
THAT MUCH MORE TO SAY, BUT I'LL
TRY TO ADD SOMETHING TO THE
DISCUSSION HERE.
I'D LIKE TO JUST QUICKLY SHARE
PHOTOGRAPHS OF PEOPLE PAST AND
PRESENT WHO HAVE CONTRIBUTED TO
THESE PROJECTS, EVERYTHING I'M
GOING TO SHOW DEPENDED
CRITICALLY ON PEOPLE HERE IN
THESE PICTURES.
SO JUST TO ORIENT US, I MEAN, I
THINK EVERYONE HERE IS QUITE
FAMILIAR WITH THIS STRUCTURE OF
THE RETINA, BUT IT BEARS
MENTIONING NEAR-INFRARED WAY.
SO I'M GOING TO BE TALKING ABOUT
WHAT HAPPENS TO THE OUTER
SEGMENT OF THE PHOTO RECEPTORS
WHEN YOU STIMULATE THEM WITH
LIGHT, AND AGAIN, RAM HAS GIVEN
A LOT OF THE BACKGROUND HERE.
I'LL TRY TO -- I THINK WHAT I'LL
SAY, I'LL SAY A LITTLE MORE
ABOUT HOW THESE EFFECTS ARE
CAPTURED IN O.C.T., AND THAT
WILL LEAD ME INTO SOME
CONCLUDING REMARKS I HAVE ABOUT
FUTURE DIRECTIONS.
BUT YEAH, WE'RE GOING TO BE
LOOKING AT HOW LIGHT CHANGES
THESE OUTER SEGMENTS OF THE
PHOTO RECEPTORS.
THERE ARE TWO KIND OF CRITICAL
PROCESSES HERE.
WE'RE TALKING -- WE USE THE TERM
FUNCTIONAL IMAGING, AND I THINK
A LOT OF PEOPLE USE IT WITHOUT
REALLY WONDERING OR SAYING WHAT
FUNCTION IS.
OBVIOUSLY THE FUNCTION OF THE
PHOTO RECEPTORS IS TO TRANSDUCE
AN ELECTRICAL SIGNAL AFTER
ABSORBING PHOTONS, BUT THERE'S
KIND OF A RICH SET OF PROCESSES
THAT WE'RE POTENTIALLY ABLE TO
PROBE.
TWO OF THEM BEING CLOSEST TO THE
PHOTORECEPTOR ARE, OF COURSE,
PHOTO TRANSDUCTION, THE VISUAL
CYCLE, AND THE REASON I NAMED
THESE TWO PROCESSES IN
PARTICULAR IS BECAUSE THERE ARE
A NUMBER OF PROTEINS OR GENES
INVOLVED IN THESE TWO PROCESSES
WHICH ARE SUSCEPTIBLE TO
MUTATION AND THE CAUSE OF MANY
OF OUR WELL-KNOWN INHERITED
RETINAL DEGENERATIONS.
IF YOU -- IF ALL YOU HAVE IS AN
OPTOROENTGENOGRAM, EVERYTHING
LOOKS LIKE A PHOTORECEPTOR
DISEASE, SO THERE ARE TWO REALLY
TWO CLASSES OF DISEASE THAT
WE'RE ABLE TO POTENTIALLY STUDY
AT THIS STAGE, AND THEY ARE
AGE-RELATED MACULAR
DEGENERATION, WHICH MAY NOT BE
THOUGHT TO BE PRIMARILY A
DISEASE OF PHOTO RECEPTORS BUT
CERTAINLY IT AFFECTS THEM EARLY
AND THEN INHERITED RETINAL
DEGENERATIONS WHICH ARE DISEASES
OF THE PHOTO RECEPTORS OR OF THE
RPE CELLS WHICH ARE CRITICAL FOR
THE HOMEOSTASIS AND THE PHOTO
RECEPTORS.
HERE WE SEE A PREFERRED PRACTICE
PATTERN FOR STAGING AND
DIAGNOSIS OF A.M.D.
THERE ARE SOME STRUCTURAL AND
FUNCTIONAL COMPONENTS.
ON THE FUNCTIONAL SIDE, THE
AMSLER GRID IS THE ONLY,
MICROPERIMETRY IS MENTIONED IN
PASSING BUT IT'S NOT LIKE A
CRITICAL ASPECT OF DIAGNOSIS.
ADAPTIVE OPTICS IS ALSO
MENTIONED ON THE STRUCTURAL SIDE
BUT IT'S NOT A MAINSTAY.
FOR IRDs, WE SEE A LITTLE BIT
RICHER SET OF TESTS ON THE
STRUCTURAL SIDE AND FUNCTIONAL
SIDE, BCVA, VISUAL FIELDS AND
MICRO PRIM TRI IS CALLED FOR,
ELECTRORETINOGRAPHY IS CALLED
FOR BUT I DO KNOW THAT ERGs
ARE RARELY ORDERED OR NOT RARELY
BUT OFTEN ARE NOT ORDERED FOR
IRD PATIENTS.
OF COURSE GENETIC TESTING IS
GROWING, IT'S GROWING IN
SIGNIFICANCE AS THE COST OF
GENETIC TESTING BECOME MORE
TRACTABLE, IT'S BECOMING A MORE
COMMON PART OF THE DIAGNOSIS OF
INHERITED RETINAL DEGENERATIONS.
SO EXISTING STRUCTURAL ASSAYS
REVEAL SOME OF THE WEAKNESSES OF
EXISTING ASSAYS.
EXISTING STRUCTURAL ASSAYS
REVEAL CHANGES ONLY AFTER
PHOTORECEPTORS ARE LOST AND THEY
LACK FUNCTIONAL INFORMATION.
EXISTING FUNCTIONAL ASSAYS,
THEY'RE OFTENTIMES SUBJECTIVE
AND SUFFER FROM ASSOCIATED
SOURCES OF NOISE LIKE LEARNING
EFFECTS AND FATIGUE, AND THEY
PROVIDE LIMITED SPATIAL
LOCALIZATION AND NEURAL
SPECIFICITY.
SO OPTORETINOGRAPHY I SEE AS A
NICE COMPLEMENT TO THESE, ALONG
WITH AN IMAGE, IT HAS TO HAVE AN
IMAGE ATTACHED TO IT.
LIKE RAM MENTIONED, WE'VE BEEN
DOING THIS FOR QUITE A WHILE,
AND I PUT THIS SLIDE UP NOT TO
TOOTHTOOT MY OWN HORN AS MUCH AS
DON'S, I'M PROBABLY GOING TO
SKIP SOME SLIDE HERE, WHEN -- SO
DON AND I WERE UNDER SOME
PRESSURE TO PRODUCE SOME RESULTS
BACK THEN, AND WE WERE -- THIS
WAS A KIND OF LIKE A TANGENT
FROM THE MAIN O.C.T. PROJECT,
AND WE STARTED SEEING IN THESE
SCINTILLATIONS OF CONES AND WE
WERE -- I WAS TASKED WITH
PRODUCING A NICE IMAGE OF THE
PHOTORECEPTOR MOSAIC AND DONE
DON ANDI WERE SITTING THERE LOOT
THESE TOGETHER AND I WAS LIKE I
CAN AVERAGE THESE OUT AND DON
WAS LIKE SLOW DOWN, THERE'S
PROBABLY SOMETHING THERE, AND IT
WAS WITHIN MINUTES WHERE HE'S
LIKE WELL, THINK THIS MIGHT BE
AN INTERFERENCE EFFECT AND THAT
LED TO THIS WHOLE FIELD REALLY,
AND ALSO IS WHAT KIND OF
CONVINCED ME TO DO A PH.D. IN
THE PROJECT.
SO IT'S NICE TO SEE IT IN THAT
AERIAL IMAGING MODALITY LIKE
THAT.
THAT AREA IS CONTINUING TO BE
INVESTIGATED.
WE'RE SORT OF WORKING ON IT BUT
JESSICA MORGAN IS ESPECIALLY
WORKING ON IT, HER FORMER
STUDENT ROB COOPER WORKING ON IT
AND I'LL SAY MORE ABOUT THAT
AGAIN AND WHY I THINK IT'S
IMPORTANT TO MAINTAIN THIS SORT
OF DIVERSITY OF APPROACHES.
BUT OF COURSE IT WOULD BE NICE
DO THIS WITH AOCT AND SO WE'VE
SEEN AN INTRODUCTION TO
AO-O.C.T.
IT'S A THREE-DIMENSIONAL
CELLULAR RESOLUTION IMAGE OF THE
PHOTORECEPTOR MOSAIC AND -- OR
THE WHOLE RETINA.
SO HERE WE'RE SEEING THE TOP OF
THE PHOTORECEPTORS, THE ISOS AND
HERE WE'RE SEEING THE BACK OF
THE PHOTORECEPTORS, THE COST,
HERE WE SEE CROSS-SECTIONAL
IMAGES THROUGH THE MOSAIC.
AND THIS KIND OF -- ONCE WE
STARTED GETTING IMAGES LIKE THIS
HAVE SORT OF OPENED UP THE WORLD
OR IT OPENED A NEW WORLD OF
AVENUES OF INVESTIGATION.
I WAS INSPIRED IN THINKING ABOUT
THE PHASE SENSITIVE O.C.T. PAPER
VERY MUCH BY THIS PAPER BY MIKE
CHOMA AND MIKE ISAT'S GROUP.
HE WAS ABLE TO SHOW THAT YOU CAN
USE THE PHASE OFS O.C.T. SIGNAL,
SO IF YOU EXPRESS THE O.C.T.
SIGNAL THE FRINGE THIS WAY,
AFTER 4A TRANSFORM YOU GET THE
PHASE OUT HERE IN THIS
COMPONENT.
AS ROBERT MENTIONED IN HIS TALK
YOU CAN COMPUTE THE SENSITIVITY
OF THE -- THE PHASE SENSITIVITY
ON THIS, IT DEPENDS ON THE SNR
OF THE O.C.T. BUT FOR
PHOTORECEPTORS WHICH ARE
EXTREMELY BRIGHT, WE CAN GET
DOWN TO A FEW NANOMETERS OF
PHASE SENSITIVITY.
WHAT MIKE DID WAS APPLY THIS TO
CHICKEN CARDIOMYOCYTES IN VITRO,
AND WAS ABLE TO SHOW THEM
BEATING THE WAY THAT THEY OUGHT
TO, AND WHAT I THOUGHT WAS,
WELL, THE PROBLEM WITH THE HUMAN
EYE IS THAT IT'S MOVING AROUND A
LOT, SO THE ABSOLUTE PHASE OF
THE O.C.T. SIGNAL AT ANY GIVEN
TIME IS KIND OF MEANINGLESS, YOU
ABOUT WHAT I PROPOSED WAS THAT
IF YOU LOOK AT PHASE DIFFERENCES
INSIDE THE TISSUE, THEN YOU CAN
EXTRACT -- YOU KIND OF REFERENCE
THE OBJECT OF INTEREST AS
SOMETHING ELSE IN THE TISSUE.
OR IN THE EYE.
AND THEN IN SO DOING, YOU CAN
GET SOME VERY NICE CORRELATION
OF THE PHASE WITHIN
PHOTORECEPTORS -- SORRY, THIS IS
A PHASE CORRELATION WITHIN PHOTO
RECEPTORS.
AND THAT LED TO THIS KIND OF
MAIN OBSERVATION.
THE FIRST TO OBSERVE IT -- I
MEAN, THE PROBLEM BACK THEN WHEN
I PUBLISHED THAT PAPER WAS THAT
THE O.C.T. SYSTEMS WERE NOT FAST
ENOUGH TO MEASURE THESE CHANGES.
AND IT WASN'T UNTIL GARY AND
HOODMAN BUILT THIS PHENOMENALLY
FAST SYSTEM IN GERMANY IN 2016,
I'M SORRY I DON'T HAVE A
CITATION BUT I THINK ROBERT
SHOWED IT, THAT THEY WERE ABLE
TO MEASURE THESE IN REALTIME IN
A REAL HUMAN.
BUT THE IDEA IS THAT WE'RE
GETTING LIGHT BACK FROM THE
FRONT AND BACK OF THE OUTER
SEGMENT, AND WE'RE MONITORING
THE PHASE DIFFERENCE BETWEEN
THOSE TWO IN ORDER TO MONITOR
CHANGES IN THE OPTICAL PATH
LENGTH OF THE CELL, OR OF THE
OUTER SEGMENT.
SO IN OUR GROUP, WE HAVE FOUR
DIFFERENT APPROACHES TO STUDY
THIS PHENOMENON.
THE FIRST WAS THE SCANNING
AO-O.C.T.
I'LL SHOW SOME RESULTS FROM
THESE ALTHOUGH THEY OVERLAP A
LOT WITH WHAT RAM HAS SHOWN.
BUT THE FIRST WAS THE SCANNING
AO-O.C.T. AND MORE RECENTLY
WE'VE BEEN TAKING H MEASUREMENTS
WITH THE FULL FIELD AO-O.C.T.
I'LL KIND OF GROUP THESE
TOGETHER.
THEY HAVE THEIR OWN VIRTUES.
THEY'RE EXTREMELY COMPLICATED
SYSTEMS AND DIFFICULT TO
MAINTAIN AND OPERATE, BUT
BECAUSE THEY HAVE -- BASICALLY
THE DIFFERENCE BETWEEN THE TWO
IS THIS ONE HAS BETTER
SENSITIVITY AND BETTER
RESOLUTION.
AND WE'RE ABLE TO MEASURE ROD
RESPONSES, FOR INSTANCE, AND
FOVEAL CONE RESPONSES.
THE FULL FIELD AO-O.C.T. IS
FASTER SO WE'RE ABLE TO MEASURE
MORE OF THE DYNAMICS AND THE
RESPONSE OF THE ORG.
AND THEN I'LL MOVE ON TO TALK
ABOUT THE PROTO CLINICAL O.C.T.
LATER.
AND THEN I JUST WANT TO MENTION
THAT WE'RE STILL INTERESTED IN
THIS COHERENT AO-SLO APPROACH
BECAUSE COMPARED TO ALL OF THE
OTHERS -- WELL, PERHAPS NOT THE
CLINICAL O.C.T. BUT DEFINITELY
COMPARED TO THESE TWO, IT'S A
KIND OF LIGHT WAIT METHOD.
THE DATA VOLUMES ARE THREE
ORDERS OF MAGNITUDE SMALLER AND
THE COMPUTATIONAL BURDEN IS WAY,
WAY LESS, SO IF YOU START
THINKING ABOUT THE POSSIBILITY
OF TRANSLATING THESE THINGS INTO
THE CLINIC, IT DEFINITELY HAS
MORE PROMISE THAN EITHER OF
THESE TWO.
MAYBE TIED WITH THIS ONE.
SO HERE'S A SCHEMATIC OF OUR
SCANNING AO-O.C.T. SYSTEM, IT
HAS AN SLO CHANNEL AS WELL.
I MENTIONED FOUR DIFFERENT
APPROACHES TO MEASURING THE ORK,
TWOORG,TWO ARE REALLY IN THE SAE
SYSTEM, THIS ONE WITH ADAPTIVE
OPTICS.
HERE WE SEE THE SLO IMAGE AND
THE O.C.T. IMAGE FROM THE SYSTEM
A COUPLE OF DEGREES FROM THE
FOVEA.
AND HERE ARE SOME EXAMPLES OF
AGES OF THE ROD AND CONE MOSAIC.
WE'RE USING THE SYSTEM TO
MEASURE RESPONSES IN RODS AND
CONES.
AND THIS IS WHAT WE SAW.
THIS IS BACK IN 2019 WHERE THE
CONE MEASUREMENTS IN 2020, THE
ROD MEASUREMENTS.
SO I'M SURPRISE DO SURPRISED BYG
THAT RAM SHOWED.
WE HAVE QUITE DIFFERENT
OBSERVATIONS, SO THERE MAY BE
SOME CAUSE FOR DISCUSSION LATER.
BUT WE SHOW BASICALLY -- I'LL
DIRECT YOUR ATTENTION TO THIS
PANEL HERE, F, WHICH SHOWS KIND
OF MOST CLEAR LEGAL -- WELL,
THIS F AND G, WHICH SHOW MOST
CLEARLY THE DIFFERENCES BETWEEN
THE RESPONSE OF RODS AND CONES.
TO US IT LOOKS LIKE THE CONES
RESPOND FAST AND WITH A LITTLE
BIT LESS SENSITIVITY, SO THE
SENSITIVITY DIFFERENCE IS
VISIBLE HERE.
YOU CAN SEE THE RODS ARE
BLEACHED LESS THAN THE CONES IN
THIS CASE, AND YET RESPOND WITH
A LONGER ELONGATION OR GREATER
ELONGATION.
SO I DON'T KNOW, IT'S FOOD FOR
THOUGHT.
IT'S CERTAINLY AN INTERESTING
DIFFERENCE TO SAY THE RODS ARE
MORE SENSITIVE AND SLOWER THAN
THE CONES KIND OF BEARS SOME
SIMILARITY TO WHAT WE THINK
ABOUT BEHAVIOR IN, YOU KNOW --
IN THE VISUAL SYSTEM.
I WANT TO SHOW YOU THE RESPONSES
TO RODS HERE, ONLY TO INDICATE,
WELL, THERE'S THIS
DOSE-DEPENDENCE WHICH KIND OF
CONVINCED US THAT WE WERE
SEEING, YOU KNOW, A REAL
FUNCTIONAL RESPONSE IN THE RODS.
BUT ALSO TO THE -- WE HAVE SK
SOMETHING LIKE -- WHAT IS THIS,
LET'S CALL IT FOUR ORDERS OF
MAGNITUDE -- SOMEWHERE BETWEEN K
THAT FOR WHEN WE COME TO SOME OF
THE LATER STUFF.
SO THE SYSTEM WAS NOT FAST
ENOUGH TO MEASURE, SO AFTER WE
REPORTED THOSE OWE LON GAITION N
RESULTS, WE WANTED TO BE ABLE TO
MEASURE THAT AS WELL IN ORDER TO
HAVE A COMPLETE PICTURE OF THE
ORG AND SO WE BUILT A FULL FEEL,
I SAY WE, REALLY MY POSTDOC
EXTREMELY TALENTED POSTDOC
DENISE BUILT A FULL FIELD A
AO-O.C.T. SYSTEM IN WHICH WE
COULD GET IMAGES OF THE CONE
MOSAIC AND VOW EU METRIC RATES
AT UP TO 1-KILOHERTZ, SO JUST ME
NOMINAL, PHENOMENAL RATES.
WE SHOW THIS DOSE DEPENDENCE
RESPONSES VERY MUCH LIKE WHAT
RAF SHOW WHAT
RAV SHOWED, THE INITIAL
CONTRACTION OF THE OUTER
SEGMENT.
SO AFTER WE SHOWED ALL THAT, I
STARTED TO WONDER, HOW ARE WE
GOING TO DO THIS CLINICALLY?
AND WHAT HAPPENS IF WE REALLY
SLOW THINGS DOWN?
SO IN 20 -- STARTING AROUND 2019
OR 2020, I WITH ANOTHER POSTDOC
BUILT A SYSTEM THAT WAS
INTENTIONALLY OLD-FASHIONED, A
RELATIVELY SLOW LIGHT SOURCE,
NOTHING ESOTERIC OR FANCY IN THE
SCANNERS, VERY BOILERPLATE
BALANCE DETECTION, SO JUST -- I
MEAN, THE THOUGHT WAS LIKE -- I
MEAN, THIS IS SOMETHING THAT
COULD BE COMMERCIALIZED TODAY,
IN FACT, IT PROBABLY COULDN'T BE
BECAUSE IT'S TOO OLD-FASHIONED
FOR COMPANIES ALREADY.
NOW, HOW DO WE EXTRACT THE
SIGNAL FROM HERE?
I'LL TAKE A MOMENT WITH THIS
SLIDE AND I'LL TRY TO -- THERE
ARE BLOCK DIAGRAMS IF THAT HELPS
YOU TO UNDERSTAND IT, FEEL FREE
TO -- IF YOU CAN'T TRACK -- SO
IF YOUR O.C.T. IS THIS SLOW, YOU
CAN'T HOPE TO DO VOLUMETRIC ORG.
SO WE DO SERIAL LINE SCANNING.
SO WE'RE JUST SCANNING THE
RETINA IN ONE PLACE.
BUT OF COURSE THE RETINA IS
MOVING, RIGHT?
SO THAT'S A PROBLEM.
HOW DO YOU EXTRACT AN
OPTORETINOGRAPHIC SIGNAL IF THE
RETINA IS MOVING AND YOU'RE
SCANNING IN ONE PLACE OR
EQUIVALENTLY SCANNING DIFFERENT
PARTS OF THE RETINA.
SO WHAT WE -- THE METHOD IS --
IT'S KIND OF LIKE WHAT I WAS
CONCOCTING IT, I WAS INSPIRED
REALLY BY A LOT OF WHAT WAS
HAPPENING IN OCTA.
THE IDEA IS THAT OVER THE COURSE
OF THE ONE SECOND YOU NEED TO
TAKE A COMPLETE MEASUREMENT, THE
RETINA DOES MOVE, BUT THERE ARE
MAYBE 10 MILLISECOND WINDOWS IN
THERE IN WHICH THE RETINA
DOESN'T MOVE, AND BY DOESN'T
MOVE, I MEAN IT DOESN'T MOVE
RELATIVE TO THE 15-MICRON SPOT
SIZE ON THE RETINA.
YOU'RE ESSENTIALLY LOOKING AT
THE SAME TISSUE.
SO WE TAKE THE SERIES OF B SCANS
AND WE DIVIDE IT UP INTO THESE
OVERLAPPING BLOCKS AND IN THOSE
OVERLAPPING BLOCKS INSTEAD OF
LOOKING AT THE POSITION OF THE
LAYERS, WE COMPUTE THE PHASE
VELOCITIES OF THE LAYERS, SO YOU
GO TO THE LAYERS OF INTEREST,
YOU COMPUTE THE PHASE VELOCITIES
AND THEN YOU TRACK THAT VELOCITY
OVER TIME.
AND WE GOT SOME VERY NICE
RESULTS.
IN NOW FAR MORE SUBJECTS.
THESE WERE PUBLISHED IN 2022,
BUT IN MANY MORE SUBJECTS THAN
THIS, WE'VE HAD THIS HIGHLY
REPRODUCIBLE PATTERN OF
CONTRACTION AND ELONGATION THAT
BEARS SIMILARITY TO WHAT WE'VE
SHOWED WITH THE POSITION BASED
ORG.
THE RESPONSES ARE DOSE DEPENDENT
ALTHOUGH WITH A HIGHLY -- A MUCH
SMALLER DYNAMIC RANGE,
PROBABLY -- 10 TO 20DB.
SO THAT'S IMPORTANT TO NOTE, AB
IMPORTANT POTENTIAL WEAKNESS OF
THIS APPROACH.
AND WE SEE EE CENTRICITY
DEPENDENCE THAT WE'VE ALL
OBSERVED WITH THE POSITION-BASED
ORGs AS WELL.
AND THEN JUST -- I JUST WANT TO
TOUCH ON THE APPLICATION TO
DISEASE HERE, WE'RE SEEING --
WE'VE MEASURED -- WELL, OKAY,
JUST TO BE COMPLETELY HONEST,
WE'VE MEASURED PROBABLY 30
PATIENTS, AND IN THE MAJORITY OF
THESE PATIENTS, THE RETINAL
LAYERS ARE NOT GOOD ENOUGH FOR
US TO GET AN ORGAN ORG OUT THERO
DEGENERATED, TOO MESSED UP, SO
ARE THERE BLUNTER WAYS IN WHICH
WE CAN ASSESS THE DISEASE.
BUT STILL, WE HAVE SOME PATIENTS
WITH SOME INTERESTING CHANGES
AND IF WE THROW SOME AD HOC KIND
OF METHODS OF QUANTIFYING THESE
CHANGES, WE CAN SEE REAL
DIFFERENCES BETWEEN THE NORMAL
AND THE DISEASE AFFECTED RETINA.
SO THESE ARE NORMALIZED BY THE
NORMAL RESPONSE, AND WE CAN SEE
THAT THE VMIN, THAT'S THE
MAXIMUM CONTRACTION AND V20 TO
40, VMIN LOOKS LIKE IT'S NORMAL
IN MANY OF THE LOCATIONS WE
IMAGED WHEREAS THE ELONGATION
COMPONENT SEEMS COMPROMISED.
NOW, I'LL TRY AND GET THROUGH, I
HAVE A SLIDE AFTER THE
CONCLUSION SO I'LL TRY TO --
I'LL GO THROUGH THIS VERY
QUICKLY.
WELL, I DON'T NEED TO READ THESE
CONCLUSIONS TO YOU.
I JUST WANT TO GET TO THE LAST
CONCLUSION AND SAY THAT I WAS --
I ADDED THIS NEXT SLIDE JUST
TODAY BECAUSE I WAS KIND OF
INSPIRED BY COMMENTS THAT MIKE
MADE AND JIM IN THEIR MORNING
TALKS TODAY ABOUT HARMONIZATION
AND THE IMPORTANCE OF DEPLOYING
THINGS CLINICALLY OR AT LEAST
BROADLY FOR THE SAKE OF THE
SCIENCE, NOT JUST FOR THE SAKE
OF DISEASE APPLICATIONS BUT FOR
THE SAKE OF THE SCIENCE.
IT'S THIS KIND OF ITERATIVE
CYCLE OF LEARNING MORE ABOUT
WHAT YOU'RE MEASURING AND THEN
REFINING YOUR INSTRUMENTATION
AND GOING BACK AND FORTH AND SO
I REALLY WANT TO SAY A FEW WORDS
ABOUT STANDARDS AND
HARMONIZATION.
SO THIS IS A PEEK AT WHAT WE'RE
WORKING ON NOW.
SO THIS IS A RESPONSE FROM OUR
FULL FIELD AOCT SYSTEM AND --
JUST 15 MORE SECONDS.
THIS IS A RESPONSE FROM SOME
CONES IN THE FULL FIELD SYSTEM
AND NOW WHAT WE'RE TRYING TO DO
IS TO MODEL THE RESPONSE IN A
WAY THAT WE CAN EXTRACT SOME
PARAMETERS OF INTEREST, AND SO
THIS MODEL THAT WE'RE USING
RIGHT NOW, IT'S A WORKING MODEL,
IT'S NOT NECESSARILY THE BEST
MODEL OF THE RESPONSE, BUT IT
WORKS PRETTY WELL.
AND IT HAS THESE DISTINCT
PARAMETERS HERE WHICH CAN BE
EXTRACTED FOR ASSESSMENT.
SO THOSE INDIVIDUAL PARAMETERS
CAN BE LOOKED AT AS FUNCTIONS OF
DISEASE OR EE CENTRICITY OR
WHATEVER AND WE DO SEE SOME
INTERESTING RELATIONSHIPS
INTEREST.
FROM A MODEL LIKE THIS, WE CAN
DERIVE FIGURES OF MERIT LIKE
SIMPLER FIGURES OF MERIT SUCH AS
T MAX LIKE WHEN DOES THIS REACH
ITS MAXIMUM ELONGATION.
AND THEN WE CAN ALSO TAKE STEPS
TOWARDS HARMONIZATION, LIKE FOR
INSTANCE, GIVEN AN EXPRESSION
LIKE THIS, WE CAN
STRAIGHTFORWARDLY COMPUTE THE
VELOCITY, SO NOW WE HAVE A
SIMILAR -- ABOUT A MODEL THAT WE
CAN USE TO MODEL THE PHASED
VELOCITY APPROACH AS WELL AND WE
CAN EXTRACT WHAT YOU WOULD SEE
IN THE -- APPROACHES.
IT'S LIKE DEVELOPING A KIND OF
GRAMMAR FOR THE ORG THAT WOULD
ALLOWL THE DIFFERENT SYSTEMS AND
DIFFERENT PRACTITIONERS TO TALK
TO ONE ANOTHER AND PRESERVE SOME
HOPE.
BEFORE IT GETS -- I MEAN, IF IT
GETS COMMERCIALIZED, BUT BEFORE
IT GETS COMMERCIALIZED, HAVE
SOMETHING IN PLACE WHERE WE CAN
KIND OF, YOU KNOW, EXCHANGE
IDEAS, EXCHANGE DATA, AND IT
BE -- AND HAVE IT BE MEANINGFUL
FOR ONE ANOTHER.
THAT'S NOT IMPORTANT.
THANKS.
[APPLAUSE]
>> ALL RIGHT.
OUR FINAL SPEAKER OF THIS
AFTERNOON'S SESSION IS CHAO ZH
ZHOU, PROFESSOR OF BIOMEDICAL
ENGINEERING SPEAKING ON
SPACE-DIVISION MULTIPLEXING
OPTICAL COHERENCE TOMOGRAPHY AND
FOE TONPHOTONIC INTEGRATION.
>> GOOD AFTERNOON.
I KNOW I'M THE LAST PERSON FOR
THE TALK.
I'M BETWEEN YOU AND THE REST OF
YOUR DAY.
I HOPE -- ALSO FULL DISCLOSURE,
MY TALK IS NOT ON ORG BUT I HOPE
YOU'LL FIND IT EQUALLY
INTERESTING.
I WANT TO ADD MY CONGRATULATIONS
TO PROFESSOR JIM IF YOU GEEMOTO,
ERIC AND DAVID SWON SON FOR
THEIR PIONEERING WORK STARTING
THIS FIELD.
ALSO THAT'S THE REASON WE ARE
HERE IN THIS ROOM, ALSO THAT'S
THE REASON WE HAVE A HUGE AND
GROWING COMMUNITY IN THE O.C.T.
FIELD.
SO TODAY I'M GOING TO SHARE SOME
OF THE WORK WE DO WITH SPACE
DIVISION MULTIPLEXING, AND THIS
IS -- YOU HAVE SEEN THE SLIDES
FROM DR. FUJIMOTO'S TALK.
WHAT I WANT TO EMPHASIZE HERE IN
ADDITION TO THE HUGE IMPACT
O.C.T. MADE IN OPHTHALMOLOGY, I
WANT TO POINT OUT THAT THESE RED
BARS, AND THOSE FOR TECHNOLOGY
DEVELOPMENT.
IT'S FOR ONE FIELD EVEN AFTER
THREE DECADES, THERE'S STILL
VERY ACTIVE DEVELOPMENT IN
TECHNOLOGIES, AND YOU HAVE HEARD
THAT MANY GROUPS ARE WORKING ON
IMPROVING THE RESOLUTION,
IMPROVE THE IMAGING SPEED,
IMPROVING THE FUNCTIONALITY OF
THIS TECHNOLOGY.
SO THIS IS A VERY EXCITING FIELD
AND THERE ARE STILL A LOT MORE
WE CAN DO TO ADVANCE THIS FIELD.
SO ONE THING WE'RE LOOKING INTO
THIS, THERE'S STILL A LOT OF
TECHNICAL CHALLENGE -- CLINICAL
CHALLENGES, UNMET CLINICAL
NEEDS, AND TRADITIONAL O.C.T.
IMAGING RELIES ON RASTER SCANS.
WE BASICALLY HAVE A SINGLE
IMAGING BEAM SCAN BACK AND FORTH
ON THE SAMPLE IN ORDER TO GET A
HIGH DEFINITION 3D VOLUMETRIC
SET FROM THE IMAGES YOU HAVE TO
COVER ENTIRE FIELD AND ALONG THE
HORIZONTAL -- WE CAN GET REALLY
HIGH QUALITY LIKE HIGH
RESOLUTION CROSS-SECTIONAL VIEW
OF THE RETINA.
BUT ALONG THE -- SCANNING AXIS
WE CAN SEE A LOT OF MOTION
ARTIFACT.
SO FURTHER IMPROVING THE SPEED
WILL HELP US TO MINIMIZE THE
MOTION ARTIFACT, AND ALSO THAT
WILL HELP TO IMPROVE THE
DIAGNOSIS AND TO TRACK DISEASE
PROGRESSION OVER TIME MORE
ACCURATELY.
THE OTHER ASPECT IS IF IT CAN
IMPROVE THE IMAGING FIELD, AND
WE'LL BE ABLE TO SIGNIFICANTLY
IMPROVE THE FIELD OF VIEW THAT
CAN BE COVERED WITHIN THE SAME
AMOUNT OF TIME.
AND THIS WILL BE VERY BENEFI
BENEFICIAL, TODAY YOU HAVE HEARD
ABOUT USING WILD FIELD O.C.T.
AND O.C.T. ANGIOGRAPHY AND THAT
REALLY ALLOWS US TO SEE LIKE NOT
JUST CENTRAL VISION BUT
PERIPHERAL WHERE OFTEN SOME
DISEASE HAPPENS WITHOUT BEING
NOTICED BY THE PATIENT.
SO THIS MOTIVATED US TO FURTHER
IMPROVE THE IMAGING SPEED.
THE OTHER UNMET TECHNICAL NEED
AND CLINICAL NEED IS THAT THE
CURRENT SYSTEM, THEY ARE GREAT,
THEY PERFORM VERY, VERY WELL BUT
THEY ARE BULKY AT THE SAME TIME
THEY ARE VERY EXPENSIVE.
NOT EVERYONE CAN AFFORD IT, SO
IF WE CAN FURTHER IMPROVE THE
TECHNOLOGY TO MAKE IT MORE
COMPACT, MORE PORTABLE, AT THE
SAME TIME IMPROVE THE
PERFORMANCE, FOR EXAMPLE, IF YOU
CAN IMPROVE THE SPEED BY A
FACTOR OF 10 OR EVEN MORE, AND
THAT WILL BE VERY BENEFICIAL.
SO WITH THAT, WE WERE THINKING
TRADITIONAL O.C.T. RELIES ON
CIRRUS SCANNING, AND THEN IF IT
CAN FIND THE WAYS TO IMPROVE THE
IMAGING -- THAT THROUGH PARALLG
THAT WILL IMPROVE THE SPEED.
TRADITIONALLY THIS IS VERY
STRAIGHTFORWARD, STILL NOT
FINISHED YET, SO CONCEPTUALLY IT
VERY STRAIGHTFORWARD, AND WE ALL
KNOW THAT FROM OUR -- LIKE
EVERYDAY -- EVERY COMPUTER WE
HAVE, WE HAVE MULTIPLE CORES.
SO PARALLEL PROCESSING IS A KEY
TO IMPROVE THE PERFORMANCE AND
THROUGHPUT.
BUT FOR O.C.T., IT'S NOT THAT
TRIVIAL.
IF YOU THINK ABOUT WHERE'S THE
STANDARD O.C.T. SYSTEM IF YOU
WANT TO HAVE PARALLEL IMAGE, YOU
CAN PUT THE 60 O.C.T. SETUP
THERE, ONE THE COST WILL
DRAMATICALLY INCREASE AND NOBODY
CAN AFFORD IT, AND TWO, THE
COMPLEXITY OF THE SYSTEM WILL BE
DRAMATICALLY INCREASED.
NOW YOU HAVE TO HAVE TO WORRY
ABOUT HOW TO SYNCHRONIZE
DIFFERENT CHANNELS, AND THERE'S
ALSO A HUGE AMOUNT OF DATA YOU
HAVE TO FIGURE OUT HOW TO DO IT
EFFICIENTLY.
SO WE CAME UP WITH APPROACH WE
CALL THE SPACE DIVISION
MULTIPLEXING O.C.T.
SO THIS IS BASED ON -- SOURCE
O.C.T.
EARLIER TODAY YOU HEARD LIKE
PROFESSOR FUJIMOTO TALK ABOUT
THAT, NOW WE CAN EVEN HAVE LIKE
WITH THE CURRENT -- TECHNOLOGIES
THE COHERENCE CAN BE VERY LONG.
-- IS POSSIBLE IS BECAUSE FOR
THOSE WEB SOURCE LASERS AT EACH
MOMENT THE INSTANTANEOUS
LANGUAGE IS VERY, VERY NARROW.
THAT GAVE US A VERY LONG-RANGING
USING THE TECHNIQUE.
BUT ON THE OTHER HAND, IF YOU
LOOK AT OUR O.C.T. IMAGING AND
WOULD HE AREWE ARE ONLY USING AD
MICRONS OF IMAGING DEPTH, OF
COURSE WE CAN USE A RANGE OF
THAT TO ACCOMMODATE MOTION BUT
THE ACTUAL IMAGES WE GOT IS ONLY
A FEW HUNDRED MICRONS.
HOW CAN WE UTILIZE THE STEPS
THAT'S AVAILABLE?
AND HAVING LIKE MULTIPLE IMAGES
STACKED INTO THE ENTIRE IMAGING
ACQUISITION RANGE.
SO WE INTRODUCED THIS DIVISION
MULTIPLEXING APPROACH FOR OUR
FIRST GENERATION IS VERY
STRAIGHTFORWARD, IT'S BASICALLY
ON THE -- WE JUST HAVE A LIGHT
SPLITTER.
IT'S A PASSIVE LIGHT SPLITTER.
WE CAN SPLIT ONE BEAM INTO
MULTIPLE BEAMS AND BETWEEN EACH
BEAM, WE CAN INTRODUCE A FEW
MILLIMETERS OF OPTICAL DELAYS,
BASICALLY -- THE FIBERS.
WITH THAT, EACH BEAM WILL BE
PROJECTED AT DIFFERENT LOCATIONS
ON THE SAMPLE.
WITH THAT, WHEN WE COLLECT THE
INTERFERENCE SIGNAL BACK FROM
THE TISSUE, THEY ARE ALL IN --
WITH THE SAME REFERENCE MIRROR
BECAUSE EACH CHANNEL HAS A
DIFFERENT DELAY AND THEN THE
INTERFERENCE FREQUENCY WILL SHOW
UP IN DIFFERENT FREQUENCY GAPS.
SO IN A SENSE, WHAT WE ARE -- I
ALWAYS USE THIS ANALOGY IS THAT
WE ALL LIKE LISTEN TO RADIO, AND
DIFFERENT STATIONS ARE IN THE
AIR, THEY ARE PLAYED IN THE AIR
AT THE SAME TIME.
RIGHT?
THE REASON THEY ARE ALL IN THE
AIR AT THE SAME TIME AND NOT GET
MIXED UP IS BECAUSE THEY ARE
CARRIED BY -- THEY ARE -- LIKE
THEY HAVE A DIFFERENT CARRIER
FREQUENCIES.
SO IF WE WANT TO LISTEN TO
CERTAIN CHANNEL WHICH IS TUNED
TO THE CARRIER FREQUENCY, THEN
WE WILL HEAR THE PROGRAM FROM
THAT SPECIFIC STATION.
SO IN THIS CASE, WE ARE USING
THESE OPTICAL DELAY AS TO
INTRODUCE THIS OPTICAL
MODULATION OF THE INTERFERENCE
SIGNAL AND THEN IF WE WANT TO
LOOK AT THE IMAGE AS DIFFERENT
CHANNELS, WE JUST -- OF COURSE
WE ACQUIRE ALL TH THE DATA AT TE
SAME TIME, TH THAT'S HOW WE CANT
A CONCURRENT MEASUREMENT FROM
ALL DIFFERENT CHANNELS AND THEN
IF WE WANT TO SHOW THE IMAGE OF
INDIVIDUAL CHANNEL, WE JUST
FOCUS ON THAT FREQUENCY BAND.
SO WE DEMONSTRATE THE FIRST
PROTOTYPE OF THE SYSTEM A COUPLE
YEARS AGO, SO THIS IS USING A
1 BY 8 ARRAY AND I WILL PLAY
THIS AGAIN SO YOU CAN SEE, WE
CAN SCAN EIGHT BEAMS ON THE
SAMPLE AT ONCE.
THEN WITHIN ONE ACQUISITION, WE
GET IMAGES FROM EIGHT DIFFERENT
LOCATIONS SIMULTANEOUSLY.
SO THE TOTAL DEPTH RANGE IS LIKE
TENS OF MILLIMETER.
THAT'S ENABLED BY THE LASER,
EVERYONE CAN GET NOW.
SO ONE ACQUISITION, YOU GET
EIGHT IMAGES.
AND THEN IF WE STITCH THOSE
EIGHT IMAGES TOGETHER, AND EACH
IMAGE FOCUSES AT A DIFFERENT
SAMPLE LOCATION THEN YOU CAN GET
AN ENTIRE 3D SCAN OF THE SAMPLE
WITHIN A VERY SHORT TIME.
SO BASICALLY USING THIS
APPROACH, WE CAN JUST INTRODUCE
A PASSIVE COMPONENT, WE CAN
BOOST IMAGING SPEED BY A FACTOR
OF 8.
SO FOR THOSE OF YOU WHO KNOW MY
LAB, WE DO A LOT OF FRUIT FLY
STUDIES, SO FRUIT FLY IS KIND OF
THE FAVORITE SUBJECT IN OUR LAB,
AND WITH THE FRUIT FLY, ACTUALLY
WE CAN LOOK AT THE DIFFERENT
DEVELOPMENTAL STAGES AND THIS IS
FOR THE STUDY WE'RE USING EIGHT
BEAM SCAN ON THE FLIES, AT THE
SAME TIME ONE THING TO NOTICE IS
EACH CHANNEL, THE SCANNING IS
EXACTLY COMPLETELY SYNCHRONIZED.
BECAUSE WE'RE USING THE SAME
SCANNER, ALL THE BEAMS ARE MOVED
IN THE SAME WAY.
SO THREE BEAMS SCAN ON THE
SAMPLE IN THE A5, A6,
A7 DIFFERENT SEGMENT OF THE FLY
BODY.
AND YOU CAN SEE THE HEARTBEATING
FROM THE FLY.
THE ONE THING IF YOU NOTICE IS
THAT FOR DIFFERENT SEGMENT, YOU
CAN SEE DIFFERENT PHASES OF THE
CONTRACTION, OKAY?
SO IF YOU PLOT THE DIAMETER OF
THE FLY HEART TOO, YOU WILL BE
ABLE TO SEE A DIFFERENT FLY
SEGMENT, THERE'S A TIME DELAY OF
THE CONTRACTION OF DIFFERENT FLY
HEART -- THAT SHOWS HOW THE --
FROM THE BACK OF THE BODY TO THE
FRONT PART.
YOU CAN SEE THE SYSTOLIC LIKE
PULSATION OF THE ANIMAL.
SO ARE HERE I EMPHASIZE YOU CAN
USE THIS APPROACH TO SYNCHRONIZE
THE IMAGING BUT AT THE SAME
TIME, THIS TECHNOLOGY HAS SOME
ADDITIONAL BENEFIT THAT CAN BE
VERY HELPFUL.
FOR EXAMPLE, LIKE NOW WITH -- IN
ORDER TO DO O.C.T. ANGIOGRAPHY,
WE HAVE TO REALLY SCAN -- WE
HAVE TO DO REPEATED SCAN, ONE TO
SLOW DOWN THE IMAGING SPEED AND
IF WE'RE USING HIGH SPEED LASER,
WE HAVE TO DRIVE THE GAVEL
REALLY AGGRESSIVELY TO MAKE THE
GAVEL MOVE VERY FAST, BUT IF WE
CAN USE THIS APPROACH, ALL THE
BEAMS WILL BE SCANNED AT THE
SAME TIME.
TO IMPROVE THE IMAGING SPEED IS
THROUGH THE PARALLEL IMAGING
RATHER THAN DRIVING THE GAVEL
LIKE CRAZY.
THERE ARE OTHER ADVANTAGES AS
WELL.
SO AFTER OUR FIRST DEMONSTRATION
AND WE ACTUALLY WERE FACING ONE
OF THE CHALLENGES IS THAT OUR
FIRST PROTOTYPE WAS BUILT ON
THIS FIBEROPTICS.
IT'S VERY -- IT'S GOOD THAT WE
SHOW THE PROOF OF PRINCIPLE.
THIS APPROACH WORKS.
BUT ON THE OTHER HAND, IT'S VERY
TEDIOUS AND VERY HARD TO MAKE
THIS FIBER ARRAY BECAUSE IF YOU
ACCIDENTALLY BREAK ONE FIBER,
THE ENTIRE ASSEMBLY IS DONE.
YOU HAVE TO REDO IT.
AND ALSO YOU HAVE TO PRECISELY
CONTROL THE DELAY OF DIFFERENT
CHANNELS AND THAT'S VERY HARD TO
DO, REPEATEDLY.
SO WITH THAT IN MIND, WE
DEVELOPED OUR FIRST GENERATION
PHOTONIC CHIP.
THIS IS PURELY A PASSIVE CHIP.
THIS IS A SILICON INSULATOR WITH
THE WORKING WAVELENGTHS AT
1.3-MICRON.
IT'S VERY SIM BELL PEL SIMPLE, E
LIGHT INPUT AND IT SPLIT INTO
MULTIPLE -- LIKE EIGHT DIFFERENT
CHANNELS.
EACH CHANNEL, WE CAN INTRODUCE
OPTIC DELAY THAT I MENTIONED
EARLIER.
SO IN THIS CASE, WE CAN PROJECT
EIGHT BEAMS ON THE SAMPLE, WE
CAN GO BACK TO THE SAME CHIP AND
GET -- WITH THE REST OF THIS
LIKE A REFERENCE ARM AND YOU CAN
DETECT IT.
SO WITH THIS CHIP BASED SYSTEM,
THE ADVANTAGE IS THAT ONCE YOU
HAVE THE DESIGN, YOU CAN MAKE AS
MANY AS YOU WANT.
THEY ALL HAVE THE SAME
PERFORMANCE, THEY ALL HAVE THE
SAME DELAYS IN THE SPACING AND
POTENTIALLY THIS APPROACH CAN BE
SCALABLE.
THE PER-UNIT COST CAN BE VERY,
VERY LOW ONCE YOU HAVE YOUR
DESIGN.
AND WITH THIS CHIP AND LIKE THIS
ONE BECAUSE IT'S ON SILICON,
SILICON INSULATOR, IT'S WORKING
AT 1.3-MICRON AP THEN -- BUT WE
WERE ABLE TO SHOW THAT WITH THIS
8-CHANNEL SYSTEM, WE WERE ABLE
TO SCAN THE ANTERIOR SEGMENT OF
A -- AND THIS IS EX VIVO.
THE ENTIRE 3D SCAN CAN BE
FINISHED IN LESS THAN ONE
SECOND.
AND ALSO IF WE SCAN THE FINGER,
WE CAN REVIEW THE DETAILS OF THE
FINGERPRINT AND ENTIRE 3D SCAN
COVERING 18 BY 14-MILLIMETER
RANGE CAN BE FINISHED IN ONE
SECOND.
AND OF COURSE THE MOST IMPACT
FOR OPHTHALMOLOGY IS IN -- MOST
IMPACT OF O.C.T. IS IN
OPHTHALMOLOGY AND WE BUILD THE
FIRST PROTOTYPE USING 1060 --
LASER BUT FOR THIS FIRST
GENERATION WE WERE STILL RELYING
ON FIBEROPTICS AND BECAUSE THE
CHIPS WERE NOT READY FOR THIS
YET.
SO WE HAVE FOUR FIBERS COMBINED
TOGETHER WITH -- DELAY AND WE'RE
ABLE TO SCAN ENTIRE BACK OF THE
RETINA IN LESS THAN ONE SECOND.
AND HAVE A VERY DECENT PICTURE.
AND THIS IS COLLABORATION WITH
DR. BRUCKER AT UNIVERSITY OF
PENNSYLVANIA.
WE CAN COVER A WIDER FIELD OF
VIEW, AND WE HAVE MORE SLICES
FOR THE CUBE SCAN AND WE
DEMONSTRATED THE TECHNOLOGY IN A
FEW CLINICAL CASES OF DIABETIC
RETINOPATHY AND RETINAL
CHALLENGES.
WE ALSO SHOW THAT O.C.T. ANG GA
FEE IS FEASIBLE USING THIS
APPROACH, AND WE CAN GET LIKE A
DEPTH RESULT IMAGES OF THE
FINGERNAIL AND A LOOK AT THE
CAPILLARIES AT DIFFERENT DEPTHS.
SO OF COURSE WE ARE NOT THE ONLY
ONES WHO ARE WORKING ON
EXPLORING PARALLEL O.C.T.
IMAGING SYSTEM AND THIS IS ONE
OF THE EARLIER WORK FROM
PROFESSOR AUDREY ELLERBE'S LAB
AT THAT TIME SHE WAS AT
STANFORD, THE INTERLEAVED O.C.T.
SYSTEM WHERE THEY USE -- ARRAY
TO PROJECT THE LIGHT FROM ONE
BEAM TO MULTIPLE BEAM LOCATIONS
AND ALSO THE GROUP AT MGH ALSO
TOOK THE APPROACH OF USING
MULTIPLE FIBERS, FIBER ARRAYS TO
PROJECT THE BEAM ON THE SAMPLE
TO ACHIEVE THE PARALLEL IMAGING
SYSTEM.
SO THIS IS LIKE A PARALLEL
IMAGING SYSTEM IN ORDER TO
FURTHER SCALE THIS, AND THESE
APPROACHS ARE NOT VERY EASY TO
FURTHER SCALE THE TECHNOLOGY TO
EVEN MORE CHANNELS TO MAKE IT
SIMPLER, AND SO WE ARE WORKING
TOWARDS DEVELOPING THE NEXT
SCANNING GENERATION FOR DEVICES.
DR. FUJIMOTO'S GROUP DID A
WONDERFUL STUDY A COUPLE YEARS
AGO COMBINING USING INTEGRATIVE
PHOTONIC CHIP TO -- LIKE PS
O.C.T. RECEIVERS AND THAT CAN BE
USED FOR -- SENSITIVE O.C.T.
MEASUREMENT, AND PROFESSOR
DREXLER'S GROUP OVER IN VIENNA
ARE WORKING ON INTEGRATING LIKE
SPECTROMETERS ON THE CHIP AND SO
THAT YOU CAN GET LIKE A LOW COST
SPECTROMETER, SPECTRAL DOMAIN
O.C.T.-BASED SYSTEM.
LIKE DR. DREXLER AS WELL AS --
DEMONSTRATING ANOTHER FOUR
CHANNEL O.C.T. SYSTEM BASED ON
THE PHOTONIC CHIP AND THEN LIKE
PART OF THE SYSTEM WERE
INTEGRATED ON THIS CHIP DEVICE.
SO IT'S A VERY EXCITING FIELD,
AND WE'RE VERY FORTUNATE OF
RECEIVING LIKE THIS GRANT
THROUGH THE OPEN PA MECHANISM SO
OUR GOAL IS IN THE NEXT FEW
YEARS, WE WANT TO FURTHER
DEVELOP THE PHOTONIC CHIP BASED
SYSTEM INTEGRATING MANY
COMPONENTS OF SWEPT SOURCE
O.C.T. SYSTEM INSIDE THE CHIP.
SO OUR FIRST APPROACH IS TO
INCLUDE -- INTEGRATE ALL THE
PASSIVE COMPONENTS ON TO THE
CHIP, AND POTENTIALLY HAVE EIGHT
CHANNELS, 16 CHANNELS, 32
CHANNELS SCALE THE IMAGING
SPEED, AND LATER ON, WE WANT TO
BE ABLE TO INCLUDE THE ACTIVE
COMPONENTS, INCLUDING PHOTO
DETECTORS, AND INCLUDING LIKE
PHASE MODULATORS, INCLUDING
THE SWEPT SOURCE LASER IF
GETTING TO THAT POINT, MAKE THE
WHOLE SYSTEM COMPLETELY
INTEGRATABLE.
AND OF COURSE WE WANT TO ALSO
INCLUDING OTHER DETECTED
CUSTOMIZED ELECTRONIC CIRCUIT
THAT CAN HELP TO IN REALTIME
PROCESS THE DATA, PRECONDITION
THE DATA SO THAT WE WERE ABLE TO
INCLUDE EVERYTHING IN THIS THESE
PORTABLE DEVICES.
SO THE CHALLENGES NOW, MOST OF
THE WORK WILL FOCUS ON O BAND OR
LIKE A C BAND OR IN THE TELECOM
WAVELENGTH RANGE, AND FOR THE
WAVELENGTHS WE WANT TO USE FOR
OPHTHALMOLOGY, 1060 OR
800-NANOMETER, THERE'S ALMOST
NOTHING OUT THERE.
SO WHAT WE'RE DOING RIGHT NOW IS
BASICALLY WE WANT TO DEVELOP
ENABLING TECHNOLOGIES AND WE
DEVELOPED THE PROCEDURE LIKE
VALIDATED THE STRUCTURE SO THAT
MORE AND MORE PEOPLE WILL BE
ABLE TO BENEFIT FROM THIS
POTENTIAL PHOTONIC INTEGRATION.
AND JUST TO BRIEFLY DESCRIBE ONE
THING IS THAT WE HAVE TO USE A
DIFFERENT MATERIAL PLATFORM.
SO SILICON INSULATOR IS NO
LONGER LIKE FEASIBLE BECAUSE AT
THE SHORTER WAVELENGTHS, THE
LOSS IS VERY HIGH.
AND SO WE'LL FOCUS ON DEVELOPING
SILICON NITRIDE BASED DEVICES
THAT HAVE VERY LOW LOSS AND
VERY -- LIKE KIND OF A TIGHT
BENDING RADIUS, AND THE
PERFORMANCE IS PRETTY GOOD, CAN
BE VERY GOOD.
AND THEN THERE ARE LIKE
INDIVIDUAL PIECES, FOR EXAMPLE,
THE 2 BY 2, 1 BY 2 INFRAFUROM
ESHES TERS, AND THE CROSSINGS OF
LIKE A CIRCUIT THAT HAS TO BE
DEVELOPED AND OPTIMIZED.
JUST ONE CHALLENGE I MENTION
LIKE I'LL USE AN EXAMPLE FOR
THESE WAVE GUIDE, IT'S ONLY
ABOUT A 200-NANOMETERS THICK AND
ONLY ABOUT LESS THAN ONE MICRON
IN THE WIDTH.
BUT COMPARED TO THE OPTICAL
FIBER WE'RE USING THE
MULTI-FIELD DIAMETER CAN BE 7 OR
8-MICRON.
SO THE LOSS COULD POTENTIALLY BE
VERY, VERY HIGH.
BUT CURRENTLY WE'RE EXPLORING
WAYS TO MINIMIZE OUR LOSS TO
LESS THAN LIKE 2DB PER FACET,
OKAY?
SO WITH THAT, I WANT TO THANK
PROFESSOR FUJIMOTO FOR THE
TRAINING HE PROVIDED ME, AND
ALSO FOR THE WONDERFUL LIKE
COMMUNITY WE'RE BUILDING, LIKE
AROUND THE O.C.T. TECHNOLOGY.
I WANT TO THANK DR. BRUCKER FOR
THE COLLABORATION THAT REALLY
ALLOWED US TO BUILD THE FIRST
PROTOTYPE AND TEST IT IN HUMAN
SUBJECTS, AND AS WELL AS MY
FORMER STUDENTS WHO ARE ACTIVELY
WORKING ON INTEGRATING THE
DEVICES ON THE CHIP AND FUNDING
FROM NIH, NEI AND NIBIB, NSF,
AND RPB, AS WELL AS OUR RECENT
FUNDING FROM -- WORKING WITH
FANTASTIC TEAM OF RESEARCHERS
WITH BOTH EXPERTISE IN BOTH
ELECTRONIC ENGINEERING, ELECTRIC
ENGINEERING PHOTONIC DEVICES AS
WELL AS THE CLINICAL ASPECT WITH
LIKE -- AND I THANK YOU VERY
MUCH FOR YOUR ATTENTION.
[APPLAUSE]
>> THANK YOU FOR JUST A
FASCINATING SESSION.
IF I COULD HAVE THE SPEAKERS
COME JOIN UP FRONT AND WE WILL
OPEN THIS UP FOR DISCUSSION IF
THERE'S QUESTIONS.
GO AHEAD.
>> TH A MORE TECHNICAL QUESTION.
WHEN YOU HAVE SINGLE MODE
COUPLING ALLOWED, HOW YOU CAN
MANAGE THE SPACE IF IT'S 1 TO 8?
AND THEN DO YOU FIBERIZE IT OR
YOU HAVE AN ENL COUPLING FOR THE
PERFORMANCE AFTERWARDS?
>> SO YOU WERE SAYING LIKE FOR
SINGLE MODE, COUPLING IN AND
OUT, HOW DO YOU GET AFTER
SPLITTING.
SO THAT PART, WHEN WE HAVE
8 CHAJS, WE8 CHANNELS, WE HAVE E
SO IT WILL BE RELAYED BY THE
LENS AND PROJECTED ON THE
SAMPLE.
SO IF WE WERE USING THAT ON THE
DETECTION SIDE, WE CAN USE A
FIBER ARRAY TO COUPLE INTO
THE --
>> SO FROM THE FIBER ARRAY, YOU
USE A SINGLE -- FOR -- COUPLING?
>> FROM THE CHIP TO THE -- YEAH,
THAT'S A FREE SPACE COUPLING.
>> I SEE.
AND FOR THE DISPERSION
COMPENSATION OF THE DELAY
LIERNTION YOU JUST CONSIDER THEY
ARE COMPENSATED BY THE SAME
DELAY LINE FOR THE --
[INAUDIBLE]
>> SO CURRENTLY THE SIMPLEST IS
TO USE THE SAME -- DISPERSION
COMPENSATION, YEAH.
BUT LATER WE COULD EXPLORE
ACTIVE COMPENSATION TO MODULATE
THE SIGNAL FOR DIFFERENT
CHANNELS.
>> DON, GO AHEAD.
>> A QUICK FOLLOW-UP QUESTION.
WHEN YOU GO TO A 1 TO 8 COUPLER,
WHAT IS THE EFFICIENCY LIKE?
I THINK YOU MENTIONED IT BUT I
DIDN'T PICK IT UP.
WHAT IS THE EFFICIENCY LOSS IN
DB?
>> SO IF IT'S A 1 TO 8, I THINK
IN THE FORWARD DIRECTION IT'S
JUST EVENLY SPLIT, BUT ON THE
WAY BACK, AND 1 BY 8 YOU HAVE A
9DB LIKE INSERTION LOSS, BUT WE
ARE TRYING TO -- WE HAVE A WAY
IN THE PHOTONIC SYSTEM, NEXT
GENERATION DEVICES, ROUTED THE
SIGNAL TO AVOID -- TO ONLY HAVE
3D LOSS AND AVOID ALL THE OTHER
LOSSES.
>> AUSTIN.
>> YEAH, QUESTION FOR THE ORG
FOLKS.
SO I THINK, RAM, I THINK YOU
SHOWED THAT THE MAGNITUDE OF THE
ORG LENGTH CHANGE WAS
PROPORTIONAL TO THE LENGTH OF
THE OUTER SEGMENT.
BUT ALSO, IN DISEASES LIKE RP,
THE OUTER SEGMENTS ARE A LITTLE
SHORTER.
SO ARE YOUR RP CHANGES JUST DUE
TO DIFFERENCES IN LENGTH OF THE
OUTER SEGMENT OF THESE DISEASES?
AND IF SO, THEN WHY NOT JUST DO
A STRUCTURAL MEASUREMENT AND NOT
A FUNCTIONAL MEASUREMENT?
SOUNDS LIKE A VERY NEGATIVE
QUESTION, BUT HOPEFULLY YOU HAVE
A POSITIVE ANSWER.
>> SO I THINK THE SIMPLE ANSWER
IS THAT THE ORG AMPLITUDE DOES
NOT SCALE WITH OUTER SEGMENT
LENGTH, AND THAT THERE ARE
FACTORS BESIDES THE OUTER
SEGMENT LENGTH SUCH AS WAVE
GUIDE COUPLING AND WAVE GUIDE
EFFICIENCY AND BLEACHING THAT IS
VARIED IN RP THAT DOESN'T FULLY
EXPLAIN THE CHANGES THAT WE
CAPTURE, SO NO, IT WON'T BE
SUFFICIENT TO ONLY MEASURE THE
OUTER SEGMENT BANDS.
>> I THINK ALSO --
>> JUST AS A FOLLOW-UP, OUR
MEASUREMENTS ON RP, THEY ARE
PROPORTIONAL TO OUTER SEGMENT
LENGTH.
SO AS YOU SHORTEN IT, THE ORG
SIGNAL CLEARLY GETS LESS.
WHEN YOU GET MULTIPLE
REFLECTIONS IN AN INDIVIDUAL
CONE, AIM NOT UP THERE --
>> SO TO CLARIFY THAT, IN EARLY
STAGE RP, YES, BUT I THINK AS
THINGS GET MORE AND MORE --
>> ACTIVELY UNDERGOING ATROPHY,
SO THAT'S NOT EARLY.
SORRY.
>> MAYBE I COULD ASK RAVI AND
RAM, HAVING SEEN EACH OTHER'S
PRESENTATIONS NOW, WHAT DO WE
THINK ABOUT THE RODS?
WITH THOSE ORG MEASUREMENTS?
ARE YOU -- MAYBE MORE DIRECT
QUESTION, ARE YOU BOTH OPERATING
IN A DARK ADAPTED STATE?
LIKE FULLY DARK ADAPTED AND YOUR
BLEACHES ARE IN ROD BLEACHING
NOT CONE BLEACHING?
>> SO OURS ARE 30 MINUTES OF
DARK ADAPTATION, WE'RE DOING
CONE AND ROD MEASUREMENTS AT THE
SAME TIME.
THE -- SO IT'S A SINGLE -- IT'S
ONE -- WE ONLY HAVE ONE STIMULUS
SOURCE AROUND 550 NANOMETERS AND
THE L & M CONES ARE -- SHOULD BE
MORE SENSITIVE THAN THE RODS
THERE.
I THINK I -- I THINK THAT'S
RIGHT.
SO WE HAVE THE EFFECTIVE -- WE
REPORTED THE EFFECTIVE BLEACHING
THAT SHOWED THAT EVEN IF THE
RODS HAVE LOWER PHOTO PIGMENT
ISOMERIZATIONS, THEY ELONGATE
MORE.
NOW THERE ARE SOME ODDITIES WITH
THIS WHICH IS THAT IN THE CONES,
YOU HAVE LIKE CLEAR REFERENCE OF
THE ISO -- KODZ, IN THE RODS, WE
HAVE A CLEAR REFERENCE POINT,
IT'S BOTH AXIALLY AND LATERALLY
SEGREGATED FROM THE CONES BUT
WHEN YOU GET TO THE ISOS LAYER,
THERE'S NO -- WE HAVEN'T SEEN
LIKE A CLEAR ISOS -- MOSAIC AND
WE HAVE SOME SORT OF
CIRCUMSTANTIAL EVIDENCE THAT
THAT ISOS OF RODS MIGHT BE
AXIALLY DISPLACED COMPARED TO
ITS CONE COUNTERPARTS.
THERE ARE SOME QUESTIONS FOR
SURE, BUT WE -- YOU KNOW, WE'VE
MEASURED IT IN SEVERAL SUBJECTS
AND I MEAN, UNLESS THERE'S A --
I DON'T THINK IT'S AN ARTIFACT.
I SHOULD ALSO SAY THAT RAM'S
RESPONSE LOOKS A BIT MORE LIKE
WHAT WAS REPORTED BY -- IT'S AN
SPIE PROCEEDINGS, SHOWING -- NO,
OR IS IT A -- DO YOU KNOW?
NEAR-INFRARED WAY, HER LAST NAME
IS PFAFFLE, AND SHE HAS A ROD
RESPONSE THAT LOOKS KIND OF LIKE
WHAT YOU SHOWED, SORT OF SLOW
AND VERY ATTENUATED.
SO QUITE DIFFERENT FROM WHAT WE
SEE.
>> YEAH, SO I THINK IN OUR
HANDS, RODS ARE MORE SENSITIVE
BUT SLOWER, AND I THINK THE
SLOWER -- THE SLOWNESS IS
BECAUSE OF THE FACT THAT THEIR
MEMBRANES ARE NOT FULLY EXPOSED
TO THE CYTOSOL IN THE SENSE THAT
THEY'RE PINCHED TO THE WAY --
UNLIKE THE CONE DISKS ARE, WHICH
ARE COMPLETELY EXPOSED, SO THEY
HAVE LESS EFFECTIVE PERM YANT SO
WE'D EXPECT THEM TO SATURATE A
LOT SLOWER COMPARED TO CONES.
THE ROD AND CONE ORG TRACES THAT
I SHOWED I THINK IN THE CORE
SCALE SITUATION ARE NOT TAKEN
SIMULTANEOUSLY, THOSE ARE
EXAMPLES IN THE SENSE THAT THE
ROD BLEACHES ARE ABOUT FIVE
TIMES SMALLER THAN THE CONE
BLEACHES.
BUT IN THE SINGLE CONE SCENARIO
WHERE THERE WAS A 669 -- BLEACH
IS SUFFICIENT TO SEPARATE OUT
LMS CONES AS WELL AS RODS AT 66L
AMOUNT OF BLEACH FOR THE RODS,
WE CAN CALCULATE WHAT THAT IS
BUT IT --
>> THE WHOLE QUESTION MIGHT BE A
MISUNDERSTANDING.
I THOUGHT THAT --
>> I THINK I MISSPOKE.
>> OKAY, NEVER MIND.
>> MAYBE WE CAN COME DOWN HERE.
>> THANK YOU.
THESE ARE GREAT TALKS, AND I
JUST WANTED TO -- SEVERAL OF
YOU, I REALLY LEARNED A LOT
ABOUT WHAT YOU DO THROUGH THE
NEI'S AUDACIOUS GOALS
INITIATIVE, AND I THINK IT'S
BEAUTIFUL WORK, AND I JUST -- IT
SPAWNED A FAIR AMOUNT OF
DISCUSSION HERE IN BETHESDA
ABOUT, YOU KNOW, HOW COULD THE
AVERAGE OPHTHALMOLOGIST ADOPT
THESE AND, YOU KNOW, WHAT WOULD
MAKE THEM WANT TO ADOPT THESE IN
CLINICAL PRACTICE.
SO I WANTED TO USE THAT TO
REALLY INTRODUCE A QUESTION NOT
ONLY TO THE PANEL BUT ALSO TO
JIM AND TO DAVID, BECAUSE IF I
THINK BACK, O.C.T. REALLY FROM
WHEN YOU PUBLISHED THESE PAPERS
TO WHEN IT BECAME USED
MAINSTREAM WAS LET'S SAY MAYBE
20 YEARS PLUS OR MINUS, AND I'D
LOVE TO HEAR WHAT LESSONS YOU
FEEL LIKE WE HAVE LEARNED ABOUT
HOW TO TRANSLATE TECHNOLOGIES
INTO REAL WORLD CLINICAL USE OF
THIS SORT, AND ARE THERE THINGS
THAT YOU'VE LEARNED THAT WE CAN
TAKE ADVANTAGE OF AS A COMMUNITY
ABOUT HOW TO INCREASE THE CYCLE
TIME OF DOING THAT, OR HOW TO
RECOGNIZE WHEN SOMETHING IS
TRANSLATABLE AND IS THERE
ANYTHING WE SHOULD BE DOING AT
NIH TO HELP SUPPORT THAT?
>> WHO WANTS TO TACKLE THAT?
I MEAN, WILL WE BE --
>> PART OF THE QUESTION IS
DIRECTED TO OPTORETINOGRAPHY SO
I CAN'T RESPOND IN THAT CONTEXT.
I THINK THE -- THE COMPLICATED
PROCESS, AND IN O.C.T., WE SAW
THAT JUST HAVING A DIAGNOSTIC
WAS NOT ENOUGH LINKING SOMETHING
TO THERAPY, WHICH WAS REALLY THE
CLINICAL ADVANCE BY THE CLINICAL
COMMUNITY, THAT WAS A CRITICAL
STEP.
I THINK THE BUSINESS MODEL FOR
INSTRUMENTATION IS VERY HARD.
THE MARKET IS VERY SMALL, YOU
KNOW, COMPARED TO OTHER MARKETS,
THE REGULATORY PATH IS LONG.
AND SO THE PATH IF YOU SAY TO GO
TO FUNDAMENTAL RESEARCH IF
YOU'RE SELLING TO THE
CLINICAL -- I'M SORRY -- THE
BASIC RESEARCH COMMUNITY THAT'S
MUCH EASIER BUT THAT'S ALSO
SMALL RELATIVE TO SOFTWARE IN
GENERAL.
SO I THINK IT'S A VERY
CHALLENGING ISSUE AND IT'S NOT
CLEAR WHAT THE ANSWER IS.
MAYBE DAVID HAS A DIFFERENT
OPINION ON THIS THOUGH.
>> I'M GOING TO TALK ABOUT THAT
A LITTLE BIT TOMORROW MORNING,
BUT BASICALLY I THINK IN ORDER
FOR A TECHNOLOGY TO BE WIDELY
USED BY CLINICIANS, WE NEED
PEOPLE IN THE INDUSTRY, IN THE
BUSINESS COMMUNITY TO RECOGNIZE
THE CLINICAL POTENTIAL, AND THAT
TAKES VISION, AND SO THAT IS
PROBABLY ONE OF THE IMPEDIMENTS,
IS TO HAVE PEOPLE IN THE
INDUSTRY WHO HAS THE VISION AND
WE NEED -- WE OFTEN WANT OUR
STUDENTS TO COME BACK TO THE
ACADEMIA, YOU KNOW, YOU WANT TO
KNOW HOW MANY OF YOUR STUDENTS
AND POSTDOCS BECOME PROFESSORS,
BUT ACTUALLY I THINK IT MAY MAKE
BIGGER IMPACT IF YOU STUDENTS GO
OUT IN THE INDUSTRY AND BECOME
LEADERS IN THE INDUSTRY THAT
CREATES PRODUCTS.
AND I THINK NIH HAS FACILITATED
THESE WITH SBIR/STTR GRANTS, BUT
PROBABLY WHAT MAKES BIGGER
IMPACT IS REIMBURSEMENT FOR
THESE, AND OF COURSE LINKING TO
THERAPEUTICS IS VERY IMPORTANT
FOR THAT.
AND ALSO REIMBURSEMENT FOR THE
DIAGNOSTIC PROCEDURES, AND THOSE
HAVE BEEN -- THE FACT THAT THEY
ARE AVAILABLE HAS BEEN VERY
HELPFUL, THE LENGTHY DELAYS WERE
NOT HELPFUL, SO THERE WERE A LOT
OF PLUSES AND MINUSES AND IT'S
COMPLICATED, BUT I THINK THAT'S
PROBABLY ONE OF THE BIGGEST
FACTORS.
SO THAT'S WHAT I'VE LEARNED, AND
I THINK CLINICIANS ON THE GROUND
ACTUALLY PROBABLY HAVE THE MOST
ACCURATE PICTURE, PEOPLE IN
ACADEMICS SOMETIMES ARE ACTUALLY
RESISTANT TO CHANGE IN WHAT THEY
ARE TEACHING AND CAN ACTUALLY
HOLD THINGS BACK, BUT ONCE
SOMETHING HAS DEMONSTRATED
CLINICAL POTENTIAL, THE
CLINICIANS WILL TALK ABOUT IT
AND IT TAKES OFF REALLY QUICKLY,
IT JUST GOES VIRAL.
SO I HOPE ORG WILL GO VIRAL
THROUGH SOME SORT OF PHARMA
TRAIL WHERE YOU HAD A KILLER APP
JUST LIKE ORIGINAL O.C.T. WITH
VEGF SO I HOPE THAT'S POSSIBLE
AND I HOPE THAT WILL HAPPEN.
>> THE FIRST TIME I SHOWED THE
RESULTS TO LARRY MORSE, WHO MANY
OF YOU KNOW, HE WAS LIKE WOW,
THAT'S AMAIDSING, I CAN'T
BELIEVE WHAT YOU'RE SEEING, AND
I SAID LARRY, WOULD YOU USE THIS
IN YOUR CLINIC?
HE SAID NO, NO WAY!
WHAT WOULD I USE THIS FOR IN MY
CLINIC?
THEN ONE OTHER THING, ANOTHER
LITTLE ANECDOTE, I WAS TALKING
TO -- YOU KNOW, WHEN WE FIRST
STARTED PRESENTING THE PROTO
CLINICAL ORG, THERE WAS SOME
COMMERCIAL INTEREST AND PEOPLE
WERE TALKING TO ME AND ROBERT
ABOUT IT AND ONE PERSON WHO'S
KIND OF MORE ON THE VC SIDE WAS
ASKING A LOT OF QUESTIONS AND
LIKE HOW LONG DOES THE TEST TAKE
AND I SAID WELL I THINK WE CAN
DO IT IN FIVE MINUTES, HE'S LIKE
FORGET IT, THAT'S WAY TOO LONG.
>> I AGREE -- UNLESS YOU GET THE
INDUSTRY IN, IT'S GOING TO
REMAIN IN THE LAB ON A BENCH AND
WE'RE GOING TO TALK ABOUT IT
BETWEEN US, BUT JOHN MOREVICH,
WHEN HE GOT STARTED HE GOT FIRED
BECAUSE HE WASN'T GENERATING
ENOUGH -- WHEN I STARTED WITH
O.C.T. PEOPLE THOUGHT I NEED TO
EXAMINE MY BRAIN, NOBODY COULD
FIRE ME BECAUSE IT WAS MY MONEY
BUT I WAS ON THE VERGE OF
BANKRUPTCY BECAUSE IT WAS TOO
EARLY AND CLINICIANS DID NOT
KNOW WHAT TO DO WITH IT, AND
THEN SUDDENLY THEY DISCOVERED
THAT THEY CAN USE IT.
SO IT'S THE SAME PROBLEM.
WE NEED TO ENCOURAGE THE
INDUSTRY TO PUT THEIR HAND IN
THEIR POCKET AND TAKE THE RISK
AND PROGRESS FORWARD, OTHERWISE
IT WILL REMAIN IN THE LAB.
GREAT INNOVATIONS FOR MANY OF
THE LAB FOR MANY, MANY, MANY
YEARS.
BECAUSE PEOPLE ARE AFRAID TO
TAKE THE RISK.
>> ALL RIGHT.
WELL, WE'VE HAD JUST A FANTASTIC
DAY TODAY.
I MYSELF IS LEARNED SO MUCH, I
DEFINITELY WANT AN ADAPTIVE
OPTIC O.C.T. WITH
SUPERRESOLUTION IN VISIBLE
WAVELENGTHS WITH EIGHT CHANNELS.
SO IF ANYBODY WANTS TO DEVELOP
THAT WITH ME, LET'S CHAT.
I GUESS AT DINNER.
THANK YOU ALL FOR THIS FABULOUS
LAST SESSION.
THANKS TO OUR SPEAKERS AGAIN.
[APPLAUSE]
>> WELL, THANK YOU, EVERYONE,
FOR A STIMULATING DAY OF
PRESENTATIONS AND QUESTIONS AND 10130 07:16:11,645 DISCUSSION.