Nutrition

We are what we eat: nutrition, genes, cognition & deep learning in age-related macular degeneration

>> GOOD AFTERNOON TO ALL OF YOU. WELCOME DO A VERY SPECIAL WEDNESDAY AFTERNOON LECTURE, THE ASTUTE CLINICIAN LECTURE. WE'RE FORTUNATE TO HEAR FROM OUR OWN EMILY CHEW, DEPUTY CLINICAL DIRECTOR OF THE NATIONAL EYE INSTITUTE. IT FEELS A LITTLE WEIRD TO HAVE THIS LECTURE IN LIPSETT BECAUSE FOR ALL THE TEN YEARS THAT I HAVE BEEN NIH DIRECTOR THESE HAVE GENERALLY BEEN HAPPENING IN MASUR BUT MASUR IS UNDER CONSTRUCTION AT THE MOMENT SO UNTIL MARCH WE WILL BE MEETING HERE INSTEAD. IT Induces IT COZY. WELCOME TO ALL THE PEOPLE LISTENING BY VIDEO, BECAUSE IN GENERAL THERE'S A LOT MORE OF YOU THAT I CAN'T SEE THAN I CAN SEE. I'M GLAD YOU ARE OUT THERE AS WELL, I Guess WE ARE Running TO HAVE A VERY INTERESTING SET OF IDEAS AND PRESENTATIONS PUT FORWARD BY DR. CHEW THIS AFTERNOON. TO RUN QUICKLY THROUGH HER ACADEMIC CREDENTIALS. THEY ARE SUBSTANTIAL. SHE'S ONE OF THOSE PEOPLE WHO ENROLL IN A PROGRAM WHICH TOOK YOU IN SIX YEARS FROM HIGH SCHOOL GRADUATION TO M.D..SHE DID THAT AT THE UNIVERSITY OF BRITISH COLUMBIA. FOR A Year THEN TO THE UNIVERSITY OF TORONTO. BUT SO IN THOSE SIX YEAR PERIOD A LOT MUST HAVE GOTTEN PACKED INTO THAT TIME. FINISHING HER M.D. SHE THEN DID AN INTERNSHIP IN INTERNAL MEDICINE AND THEN RESIDENCY IN OPHTHALMOLOGY. AGAIN AT THE UNIVERSITY OF TORONTO. AND THEN SOME FELLOWSHIPS IN MEDICAL RETINAL SCIENCE AND GENETICS AT HOPKINS AND NETHERLANDS. RETURNING TO RON TOE DEPARTMENT OF OPHTHALMOLOGY AS ASSISTANT PROFESSOR SHE WORKED THERE FOR THREE YEARS AND THEN BACK IN 1987 WE WERE FORTUNATE TO LURE HER HERE TO NIH INITIALLY AS VISITING SCIENTIST, IN NEI THEN OVER THE COURSE OF YEARS, ROCKETING UP THROUGH VARIOUS POSITIONS OF INCREASING RESPONSIBILITY TO HER CURRENT ROLE AS DEPUTY CLINICAL DIRECTOR.CHIEF OF THE CLINICAL TRIALS BRANCH AND DIRECTOR OF THE DIVISION OF EPIDEMIOLOGY AND CLINICAL APPLICATIONS. HER WORK HAS BEEN RECOGNIZED BY A NUMBER OF IMPORTANT AWARDS, I'LL MENTION PARTICULARLY THAT SHE RECEIVED AWARDS FROM THE NIH DIRECTOR FOR MENTORING, SOMETHING SHE PAID ATTENTION TO, MADE A REAL PRIORITY. SHE'S ALSO WON THE HELEN CELLAR PRIZE IN VISION RESEARCH IN 2014. SHE WON A LIFETIME ACHIEVEMENT AWARD AND JACKSON MEMORIAL LECTURE FROM THE AMERICAN ACADEMY OF OPHTHALMOLOGY. SHE WAS Likewise PRESIDENT OF THE ASSOCIATION FOR RESEARCH ON VISION AND OPHTHALMOLOGY AND RECEIVED THEIR DISTINGUISHED SERVICE AWARD. SO YOU CAN TELL BY ALL OF THAT THIS THIS IS A TRUE LEADER IN THE FIELD OF OPHTHALMOLOGY RESEARCH.HER CURRENT RESEARCH INCLUDES PARTICULARLY FOCUSED ON CLINICAL TRIALS IN EPIDEMIOLOGICAL STUDIES IN RETINOVASCULAR DISEASE, PARTICULARLY AGE RELATED MACULAR DEGENERATION BUT ALSO DIABETIC RETINOPATHY AND OTHER DISEASES INCLUDING RARE DISEASES, SHE IS INTERESTED AND INVOLVED IN PA LOT OF INTERESTING AREAS IN OPHTHALMOLOGY. SHE WAS A COSECOND AUTHOR IN ONE OF THE PAPERS THAT WAS MOST SEMINOLE IN THE EARLY DAYS OF GENOME WIDE ASSOCIATION STUDIES. THAT IS THE IDENTIFICATION OF A VARIANT IN COMPLIMENT FACTOR H ASSOCIATED WITH AGE RELATED MACULAR DEGENERATION. THAT PAPER IN SCIENCE LECTTRY MID PEOPLE WHO WERE HOPING THIS METHOD WOULD WORK, THAT WAS THE FIRST TRUE SUCCESS. ELECTRIFIED. SHE Depletes A Plunder OF HER TIME AS A LOT OF HER TIME AS CHAIR OF VARIOUS LARGE SCALE EPIDEMIOLOGICAL STUDIES AND I THINK THAT'S A LOT OF WHAT WE'LL TALK TO US ABOUT HERE TODAY. THE AGE RELATED EYE DISEASE STUDY BEING A FAMOUS EXAMPLE AND NOW THE FOLLOWUP ON THAT ARADS 2 AND ALSO CHAIRING THE ACCORD EYE STUDY, ABOUT CARDIOVASCULAR RISK IN DIABETES. SO I GUESS THIS SOMEBODY WHO DOESN'T SLEEP, LEAST JUDGING BY NUMBER OF THINGS SHE'S CURRENTLY JUGGLING AND HAS DONE SO FOR SOME TIME, WE ARE VERY PROUD TO HAVE HER AS PARTS OF OUR INTRAMURAL PROGRAM.PLEASE JOIN ME IN WELCOMING THE ASTUDENT CLINICIAN LECTURER PRESENTER DR. EMILY CHEW.[ APPLAUSE] >> THANK YOU, DR. COLLINS FOR THAT GRACIOUS INTRODUCTION. I'M VERY HONORED AND PRIVILEGED TO BE THE 2019 ASTUTE CLINICIAN LECTURE, THIS IS TRULY AMAZING BECAUSE I JOINED A GROUP OF INCREDIBLE INTRAMURAL EXTRAMURAL COLLEAGUES AND FRIENDS WHO HAVE DONE AMAZING WORK IN THIS AREA. SO I'M VERY HONORED TO BE PART OF THIS STELLAR GROUP. I HAVE NO FINANCIAL DISCLOSURES. THE NEI HOLDS A ROYALTY BEARING LICENSE TO ISSUE TO BOTH AND LOAM FOR THE AHRA SUPPLEMENT I'LL TALK ABOUT.AS A YOUNG CHILD IN AN IMMIGRANT CHINESE FAMILY IN VANCOUVER ISLAND IN CANADA, MY MOTHER WOULD COOK WITH THESE GOLGI BERRIES AND SAY THIS IS GOOD FOR YOUR EYES. THIS IS FILLED WITH LUTEIN. AND TOUGH EXAM MY FA HER WOULD SAY YOU NEED BRAIN FOOD LET'S HAVE FISH AND HE WOULD COOK FISH LIKE THIS. SO LITTLE WOULD THEY KNOW THAT DECADE LATER THAT THEIR GIRL WOULD BE TALKING NUTRITION AND OCULAR HEALTH. WE ARE WHAT WE EAT. THIS IS FROM MY KITCHEN ACTUALLY. SO I'M GOING TO TALK ABOUT THE LEADING CAUSE OF BLINDNESS WHICH IS AGE RELATED MACULAR DEGENERATION, IT IS LEADING CAUSE IN THE UNITED Moods, TOO MANY PEOPLE HAVE THE DISEASE, AND 8 MILLION PEOPLE AT RISK.IT Grades THIRD IN GLOBAL CAUSES OF VISUAL IMPAIRMENT YOU CAN SEE BY 2040, 28 ING MILLION PEOPLE WILL BE AFFECTED BY THIS CONDITION. THE RISK FACTORS ARE AGING, SMOKING, EDUCATION, I WILL NO CUSS ON NUTRITION AND GENETICS. I WILL TALK ABOUT AGE DISEASE STUDY DR. COLLINS TALKED ABOUT, BOTH CLINICAL TRIAL AS WELL AS OBSERVATIONAL DATA. I WILL DO COGNITIVE FUNCTION TESTING WE DID WITH PATIENTS WITH MACULAR DEGENERATION AND ROLE OF GENETICS. YOU HEARD THE PREVIEW OF GWAS WE DID, ON A WHIM SO LUCKY. Also END UP IN DEEP LEARNING WHICH IS AN INCREDIBLE TOOL WE HAVE, NIH IS VERY MUCH MOVING FORWARD ON THIS, I WILL Sacrifice YOU TASTE OF THIS AS WE TWO ON.MACULAR Degeneration IS MOSTLY BASED COPYING MEN TEAR CHANGES PIG BASED ON PIG MEN TEAR CHANGES. THIS YELLOW SPOT HERE AND IN THIS LARGE AREA, SO EARLY AMD IS A MATTER OF HAVING RECALL MEETING SIZE INTERMEDIATE AMD THOSE WITH LARGE DRUZIN. “If youre having” A LATE DISEASE WHICH IS A VISION THREATENING PART, NEOVASCULAR AMD ARE ATROPHY WHICH THERE'S NO EFFECTIVE THERAPY. YOU CAN Also HAVE GEOGRAPHIC ATROPHY ELSEWHERE NOT IN THE CENTER. THIS IS A Patient OF MINE THAT FOLLOWED FOR 20 Years AT NEI.I WANT TO SHOW YOU THE PROGRESSION OF MACULAR DEGENERATION. IT STARTS WITH DRUZIN, GROW, THEY GET LARGING PIG MEANT CHANGES WHEN THEY DISAPPEAR THEY CAUSE HAVOC. YOU SEE THE ATROPHY. THE DARK PIGMENT IS CENTER OF THE EYE PRESERVED THE PATIENT STILL HAS 2020 VISION BUT CENTRAL PAIR AND PARACENTRAL PART DISAPPEARED. THE PATIENT HAS TERRIBLE DYSFUNCTION FROM THIS. IF WE SEE FROM THE PATIENT PERSPECTIVE, THEY MAY HAVE GOOD VISION IN THOSE WITH LARGE DRUZIN. I CAN GET THIS GOING, MAYBE HAVE GOOD VISION LIKE THIS, 20 FOR SOME TIME, BUT AS TIME GOES ON YOU WILL SO AN AREA OF SCETOMA WHICH IS CENTRAL AND THEY ROB OF THEIR MOP SITE, SEE IF I CAN GET THIS TO TO GO BETTER.SO YOU END UP WITH PATIENT WITH CENTRAL SCETOMA AND PERIPHERAL VISION THAT IS QUITE BLURRY. THIS IS THE SYNDROME OR VISUAL HALLUCINATIONS PATIENTS MAY HAVE. ALMOST 15% OF Cases ACTUALLY EXPERIENCE THIS WE JUST ASKED THEM IN FOLLOWUP STUDY. THIS IS AN Unique Kind WHERE Cases Construe PATTERNS BEGIN WITH THEY SEE FLOWERS THEY KNOW IT'S NOT THERE BUT THESE HALLUCINATIONS THEY Realize ARE NOT REAL BUT THEY HAVE IT BUT THEY ARE AFRAID TO TELL YOU BECAUSE THEY THINK THEY'RE GOING MAD. BY THE END THEY MAY GET FACES AND MAY SEE BUILDING. THIS IS PAINTED BY A PATIENT. THESE ARE PERCEPTIONS OF HER VISUAL HALLUCINATIONS OVER TIME. SO I WILL Make A CONTEXT WHERE AMD TREATMENT HAS GONE, GIVE YOU AN IDEA WHERE WE TALK ABOUT SUPPLEMENT YOU CAN SEE 1982 WE HAD LASER TREATMENTS WHICH WS& QUITE DIFFICULT TO USE AND PATIENTS EVENTUALLY LOST VISION. FURTHERMORE IT Applied TO BE CALLED SENILE MACULAR DEGENERATION. IMAGINE HOW PATIENTS FELT ABOUT THAT, AS OPHTHALMOLOGISTS GOT OLDER THEY DECIDED IT WAS NOT A GOOD NAME, CALL IT AGE RELATED MACULAR DEGENERATION.IN 1999 THE PHOTO TOE DYNAMIC THERAPY, A PHOTO WHICH IS A( INDISCERNIBLE) DYE YOU PUT INTO THE BODY AND YOU ACTUALLY TREAT IT WITH A LASER AND THAT WAS SOMETHING THAT WE HAD THAT HELD OFF TREATMENT FOR A LITTLE BIT BUT REALLY THE MAIN THING HAS BEEN THE WET TREATMENT WITH THE ANTIVEGF THERAPY IN 2006. IN 2001 AND 2012 WHEN WE CAME ON THE SCENE WITH OUR ARAD SUPPLEMENT SO WE WILL TALK MORE NUTRITION AT THIS POINT NOW. THE FIRST CLUE THAT NUTRITION IS IMPORTANT COMES FROM EXAMINATION OR N HAYNES SURVEY 1988, IT WAS CLEAR PEOPLE WHO ATE DIETS RICH IN FRUIT AND VEGETABLE VITAMIN A AND C MUCH LESS MACULAR DEGENERATION.IN 1992 THE NATIONAL EYE INSTITUTE STARTED AGE RELATED EYE DISEASE STUDY MOSTLY AS A CLINICAL NOT CLINICAL TRIAL BUT NATURAL HISTORY STUDY. BUT WE DECIDED WE NEEDED TO DO A CLINICAL TRIAL AND WE FOLLOW PATIENTS SIX YEARS AND THEN HAD ANOTHER FIVE YEARS OF CLINICAL TRIAL BEING STOPPED, EPI STUDY LOOKING AT FOLLOWUP OF PATIENTS, CHAIRED BY DR. RICK FERRIS AN AMAZING TEAM OF 11 INVESTIGATORS THROUGHOUT THE U.S .. WE ENROAM PATIENTS WITHOUT AMD AS WELL AS EARLY AND LATE AMD. WE TREATED THEM OR RANDOMIZE THEM TO A CONCOCTION OF ANTIOXIDANT ITEMS POPULAR AT THAT TIME FOR CANCER AND CARDIOVASCULAR DISEASE. LARGE DOSE VITAMIN C E AND BETA CAROTENE AN ZINC.WE FOUND THE COMBINATION OF VITAMINS AN ZINC RESULTED IN 25% REDUCTION OF LATE AMD IN FIVE YEARS. Z YOU SEE FACTOR RAIL DESIGN THE ZINC AND ABOUT OXIDANT SINGLY BUT TOGETHER WAS 25% REDUCTION. WE FOLLOW THEM ANOTHER FIVE YEAR WITHOUT THE CLINICAL TRIAL YET STILL SAW BENEFICIAL EFFECT EVEN TEN YEARS WE SAW A 27% REDUCTION, FIVE YEARS AFTER THE CLINICAL TRIAL HAD ACTUALLY STOPPED. WHO SHOULD TAKE THIS SUPPLEMENT? THESE PATIENTS HAVE INTERMEDIATE AMD, THOSE WITH LATE AMD IN ONE EYE, BUT NOT FOR CURRENT Smoker, BETA CAROTENE INCREASED RISK OF LUNG CANCER FOR STUDIES SO FOR THAT REASON WE WERE CONCERNED ABOUT BETA CAROTENE, INTERESTINGLY ENOUGH FOR UNAFFECTED CHILDREN OF INDIVIDUALS QUITE OFTEN THE CHILDREN COME IN AND SAY MY DAD HAS TEAR TERRIBLE DISEASE SHOULD I TAKE THIS, THE ANSWER IS NO BECAUSE IT'S ONLY EFFECTIVE IN PATIENTS WITH INTERMEDIATE AMD SO A SECONDARY PREVENTION AND NOT THOSE WHO DO NOT HAVE THE DISEASE.PUBLIC SIGNIFICANCE IS HUGE, OVER FIVE YEARS 300,000 PEOPLE ARE SAFE FROM HAVING LATE AMD. IN 2006 WE STARTED ARADS 2, WHY? BECAUSE DURING THE COURSE OF THE 1 WE FOUND PEOPLE WHO ATE LOT OF GREEN VEGETABLES, SOMETHING YOUR MOTHER TOLD YOU TO EAT, SPINACH KALE COLLARD GREENS AND PICKING FISH, THE HIGHER THE INTAKE OF THOSE, THE LOWER THE RISK OF HAVING MACULAR DEGENERATION. For those working REASONS WE ACTUALLY ADDED LUTEIN OMEGA THREE FATTY ACIDS ONE GRAM TO THE ARAD SUPPLEMENTS SO ADDING THESE TO SEE WHETHER WE HAVE ANY EFFECT ON LATE AMD. THESE Cases HAVE AMD SO THE MAJORITY OF PATIENTS HAVE LATE AMD OR INTERMEDIATE AMD. THAT'S ANOTHER 4,000 PATIENTS IN 82 Places. WE THEN ELIMINATE BETA CAROTENE AND ZINC AS WELL BECAUSE OF THE CANCER ISSUE. WHAT DID WE FIND? PRIMARY RANDOMIZATION SHOW THAT OMEGA THREE FATTY ACIDS WAS NEITHER BENEFICIAL NOR HARMFUL, THE LUTEIN HAD INCREMENTAL INCREASE IN BENEFIT REDUCE PROGRESSION OF TO LATE AMD. IT WAS Extremely SO IN PATIENTS WHO DID NOT EAT GREENS SO LOW DIETARY INTAKE PEOPLE WHO ATE ZERO GREEN THERE IS 25% REDUCTION IN LATE AMD WITH LUTEIN XANTHINE, IF YOU DO A HEAD TO HEAD COMPARISON BETWEEN LUTEIN AND BETA CAROTENE THERE'S A 20% INCREASE IN THE BENEFICIAL EFFECTS SO LUTEIN WON OUT.MOST IMPORTANT FINDING IS THE FACT THERE'S TWO FOLD INCREASE RISK OF LUNG CANCER TO THOSE BETA CAROTENE VERSUS LUTEIN AND XANTHINE. WE Superseded THE BETA CAROTENE WITH LUTEIN XANTHINE TO LOOK LIKE THIS, THIS IS THE ARA 2 FORMULATION. WE DID NOT ADD OMEGA 3 BECAUSE IT WAS NOT Beneficial. THIS IS THE FORMULATION WE RECOMMEND FOR OUR PATIENTS. TURN OUR ATTENTION TO DIET NOW. THE MEDITERRANEAN DIET EPIDEMIOLOGICAL STUDIES SHOW GREECE IN NUMBER OF YEARS AGO CARDIOVASCULAR DISEASE WAS MARKEDLY REDUCED ASSOCIATED WITH THEIR MEDITERRANEAN DIET. THIS IS TESTED IN A RANDOMIZED TRIAL. THE TRIAL WAS RANDOMIZED IN SPAIN LOOKING AT PATIENTS RANDOMIZE TO MEDITERRANEAN DIET SUPPLEMENTED WITH MIXED NUTS EXTRA VIRGIN OLIVE OIL AND CONTROLLED LOW FAT DIET. THIS STUDY SHOWED 30% REDUCTION IN CARDIOVASCULAR DISEASE. THIS IS A PREVALENT DISEASE SO THIS AMOUNT OF REDUCTION IS SIGNIFICANT. THE RESEARCH QUESTION WE HAVE, WHAT IS ASSOCIATION MEDITERRANEAN DIET WITH AMD? THERE'S PREVIOUS STUDIES LOOKING AT THIS, USING OUR ARAS DATA, DR.MURRAY AND ONE OF OUR INVESTIGATORS, LOOKED AT THE LONGITUDINAL ASPECT OF IS STUDY IRISK CONSORTIUM, THEY FOUND HIGH MEDITERRANEAN DIET ADHERENCE ASSOCIATE WITH LESS PROGRESSION TO LATE BY AS MUCH AS 25 TO 40% SO ESTABLISH TO A CERTAIN EXTENT. WHAT IS IN THE MEDITERRANEAN DIET? LOW ON RED MEAT AND REFINED SUGARS, HIGH FRUITS VEGETABLES LEGUMES, FISH AND HIGH UNSATURATED FATTY ACID SUCH OLIVE OIL. IN A RAS 1 AND 2 WE HAD THE ABILITY TO LOOK AT NUTRITION AT BASELINE. WE HAD TWO QUESTIONNAIRES SELFREPORTS IN THE PAST YEAR, IN THE BLOCK USED BY THE NCI AND HARVARD. DIETARY QUESTIONNAIRE. WE Ogle AT Participates WITH NO BASELINE LATE AMD. THOSE ARE ALMOST 8,000 Cases WHO WERE IN THE STUDY. THIS IS THE COMBINED COHORT. WHEN WE Inspect AT PROGRESSION TO LATE AMD WET OR DRY, YOU CAN Appreciate THE FOREST PLOT SHOWS TO THE LEFT, PROTECTIVE IN GREEN ZONE AND IF YOU EAT MORE HIGHER YOU ARE THE MORE PROTECTION YOU HAVE SO IT SOUNDS LIKE A DOSE RESPONSE FOR THOSE WHO LIKE NUMBERS THIS IS WHAT IT Glances LIKE.THESE ARE HAZARD RATIOS. THERE IS REDUCTION OF 29% OF GEOGRAPHIC ATROPHY. SO THE HIGHER INTAKE OF MED TERRAIN DIET ASSOCIATE TO DEGREES PROGRESSION OF LATE AMD FOR NEOVASCULAR AND GEOGRAPHIC ATROPHY. WE Glance FOR THE NINE COMPONENTS WHICH WAS IT? TURNS OUT TO BE FISH. IT'S IMPORTANT. HAVARD RARE HAZARD RATIO IS. 69, ESPECIALLY GEOGRAPHIC ATROPHY. AND EVEN IF YOU LOOK AT PATIENTS WHO DIDN'T HAVE LARGE DRUZIN THAT'S INTERMEDIATE STATE AMD, THESE ARE EARLY CASES WITH ADULT AMD YOU CAN SEE A PROTECTIVE EFFECT OF 25% REDUCTION IN RISK OKAY DEVELOPING LARGE DRUZIN. DIET IS IMPORTANT. THIS IS SUMMARY WE FOUND COHORT COMBINE VERSUS THE ARAD 1 AND 2. IN BETWEEN DIET WAS IMPORTANT FOR GEOGRAPHIC ATROPHY AND THIS WE APPLY( INDISCERNIBLE) CORRECTION TO THIS, YOU WILL BE DOING A NUMBER OF TESTS YOU HAVE TO CORRECT FOR THAT, PUTTING YOUR HANDS IN THE COOKIE JAR A HUNDRED TIMES YOU GET SLAP CERTAIN RULE ON THAT. SO THAT MAKES YOUR P VALUE HIGHER SO AND IN THIS CASE YOU SEE GEOGRAPHIC ATROPHY IS REALLY IMPORTANT.IN EARLIES THE OF MEDITERRANEAN DIET IN PARTICULAR. NEOVASCULAR NOT IN AREDS 1 AND 2 BUT STILL SAME DIRECTION OF PROTECTIVE. IF WE LOOK AT FISH AND GEOGRAPHIC ATROPHY IN PARTICULAR IS IMPORTANT AND HIGHLY SIGNIFICANT FOR AMD. SO DECREASE IN PROGRESSION LATE AMD AND THOSE WITH INTERMEDIATE AMD WAS SEEN IN MEDITERRANEAN DIET ASSOCIATION FROM EARLY AMD TO LARGE DRUSIN ASSOCIATION WAS SEEN SO IMPORTANT IN EARLY AND LATE AMD SO MAYBE NEVER TOO LATE TO START MEDITERRANEAN DIET, ASSOCIATION OF COURSE IS NOT RESULT OF CLINICAL TRIAL BUT THESE ARE ONLY COMPELLING DATA. LET'S TURN TO COGNITIVE FUNCTION. WE DID TESTING IN AREDS 2 BECAUSE WE WERE INTERESTED IN OMEGA 3, IT WAS RANDOMIZE DRUG WE WERE REALLY INTEREST IN SEEING IF IT HAD EFFECT ON COGNITIVE FUNCTION.WE KNOW THIS IS A HUGE EPIDEMIC, 46 MILLION Beings WIDE AFFECTED RIGHT NOW, 5.2 IN THE U.S ., TRIPNAL THE NEXT FOUR DECADES 135.1 MILLION BY 2050. OUR HYPOTHESIS LONG CHAIN ACIDS HAVE ANY TREATMENT ON COGNITIVE IMPATIENT? WE KNOW CONSUMPTION OF FISH HAVE BEEN REPORT TO HAVE DECREASE PROGRESSION OF IMPAIRMENT. SO WE DID COGNITIVE ATTENTION TESTING BY TELEPHONE, WE FIRST TESTED THEIR HEARING MAKE SURE THEY COULD HEAR WELL, TEST FOR DEPRESSION BECAUSE THAT AFFECTS COGNITIVE FUNCTION AND THEN BATTERY OF TESTS VALIDATED TESTS DONE FOR NUMBER OF STUDIES, WE LOOK AT THE TICKSES MENTAL STATE WHICH IS BY TELEPHONE, VERY SIMILAR TO WHAT WE CALL MANY MENTAL AND IMMEDIATE DELAY RECALL, CATEGORY FLUENCY, BACKWARDS COUNTING TASK. AND THESE WERE DONE AT BASELINE IN EVERY TWO YEARS BY CERTIFY EXAMINERS. SO WAS A BIG UNDERTAKING WE HAVE VERY FORTUNATE WE HAD NUMBER OF INSTITUTES WHO GAVE US ACTUAL HI QUITE A BIT OF Reserve TO DO THIS STUDY OVER THE COURSE OF THE STUDY.OUR PRIMARY OUTCOME WAS EFFECT OF OMEGA 3 ON NUTRITION AND OTHER NUTRITIONAL FAXES TO AS WELL, CHANGE IN GLOBAL SCORE, THE COMPOSITE SCORE, AS WELL AS CHANGE IN TEXT THAT WE TALKED ABOUT AND WE ADJUST FOR THINGS THAT ARE IMPORTANT FOR COGNITIVE FUNCTION AGE SEX RACE EDUCATION LEVEL AND HYPERTENSION. WE ADJUST FOR ALL THAT. SO YOU CAN SEE THAT IN THIS RANDOMIZE TRIAL THE FOREST PLOT INCLUDES ONE, THAT Symbolizes THERE'S NO SIGNIFICANT FINDINGS AT ALL.SO WE FOUND THAT OMEGA 3 FISH OIL HAD NO BENEFICIAL OR HARMFUL EFFECT ON COGNITION. WE Too Appear AT LUTEIN AND AGAIN YOU SEE THE FOREST PLOTS ALL INCLUDE ONE SO NONE OF THESE WERE SIGNIFICANT, NO HARMFUL OR BENEFICIAL EFFECT ON COGNITION WITH LUTEIN XANTHINE, SO WE FOUND WHAT ABOUT FOODS? THE DATA SUGGESTS EATING FISH MAYBE VERY IMPORTANT AND RATHER SUPPLEMENTS MA I NOT HAVE AN EFFECT SO WE DID ANALYSIS LOOKING AT THE DIET. SO THE AREDS STUDY HAD A COGNITIVE STUDY DONE IN 2000 TO 2004 ADDED TO THE PROTOCOL AND THIS IS BECAUSE AT THAT TIME WE HAD HIGH DOSE OF ZINC RANDOMIZE TO THIS TRIAL, IT TURNS OUT THAT ZINC IN THE TEST TUBE CAUSES A LOT OF THESE TANGLES THAT ARE AKIN TO ALZHEIMER'S SO WE WERE CONCERNED THAT WE WOULD HAVE PROBLEMS WITH PATIENTS TAKING ZINC, IN FACT WE FOUND NOTHING.WE DID THE SIMILAR TESTS DONE IN PERSON BY SIMILAR CERTIFY INTERVIEWERS EXACT BATTERY OF TESTS I TOLD YOU. SO OF COURSE AREDS 2 WE HAVE LONGITUDINAL DATA WHICH WE DO NOT HAVE IN AREDS 1 AND WE LOOK AT THE DATA TO SEE WHETHER MED TEAR RAINIAN DIET COME BY NIGHTS WOULD HAVE ANY EFFECT. SO WE LOOK SEPARATELY FOR AREDS BECAUSE THE DATA IS SOMEWHAT DIFFERENT. YOU CAN Visualize THE HIGHER THE INTAKE TERTILE 3 THE HIGHER INTAKE OF MEDITERRANEAN DIET, THE BETTER THE REDUCTION IN COGNITIVE FUNCTION. SAME WITH COMPOSITE SCORE. SIGNIFICANT REDUCTION IN EATING GOOD MEDITERRANEAN DIET IN THIS CASE. SO HIGH HERE MEDITERRANEAN DIET ASSOCIATED WITH DECREASED COGNITIVE IMPATIENT, 63% REDUCTION IN TERTILE 3 WITH MANY MENTAL WHICH IS CONSIDERING VERY IMPORTANT MEASURE OF COGNITIVE FUNCTION. AREDS 2 WE FOUND SIMILAR FINDINGS AGAIN ODDS RATIOS ARE QUITE LOW IN TERMS AGAIN 44% REDUCTION IN TERMS OF THE HIGH MEDITERRANEAN DIET ASSOCIATED WITH DECREASE COGNITIVE IMPAIRMENT.WHAT HAPPENS WITH COMPONENT? FISH POPS UP AGAIN, HAZARD RATIO. 36 SO 64% DECREASE IN RISK OF COGNITIVE FUNCTION IN THOSE PEOPLE WHO TOOK THE HIGHEST INTAKE OF FISH. THAT Makes TWO Performs PER WEEK, THAT'S WHAT IT MEANS TO BE HIGH INTAKE OF FISH. AGAIN, IN AREDS 2 WE FOUND A VERY SIMILAR HAZARD RATIO. SO THIS IS CONSISTENT THAN ALTHOUGH THE OMEGA 3 SUPPLEMENTATION DIDN'T WORK WE FOUND THAT TAKING FISH WAS IMPORTANT. SO CLOSER HERE IS MEDITERRANEAN DIET AIDS SOCIOIATED WITH LOWER RISK OF COG NOWTIVE IMPAIRMENT, WHEN WE LOOK AT FISH THIS AGAIN TO BE IMPORTANT FOR DECREASE RISK OF CON COGNITIVE IMPAIRMENT. WE Seem FOR PROGRESSION AREDS 2 MEDITERRANEAN DIET DIDN'T DECREASE PROGRESSION BUT FISH ITSELF IMPROVED THE DECREASE INCLINE SO IT'S INTERESTING FISH HAS SUCH IMPORTANT OUTCOME. LET'S TURN ATTENTION TO GENETICS. YOU HEARD ABOUT THIS ALREADY FROM DR. COLLINS. SO WE WERE APPROACHED BY DR. JOE SEEN AT YALE UNIVERSITY AND SHE WAS GOING TO DO THIS CHIP WE DIDN'T KNOW MUCH ABOUT, 100,000 SNPS IN THERE, THIS IS THE FIRST GENOME WIDE ASSOCIATION IN EYES.WE THOUGHT OUR SAMPLE SIZE WILL BE 200 PER CASES, NEOVASCULAR AMD, 200 GEOGRAPHIC ATROPHY AND 200 ACTUAL CONTROLS. BUT SHE SAID MAYBE WE SHOULD JUST DO A PILOT, GO SLOW AND NOT SPEND ALL OUR Assets At once. SO WE JUST DID 146 Actions, INSTEAD OF 600. LOW AND BEHOLD WE FOUND THAT THERE WAS A 7 FOLD INCREASE RISK OF LATE AMD HOMOZYGOUS, WHAT WAS MORE IMPORTANT IS THREE OTHER GROUPS ACTUALLY PUBLISHED IN THE SAME JOURNAL WITH DIFFERENT METHODOLOGY CAME TO THE SAME CONCLUSION AND DR. HAGEMAN CAME TO THE SAME CONCLUSION PUBLISHED LATER THAT YEAR SO LOVELY WE HAVE DIFFERENT METHODOLOGY AND THIS WAS A BANNER YEAR FOR AMD GENETICS.SINCE THEN, THIS WAS DONE BY DR. SIE SHOWING THE FACTOR RATIOS IN THE EYE DONE IN HUMAN EYE, DONE HERE, SO THE NIH OR NEI SUPPORTED A CONSORTIUM, INTERNATIONAL AMD CONSORTIUM OF 26 STUDIES AND WE WERE PART OF THAT. WE CONTRIBUTE OUR AREDS 1 AND 2 DATA TO THIS CONSORTIUM WITH 16,000 PATIENTS AND 17,000 Dominations. WE ANALYZED 12 MILLION Variants THIS Epoch. THIS IS Likened TO THE HUNDRED THOUSAND WE DID BACK IN 2005. SO THINGS HAVE PROGRESSED OVER TIME. WE HAVE 52 INDEPENDENT VARIANTS AND 34 LOCI AND CHROMOSOME ONE WHICH IS FACTOR H AND CHROMOSOME 10 ARMS TWO REMAIN THE MOST IMPORTANT SNPS IN OUR ARMAMENTARIUM HERE. RESEARCH QUESTIONS WE HAD, WHAT IS ROLE OF GENETICS ON AMD PATHOGENESIS, DIFFERENT PATHWAYS BEING USED HERE. ARE THE AMD PROGRESSION, AFFECTED BY GENETICS? DIETARY INTAKE SUCH AS MEDITERRANEAN DIET, IS THERE Accomplish WITH INTERACTION WITH GENETICS AT ALL? SO THERE ARE INSIGHTS IN MECHANISM OF DISEASE YOU CAN SEE DIFFERENT PATHWAYS THESE ARE SOME OF THE PATHWAYS FROM THAT PAPER THAT WE DID IN 2016, SO IT Passes INSIGHT TO WHERE THIS MIGHT BE IMPORTANT AND WHEN WE MAYBE ABLE TO DO WORK IN TERMS OF TREATMENT.THIS IS ALSO TRUE THE DIFFERENT SUBTYPES AMD MAY HAVE DIFFERENT GENETIC ASSOCIATIONS AS WELL. ARMS 2 MORE SO WITH GA, MMP 9 CTP AND ATTEMPT 3 IS IMPORTANT FOR THE NEOVASCULAR FORM. SO HOPING TO GIVE SOME CLUES TO THE PATHOGENESIS OF THIS. SO AMD IS A COMPLEX GENETIC DISEASE, MULTIPLE GENES INVOLVED. MENTION CHROMOSOME 1 AND ARMS ACCOUNTED FOR 60% HEREDITARY. WE ALSO DID A ANALYSIS USING ALL 52 SNPS, THIS WAS IMPORTANT TO LOOK AT THIS. THESE ARE MY COLLABORATORS, AND DR. RICKY IS VERY IMPORTANT IN OUR OWN INSTITUTION TO HELPED US A GREAT DEAL WITH THIS.WE WORK WITH UNIVERSITY OF MICHIGAN, AND ALSO A GREAT INVESTIGATOR, MIKE KLINE WHO HAS BEEN INTERESTED IN GENETICS OF AMD FOR MANY DECADES. OF COURSE OUR FRIENDS FROM THE UNIVERSITY OF PITTSBURGH VERY IMPORTANT IN THIS ANALYSIS. I WILL Sharpen ON ONE ASPECT OF THIS LOOKING AT THE SECONDARY GOAL OF PREDICTION MODELS USING GENETIC AFFECTS ON AMD PROGRESSION. WE GOT FIVE Simulations LOOKING AT BASELINE AGE EDUCATION SMOKING, ALL RISK FACTORS FOR MACULAR DEGENERATION. WE THEN Computed THE GENETIC RISK SCORE, YOU CAN Examine THAT WAS GOOD WHICH IS BASELINE EDUCATION IN SMOKING SO JUST LIKE THE ERROR UNDER CURVE, HIGHER THE NUMBER BETTER THE CORRELATION. YOU CAN Check ADDING THE GENETIC RISK SCORE DID HELP QUITE A BIT BUT IF YOU LOOK AT BASELINE SEVERITY AMD WHAT IT LOOKS LIKE IN TERMS OF. 88, THAT'S A REALLY IMPORTANT RISK FACTOR.IF YOU ADD THE PREVIOUS LIST FACTORS, IT JUMP RISK FACTORS IT JUMPS A POINT, WHEN YOU ADD THE RISK SCORE IT DOESN'T ADD MUCH SO WE WERE SURPRISED BY THE FACT THE MOST IMPORTANT PREDICTION OF THIS RISK MODEL IS ACTUALLY WHAT YOU SEE IN YOUR EYE. SO GETTING AN EYE EXAM IS REALLY IMPORTANT. SO OVERWHELMING THE FINDINGS WERE MUCH MORE IMPORTANT. WE HOPE TO USE GENETICS TO PERSONALIZE TREATMENTS, AT THIS POINT WE ARE NOT QUITE THERE YET.WE WILL BE THERE SOMETIME SO CLEARLY IT'S IMPORTANT TO GET EYE EXAM, GENETIC TESTING IS EXTREMELY IMPORTANT FOR RESEARCH. CLINICAL PRACTICE AT THIS POINT. SO LET'S LOOK AT INTERACTION WITH GENETICS IN MEDITERRANEAN DIET. THIS IS NOW LOOKING AT PATIENTS THAT I Presented YOU EARLIER WITH AMD AND GENETICS AND YOU CAN SEE THAT THESE ARE P VALUES, NONE ARE SIGNIFICANT SO THERE'S NO GENETIC INTERACTION WITH MEDITERRANEAN DIET. IN THE COMBINE AREDS AND AREDS 2 Population. LOOK AT THE EREDS ITSELF WE FIND ONE SIGNIFICANT FINDING, GEOGRAPHIC ATROPHY AND FISH. AND THIS INTERESTINGLY FISH INTAKE AGAIN COMES UP AS BEING VERY IMPORTANT.SO THOSE PATIENTS WITH PROTECTIVE ALLELES FACTOR H HAD INCREASE BENEFICIAL EFFECT ON REDUCING DEVELOPMENT OF GEOGRAPHIC ATROPHY. HOPEFULLY THIS WILL GIVE MORE INSIGHT INTO THE MECHANISM OF DISEASE, WHY IS THAT SO. THIS IS VERY INTERESTING THE MORE HIGHER YOU HAVE OF FACTOR H WITH PROTECTIVE EFFECT MORE LIKELY YOU HAVE BENEFICIAL EFFECT FROM EATING FISH. SO GENETIC TESTING CAN BE DONE IN AMD, IT'S Offered in 23 AND ME AND OTHERS HAVE OFFERED A MD EVALUATION. CERTAINLY I DON'T Envision IT'S IMPORTANT FOR DIETARY RECOMMENDATIONS, WE HAVE NOT FOUND IT USEFUL FOR ANTIVEGF THERAPY, THERE'S STUDIES Intimating THAT'S TRUE, AND CERTAINLY ENOUGH FOR AREDS 2 SUPPLEMENT FOR AMD. WE HAVE PROVEN THAT'S NOT IMPORTANT TO DO IT, BECAUSE THERE'S NO PERSPECTIVE TO SUPPORT TESTING FOR PREDICTION OF TESTING OR RESPONSE FOR TREATMENT OR DIETARY RECOMMENDATIONS. A GENETIC TESTING IS NOT RECOMMENDED BY AMERICN ACADEMY OF OPHTHALMOLOGY AT THIS POINT SO WE HOPE WE WILL BE ABLE TO DO FURTHER.FINALLY, THE ARTIFICIAL INTELLIGENCE PART VERY INTERESTING. DEEP LEARNING IS PART OF MACHINE LEARNING WHICH IS A SUBSET OF ARTIFICIAL INTELLIGENCE. WE ARE Terribly LUCKY TO HAVE WONDERFUL COLLEAGUES ACROSS CAMPUS SO WE TALK TO MENTORING, AS PARENTS YOU MAKE FRIENDS THROUGH YOUR CHILDREN. THIS IS WHAT WE DID WITH DR. I DON'T Conclude THROUGH AND MYSELF, WE HAD A MEDICAL STUDENT WHO CAME TO US THREE OR FOUR YEARS AGO WITH NATURAL LANGUAGE PROCESSING, WE WORKED WITH HIM AND FURTHER FOUND MORE COLLABORATIONS AND THROUGH THAT RELATIONSHIP WITH WORK WITH OOHED MEDAL STUDENT NOW A OPHTHALMOLOGY RESIDENT AT WILMER HOPKINS EYE INSTITUTE ALONG WITH HIS TEAM AND WE HAVE EXCELLENT CLINICIAN SCIENTISTS, DR.KEENAN AND DR. WONING OUR TENURE INVESTIGATOR HAVE COMBINED TOGETHER TO PUT THIS WORK TOGETHER ON DEEP LEARNING. BECAUSE WE HAVE GREAT IMAGES FROM THESE TWO STUDIES, IT WAS A NATURAL PLACE FOR US TO COLLABORATE AND UNDERSTAND SOME OF THESE. OUR MAIN GOAL WAS TO DETECT FEATURES OF AMD. WHETHER IT BE LARGE DRUSIN, RETICULAR DRUSIN PEGMENT CHANGES PIGMENT CHANGES. ASTRO MY, BASED ON SEVERITY ON A PERSON LEVEL USING BOTH EYES TO HELP PREDICT PROGRESSION OF AMD. I WON'T TALK MUCH MORE ABOUT PROGRESSION BECAUSE THAT'S LONG LECTURE, WE WILL TALK THESE TWO PAPERS THAT WE ARE TALKING ABOUT.THE DEEP C NET IS ALGORITHM THAT DR. LU AND OUR HIS COLLEAGUES PUT TOGETHER AND THIS IS USED TO LOOK AT ASSESS FEATURES OF AMD ON COLOR FUNDED PHOTOGRAPHS. FROM GOOGLE THEY HAVE DONE WORK ON THIS AND AREDS IS DOWNLOAD AND MANY USE IT AND ESTIMATE WHETHER YOU'RE FEMALE OR MALE BASED ON COLOR PHOTOGRAPH, AMAZING AND HOW MUCH YOU CAN LOOK AT IN TERMS OF CARDIOVASCULAR RISK ET CETERA SO WE WANT TO DETECT MACULAR DEGENERATION AND CLASSIFY THEM BASED ON A SIMPLIFIED SEVERITY SCALE WE DEVELOPED FROM AREDS.TO LOOK AT PREDICTION OF RISK OF AMD. SO FOR THIS WE DEVELOPED ABOUT TEN YEARS AGO THIS IS BEING USED BY CLINICIANS WHICH IS MOSTLY AT THE EVIDENCE OF LARGE DRUSIN OR PIGMENTARY CHANGES IN RETINA AND COUNT IN BOTH EYES WHETHER THEY'RE PRESENT OR NOT. PRESENCE YES UP TO FOUR THAT MEANS MORE SEVERE, YOU HAVE ADVANCE DISEASE THEN FIVE, MEANS LATE DISEASE IN THIS CASE.SO THIS IS IMPORTANT BECAUSE WITH EACH INCREASING RISK FACTOR THERE'S INCREASING RISK OF PROGRESSION IN FIVE YEARS. IF YOU HAVE A RISK SCORE OF FOUR OR ADVANCE DISEASE IN ONE EYE, YOUR RISK OF DEVELOPING AMD IN FIVE YEARS IS 50% FOR THAT EYE OR FOR THOSE TWO Sees. IF IT'S ONLY THREE RISK FACTORS, IT'S ONLY IT'S ONLY HAVING OF THAT, 25%, “If youre having” ONLY TWO Influences ONLY 12%. IF YOU HAVE ZERO FACTORS IT'S. 5% IN FIVE Years DEVELOPING AMD. SO THIS IS USEFUL SCALE CLINICIANS USE SO WE WANT TO TEST THIS IN OUR DEEP LEARNING SO WE DEVELOP THIS BY LOOKING AT COLOR PHOTOGRAPHS IN BOTH EYES.THERE'S THREE NEURAL NETWORK ONE IN THE HERE WE HAVE OOPS SORRY. ONE FOR DRUSIN MEASURED BY SMALL MEDIUM OR LARGEMENT PIGMENT CHANGE PRESENT OR ABSENT. AND IN PRESENCE OR ABSENCE OF ADVANCE OR LATE AMD AND THIS ALL GOES INTO OUR ALGORITHM AND WE CAN COME UP WITH A SIMPLIFIED SCORE 0, 1, 2, 3, 4, 5, WE HAVE ALREADY CURATED IN OUR DATA SET WE KNOW WHAT THESE ARE. WE TRAIN ON 58,000 Idols, 4,549 AREDS Players AND TESTED ON 900 Epitomes. 900 Participates WITH Likeness. OUR MAIN OUTCOME WAS TO LOOK FOR ACCURACY, SPECIFICITY AND SENSITIVITY AS WELL. GOLD STANDARDS WERE THE READING CENTER. THIS IS READ BY A HUMAN GRADER WHO THEN WAS ACTUALLY TWO GRADERS UNDER RISK CONSENSUS BILLETS ON THESE, WE SPENT MILLIONS OF DOLLARS DOING THIS FOR PART OF THE STUDY AND WE WANT TO PERFORM SEE WHAT THIS LOOKED LIKE WHEN COMPARED TO DEEP LEARNING. WE ALSO COMPARED TO OUR 88 RETINAL SPECIALISTS. SO YOU CAN SEE HERE THE DEEP LEARNING IS ON THE LEFT RETINAL SPECIALIST ON RIGHT. WE Glance FOR DRUSIN PIGMENTARY CHANGE, ALL THE ONES BOLDED ARE DEFINITELY MORE SIGNIFICANT THAN THE ONES THAT ARE NOT: BY AND LARGE YOU CAN SEE THE DEEP LEARNING DID BETTER IN DETECTING AND NOTING SIZE OF THE DRUSIN AS WELL AS PIGMENT ARY CHANGE, FOR LATE AMD THIS IS NOT TRUE AND RETINAL SPECIALIST DID BETTER THAN DEEP LEARNING PARTLY BECAUSE WE DIDN'T HAVE LATE AMD IN OUR TRAINING SET, WE TRAIN FURTHERMORE WITH OTHER DATA SETS, THAT WILL PROBABLY HELP IMPROVE THIS SITUATION.OVERALL PERFORMANCE FOR THIS SIMPLE SCALE WAS BY FAR MUCH BETTER IN DEEP SEE NET DEEP LEARNING THAT IT WAS FROM RETINAL SPECIALIST SO CLEARLY WE CAN DO BETTER. AS I'M NOW RECRUITING FOR ANOTHER STUDY, I UNDERSTAND IT'S VERY DIFFICULT FOR THE OPHTHALMOLOGIST TO UNDERSTAND WHAT THE SIZE OF THE DRUSIN IS ACTUALLY VERY DIFFICULT SCENARIO. SO OVERALL, DEEP SEED LEARNING WAS SUPERIOR TO RETINAL SPECIALISTS. I Crave TO SPEAK ON ONE PARTICULAR LESION WHICH IS NOT EVEN FAMILIAR FOR A LOT OF OPHTHALMOLOGISTS, IT'S CALLED RETICULAR PSEUDODRUSIN. VERY DIFFICULT FROM THE USUAL DRUSIN WE SEE, THIS HERE IS PIGMENT EPIHELIUM, ARTIST DEPICTION OF LAYER HERE, TYPICAL DRUSIN IS UNDERNEATH THE AREA BUT THE NEW DRUSIN CALLED SUBRETINAL PSEUDODRUSIN IS ON TOP OF RPE. YOU CAN Identify Now ON THE ACTUAL PATHOLOGY THAT WE SEE THIS IS ON TOP OF RPE.THIS IS THE RETICULAR PSEUDODRUSE INSTEAD OF UNDERNEATH RPE. YOU CAN Realise IT NICELY ON A FUNDUS PHOTOGRAPH BUT THIS IS UNUSUAL WE DON'T SEE IT VERY WELL IN COLOR PHOTOGRAPHS. THIS Patient HAS THE TYPICAL LARGE DRUSEN, WITH THE WHITE ARROW. THE BLACK SHOWS RETICULAR PSEUDODRUSEN. WHAT'S IMPORTANT IN THIS GROUP? CATHY COOKER ONE OF MY COLLEAGUES LOOKED AT THIS AND SHOWN THESE ARE VERY IMPORTANT RISK FACTORS FOR PROGRESSION TO LATE A MANYHD AND ALSO ASSOCIATED WITH POOR ADAPTATION, FUNCTIONALLY VERY DIFFERENT SO IT'S VERY IMPORTANT FOR US TO IDENTIFY THIS PARTICULAR LESION.IN AREDS YOU CAN Learn THIS AS BLACK AND WHITE PHOTOS OF THE RED FREE PHOTOGRAPHS, ON THE LEFT DOWN HERE OR ON THE RIGHT DOWN HERE YOU CAN SEE THIS IS THE OCT OPTICAL COHERENCE TOMOGRAPHY SHOWING FINE LAYER OF RETINA AND SHOWS THIS LOOKS TYPICAL SAW TOOTH APPEARANCE OF THE THE ACTUAL DRUSEN, VERY SPECIFIC FINDINGS FOR THIS. SO THE AREDS 2 HAD FUNDUS AUTOFLUORESCENCE IMAGES BLACK AND WHITE AND COLOR PHOTOGRAPHS IN THE SAME VISIT, A DEEP LEARNING TRAIN DEVELOP MODELS BASED ON THE BLACK AND WHITE, THAT'S THE BEST WAY OF DETECTING THE RETICULAR PSEUDODRUSIN THEN WE USE LABEL TRANSFER TO SEE WE CAN USE TO IDENTIFY THESE LESIONS ON COLOR PHOTOGRAPHS.THIS ENABLES TRAINING MODELS IMAGES TO CONTAIN FEATURES NOT CONSISTENTLY DISCERNIBLE BY HUMAN EXPERTS SUCH AS RPD SO I WILL SHOW AN EXAMPLE. THIS IS ONE OF MY FAVORITE PATIENTS. I FOLLOWED HIM FOR 27 Years. HE IS AN AREDS PATIENT, HE'S 97 Years OLD NOW, HE STILL TELLSES ME HE CAN DRIVE HERE, HE'S 2020 AND HE DOES DRIVE HERE. HE HAD PSEUDODRUSEN, IT'S BLONDE FUNDUS YOU CAN'T SEE IT WELL. HE HAS POOR ADAPTATION, HE COMES DURING THE DAY SO IT'S OKAY. YOU CAN Check THE BLACK AND WHITE YOU SEE THE DRUSEN BUT WITH DEEP LEARNING WE CAN IDENTIFY THESE LESIONS ON THE COLOR PHOTOGRAPHS.WHICH I THINK IS GOING TO BE VERY IMPORTANT FOR FUTURE RESEARCH. THIS IS CASE THE PATIENT. SO THIS EREDS PATIENT IDENTIFY AS HAVING RETICULAR PSEUDODRUSEN USING LABEL TRANSFER TECHNIQUE SPELLS WELL FOR OUR FUTURE RESEARCH AND MODELS USING THE FAF AND THE MODELS USING THE COLOR PHOTOGRAPHS PERFORMED BY SUPERIOR TO THE FOUR RETINAL SPECIALISTS LOOKING AGENT THE RPD. SO IN OTHER WORDS, AGAIN DEEP LEARNING WAS SUPERIOR TO THE RETINAL SPECIALIST AND I WAS ONE OF THEM. THEY WERE MUCH BETTER THAN I AT THIS SO A DEEP CLEARLY DETECT LESIONS NOT DISCERNIBLE BY HUMAN EXPERTS. WHERE DOES THIS Contribute US? ABRAHAM AN AUTHOR FEELS COMPUTER REALLY NEEDS A PHYSICIAN. WE ARE NOT READY TO GIVE UP EVERYTHING.WE WILL NOT REPLACE CLINICIAN BUT ENHANCE DIAGNOSTIC SKILLS, IMPROVE CLINICAL MAGMENT, AS A CLINICAL RESEARCHER MY HOPE IS FOR MORE PRECISE MEASUREMENT FOR IMPROVEMENTED EFFICIENCY OF CLINICAL TRIALS. THERE'S STILL A MUCH OF STEPS WE HAVE TO IMPLEMENT BEFORE WE CAN ACTUALLY USE IT IN THE CLINICAL CARE BUT STILL VERY IMPORTANT FOR RESEARCH BUT CLEARLY DEEP LEARNING IS HERE AND VERY IMPORTANT FOR US TO GO ON AND DO MORE WORK ON THIS AREA. BY SIMULATING HUMAN RATING PROCESS DEEP SEE NET DEMONSTRATES HIGH ACCURACY WITH MACULAR DEGENERATION RISK CATEGORIES BASED ON THE AREDS SIMPLIFIED SCALE WE NEED TO THINK DEEP LEARNING TO ENHANCE CLINICAL DECISION MAKING TO DETECT AND ALSO PREDICT PRODUCTION OF DELAY AND DEVELOPMENT IN THE FUTURE OF AMD.SO THIS IS A SUMMARY OF WHAT I PRESENTED TO YOU. AREDS 2 FORMULATION RECOMMENDED FOR PERSONS WITH INTERMEDIATE AMD OR LATE IN ONE EYE AND NOT BEFORE THAT. GENETIC TESTING IS ENCOURAGED especially for experiment purpose , not nor clinical care at this degree. DEEP LEARNING MAYBE HELP MORE ACCURATE EFFICIENT CLINICAL PRACTICE AND CERTAINLY GREAT RESEARCH TOOL BUT WILL NOT REPLACE US. THE IMPORTANCE OF MEDITERRANEAN DIET AND FISH FOR AMD AND COGNITIVE FUNCTION MAYBE BENEFICIAL EVEN WITH EARLY OR INTERMEDIATE AMD SEEM BENEFICIAL.REMEMBER WE ARE WHAT WE EAT. WHAT ABOUT THE FUTURE? TRANSLATIONAL RESEARCH IS DONE AT NEI AND AGAIN I WANT TO POINT OUT THAT AREDS 2 PATIENT IS BLOOD WAS USED TO PRODUCE INDUCE PLURIPOTENT STEM CELL TECHNOLOGY TO DEVELOP IPSC CELLS IN WHICH DR. COUPLE ONE OF OUR GREAT INVESTIGATORS AT NEI IS GOING TO LOOK AT IN VITRO DISEASE MODELS, SETTING UP HIGH THROUGH PUT DRUG SCREENS WITH DR. HENRY ONE OF All my fellow members, A GREAT SURGEON, TO DEVELOP CELL BASED THERAPY USING RPE CELLS FOR LATE STAGES OF MACULAR DEGENERATION. ANOTHER IMPORTANT GOAL IS TO DO PREVENTIVE THERAPY FOR A MD. PRIOR TO THIS STAGE OF AMD PERHAPS THIS LEADS TO AREDS 3, NOT SURE BUT THERE ARE SIGNS THAT IT MAYBE IMPORTANT FOR US TO LOOK AT PRIMARY PREVENTION. WITH THAT I WOULD LIKE TO THANK MY AREZS INVESTIGATORS ESPECIALLY THE PATIENTS, THOUSANDS OF PATIENTS WHO HAVE SPENT MORE THAN TEN YEARS WITH US ON THIS STUDY. THIS IS DEDICATION. OUR LOSS TO FOLLOWUP WAS ONLY 3% SO AMAZING, AMAZING STUDY. TO MY NIH FAMILY, THEY ARE TREMENDOUS.I THINK THEY ARE DEDICATION TO PUBLIC SERVICE IS AMAZING. THESE ARE GREAT INVESTIGATORS. DR. PAUL COATS HELPED US A LOT WITH SUPPORTING OUR STUDIES AS WELL AS JOCIE BRIGGS, BOTH RETIRED AND JANINE CLAYTON IS HELPFUL IN PROVIDING Assets FOR OUR STUDY AND OF COURSE ALL MY COLLEAGUES ARE REALLY IMPORTANT HERE. I WOULD LIKE TO ACKNOWLEDGE OF COURSE NCBI NLM FOLKS, DR. LU AND HIS GROUP AS WELL ADS ENNIS CORPORATION HELPED WITH STUDY, DR. WHO HELPED WITH GENETICS AS WELL AND OF COURSE OUR CLINICAL CENTER THE COORDINATORS, PHOTOGRAPHERS TECHNICIAN AND MEMBERS OF DIVISION ARE TREMENDOUS IN HELPING US.AND TO MY FAMILY WHO GAVE ME SOME SUPPORT AND PUTTING UP WITH ME AND MY COOKING. AND FINALLY I WOULD LIKE TO THANK ALL OF YOU FOR ATTENDING.[ APPLAUSE] >> THANKS FOR A WONDERFUL ROMP THROUGH A LOT OF WORK AND A LOT OF DATA AND VERY INTERESTING CONCLUSIONS AN LOTS OF WORK YET TO DO. WE HAVE TIME FOR QUESTIONS AND I WOULD ENCOURAGE THOSE WHO HAVE QUESTIONS TO USE THE MICROPHONES IN THE AISLE SO PEOPLE LISTENING BY VIDEO CAN ALSO HEAR. WE CAN START HERE. >> CONGRATULATION, EMMY ALREADY PHON OUTSTANDING WORK AND SUPER PRESENTATION. SO QUESTION DELAYS TO THE ISSUES OF THE COMPOSITION, AS YOU HAVE SHOWN THE THEY EVOLVED SO YOU ARE LIMITED SOME, YOU ADDED.SO AND IT IS Interested that IT AFFECTED BOTH THE NEOVASCULAR AMD AND ALSO GEOGRAPHIC ATROPHY. SO I WAS WONDERING HOW THIS COMPOSITION OF SEVERAL Information AFFECTING BOTH DISEASE WITH DIFFERENT MECHANISMS FOR THE DISEASE. >> SO I DIDN'T CUT INTO THE GEOGRAPHIC ATROPHY NEOVASCULAR AMD. SO THE AREDS SUPPLEMENT FOR EXAMPLE WHICH IS BETA CAROTENE AND VITAMIN C AND LUTEIN NOW HAVE MORE EFFECT ON NEOVASCULAR SO SEEMS TO HAVE STOP NEOVASCULAR MORE SO THAN GEOGRAPHIC ATROPHY.WHEN WE LOOK AT THE HOLES OF DATA, I DIDN'T SHOW ALL FOR THE DIET, SEEMS TO BE MORE LIKE THE FISH IN PARTICULAR IS MUCH MORE IMPORTANT FOR GEOGRAPHIC ATROPHY. SO SIMPLY SIGNIFICANT FINDINGS MOSTLY WERE GEOGRAPHIC ATROPHY WHICH IS A DISEASE WE HAVE NO TREATMENT FOR. SO IT'S VERY IMPORTANT TO LOOK AT THE MECHANISM AND WHY FACTOR H PROTECTIVE ALLELE IS SO MUCH BETTER. SO WE DON'T REALLY KNOW AND OBVIOUSLY WE ARE NOT GOING TO BE ABLE TO KNOW FOR SURE, THIS IS COMBINATION OF THINGS. WE ARE Glancing AT NUTRIENTS, LOOKING AT LONG CHAIN FATTY ACID THAT MAYBE VERY IMPORTANT. C 28 TO 34 RATHER THAN C 22 WHAT WE HAVE FOR OMEGA 3 FATTY ACID SO THERE'S A NUMBER OF THINGS WE ARE LOOKING AT THAT MIGHT BE IMPORTANT.WE HAVEN'T AND THERE'S INCREASING DATA FROM BASIC SCIENCE LABS, NICK BAZON FROM NEW ORLEANS HAS BEEN TALKING TO US ABOUT SOME OF THE THINGS HE'S BEEN DOING AND LOOKING AT LONG CHAIN FATTY ACIDS AND THERE'S A WHOLE HOST OF OTHER THINGS, MITOCHONDRIA MAYBE IMPORTANT WHICH WE KNOW MITOCHONDRIA IS IMPORTANT IN OUR PATHWAYS SO THERE'S A NUMBER OF THINGS WE CAN TRY AND HOPEFULLY COUPLE WILL HELP US HIS DISEASE MODEL THAT WE MAY ACTUALLY GO TO HIGH LIEU PUT CERTAIN DRUGS AND SEE WHETHER THAT IS HELPFUL AS WELL SO THERE'S A NUMBER OF THINGS WE CAN BUT HARD TO KNOW EXACTLY WHAT COMPOSITION WOULD BE. >> AFTER LISTENING TO YOU I STARTED TAKING LUTEIN AND XANTHINE COMBINATION. I Bid YOU CAN INCLUDE CHOCOLATE. >> FOLLOWUP A LITTLE BIT ON IT BECAUSE WE ARE INTEREST TO SEE WHILE OMEGA 3 DIDN'T APPEAR TO BENEFIT, THERE IS ASSOCIATION WITH FISH SO WONDERING USUALLY WHEN PEOPLE TALK ABOUT BENEFITS OF FISH THE LIGHT BULB GOES ON, IT MUST BE OMEGA 3, IN THIS CASE IT DOESN'T SEEM TO BE THE RIGHT ANSWER. OF COURSE ONE DOES HAVE TO Noted, AT LEAST I GOT THIS RIGHT I THINK THAT THE ASSOCIATION WITH FISH WAS ASSOCIATION, IT WAS NOT RANDOMIZED TRIAL .>> EXACTLY RIGHT. >> ONE DOES THEN WONDER WHAT OTHER CONFOUNDERS MIGHT BE THERE, PEOPLE WHO EAT MORE FISH DOING SOMETHING ELSE THAT WASN'T MEASURED THAT WAS WHAT PROVIDED THE BENEFIT. I Presume YOU LOOKED AT ALL KINDS OF OTHER HEALTH BEHAVIORS TO TRY TO SEE IF THERE IS ANYTHING ELSE IN THE THERE. ANYTHING Turn up? >> NO, WE DIDN'T FIND ANYTHING, OBVIOUSLY PEOPLE WHO EAT BETTER, TAKE BETTER CARE OF THEMSELVES, TAKE THEIR BLOOD PRESSURE LOT MORE THAN OTHERS MUCH MORE COMPLIANT SO THEY PROBABLY SOMEWHAT DIFFERENT. EDUCATION IS OBVIOUS VERY IMPORTANT SO WE LOOK AT EDUCATION AND HOW MUCH THAT CONTRIBUTES, AND THAT'S TIED TO YOUR DIET AS WELL. EDUCATION IS A RISK FACTOR FOR MACULAR DEGENERATION. SO YOU ARE ABSOLUTELY RIGHT, THEY ARE CONFOUNDING, WE ARE NOT SAYING THIS IS IT BUT CERTAINLY THERE'S COMPELLING REASON TO CONSIDER IT BUT WE DON'T REALLY KNOW FOR SURE. UNLESS WE DO A RANDOMIZED TRIAL. >> AN ADDITIONAL COMMENT, LIPOFUSION DISTRIBUTION IS PROPOSED AS A TREATMENT FOR THIS H.I HAVE THE PAPER HERE INCIDENTALLY THAT I CARRY AROUND THAT I SAW FROM A PRIOR LECTURE ON CELLULAR SENESCENCE. I MENTION AS TREATMENT FOR PROBABLY IN THE FUTURE WOULD BE A TREATMENT FOR SOME THINGS AND LOW AND BEHOLD IT HAS BEEN SUGGESTED. I WILL Establish YOU THE PAPER AFTER. THE OTHER QUESTION, REAL QUESTION I HAVE IS THAT YOU SUGGESTED FISH BUT NOWADAYS THERE'S MANY VARIETIES OF FISH AND THERE'S FIREARMING. FOR EXAMPLE I WAS LOOKING AT THE BENEFITS OF TILAPIA, I DON'T KNOW IF SPANISH OR ENGLISH BUT THEY SAY IT'S FISH FARMED OR GET IT WILD AND THE ONE THAT'S FISH FARMED DOESN'T HAVE THE SAME NUTRITIONAL VALUE AS THE FARMED& FISH. SO MAYBE IT'S SOMETHING THAT'S WRITTEN WITHIN THE MEDITERRANEAN DIET WHICH I HAVE NOT READ BUT PERHAPS BE MORE SPECIFIC ON TYPE OF FISH MOST BENEFICIAL .>> >> THAT'S A VERY GOOD QUESTION. WE DON'T HAVE GOOD DATA ON THAT BECAUSE WE DO NOT ASK SPECIFICALLY WHAT TYPE OF FISH BUT IT'S ALWAYS BEEN THOUGHT THE COLD WATER FISH SUCH AS SALMON, SARDINES TEND TO BE A BETTER SOURCE OF WHATEVER THE SOURCE IS IMPORTANT BUT WE REALLY DON'T KNOW FOR SURE WHAT THAT MIGHT BE. AND WE NEED FURTHER QUESTIONNAIRES MIGHT BE ABLE TO FIND THAT OUT BETTER. WE DON'T HAVE THAT DATA UNFORTUNATELY. >> THANK YOU. >> OVER HERE. >> ALONG THESE LINES, IS IT POSSIBLE THAT FISH PROTECT NOT BECAUSE THEY ARE FISH BUT THEY COME INSTEAD OF SOMETHING THAT IS HARMFUL? >> SAY THAT AGAIN. >> >> IS IT POSSIBLE THAT FISH PROTECT NOT BECAUSE THEY ARE FISH AND ESPECIALLY THERE'S NO CORRELATION WITH OMEGA 3 WHAT WE USUALLY Contemplate ABOUT, IS IT POSSIBLE THAT FISH PROTECT NOT BECAUSE THEY ARE FISH BUT BECAUSE YOU HAVEN'T EATEN RED MEAT WHICH IS HARMFUL SO TAKING AWAY THE DETRIMENTAL INFLUENCE OPPOSED TO PROVIDING A POSITIVE INFLUENCE. >> THAT'S A VERY GOOD POINT.PEOPLE THOUGHT ABOUT THAT, REPLACING SOMETHING INSTEAD OF THAT. WE Seem AT IT WOULD RED MEAT AND IT'S STILL BENEFICIAL. SO MY SECOND QUESTION WOULD BE AREKS 2 IS RECOMMENDED IN LATE AMD BUT DOESN'T PROVIDE BENEFIT IN EARLY AMD. WHY? >> WE DON'T KNOW THE MECHANISM OF DISEASE, THINK THAT'S ONE THING YOU SEE, THEY DON'T KNOW HOW IT WORKS BUT WE HAVE LASER THAT WORKS WE DON'T KNOW HOW IT WORKS EITHER SO WE DON'T KNOW WHY THAT IS. CLEARLY I Reckon IS THAT THERE ARE TWO Pathways, DEVELOPING A DRUSIN FOR MACULAR DEGENERATION IS ONE PATHWAY, TO GET TO LATE DISEASE IS ANOTHER PATHWAY, THAT'S WHAT THE DIFFERENCES MIGHT BE. I DIDN'T SHOW THE DATA, WE DID DEEP PHENOTYPING OF ALL OUR CASES AND CLEARLY A COUPLE FACTOR H IS ASSOCIATED WITH FORMATION OF DRUSEN. SO VISION LOSS THERE'S DIFFERENT MECHANISMS WHICH THE DISEASE STARTS AND THEN SOMEHOW IT Exits TO CERTAIN STAGE, SOMETHING ELSE HAS TO KICK IN. SO THAT PROBABLY IS THE REASON WHY SOME THINGS WORK FOR ONE AND NOT FOR THE OTHER. >> GREAT TALK.A LOT OF PEOPLE LIVE IN FOOD DESERTS WHERE THEY CAN'T GET FRESH FOOD. IS THERE INDICATION ABOUT CANNED FISH VERSUS FRESH FISH? >> APPARENTLY WHEN WE Glance AT THAT, WE Glance AT THINGS LIKE CANNED TUNA AND THAT WORKS JUST AS WELL. SO I Mull THAT THAT PROBABLY IS A GOOD SOLUTION FOR PEOPLE WHO CAN'T GET THE FRESH FOOD. I Review THAT WOULD BE VERY IMPORTANT, THAT'S VERY IMPORTANT QUESTION. >> THANK YOU. >> ONE MORE. >> THIS QUESTION IS ABOUT THE OMEGA 3 AND FISH. MY UNDERSTANDING IS THAT OMEGA 3 IS Obtained FROM THE LIPID PRESENT IN THE SKIN OF THE FISH AND WHEN YOU ARE EATING FISH YOU HAVE MANY OTHER COMPONENTS. SO IS THAT THE DISCREPANCY? >> I'M SORRY, I THE QUESTION, THERE IS >> WHEN OMEGA 3 IS Descended FROM THE LIPID, IT'S A LIPID, IT'S IN THE FISH SKIN, AM I WRONG? >> IS IT IN THE FISH SKIN? I >> COMPONENT OF FISH .>> OMEGA 3 IS THROUGHOUT THE FISH NOT JUST THE SKIN ITSELF BUT I'M NOT I'M NOT A FISH I DON'T KNOW THAT FOR SURE. I GO FISHING BUT I NEVER FIGURE OUT WHETHER THE SKIN HAS IF YOU TALK TO MY FATHER HE SAYS EVERYTHING IS IN THE SKIN, YOU HAVE TO EAT THE SKIN. YOU HAVE TO EAT THE POTATO SKIN, ALL THE SKIN. SO I DON'T KNOW THAT'S REALLY TRUE. I'M SORRY, I CAN'T HELP YOU WITH THAT ONE. >> I WANT TO SAY WHAT AN INTERESTING PRESENTATION COVERING A LOT OF GROUND. WE ARE Croaking TO HAVE A LITTLE RECEPTION OUT HERE WHICH IS GOING TO SERVE FISH WITH THE SKIN ON. I HOPE YOU ALL WILL ADJUST YOUR DIET ACCORDINGLY FROM NOW ON BECAUSE Y'ALL WANT TO SEE FOR A LONG TIME. EMILY, Thank you very much FOR A WONDERFUL PRESENTATION.[ APPLAUSE] >> Thank you very much VERY MUCH.THANK YOU FOR HAVING ME ..

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