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Age related macula degen
 

Age related macula degen

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May 2012 discussion of age related macular degeneration to a lay audience by 5 different doctors

May 2012 discussion of age related macular degeneration to a lay audience by 5 different doctors

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  • Amsler grids are everywhere. Check the vision in each eye daily.
  • Throughout the history of medicine, doctors have observed treatment variability among patients which we know now to be due to genetic differences. Why some people respond well to one drug and others don’t or why some people develop certain side effects and others don’t is due to small differences in genetic make up between us. Some preliminary pharmacogenetic relationships have been reported to exist between genetic risk factors associated with AMD and the response to treatment. These pharmacogenetic associations could be used in the future to create a personalized therapeutic plan whereby patients with different genotypes are offered different treatments.
  • So how can we use our knowledge of genetics to actually treat patients. Many diseases come about b/c of an abnormal protein produced by a faulty gene. Gene therapy aims to alter or stop the formation of proteins that lead to disease. This approach is still a long way off in treating AMD but is being used to treat other eye diseases. On the other hand creating a so called “biofactory” by injecting genes that produce proteins such as anti-VEGF compounds drugs would obviously be very helpful for patients with wet AMD. An injection every year or two rather than monthly is not an unrealistic possibility.
  • The wet form of AMD with bleeding and scarring (shown in the top picture) and the Atrophic form (bottom picture) with thinning and and loss of retinal tissue are the primary causes of severe loss of vision in pts with macular degeneration. The treatments I’ll discuss here pertain primarily to this subset of patients. Both of these forms of AMD will become less prevalent as we become better at indentifying those patients who are at greatest risk and as preventative treatments become available.
  • Three models are now in development or testing. Model 1, with 16 electrodes, has been implanted in six patients. As of mid-July 2009, a second model integrating a 60-electrode array has been implanted in 30 human subjects domestically and internationally. A third model, an array with a higher electrode count, is under development.
  • May 2012 – details released of a wireless, subretinal 256 channel implant being developed in Boston. Disadvantages: more complex surgical procedure. All the implant designs in development have advantages and disadvantages not the least of which is the complexity of the surgical procedure, the lack of long term follow-up and cost ($100K)
  • Moore’s law loosely defined says that the power of a computer chip doubles approximately every 2 years. Timeline for progress of the artificial retina. Progress started with the installation of the first 16-electrode device in 2002, which restored light perception and the ability to perform simple visual spatial and motion tasks (hand motion level). Theoretically, there is improvement with 60 and 200+ electrode implants (finger count level) with the possibility of face recognition and reading ability with a 1000+ electrode device. (Left scale) Progression in vision from bare hand motion to face recognition. At 20/200 visual acuity, large letters can be recognized. At 20/20, small letters can be seen with good reading ability. (Right scale) Number of patients potentially helped with the different generations of prosthetic devices.
  • Pixels (short for picture element) are the smallest controllable element of a digital image. It is a single point in a graphic image. The more pixels on the display the higher the resolution. Examples of pixilated vision. Lower resolution may allow crude shape recognition, but increasing resolution can lead to reading letters on an eye chart and face recognition.
  • AL-8309 protects the photoreceptors and RPE cells from photo-oxidative stress and may be a useful pharmacotherapy for AMD
  • Reducing the speed of the visual cycle has been shown to protect the retina from light damage, improve retinal vasculature (the arrangement of blood vessels) and reduce the accumulation of retinal-related toxic by-products, including A2E, which is implicated in AMD. RPE cells continually consume the tips of Photoreceptors as they grow (at a constant rate of speed), accumulating toxic by-products of the visual cycle. ACU 4429 slows Visual cycle modulation resulting in a decrease of toxic by-product accumulation, and a slowing of AMD.
  • Dry or atrophic AMD has become an orphan disease – we know a lot about it but we have no effective treatments. My point is not to overwhelm you with technical information but to highlight the exciting and extensive ongoing research in dry AMD.
  • This model consists of rats with a genetic disorder where they do not have one of the enzymes needed for the RPE cell layer to function. As a result, the rats become blind due to deterioration of their photoreceptors. Following transplantation of human ES cells, injected into the sub-retinal area of the eye, rats displayed recovery of their photoreceptors and improved visual ability compared to the control rats, which were injected with a mock treatment and showed no significant improvement.  
  • RPE dysfunction is the most common cause of blindness in people over 60 in the United States, and it affects over 30 million people worldwide.

Age related macula degen Age related macula degen Presentation Transcript

  • Trouble with vision as we get older...• Is not always due to Age- related macular degeneration !• Your doctor needs to perform a complete eye exam before reaching a diagnosis
  • Eye Examination - DiagnosisVisual Acuity, Color Vision, Amsler Grid,Fundus Camera, Fluorescein Angiography, Optical Coherence Tomography
  • Amsler Grid Testing
  • Drusen, the yellow spots so characteristic of Age-related Macular Degeneration
  • Drusen are sometimes more easily detectedOn Color Fundus photos than doctor’s exam
  • FluoresceinAngiography
  • Colour photography isroutinely undertaken withangiography. It helps todetermine the nature ofchanges seen on theangiogram… particularlythe cause of blockedfluorescence due tohaemorrhage, pigment orother cause.
  • Side by side comparisonof the color photo and the fluorescein pictureoften complement each other !
  • -
  • Optical Coherence Tomography
  • • Diagnostic imaging technique that examines living tissue non-invasively. It is based on a complex analysis of the reflection of low coherence radiation from the tissue under examination.• Real time cross sectional analysis
  • • Macular Degeneration Leading cause of blindness in people over 55 • 1:10 people over 55 • Increases by a factor of 6 in people over 80 • 1.75 million Americans over age 40 have severe AMD • Estimated that 2.95 million people affected by 2020
  • How Does the Eye Work?
  • • What is Macular Idiopathic• Central vision Degeneration? loss • Peripheral vision preserved• Two forms • Dry (Nonexudative) • 90% of people • Wet (Exudative) • Affects 10% of people
  • What does my Doctor• • Drusen see? Metabolic waste products accumulating under the retina• Pigment clumping and atrophy • Death of support cells under retina• Geographic atrophy • Large areas of cell death• Hemorrhage (blood) • Hallmark of wet AMD
  • My Doctor told me I have Macular Degeneration. Will I go blind?• Not necessarily• Only 10% develop the wet form which is responsible for 90% of blindness from AMD • Newer treatments may reduce risk of blindness• Only 10% of the dry patients will develop severe vision loss
  • Risk factors for Vision• Non-modifiable: things we cannot loss change • Age • (If you figure out how to stop aging, please let me know) • Caucasian race • Female gender • Family history • 2.5x increased risk of first degree family relative
  • Risk factors for Vision• Modifiable • Smoking Loss • Hypertension • High Cholesterol • Obesity • Sedentary Lifestyle• Heart Health= Eye
  • What about thoseAREDS study• Vitamins? II Followed 3640 patients for average 6.3 years • AREDS• High doses of antioxidant vitamins • Started in 2006 – ongoing• Hope they will reduce oxidative stress in • Added macula • Lutein: forms macular • Vitamin A pigment • Vitamin C • Zeaxanthin • Vitamin E • Subtracted • Zinc: antioxidant in • Vitamin A: Potential conjunction with C and increased risk of lung E cancer in smokers • Copper
  • • Vitamins Not found helpful for everyone• No benefit • No AMD • Benefit: • Mild AMD • If everyone took AREDS,• Beneficial 300,000 people could be prevented from developing • Moderate AMD advanced AMD over 5 year • Severe AMD • Persons with wet AMD • Unfortunately will not stop progression of AMD in all• Benefit patients • Reduced risk of progression of AMD by 25% • Reduced risk of vision
  • Which is the best Multivitamin?• They are all basically the same as long as they have the AREDS formula• Differences in brands • AREDS I vs AREDS II formula • Dosing • Price • Packaging • Advertising
  • • Stop Smoking Summary• Exercise• Heart Healthy Diet• Eat leafy green vegetables• Control blood pressure and cholesterol• AREDS Multivitamin if indicated by your eye doctor• Monitor vision and regular eye checks
  • • Macular Degeneration Leading cause of blindness in people over 55 • 1:10 people over 55 • Increases by a factor of 6 in people over 80 • 1.75 million Americans over age 40 have severe AMD • Estimated that 2.95 million people affected by 2020
  • How Does the Eye Work?
  • • What is Macular Idiopathic• Central vision Degeneration? loss • Peripheral vision preserved• Two forms • Dry (Nonexudative) • 90% of people • Wet (Exudative) • Affects 10% of people
  • What does my Doctor• • Drusen see? Metabolic waste products accumulating under the retina• Pigment clumping and atrophy • Death of support cells under retina• Geographic atrophy • Large areas of cell death• Hemorrhage (blood) • Hallmark of wet AMD
  • My Doctor told me I have Macular Degeneration. Will I go blind?• Not necessarily• Only 10% develop the wet form which is responsible for 90% of blindness from AMD • Newer treatments may reduce risk of blindness• Only 10% of the dry patients will develop severe vision loss
  • Risk factors for Vision• Non-modifiable: things we cannot loss change • Age • (If you figure out how to stop aging, please let me know) • Caucasian race • Female gender • Family history • 2.5x increased risk of first degree family relative
  • Risk factors for Vision• Modifiable • Smoking Loss • Hypertension • High Cholesterol • Obesity • Sedentary Lifestyle• Heart Health= Eye
  • What about thoseAREDS study• Vitamins? II Followed 3640 patients for average 6.3 years • AREDS• High doses of antioxidant vitamins • Started in 2006 – ongoing• Hope they will reduce oxidative stress in • Added macula • Lutein: forms macular • Vitamin A pigment • Vitamin C • Zeaxanthin • Vitamin E • Subtracted • Zinc: antioxidant in • Vitamin A: Potential conjunction with C and increased risk of lung E cancer in smokers • Copper
  • • Vitamins Not found helpful for everyone• No benefit • No AMD • Benefit: • Mild AMD • If everyone took AREDS,• Beneficial 300,000 people could be prevented from developing • Moderate AMD advanced AMD over 5 year • Severe AMD • Persons with wet AMD • Unfortunately will not stop progression of AMD in all• Benefit patients • Reduced risk of progression of AMD by 25% • Reduced risk of vision
  • Which is the best Multivitamin?• They are all basically the same as long as they have the AREDS formula• Differences in brands • AREDS I vs AREDS II formula • Dosing • Price • Packaging • Advertising
  • • Stop Smoking Summary• Exercise• Heart Healthy Diet• Eat leafy green vegetables• Control blood pressure and cholesterol• AREDS Multivitamin if indicated by your eye doctor• Monitor vision and regular eye checks
  • Age-related Macular Degeneration
  • What is Age-Related Macular Degeneration?• Age-related macular degeneration (AMD) is a deterioration or breakdown of the eyes macula.• The macula is a small area in the retina — the light-sensitive tissue lining the back of the eye.• The macula is the part of the retina that is responsible for your central vision, allowing you to see fine details clearly. • American Academy of Ophthalmology
  • What is going on in the eye?
  • Where exactly?
  • Where exactly?
  • Genetics• DNA• All information of life encoded in DNA and expressed by proteins.• James Dewey Watson (US) & Francis Crick (UK) – Co-discoverers Structure of DNA 1953• Awarded Nobel Prize in Physiology or Medicine 1962
  • Before…
  • …After…Age-related changes
  • Genetic Basics…get small…• The human body is made up of trillions of Cells,• and with a few exceptions, each cell contains a Nucleus• and with a few exceptions, each nucleus contains a COMPLETE set of Chromosomes• And the chromosomes are made of DNA
  • From DNA…to You and Me…
  • …and smaller…From Cells to Nucleus to Chromosomes• Every human cell contains 23 pairs of chromosomes, for a total of 46 chromosomes.• Each Chromosome is made up of• a double- stranded,• Tightly-coiled,• helix of DNA
  • Human Chromosomes
  • …and smaller…• A CHROMOSOME contains hundreds to thousands of genes.• A GENE is a segment of DNA containing the code used to synthesize a protein.• A TRAIT is any gene-determined characteristic and is usually determined by more than one gene.• Some traits are caused by abnormal genes that are inherited or that are the result of a mutation.
  • From Chromosomes to Genes
  • WhatStudies we know?…• Genetic do• 1988-2010 so far • DNA and Gene-Environment Data Collection • Twin Study – WWII Registry• 1997 Familial Aggregation Study – Relatives of Cases with Wet AMD. Relatives of controls.• 1997 Phenotypic Heterogeneity in Families with AMD • Johanna M. Seddon, M.D., Sc.M.
  • What do we know?… so far• From the US Twin Study, we’ve learned• Substantial Genetic Component – • 46 to 71% of the variation in phenotype • Important Environmental Influence: 19 to 37%
  • OK…what “Genetic Factors”?...• It’s not so much as a “bad” gene, but rather• Variations of “normal genes” that influence the risk of developing AMD.• Specific DNA chromosomes associated with the defective genes are located on chromosomes• 1q and 10q
  • From Chromosomes to Genes
  • Genes associated…so• CFH – Y402H far• CFH – rs1410996 • Hepatic Lipase C (LIPC)• CFB • CETP• C2 • ABCA1• Complement Component • TIMP 3 / SYN3 3 (C3) • VEGFA• Complement Factor I CFI • COL10A1• ARMS2/HTRA1 gene • COL8A1 region • TNFRSF10A
  • Gene location… leads to therapy• For example, the VEGFA locus and the development of• Avastin• Lucentis and recently• Eylea
  • Antigen/Antibody cell membrane Bayer Healthcare – Bayer Schering Pharma
  • Surfaceantigens/antibodies Eylea.com
  • Relative risk of Genetic loci Nature Genetics 38: 1057, 2006
  • Epidemiology• Epidemiology is the study of• the distribution and patterns of health-events,• health-characteristics and• their causes or influences in well-defined populations.
  • Epidemiology• It is our principal method of public health research, and• helps us make policy decisions as well as evidence-based medicine• by identifying risk factors for disease and helps us with recommendations for appropriate preventive medicine.
  • Epidemiologic studies looking at• Meta-analysis of 15 genome-wide the genetics of AMD association studies• Began in 2009• 8,000 cases and 50,000 controls• 19 groups from 13 countries• 19 genomic loci associated with AMD• Six novel loci not previously associated with disease• Pathways similar to other known genes. • ASHG Oct 2011
  • Epidemiology and CausationRisk factors for cardiovascular disease (CVD) are associated with age-related AMD; • Smoking • Dietary antioxidants, fats, omega-3 fatty acids • Physical activity • Obesity, abdominal adiposity • Hypertension • Cholesterol • CRP (C-reactive protein)
  • Epidemiology and Causation• For the homozygous (pure trait) risk genotype• Risk of AMD was • Increased for BMI (Body Mass Index) and • Increased with smoking
  • So what can we say?• Genetic mutations make us susceptible to the development of AMD• Multiple genetic factors are at work• Risk profiles help us to change life style to decrease the chance of AMD development• Which leads us to…
  • The big question (at least for the retina specialists)• What information from• TV,• Radio,• Internet,• YouTube,• Email,• Fax, Photocopy, Text, Blog, Wikipedia….etc• Should You believe?
  • Types of Optical Devices Near Devices
  • Stand Magnifier
  • Dome Magnifier
  • Illuminated Stand Magnifier
  • Hand Held Pocket Magnifier
  • Hand HeldIlluminated
  • Microscopes or Reading Glasses
  • Types of Optical Devices Distance Devices
  • Binoculars
  • Monocular
  • Full-Field Telescopic Systems
  • Bioptic Systems
  • Sunfilters
  • Night Vision Scopes
  • Getting the Right Device(s)devices• Because there is such a variety of available, it can be somewhat overwhelming to locate the correct device.• Individuals should receive an evaluation from an Optometrist who specializes in treating individuals with low vision.• This assures that the individual receives the correct device with consideration of all goals and needs.
  • What’s New inLow Vision Technology
  • Handheld Magnifying Cameras• Miracle Mouse Electronic TV Magnifier• MonoMouse-RM B&W Electronic Magnifier• Max Digital Color Magnifier• Primer 2 Color Electronic Magnifier
  • Traditional CCTV Video Magnifiers reading • Increased speed • Increased duration • Reduced visual effort • Comfortable• Desktop systems working position• Variable Magnification• Color, W/B, B/W• Large Field of View
  • Magnifiers Integrated LCD• Available from all major vendors Displays• Sizes: 17” to 24” + with WS• Adjustable height screens• High contrast• Flicker free• Improved response rates• Well received by consumers
  • Integrated LCD Systems
  • Video Magnification• Variable Systems Magnification• Adjustable brightness• Selectable contrast setting• Wide field of view for better viewing abilities
  • Magnification
  • Brightness
  • Contrast
  • Windowing and Underlining
  • Portable Video• More Compact, 7-inch screens Magnifiers• Extensive reading tasks• Two handed use• Optelec Traveler• FS Sapphire• EV Amigo• Fusion 7” LCD Portable Video Magnifier
  • Compact Video Magnifiers:• Variable Magnification• Replaceable Batteries• Longer battery life• Image Freeze• Color Select• Light off mode: for reading cell phones, other displays• Writing Cameras• Distance Viewing• Smaller Designs
  • Compact/PocketVideo Magnifiers • Advantages • Wide field of view • Image at display level • Use at arms-length • Reverse contrast available • Cell phone, PDA displays! • Short-term writing tasks • Kids reading comic books under the blanket
  • Compact Systems with Distance Capabilities• Near and distance capabilities• Read mail, products on a shelf and get a better view of distance object.• Allows users to see an object that is at distance close up on the screen• Limited clarity and magnification at a distance
  • GW Micro Sense View Duo• Two cameras• Stores up to 20 images• 3X to 13X magnification• Lights off mode• Image panning• 7 Viewing modes, 4 Brightness levels• 4.5 hour battery life, integrated, rechargeable• Cost: $1299.00
  • Ash TechnologyQuicklook Focus
  • Desktop Video Magnifiers• Full Size screen Features• Full Features• Remote Controllable• Near and Distance Viewing• For Classroom, Conference or In- Service Training Activities• Transportable “Luggable”• AC or optional battery
  • Vision Technology: VIEW
  • Enhanced Vision Acrobat LCD
  • Onyx Deskset
  • Laptop Compatible Video Magnifiers• Most students use laptop computers• Video magnification could be helpful• Portable camera using notebook display
  • Clarity PCMate• Powered by USB• Requires 2 USB 2 ports • Sequence, setup• Remote control camera• Keyboard controlled software
  • OptelecClearNote • Ease of camera aiming • Built in Light source • Camera control positioning • Keyboard controlled software • Keyboard controlled camera • Dolphin, Zoom Text compatible
  • Freedom Scientific Onyx PC Edition arm and flex • Swing arm models • Remote control • MAGic with EyeMerge software included • Camera can be powered by USB port • Distance, desktop, self view modes • Cost: $2895.00
  • Specialty Video Magnifiers• Flipper• Shoppa
  • Headborne Low Vision System • Eyetonomy SightMate LV920 • www.vuzix.com/medical/lv920.h tml • Zoom at near: 3X optical, 4X digital • Zoom at distance: 0.5X to 6X • Edge contrasting, Inverse mode • Sleek design, 8 ounces • $3499.00 • Not yet available for purchase or review
  • Scan and Read Devices• Kurzweil 1000 (software)• ABiSee Zoom-Ex, EyePal Vision (portable, Solo)• FS Pearl (laptop compatible)• KNFB Reader (smartphone)• AI Squared ZoomReader (app)
  • Assessment functioning• Evaluation of visual Factors• Response to low vision approaches• Analysis of tasks, task specific• Required performance level• Integration of systems• Training• Trial of system; speed, duration, productivity• Modifications• Provision
  • Types of Optical Devices Near Devices
  • Stand Magnifier
  • Dome Magnifier
  • Illuminated Stand Magnifier
  • Hand Held Pocket Magnifier
  • Hand HeldIlluminated
  • Microscopes or Reading Glasses
  • Types of Optical Devices Distance Devices
  • Binoculars
  • Monocular
  • Full-Field Telescopic Systems
  • Bioptic Systems
  • Sunfilters
  • Night Vision Scopes
  • Getting the Right Device(s)devices• Because there is such a variety of available, it can be somewhat overwhelming to locate the correct device.• Individuals should receive an evaluation from an Optometrist who specializes in treating individuals with low vision.• This assures that the individual receives the correct device with consideration of all goals and needs.
  • What’s New inLow Vision Technology
  • Handheld Magnifying Cameras• Miracle Mouse Electronic TV Magnifier• MonoMouse-RM B&W Electronic Magnifier• Max Digital Color Magnifier• Primer 2 Color Electronic Magnifier
  • Traditional CCTV Video Magnifiers reading • Increased speed • Increased duration • Reduced visual effort • Comfortable• Desktop systems working position• Variable Magnification• Color, W/B, B/W• Large Field of View
  • Magnifiers Integrated LCD• Available from all major vendors Displays• Sizes: 17” to 24” + with WS• Adjustable height screens• High contrast• Flicker free• Improved response rates• Well received by consumers
  • Integrated LCD Systems
  • Video Magnification• Variable Systems Magnification• Adjustable brightness• Selectable contrast setting• Wide field of view for better viewing abilities
  • Magnification
  • Brightness
  • Contrast
  • Windowing and Underlining
  • Portable Video• More Compact, 7-inch screens Magnifiers• Extensive reading tasks• Two handed use• Optelec Traveler• FS Sapphire• EV Amigo• Fusion 7” LCD Portable Video Magnifier
  • Compact Video Magnifiers:• Variable Magnification• Replaceable Batteries• Longer battery life• Image Freeze• Color Select• Light off mode: for reading cell phones, other displays• Writing Cameras• Distance Viewing• Smaller Designs
  • Compact/PocketVideo Magnifiers • Advantages • Wide field of view • Image at display level • Use at arms-length • Reverse contrast available • Cell phone, PDA displays! • Short-term writing tasks • Kids reading comic books under the blanket
  • Compact Systems with Distance Capabilities• Near and distance capabilities• Read mail, products on a shelf and get a better view of distance object.• Allows users to see an object that is at distance close up on the screen• Limited clarity and magnification at a distance
  • GW Micro Sense View Duo• Two cameras• Stores up to 20 images• 3X to 13X magnification• Lights off mode• Image panning• 7 Viewing modes, 4 Brightness levels• 4.5 hour battery life, integrated, rechargeable• Cost: $1299.00
  • Ash TechnologyQuicklook Focus
  • Desktop Video Magnifiers• Full Size screen Features• Full Features• Remote Controllable• Near and Distance Viewing• For Classroom, Conference or In- Service Training Activities• Transportable “Luggable”• AC or optional battery
  • Vision Technology: VIEW
  • Enhanced Vision Acrobat LCD
  • Onyx Deskset
  • Laptop Compatible Video Magnifiers• Most students use laptop computers• Video magnification could be helpful• Portable camera using notebook display
  • Clarity PCMate• Powered by USB• Requires 2 USB 2 ports • Sequence, setup• Remote control camera• Keyboard controlled software
  • OptelecClearNote • Ease of camera aiming • Built in Light source • Camera control positioning • Keyboard controlled software • Keyboard controlled camera • Dolphin, Zoom Text compatible
  • Freedom Scientific Onyx PC Edition arm and flex • Swing arm models • Remote control • MAGic with EyeMerge software included • Camera can be powered by USB port • Distance, desktop, self view modes • Cost: $2895.00
  • Specialty Video Magnifiers• Flipper• Shoppa
  • Headborne Low Vision System • Eyetonomy SightMate LV920 • www.vuzix.com/medical/lv920.h tml • Zoom at near: 3X optical, 4X digital • Zoom at distance: 0.5X to 6X • Edge contrasting, Inverse mode • Sleek design, 8 ounces • $3499.00 • Not yet available for purchase or review
  • Scan and Read Devices• Kurzweil 1000 (software)• ABiSee Zoom-Ex, EyePal Vision (portable, Solo)• FS Pearl (laptop compatible)• KNFB Reader (smartphone)• AI Squared ZoomReader (app)
  • Assessment functioning• Evaluation of visual Factors• Response to low vision approaches• Analysis of tasks, task specific• Required performance level• Integration of systems• Training• Trial of system; speed, duration, productivity• Modifications• Provision
  • Pharmacogenomics• Treatment based on genetic profile• “Personalized medicine”• AREDS – 70% with certain gene did not progress (vs. 11% without)• Relationship between certain genes and outcomes with Lucentis and Avastin
  • Gene Therapy for retinal diseases
  • • Trials Phase I Dose Escalation Safety Study of RetinoStat in Advanced Age- Related Macular Degeneration (AMD) Oxford BioMedica • Subretinal injection of virus vector that produces anti-VEGF proteins• Safety and Efficacy Study of rAAV.sFlt-1 in Patients With Exudative Age-Related Macular Degeneration • Intravitreal injection of a non-pathogenic virus to express a therapeutic protein within the eye
  • WetDry AMD Atrophi c
  • So What Have We Learned? Lory C. Snady-McCoy, MD
  • Answers to Common QuestionsWhat defines macular degeneration?
  • What tests are used?Why are they necessary in the diagnosis and management? Not everything that looks like macular degeneration is macular degeneration Importance of continued monitoring and care50% chance of developing wet AMD in fellow eye over 5 years
  • What Should I Eat?
  • • Foods rich in antioxidants may delay the progression of AMD• Green leafy vegetables, berries, nuts, seaweed (?) Beta-carotene, omega 3 fatty acids, lutein
  • Which vitamins should I use?
  • • AREDS vitamins shown to be beneficial in patients with high risk AMD• Vitamins slow the progression; they do not stop it• Benefits of AREDS II not proven yet
  • Will the high dose of vitamins in the AREDS formula have side effects?• Vitamin A in smokers - lung cancer• Vitamins A and E stored in the liver - potential liver toxicity• Zinc - anemia if not taken with copper• Vitamin E - cardiovascular issues not typical in dose prescribed, prostate cancer?• AREDS II - High dose Vitamin A removed; Lutein and Zeaxanthin added
  • Is AMD hereditary?Are my children at risk?
  • • Genetics of AMD is complex with many associated genes• Hereditary forms exist and can express themselves at different ages and in different degrees of severity• Environmental factors may trigger the disease in susceptible people
  • Known risk factors:• Smoking, diet, exercise, obesity (BMI)• Hypertension, Hypercholesterolemia• Does this sound familiar??
  • Will I go totally blind?• AMD causes central vision loss with preservation of peripheral vision• 90% of severe vision loss occurs in the wet (neovascular) type. 10% of patients have wet AMD• 90% of patients have dry (atrophic) AMD. 10% of these with develop severe vision loss
  • Are there anynew treatments in the making?
  • • Millions of dollars have been appropriated to AMD research• Medications based on a person’s individual genetic profile (pharmacogenomics)• Gene therapy to enhance a person’s own production of beneficial compounds• Retina implant / retinal prosthesis• Stem cells• Antioxidant eye drops for dry / atrophic AMD
  • Which treatment is best for me and why?• Thermal “Hot” Laser (1970’s)• PDT “Cold” Laser (Visudyne)• Macugen - First anti-VEGF intraocular treatment• Lucentis - First to show improved vision 95% stabilized 40% improved• Avastin - Cost• Eylea - Less frequent treatment
  • Argon/Krypton/Dye/Diode Laser PDT Laser/Visudyne
  • MacugenLucentis/Avas tin Eylea
  • How many injections will I need? Is there a limit to the number of treatments I can get? What is the side effect of long-term treatment?Lucentis Study - injection every 4 weeks. May still give best outcomeTreat and Extend protocolDouble-dosingCombined PDT with anti-VEGF therapyRisks: Infection, Retinal detachment, Cataract, Inflammation, GlaucomaTherapy for a chronic condition requires long term treatment. Underlying degenerative changes will continue with potential gradual vision loss even with treatment.
  • What will happen if I do nothing?• Natural history of AMD is to cause significant and permanent loss of central vision leading to legal blindness
  • Will changing my glasses help?Multiple aids to help people with decreased vision with AMD:• Spectacle-mounted magnifiers• Hand-held and spectacle-mounted telescopes• Hand-held and stand magnifiers• Video magnification / Computer devices• Importance of illumination, brightness and increased contrast• Writings devices, voice command, “gadgets”• Importance of early evaluation when moderate vision loss by a low vision specialist• Devices require training; use of eccentric vision
  • Congratulations! You have now earned your diploma!
  • So What Have We Learned? Lory C. Snady-McCoy, MD
  • Answers to Common QuestionsWhat defines macular degeneration?
  • What tests are used?Why are they necessary in the diagnosis and management? Not everything that looks like macular degeneration is macular degeneration Importance of continued monitoring and care50% chance of developing wet AMD in fellow eye over 5 years
  • What Should I Eat?
  • • Foods rich in antioxidants may delay the progression of AMD• Green leafy vegetables, berries, nuts, seaweed (?) Beta-carotene, omega 3 fatty acids, lutein
  • Which vitamins should I use?
  • • AREDS vitamins shown to be beneficial in patients with high risk AMD• Vitamins slow the progression; they do not stop it• Benefits of AREDS II not proven yet
  • Will the high dose of vitamins in the AREDS formula have side effects?• Vitamin A in smokers - lung cancer• Vitamins A and E stored in the liver - potential liver toxicity• Zinc - anemia if not taken with copper• Vitamin E - cardiovascular issues not typical in dose prescribed, prostate cancer?• AREDS II - High dose Vitamin A removed; Lutein and Zeaxanthin added
  • Is AMD hereditary?Are my children at risk?
  • • Genetics of AMD is complex with many associated genes• Hereditary forms exist and can express themselves at different ages and in different degrees of severity• Environmental factors may trigger the disease in susceptible people
  • Known risk factors:• Smoking, diet, exercise, obesity (BMI)• Hypertension, Hypercholesterolemia• Does this sound familiar??
  • Will I go totally blind?• AMD causes central vision loss with preservation of peripheral vision• 90% of severe vision loss occurs in the wet (neovascular) type. 10% of patients have wet AMD• 90% of patients have dry (atrophic) AMD. 10% of these with develop severe vision loss
  • Are there anynew treatments in the making?
  • • Millions of dollars have been appropriated to AMD research• Medications based on a person’s individual genetic profile (pharmacogenomics)• Gene therapy to enhance a person’s own production of beneficial compounds• Retina implant / retinal prosthesis• Stem cells• Antioxidant eye drops for dry / atrophic AMD
  • Which treatment is best for me and why?• Thermal “Hot” Laser (1970’s)• PDT “Cold” Laser (Visudyne)• Macugen - First anti-VEGF intraocular treatment• Lucentis - First to show improved vision 95% stabilized 40% improved• Avastin - Cost• Eylea - Less frequent treatment
  • Argon/Krypton/Dye/Diode Laser PDT Laser/Visudyne
  • MacugenLucentis/Avas tin Eylea
  • How many injections will I need? Is there a limit to the number of treatments I can get? What is the side effect of long-term treatment?Lucentis Study - injection every 4 weeks. May still give best outcomeTreat and Extend protocolDouble-dosingCombined PDT with anti-VEGF therapyRisks: Infection, Retinal detachment, Cataract, Inflammation, GlaucomaTherapy for a chronic condition requires long term treatment. Underlying degenerative changes will continue with potential gradual vision loss even with treatment.
  • What will happen if I do nothing?• Natural history of AMD is to cause significant and permanent loss of central vision leading to legal blindness
  • Will changing my glasses help?Multiple aids to help people with decreased vision with AMD:• Spectacle-mounted magnifiers• Hand-held and spectacle-mounted telescopes• Hand-held and stand magnifiers• Video magnification / Computer devices• Importance of illumination, brightness and increased contrast• Writings devices, voice command, “gadgets”• Importance of early evaluation when moderate vision loss by a low vision specialist• Devices require training; use of eccentric vision
  • Congratulations! You have now earned your diploma!
  • • Can only be used in patients with functioning inner retinal cells – for example AMD and RP • Uses an artificial means to detect light (video camera) • Converts light energy into an electrical signal • Deliver the electrical signal to the retinal neurons other than photoreceptors to elicit activity that is interpreted as vision • Vision equivalent to 20/1260
  • Retinal Implant
  • ARGUS II Implant 60 electrodes (16 in ARGUS I)250 electrode array in development
  • Subretinal implant
  • Microprocessor power
  • Emerging treatments for Dry AMDAtrophic AMD AL-8309B (Alcon Laboratories) • 2 year study evaluating an Eye drop for dry AMD • Primary endpoint is size of the atrophic area • Randomized, double blind • 772 patients • Study completed July 2011
  • ACU-4429 - Acucela  Phase II granted fast track statusFenretinide  Phase III began 2011
  • Emerging treatments for dry AMD• Encapsulated human cells genetically modifiedto secrete ciliary neurotrophic factor (CNTF)• CNTF is a growth factor capable of rescuingdying photoreceptors and protecting them fromdegeneration
  • Emerging treatments• OT- 551 Antioxidant Eye drops for Dry AMD • Othera Pharmaceuticals/ National Eye Institute• A Multicenter, Proof-Of-Concept Study Of Intravitreal AL-78898A In Patients With Geographic Atrophy • Alcon
  • Human embryonic stem • Can differentiate into any of cells the 220 cell type in the human body • Cells acquired from unwanted or discarded embryo • Can propagate indefinitely • Proposed for regenerative medicine and tissue replacement after injury or disease
  • Stem Cell Research
  • • hES Cells modified to become RPE cells whichnourish damaged photorecptors•First study of human transplantation reported inJanuary 2012• Study of safety and tolerability of subretinaltransplantation• 2 patients studied, one with AMD and one withStargardt’s disease, vision did not worsen in either one• No tumor formation or signs of rejection
  • Stem Cells – Current• Rejection Problems• Tumor formation• Expense – producing and cultivating cell lines is costly• Intellectual property rights• Ethics• No good animal models of macular degeneration