Age related macula degen

Editor's Notes

• #10: Amsler grids are everywhere. Check the vision in each eye daily.
• #186: 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.
• #187: 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.
• #189: 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.
• #233: 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.
• #235: 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)
• #236: 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.
• #237: 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.
• #238: AL-8309 protects the photoreceptors and RPE cells from photo-oxidative stress and may be a useful pharmacotherapy for AMD
• #239: 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.
• #241: 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.
• #243: 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.  
• #244: 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.