in central vision. This progressive loss of cells in the macula, called macular atrophy, is an advanced stage of dry AMD. In about 20 percent of patients with dry AMD, the lack of oxygen in photoreceptors and RPE triggers production of vascular endothelial growth factor (VEGF). This protein stimulates new blood vessels to sprout from those damaged by complement, providing an alternative source of oxygen that can slow the progressive damage to photoreceptors and prevent atrophy. The new blood vessels often leak, however, and fluid collects under and between photoreceptors. The blood vessels also produce substances that recruit cells from elsewhere to congregate around them, resulting in fibrosis (scarring) under the retina, which damages the photoreceptors and leads to macular atrophy. The resulting dysfunction, called “wet” AMD , was the cause of reduced vision in my patient’s right eye. “What about my other eye?” my patient asked. “The development of wet AMD in your right eye and the presence of large drusen in your left eye increase the risk of developing wet AMD in your left eye, but I would like you to take an antioxidant vitamin, which can decrease that risk somewhat.” “Is it possible my condition might be treated with LASIK (laser-assisted in situ keratomileusis—reshaping the cornea) or a pair of glasses with a strong prescription?” he asked. “I’m sorry but LASIK or a prescription for glasses would have
no effect on AMD,” I answered. “Both simply change the focus on the retina. If the retina is diseased, neither approach can improve vision.” Treating the Problem My complex explanation about the cause of macular degeneration elicited a simple query: “Can anything be done?” Indeed, the bad news for my patient was that he had both dry and wet AMD, both chronic, vision-threatening conditions. But the good news was that academic and pharmaceutical research had led drug companies to develop proteins that bind VEGF, and injections of these proteins could improve his vision in his right eye. His uneasy response to this was understandable: “Wait a minute, you’re telling me that the good news is that you want to stick a needle in my eye?” “It sounds worse than it is,” I said. “We can numb the eye pretty well so you will feel mostly pressure and maybe a little pain, but it only lasts a second.” The injection deposits a large excess of the VEGF-blocking protein in the center of the eye. The drug diffuses into the retina and binds the vast majority of VEGF, and gradually exits the eye carrying VEGF with it. After a month there is none of the protein left in the eye. At that point VEGF can build up again, causing the vessels to leak again and fluid to re-collect in the macula. Then it would be necessary to inject the protein again. “How many injections will I need?” he asked.
FIGURE 2. The port delivery system
The port delivery system is a refillable reservoir consisting of a (A) flange that contains a self-sealing septum on one side and a release control element on the other. It is implanted through a small incision in the sclera. When a patient looks straight ahead, the implant cannot be seen (B) , but when looking up and out (C) , the release control element can be seen within the eye, where it slowly releases a protein that blocks VEGF. When a patient looks down and in (D) , the septum is seen beneath the conjunctiva. Every six months, a needle is inserted through the conjunctiva and septum into the reservoir to replenish the protein that blocks VEGF. This allows uninterrupted delivery of the therapeutic protein to the retina of a patient with wet AMD, eliminating leakage from new blood vessels, and providing maintenance of good vision.
A Extrascleral flange
Release control element
24 DANA FOUNDATION CEREBRUM | Spr ing 2021
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