Cerebrum Spring 2021

with monthly injections. These successful clinical trials may have paved the way for Federal Drug Administration approval for this new implantation procedure by the Fall. Another treatment now in clinical trials uses a molecule that blocks VEGF receptors that stimulate the formation of new blood vessels. The chemical is incorporated into a biodegradable polymer and injected into the eye in the form of microparticles. The microparticles slowly release the inhibitor molecule, preventing leakiness from abnormal blood vessels for at least six months. Finally, a gene therapy now in clinical trials utilizes a harmless virus to deliver a gene that encodes for an anti-VEGF protein. Injected under the retina, the virus carries the gene into retinal cells, where it makes the protein. Any of these approaches would eliminate the need for monthly visits for injections and improve long-term visual outcomes. While there are as yet no approved treatments for dry AMD, two phase two clinical trials involving monthly injections showed promise. Each trial involved a different protein that blocked a different component of the complement cascade, and both slowed the progression of macular atrophy. Phase three clinical trials are currently underway. I advised my patient that a treatment plan would most likely put him on the path to taking satisfying photos again. He was encouraged about his prospects for better vision, even if his response was a bit irreverent: “I’m certainly not as despondent as I was at the beginning of our conversation and, while it feels a bit strange to say this out loud: ‘Please stick a needle in my eye.’” l v i s ua l o u tc o m e s— a s g o o d a s r e s u lt s w i t h m o n t h ly i n j ect i o n s . T w o p h a s e t h r e e c l i n i ca l t r i a l s d e m o n s t r at e d t h at w e t A M D pat i e n t s w h o h a d i m p l a n tat i o n o f t h e d e v i c e , w i t h r e f i l l s e v e r y s i x m o n t h s , h a d e xc e l l e n t

“Many, probably every or one or two months for the rest of your life,” I told him. “I hope that’s a long time, and if it is, that will mean a lot of injections,” he said. “Is there an alternative?” Fifteen Years of Progress I told my patient that there is simply no alternative to injections. Prior to 2006, when this treatment became available, wet AMD meant permanently reduced vision to the level of legal blindness or worse. But blocking VEGF with injections improves vision by drying out the retina, and usually stops new blood vessels from growing and recruiting cells that result in fibrosis. Proof of the value of treatment is that many of my patients who have received regular injections since 2006 have retained excellent vision. This patient wanted a guarantee that injections would improve his vision and maintain it for the rest of his life. That was not something I could promise. While most patients do very well with regular injections, a small percentage do not have complete elimination of fluid and growth of unhealthy blood vessels. These individuals are more prone to subretinal fibrosis and loss of vision. In addition, many patients are unable to return regularly for the needed injections. I always caution my patients that sometimes life—for any number of reasons—gets in the way. A missed appointment is generally not a problem, but longer delays make subretinal fibrosis and vision loss more likely. During the pandemic, some patients were understandably anxious about visiting a hospital or doctor’s office. Sadly, some patients missed a number of visits and consequently lost vision. Next Steps Research on the development of new treatments to provide sustained suppression of VEGF shows great promise for treatment of wet AMD. The most advanced approach involves a surgically implanted device that contains a flange—a rim that sits on the outside of the sclera (connective tissue popularly called the “white of the eye”)—attached to a refillable reservoir. The device passes through the sclera into the vitreous cavity, a fluid-containing chamber lined by the retina. (Figure 2). A release control element in the device slowly releases a VEGF- neutralizing antibody from the reservoir into the vitreous cavity. In the center of the flange is a self-sealing septum, covered by the conjunctiva to prevent infection from the environment. Periodically, the doctor will pass a needle through the conjunctiva and septum to refill the reservoir. Two phase three clinical trials demonstrated that wet AMD patients who had implantation of the device, with refills every six months, had excellent visual outcomes—as good as results



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