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EYE                                                                                                                                                                                                             EYE CARE AND
         EYE CARE ANDCARE AND
      QUALITY OF LIFE                                                                                                                                                                                                 QUALITY OF LIFE
       QUALITY OF LIFE



                                                                                                                                 factor are one of the most common procedures performed in the retina
                                                                                                                                 clinic. These injections result in maintenance of vision for millions of
                                                                                                                                 patients who would otherwise become legally blind.
                                                                                                                                    The understanding that the complement pathway plays a role in
                                                                                                                                 the development of age-related macular degeneration has also led to
                                                                                                                                 revolutionary changes in the care of patients. In 2023, two medica-
                                                                                                                                 tions were FDA approved for the treatment of dry AMD. Patients
                                                                                                                                 with “dry” or atrophic AMD may or may not develop neovasculariza-
                                                                                                                                 tion (Figure 3). However, they have progressive loss of the outer retina
                                                                                                                                 and RPE cells. This produces dense scotomas or blind spots. Today,
                                                                                                                                 patients with the atrophic form receive intravitreal injections to help
                                                                                                                                 preserve the retina and preserve visual function, such as reading, driv-
                                                                                                                                 ing and recognizing faces. Inhibitors of complement C3 and C5 have   Figure 2.  Neovascular AMD demonstrating choroidal
                                                                                                                                 proven to slow the growth rate of these atrophic lesions.    neovascularization with subretinal and intraretinal
                                                                                                                                    The future is becoming even brighter for patients with age-related   hemorrhage. (Brown, Jeremiah. All About Macular
                                                                                                                                 macular degeneration. Current therapies enable a longer duration of   Degeneration, AMD Association Meeting Houston, Texas,
                                                                                                                                                                                              June 10, 2023.)
                                                                                                                                 effect, reducing the number of injections required to maintain vision.
                                                                                                                                 Gene therapy is a promising strategy to enable the retina to produce a
        Revolutionary Changes in Treatment                                                                                       protein inhibitor of vascular endothelial growth factor. This strategy
                                                                                                                                 may allow patients to go a year or more between injections compared
        of Age-Related Macular Degeneration                                                                                      to the five to six weeks required for many patients currently. Gene
                                                                                                                                 therapy may also prove to be an effective strategy for patients with the
                                                                                                                                 atrophic form of AMD, once again, reducing the number of injections
                                                                                                                                 required to maintain vision. Other strategies in clinical trials today
        By Jeremiah Brown, Jr., MS, MD
                                                                                                                                 strive to reduce inflammation in the retina via other pathways with the
                                                                                                                                 goal of greater efficacy, and hopefully fewer injections.
              evolutionary events are happening in the treatment of age-re-  Approximately one in seven patients with macular degeneration   Age-related macular degeneration is a fascinating, scientifically
              lated macular degeneration (AMD). Despite being the leading  develops the exudative form of AMD. In these patients, neovascular   challenging and impactful disease. This area of research is one of my
        Rcause of blindness in patients over age 60, significant advances   tissue grows from the choroid into the retina, causing exudation, intra-  passions, and it is so rewarding to see the effects of years of research
        have occurred, leading to many additional years of useful functional  retinal edema and subretinal fluid (Figure 2). The neovascular tissue   reaching the clinic and preserving patients’ vision.
        vision for our patients.                               and surrounding edema produce blurred vision, distorted vision and                                                             Figure 3.  Atrophic dry AMD. This image demonstrates
           Age-related macular degeneration is a multifactorial degenerative   ultimately, blind spots. Unfortunately, this exudation usually develops                                        atrophy involving the foveal center. Numerous yellow
        disease of the retina. Approximately 70 percent of the risk of devel-  in the macula, resulting in loss of the most precious area of detailed                                         drusen are also noted. Courtesy of Dr. Jeremiah Brown.
        oping macular degeneration is genetic. Environmental factors such as   central vision in our patients. Massive hemorrhages can also occur,   subretinal
        smoking, diet and UV light exposure also play a role. Lastly, the inci-  resulting in abrupt severe vision loss.            drusenoid
        dence of macular degeneration increases with age. In the early stages   For many years, it was suspected that macular degeneration had   deposits
        of this condition, small extracellular deposits called drusen build up  a genetic component. However, this was difficult to prove as most
        at the level of the retinal pigmented epithelial cells (RPE) and Bruch’s  patients’ parents were no longer living and their children were too young
        membrane beneath the neurosensory retina. As time progresses, these   to demonstrate phenotypic features of AMD. In the late 1990s, dramatic
        deposits, along with chronic inflammation and oxidative stress, cause  discoveries of activated complement fragments within drusen deposits
        degeneration of the overlying photoreceptors, the light sensing cells in   helped to refine the search for genetic causes. In 2006, several groups
        the retina and RPE (Figure 1). This slow gradual degeneration caus-  simultaneously identified complement factor H as the locus conveying
        es distortion and gaps in an affected patient’s vision. Eventually blind  the most risk for developing age-related macular degeneration. Since
        spots may develop and visual acuity can be reduced to as low as count-  that time, numerous other genes in the complement pathway have been
        ing fingers, meaning that patients are unable to read any letters on the   implicated, and have been proven to add additional risk or convey bene-   Figure 1.  Signs of intermediate   Dr. Jeremiah Brown is a graduate of Harvard University. A U.S.
        vision chart and can only count fingers held in front of them.  fit to the development of age-related macular degeneration.                          AMD with drusen and subretinal   Army veteran, Dr. Brown served as director of ophthalmology
           Nutritional supplements were demonstrated in two large clinical   Another revolutionary finding was understanding that vascular                   deposits. Fleckenstein M, Keenan   research at the U.S. Army’s Laser Research Laboratory at Brooks
        trials to have a beneficial effect in reducing the rate of progression to   endothelial growth factor played a role in the development of choroidal   TDL, Guymer RH, Chakravarthy   Air Force Base, a division of the Walter Reed Army Institute of
        advanced stages of macular degeneration. These supplements contain  neovascularization. Dramatic clinical trials in the early 2000s demon-           U, Schmitz-Valckenberg S,   Research. He has co-authored more than 25 peer-reviewed articles in
        vitamin C, vitamin E, zeaxanthin and zinc with supplemental copper.   strated that with an antibody-derived inhibitor of vascular endothelial        Klaver CC, Wong WT, Chew   ophthalmology research as well as textbook chapters. He is a frequent
        Epidemiologic surveys have also confirmed that a diet with green leafy  growth factor, the abnormal vessels could be regressed and visual acuity     EY. Age-related macular   lecturer to ophthalmology residents as well as practicing ophthalmologists.
                                                                                                                                                             degeneration. Nat Rev Dis
        vegetables such as spinach and kale, as well as oily fish such as salmon   could be improved. Prior to this discovery, there had been no therapy     Primers. 2021 May 6;7(1):31.   Dr. Brown practices vitreoretinal diseases in San Antonio and Schertz,
        and tuna, at least one to two times per week, also have a beneficial   that could actually improve vision for patients with neovascular AMD.         doi: 10.1038/s41572-021-  and is a member of Retina Consultants of Texas and the Bexar County
        effect in slowing progression.                         Today, intravitreal injections of inhibitors of vascular endothelial growth                   00265-2. PMID: 33958600   Medical Society.



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