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Age-related macular degeneration in 2019

AMD is a chronic and progressive disease that starts with the build up of waste material under the retina, seen clinically as drusen, and disruption of the retina’s support layer, the retinal pigment epithelium (RPE), seen clinically as pigmentary changes (see image, top left). Drusen and pigment changes are the hallmark features of early and intermediate dry AMD. Patients are typically asymptomatic early in the disease. Over time, however, these changes lead to disruption and dysfunction of photoreceptors, causing reduced central reading vision with preservation of peripheral vision. In the advanced stage of dry AMD, photoreceptors and RPE cells atrophy leading to substantial vision loss in the affected areas, a process known as geographic atrophy (see image, top left). The development of geographic atrophy often takes years but is irreversible. Unfortunately, we remain without medical treatments for advanced dry AMD.

The primary risk factors for AMD include increasing age, smoking, race (much more common in Caucasians), genetic factors and diet. The Age-Related Eye Disease Studies (AREDS) demonstrated the benefit of vitamin supplementation in reducing the risk of progression to wet AMD by ~20 to 25 percent over five years. Exactly who should use AREDS vitamins is a common cause of confusion. Vitamins should only be recommended to patients with intermediate or advanced AMD. No benefit was seen in patients without AMD or with early dry AMD. The original AREDS formulation included high doses of vitamins C and E, beta-carotene, as well as zinc and copper. However, beta-carotene has been linked to an increased risk of lung cancer in patients with a history of smoking. Therefore, beta-carotene was replaced with lutein and zeaxanthanin, two macular pigment molecules, in AREDS2, which is the currently recommended supplement. Omega-3 fatty acids also were studied in AREDS2 but were not found to provide any further benefit when combined with the other supplements.

Wet AMD develops in approximately 10 percent of cases. Disruption of the barrier layer, Bruchs’ membrane, which separates the neurosensory retina from the underlying vasculature, the choroid, leads to growth of new blood vessels under or into the retina. These new blood vessels often leak and bleed resulting in retinal damage and vision loss (see image, top right). This process, known as choroidal neovascularization, is the hallmark of wet AMD and can cause significant vision loss very quickly. Choroidal neovascularization is largely driven by a protein called vascular endothelial growth factor (VEGF), and inhibiting this protein has revolutionized the treatment of wet AMD. I’ve been fortunate to train and now practice in the anti-VEGF era, in which patients with wet AMD have an excellent chance of maintaining vision. In fact, up to a third of eyes can experience visual improvement with these treatments.

Despite these successes, anti-VEGF therapy poses a significant treatment burden on patients, especially those with multiple comorbidities, because it often requires visits to the retina clinic every one to three months for intravitreal injections to maintain vision. While not yet available, new treatment options are on the horizon, including injectable medications that may last longer and require fewer treatments, a surgically implanted refillable reservoir for medication that can be refilled in the office potentially as infrequently as biyearly, as well as gene therapies targeted at long-term production of VEGF inhibitors.

Furthermore, therapeutic options are being developed to replace damaged cells lost to advanced AMD. Stem cell therapy is still in the early stages, but studies are promising in terms of producing RPE from stem cells that appear well tolerated when transplanted into the subretinal space. Artificial retinal prostheses also are under development that show promise for inducing visual perception in areas of non-functioning retinal tissue.

Another aspect of AMD care involves the technology used to monitor AMD patients. Optical coherence tomography (OCT) is a non-invasive imaging modality that utilizes long-wavelength light to create an optical map of the retina, clearly defining the retinal layers and any abnormality in or under the retina (see image, bottom row). OCT technology continues to progress with faster and higher resolution scans. OCT instruments are now able to map the retinal vasculature based on the movement of red blood cells with a technology known as OCT angiography (OCTA). OCTA allows for non-invasive imaging of the abnormal blood vessels associated with wet AMD, something that required intravenous injection of dye with specialized fundus photography in the past.

The next wave of advancement in OCT technology will likely incorporate artificial intelligence (AI). Current research algorithms achieve very high sensitivity and specificity in identifying retinal diseases from OCT scans. While not a replacement for physicians independently interpreting the images, AI will hopefully enhance the diagnostic accuracy of retinal diseases. This technology also may allow for the placement of OCT scanners in general medical facilities for screening purposes and expedite referral of at-risk patients to the retinal specialist.

It is a very exciting time to be involved in the care of patients with AMD as the technologies to diagnose, monitor and treat this blinding condition continue to advance and reduce the risk of vision loss from AMD.

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