An Introduction to Wet Macular Degeneration for Ophthalmology Residents

Mar 11, 2020
11 min read
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Macular degeneration (AMD) is one of the main causes of central vision loss in the developed world and affects approximately 25% of people above age 75. This debilitating ocular disease appears clinically in one of two presentations, either dry or wet forms. Wet AMD, also known as “exudative” or “neovascular” AMD, is significantly more sight-threatening than the dry, non-exudative form.

Advanced AMD affects approximately 2 million Americans. Advanced AMD occurs when dry AMD progresses to geographic atrophy (GA) or when wet AMD leaves a disciform scar after the presence of prolonged choroidal neovascular membrane (CNVM).

The easiest way for patients to understand the disease process of macular degeneration is by explaining the compromised exchange of nutrients and waste products within the eye. Numerous mechanisms are proposed in the clinical manifestation of AMD. In general, AMD occurs when the retina/retinal pigment epithelium’s (RPE) ability to metabolize waste products is compromised. It can also occur when the choriocapillaris is unable to adequately deliver nutrients to (or adequately remove waste products from) the retina.

The progression of AMD can be variable, depending on the patient’s age, systemic/lifestyle risk factors, and family ocular history. Age is the greatest risk factor for developing AMD, followed by Caucasian race and history of past/present smoking. A positive family history also increases patients’ risk for developing AMD.

Several emerging therapies are making headway in addressing the unmet need of more durable suppression of this sight-threatening disease. Over the past decade, anti-vasoendothelial growth factor agents (anti-VEGF) have dramatically transformed the treatment approach to macular degeneration, particularly wet AMD.

I thought it would be interesting to write an update on what we have to look forward to in the management of Wet AMD. I love to tell my patients about these upcoming advancements on the horizon, keeping them excited for the future and letting them know they are not destined to see me every four-to-six weeks for the rest of their lives!

Pathogenesis of macular degeneration

The etiology and pathogenesis of macular degeneration is multifaceted and thought to occur via several mechanisms. Regardless of AMD presentation, the retinal pigment epithelium (RPE) and choriocapillaris are greatly compromised. Through various age-related retinal changes, the RPE’s ability to maintain photoreceptor cells is slowly diminished.

The “sick RPE” theory proposes that the RPE layer is unable to fully metabolize photoreceptor waste products. This occurs by the altered permeability and degeneration of RPE/Bruch’s complex, leading to the formation of subretinal drusen deposits, pigment epithelial detachments, CNVM, and eventual geographic/outer retinal atrophy.

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Figure 1: Fundus photo showing small/medium sized drusen deposits in intermediate dry AMD. Large drusen are defined as > 125 micrometers in size (diameter of central retinal vein) Photo courtesy of Kevin Cornwell, OD