A Collaborative Approach to Geographic Atrophy Management

Dry age-related macular degeneration (AMD) is among the leading causes of visual impairment worldwide. As the baby boomer population ages, eye care providers should expect to see an increased prevalence of all forms of macular degeneration and a growing need for effective treatments to slow or stop the progression of dry AMD.

As with other progressive diseases of the eye, early diagnosis coupled with early intervention can dramatically alter the disease course. Patients with early macular degeneration may be asymptomatic, often resulting in delayed diagnosis and potentially poorer outcomes. Because the late stages of dry AMD can be devastating to visual function, research is underway to find effective treatments for geographic atrophy (GA). As the list of potential interventions in dry AMD grows, optometrists and ophthalmologists can play valuable, collaborative roles in managing these patients.

GUIDING FACTORS

When GA secondary to dry AMD is detected, several factors help guide both treatment and potential referrals. The most important factor affecting treatment decisions is the location—central (fovea-involving), juxtafoveal, or extrafoveal—of GA lesions. Typically, progressive GA secondary to AMD follows a ring pattern and involves the fovea within approximately 2 years, but central GA can present earlier in the process as well (15%–20% of cases).¹ Regardless of location, treatment is aimed at slowing and/or preventing the spread of GA lesions to preserve the patient’s visual acuity and reduce the expansion of scotomas that might inhibit visual function.

Additional considerations include the age of the patient, the activity of GA lesions, and the rate of progression. Young patients with slowly progressive extrafoveal GA may derive a greater long-term benefit from aggressive treatment, whereas older patients with slowly progressive extrafoveal GA may benefit less. Conversely, rapidly progressive disease in both young and old patients may warrant aggressive treatment depending on the location and extent of the GA lesions. The rate of progression of GA can be measured on color fundus photographs as a function of change in GA area over time and/or change in GA proximity to the fovea over time. Depending on the manufacturer, some OCT devices may also estimate these values.

RISK ASSESSMENT

Risk assessment is critical for patients with GA. A combination of fundus autofluorescence (FAF) and OCT is used to determine disease activity and the risk of progression. FAF images are evaluated for the presence of a hyperautofluorescent halo at the margins of the GA lesions, which represents lipofuscin accumulation within the retinal pigment epithelium (RPE) and RPE dysfunction (Figures 1–3). Hyperautofluorescence is strongly predictive of GA formation.² Lesions that show a reduction or absence of hyperreflectivity following treatment may demonstrate slower rates of progression (Figure 4).

The Consensus on Atrophy Meeting (CAM) group used OCT to broadly define the umbrella term macular atrophy as a loss of the outer retina, loss of the RPE, and choroidal hypertransmission. Whereas macular atrophy is a nonspecific term and can apply to atrophic changes associated with any condition from dry AMD to inherited retinal disease, the term GA applies specifically to macular atrophy secondary to dry AMD. CAM further classified GA into two primary categories: complete RPE and outer retinal atrophy (cRORA) and incomplete RPE and outer retinal atrophy (iRORA). For lesions to qualify as cRORA, they must meet all criteria for macular atrophy on OCT with at least 250 µm of both RPE loss and choroidal hypertransmission (Figure 5). As the name implies, iRORA applies to macular atrophy that does not meet all three criteria to be classified as cRORA (Figure 6). Some early evidence suggests that iRORA may carry an increased risk of progression to cRORA and/or GA.³

An OCT biomarker called nascent GA was recently described and is currently the best-known risk factor for progression to cRORA and/or GA. Nascent GA is defined on OCT by the presence of subsidence—a sinking appearance of the outer plexiform layer and inner nuclear layer—and/or a hyporeflective wedge in the Henle fiber layer. Features of iRORA are often present in nascent GA, but they are not defining characteristics of nascent GA (Figure 7). The probability of lesion progression to GA within 24 months increased to 38% when nascent GA was present on OCT.⁴ The Table summarizes the differences in the CAM group’s OCT classification of macular atrophy and GA versus nascent GA.

In addition to nascent GA, OCT findings that may predict an increased risk of progression to advanced AMD (including both GA and wet AMD) are abnormal total retinal thickness, disruption of the external limiting membrane, drusenoid pigment epithelial detachment, retinal pigmentary hyperreflective material, and choroidal vessel abnormalities.⁵

MEDICAL TREATMENT

In addition to optical treatments, several medical treatments are currently available for GA that can be tailored to the patient based on their clinical presentation and goals. A study published in January suggested AREDS2 supplementation may slow noncentral GA progression toward the fovea. Researchers also found that supplementary beta-carotene (15 mg) and a reduction in zinc supplementation from 80 mg (in the original AREDS2 formula) to 25 mg slowed the rate of GA expansion by area. No benefit was elicited with AREDS2 supplementation in patients with central GA.⁶ It is important to note that beta-carotene supplementation in smokers increases the risk of lung cancer.⁷

In 2023, the FDA approved two intravitreal injections that target the complement cascade for the treatment of GA: pegcetacoplan (Syfovre, Apellis) and avacincaptad pegol (Izervay, Astellas). Both medications are administered indefinitely and have been shown to slow the progression of GA by roughly 15% to 20% by inhibiting different steps of the complement cascade.^8-10 Pegcetacoplan is a C3 inhibitor and is dosed every 25 to 60 days depending on provider discretion. Avacincaptad pegol targets, binds to, and prevents the cleavage of complement protein C5, which is slightly farther downstream in the complement cascade. This drug is administered either monthly or every 2 months based on provider discretion.

The risk profiles of pegcetacoplan and avacincaptad pegol are similar to those of other intravitreal injections. Potential complications include endophthalmitis, retinal detachment, and a transient increase in IOP. Both medications have also been associated with a 7% to 12% increased risk of wet AMD. Should wet AMD be detected during the course of therapy, some specialists treat both wet AMD and GA during the same visit, whereas others may delay anticomplement therapy or stagger visits. Ischemic optic neuropathy may be an additional risk for patients receiving pegcetacoplan, so avacincaptad pegol may be considered in patients whose optic disc is already at increased risk for the condition.^9,10

THE PATH FORWARD

From diagnosing GA to discussing treatment options and prognosis to optimizing vision correction—optometrists play a critical role in comanaging GA patients with retina specialists.

Closely monitoring patients with fundus photography and OCT imaging can assist in determining an initial rate of disease progression, while FAF can aid in risk assessment. Even those actively receiving intravitreal injections for GA, however, should continue to see their optometrist at least yearly for OCT imaging, fundus photography, and screening for wet AMD. The early identification of high-risk GA patients allows earlier intervention, which may preserve functional vision. Those with advanced vision loss may benefit from a referral to low vision services.