Although geographic atrophy (GA) is irreversible, the recent availability of treatment, in the form of complement inhibitors, is changing the long-term prognosis for patients affected by this eye disease. Because the goal of therapy is to slow down disease progression, early treatment may improve the prospect of preserving viable retina, and with it, functional vision. Success will depend on understanding what to look for in the clinic and on imaging, how to discuss treatment with patients, and, ultimately, whether community eye care practitioners are diligent in recognizing early warning signs and referring promptly.

What to Look For

Treatment option availability for GA has altered how patients with intermediate age-related macular degeneration (AMD) are followed over time. Prior to the advent of complement inhibitors, most patients with intermediate AMD were seen on an annual schedule for an examination and OCT imaging. Now, for patients with findings on OCT that are indicative of progression to GA, we prefer to see them back in the clinic every 6 months at a minimum, and even sooner if the eye is showing nascent GA on imaging. Furthermore, we are incorporating fundus autofluorescence (FAF) imaging more often and earlier in the patient’s journey to look for the hallmark hypofluorescence associated with GA and for signs of hyperfluorescence (bright areas at the lesion margin), which show areas of potential GA expansion.1

Although FAF is a crucial modality for recognizing GA—it was used during the pivotal trials of each on-market complement inhibitor to track, measure, and follow lesion growth over time—OCT still has a critical role in following patients over time, and even before GA becomes apparent. For example, certain imaging biomarkers that can be identified on OCT are associated with a higher risk of GA development, including:

  • subretinal drusenoid deposits (also known as reticular pseudodrusen),
  • large soft drusen collapse,
  • loss of the ellipsoid zone,
  • sinking of the inner nuclear layer (INL) and outer plexiform layer (OPL),
  • hyporeflective wedges,
  • and hyperreflective foci.2

As well, OCT is useful for detecting both incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA) and complete RPE and outer retinal atrophy (cRORA); each of these are considered nascent forms of GA, and their detection may identify patients who would benefit from therapy.3 Finally, OCT is used to monitor for development of neovascularization, which may be especially important for those on complement inhibitors, as there was an increased risk of choroidal neovascularization in treated patients compared to sham in each of the pivotal studies for avacincaptad pegol (Izervay, Astellas)4 and pegcetacoplan (Syfovre, Apellis).5

Patient Conversations

With complement inhibitors, the objective is to slow down the disease state, and, importantly, not to reverse or stop GA lesion growth. Because patients will not experience improved vision, and because at the current time there are not objective parameters for gauging treatment success, getting patients to commit to long-term treatment can be challenging, especially if they are asymptomatic. Nevertheless, a commitment to educating patients about what is going on in their eye, their options for treatment, and their potential for future loss of functional vision is fundamental to gaining their buy-in to long-term treatment.

Showing patients their own imaging gives them a visual perspective on the changes taking place at the back of the eye. FAF clearly shows GA lesions, and even near-infrared reflectance imaging, which shows GA as areas of hyperreflectivity,6 can be helpful for education purposes.

Working With Community Partners

In a paradigm in which we want to encourage patients to think about treatment options early in their disease continuum, perhaps even before they are symptomatic, success will hinge on whether community eye care practitioners recognize the earliest warning signs and refer promptly. For this reason, it is important to educate referral sources about the availability of treatment options, and particularly about the early imaging findings associated with progression to GA. Community eye care practitioners already play an important role in educating patients about the health of their eyes; advancing their knowledge about GA empowers them to have meaningful conversations with prospective patients about their options so they are more informed when they arrive in our clinics.

1. Fleckenstein M, Mitchell P, Freund KB, et al. The progression of geographic atrophy secondary to age-related macular degeneration. Ophthalmology. 2018;125(3):369-390.

2. Jaffe GJ, Chakravarthy U, Freund KB, et al. Imaging features associated with progression to geographic atrophy in age-related macular degeneration: Classification of Atrophy Meeting Report 5. Ophthalmol Retina. 2021;5(9):855-867.

3. Sadda SR, Guymer R, Holz FG, et al. Consensus definition for atrophy associated with age-related macular degeneration on OCT: Classification of Atrophy Report 3. Ophthalmology. 2018;125(4):537-548.

4. Izervay FDA Label. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/ label/2023/217225s000lbl.pdf. Accessed December 6, 2024.

5. Syfovre FDA Label. Available at: chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https:// www.accessdata.fda.gov/drugsatfda_docs/label/2023/217171s000lbl.pdf. Accessed December 6, 2024.

6. Abdelfattah NS, Sadda J, Wang Z, et al. Near-infrared reflectance imaging for quantification of atrophy associated with age-related macular degeneration. Am J Ophthalmol. 2020;212:169-174.