Treating the Second Eye in Geographic Atrophy

In this installment of Ready, Set, Retina, Daniel Epshtein, OD, FAAO, sits down with Michael Ammar, MD, to review a case of bilateral geographic atrophy (GA).

Dr. Ammar is a board-certified vitreoretinal surgeon and the co-director of clinical research at Retina Consultants San Diego as well as the chief of the ophthalmology department at Scripps Memorial Hospital, La Jolla.

Geographic atrophy fast facts

Geographic atrophy is an advanced form of “dry” age-related macular degeneration (AMD) that is characterized by localized, sharply demarcated atrophy of the retinal pigment epithelium (RPE).¹ Each year in the United States, an estimated 160,000 new cases of GA are diagnosed—adding to the current 1 million patients diagnosed with the condition.²

In 2023, the US Food and Drug Administration (FDA) approved two intravitreal complement inhibitors for the treatment of GA secondary to AMD:³

SYFOVRE (pegcetacoplan, Apellis Pharmaceuticals)
- Approved February 2023
- Complement factor 3 (C3) inhibitor
IZERVAY (avacincaptad pegol, Iveric Bio, an Astellas company)
- Approved August 2023
- Complement factor 5 (C5) inhibitor

Case presentation

A 75-year-old female patient presented to the clinic with a complaint of reduced vision that was worse in the right eye than in the left. The patient had been lost to follow-up, and had a history of intermediate AMD diagnosed 5 years prior.

At the time, her physician recommended that she initiate AREDS 2 supplementation BID. However, at the follow-up visit she noted that her compliance with the supplements had been poor.

Consistent with the patient’s chief complaint, her best-corrected visual acuity (BCVA) was 20/40 in the right eye (OD) and 20/30 in the left eye (OS).

Baseline multimodal imaging

Figure 1: Baseline fundus photography OD; significant drusen in the macula and subtle juxtafoveal RPE changes can be visualized.

^{Figure 1: Courtesy of Michael Ammar, MD.}

Figure 2: Baseline fundus autofluorescence (FAF) OD; we can see hyperautofluorescence consistent with drusen, mottled areas of hypoautofluorescence throughout the macula, and an expansion of foveal hypoautofluorescence.

^{Figure 2: Courtesy of Michael Ammar, MD.}

Figure 3: Baseline fundus photography OS; dense drusen with a mottled appearance can be appreciated in the macula and fovea.

^{Figure 3: Courtesy of Michael Ammar, MD.}

Figure 4: Baseline FAF imaging OS, revealing both hyper- and mottled hypoautofluorescence within the macula.

^{Figure 4: Courtesy of Michael Ammar, MD.}

Figure 5: Baseline optical coherence tomography (OCT) OD; drusen can be visualized, but more concerningly, there is a confluent area of hypertransmission in the fovea (yellow arrow). This defect is called cRORA (complete RPE and outer retinal atrophy), noted Dr. Ammar, and is understood to exist on a spectrum with GA.⁴

^{Figure 5: Courtesy of Michael Ammar, MD.}

Figure 6: Baseline OCT OS; dense drusen that resemble a drusenoid pigment epithelial detachment (PED) can be visualized, but there are no signs of hypertransmission defects or atrophy.

^{Figure 6: Courtesy of Michael Ammar, MD.}

After reviewing the patient’s fundus, FAF, and OCT imaging, Dr. Ammar explained that he was concerned that her right eye was at risk for GA and that the left eye required monitoring. At the time, there were no US Food and Drug Administration (FDA)-approved treatments for GA, so he recommended that she come back in 1 year for another follow-up and that she continue AREDS 2 supplementation.

2-year follow-up visit

The patient returned 2 years later with a BCVA of 20/70 OD and 20/60 OS.

Figure 7: Fundus photography OD 2 years later; a confluent area of RPE changes can be appreciated that is noteworthy for atrophy.

^{Figure 7: Courtesy of Michael Ammar, MD.}

Figure 8: FAF OD 2 years later; a corresponding area of dense, increased hypoautofluorescence can be seen, which is concerning for foveal-involving GA.

^{Figure 8: Courtesy of Michael Ammar, MD.}

Figure 9: Fundus photography OS 2 years later; drusen regression with possible early foveal atrophy is shown.

^{Figure 9: Courtesy of Michael Ammar, MD.}

Figure 10: FAF OS 2 years later; an increasingly mottled appearance can be appreciated, with greater foveal hypoautofluorescence.

^{Figure 10: Courtesy of Michael Ammar, MD.}

Figure 11: Near-infrared reflectance (NIR) and OCT imaging OD at the 2-year follow-up visit; the OCT imaging confirms a larger confluent area of hypertransmission, which indicates worsening foveal-involving atrophy.

^{Figure 11: Courtesy of Michael Ammar, MD.}

Figure 12: NIR and OCT imaging OS at the 2-year follow-up visit; hypertransmission defects can be visualized, which are concerning for GA.

^{Figure 12: Courtesy of Michael Ammar, MD.}
Of note, SYFOVRE had been approved by the FDA in the 2 years between the follow-up visits. Consequently, Dr. Ammar reviewed the risks and benefits as well as the side-effect profile of SYFOVRE with the patient, and she opted to initiate treatment.

In line with data from the phase 3 clinical trials for SYFOVRE (OAKS [NCT03525613] and DERBY [NCT03525600]), Dr. Ammar prefers to recommend every-other-month (EOM) dosing because it had a lower side effect profile compared to monthly injections.⁵ He decided to start treatment with the right eye because that was where the patient experienced more severe vision loss.

1 year after treatment with SYFOVRE

Figure 13: NIR and OCT imaging OD after 1 year of treatment with SYFOVRE; while there are signs of slight GA progression, her vision remains stable.

^{Figure 13: Courtesy of Michael Ammar, MD.}

Figure 14: NIR and OCT imaging OS after an additional year of monitoring without treatment; there are subtle signs of progression to GA in the left eye. Dr. Ammar noted that the patient recently started SYFOVRE treatments in the left eye as well.

^{Figure 14: Courtesy of Michael Ammar, MD.}

Treating patients with bilateral geographic atrophy

Retina specialists continue to discuss how to best manage patients with GA in both eyes, and deciding which eye to treat first is important because there are known safety risks with SYFOVRE, particularly following the first injection of the drug.

The occurrence of retinal vasculitis after the first injection is about 1:4000 for the first injection.⁶ Dr. Ammar added that, generally, if patients don’t have a reaction after the first injection, they tend not to have one throughout the treatment course.

He remarked that his risk-averse approach to choosing which eye to treat first is based on addressing the worse-seeing eye first, if possible. He explained that in the rare event that the patient has an adverse reaction to the drug, he would prefer not to compromise their better-seeing eye.

As a result, after two EOM injections in the worse-seeing eye, he checks in with the patient to see if they want to continue the existing course of treatment or switch to the better-seeing eye, and he then adjusts accordingly.

Real-world safety data on intravitreal pegcetacoplan presented by Janani Singaravelu, MD, at the 2024 American Society of Retina Specialists (ASRS) conference indicated that the conversion rate from dry to neovascular AMD during treatment was 5.2%, which was similar to the 7.2% rate demonstrated in the GALE extension study (NCT04770545).⁷

Based on the results from this study, Dr. Ammar explained that if the patient is seeking bilateral treatment, he is willing to move forward as long as the injections are on separate visits and the treated eye is staggered EOM to minimize the risk of infection, inflammation, or anything that may put both eyes at risk of vision loss simultaneously.

Imaging tools for identifying GA

OCT is a critical tool for identifying and monitoring patients with GA that he uses at every visit because it allows for a high level of detail that eyecare practitioners can utilize to visualize progression on a local level.

He added that FAF has proven to be effective in screening and monitoring patients for GA, and it helps with clearly delineating the areas of atrophy. Although he doesn’t use FAF at every visit, he tries to order it sporadically throughout the year to monitor the patient and use it as an educational tool to show how their condition changes over time.

Conclusion

This case report highlights how eyecare practitioners can monitor GA progression and navigate treating bilateral GA.

Multimodal imaging allows eyecare practitioners to proactively detect and predict the course of the disease, while intravitreal complement inhibitor treatments offer a level of hope to patients to potentially maintain vision for a longer period of time.