On this episode of Ready, Set, Retina, Daniel Epshtein, OD, FAAO, is joined by Mark Dunbar, OD, FAAO, to review a case of geographic atrophy (GA) that received treatment with a complement inhibitor.
Dr. Dunbar has been on staff at the University of Miami’s Bascom Palmer Eye Institute for over 25 years and currently serves as the Director of Optometric Services.
The shifting GA treatment landscape
The prevalence of GA is believed to be about 5 million people worldwide; however, in the United States, there are approximately 1 million people with GA, and roughly 160,000 new cases every year.1,2 The incidence of GA is projected to increase in the next 20 years due to an expanding elderly population and heightened awareness of the disease state.3
Both age-related macular degeneration (AMD) and GA have been at the center of many conversations since early 2023 due to the development and approval of two novel complement inhibition therapies to slow the progression of GA, noted Dr. Dunbar.
These treatments take the form of intravitreal pegcetacoplan (SYFOVRE, Apellis Pharmaceuticals, Waltham, MA) and avacincaptad pegol (IZERVAY, Astellas Pharma US, Northbrook, IL).1 Although both treatments are complement inhibitors, pegcetacoplan works by inhibiting complement factor 3 (C3), whereas avacincaptad pegol is a complement factor 5 (C5) inhibitor.
Geographic atrophy case report
Case presentation
Dr. Dunbar assumed post-operative care for an 85-year-old Hispanic female patient following successful and uneventful bilateral cataract surgery in January 2022. Eight months later, Dr. Dunbar identified subtle bilateral macular changes, and subsequently performed near-infrared reflectance (NIR) and optical coherence tomography (OCT) imaging, revealing drusenoid changes in the right eye consistent with intermediate dry AMD.
The patient’s best-corrected visual acuity (BCVA) was 20/25 in the right eye (OD) and 20/20 in the left eye (OS). Dr. Dunbar added that he typically follows up with intermediate dry AMD patients every 6 months to monitor for fluid or elevation, either of which may signal conversion to “wet” or neovascular AMD (nAMD).
Baseline imaging
Figures 1 and 2: NIR imaging OD and OS, respectively, of the patient at baseline.
Figure 1: Courtesy of Mark Dunbar, OD, FAAO.
Figure 2: Courtesy of Mark Dunbar, OD, FAAO.
Figures 3 and 4: OCT imaging OD and OS, respectively, of the patient at baseline; hyperreflective foci can be visualized OD, which is an indication that the patient is at greater risk for AMD progression.4
Figure 3: Courtesy of Mark Dunbar, OD, FAAO.
Figure 4: Courtesy of Mark Dunbar, OD, FAAO.
2-month follow-up appointment
The patient returned 2 months after the initial visit with a chief complaint of distortion in her right eye. Her BCVA had decreased to 20/30 OD, although it remained stable at 20/20 OS. Accordingly, Dr. Dunbar repeated the NIR and OCT imaging to check for choroidal neovascular membrane formation.
Figures 5 and 6: NIR imaging OD and OS, respectively, of the patient at the 2-month follow-up visit.
Figure 5: Courtesy of Mark Dunbar, OD, FAAO.
Figure 6: Courtesy of Mark Dunbar, OD, FAAO.
Figures 7 and 8: OCT imaging OD and OS, respectively, at the same 2-month follow-up; there is no sign of fluid accumulation on either scan, although significant drusenoid changes can be visualized OD.
Figure 7: Courtesy of Mark Dunbar, OD, FAAO.
Figure 8: Courtesy of Mark Dunbar, OD, FAAO.
6-month follow-up visit
Six months later, Dr. Dunbar repeated OCT imaging and ordered color fundus photography (CFP) as well as fundus autofluorescence (FAF). The patient’s BCVA had remained stable in both eyes at 20/30 OD and 20/20 OS. OCT imaging revealed drusenoid changes and hypertransmission defects in the choroid that suggested progression to GA in the right eye.
This appointment was in March 2023, which is important because SYFOVRE was approved by the Food and Drug Administration (FDA) in February 2023.5
Figures 9 and 10: OCT imaging of the right and left macula, respectively. In the right eye, we can see that the drusen have begun to collapse. Additionally, a portion of the inner/outer segment (IS/OS) junction is missing, and there are hypertransmission defects visible at the level of the choroid.
Figure 9: Courtesy of Mark Dunbar, OD, FAAO.
Figure 10: Courtesy of Mark Dunbar, OD, FAAO.
Figures 11 and 12: CFP and FAF images of OD and OS, respectively. The CFP in the right eye shows two distinct islands of GA OD. FAF confirms these findings, while delineating foveal-sparing hypofluorescent lesions OD. Thankfully, the left eye remained stable with no evidence of progression to GA or nAMD.
Figure 11: Courtesy of Mark Dunbar, OD, FAAO.
Figure 12: Courtesy of Mark Dunbar, OD, FAAO.
Dr. Dunbar then utilized a Zeiss Cirrus OCT device to perform Advanced RPE Analysis, which can help with evaluating the degree of progression by comparing retinal pigment epithelium (RPE) elevation maps and sub-RPE illumination maps.
Figure 13: Advanced RPE Analysis report OD, taken with the Cirrus OCT device.
Figure 13: Courtesy of Mark Dunbar, OD, FAAO.
Complement inhibition treatment
Subsequently, Dr. Dunbar referred the patient to a retina specialist to inquire as to whether she would be a good candidate for SYFOVRE. He emphasized that not all retinal specialists currently utilize complement inhibition therapies for their patients with GA.
In this case, the retinal specialist decided to pursue treatment, and this patient was one of the first to receive SYFOVRE injections at Bascom Palmer Eye Institute. The patient has to date received six or perhaps seven SYFOVRE injections, and her last injection was on July 9, 2024. The patient’s VA was 20/40 OD in April 2024.
Figure 14: OCT imaging OD from December 2023, which shows that the patient’s condition has remained relatively stable, although there was slight enlargement of the transillumination defect.
Figure 14: Courtesy of Mark Dunbar, OD, FAAO.
Figure 15: CFP and FAF imaging of the patient from April 2024; the GA lesions are slightly more defined, and continue to be foveal-sparing. On FAF, the more inferior lesion has grown slightly since March 2023.
Figure 15: Courtesy of Mark Dunbar, OD, FAAO.
Discussion
Dr. Dunbar noted that complement inhibition treatments tend to take a while (i.e., 6 to 12 months) before the treatment effect can be seen, with the greatest impact taking place after 2 to 3 years. One study demonstrated that, compared to sham treatment, C3 and C5 inhibition likely reduces the change in square foot GA area at 12 months and untransformed GA area at 24 months.6
He added that his main guideline for referring GA patients to a retina specialist is identifying those with vision-threatening GA. For patients with large central lesions who already have marked vision loss, he typically opts not to refer for treatment, because they would have to bear the entire treatment burden with little to no potential benefit.
He added that he factors in whether the patient is motivated to pursue regular treatments (i.e., monthly or bimonthly intravitreal injections). Similarly, Dr. Epshtein chooses to refer patients who are likely to develop vision-threatening GA (i.e., will progress in the next 1 to 2 years) to give them the option of starting treatment early in the hopes of preserving retinal integrity and associated acuity.
Conclusion
This case report highlights the drusenoid changes associated with intermediate AMD, and the subsequent conversion to GA in an elderly patient. Moreover, it demonstrates how complement inhibition therapy potentially slows the progression of GA, even within 1 year of treatment initiation.
Dr. Dunbar remarked that the changing treatment landscape for GA has pushed him to reframe his understanding of dry AMD, and to shift from primarily looking for signs of conversion to wet AMD to also proactively assessing patients for progression to GA.
