What is your approach for treating GA with concomitant neovascular AMD?
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Injections not on the same day
The clinical trials have purposefully strict inclusion and exclusion criteria to control the variables that might affect the outcomes of an intervention.
However, the real-world target patient population to whom the study results might be applied could be significantly more complex and heterogenous. Patients with concomitant geographic atrophy (GA) and neovascular age-related macular degeneration with active exudation are a prime example of this.
In the pivotal GA studies, a history of neovascular AMD in the study eye, or in some cases either eye, was an exclusion criterion. However, in the real world, retina specialists frequently take care of neovascular AMD patients who develop progressive GA in an eye actively being treated for exudation as well as GA patients who develop active exudation in the course of their disease. The number of the former patients might in fact be underestimated in the large databases that rely on ICD-10 coding as it has been reported that patients with coexisting GA and neovascular AMD may be less likely to have a documented ICD-10 diagnosis of GA within the electronic medical record. In one study by Park and co-authors, among patients with neovascular AMD and those with evidence of GA on OCT, only 8% had GA documented as a diagnostic code.
In addition to patients with GA developing neovascular AMD as a natural course of the disease, treatment with complement inhibitors has been associated with a higher rate of exudation as compared with controls.
There is currently little guidance as to the management approach of patients who might potentially benefit from treatment of both GA and neovascular AMD. Given the relatively slow progression of GA and risk of profound vision loss with untreated neovascular AMD, treatment of macular neovascularization should not be delayed. In FILLY, dosing of pegcetacoplan was discontinued after the diagnosis of exudation, whereas in the phase 3 DERBY and OAKS trials and the ongoing extension GALE trial, the patients continued study drug treatment during the trial and received on-label anti-VEGF therapy at investigator discretion.
If one elects to use two therapeutics, the question arises if same-day injections can be performed. While it might be convenient not to have the patient come back another day for the second treatment, one should be aware of the IOP fluctuations that happen after an intravitreal injection. It is important for the IOP to come to physiologic levels before performing the second injection. Moreover, insurance might not cover same-day injections. Another argument against same-day treatment is that, in case of a complication, it would be hard to determine which therapeutic might have been the cause. Follow-up appointment scheduling might become more complex as the most frequently utilized anti-VEGF regimen includes a treat-and-extend approach, and that would not be applicable to the GA drugs.
The real-world experience and potential investigator-initiated trials in the future might guide us on the best approaches to patients who have both GA and neovascular AMD in need of treatment.
- References:
- Hwang CK, et al. Ophthalmol Retina. 2021;doi:10.1016/j.oret.2020.10.008.
- Park JG, et al. Ophthalmol Retina. 2023;doi:10.1016/j.oret.2023.03.011.
- Patel SS, et al. Eye (Lond). 2023;doi:10.1038/s41433-023-02497-w.
- Steinle NC, et al. Am J Ophthalmol. 2021;doi:10.1016/j.ajo.2021.02.031.
- Study to compare the efficacy and safety of intravitreal APL-2 therapy with sham injections in patients with geographic atrophy (GA) secondary to age-related macular degeneration. https://clinicaltrials.gov/study/NCT03525600. Updated June 18, 2023. Accessed Aug. 7, 2023.
- Syfovre prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217171s000lbl.pdf. Accessed Aug. 7, 2023.
- Wykoff CC, et al. Ophthalmology. 2021;doi:10.1016/j.ophtha.2021.02.025.
- Xu L, et al. Retina. 2015;doi:10.1097/IAE.0000000000000374.
- Zimura in participants with geographic atrophy secondary to dry age-related macular degeneration. https://clinicaltrials.gov/study/NCT02686658. Updated May 11, 2023. Accessed Aug. 7, 2023.
- For more information:
- Aleksandra Rachitskaya, MD, is an ophthalmologist with Cleveland Clinic.
Staggered injections
It is exciting to be able to offer patients therapeutic options for geographic atrophy associated with age-related macular degeneration.
There are now two FDA-approved agents for the treatment of geographic atrophy (GA): Syfovre (pegcetacoplan, Apellis Pharmaceuticals) and Izervay (avacincaptad pegol, Iveric Bio). In the phase 2 FILLY trial, one unexpected finding was an increased rate of choroidal neovascular membrane (CNVM) formation in patients receiving active treatment. This dose-dependent conversion to wet AMD with complement inhibition was confirmed in the phase 3 OAKS, DERBY, GATHER1 and GATHER2 clinical trials for both C3 and C5 complement inhibition. Increased CNVM rates have been seen in the GALE pegcetacoplan extension trial as well.
Given these clinical trial results, how should we best treat patients in our clinics with concurrent GA and wet AMD? In my clinics, I have been alternating injections for GA and wet AMD. Although in the clinical trials patients could receive complement inhibition and anti-VEGF injections on the same day, the implementation of two separate injections in one eye on the same visit is challenging in the real-world setting. Concerns include 1) increased IOP with more volume administered, 2) hindrance to patient flow in busy retina practices, 3) unknown payer responses to two different injectable drugs on the same day in the same eye, and 4) increased patient discomfort due to two separate antiseptic ocular preps performed back to back.
In light of these concerns, I have been treating patients every 3 to 4 weeks with complement inhibition, alternating every 3 to 4 weeks with an anti-VEGF inhibitor. Thus, patients receive complement inhibition every 6 to 8 weeks and anti-VEGF every 6 to 8 weeks as well. If a patient has both dry and wet AMD bilaterally, I stagger therapies so that a patient receives an injection of complement inhibition in one eye and anti-VEGF in the fellow eye. In this manner, I am not treating with the same agent in both eyes on the same day. This allows me to monitor for rare safety events unilaterally as we become more familiar with complement inhibition in the clinic setting.
I look forward to hearing how other providers approach this growing patient population.
- For more information:
- Nathan C. Steinle, MD, is an ophthalmologist with California Retina.
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