Geographic atrophy (GA) is an advanced form of dry age-related macular degeneration (AMD) characterized by the loss of photoreceptors and retinal pigment epithelial (RPE) cells in the macula. Progression of GA ultimately leads to permanent vision loss and associated deterioration in quality of life.¹ Despite advances in the treatment of neovascular AMD, currently there is no approved treatment for GA.

Recently, the US Food and Drug Administration (FDA) granted priority review designation to intravitreal pegcetacoplan anti-complement component-3 therapy for GA developed by Apellis Pharmaceuticals. This designation was based on results from the phase 3 DERBY and OAKS studies, including the latest data at 24 months,² and the phase 2 FILLY study at 12 months.³ In these studies, both monthly and every-other-month pegcetacoplan resulted in clinically meaningful reduction of GA lesion growth and a favorable safety profile. If approved, pegcetacoplan would become the first available treatment for GA. The FDA has also granted breakthrough therapy designation for avacincaptad pegol (Zimura; Iveric Bio), a complement C5 inhibitor, based on more recent results from the GATHER1 and GATHER2 phase 3 studies.⁴

Approved new treatments will results in a major shift in our treatment paradigm and practice patterns. As such, there are various aspects of daily clinic workflow and practice operation that may be impacted.

REFERRAL CONSIDERATIONS

Retina specialists work with optometrists and other non-retina ophthalmologists daily. Many of these providers routinely advise and manage patients with early to intermediate dry AMD. Some may also feel comfortable following patients with early focal GA. In these cases, retina specialists should inform these referring providers when a treatment for GA becomes available. This is important not only to initiate the discussion regarding treatment but also to educate eyecare professionals on how to identify early GA on various imaging devices to identify patients at risk and monitor for progression.

IMAGING CONSIDERATIONS

In the current management of dry AMD, optical coherence tomography (OCT) is obtained routinely for almost every patient visit to monitor for the development of neovascularization. Fundus autofluorescence (FAF) has also emerged as a critical imaging modality for monitoring of GA and its progression. Distinct phenotypic patterns of atrophy on FAF may have an impact on GA progression and therefore prognostication.⁵ Regardless, under current practice patterns, providers may not routinely obtain FAF because there is no effective treatment even when progression occurs. However, once treatment is available, FAF will become even more critical in monitoring GA progression and treatment response.

There are some implications with increased utilization of FAF. First, FAF can be obtained on several imaging platforms. Some are integrated with OCT capability and others with color fundus photography. Because OCTs are routinely performed in this patient population, the optimal workflow may involve devices with both OCT and FAF capabilities. Otherwise, patients will need to be moved to a different device, leading to increased testing time, creating a potential bottleneck for clinic workflow. If there are no immediate plans for purchasing a combined imaging platform, practices may need to consider the proximity between the OCT and FAF imaging devices to minimize staff and patient movement through the clinic. For practices currently considering replacing or upgrading existing OCT machines, this should factor into the decision-making process.

Progression of GA can be identified and monitored on OCT scans, but perhaps not as intuitively as on FAF (Figure 1). At present, there is no commercially available software to track the progression of GA and measure the rate of progression on either OCT or FAF. However, this information will be essential in future treatment decisions. Patients with faster progression may need more frequent dosing compared to patients with slower progression. Some investigators have demonstrated the ability of artificial intelligence and deep-learning algorithms to automatically quantify GA and measure progression.^6,7 Such tools are essential for further understanding of disease progression and to optimally guide GA management.

OPERATIONAL CONSIDERATIONS

Once a treatment for GA is approved, there may be an influx of new patients into retina practices. These may include patients who were previously monitored elsewhere and are now being referred in for treatment. Furthermore, if treatment is warranted, this may create additional stresses, especially to already busy practices, due to the frequency of intravitreal injection visits. Practices with limited capacity for new appointments may want to expand by hiring additional providers to accommodate the increased volume. A temporary solution to minimize patient wait times could be to increase injection-only visits. However, this needs to be balanced with the risk of missing early choroidal neovascularization (CNV) during injection-only visits without imaging. Lastly, practices may want to initiate the discussion of treatment as patients return for previously scheduled follow-up appointments rather than moving up their appointments for initiation of treatment.

It is unclear now what the initial uptake of treatment will be. Some patients will be eager for treatment while some patients with early asymptomatic focal GA not involving the fovea may decide against treatment, at least initially. Ultimately, retina practices should be prepared for a potential surge in demand for GA treatment.

TREATMENT CONSIDERATIONS

In the phase 3 trials for pegcetacoplan, both the monthly and the every-other-month arms showed reduction in GA lesion growth. In the real world, it is still unclear what the optimal treatment strategy will be. The monthly arm had more significant reduction in GA growth, but also saw an increased rate of CNV. While excellent treatments for neovascular AMD exist, they involve significant additional treatment burden. The same problem will apply for those with existing concurrent neovascular AMD and GA. Different adaptation strategies will be needed whether patients will be treated for both conditions concurrently at the same visit or on alternating visits. Pegcetacoplan is very viscous and given in a 0.10 mL dose. Due to the viscosity and volume of the treatment, approximately 30 minutes is needed between administration of anti-VEGF and pegcetacoplan, similar to the treatment protocol in OAKS and DERBY for patients who required both. Treatment intervals of anti-VEGF in patients with preexisting CNV may also need to be adjusted with the addition of treatment for GA.

SUMMARY

With the potential approval of intravitreal anti-complement injections for the treatment of GA, various aspects of day-to-day operations in retinal practices may be impacted. Practices are likely to see an increase in the number of patient visits and volume of injections. Preparations and optimizations for this increase in volume of patients will make for a smoother transition into this new treatment paradigm. RP

Editor’s note: This article is part of a special edition of Retinal Physician that was supported by Apellis Pharmaceuticals. Authors and editors maintained editorial control for all articles in this special edition.

REFERENCES

1. Sarda SP, Heyes A, Bektas M, et al. Humanistic and economic burden of geographic atrophy: a systematic literature review. Clin Ophthalmol. 2021;15:4629-4644. doi:10.2147/OPTH.S338253
2. Apellis announces FDA acceptance of NDA amendment and new PDUFA date of february 26, 2023 for pegcetacoplan for geographic atrophy (GA). News release. Accessed November 30, 2022. https://investors.apellis.com/news-releases/news-release-details/apellis-announces-fda-acceptance-nda-amendment-and-new-pdufa
3. Liao DS, Grossi FV, El Mehdi D, et al. Complement C3 inhibitor pegcetacoplan for geographic atrophy secondary to age-related macular degeneration: a randomized phase 2 trial. Ophthalmology. 2020;127(2):186-195. doi:10.1016/j.ophtha.2019.07.011
4. Iveric Bio. Iveric Bio announces FDA has granted breakthrough therapy designation for avacincaptad pegol for geographic atrophy. News release. November 17, 2022. Accessed January 4, 2023. https://investors.ivericbio.com/news-releases/news-release-details/iveric-bio-announces-fda-has-granted-breakthrough-therapy
5. Holz FG, Bindewald-Wittich A, Fleckenstein M, et al. Progression of geographic atrophy and impact of fundus autofluorescence patterns in age-related macular degeneration. Am J Ophthalmol. 2007;143(3):463-472. doi:10.1016/j.ajo.2006.11.041
6. Riedl S, Vogl WD, Mai J, et al. The effect of pegcetacoplan treatment on photoreceptor maintenance in geographic atrophy monitored by artificial intelligence-based OCT analysis. Ophthalmol Retina. 2022;6(11):1009-1018. doi:10.1016/j.oret.2022.05.030
7. Vogl W-D, Riedl S, Mai J, et al. Predicting topographic disease progression and treatment response of pegcetacoplan in geographic atrophy quantified by deep learning. Ophthalmol Retina. 2022:S2468-6530(22)00376–1.