Focusing on GA: Imaging techniques and emerging therapies

(Image credit: Adobe Stock / KONSTANTIN SHISHKIN)

Steven Ferrucci, OD, FAAO, and Carolyn Majcher, OD, FAAO, presented a lecture entitled “Imaging Techniques and Emerging Therapies for Geographic Atrophy” at the American Academy of Optometry Academy 2023 meeting in New Orleans, Louisiana. They covered the latest information gleaned from multimodal imaging and discussed the 2 treatments recently approved by the US Food and Drug Administration (FDA).

The prevalence data for age-related macular degeneration (AMD) are staggering: The disease is the leading cause of blindness in high-income countries in patients older than 50 years, and the prevalence is expected to increase to 22 million cases by 2050. Two new drugs have recently been FDA approved for the management of geographic atrophy (GA). Importantly, the prevalence of advanced AMD—both central and neovascular—is expected to more than double from 1.7 million cases in 2010 to 3.8 million cases in 2050.

The numbers underscore the importance of early detection and treatment to maximize the visual outcomes. In an interview with Optometry Times, Ferrucci said, “It’s important as optometrists to recognize and diagnose patients with GA and then refer those patients who might be good [for] potential treatment to the retinal specialists to at least consider treatment.”

Imaging technologies

According to the investigators, a multimodal imaging approach is optimal to ferret out and measure GA lesions. This includes optical coherence tomography (OCT), fundus autofluorescence (FAF), near-infrared reflectance, and color photographs. Ferrucci and Majcher provided the pros and cons of the various modalities.

Color fundus photographs are useful but less sensitive for detecting early GA and are not ideal to track enlargement of GA lesions over time. FAF is a primary method for detecting and monitoring lesions and is considered superior for detecting early GA compared with color fundus photography. Ferrucci and Majcher demonstrated the prognostic value of the GA phenotypic FAF patterns. Near-infrared reflectance images show GA as hyperreflective (ie, bright) in contrast with FAF, which displays dark GA lesions (ie, hypo-autofluorescent).

OCT is the gold standard for imaging GA. Ferrucci advised that when using OCT, clinicians should look for loss of the photoreceptors along with choroidal hypertransmission defects where the OCT light source penetrates through the choroid more in GA areas because of loss of the retinal pigment epithelium.

OCT shows biomarkers that are predictive of GA development and progression. These include sinking of the inner nuclear and outer plexiform layer, external limiting membrane and/or photoreceptor ellipsoid zone loss, hyporeflective wedges, and drusenoid pigment epithelial detachment collapse. Other high-risk features include intraretinal hyperreflective foci, reticular pseudodrusen/subretinal drusenoid deposits, and drusen with hyporeflective cores.

New treatments

Two new therapies for GA recently became available: pegcetacoplan (Syfovre; Apellis Pharmaceuticals), approved by the FDA for GA in February 2023, and avacincaptad pegol (Izervay; IVERIC bio), approved in August 2023. Both drugs are complement inhibitors.

Approval of pegcetacoplan was based on results from the OAKS and DERBY studies, in which patients received a 15-mg intravitreal injection every 25 to 60 days (ie, monthly or every other month). With 2 years of treatment, the GA growth decreased by approximately 20% compared with monthly sham dosing and the treatment effect was observed to increase over time. The investigators also saw greater reductions in GA growth with extrafoveal lesions. In addition, post hoc analysis of eyes with extrafoveal lesions demonstrated preservation of approximately 1 line of visual acuity with treatment compared with sham-treated eyes and better vision-related quality-of-life outcomes at 2 years. The drug was associated with slower visual loss and better-quality vision in patients with extrafoveal lesions.

Approval of avacincaptad pegol was based on results from the Gather 1 and 2 trials. A post hoc analysis found that there was a 56% risk reduction in persistent visual loss compared with that of sham at 12 months. Another finding was that greater growth of GA lesions was associated with worsening visual acuity in both study arms.

Several rare cases of severe intraocular inflammation have been reported with real-world use of pegcetacoplan after FDA approval. In addition, ischemic optic neuropathy is an adverse event that occurred for a small percentage of patients. Both drugs increased the risk of neovascular conversion, and clinicians are advised to “vigilantly” monitor patients undergoing treatment and educate patients to monitor themselves for exudative conversion.

Other treatments

Brimonidine, which has a neuroprotective effect, was considered as a treatment to reduce GA lesion size. However, it did not meet its primary end point of decreased lesion size in a clinical trial.

Several other potential GA therapies are at various points in the drug pipeline. Two that are the furthest along in development are ALK-001 (Alkeus Pharmaceuticals) and ANX007 (Annexon Biosciences). The former, an oral formulation of modified vitamin A, is in a phase 2/3 trial, the results of which are expected at the end of 2023. The latter, an intravitreal antigen-binding fragment to complement factor ql, is in a phase 2 trial, with top-line data expected by summer 2024.

The take-home point, according to Majcher,is that“it is very exciting to now have 2 newly approved therapies that slow the progression of GA, and this is just the beginning. When analyzing AMD imaging data, especially OCT scans, eye care providers must intently and carefully look for both exudative/neovascular disease and GA. Don’t wait for visual acuity decline to refer [because] acuity is often spared until the fovea becomes involved, which results in irreversible central vision loss.”