BLOG: Optometrists, retina specialists, industry work together to slow progression of GA
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Age-related macular degeneration is the leading cause of vison loss among older adults.
Geographic atrophy (GA) represents the advanced stage of AMD, affecting more than 1 million Americans (Sacconi et al.). These numbers may be even higher, as many cases are undiagnosed or underreported. This is attributed to the fact that initial signs are subtle, and GA does not initially affect central vision. Yet, as the disease progresses, it’s been estimated that irreversible, severe vision loss may affect up to two-thirds of cases (Chakravarthy et al.).
The hallmark of the disease is drusen, a metabolic byproduct at the level of the retinal pigment epithelium (RPE). Intermediate AMD is the precursor of GA and characterized by numerous medium-sized drusen (63-124 µm), a single druse measuring 125 µm (this is the diameter of the central retinal vein as it leaves the optic nerve) and, possibly, associated pigmentary changes denoted at the level of the RPE. The accumulation of drusen in addition to the development of lipofuscin results in atrophy of the RPE, choriocapillaris and photoreceptors.
Initial funduscopic evaluation of GA will show a well-delineated parafoveal depigmented lesion with exposure of the underlying choroidal architecture. Growth of the lesion varies dramatically within individuals, ranging from 0.53 mm2 to 2.6 mm2 per year (Fleckenstein et al.). The growth is observed as a centrifugal pattern, resembling a horseshoe-shaped lesion around the fovea, eventually encompassing the central fovea and resulting in vision loss.
OD perspective
Given the fact that today’s treatment options for GA may slow the progression of the disease, optometrists need to be that much more cognizant of the signs associated with GA and its progression to refer patients promptly for proper treatment.
The use of multimodal imaging, including OCT and fundus autofluorescence (FAF), are useful in the evaluation of GA and can further aid in assessing the presence of precursor associated with progression. Distinct OCT findings associated with increased risk for progression include intraretinal hyperreflective foci, hyporeflective wedged-shaped bands, and reticular pseudodrusen. FAF can also show distinct patterns associated with progression of disease, such as diffuse hyperfluorescence surrounding the hypofluorescent lesion.
OCT findings of GA are described as hypertransmission at the choroid level, due to loss or disruption of the overlying outer retina and RPE. On the other hand, FAF will show a hypofluorescent lesion, resulting from loss of the RPE.
Ophthalmology perspective
Until recently, we only kept a “watchful eye” over GA. However, there has been a paradigm shift, with FDA-approved treatment options for patients with GA.
Two recent ones have proven to slow the progression of the disease. The first is Syfovre (pegcetacoplan, Apellis Pharmaceuticals), an anticomplement intravitreal injection targeting C3, and the second is Izervay (avacincaptad pegol, Iveric Bio/Astellas Pharma), an anticomplement intravitreal injection targeting C5.
Pegcetacoplan is approved for monthly or every-other-month intravitreal dosing. The DERBY study demonstrated a 19% reduction in the monthly arm and a 16% reduction in the every-other-month arm at 2 years, while the OAKS study showed a 22% reduction in the monthly arm and 19% in the every-other-month arm at 2 years (Heier et al.).
The GALE extension study showed reduced GA lesion growth of 39% in the monthly arm and 32% in the every-other-month arm at 30 months, compared with projected sham, Apellis reported.
Avacincaptad pegol is currently approved for monthly dosing, although it is possible that this will get a label update, based on the 2-year GATHER2 results, to include every other month dosing. According to Astellas Pharma, patients in the GATHER2 trial had a 14% reduction in the mean rate of GA growth with monthly injections and 19% with every-other-month injections.
There are risks to anticomplement injectables. Both drugs can slightly increase the risk for wet AMD, thereby requiring patients to have anti-VEGF injections concurrently with anticomplement injections. Pegcetacoplan, at least currently, seems to carry additional risks, including higher rates of intraocular inflammation, nonarteritic anterior ischemic optic neuropathy and rare, post-marketing reports of occlusive retinal vasculitis.
The decision to treat a patient is complicated and multifactorial and varies extensively in the retina community. Factors to consider include patient age, compliance, fellow eye status and motivation to get recurring intravitreal injections. The most important thing to stress to patients is that these medications slow progression of disease but do not reverse or stop progression. However, these drugs represent the first hope for patients to prevent worsening of their otherwise blinding condition.
Careful diagnosis and monitoring of GA is essential to better understand the disease and its progression, as well as the impact of the disease on our patients. Today’s new treatment options may slow the progression of the disease, allowing for older patients to retain independence and increase quality of life for a longer period of time.
References:
- Chakravarthy U, et al. Ophthalmology. 2018;doi:10.1016/j.ophtha.2017.11.036.
- Fleckenstein M, et al. Ophthalmology. 2018;doi:10.1016/j.ophtha.2017.08.038.
- Heier JS, et al. Lancet. 2023;doi:10.1016/s0140-6736(23)01520-9.
- Izervay (avacincaptad pegol intravitreal solution) monthly or every other month reduced geographic atrophy lesion growth through 2 years. https://newsroom.astellas.us/2023-11-04-IZERVAY-TM-avacincaptad-pegol-intravitreal-solution-Monthly-or-Every-Other-Month-Reduced-Geographic-Atrophy-Lesion-Growth-Through-2-Years. Published Nov. 4, 2023.
- Sacconi R, et al. Ophthalmol Ther. 2017;doi:10.1007/s40123-017-0086-6.
- Syfovre (pegcetacoplan injection) continued to demonstrate increasing treatment effects over 30 months in patients with geographic atrophy (GA). https://investors.apellis.com/news-releases/news-release-details/syfovrer-pegcetacoplan-injection-continued-demonstrate. Published July 30, 2023.
For more information:
Diana Shechtman, OD, FAAO, is a consultative optometrist at Retina Consultants of Miami and Loh Ophthalmology & Associates. She can be reached at dianashe@comcast.net; Instagram: @dianashe1.
Priya Sharma Vakharia, MD, practices at Retina Vitreous Associates of Florida in Tampa. She can be reached at [***still need email, she has no social media handles**]
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