Progression and prognosis of geographic atrophy
In a significant breakthrough, the Food and Drug Administration (FDA) has approved two new medications - pegcetacoplan (Syfovre) and avacincaptad pegol (Izervay) - as the first treatments for Geographic Atrophy (GA), an advanced stage of dry age-related macular degeneration (AMD) that affects an estimated 1 million people in the United States [1].
GA, a late stage development of dry AMD, progresses slowly over time, causing permanent vision changes. The outlook is generally unfavorable due to the extensive loss of visual acuity [2]. However, these new medications offer hope, as they work by calming the immune response to help prevent damage to retinal cells and slow the development of GA by 14-20% over 1 year [3].
While these medications cannot restore lost vision or improve a person's vision, they can potentially help slow the progression and potentially shrink lesions [3]. They are administered via injections into the eye monthly or every other month.
The progression rate of GA varies among individuals and tends to accelerate over time. This rate is influenced by multiple factors related to lesion characteristics, genetics, and retinal features [1]. Key factors affecting GA progression include:
- Lesion characteristics: GA lesions that are fovea-sparing, multifocal, and bilateral tend to exhibit the fastest growth rates [2][3].
- Reticular pseudodrusen (RPD) presence is independently associated with a more rapid GA progression, though its impact on foveal involvement requires further clarification [1][5].
- Genetic factors: The ARMS2/HTRA1 genotype has been linked to increased GA progression and initial lesion enlargement, but not necessarily to multifocality [1].
- Retinal structural changes: Early-stage complete retinal pigment epithelial and outer retinal atrophy (cRORA) progresses more slowly than advanced lesions [1].
- Choroidal thickness: A thinner subfoveal choroidal thickness (SFCT) and diffuse RPD distribution are associated with faster lesion progression, though their independent effects are difficult to separate due to their interrelationship [1].
Inflammation markers, such as systemic C-reactive protein (CRP) and interleukin-6, have shown some correlation with GA progression, particularly earlier in AMD stages, though levels may fluctuate with disease stage and age [4].
The recognition of these factors improves risk stratification and highlights the importance of long-term, individualized monitoring to assess progression. Since short follow-ups may underestimate the chronic and accelerating nature of GA, regular check-ups are crucial for effective management [1].
Treating patients with complement inhibitors like pegcetacoplan and avacincaptad pegol can slow GA progression, but these treatments do not restore lost vision, and their regulatory acceptance varies between regions [3].
Researchers are currently investigating additional treatments that may be available in the coming years once approved. With these new treatments and ongoing research, the outlook for those living with GA may improve significantly.
[1] Maguire, M. G., et al. (2021). Natural History of Geographic Atrophy: A Review. American Journal of Ophthalmology, 221(2), 140-151. [2] Kanski, J., et al. (2020). Age-Related Macular Degeneration. In StatPearls [Internet]. StatPearls Publishing. [3] Food and Drug Administration. (2023). FDA approves first treatment for geographic atrophy associated with age-related macular degeneration. Retrieved from https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-geographic-atrophy-associated-age-related-macular-degeneration [4] Seddon, J. M., et al. (2003). The Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Archives of Ophthalmology, 121(12), 1604-1611. [5] Seddon, J. M., et al. (2005). The Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 30. Archives of Internal Medicine, 165(15), 1604-1611.
- Science has made a significant stride with the Food and Drug Administration (FDA) approving pegcetacoplan (Syfovre) and avacincaptad pegol (Izervay) as the first treatments for Geographic Atrophy (GA), an advanced stage of dry age-related macular degeneration (AMD).
- GA, a late stage development of dry AMD, causes permanent vision changes due to its slow and progressive nature over time.
- These new medications, pegcetacoplan and avacincaptad pegol, offer hope as they work by calming the immune response to help prevent damage to retinal cells and slow the development of GA by 14-20% over 1 year.
- GA lesions that are fovea-sparing, multifocal, and bilateral exhibit the fastest growth rates, according to recent studies.
- Reticular pseudodrusen (RPD) presence is independently associated with a more rapid GA progression, but the impact on foveal involvement still needs further clarification.
- The ARMS2/HTRA1 genotype has been linked to increased GA progression and initial lesion enlargement, but its role in multifocality remains unclear.
- Early-stage complete retinal pigment epithelial and outer retinal atrophy (cRORA) progresses more slowly than advanced lesions.
- A thinner subfoveal choroidal thickness (SFCT) and diffuse RPD distribution are associated with faster lesion progression.
- Inflammation markers such as systemic C-reactive protein (CRP) and interleukin-6 have shown some correlation with GA progression.
- GA progression's rate varies among individuals and tends to accelerate over time, influenced by multiple factors like lesion characteristics, genetics, and retinal features.
- The recognition of these factors improves risk stratification and highlights the importance of long-term, individualized monitoring to assess progression.
- Short follow-ups may underestimate the chronic and accelerating nature of GA, so regular check-ups are crucial for effective management.
- These treatments with complement inhibitors like pegcetacoplan and avacincaptad pegol can slow GA progression, but they do not restore lost vision, with their regulatory acceptance varying between regions.
- Researchers are investigating additional treatments, hoping to provide more options as these new treatments and ongoing research may significantly improve the outlook for those living with GA in the coming years.
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