Future perspectives for treating patients with geographic atrophy

Abstract

Purpose Geographic atrophy (GA) is a late-stage form of age-related macular degeneration (AMD) characterized by the expansion of atrophic lesions in the outer retina. There are currently no approved pharmacological treatments to prevent or slow the progression of GA. This review describes the progression and assessment of GA, predictive imaging features, and complement-targeting investigational drugs for GA. Methods A literature search on GA was conducted. Results Expansion of atrophic lesions in patients with GA is associated with a decline in several measures of visual function. GA lesion size has been moderately associated with measures obtained through microperimetry, whereas GA lesion size in the 1-mm diameter area centered on the fovea has been associated with visual acuity. Optical coherence tomography (OCT) can provide 3-dimensional quantitative assessment of atrophy and is useful for identifying early atrophy in GA. Features that have been found to predict the development of GA include certain drusen characteristics and pigmentary abnormalities. Specific OCT features, including hyper-reflective foci and OCT-reflective drusen substructures, have been associated with AMD disease progression. Lesion characteristics, including focality, regularity of shape, location, and perilesional fundus autofluorescence patterns, have been identified as predictors of faster GA lesion growth. Certain investigational complement-targeting drugs have shown efficacy in slowing the progression of GA. Conclusion GA is a progressive disease associated with irreversible vision loss. Therefore, the lack of treatment options presents a significant unmet need. OCT and drugs under investigation for GA are promising future tools for disease management.

The roadmap to geographic atrophy treatment: A journey of trials and promise

“…Over the past decade, a multitude of clinical trials have been conducted, each contributing significantly to our understanding of geographic atrophy (GA) and its potential therapeutic interventions (Loewenstein & Trivizki, 2023).…”

Microglia depletion/repopulation does not affect light-induced retinal degeneration in mice

“…Activation of the retinal immune system and accumulation of mononuclear phagocytes in the subretinal space are a common hallmark for AMD pathology in humans ( 5 ). Of note, targeting the innate immune system has been recently proposed as a therapeutic option for the treatment of atrophic AMD ( 6 ).…”

Patient acceptability of intravitreal complement inhibitors in geographic atrophy (GA): protocol for a UK-based cross-sectional study

“…3 Regular intravitreal injections (injections into the eye) are the standard of care for wet AMD and a common mode of delivery in the current pipeline of treatments for GA in clinical trials. Dysregulation of the complement cascade has been implicated in the pathogenesis of GA, and recent positive results from phase 3 clinical trials of two intravitreal complement inhibitors have paved a way for new therapies to treat GA. 4 Findings from the DERBY and OAKS trials of pegcetacoplan have shown that at 24 months, GA lesion growth was reduced by 21% with monthly intravitreal injections…”