Progression Rate of Macular Retinal Pigment Epithelium Atrophy in Geographic Atrophy and Selected Inherited Retinal Dystrophies. A Systematic Review and Meta-Analysis

Purpose: To compare the macular retinal pigment epithelium (RPE) atrophy progression rate of selected degenerative and macular inherited retinal diseases (IRD). Design: Systematic review and meta-analysis. Methods: The protocol was registered on the PROSPERO database. Medline, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar were searched up to September 15, 2023 for articles reporting the RPE atrophy growth rate in treatment-naïve eyes with geographic atrophy (GA), Stargardt disease (STGD1), Best disease, pseudoxanthoma elasticum (PXE), central areolar choroidal dystrophy (CACD), or pattern dystrophies with no previous or current macular neovascularization and a minimum follow-up time of 12 months. Meta-analyses determined mean RPE atrophy growth rates per disease, imaging modality (fundus autofluorescence [FAF], optical coherence tomography [OCT], or color fundus photography [CFP]) and metric (mm²/y or mm/y). The Newcastle-Ottawa scale and the Cochrane Risk-of-Bias tool assessed the risk of bias, and funnel plots were used to evaluate small-study effects. Results: From 4354 publications, 85 were included for meta-analysis: 69 studies (7815 eyes) on GA, 15 (1367 eyes) on STGD1, and one on both. Two studies on PXE were only eligible for review. No studies for other diseases met our eligibility criteria. The overall mean RPE atrophy growth rate for GA using FAF was 1.65 mm²/y (95% confidence interval [CI], 1.49-1.81) and 0.35 mm/y (95% CI, 0.28-0.41); using OCT, it was 1.46 mm²/y (95% CI, 1.28-1.64) and 0.34 mm/y (95% CI, 0.28-0.40); and on CFP it was 1.76 mm²/y (95% CI, 1.56-1.97) and 0.30 mm/y (95% CI, 0.28-0.31). For STGD1, using FAF it was 1.0 mm²/y (95% CI, 0.77-1.23) and 0.20 mm/y (95% CI, 0.17-0.23); on OCT, it was 0.80 mm²/y (95% CI, 0.72-0.88). No studies on STGD1 reported the growth rate with other imaging modalities or metrics. Growth rates in GA were faster than in STGD1 (p <. 05). A larger baseline area of atrophy was generally associated with faster growth rates. Conclusions: The RPE atrophy growth rate in GA is faster than in STGD1 but with great variation between studies and imaging modalities. Limited information was available for other macular IRD, suggesting further research is needed.