Background The macular central 1 mm diameter zone is crucial to patients’ visual acuity, but the long-term natural history of central sparing in eyes with geographic atrophy (GA) is unknown.
Methods We manually segmented GA in 210 eyes with GA involving central 1 mm diameter zone (mean follow-up=3.8 years) in the Age-Related Eye Disease Study. We measured the residual area in central 1 mm diameter zone and calculated central residual effective radius (CRER) as square root of (residual area/π). A linear mixed-effects model was used to model residual size over time. We added a horizontal translation factor to each data set to account for different durations of GA involving the central zone.
Results The decline rate of central residual area was associated with baseline residual area (p=0.008), but a transformation from central residual area to CRER eliminated this relationship (p=0.51). After the introduction of horizontal translation factors to each data set, CRER declined linearly over approximately 13 years (r2=0.80). The growth rate of total GA effective radius was 0.14 mm/year (95% CI 0.12 to 0.15), 3.7-fold higher than the decline rate of CRER (0.038 mm/year, 95% CI 0.034 to 0.042). The decline rate of CRER was 53.3% higher in eyes with than without advanced age-related macular degeneration in the fellow eyes at any visit (p=0.007).
Conclusions CRER in eyes with GA declined linearly over approximately 13 years and may serve as an anatomic endpoint in future clinical trials aiming to preserve the central zone.
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Contributors Conception and design: LLS, LVDP. Data collection: LLS, MS, AA, MMP, BKY. Data Analysis: LLS. Data interpretation, LLS, LVDP. Obtained funding: LLS and LVDP. Manuscript writing: LLS, MS, AA, MMP, BKY, EML, CT, LVDP.
Funding This publication was made possible by the Yale School of Medicine, Richard K. Gershon, MD, Student Research Fellowship (Grant number: None; Recipient: Shen), and P30 EY026878 from the National Eye Institute (NEI) (Recipient: Yale Vision Science Core).
Disclaimer The sponsor or funding organisation had no role in the design or conduct of this research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the institution or funder.
Competing interests EML, Scientific advisory board—Apellis Pharmaceuticals, Galimedix, Retrotope; Consultant—Genentech/Roche, Novartis, Gemini Therapeutics, Allegro Ophthalmics; Research funding through her University—Roche, Apellis Pharmaceuticals, LumiThera; CAT, Royalties through her university—Alcon and Hemosonics; LVDP, Consultant—Astellas Institute for Regenerative Medicine, LambdaVision; Scientific advisory board—Tissue Regeneration Sciences; Scientific and clinical advisors—CavTheRx.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement The data in the age-related eye disease study is available in the database of Genotypes and Phenotypes (dbGaP Study Accession: phs000001.v3.p1). The raw data in our study are available on reasonable request sent to the corresponding author.
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