Symmetry in the Enlargement Rates of Large Hypertransmission Defects between Eyes in Age-Related Macular Degeneration.

Authors

Sara Beqiri, Gissel Herrera, Mengxi Shen, Alessandro Berni, Omar S El-Mulki, Omar Badla, Winston Lam, Eduardo Herrera, Niccolò Ascioti, Jillene Moxam, Scott Shuldiner, Nithya Boopathiraj, Yuxuan Cheng, Viet Hoan Le, Omer Trivizki, Robert C O'Brien, Ruikang K Wang, Giovanni Gregori, Philip J Rosenfeld

Published in

Ophthalmology science. Volume 6. Issue 10. Pages 101333. Epub Jul 22, 2026.

Abstract

The symmetry of macular atrophy growth rates between eyes of patients with bilateral nonexudative age-related macular degeneration (AMD) was assessed to determine if both eyes could be used in clinical trials to test therapies that might slow the growth of atrophy.
Retrospective review of prospectively collected swept-source OCT angiography images.
Patients with bilateral nonexudative AMD with ≥1 large hypertransmission defect (hyperTD) in both eyes were included.
All large hyperTDs, defined by a greatest linear dimension ≥250 μm, were identified by 2 independent graders and annotated using a semiautomated algorithm. Growth rates were assessed using the area, square root (sqrt) area, and the perimeter-adjusted growth-rate strategies. Baseline lesion sizes were stratified using a size breakpoint of 0.9 disc area (DA). Intereye comparisons of annual hyperTD growth rates were performed. Power analyses were calculated to determine the sample sizes needed for different clinical trial designs.
Intereye concordance of growth rates was evaluated using Lin concordance correlation coefficients, and inter eye growth-rate agreement was evaluated using Bland-Altman analyses. Sample sizes for a 2-arm clinical trial design were calculated to detect a 30% reduction in growth rates in the treatment arm with 80% power and a 2-sided α = 0.05.
Sixty-four subjects (128 eyes) were followed for a mean of 4.2 ± 1.9 years, providing 942 annualized growth-rate intervals. Prior to stratification by baseline size of 0.9 DA, intereye concordance was high (r_c = 0.76) for the total area growth rate, but lower for the sqrt and perimeter-adjusted growth rates (r_c = 0.51, r_c = 0.60, respectively). Upon stratification, lesions <0.9 DA showed low correlation (0.39-0.46) across the 3 growth rates, but lesions ≥0.9 DA showed high correlation regardless of the transformation strategy (0.73-0.78).
High intereye concordance in hyperTD growth rates was observed for lesions ≥0.9 DA using 3 different growth-rate strategies. Regardless of the growth-rate strategy used, recruitment of fellow eyes in a paired-eye study for localized treatments or both eyes for systemic treatments resulted in a marked reduction in sample sizes, with improved clinical trial efficiency.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

PMID:
42668661
Bibliographic data and abstract were imported from PubMed on 30 Aug 2026.

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