Sridevi Thottarath, Sarega Gurudas, Syed Kubravi, Dimitrios Kazantzis, Ayşe Merve Keskin, Sobha Sivaprasad, EYENEON Study Group, Benjamin Burton, Geeta Menon, Manju Chandran, Ian Pearce, Savita Madhusudhan, Anna Grabowska, Faruque Ghanchi, James Talks, Richard Gale, Martin McKibbin, Ajay Kotagiri, Niro Narendran, Afsar Jafree, Saad Younis, Claire Bailey, Priya Prakash, Christiana Dinah, Louise Downey, Andrew Lottery, Paritosh Shah, Romi Chhabra, Narendra Dhingra, Indra Dias, Mary Freeman, Daren Hanumunthadu
IMPORTANCE: Nonexudative macular neovascularization (neMNV) is a risk factor for exudation in fellow eyes of patients with unilateral exudative age-related macular degeneration (AMD). Accurate estimation of prevalence of neMNV is required for sample size calculations for clinical trials evaluating novel interventions to delay exudation from neMNV. Certain dimensions of double-layer sign (DLS) on optical coherence tomography (OCT) are often regarded as a surrogate for neMNV. OBJECTIVE: To assess the prevalence of fellow-eye neMNV on OCT angiography (OCT-A) in eyes with AMD with DLS on OCT among patients with unilateral new-exudative AMD in the first eye. Design, Setting, and Participants: This prospective observational cohort multicenter study took place in the United Kingdom from January 2021 through June 2025. The study included 862 participants with OCT and OCT-A within 3 months of initiation of anti-vascular endothelial growth factor (VEGF) therapy, of whom 550 (63.8%) had both OCT and OCT-A performed within 30 days of the date of the first anti-VEGF injection to the fellow eye. These data were analyzed from July 2025 through October 2025. MAIN OUTCOMES AND MEASURES: Prevalence of DLS, neMNV, and assessment of univariable and adjusted associations with neMNV and DLS were assessed using logistic regression models. RESULTS: Among 550 eyes (mean [SD] participant age, 78.0 [7.6] years; 315 female [57.3%] and 235 male [42.7%]), 112 (20.4%; 95% CI [Wilson score], 17.1%-24.0%) had DLS and 47 eyes (8.5%; 95% CI [Wilson score], 6.4%-11.3%) had neMNV at baseline, including 42 (89.36%) within DLS, 3 (6.4%) in fibrovascular irregular shallow-pigment epithelial detachment, and 2 (4.3%) below drusen. Prevalence of neMNV was higher among eyes with thick DLS (n = 36 [48%]) compared with those with thin DLS (16.2%; n = 6; difference = -31.8%; 95% CI [Wilson score], -46.9% to -11.7%; P = .002). CONCLUSIONS AND RELEVANCE: While 1 in 5 fellow eyes had DLS on OCT among patients with unilateral new-onset exudative AMD in the first eye, the prevalence of neMNV on OCT-A was only 40% among these eyes with DLS. These results suggest DLS on OCT in fellow eyes of patients with new-onset exudative AMD in the first eye is not a good surrogate for neMNV. Trial Registration: ISRCTN registry Identifier: ISRTCTN13798759.