Work

From Subretinal to Intraretinal Fluid in Type 1 Macular Neovascularization: A Clinicopathologic Disease Transition Model

Year: 2026

Type: article

Abstract: Purpose: To characterize the transition from subretinal fluid (SRF)-dominant to intraretinal fluid (IRF)-dominant exudation in type 1 macular neovascularization (MNV) secondary to neovascular age-related macular degeneration (nAMD), using longitudinal optical coherence tomography (OCT) phenotyping and exploratory clinicopathologic correlation. Methods: Serial OCT volumes from eyes with type 1 MNV and baseline SRF without IRF were retrospectively reviewed to define the temporal sequence of subretinal hyperreflective material (SHRM) formation, external limiting membrane (ELM) disruption and descent, IRF emergence, and outer retinal remodeling. Time-dependent Cox regression identified predictors of IRF development, and linear mixed-effects models related structural transitions to visual acuity (VA). Exploratory immunohistochemistry for glial fibrillary acidic protein and aquaporin-4 (AQP4) was performed in a donor eye with nAMD. Results: Among 143 eyes (130 patients; median follow-up, 49.2 months [interquartile range, 28.2-90.8]), SHRM developed in 85 eyes (59%), ELM disruption or descent in 67 eyes (47%), and IRF in 44 eyes (31%). ELM alterations preceded IRF occurrence in 74% of eyes (hazard ratio, 12.94; 95% CI, 6.41-26.11). IRF onset was associated with worse VA (β = +0.07 logMAR; P < 0.001) and accelerated visual decline (time × IRF interaction: β = +0.019 logMAR/year; P = 0.004). Histopathology demonstrated Müller cell extension beyond the ELM into fibrovascular tissue, reactive gliosis, and AQP4 redistribution, mirroring ELM descents and outer retinal adhesions observed on OCT. Conclusions: In type 1 MNV, the shift to IRF-dominant exudation may reflect a structural disease state transition in which ELM disruption, Müller cell remodeling, and altered AQP4-mediated fluid transport are contributing mechanisms. These findings provide a possible clinicopathologic framework for developing outer retina-preserving therapeutic strategies in nAMD.

Source: Investigative Ophthalmology & Visual Science

DOI: 10.1167/iovs.67.10.57

Authors: Maria Vittoria Cicinelli, Lorenzo Bianco, Alessio Antropoli, Francesco Bandello, Enrico Borrelli, Malia Edwards