Multimodal imaging of photoreceptor and vascular changes in lamellar macular hole and epiretinal membrane-associated foveoschisis

Lamellar macular hole (LMH) and epiretinal membrane–foveoschisis (ERM-FS) are distinct subtypes of lamellar macular defects, but clinical differentiation remains challenging. Adaptive optics (AO) and optical coherence tomography angiography (OCTA) may offer novel biomarkers for structural and vascular differences. This study aimed to evaluate photoreceptor integrity and macular microvasculature in LMH and ERM-FS compared with healthy controls. This prospective observational cross-sectional study was conducted at the Department of Ophthalmology, Technical University of Munich, between January 2022 and January 2025. Sixty-one eyes were included: 20 LMH, 21 ERM-FS, and 20 healthy controls. Exclusion criteria were other retinal diseases, high myopia, or prior intraocular surgery except cataract extraction. Best-corrected visual acuity (BCVA), spectral-domain OCT (SD-OCT), OCTA, and AO retinal imaging (rtx1, Imagine Eyes, Orsay, France) were performed. AO-derived metrics included cone density (CD), spacing, regularity, and dispersion. OCTA evaluated foveal and parafoveal vessel density (VD) in the superficial (SCP) and deep capillary plexus (DCP), foveal avascular zone (FAZ), and choriocapillaris flow. SD-OCT assessed central subfield thickness (CST), central subfield volume (CSV), and outer retinal integrity. Mean [SD] age was 75.7 [7.5] years for LMH, 70.6 [8.7] for ERM-FS, and 71.5 [7.1] for controls. ERM-FS eyes showed increased cone spacing (e.g. at 4° inferior ERM-FS vs. LMH, P = 0.0159, Table 2) and dispersion (e.g. at 4° inferior ERM-FS vs. CG, P = 0.0115, Table 2) compared with LMH and controls, whereas cone density (e.g. at 0° ERM-FS vs. LMH, P =. 0.036, Table 2) and regularity (e.g. at 4° inferior ERM-FS vs. LMH, P = 0.060, Table 2) followed the same direction but did not remain statistically significant after correction for multiple testing. FAZ was larger in LMH than ERM-FS (0.342 vs. 0.236 mm²; P = 0.01). Foveal SCP VD was higher in ERM-FS than LMH and controls (28.16% vs. 22.53% vs. 21.82%; P = 0.01 ERM-FS vs. LMH). LMH eyes more frequently showed ellipsoid zone and external limiting membrane disruptions. ERM-FS was associated with greater CST and CSV. AO and OCTA reveal distinct photoreceptor and vascular alterations in LMH and ERM-FS. LMH is characterized by larger FAZ and more outer retinal disruption, whereas ERM-FS shows increased retinal thickness and more pronounced photoreceptor mosaic disorganization (increased cone spacing/dispersion), with trends toward lower cone density and reduced regularity. Higher foveal SCP VD in ERM-FS may, at least in part, reflect traction-related mechanical effects. Multimodal imaging may enhance diagnostic accuracy and monitoring in lamellar macular defects.