Ultrastructural Findings of the Internal Limiting Membrane with and without Epiretinal Membrane: A Comparative...

To describe and compare the histopathological and ultrastructural findings of the internal limiting membrane (ILM) with and without epiretinal membrane (ERM), and investigate differences between idiopathic and secondary ERM, using light and transmission electron microscopy.

Cross-sectional analytical study, with pathologists and image assessors masked to clinical and imaging information.

Consecutive participants undergoing pars plana vitrectomy (PPV) with peeling of ILM, ERM, or both were enrolled. One eye per participant was included.

Specimens were collected intraoperatively following a standardized protocol and analyzed for cellular morphology, extracellular matrix composition, and ultrastructural alterations. Fisher exact test and unpaired t tests were used for group comparisons. Univariate and multivariate regression models assessed associations between clinical and imaging characteristics and histopathological features, with significance set at P < 0.001.

Cellular and extracellular matrix ultrastructural features and their associations with clinical characteristics and imaging findings.

A total of 107 eyes (90 ILM with ERM; 17 ILM without ERM) from 117 participants were analyzed. Mean age was 64.4 ± 10.9 years, and 59.8% were female. Internal limiting membrane with ERM exhibited cellular proliferation with fibrous astrocytes, fibroblasts, myofibroblasts, fibrocytes, and retinal pigment epithelium (RPE) cells, accompanied by extracellular matrix remodeling and newly formed collagen. Common ultrastructural features included ILM vacuolization, Müller cell fragments, electron-lucent bands, and disorganized collagen fibrils. Intraocular lens implantation (incidence rate ratio [IRR] = 0.333, P = 0.012) and proliferative diabetic retinopathy (IRR = 0.190, P = 0.002) were associated with reduced ILM vacuolization. Secondary ERM demonstrated significantly higher proportions of RPE cells (40.5% vs 2.8%, P < 0.001), intraretinal cysts (73.0% vs 31.8%, P < 0.001), and subfoveal ellipsoidal band loss (64.1% vs 15.9%, P < 0.001) compared to idiopathic ERM.

This study provides a comparative ultrastructural assessment of ILM and ERM, revealing distinct differences between idiopathic and secondary ERM. These findings suggest differing underlying biological processes that merit future mechanistic investigation. According to fibrocellular changes reported, macular disruption observed on OCT in older eyes may indicate susceptibility to secondary ERM, raising the possibility, yet to be validated, that ILM peeling during PPV for other indications could offer prophylactic benefit.

The author has no/the authors have no proprietary or commercial interest in any materials discussed in this article.