Lamellar Hole–Associated Epiretinal Proliferation in Comparison to Epiretinal Membranes of Macular Pseudoholes

Purpose To compare immunocytochemical and ultrastructural characteristics of “lamellar hole–associated epiretinal proliferation” in lamellar macular holes with “conventional epiretinal membrane” in macular pseudoholes. Design A consecutive observational case series, laboratory investigation. Methods We analyzed surgically excised flat-mounted internal limiting membrane specimens and epiretinal membrane specimens removed from 25 eyes of 25 patients with lamellar macular holes (11 eyes) and macular pseudoholes (14 eyes) using interference and phase-contrast microscopy, immunocytochemistry, and transmission electron microscopy. By spectral-domain optical coherence tomography, epiretinal material of homogenous reflectivity without contractive properties was categorized as lamellar hole–associated epiretinal proliferation, whereas tractional epiretinal membranes presenting contractive properties were termed conventional epiretinal membrane. Results Lamellar hole–associated epiretinal proliferation was seen in 73% of eyes with lamellar macular hole. Eyes with macular pseudohole presented with conventional epiretinal membrane. In lamellar hole–associated epiretinal proliferation, positive immunoreactivity for anti–glial fibrillary acidic protein, hyalocyte markers, and anti–collagen type I and III was seen. In contrast, specimens of macular pseudoholes were positive for α-smooth muscle actin and anti–glial fibrillary acidic protein, predominantly. Cellular ultrastructure showed that lamellar hole–associated epiretinal proliferation of lamellar macular holes mainly consisted of fibroblasts and hyalocytes, whereas myofibroblasts dominated in conventional epiretinal membranes of macular pseudoholes. Conclusions Cells within lamellar hole–associated epiretinal proliferation appear to originate from vitreous and possess less contractive properties than cells of conventional epiretinal membranes. Our findings point to differences in pathogenesis in a subgroup of lamellar macular holes presenting lamellar hole–associated epiretinal proliferation on the retinal surface.