Background: The role of tangential traction exerted by epiretinal membranes in the pathogenesis of macular holes is not fully understood. Furthermore, the role of glial cells in the formation and/or closure of macular holes remains to be elucidated.
Methods: To better understand the pathogenesis of macular hole formation and to compare the ultrastructural features of epiretinal membranes associated with macular holes of primary and secondary etiology, we harvested 23 translucent epiretinal membranes associated with macular holes stages III-IV at the time of pars plana vitrectomy and examined them electron microscopically. Eighteen membranes were obtained from patients with idiopathic macular holes. 3 membranes from patients with myopic macular holes and 2 epiretinal membranes were associated with macular holes which had developed after retinal detachment surgery.
Results: Eighteen membranes contained a continuous undulating piece of inner limiting lamina (ILL). Sixteen of 18 epiretinal membranes at the margins of idiopathic macular holes, 2 of 3 membranes in myopic macular holes and both membranes associated with a macular hole after retinal detachment surgery demonstrated mono- or multilayers of fibrous astrocytes with single macrophage- or fibrocyte-like cells. Vitreous and newly formed collagen occupied the space between the ILL and the glial cells. Three macular holes were surrounded by rather firmly attached acellular ILL.
Conclusions: Glial cells and newly formed collagen may play an important role in macular hole formation by exerting tangential traction regardless of the underlying disease process. Glial cells, however, may also be involved in healing of the retinal defect and pars plana vitrectomy with peeling of an epiretinal membrane, and/or the ILL may induce directed glial cell proliferation and migration. The similar ultrastructure of epiretinal membranes associated with macular holes and "simple epiretinal membranes" as described by Foos  suggests a common pathogenesis for macular holes and macular pucker.