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Bu, Shao-Chong MD*,†,‡; Kuijer, Roel PhD†,§; van der Worp, Roelofje J.*,†; Huiskamp, Eveline A. MD*; Renardel de Lavalette, Victor W. MD*; Li, Xiao-Rong MD, PhD; Hooymans, Johanna M. M. MD, PhD*,†; Los, Leonoor I. MD, PhD*,†

doi: 10.1097/IAE.0000000000000013
Original Study

Purpose: To investigate the identity of collagens and cellular components in the epiretinal membrane (ERM) associated with full-thickness idiopathic macular hole and their clinical relevance.

Methods: Pars plana vitrectomy with the peeling of internal limiting membrane and ERM was performed by 2 surgeons in 40 eyes with idiopathic macular holes. The clinical data were reviewed and the surgical specimens were processed for flat-mount and immunohistochemical analysis.

Results: Epiretinal membrane is a GFAP-positive gliotic and fibrotic scar which contains newly formed Type I, III, and V collagens. Type VI collagen was not observed. Colocalization studies found cells coexpressing GFAP/CRALBP, GFAP/α-SMA, and α-SMA/CRALBP, which are consistent with transdifferentiation of Müller cells into fibroblasts and myofibroblasts. The clinically significant ERMs can be divided into two groups according to the amount of cells in ERM: sparse cellular proliferation and dense cellular proliferation. The latter group is associated with a higher chance of surgical difficulty during internal limiting membrane peeling (P = 0.006). Preoperative and postoperative visual function were not affected by the density of the cellular proliferation.

Conclusion: Retinal glial cells, probably transdifferentiated Müller cells, are involved in the formation of full-thickness macular hole-associated ERMs by a gliotic and fibrotic process. Such ERMs contain newly formed Type I, III, and V collagen depositions. The cell density of ERM affects its biomechanical properties and determines the difficulty of ERM peeling.

An epiretinal membrane associated with an idiopathic macular hole is a gliotic tissue containing newly formed Type I, III, and V collagens. Dense cellular proliferation in epiretinal membrane is associated with a higher chance of difficult internal limiting membrane peeling. Epiretinal membrane formation is a dynamic process in which glial cell activation and transdifferentiation are important.

*Department of Ophthalmology, University Medical Center Groningen, Groningen, the Netherlands;

W. J. Kolff Institute, Graduate School of Medical Sciences, University of Groningen, Groningen, the Netherlands;

Tianjin Medical University Eye Hospital, Tianjin, China; and

§Department of Biomedical Engineering, University of Groningen, Groningen, the Netherlands.

Reprint requests: Leonoor I. Los, MD, PhD, Department of Ophthalmology, University Medical Center Groningen, BB 61, P.O. Box 30.001, 9700 RB Groningen, the Netherlands; e-mail:

Supported by Stichting Blindenhulp (Blind Aid Foundation), the Netherlands.

None of the authors have any conflicting interests to disclose.

© 2014 by Ophthalmic Communications Society, Inc.