Clinicopathologic Correlations of Retrocorneal Membranes Associated With Endothelial Corneal Graft Failure

Purpose: To provide clinicopathologic correlations for retrocorneal membranes associated with Descemet stripping automated endothelial keratoplasty (DSAEK) failure. Design: Retrospective case series. Methods: The specimens and medical records of the patients diagnosed with clinically significant retrocorneal membranes associated with DSAEK failure at the Bascom Palmer Eye Institute or the University of Miami Veterans Hospital between October 2015 and March 2020 were reviewed for demographics, clinical presentation, comorbidities, and surgeries performed. Histopathologic analysis was performed on hematoxylin-eosin and periodic acid–Schiff sections. Immunohistochemical studies were performed for smooth muscle actin (α-SMA), pancytokeratin, and CK7. Immunofluorescence was performed for vimentin, N-cadherin, ROCK1, RhoA, ZEB1, and Snail. Results: A total of 7 patients (3 male and 4 female) were identified to have a clinically significant retrocorneal membranes at the time of graft failure. The average age at the time of first DSAEK was 70 years (range: 55-85 years). All patients were pseudophakic and had a glaucoma drainage device in place; 1 had a history of failed DSAEK. Ranging from 0 to 47 months after surgery, a variably thick retrocorneal fibrous membrane was observed, eventually leading to graft failure. Four patients underwent subsequent penetrating keratoplasty and 3 underwent repeat DSAEK. On histopathologic evaluation, a pigmented fibrocellular tissue was identified along the posterior margin of the corneas and DSAEK buttons in all cases. Further characterization with immunohistochemistry and immunofluorescence demonstrated membranes to be negative for pancytokeratin and positive for α-SMA, vimentin, CK7, N-cadherin, ZEB1, Snail, ROCK1, and RhoA. Conclusions: Fibrocellular retrocorneal membrane proliferation may be associated with DSAEK failure in patients with previous glaucoma drainage device surgery. Our results demonstrate myofibroblastic differentiation and a lack of epithelial differentiation. Positivity for markers of an endothelial-to-mesenchymal transition indicates possible endothelial origin and could be the hallmark for future targeted pharmacotherapy.