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Purpose:The incidence of and risk factors for cystoid macular edema (CME) after Descemet membrane endothelial keratoplasty (DMEK) remain uncertain. This study examines the incidence of and risk factors for CME after DMEK.Methods:This retrospective, single-center study included patients with no history of CME who had undergone DMEK. Patients were examined weekly for 1 month after surgery and at 3 and 6 months after surgery. Follow-up examinations included visual acuity (VA) assessment, pachymetry, anterior segment optical coherence tomography, biomicroscopy, intraocular pressure measurement, and fundoscopy. Eyes suspected of having CME (reduced VA and/or abnormal fundoscopic findings) underwent macular optical coherence tomography. Potential risk factors for CME examined included age, axial length, anterior chamber rebubbling, not using a topical nonsteroidal antiinflammatory after surgery, and concurrent DMEK and cataract surgery (triple-DMEK).Results:Eighty eyes (74 subjects) were included. Eleven eyes (13.8%) developed CME within 6 months after undergoing DMEK. Univariate analyses did not identify any significant CME risk factors. Interestingly, the triple-DMEK procedure did not put subjects at risk for developing CME (P = 0.184). Visual prognosis after medical treatment for CME was excellent, and subjects with and without CME had comparable VA at 6 months [CME: logarithm of the minimum angle of resolution (logMAR) VA = 0.3 (first–third quartile: 0.1–1.0), 20/40; no CME: logMAR VA = 0.3 (0.1–0.5), 20/40; P = 0.391].Conclusions:Although CME frequently occurred after DMEK, no CME risk factors were identified. In addition, CME did not significantly affect long-term visual outcomes when it was appropriately treated.

Corneal transparency is maintained by a monolayer of corneal endothelial cells. Defects in corneal endothelial cells (CEnCs) can be rectified surgically through transplantation. Fuchs’ endothelial corneal dystrophy (FECD) is the foremost cause of endothelial dysfunction and the leading indication for transplantation. Increased sensitivity of CEnCs to oxidative stress is thought to contribute to the pathogenesis of FECD through increased apoptosis. In part, this is thought to be due to loss of NRF2 expression: a global regulator of oxidative stress. We demonstrate that expression of the redox sensor, peroxiredoxin 1 (PRDX1) is selectively lost from CEnCs in FECD patient samples. We reveal that expression of PRDX1 is necessary to control the response of CEnCs to agents that cause lipid peroxidation. Iron-dependent lipid peroxidation drives non-apoptotic cell death termed ferroptosis. We establish that the inhibitor of ferroptosis, ferrostatin-1 rescues lipid peroxidation and cell death in CEnCs. Furthermore, we provide evidence that the transcription factor NRF2 similarly regulates lipid peroxidation in CEnCs.

The corneal endothelium regulates corneal hydration to maintain the transparency of cornea. Lacking regenerative capacity, corneal endothelial cell loss due to aging and diseases can lead to corneal edema and vision loss. There is limited information on the existence of corneal endothelial progenitors. We conducted ultrastructural examinations and expression analyses on the human transition zone (TZ) at the posterior limbus of corneal periphery, to elucidate if the TZ harbored progenitor-like cells, and to reveal their niche characteristics. Within the narrow TZ (~190 μm width), the inner TZ—adjacent to the peripheral endothelium (PE)—contained cells expressing stem/progenitor markers (Sox2, Lgr5, CD34, Pitx2, telomerase). They were located on the inner TZ surface and in its underlying stroma. Lgr5 positive cells projected as multicellular clusters into the PE. Under transmission electron microscopy and serial block face-scanning electron microscopy and three-dimensional (3D) reconstruction, the terminal margin of Descemet’s membrane was inserted beneath the TZ surface, with the distance akin to the inner TZ breadth. Porcine TZ cells were isolated and proliferated into a confluent monolayer and differentiated to cells expressing corneal endothelial markers (ZO1, Na+K+ATPase) on cell surface. In conclusion, we have identified a novel inner TZ containing progenitor-like cells, which could serve the regenerative potential for corneal endothelium.