Assessing Endothelial Integrity in Patients With Progressive Keratoconus and Thin Corneas Treated With the Sub400 Corneal Cross-linking Protocol.

Abstract

Purpose: To investigate the corneal endothelial integrity in patients who underwent corneal cross-linking (CXL) with the Sub400 protocol, which treats progressive ectasia not eligible for standard CXL due to a stromal thickness of less than 400 µm.

Methods: This was an investigator-initiated, retrospective, single-center study conducted at the Department of Ophthalmology at the University Hospital Zurich in collaboration with the ELZA Institute in Zurich, Switzerland. Confocal endothelial measurements were performed before and up to 24 months after CXL. We applied a linear mixed-effect model to compare endothelial cell density (ECD) differences depending on time and treatment. At the 1-month follow-up visit, the demarcation line (DL) depth was assessed using anterior segment optical coherence tomography.

Results: From August 2021 to August 2024, 17 eyes from 17 patients (3 [17.6%] women) were included, all receiving unilateral treatment. The median (IQR [range]) age was 33.1 (24.5 to 35.8 [16.8 to 70.2]) years. The median (IQR [range]) corneal thickness was 357 (317 to 367 [210 to 388]) µm. None of the patients showed clinical signs of endothelial decompensation. The median (IQR [range]) distance from the DL to the endothelium was 80 (45 to 91 [21 to 174]) µm. The mean difference in ECD measurements before and after treatment was 56.4 (95% CI: -9.6 to 122.4) cells/mm² (P = .09).

Conclusions: This study demonstrated the safety of the Sub400 protocol based on ECD measurements, clinical outcomes, and the observed DL, which aligns with the initial depth estimate initially proposed. Future studies should reevaluate the endothelium in a larger study population and include other morphologic endothelial parameters. [J Refract Surg. 2025;41(7):e682-e689.].