Five-Year Follow-up of the ELZA-sub400 Protocol: Individualized Corneal Cross-linking With Riboflavin and UV-A in Ultrathin Keratoconic Corneas.

Purpose

To evaluate the 5-year safety and efficacy of the ELZA-sub400 protocol, an individualized stromal thickness-guided corneal cross-linking (CXL) technique, in eyes with progressive keratoconus and corneal stroma thickness of less than 400 µm.

Methods

In this retrospective interventional case series, 39 eyes of 33 patients with progressive keratoconus or primary ectasia and stromal thickness between 214 and 398 µm underwent CXL using the ELZA-sub400 protocol. Following epithelial removal and riboflavin loading, ultraviolet-A irradiation at 3 mW/cm2 was applied for durations tailored to stromal thickness, targeting a demarcation line (DL) 70 µm anterior to the corneal endothelium. Outcome measures included anterior radius of curvature over the central 3 mm (ARC3mm), maximum keratometry (Kmax), corrected distance visual acuity (CDVA), refractive error, stromal thickness, and corneal densitometry, assessed by Scheimpflug tomography (Pentacam HR; Oculus Optikgeräte GmbH) annually for 5 years. Mean follow-up was 3.6 ± 1.5 years (range: 1 to 5 years), with 18 of 39 eyes (46.2%) completing the 5-year follow-up.

Results

At 5 years after CXL, 84.6% of eyes (33/39) remained stable or flattened (Kmax change ≤1.00 diopters [D]). Kmax decreased significantly from baseline (mean: -2.74 ± 2.65 D, P < .001). ARC3mm-derived dioptric power decreased significantly over 5 years (-1.29 D, P = .014). Median CDVA was unchanged (0.40 logMAR, P = .572). No significant change was observed in spherical (P = .211) or cylindrical (P = .280) refractive error. DL depth averaged 275 ± 61 µm; no endothelial decompensation occurred. Minimum corneal thickness declined modestly (median -10 µm, P = .049). Anterior densitometry increased slightly (+2.40 grayscale units, P = .007), remaining within mild clinical ranges.

Conclusions

The ELZA-sub400 protocol safely stabilized keratoconus in 84.6% of ultrathin corneas over 5 years, with no signs of endothelial damage. Individualized fluence enabled effective treatment of corneas previously ineligible for standard CXL.