Five-year follow-up of the ELZA-sub400 protocol: individualized corneal cross-linking with riboflavin and UV-A in ultrathin keratoconic corneas

Torres-Netto, Emilio A., Kling, Sabine, Akcan, Rüştü Emre, Kollros, Léonard, Aydemir, M. Enes, Hillen, Mark, Furrer, Michalina, Khurramov, Jaloliddin, Hafezi, Nikki L., Lu, Nan-Ji, Awwad, Shady T., Knyazer, Boris, Blaser, Frank and Hafezi, Farhad 2026. Five-year follow-up of the ELZA-sub400 protocol: individualized corneal cross-linking with riboflavin and UV-A in ultrathin keratoconic corneas. Journal of Refractive Surgery 42 (10) , pp. e416-e424. 10.3928/1081597x-20260728-01

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Optometry and Vision Sciences
ISSN:	1042-962X
Date of Acceptance:	15 July 2026
Last Modified:	15 Oct 2026 13:45
URI:	https://orca.cardiff.ac.uk/id/eprint/190253

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