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Updated: Jun 29, 2026

Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis
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Second-Generation ELZA-sub400 Protocol: Individualized High-Fluence Cross-Linking for Ultra-Thin Keratoconus Corneas.

Farhad Hafezi1, Rüstü Emre Akcan2, Sabine Kling3

  • 1Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Switzerland; ELZA Institute, Dietikon, Switzerland; Dept. of Ophthalmology, New York University Grossman School of Medicine, New York University, New York, NY, USA; Faculty of Medicine, University of Geneva, Geneva, Switzerland; USC Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, USA; School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, China.

American Journal of Ophthalmology
|June 27, 2026
PubMed
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This summary is machine-generated.

This study shows that a new corneal cross-linking (CXL) protocol effectively halted ectasia progression in 76% of ultrathin corneas within 12 months. The treatment demonstrated a good safety profile, making it a promising option for managing progressive keratoconus and post-LASIK ectasia.

Area of Science:

  • Ophthalmology
  • Corneal Ectasia Treatment
  • Corneal Cross-Linking (CXL)

Background:

  • Corneal ectasia, including progressive keratoconus and post-LASIK ectasia, poses a significant challenge, particularly in ultrathin corneas.
  • Standard corneal cross-linking (CXL) protocols may have limitations in treating corneas with a thinnest stromal thickness below 400 µm.
  • Developing safe and effective CXL methods for these challenging cases is crucial for preventing further visual deterioration.

Purpose of the Study:

  • To evaluate the safety and efficacy of a second-generation individualized corneal cross-linking (CXL) protocol, ELZA-sub400, in ultrathin ectatic corneas.
  • To assess the ability of this high-fluence UV-A irradiation protocol to halt ectasia progression.
  • To determine the short-term safety profile of the ELZA-sub400 protocol in this patient cohort.
Keywords:
CXLcorneal cross-linkingcustomized CXLectasiakeratoconusthin corneaultra-thin cornea

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Main Methods:

  • A retrospective, single-center study included 29 eyes of 24 patients with progressive keratoconus or post-LASIK ectasia and thinnest stromal thickness <400 µm.
  • Epithelial removal, riboflavin soaking, and continuous UV-A irradiation (365 nm) at 3 or 9 mW/cm² were employed, with total fluence titrated up to 10 J/cm².
  • Outcomes were assessed up to 12 months, measuring corrected distance visual acuity (CDVA), keratometry (Kmax), stromal thickness, and demarcation line depth using advanced imaging techniques.

Main Results:

  • At 12 months, 76% of eyes (22/29) met the non-progression criterion (defined as <1.0 D increase in Kmax).
  • The mean change in Kmax was -0.77 ± 5.10 D, indicating no statistically significant progression.
  • The demarcation line remained within the stromal layer in all eyes, with no observed deep stromal haze or endothelial decompensation, indicating a favorable safety profile.

Conclusions:

  • The second-generation ELZA-sub400 CXL protocol successfully halted ectasia progression in 76% of ultrathin corneas at 12 months.
  • The protocol demonstrated an acceptable short-term safety profile, characterized by stromal-confined demarcation lines and absence of endothelial complications.
  • While a numerical decline in CDVA was noted, it did not reach statistical significance, warranting further investigation in larger prospective studies.