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Evaluating the safety and effectiveness of the sub-400 corneal cross-linking protocol: initial clinical and morphological findings

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Abstract

Purpose

To assess the safety and the efficacy of the “Sub-400 corneal cross-linking (CXL) protocol” for progressive keratoconus (KC) in ultrathin corneas.

Methods

The study included thirty four patients with progressive KC, who underwent CXL using the “Sub-400” protocol due to intraoperative thinnest corneal pachymetry ranging from 295 to 398 μm after epithelial removal. After the epithelium was removed, the following ultraviolet A irradiation was applied at a fluence of 3 mW/cm2 and the duration was adjusted based on the specific corneal stromal thickness. In addition to slit-lamp microscopy and visual acuity assessment, our evaluation included measurements of the maximal anterior keratometry value (Kmax), mean anterior and posterior K values (Kmean), thinnest corneal thickness (TCT), central corneal thickness, intraoperative pachymetry, and corneal endothelial cell density (ECD) preoperatively and 1 year postoperatively. Stromal demarcation line depth (DL) was measured in the first postoperative month.

Results

At the first year postoperative follow-up visit, 88% (30 eyes) exhibited tomographic stability, with average values of change in Kmax (ΔKmax) 0.61 ± 6.45 D after CXL. None of the eyes showed signs of endothelial decompensation. The mean DL depth was 250.76 ± 44.05 μm. Moderate positive correlations were observed between DL and ultraviolet A irradiation time, DL, and intraoperative stromal thickness (r = 0.473, p = 0.005 and r = 0.517, p = 0.002, respectively). ΔKmax was negatively correlated with preoperative Kmax (r =  − 0.559, P = 0.001) and positively correlated with preoperative TCT (r = 0.373, P = 0.030).

Conclusion

The “Sub-400 protocol” for CXL has a broad application possibility for ultrathin corneas with KC and has shown promising results.

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Data Availability

The data that support the findings of this study are available from the corresponding author [EEK] upon reasonable request.

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Authors and Affiliations

Authors

Contributions

E.E.K. and Y.A. wrote the main manuscript. E.E.K. and O.E.K. made substantial contributions to the conception or design of the work and interpretation of data. Y.A. O.E.K. and D.M.U. made contributions to data collection. E.E.K prepared the figures D.M.U. prepared the tables. O.E.K. made the literature search. All authors drafted the work and revised it critically for important intellectual content; All authors approved the version to be published; and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Emine Esra Karaca.

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Karaca, E.E., Asfuroğlu, Y., Ulusoy, D.M. et al. Evaluating the safety and effectiveness of the sub-400 corneal cross-linking protocol: initial clinical and morphological findings. Int Ophthalmol 45, 16 (2025). https://doi.org/10.1007/s10792-024-03371-8

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