SECOND-GENERATION “SUB400” PROTOCOL FOR CORNEAL CROSS-LINKING IN ULTRATHIN CORNEAS: ONE-YEAR FOLLOW-UP DATA
Published 2025 - 29th ESCRS Winter Meeting
Reference: PO030 | Type: Free Paper | DOI: 10.82333/vj9p-xf43
Authors: Emilio A. Torres-Netto* 1 , M. Enes Aydemir 1 , Mark Hillen 2 , Léonard Kollros 3 , Nikki Hafezi 3 , Boris Knyazer 4 , Ludimila Nascimento 5 , Luciene Barbosa 5 , Frank Blaser 6 , Farhad Hafezi 1
1ELZA Institute,Zurich ,Switzerland, 2ELZA Institute,Zurich,Switzerland, 3ELZA Institute ,Zurich ,Switzerland, 4Soroka University Medical Center,Beer-Sheva,Israel, 5Federal University of São Paulo,Sao Paulo,Brazil, 6University Hospital Zurich,Zurich,Switzerland
Purpose
The original sub400 protocol is an epi-off CXL used to strengthen ultra-thin (~180–≤400µm) corneas. It uses pre-irradiation thinnest-point stromal pachymetry measurements and a validated algorithm to adapt irradiation duration (and therefore fluence), leaving a ~70 µm safety margin region above the endothelium. The original sub400 protocol is based on 3 mW/cm² intensity and a fluence of 5.4 J/cm2 at 400 µm of stromal thickness.
The second-generation sub400 protocol modifies this approach in two ways. First, its starting fluence increases from 5.4 to 10 J/cm2 at 400 µm of corneal stroma and second, it delivers the same efficacy and safety as earlier sub400 CXL but in a shorter (sub-20 minute) period. We will present one-year follow-up data.
Setting
The study was conducted at the ELZA Institute, Zurich, Switzerland.
Methods
The study included eyes with progressive keratoconus and corneal thickness below 400 µm, treated with the second-generation sub400 protocol. UV irradiation intensity was adjusted based on corneal thickness: 9 mW/cm² for cornea with pachymetries ≥330–400 µm, and 3 mW/cm² for those below 330 µm. Fluence at 400 µm of stromal thickness was 10 J/cm2 and was then consecutively lowered following our published algorithm. Outcome measures included keratoconus progression, visual acuity, and corneal topography and tomography, as well as corneal endothelial cell counts in a subset of patients. No significant changes were found in CDVA (P = 0.142), sphere (P = 0.458), and cylinder (P = 0.631) from baseline to 12 months postoperatively. No eyes showed signs of endothelial decompensation.
Results
Scheimpflug data showed that, on average, there was significant increase from baseline at 12 months in ARC3 mm (0.69 ± 0.40 mm, P = 0.048), but no difference in minimum corneal thickness (median: -4.0 μm, IQR: -20.0 to 7.0 μm, P = 0.309), in Kmax (-0.77 ± 5.10 D, P = 0.418). ARC3 mm values were 5.45 ± 0.95 mm at baseline and 5.75 ± 1.20 mm at 1 year after. Mean Kmax values were 71.8 ± 13.7 D at baseline and 71.0 ± 15.3 D at 1 year after. No significant changes were found in CDVA (P = 0.142), sphere (P = 0.458), and cylinder (P = 0.631) from baseline to 12 months postoperatively. No eyes showed signs of endothelial decompensation.
Conclusion
The second-generation sub400 protocol offers a tailored approach to CXL in ultrathin corneas, with UV irradiation intensity and duration adjusted according to specific corneal thickness measurements. Initial observations suggest no adverse effects on endothelial cell density, with forthcoming data expected to provide further insight into the protocol’s safety and efficacy in managing keratoconus over a one-year period.