Manually Assisted Customised Epi-On Corneal Cross-Linking (Mace): A New Approach To Customized Corneal Cross-Linking

To describe MACE, a new technique of corneal cross-linking (C-CXL), and to evaluate its early outcomes for progressive keratoconus treatment. This technique is an adaptation of Phototherapeutic Keratectomy-Assisted Customized Epi-On Corneal Cross-Linking (PACE). By replacing laser ablation with manual epithelium removal, this method aims to maintain the ability to perform customized epi-on C-CXL in centers that do not present an excimer laser. These techniques aim to improve outcomes, when compared to conventional C-CXL techniques, by creating a chemical gradient, with higher riboflavin stromal concentration in the apex area without epithelium, as well as an energy gradient, with the apical area receiving a higher energy dose.

Single-center prospective study conducted at Unidade Local de Saúde de São João, a tertiary university hospital from Porto, Portugal.

Patients with progressive keratoconus, documented with the Pentacam HR®, were prospectively included. The MACE technique included 20% alcohol-assisted manual corneal epitheliectomy, in a 6mm diameter circular area, centered on the apex of the cone, followed by corneal instillation of a transepithelial riboflavin preparation every 3 minutes for 30 minutes, and finally UV-A irradiation for 10 minutes, while maintaining riboflavin instillation every 3 minutes during this period.  Corrected distance visual acuity (CDVA), flat and steep keratometry (K1 and K2, respectively), maximum keratometry (Kmax), minimum pachymetry (PachyMin) and topometric indices were assessed preoperatively, at 1 week and at 1 month postoperatively. 

9 eyes from 9 patients were included, with a mean age at crosslinking of 22±3.81 years. There were no significant differences at 1 week postoperatively (p>0.05), though corneal tomography revealed a clinically relevant applanation profile of the procedure on the area of the cone apex. One month after the procedure, there was a clinically relevant reduction of Kmax (-0.73±2.19D; p=0.413) and K2 (-0.30±1.29D; p=0.532), though none were significant. As expected, there was a non-significant reduction of the PachyMin (-5.29±6.87 µm; p=0.088). CDVA remained stable (p=1.000) and there were no clinically relevant complications of the procedure.

MACE effectively stabilized keratoconus progression in young patients with previously progressive keratoconus, with no statistically significant differences observed in visual or tomographic outcomes in the first month after the procedure. No adverse effects were observed with this technique, reinforcing its high safety profile. Studies with a higher sample size and longer follow-up are naturally required to validate this innovative C-CXL technique.