Corneal Cross-linking in Thin Corneas: From Origins to State of the Art

Corneal cross-linking (CXL) can halt ectasia progression and involves saturating the stroma with riboflavin, followed by ultraviolet-A (UV-A) light irradiation. This generates reactive oxygen species that covalently cross-link together stromal molecules, strengthening the cornea. The ‘Dresden protocol’ left a 70 µm uncross-linked region at the base of the stroma to protect the corneal endothelium from UV damage; however, this limited CXL to corneas ≥400 µm. Approaches made to overcome this limitation involved artificial corneal thickening to ≥400 μm through swelling the stroma with hypo-osmolaric riboflavin, applying riboflavin-soaked contact lenses during UV irradiation or leaving ‘epithelial islands’ over the thinnest corneal regions. The drawbacks to these three approaches are unpredictable swelling, suboptimal stiffening and unpredictable cross-linking effects, respectively. Newer approaches adapt the irradiation protocol to the cornea to deliver CXL that maintains the 70 μm uncross-linked stroma safety margin. The sub400 protocol employs an algorithm that models the interactions between UV-A energy, riboflavin, oxygen diffusion and stromal thickness. It requires only corneal pachymetry measurements at the thinnest point and the selection of the appropriate UV irradiation time from a look-up table to cross-link corneas as thin as 200 µm safely and effectively.