Corneal Crosslinking Associated with Risk, Short-Term Benefits in Bullous Keratopathy

keratopathy bullous condition in eye of elderly patient before penetrating keratoplasty
Patients with bullous keratopathy saw reduced corneal thickness, but no improvement in pain, corneal clarity or vision after the procedure.

While collagen crosslinking (CXL) reduced corneal thickness in eyes with bullous keratopathy, the procedure was also associated with recurrent epithelial defect in a small group of patients, according to a study published in the November issue of Cornea.

The researchers conducted a randomized controlled trial to determine the long-term safety and effects of CXL in patients with bullous keratopathy (BK). No effective treatment currently exists for BK patients with poor visual potential, though symptoms can be managed. Until this study, only small studies without control groups examined CXL in these cases. However, the authors concluded that the short-term benefit of CXL likely wasn’t worth the risk of possible recurrent epithelial defects in this patient population. 

In the study, 42 people with BK were randomized to receive the standard protocol CXL for keratoconus treatment (26 subjects) or a placebo treatment (16 subjects). Assessment happened at baseline and up to 12 months following treatment, with central corneal thickness (CCT) and pain scores the primary outcomes. 

Researchers found reduction in CCT was significantly higher in the CXL group than the placebo group at 2 and 4 weeks but had no statistical difference at 12 weeks and beyond. The procedure was also associated with increased recurrent epithelial defect (12%), and 2of the 3 patients who developed recurrent epithelial defect required amniotic membrane transplant. Researchers also found no differences in pain score, corneal clarity, or visual acuity between the CXL and placebo groups at 1 year.

“Therefore, CXL might offer a short-term benefit in corneal thickness in patients with BK, although there was no improvement in pain, corneal clarity, and vision that were of more clinical relevance to the patients,” according to the investigators. 

“Considering its side effects of recurrent epithelial defect, which might require further treatment, including amniotic membrane transplant, CXL might not be warranted as a treatment alternative in patients with BK.”


Choy B, Ng A, Zhu M, Liu C, Xu S, Lai J. Randomized control trial on the effectiveness of collagen cross-linking on bullous keratopathy. Cornea. 2020:39(11):1341-1347. doi: 10.1097/ICO.0000000000002395.