Corneal cross-linking for infectious keratitis of various causes: an umbrella review

To explore the therapeutic role of corneal cross-linking (CXL) for infectious keratitis.

This is an umbrella review of the systematic reviews and meta-analysis concerning the role of corneal CXL in treating infectious keratitis. Appropriate keywords were carefully selected following the identification of PICO (Population: People who have corneal cross-linking for infectious keratitis; Intervention: corneal cross-linking; Comparison: other treatments such as antibiotic therapy; Outcome: Primary outcome was considered as the efficacy of treatment using re-epithelization and heal rate, and secondary outcome was considered need to penetrating keratoplasty (PK)). The electronic search across various databases, including Cochrane, PubMed, MEDLINE, Embase, SCOPUS, CINAHL, Psychoinfo, and ProQuest, was performed until August 2024.

Five systematic reviews out of 53 identified records are included in the umbrella review. Due to the structure of the included studies, statistical analysis was not possible to be conducted. Four studies were included that mainly evaluated the role of adjuvant corneal CXL in bacterial keratitis, and the other study focused mainly on fungal keratitis. The studies reported heterogeneous results. Two systematic reviews reported a shorter period for corneal epithelium healing in the adjuvant CXL group compared to the standard antibiotic therapy (SAT), especially in fungal keratitis. However, two studies showed no significant change in re-epithelization duration. One meta-analysis reported a reduction in corneal infiltrate size 7 days after adjuvant corneal CXL compared to the SAT. None of the included studies reported a difference in corneal complications, such as perforation and the need for PK in the CXL group compared to SAT.

The corneal CXL in infectious keratitis has no uniform protocol, especially regarding the de-epithelization procedure before CXL, leading to heterogeneity in the trial results. However, it seems the adjuvant corneal CXL next to SAT is not inferior to the unaccompanied SAT and may be superior in some cases, including fungal etiologies, regarding faster corneal healing.