Photoactivated chromophore for infectious keratitis - Corneal cross-linking (PACK-CXL): A systematic review and meta-analysis

Purpose: To examine the efficacy of adjuvant photoactivated chromophore for infectious keratitis-corneal cross-linking (PACK-CXL) for the treatment of infectious keratitis (IK). Methods: Electronic databases, including MEDLINE, EMBASE and Cochrane Central, were searched for articles related to PACK-CXL. All clinical studies, including randomized controlled trials (RCTs), non-randomized controlled studies, case series and case reports, were included. A meta-analysis was further performed when there were sufficient similarities in the included RCTs. Primary outcome measure was time to complete corneal healing and secondary outcome measures included size of epithelial defect and infiltrate, corrected-distance-visual-acuity (CDVA), and adverse events. Results: Forty-six eligible studies (including four RCTs) with 435 patients were included. When compared to standard antimicrobial treatment (SAT) alone, adjuvant PACK-CXL resulted in shorter mean time to complete corneal healing (-7.44 days; 95% CI, -10.71 to -4.16) and quicker resolution of the infiltrate at 7 days (-5.49 mm(2); 95% CI, -7.44 to -3.54) and at 14-30 days (-5.27 mm(2); 95% CI, -9.12 to -1.41). There was no significant difference in the size of epithelial defect, CDVA and risk of adverse events. Evidence on the use of PACK-CXL in acanthamoeba and mixed IK was insufficient. Conclusions: Our study demonstrates that adjuvant PACK-CXL expedites the healing of IK when compared to SAT alone (low-quality evidence). Further adequately powered, high-quality RCTs are required to fully ascertain the therapeutic effect of PACK-CXL.