Purpose: Corneal ectasias are progressive, degenerative diseases defined by abnormal structural changes in the cornea, leading to distortion of vision and substantial reduction in quality of life. Corneal collagen cross-linking (CXL) increases the biomechanical rigidity of the cornea against ectatic processes. CXL requires delivery of 5.4 J/cm2 of ultraviolet A (UVA) radiation to a cornea saturated with riboflavin in order to induce cross-link formation. The standard CXL protocol achieves this fluence with 3mW/cm2 of UVA light applied for 30 minutes. To minimize risks associated with increased corneal exposure and UVA irradiation time, some surgeons have proposed accelerated protocols which use higher-powered UVA light and a shorter time period to achieve the same fluence, as theorized by the Bunsen-Roscoe Law of Reciprocity. The purpose of this study is to review the evidence on accelerated CXL and compare it to the conventional protocol. 

Study Design: Systematic review and meta-analysis.

Methods: We searched 16 electronic databases including MEDLINE, EMBASE, and Web of Science from inception until July 14, 2019 for randomised trials comparing accelerated and conventional CXL for corneal ectasia. Our electronic search was supplemented with screening of the grey literature, hand-searching, and reviewing conference proceedings. Our primary outcome was change in maximal keratometry (Kmax) at 12 months after CXL and we examined additional patient- and procedure-specific outcomes. We calculated weighted mean differences (MDs) with associated 95% confidence intervals (CIs) for continuous outcomes and relative risks (RRs) with 95% CIs for dichotomous outcomes.

Results: 11 trials (totalling 518 eyes) met our eligibility criteria. The change in Kmax at 12 months (MD 0.33, 95% CI -0.04-0.70, p=0.08) was comparable between accelerated and conventional CXL. Changes in uncorrected distance visual acuity (MD -0.04, 95% CI -0.09-0.02, p=0.21) and corrected distance visual acuity (MD -0.01, 95% CI -0.06-0.03, p=0.53) were not significantly different between the two protocols. 

Conclusions: Accelerated CXL and conventional CXL have comparable visual outcomes and efficacy.

Accelerated versus conventional corneal collagen cross-linking for corneal ectasia: A systematic review and meta-analysis of randomised controlled trials

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