Siddharth Nath1, Carl Shen2, Alex Koziarz3, Laura Banfield4, Behnam Nowrouzi-Kia5, Mark A Fava2, William G Hodge6. 1. Department of Ophthalmology and Visual Sciences, McGill University, Montréal, Canada. Electronic address: siddharth.nath@medportal.ca. 2. Division of Ophthalmology, Department of Surgery, Faculty of Health Sciences, McMaster University, Hamilton, Canada. 3. Faculty of Medicine, University of Toronto, Toronto, Canada. 4. Health Sciences Library, McMaster University, Hamilton, Canada. 5. Michael G. DeGroote School of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Canada. 6. Department of Ophthalmology, Ivey Eye Institute, Schulich School of Medicine and Dentistry, Western University, London, Canada; Department of Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University, London, Canada.
Abstract
TOPIC: To evaluate the safety and efficacy of transepithelial corneal cross-linking in comparison with the established epithelium-off technique for corneal ectasia. CLINICAL RELEVANCE: Considerable debate exists regarding whether transepithelial and epithelium-off cross-linking are comparable in their safety and efficacy. METHODS: We searched 16 electronic databases, including Medline, Embase, Web of Science, and the grey literature, current to July 8, 2020, for randomized controlled trials comparing transepithelial and epithelium-off cross-linking for corneal ectasia. We excluded studies evaluating cross-linking for nonectatic indications, as well as non-randomized controlled trials. Our primary outcome was the change in maximal keratometry (Kmax) at 12 months after cross-linking, and we considered additional topographic, visual, and safety outcomes. We summarized our analyses by calculating weighted mean differences (MDs) with associated 95% confidence intervals (CIs) for continuous outcomes and relative risks (RRs) with corresponding 95% CIs for dichotomous outcomes. We conducted trial sequential analysis to determine whether the required information size was met for each outcome. The quality of individual trials was evaluated using the Cochrane Collaboration's risk of bias assessment tool, and the evidence was assessed at an outcome level using the Grading of Recommendations Assessment, Development, and Evaluation methodology. RESULTS: Twelve studies totaling 966 eyes were eligible. A significant difference was found between transepithelial and epithelium-off cross-linking groups in the change in Kmax at 12 months (MD, 0.75; 95% CI, 0.23-1.28; P = 0.004; primary outcome) and at longest follow-up (MD, 1.20; 95% CI, 0.62-1.77; P < 0.001; secondary outcome) after treatment. No significant difference was found between the 2 groups when examining uncorrected distance visual acuity (MD, 0.04; 95% CI, -0.06 to 0.14; P = 0.386) or corrected distance visual acuity (MD, 0.01; 95% CI, -0.06 to 0.09; P = 0.732). Transepithelial cross-linking was associated with significantly fewer complications than the epithelium-off approach (RR, 0.22; 95% CI, 0.06-0.79; P = 0.020), although it was associated with an increased rate of disease progression at 12 months after treatment (RR, 4.49; 95% CI, 1.24-16.25; P = 0.022). The required information size was met for our primary outcome and trial sequential analysis supported the conventional meta-analysis. The quality of evidence was rated as moderate using the Grading of Recommendations Assessment, Development, and Evaluation methodology. DISCUSSION: The efficacy of transepithelial cross-linking remains inferior to the epithelium-off approach, although it is significantly safer.
TOPIC: To evaluate the safety and efficacy of transepithelial corneal cross-linking in comparison with the established epithelium-off technique for corneal ectasia. CLINICAL RELEVANCE: Considerable debate exists regarding whether transepithelial and epithelium-off cross-linking are comparable in their safety and efficacy. METHODS: We searched 16 electronic databases, including Medline, Embase, Web of Science, and the grey literature, current to July 8, 2020, for randomized controlled trials comparing transepithelial and epithelium-off cross-linking for corneal ectasia. We excluded studies evaluating cross-linking for nonectatic indications, as well as non-randomized controlled trials. Our primary outcome was the change in maximal keratometry (Kmax) at 12 months after cross-linking, and we considered additional topographic, visual, and safety outcomes. We summarized our analyses by calculating weighted mean differences (MDs) with associated 95% confidence intervals (CIs) for continuous outcomes and relative risks (RRs) with corresponding 95% CIs for dichotomous outcomes. We conducted trial sequential analysis to determine whether the required information size was met for each outcome. The quality of individual trials was evaluated using the Cochrane Collaboration's risk of bias assessment tool, and the evidence was assessed at an outcome level using the Grading of Recommendations Assessment, Development, and Evaluation methodology. RESULTS: Twelve studies totaling 966 eyes were eligible. A significant difference was found between transepithelial and epithelium-off cross-linking groups in the change in Kmax at 12 months (MD, 0.75; 95% CI, 0.23-1.28; P = 0.004; primary outcome) and at longest follow-up (MD, 1.20; 95% CI, 0.62-1.77; P < 0.001; secondary outcome) after treatment. No significant difference was found between the 2 groups when examining uncorrected distance visual acuity (MD, 0.04; 95% CI, -0.06 to 0.14; P = 0.386) or corrected distance visual acuity (MD, 0.01; 95% CI, -0.06 to 0.09; P = 0.732). Transepithelial cross-linking was associated with significantly fewer complications than the epithelium-off approach (RR, 0.22; 95% CI, 0.06-0.79; P = 0.020), although it was associated with an increased rate of disease progression at 12 months after treatment (RR, 4.49; 95% CI, 1.24-16.25; P = 0.022). The required information size was met for our primary outcome and trial sequential analysis supported the conventional meta-analysis. The quality of evidence was rated as moderate using the Grading of Recommendations Assessment, Development, and Evaluation methodology. DISCUSSION: The efficacy of transepithelial cross-linking remains inferior to the epithelium-off approach, although it is significantly safer.
Authors: Neel S Vaidya; Arvin Daneshmand; Randy J Epstein; Parag A Majmudar; Michael W Belin; Edward C Parsons; Roy S Rubinfeld Journal: Clin Ophthalmol Date: 2022-06-08
Authors: Duoduo Wu; Dawn Ka-Ann Lim; Blanche Xiao Hong Lim; Nathan Wong; Farhad Hafezi; Ray Manotosh; Chris Hong Long Lim Journal: Front Pharmacol Date: 2021-07-19 Impact factor: 5.810