1.
Transepithelial versus Epithelium-off Corneal Collagen Cross-linking for Corneal Ectasia: A Systematic Review and Meta-analysis.
Nath, S, Shen, C, Koziarz, A, Banfield, L, Nowrouzi-Kia, B, Fava, MA, Hodge, WG
Ophthalmology. 2021;(8):1150-1160
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.
2.
Comparison of Standard Versus Accelerated Corneal Collagen Cross-Linking for Keratoconus: A Meta-Analysis.
Wen, D, Li, Q, Song, B, Tu, R, Wang, Q, O'Brart, DPS, McAlinden, C, Huang, J
Investigative ophthalmology & visual science. 2018;(10):3920-3931
Abstract
PURPOSE To systematically compare epithelial-off standard (SCXL) to accelerated corneal collagen cross-linking (ACXL) for the treatment of keratoconus. METHODS PubMed, Embase, the Cochrane Library, and the US trial registry were searched for trials comparing SCXL and ACXL for keratoconus up to October 2017. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. Primary outcomes were changes in uncorrected distance visual acuity, maximum keratometry (Kmax), and mean keratometry (mean K). Secondary outcomes were changes in corrected distance visual acuity, mean refractive spherical equivalent, central corneal thickness (CCT), and endothelial cell density (ECD). RESULTS Eleven trials were included. For primary outcomes, SCXL showed a greater reduction in Kmax (SMD 0.32; 95% CI 0.16, 0.48) than ACXL. For secondary outcomes, the decrease in CCT (SMD 0.32; 95% CI 0.03, 0.61) and ECD (SMD 0.26; 95% CI 0.06, 0.46) was less with ACXL than with SCXL. For the other outcomes, there were no statistically significant differences. CONCLUSIONS SCXL has a greater effect in terms of reduction in Kmax than ACXL, while ACXL induces less reduction in CCT and ECD than SCXL. Further well-designed randomized controlled trials comparing ACXL and SCXL are indicated.
3.
Efficacy of Corneal Collagen Cross-Linking for the Treatment of Keratoconus: A Systematic Review and Meta-Analysis.
Meiri, Z, Keren, S, Rosenblatt, A, Sarig, T, Shenhav, L, Varssano, D
Cornea. 2016;(3):417-28
Abstract
PURPOSE To examine the efficacy of corneal collagen cross-linking (CXL) for the treatment of keratoconus (KCN). METHODS A systemic literature review and meta-analysis of ocular functional and structural parameters of patients with KCN undergoing cross-linking procedures were performed using PubMed and the web of science. A literature search was performed for relevant peer-reviewed publications on population-based studies. Data were analyzed with R software (Meta library), and heterogeneity was assessed with the Cochran Q and I. A random-effects model was used for high heterogeneity; otherwise a fixed model was used. Sensitivity analysis of particular tested groups was used to explain high heterogeneity. The main outcome measures extracted from the articles were corrected distance visual acuity, uncorrected distance visual acuity, and maximum K. RESULTS An improvement in visual acuity of 1 to 2 Snellen lines was found 3 months or more after undergoing CXL. Changes were more pronounced in uncorrected visual acuity. Some topography parameters were found to be improved (0.6-1 diopters) 12 to 24 months after CXL. The refractive cylinder improved by 0.4 to 0.7 diopters. Endothelial cell density decreased by 225 cells per square millimeter in the first 3 months and thereafter returned to normal. Corneal thickness was reduced by 10 to 20 μm in the year following CXL but not after 24 months. No changes in intraocular pressure were noted. CONCLUSIONS CXL is a safe and effective method for halting the deterioration of KCN, while slightly improving visual function.
4.
Corneal Collagen Cross-Linking for Infectious Keratitis: A Systematic Review and Meta-Analysis.
Papaioannou, L, Miligkos, M, Papathanassiou, M
Cornea. 2016;(1):62-71
Abstract
PURPOSE To assess the efficacy of corneal collagen cross-linking (CXL) in the management of infectious keratitis. METHODS Comprehensive literature search was performed in MEDLINE/PubMed and Cochrane Central Register of Controlled Trials using combinations of the following search terms: "corneal collagen cross linking" or "photoactivated riboflavin" or "UVA light and riboflavin" and "infectious keratitis" or "corneal ulcer." Last search was on March 19, 2015. Extracted data from individual studies were summarized and summary proportions of eyes healed and complications for different subgroups were estimated. RESULTS Twenty-five studies were included (2 randomized controlled trials, 13 case series, and 10 case reports) with a total of 210 eyes of 209 patients, of which 175 eyes underwent CXL. Causative microorganisms were bacteria, fungi, acanthamoeba, and Herpes simplex virus in 96, 32, 11, and 2 cases, respectively. Coinfections were present in 13 and cause was inconclusive in 21 cases. Sixteen of 175 eyes received no additional antibiotics, whereas 159 underwent CXL as an adjunct to antimicrobial treatment. Proportion of eyes healed with CXL was 87.2% (95% confidence interval (CI), 81.9%, 91.8%). For bacterial keratitis, the proportion of eyes healed was 85.7% (95% CI, 78.5%, 91.7%), whereas 10/11 and 25/32 eyes with acanthamoeba and fungal keratitis, respectively, were healed (available data not sufficient to provide a valid proportion analysis). Treatment resulted in corneal melting and tectonic keratoplasty in both Herpes simplex virus cases. CONCLUSIONS CXL seems promising in the management of infectious keratitis, excluding viral infections. However, more randomized controlled trials are required to assess its efficacy.