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Corneal Cross-Linking for Paediatric Keratoconus: A Systematic Review and Meta-Analysis.

ABSTRACT: All corneal cross-linking techniques attenuated disease progression in patients with pediatric keratoconus for at least one year based on a meta-analysis. A standard and accelerated technique led to marked improvement in visual acuity. We determined the efficacy and safety of corneal cross-linking (CXL) in pediatric keratoconus by conducting a systematic review and meta-analysis. The PubMed and Cochrane databases were searched for relevant studies on the effects of standard, transepithelial, and/or accelerated CXL protocols in patients aged 18 years or younger. Standardized mean differences with 95% confidence intervals were calculated to compare the data collected at baseline and 12 months. The primary outcomes were maximum keratometry (Kmax) and uncorrected visual acuity (UCVA), and the secondary outcomes were the thinnest corneal thickness (TCT), best-corrected visual acuity (BCVA), and manifest refraction spherical equivalent or cylindrical refraction. Our search yielded 7913 publications, of which 26 were included in our systematic review and 21 were included in the meta-analysis. Standard CXL significantly improved the Kmax, UCVA, and BCVA, and significantly decreased the TCT. Accelerated CXL significantly improved UCVA and BCVA. In the transepithelial and accelerated-transepithelial CXL methods, each measurable parameter did not change after treatments. All CXL techniques attenuated disease progression in patients with pediatric keratoconus for at least one year. Standard and accelerated CXL led to marked improvement in visual acuity.

SUBMITTER: Kobashi H

PROVIDER: S-EPMC8232120 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Corneal Collagen Cross-Linking for Keratoconus: Systematic Review.

Project description:To evaluate the efficacy of collagen cross-linking (CXL) one year after treatment for keratoconus compared to no treatment by summarizing randomized controlled trials (RCTs) using a systematic review.Trials meeting the selection criteria were quality appraised, and the data were extracted by two independent authors. The outcome parameters included maximum keratometry (Kmax), corneal thickness at the thinnest point, best spectacle-corrected visual acuity (BSCVA), uncorrected visual acuity (UCVA), spherical equivalent (SE) refraction, and cylindrical refraction one year after CXL. We compared the changes in the above parameters with the control group.We identified five RCTs involving 289 eyes that met the eligibility criteria for this systematic review. The changes in BSCVA from baseline to one year exhibited a significant difference between the two groups. There was no statistically significant difference between the two groups for changes in corneal thickness and cylindrical refraction. We did not conduct a meta-analysis in Kmax, UCVA, and SE refraction because their I2 values were greater than 50%.According to the systematic review, CXL may be effective in halting the progression of keratoconus for one year under certain conditions, although evidence is limited due to the significant heterogeneity and paucity of RCTs.

| S-EPMC5485290 | biostudies-other

Comparison of Standard and Transepithelial Corneal Cross-Linking for the Treatment of Keratoconus: A Meta-analysis.

Project description:PurposeTo compare the clinical results of standard corneal cross-linking (SCXL) with transepithelial corneal cross-linking (TECXL) in progressive keratoconus using a meta-analysis.MethodsPubMed, EMBASE, and Cochrane Central Register of Controlled Trials were searched up to June 2020 to identify relevant studies. The PRISMA guidelines were followed. Primary outcomes were change in uncorrected distance visual acuity and maximum keratometry (K max) after CXL. Secondary outcomes were change in corrected distance visual acuity, mean refractive spherical equivalent (MRSE), spherical and cylindrical error, endothelial cells density (ECD), and central corneal thickness (CCT).ResultsSixteen studies with a total of 690 eyes (SCXL: 332 eyes; TECXL: 358 eyes) were included. At the last follow-up, SCXL provided a greater decrease in maximum keratometry (K max) than TECXL (weighted mean difference (WMD) -1.12; 95% confidence interval (CI) -1.96, -0.29). For the other outcomes, there were no statistically significant differences.ConclusionsExcept for a greater decrease in Kmax with SCXL group, both groups have a comparable effect on visual, pachymetric, and endothelial parameters at 24 months after surgery. Larger studies with a longer follow-up time are necessary to determine whether these techniques are comparable in the long term.

| S-EPMC7864754 | biostudies-literature

Late onset corneal haze after corneal cross-linking for progressive keratoconus.

Project description:PurposeTo present the case of a patient that underwent corneal crosslinking for progressive keratoconus and 18 months later revealed clinically significant corneal stromal haze.ObservationsA 20-year-old male presented with progressive visual loss OU for the past few years. His corrected distance visual acuity (CDVA) OD was 20/30 (-2.75 -1.75 @55) and OS 20/30 (-0.50 -1.75@110). Corneal topography revealed keratoconus OU and the patient underwent corneal crosslinking according to the Dresden Protocol. The postoperative regimen included combined tobramycin and dexamethasone qid along with lubrication until epithelium healed and then fluorometholone qid with weekly tapering. At 3 months postoperatively, his topography was stable and his corrected distance visual acuity (CDVA) was 20/25 OU. On slit lamp examination, only clinically insignificant stromal haze was observed. At 18 months postoperatively, the patient reported vision deterioration. On examination his CDVA was 20/25 in right eye, and 20/40 in his left eye. Deep stromal haze was revealed in his central cornea, more dense in his left eye. Corneal topography was stable and the CDVA loss was attributed to the notable deep stromal haze. The patient was treated with dexamethasone qid with biweekly tapering. 18 months after corneal crosslinking, the patient demonstrated clinically significant stromal haze, most prominent OS. He was treated with dexamethasone qid. One month later his CDVA OS gradually improved to 20/25, and stromal haze was still noted but less dense.Conclusions and importanceLate-onset deep corneal haze is a possible complication of corneal crosslinking in keratoconic patients.

| S-EPMC6411486 | biostudies-literature

Corneal collagen cross-linking epithelium-on vs. epithelium-off: a systematic review and meta-analysis.

Project description:BackgroundThe purpose of the study was to determine the advantages and disadvantages of epi-on corneal cross-linking (CXL) techniques compared with standard epi-off CXL.MethodsWe searched MEDLINE and EMBASE for randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) and we evaluated the selected papers according to the Cochrane risk of bias tool. We considered, as primary outcomes, average Kmax flattening, changes in uncorrected and corrected distance visual acuity (UDVA and CDVA); as secondary outcomes, we considered changes in pachymetry values and endothelial cell density (ECD). We also investigated adverse events related to the treatments and treatment failure. Meta-analysis was conducted with a fixed or random-effects model using weighted mean difference (MD) with 95% confidence interval (CI) as the effect size.ResultsA total of 15 studies were included and among these 15 trials, 9 were RCTs and 6 were NRSIs, but only 4 studies showed no high risk of bias and were included in this meta-analysis. Our analysis revealed significant postoperative differences in CDVA (MD = 0.07; 95% CI 0.04 to 0.10; P < 0.001), and no significative differences in UDVA, Kmax, central corneal thickness (CCT) and ECD (P > 0.05). Epi-on CXL protocol was found to be significantly less prompt to have risks of delay in epithelial healing (P = 0.035) and persistent stromal haze (P = 0.026).ConclusionEpi-on CXL is as effective as epi-off CXL. Except for a higher significant improvement in CDVA with current epi-on protocols, our meta-analysis demonstrates that epi-on and epi-off CXL have comparable effects on visual, topographic, pachymetric, and endothelial parameters. Epi-on CXL has clinical advantages in terms of comfort and avoidance of complications as it reduces the risk of developing delay in epithelial healing and persistent stromal haze.

| S-EPMC8465763 | biostudies-literature

Efficacy of corneal collagen cross-linking for treatment of keratoconus: a meta-analysis of randomized controlled trials.

Project description:ObjectiveTo evaluate the efficacy of corneal collagen cross-linking (CXL) for the treatment of keratoconus.MethodsWe performed a literature search for randomized controlled trials that assessed the effect of CXL in slowing progression of keratoconus. The primary outcome measures included changes of topographic parameters, visual acuity, and refraction. Efficacy estimates were evaluated by weighted mean difference (WMD) and 95% confidence interval (CI) for absolute changes of the interested outcomes.ResultsSignificant decrease in mean keratometry value, maximum keratometry value and minimum keratometry value were demonstrated in the CXL group compared with the control group (WMD = -1.65; 95% CI: -2.51 to -0.80; P < 0.00001; WMD = -2.05; 95% CI: -3.10 to -1.00; P < 0.00001; WMD = -1.94; 95% CI: -2.63 to -1.26; P < 0.00001; respectively). Best spectacle-corrected visual acuity improved significantly in CXL group (WMD = -0.10; 95% CI: -0.15 to -0.05; P < 0.00001), whereas uncorrected visual acuity did not differ statistically. Manifest cylinder error decreased significantly in patients undergoing CXL procedure compared with control patients in sensitivity analysis (WMD = -0.388; 95% CI: -0.757 to -0. 019; P = 0.04). The changes in central corneal thickness and intraocular pressure were not statistically significant.ConclusionCXL may be an effective option in stabilizing keratoconus. Further long-term follow-up studies will be necessary to assess the persistence of CXL.

| S-EPMC4436191 | biostudies-literature

Conventional and transepithelial corneal cross-linking for patients with keratoconus.

Project description:Previous studies investigating the effectiveness of conventional corneal collagen cross-linking (CXL) and transepithelial CXL in keratoconus treatment have reported conflicting outcomes. Therefore, we conducted a meta-analysis to compare the effectiveness of these treatments. We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for prospective randomized controlled trials (RCTs) with no restrictions. We included visual acuity (corrected distance visual acuity, uncorrected distance visual acuity) and corneal keratometry (K) as primary outcome parameters, and spherical equivalent, central corneal thickness (CCT), and endothelial cell density, as secondary parameters. We finally included seven reports (including six RCTs involving 305 participants and 344 eyes). Our analysis revealed significant postoperative differences in average K and CCT values between conventional and transepithelial CXL-treated patients [K: weighted mean difference (WMD) = 0.79, 95% confidence interval (CI) = 0.04-1.53, p = 0.04; CCT: WMD = 4.53, 95% CI = 0.42-8.64, p = 0.03]. In contrast, we did not find any significant differences in visual acuity, flattest K value, steepest K value, cylinder K value, apex K value, spherical equivalent, or endothelial cell density between groups. In conclusion, transepithelial CXL has a more protective influence on corneal thickness than conventional CXL, and results in lesser postoperative corneal flattening. Further investigation of the clinical outcomes of transepithelial CXL is required.

| S-EPMC5886478 | biostudies-literature

Corneal endothelial damage after simultaneous PRK and corneal cross-linking in stable keratoconus.

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Corneal Perforation After Corneal Cross-Linking in Keratoconus Associated With Potentially Pathogenic ZNF469 Mutations.

Project description:PurposeTo report a case of bilateral and repetitive corneal perforations after corneal cross-linking (CXL) for keratoconus in a woman harboring potentially pathogenic variants in the ZNF469 gene and to characterize the keratoconus phenotype in this woman and her daughter who shared the same ZNF469 mutations.MethodsClinical characterization of the proband and her daughter followed by sequencing of the genes associated with brittle cornea syndrome, ZNF469 and PRDM5, in both individuals.ResultsAn Ashkenazi Jewish woman in her sixth decade presented with diffuse corneal thinning and progressive steepening consistent with keratoconus. After CXL, epithelium-off in the first eye and epithelium-on in the second, she developed spontaneous corneal perforations in each eye. Her daughter in her fourth decade demonstrated a similar pattern of diffuse corneal thinning and progressive corneal steepening but did not undergo CXL and did not develop corneal perforation. Screening of the ZNF469 and PRDM5 genes revealed 3 missense ZNF469 variants (c.2035G>A, c.10244G>C, and c.11119A>G) in cis arrangement on 1 allele of ZNF469 in both proband and her daughter. Although the 3 variants share low (<0.01) global minor allele frequencies, each has significantly higher minor allele frequencies (0.01-0.03) in the Ashkenazi Jewish population, leading to uncertainty regarding a pathogenic role for the identified variants.ConclusionsCXL may be associated with the development of corneal perforation in particular at-risk individuals with keratoconus. Identifying clinical and genetic risk factors, including screening of ZNF469 and PRDM5, may be useful in the prevention of significant complications after CXL.

| S-EPMC6612572 | biostudies-literature

Sterile keratitis after combined riboflavin-UVA corneal collagen cross-linking for keratoconus.

Project description:PurposeTo investigate patient risk factors and to look for potential causes of sterile infiltrates following an unexpected cluster of sterile keratitis after a routine collagen cross-linking (CXL) list.MethodsThe records of all 148 cases of CXL were reviewed retrospectively. The equipment and solutions used and our clinic's standard operating procedure for CXL were reviewed. An in-vitro experiment to explore the variation in ultraviolet A (UVA) irradiance from fluctuations in the working distance of the UVA lamp was conducted.ResultsThe four patients who developed sterile infiltrates had steeper maximum corneal curvatures (68.0±7.3?D) and thinner pachymetry (389.9±49.0??m) than the 144 who did not (57.0±8.2?D, P=0.05; 454.6±45.4??m, P=0.08). A corneal curvature of >60?Dand a pachymetry of <425??m were significant risk factors. All four affected cases obtained a complete resolution with topical antibiotics and steroids. The unaided VA and the maximum K improved from their pre-operative levels in three out of four patients. A 2-mm reduction in distance of the VEGA C.B.M. X-Linker from a treated surface increased irradiance to 3.5-3.7?mW/cm(2), which is above the threshold for endothelial toxicity.ConclusionPatients with thinner and steeper corneas are at an increased risk of developing sterile keratitis. The visual outcomes despite this complication are good.

| S-EPMC4274277 | biostudies-literature

Novel Technique of Transepithelial Corneal Cross-Linking Using Iontophoresis in Progressive Keratoconus.

Project description:In this work, the authors presented the techniques and the preliminary results at 6 months of a randomized controlled trial (NCT02117999) comparing a novel transepithelial corneal cross-linking protocol using iontophoresis with the Dresden protocol for the treatment of progressive keratoconus. At 6 months, there was a significant average improvement with an average flattening of the maximum simulated keratometry reading of 0.72 ± 1.20 D (P = 0.01); in addition, corrected distance visual acuity improved significantly (P = 0.08) and spherical equivalent refraction was significantly less myopic (P = 0.02) 6 months after transepithelial corneal cross-linking with iontophoresis. The novel protocol using iontophoresis showed comparable results with standard corneal cross-linking to halt progression of keratoconus during 6-month follow-up. Investigation of the long-term RCT outcomes are ongoing to verify the efficacy of this transepithelial corneal cross-linking protocol and to determine if it may be comparable with standard corneal cross-linking in the management of progressive keratoconus.

| S-EPMC5002487 | biostudies-literature

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