ReviewEye and vision (London, England)2021
Corneal collagen cross-linking epithelium-on vs. epithelium-off: a systematic review and meta-analysis.
Review in Eye and vision (London, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 42 citations in OpenAlex.
- Comparison of epithelium-off versus iontophoresis-assisted transepithelial corneal collagen cross-linking in keratoconus: a systematic review and meta-analysis.International ophthalmology · 2026Pooled it
- Epithelium-on versus epithelium-off corneal collagen crosslinking for keratoconus: a systematic review and meta-analysis.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2024Pooled it
- Observation and assessment of the immediate use of a silicon hydrogel contact lens after transepithelial corneal cross linking: a prospective study.BMC ophthalmology · 2023Trial
- Microbubble-assisted pLIFU enhances riboflavin delivery and corneal cross-linking in an in vivo rabbit keratoconus-like model.Ultrasonics sonochemistry · 2026Article
- The Science and Clinical Evolution of Corneal Cross-Linking: Mechanism of Action, Ultra-Structural Changes, Clinical Indications, and Emerging Treatment Strategies.Ophthalmology and therapy · 2026Review
- Short-term retinal microvascular and structural changes after epi-on and epi-off corneal cross-linking assessed by SD-OCTA.International ophthalmology · 2026Article
- N, S Co-Doped Carbon Quantum Dots-Riboflavin Composite Photosensitizers for Enhanced Iontophoresis-Assisted Corneal Cross-Linking.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Randomized, Controlled Study to Evaluate the Safety and Efficacy of Oxygen-Enriched Epithelium-On Corneal Cross-Linking for the Treatment of Keratoconus.Ophthalmology and therapy · 2026Article
- Variation in corneal biomechanical properties following continuous cross-linking treatment.Eye and vision (London, England) · 2026Article
- The Critical Role of Oxygen Supplementation in Epithelium-On Corneal Cross-Linking: A Narrative Review.Advances in therapy · 2026Review
- Comparison of epithelium-on customized remodeled vision and epithelium-off accelerated crosslinking in keratoconus treatment: 2-year study.Journal of cataract and refractive surgery · 2026Observational
- The Future of Interventional Keratoconus Management: Perspectives on Integrating Epithelium-on Oxygen-Enriched Cross-Linking into Comprehensive Care Pathways.Therapeutics and clinical risk management · 2026Article
- Evidence-Based Clinical Practice Guideline for Diagnosis, Treatment, and Follow-Up of Keratoconus Patients.Clinical ophthalmology (Auckland, N.Z.) · 2026Review
- Reactive oxygen species accelerated glycation for oxygen-independent corneal cross-linking.Frontiers in bioengineering and biotechnology · 2026Article
- Interventional Keratoconus Management: The Critical Imperative for Early Detection and Treatment.Clinical ophthalmology (Auckland, N.Z.) · 2026Article
- Advancements and Innovations in Keratoconus Management: A Review of Current Practices.Journal of clinical medicine · 2025Review
- Construction and characteristics of an adjustable biomechanical in vitro corneal stromal model simulating keratoconus pathological features.Materials today. Bio · 2025Article
- Clinical Outcomes of Repeated Corneal Crosslinking for Progressive Keratoconus After Failure of Primary Procedure; Safety and Efficacy at 12-Month Follow-Up.Ophthalmology and therapy · 2025Article
- The microenvironment of ocular surface in keratoconus: a systematic review.Eye and vision (London, England) · 2025Review
- Individual Risk Assessment and Prognostication of Outcomes After Corneal Cross-Linking.Journal of ophthalmology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.