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We aimed to determine the long-term outcomes of epithelium-off cross-linking (CXL) in keratoconus patients.An observational registry study from 41 centres across 5 countries was carried out. Primary outcomes included the mean change in visual acuity (VA), Kmax, K2, and thinnest corneal thickness (TCT) at 1-5 years. Secondary outcomes included the percentage of eyes with worsening, stable and improving outcomes.There were 976 eyes of 794 patients with 1-year of complete follow-up, 501 eyes with 2-years, 355 with 3-years, 235 with 4-years and 162 with 5-years. There was a significant improvement in mean VA from baseline by 3.7 logMAR letters (p 0.001) in year 1, and 6.9 (p 0.001) in year 5. Mean Kmax decreased by 1.2 dioptres (D; p 0.01) in year 1. During subsequent years the Kmax flattening appeared sustained but this was not statistically significant. K2 flattened significantly from baseline in year 1 and then remained stable. At 1 year, 4.1% patients were poor responders to CXL in terms of VA, losing ≥15 letters. The proportion of the poor responders remained unchanged: 4.9% at 5-years. The proportion of poor responders in terms of Kmax remained similar: 5.9% steepening by ≥2D at 1-year and 7.5% at 5-years. The proportion of K2 poor responders remained stable with 4.7% steepening by ≥2D at 1-year and 5.8% at 5-years.Cross-linking is effective at stabilising keratoconus up to 5 years in most patients. However, a small proportion of eyes failed to stabilise and had reduced vision.

We set out to describe the natural history of keratoconus. We included untreated patients, and our key outcome measures were vision, refraction, and corneal curvature.Keratoconus affects 86 in 100 000 people, causing visual loss due to increasing irregular corneal astigmatism, and the quality of life declines in patients. Interventions are used to stabilize the disease or improve vision, including corneal cross-linking (CXL) and grafting, but these carry risks. Detailed knowledge of the natural history of keratoconus is fundamental in making informed decisions on when their benefits outweigh these risks.We included prospective or retrospective studies of pediatric or adult patients who reported 1 or more of visual acuity, refraction, and corneal curvature measures: steep keratometry (KOur search yielded 3950 publication titles, of which 41 were included in our systematic review and 23 were incorporated into the meta-analysis. Younger patients and those with greater KWe report the first systematic review and meta-analysis of keratoconus natural history data including 11 529 eyes. Younger patients and those with K