Eye · 8 authors, 6 centres
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Both standard (3 mW/cm² for 30 min) and accelerated (9 mW/cm² for 10 min) corneal cross-linking (CXL) were safe and effective for stabilizing keratoconus over 5 years. Standard CXL resulted in significantly greater improvements in visual acuity and keratometry than accelerated CXL. These findings support standard CXL as the preferred protocol for long-term keratoconus management.
**Background:** Keratoconus is a progressive corneal ectatic disorder that can lead to vision loss. Corneal cross-linking (CXL) strengthens the cornea and halts progression. Standard CXL (sCXL; 3 mW/cm² for 30 min) is the established protocol, but accelerated CXL (aCXL; 9 mW/cm² for 10 min) was developed to reduce procedure time. Short-term studies show mixed results; long-term comparative data are lacking. This study compared 5-year outcomes of sCXL vs aCXL using real-world registry data.
**Methods:** Data were from the Save Sight Keratoconus Registry (SSKR), a web-based multinational database. Inclusion criteria: keratoconus patients who underwent epithelium-off CXL before December 2016 and had a 5-year follow-up visit. Exclusion: age >50 years, pre-existing ocular conditions, prior ocular surgery that could affect outcomes, repeated CXL. A total of 176 eyes (141 patients) were included: 100 eyes (75 patients) sCXL, 76 eyes (66 patients) aCXL. Baseline characteristics: mean age 24.2±7.7 years, 34% female. The aCXL group had worse baseline visual acuity (55.3 vs 69.8 logMAR letters), steeper Kmax (59.1 vs 54.8 D), and thinner MCT (451.9 vs 468.8 µm) (all p<0.05). Mixed-effects regression models adjusted for age, sex, baseline visual acuity, keratometry, pachymetry, practice, and patient effects.
**Key Results:** At 5 years, both protocols improved outcomes. Adjusted mean gain in habitual visual acuity was significantly higher for sCXL (10.2 letters, 95% CI 7.9–12.5) vs aCXL (4.9 letters, 95% CI 1.6–8.2; p=0.013). Adjusted mean gain in pinhole visual acuity was 5.7 letters (95% CI 3.5–7.8) for sCXL vs 0.2 letters (95% CI −2.2 to 2.5) for aCXL (p<0.001). Adjusted mean change in Kmax: sCXL −1.8 D (95% CI −4.3 to 0.6) vs aCXL +1.2 D (95% CI −1.5 to 3.9; p=0.030). Proportion with Kmax flattening ≥1 D: sCXL 64.3% vs aCXL 42.6% (p=0.009). Progression (Kmax increase ≥1 D) occurred in 12.2% of sCXL eyes vs 26.5% of aCXL eyes (p=0.033). Adjusted mean change in K2: sCXL −0.9 D (95% CI −2.2 to 0.3) vs aCXL +0.1 D (95% CI −1.3 to 1.6; p=0.233). Adjusted mean change in MCT: sCXL −3.0 µm (95% CI −13.7 to 7.7) vs aCXL −11.8 µm (95% CI −23.9 to 0.4; p=0.240). Adverse events within 5 years: sCXL 17% of eyes (haze most common, 13%; scarring 3%; persistent epithelial defect 1%) vs aCXL 22.4% (haze 21.1%; scarring 3.9%; persistent epithelial defect 1.3%; p=0.483). At the 5-year visit, adverse events were low: sCXL 5% (haze 3, scarring 1, epithelial defect 1) and aCXL 3.9% (haze 2, scarring 1). Haze resolved in most eyes (sCXL 77%, aCXL 88%). Microbial keratitis occurred in 1 sCXL eye (15-year-old male) resulting in a scar.
**Clinical Implications:** Both sCXL and aCXL are safe and effective for long-term stabilization of keratoconus. However, sCXL provides superior visual and keratometric outcomes, with a lower rate of progression. These real-world data support sCXL as the preferred protocol when long-term efficacy is prioritized. The findings help clinicians counsel patients on expected outcomes and plan follow-up. Longer-term studies and randomized controlled trials are warranted.