LONG-TERM OUTCOMES OF CORNEAL CROSS-LINKING: NINE-YEAR FOLLOW-UP

To evaluate post-treatment morphological changes in patients diagnosed with keratoconus who underwent corneal cross-linking (CXL), particularly analyzing the remodeling process characterized by corneal thinning and flattening of keratometric values.

This study was conducted retrospectively at a single-center, tertiary-level ophthalmology clinic.

Eighteen eyes of 18 patients treated with epi-off CXL or phototherapeutic keratectomy-assisted CXL between January 2013 and December 2022 were retrospectively analyzed. Visual, refractive, corneal topographic, pachymetric, and anterior segment findings were recorded preoperatively, at 1 year, and at ≥3 years postoperatively. Progressive thinning was defined as ≥120 µm reduction in pachymetry or ≥2.0 D decrease in topographic keratometry between baseline and the last visit ≥3 years after CXL.

Among 600 patients who underwent CXL, 18 patients (3%) developed progressive late-onset corneal thinning. The mean age of affected patients was 34 ± 6.5 years (21–44 years); 15 were female and 3 were male. Thinning occurred at a mean of 7 ± 2.03 years postoperatively (3–11 years). Three female patients were in the breastfeeding period, five had pregnancy after CXL, and one was undergoing in vitro fertilization treatment. The mean thinnest pachymetry was 306 ± 60.4 µm (149–396 µm). One patient developed corneal perforation requiring penetrating keratoplasty. The incidence of progressive thinning was significantly higher in females (9.87%) compared to males (0.67%) (p < 0.001, Fisher’s Exact Test). The overall 3% prevalence showed no statistically significant difference compared with the 1.97% rate reported in the literature (p > 0.05).

Although CXL is recognized as a safe and effective treatment to halt keratoconus progression, late-onset progressive corneal thinning may occur in a small but clinically relevant proportion of patients. The significantly higher incidence in females suggests that hormonal influences—such as pregnancy, breastfeeding, or assisted reproductive treatments—may compromise postoperative corneal stability. Long-term follow-up is therefore essential, particularly in young women of reproductive age, to timely detect late biomechanical deterioration.