Delayed Bilateral Subepithelial Corneal Calcification In A Patient With Prior Corneal Collagen Cross-Linking (Cxl): A Rare Finding

Purpose: To report a rare case of bilateral subepithelial corneal calcification following corneal collagen cross-linking (CXL) for keratoconus.

We report the case of a 37-year-old female who presented with progressive bilateral decrease in vision and central corneal opacities approximately 5 years after undergoing CXL.

 In January 2023, a 37-year-old woman was referred to King Khalid Eye Specialist Hospital, Riyadh, for bilateral whitish corneal opacities with progressive visual decline over three years. She had keratoconus treated with bilateral collagen cross-linking eight years earlier. Medical history was unremarkable, with no trauma or contact lens wear. Uncorrected visual acuity was 20/40 OD and 20/50 OS, improving to 20/30 and 20/25 with rigid lenses, which she could not tolerate. Intraocular pressure was 10 mmHg bilaterally. Slit-lamp exam showed 3 mm central reticular opacities with rough whitish surfaces in both corneas. Anterior segment and fundus were normal. Topography confirmed keratoconus. AS-OCT showed anterior stromal hyperreflectivity, denser in the left eye, correlating with worse vision. Findings suggested bilateral corneal calcium deposition after CXL. Labs revealed vitamin D insufficiency (41 nmol/L) with normal calcium and thyroid levels. Superficial keratectomy with EDTA chelation was performed in both eyes. Due to persistent limitation in the left eye, lamellar keratoplasty (8.5 mm manual) was done without complications. Histopathology showed epithelial irregularity, Bowman layer disruption, subepithelial fibrosis, and calcium phosphate deposits on Von Kossa staining. At one year, vision was 20/60 (20/30 corrected) OD and 20/50 (20/25 corrected) OS; the right eye had central haze and the left graft remained clear.

Conclusions: This case report presents a rare case of bilateral subepithelial corneal calcification in a patient with multiple risk factors, including prior CXL among other potential contributors. An accurate diagnosis warrants differentiation from haze or fibrosis, and long-term follow-up is essential. Further research is warranted to clarify the role of phosphate-containing riboflavin formulations in calcific deposition