The Effects of Vitamin D on Keratoconus Progression

Purpose: The aim of this study was to assess whether vitamin D (Vit D) supplementation affects local disease progression, as well as systemic inflammation, collagen degradation, and oxidative stress in adolescents affected by keratoconus (KC) and Vit D deficiency. Design: Prospective, interventional single-center study. Subjects: Forty patients (age range, 12.2-19.9) presenting with both KC and Vit D insufficiency (<30 ng/mL) were included in the study. Methods: Vit D was prescribed for 6 months as per standard of care. Follow-up visits were scheduled for 12 months. Each visit included the measurement of best spectacle-corrected visual acuity, maximal keratometry (Kmax), and thinnest corneal thickness. Blood samples were collected at month 0 and month 6 to measure Vit D levels and systemic biomarkers of inflammation, collagen degradation, and oxidative stress by ELISA or real-time polymerase chain reaction; full RNA sequencing was performed on 20 patients at month 0 and month 6. Main Outcome Measures: The primary outcome of the study was the percentage of patients with a Kmax progression less than 1 diopter (D) throughout the entire study (ie, stable patients). Results: Overall, 65% of patients remained stable (75% of eyes) after 12 months. Specifically, best spectacle-corrected visual acuity, Kmax, and thinnest corneal thickness rates remained stable during the 12-month observational period. ELISA performed on blood plasma showed that Vit D upregulated the expression of Vit D binding protein. QPCR performed on peripheral leukocytes showed an increase in the expression of VDR and CD14 with no changes in the principal enzymes involved in Vit D activation/deactivation. ELISA and qPCR showed the modulation of collagen degradation and collagen crosslinking. Subgroup analysis with RNA sequencing showed differential response to Vit D treatment. Responder patients showed downregulation in inflammatory and platelet activation pathways, and upregulation of proteoglycan metabolism/biosynthesis enrichment. Conclusions: Our findings support the hypothesis that Vit D supplementation can affect KC progression in adolescent patients with Vit D insufficiency possibly through the modulation of systemic inflammation, inhibition of collagen degradation, and promotion of proteoglycan synthesis. Our results strongly suggest that KC may be the ocular manifestation of a systemic disorder.