The effects of Vitamin D on Keratoconus progression.

Abstract

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 (BSCVA) , maximal keratometry (Kmax) , and thinnest corneal thickness (TCT) . Blood samples were collected at month 0 (M0) and month 6 (M6) to measure Vit D levels and systemic biomarkers of inflammation, collagen degradation, and oxidative stress by ELISA or RT-PCR; full RNA sequencing was performed on 20 patients at M0 and M6. 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 (i.e.: stable patients) . RESULTS 65% of patients remained stable (75% of eyes) after 12 months. Specifically, BSCVA, Kmax, and TCT rates remained stable during the 12-month observational period. ELISA performed on blood plasma showed that Vit D upregulated the expression of VDBP. 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.