Vitamin D Supplementation Impacts Systemic Biomarkers of Collagen Degradation and Copper Metabolism in Patients With Keratoconus

Abstract

Purpose To evaluate the impact of vitamin D (Vit D) supplementation on systemic biomarkers of collagen degradation, inflammation, oxidative stress, and copper metabolism in adolescent patients with keratoconus (KC). Methods This was a prospective observational pilot study. Twenty patients (age range, 16–19 years) presenting KC and Vit D insufficiency (<30 ng/mL) were included. Vit D supplementation was prescribed by their general practitioner as per the standard of care. Patients were followed up for 12 months. At each visit, best spectacle-corrected visual acuity (BSCVA), maximal keratometry (Kmax), and thinnest corneal thickness (TCT) were evaluated. The primary outcome of the study was the proportion of patients with Kmax progression of less than 1 D throughout the 12-month follow-up time. Blood samples were collected at different time points to evaluate Vit D levels and systemic markers of collagen degradation, inflammation, oxidative stress, and copper metabolism by ELISA or RT-PCR. Results Lower Vit D levels in the plasma were correlated with higher levels of systemic biomarkers of collagen degradation. Vit D supplementation increased the cell availability of copper. Moreover, stabilization of KC progression was found in 60% of patients (72% of eyes) after 12 months with Vit D supplementation. BSCVA, Kmax, and TCT rates remained stable during the observation period. Conclusions Our findings support that Vit D administration could affect ocular and systemic biomarkers in KC and illuminate a possible mechanism that can be used to develop new treatment alternatives. Translational Relevance Although KC therapy currently relies exclusively on surgical procedures, Vit D supplementation may offer a non-invasive and inexpensive alternative with minimal associated side effects.

The candidate proteins associated with keratoconus: A meta-analysis and bioinformatic analysis

“…Studies have shown that vitamin D (Vit D) supplementation can cause a decreased MMP9 level and an increased TIMP1 expression. Vit D may control the KC progression by improving Cu metabolism, leading to an increase in endogenous collagen cross-linking and antioxidant capacity [ 70 ]. Sulforaphane could prevent KC progression by activating the Nrf-2/HO-1 antioxidant pathway in rabbit KC models [ 71 ].…”

The Role of Vitamin D3 in Ocular Diseases

“…This explanation also clarifies why keratoconus may recur after corneal grafting, as patients likely maintain or worsen their vitamin D deficiency as they age [ 23 ]. Thus, supplementation of vitamin D can become an alternative way of treatment to surgery, as it provides the stabilization of KC progression after 12 months [ 24 ]. The meta-analysis by Gupta PC suggested that a low level of vitamin D can be associated with higher odds of severe keratoconus.…”

Keratoconus: imaging modalities and management

“…In certain instances, custom-designed contact lenses, such as scleral or rigid gas-permeable lenses, enhance visual acuity and improve comfort during the advanced stages of KCN [ 12 ] . New alternatives for medical treatment, such as topical copper or supplementary vitamin D, have been investigated [ 9 , 13 ] . However, clear evidence of their efficacy and safety is lacking.…”