The effects of Vitamin D on Keratoconus progression.
Study Goal
The researchers aimed to determine whether Vitamin D supplementation affects Keratoconus progression, systemic inflammation, collagen degradation, and oxidative stress in adolescents with Vitamin D deficiency.
Results Summary
65% of patients showed stable Keratoconus progression after 12 months, with improvements in systemic biomarkers related to inflammation and collagen metabolism. RNA sequencing revealed differential responses, including downregulation of inflammatory pathways and upregulation of proteoglycan synthesis in responders.
Population
Adolescents (ages 12.2-19.9) with Keratoconus and Vitamin D insufficiency (<30 ng/mL).
Effective Dosage
Not specified
Duration
6 months of supplementation, 12 months of follow-up
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
Vitamin D supplementation | no change | best spectacle-corrected visual acuity (BSCVA) | adolescents affected by Keratoconus (KC) and Vit D deficiency | - | remained stable | #1 |
Vitamin D supplementation | no change | maximal keratometry (Kmax) | adolescents affected by Keratoconus (KC) and Vit D deficiency | - | remained stable | #2 |
Vitamin D supplementation | no change | thinnest corneal thickness (TCT) | adolescents affected by Keratoconus (KC) and Vit D deficiency | - | remained stable | #3 |
Vitamin D supplementation | increase | VDBP | adolescents affected by Keratoconus (KC) and Vit D deficiency | - | upregulated the expression | #4 |
Vitamin D supplementation | increase | VDR | adolescents affected by Keratoconus (KC) and Vit D deficiency | - | increase in the expression | #5 |
Vitamin D supplementation | increase | CD14 | adolescents affected by Keratoconus (KC) and Vit D deficiency | - | increase in the expression | #6 |
Vitamin D supplementation | no change | principal enzymes involved in Vit D activation/deactivation | adolescents affected by Keratoconus (KC) and Vit D deficiency | - | no changes | #7 |
Vitamin D supplementation | neutral | collagen degradation | adolescents affected by Keratoconus (KC) and Vit D deficiency | - | modulation | #8 |
Vitamin D supplementation | neutral | collagen crosslinking | adolescents affected by Keratoconus (KC) and Vit D deficiency | - | modulation | #9 |
Vitamin D supplementation | decrease | inflammatory pathways | Responder patients | - | downregulation | #10 |
Vitamin D supplementation | decrease | platelet activation pathways | Responder patients | - | downregulation | #11 |
Vitamin D supplementation | increase | proteoglycan metabolism/biosynthesis enrichment | Responder patients | - | upregulation | #12 |
Vitamin D supplementation | neutral | KC progression | adolescent patients with Vit D insufficiency | - | can affect | #13 |
Vitamin D supplementation | neutral | systemic inflammation | adolescent patients with Vit D insufficiency | - | modulation | #14 |
Vitamin D supplementation | decrease | collagen degradation | adolescent patients with Vit D insufficiency | - | inhibition | #15 |
Vitamin D supplementation | increase | proteoglycan synthesis | adolescent patients with Vit D insufficiency | - | promotion | #16 |
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.