A recent study published in the American Journal of Ophthalmology evaluated whether Vitamin D (VD) supplementation affects local keratoconus (KC) progression and systemic biomarkers in adolescents affected by KC and VD deficiency.
Give me some background.
KC has traditionally been considered a non-inflammatory corneal degeneration, characterized by progressive changes in corneal structure and organization of collagen.
However: Previous studies have suggested that KC could be an ocular manifestation of a systemic disease.
- Why: The substantial comorbidities observed with KC
- In particular, KC has been associated with many systemic diseases and genetic disorders (ex., atopy, Down syndrome, connective tissue disease) and ethnicities (ex., Asians).
Moreover: One study recommended that future research test whether populations with high prevalence of KC have specific genetic background or ethno-specific environmental risk factors.
Now bring in Vitamin D.
VD has anti-inflammatory, antioxidant, and immunomodulatory properties.
In fact: Studies have proposed that its antioxidant properties could address oxidative stress to heal the corneal epithelium and maintain corneal tight junctions.
- Further: KC has been found to be associated with VD deficiency.
Meaning: By inhibiting systemic inflammation and collagen catabolism with VD supplementation, adolescent patients may experience substantial clinical stabilization in KC progression.
Next: Talk about the study.
In this prospective, single-center interventional study, researchers included 40 patients (87.5% male, age range: 12.2-19.9) that presented with both KC and VD insufficiency (< 30 ng/mL) at the San Raffaele Scientific Institute in Milan, Italy.
- To manage the VD deficiency, oral cholecalciferol supplementation (50,000 IU) was prescribed once a week for the first 3 months, and then for maintenance treatment 50,000 IU was given once a month up to Month 6.
How long did they track these patients: Follow-up visits were scheduled every month for 12 months.
Main outcome measure: Percentage of patients with a Kmax progression less than 1 diopter (D) throughout the entire study (i.e., stable patients)
How were patients assessed?
The investigators analyzed a variety of factors, including:
- Local KC progression (measured at each visit)
- Best spectacle-corrected visual acuity (BSCVA)
- Maximal keratometry (Kmax)
- Thinnest corneal thickness (TCT)
- VD levels and systemic biomarkers (measured with blood samples at Month 0 and Month 6)
- Inflammation
- Collagen degradation
- Oxidative stress
In addition: Full RNA sequencing was performed on 20 patients at Months 0 and 6.
Findings?
During the 12-month observational period, 24 patients (65% of patients, 75% of eyes) remained stable in measures of local KC progression, including:
- BSCVA
- Kmax (change < 1 D)
- TCT rates
VD supplementation upregulated the expression of VD binding protein (VDBP), VD receptor (VDR), and the gene cluster of differentiation 14 (CD14)—with no changes in the principal enzymes involved in VD activation / deactivation.
Quick refresher on VD cell biology:
- VDBP is the primary transporter of VD in blood plasma
- VDR mediates the action of VD on cells
- VDRs can influence the expression of the gene CD14
Anything else?
The study authors also observed reduced collagen degradation and increased collagen crosslinking.
Finally: The RNA-sequencing subgroup showed differential responses to VD treatment, with responders showing:
- Downregulation in inflammatory and platelet activation pathways
- Upregulation of proteoglycan metabolism / biosynthesis enrichment
Limitations?
This study did not include a control group to compare the effect of VD supplementation on healthy patients.
Take home.
The findings suggest that VD supplementation can slow KC progression in adolescent patients with VD insufficiency by:
- Modulating systemic inflammation
- Inhibiting collagen degradation
- Promoting proteoglycan synthesis
The study authors added that these results strongly suggest that KC may be the ocular manifestation of a systemic disorder.