Ocular Changes and Tear Cytokines in Individuals with Low Serum Vitamin D Levels: A Cross-Sectional, Controlled Study

ABSTRACT

Background

We investigated the effects of vitamin D on the ocular surface, tear functions, corneal imaging, and tear film cytokine levels.

Methods

Fifty-two patients with vitamin D levels were examined in 3 groups according to serum vitamin D levels; 28 in group 1 (<12 ng/ml), 10 in group 2 (12–20 ng/ml), and 14 in group 3 (>20 ng/ml). Ocular surface disease index (OSDI), tear break up time (BUT), lissamine green (LG) staining, Schirmer test, in vivo confocal microscopy (IVCM), and tear collection for cytokine analysis were performed.

Results

The mean OSDI score was 35.2 ± 23.3, 36.2 ± 17.7, 24.4 ± 18.2 (p = .253), TBUT was 6.7 ± 2.5 sec, 9.3 ± 1.8 sec, 11.1 ± 2.8 sec (p < .001), Schirmer test was 16.7 ± 8.5 mm, 18.7 ± 7.6 mm, and 20.2 ± 7 mm (p = .254), median LG staining grade was 1 (0–3), 1 (0–2), 0 (0–1) (p = .008) in group 1, group 2, and group 3, respectively. Basal epithelial cell density was 4 027 ± 512 cells/mm², 4 673 ± 451 cells/mm², 5 067 ± 817 cells/mm² (p = < 0.001), sub-basal nerve density was 978 ± 204 μm/frame, 1 236 ± 172 μm/frame, 1 425 ± 290 μm/frame (p = <0.001), median number of long nerve fibers was 3 (2–4) nerve/frame, 4 (3–4) nerve/frame, 4 (3–6) nerve/frame (p = .001), and median grade of nerve fiber tortuosity was 2 (0–3), 2.5 (2–3), 3 (2–4) (p < .001) in group 1, group 2, and group 3, respectively. Mean IL-1 β (82.62 ± 15.26, 85.57 ± 17.41, and 66.44 ± 11 ng/ml in group 1, 2 and 3, respectively, p = .002), IL-17 (77.80 ± 24.91, 64.46 ± 25.47, 55.42 ± 12.05 ng/ml in group 1, 2 and 3, respectively, p = .012), and IL-2 (75.7 ± 18.4, 66.13 ± 26.78, and 59.65 ± 16.04 ng/ml in group 1, 2 and 3, respectively, p = .048) levels were significantly lower in group 3, whereas, IL-13 levels were significantly higher in group 3 (16.12 ± 5.24, 19.20 ± 4.90, and 21.6 ± 5.55 ng/ml in groups 1, 2, and 3, respectively, p = .010).

Conclusions

Vitamin D deficiency/insufficiency is associated with ocular surface changes shown with significant TBUT, LG staining, and tear film cytokine contents. Besides, significant corneal basal epithelial, sub-basal nerve density, and structural sub-basal nerve changes were associated with lower Vitamin D levels.

KEYWORDS:

• In vivo confocal microscopy
• ocular surface index
• tear cytokines
• vitamin D deficiency

List of abbreviations

Table

Author’s contributions

NCB, LO study design, participants’ selection, data analysis writing the manuscript.

DK, SK eye examinations, data collection, data analysis, writing the manuscript.

ÇT study design, analysis of cytokine, data analysis, writing the manuscript.

NDÇA, ŞGÖ, Mİ, and FIT study design, participants’ selection, data interpretation,

All authors read and approved the manuscript.

Declarations

The study protocol was approved by the Hacettepe University Ethics Committee (03.01.2017, GO 17/20-39) and was conducted in accordance with the tenets of the Declaration of Helsinki, and all participants signed informed consent.

Data availability statement

The datasets used and analyzed during the current study are available from the corresponding author on reasonable requests.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The study was funded by Hacettepe University Scientific Research Projects Unit (THD-2018-17174).