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

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 ß (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.

Hematologically important mutations: leukocyte adhesion deficiency (first update).

Leukocyte adhesion deficiency (LAD) is an immunodeficiency caused by defects in the adhesion of leukocytes (especially neutrophils) to the blood vessel wall. As a result, patients with LAD suffer from severe bacterial infections and impaired wound healing, accompanied by neutrophilia. In LAD-I, mutations are found in ITGB2, the gene that encodes the ß subunit of the ß(2) integrins. This syndrome is characterized directly after birth by delayed separation of the umbilical cord. In the rare LAD-II disease, the fucosylation of selectin ligands is disturbed, caused by mutations in SLC35C1, the gene that encodes a GDP-fucose transporter of the Golgi system. LAD-II patients lack the H and Lewis Le(a) and Le(b) blood group antigens. Finally, in LAD-III (also called LAD-I/variant) the conformational activation of the hematopoietically expressed ß integrins is disturbed, leading to leukocyte and platelet dysfunction. This last syndrome is caused by mutations in FERMT3, encoding the kindlin-3 protein in all blood cells that is involved in the regulation of ß integrin conformation.