VITAMIN D DEFICIENCY IN NEOVASCULAR VERSUS NONNEOVASCULAR AGE-RELATED MACULAR DEGENERATION

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in elderly patients and prevention remains a critical issue to reduce the burden of the disease. Modifiable risk factors for the development and progression of AMD include cigarette smoking, hypertension, abdominal obesity, physical activity, and dietary fat intake.1–5 Supplementation with high-dose antioxidants, and recently macular carotenoids, have been proven to reduce the progression from intermediate nonneovascular age-related macular degeneration (NNVAMD) to advanced AMD.6,7 Because the pathogenesis of AMD is known to be related to inflammation and angiogenesis, factors that influence these processes may affect the progression from NNVAMD to neovascular age-related macular degeneration (NVAMD).8–10 Vitamin D deficiency has been linked with a number of systemic disorders ranging from multiple sclerosis to tuberculosis.11-12 The biologically active form of vitamin D (1,25-dihydroxyvitamin D) has demonstrated anti-inflammatory and antineovascular properties. Active vitamin D has been shown to inhibit the proliferation of T-helper and cytotoxic T cells while also reducing the production of proinflammatory cytokines IL-2, IL-6, IL-8, and IL-12.12-16 Active vitamin D also demonstrates antineovascular properties because it inhibits endothelial cell proliferation and decreases levels of hypoxia inducible factor 1, which promotes the expression of vascular endothelial growth factor.17,18 Furthermore, active vitamin D has been shown to protect against oxidative stress in vitro possibly by inducing glucose-6-phosphate dehydrogenase (G6PD).19 At the tissue level, genes involved in the production and metabolism of active vitamin D, including CYP27B1 and the vitamin D receptor, are expressed in vitreous, retina, retinal pigment epithelium, and choroidal tissues.20 These findings suggest a plausible biologic link between dysregulation of the normal homeostatic role of vitamin D and the known pathobiology of AMD. The serum level of 25-hydroxyvitamin D (25OHD) is the primary indicator of vitamin D status in the body Three population-based studies have investigated the relationship between vitamin D levels and the presence of NNVAMD versus non-AMD with conflicting results.21-23 Another three studies, each with limited cohorts, have included data about NVAMD versus NNVAMD patients. Morrison et al 20 compared levels of 25OHD in 50 pairs of discordant siblings with NVAMD versus NNVAMD, and found an insignificant trend toward higher levels in the sibling with the lower AMD severity (P = 0.22). Similarly, Seddon et al 24 found that a lower dietary intake of vitamin D correlated with worse AMD disease. However, in a retrospective cohort study of the Medicare 5% data comparing a population of vitamin D deficient patients versus matched controls, Day et al 25 found no difference in the incident rates of NNVAMD or NVAMD. Our aim was to compare 25OHD levels in a large cohort of patients with NNVAMD, NVAMD, and controls. Given the antineovascular and anti-inflammatory properties of vitamin D, we hypothesized that lower 25OHD levels and vitamin D deficiency are more associated with NVAMD, versus NNVAMD and control patients.