The Link Between Vitamin D and Dry Eye Disease

The Link Between Vitamin D and Dry Eye Disease

December 20, 2021

Dry eye syndrome (DES) affects 35% of the population worldwide, and its prevalence increases with ageing.

Dry eye syndrome (DES) is a multifactorial disorder characterized by reduced quality or quantity of tears and leads to eye discomfort, visual disturbance, tear film instability and inflammation of the ocular surface.

Knowledge about the pathophysiology of dry eye has advanced from the simple concepts of deficient aqueous or lipid content to include concepts of tear hyperosmolarity, ocular surface inflammation and neurosensory abnormalities.

Moreover, recent studies have discovered that dry eye is a chronic inflammatory disease that has many features in common with autoimmune disease.

Inflammatory cytokines, metalloproteinases, and chemokines and their receptors lead to expansion of autoreactive T helper cells that infiltrate the ocular surface and lacrimal glands.

The result is a vicious circle of damage to the ocular surface and inflammation.

Vitamin D is a multifunctional hormone that can be obtained from the diet and is also produced in the skin. Apart from its well-known role in calcium metabolism and bone health, vitamin D is now recognized to have anti-inflammatory and immunoregulatory properties.

Researchers have identified vitamin D receptor (VDR) expression on the majority of immune cells (i.e. antigen-presenting cells, T cells and B cells).

Binding between active vitamin D and the VDR regulates several genes involved in inflammation, immunity, cellular proliferation, differentiation and apoptosis.

Vitamin D deficiency (VDD) and insufficiency (VDI) are increasing on a global level. VDD is associated with an increased risk of chronic diseases such as bone metabolic disorders, tumors, cardiovascular diseases, and diabetes.

Study finds A retrospective study demonstrated the increasing prevalence of VDD (28.9 percent) and VDI (41.4 percent) from 2001 to 2010.

Study participants who were black, less educated, poor, obese, current smokers, physically inactive, and infrequent milk consumers had a higher prevalence of VDD.

In the dry eye space, a 2018 study in Cornea investigated the efficacy of topical carbomer-based lipid-containing artificial tears (CLAT) and hyaluronate (HU) in patients with dry eye disease (DED) based on serum 25-hydroxyvitamin D (25HD) levels and cholecalciferol supplementation.

Data suggested the effect of topical CLAT and HU was dependent on serum 25HD levels. The authors concluded that cholecalciferol supplementation enhanced the efficacy of topical treatment and may be a useful adjuvant therapy for patients with DED refractory to topical lubricants.

Epidemiological studies have linked VDD with other ocular diseases, such as myopia, age-related macular degeneration (AMD), diabetic retinopathy, glaucoma, retinoblastoma, and uveitis. However, the underlying mechanism is not yet fully understood.

Case Report

Parts of the human eye—including the epithelium of the cornea, lens, ciliary body, and retinal pigment epithelium, as well as the corneal endothelium, ganglion cell layer, and retinal photoreceptors—contain vitamin D receptors (VDR).

Intramuscular injections of vitamin D improved tear hyperosmolarity. The recently discovered antiangiogenic, anti-inflammatory, and anti-neoplastic properties of calcitriol (the hormonally active metabolite of vitamin D) have shed some light on vitamin D’s role in the pathogenesis of ocular diseases.

Interestingly, there has been an isolated, VDD-related case report of a 40-year-old patient with persistent bilateral ocular pain for two years for whom conventional management of dry eye had failed.

Detailed ocular examination, meibography, and tear film evaluation were suggestive of bilateral meibomian gland dysfunction (MGD) and evaporative dry eye.

Topical medication failed to alleviate the patient’s symptoms. Conventional management having failed, LipiFlow (Johnson & Johnson Vision) was performed, and topical therapy with cyclosporine 0.05%, steroids, and lubricating eye drops was initiated with incomplete symptomatic relief.

To identify the cause of pain, imaging was performed with in vivo confocal microscopy and anterior segment spectral domain optical coherence tomography (OCT). Evaluation revealed severe VDD.

With parenteral therapy for VDD, there was a dramatic improvement in this patient’s symptoms. The authors suggested that inflammation aggravated by VDD resulted in an altered epithelial profile, Bowman’s layer damage, recruitment of dendritic cells, and an altered subbasal nerve plexus features in this patient with chronic DED.

Future for Dry Eye Disease

Should vitamin D serum testing be part of ODs’ DED work-up? Is vitamin D supplementation prophylactic for DED? Conflicting data exists to support this notion.

Awareness of the high prevalence of VDD and VDI among U.S. adults and related predictors could inform behavioral and dietary strategies for preventing VDD, monitoring VDI, and perhaps modulate its impact on/contribution to DED.

Eyecare practitioners hope that with more data they can answer these questions and have yet another avenue of therapy for ocular surface disease patients.