Dry Eye Disease: What Is the Role of Vitamin D?

Dry eye disease (DED) is a multifactorial condition resulting from reduced tear secretion from the lacrimal glands, increased tear water evaporation or the production of poor-quality tears. Such tear instability can lead to inflammation and damage of the ocular surface, as well as to abnormal nociception. Historically, tear substitutes and corticosteroids have been the bastion of DED therapy, but a substantial number of patients still suffer from residual symptoms even after being treated with traditional treatments. Aiming to find safe and effective alternative therapies, recent efforts have been focused on the role of vitamin D in the cellular physiology of the eye. Possibly because of its positive effect in modulating the immune and inflammatory responses, the systemic supplementation of vitamin D seems, indeed, to be an effective therapeutic strategy, especially, but not only, for patients affected by DED that does not respond to conventional treatments. In this context, this review focuses on the literature reporting on the pathogenesis and treatment of DED, with a special emphasis on the recent investigations reporting on the potential role of the systemic administration of vitamin D as a therapeutic approach in the management of such condition.

The role of systemic and topical fatty acids for dry eye treatment.

Dry eye is a prevalent condition and one of the main reasons for patients to seek ophthalmic medical care. A low systemic level of omega fatty acids is a risk factor for dry eye disease (DED). There are two groups of essential fatty acids (EFAs): the omega-6 (n-6) family and the omega-3 (n-3) family. Humans evolved on a diet in which the n-6:n-3 ratio was approximately 1:1, however the current Western diet tends to be deficient in n-3 EFAs and this ratio is typically much higher (approaching 17:1). The metabolism of EFAs generates four new families of local acting mediators: lipoxins, resolvins, protectins, and maresins. These molecules have anti-inflammatory and pro-resolution properties. We present a critical overview of animal model studies and human clinical trials that have shown that dietary modification and oral supplementation could be complementary therapeutic strategies for the treatment of dry eye. Furthermore, we discuss preliminary results of the topical application of n-3 and n-6 EFAs because these molecules may act as natural anti-inflammatory agents with positive changes of the entire ocular surface system.

The effect of an artificial tear combining hyaluronic acid and tamarind seeds polysaccharide in patients with moderate dry eye syndrome: a new treatment for dry eye.

PURPOSE: Synergistic interactions between hyaluronic acid (HA) and tamarind seed polysaccharide (TS-polysaccharide) have been demonstrated by means of nuclear magnetic resonance spectroscopy. This study was designed to investigate the potential clinical benefit of a combination of HA and TS-polysaccharide in managing dry eye disease (DED). METHODS: A total of 49 subjects with moderate DED, confirmed by Ocular Surface Disease Index (OSDI) questionnaire score between 10 and 25, tear break-up time (BUT) <10 seconds, or Schirmer I test <5.5 mm after 5 minutes, and lissamine green staining of the ocular surface >2 according to National Eye Institute score system, were enrolled into this multicenter, randomized, double-masked study to receive either combination of HA and TS-polysaccharide or carmellose sodium for 3 months, both instilled 4 times per day. The assessments included OSDI questionnaire, tear film stability (BUT), tear production (Schirmer I test), and corneal and conjunctival staining. RESULTS: Patients treated with HA and TS-polysaccharide showed a statistically significant improvement in the OSDI score at the end of the study compared to the baseline and control groups. The HA and TS-polysaccharide and carmellose sodium were equally effective in reducing BUT and the extent of injury assessed by corneal and conjunctival staining. Non-significant changes were recorded for Schirmer I test. CONCLUSIONS: Based on the results of this clinical trial, the combination of HA and TS-polysaccharide appears to be effective in improving the symptoms of dry eye, opening new scenarios in possible treatment of the disease by combining different molecules.

New findings in ATP supply in rod outer segments: insights for retinopathies.

BACKGROUND INFORMATION: The rod outer segment (OS) is the specialised organelle where phototransduction takes place. Our previous proteomic and biochemical analyses on purified rod disks showed the functional expression of the respiratory chain complexes I-IV and F1 Fo -ATP synthase in OS disks, as well as active soluble tricarboxylic acid cycle enzymes. Here, we focussed our study on the whole OS that contains the cytosol and plasma membrane and disks as native flattened saccules, unlike spherical osmotically intact disks. RESULTS: OS were purified from bovine retinas and characterised for purity. Oximetry, ATP synthesis and cytochrome c oxidase (COX) assays were performed. The presence of COX and F1F0-ATP synthase (ATP synthase) was assessed by semi-quantitative Western blotting, immunofluorescence or confocal laser scanning microscopy on whole bovine retinas and bovine retinal sections and by immunogold transmission electron microscopy (TEM) of purified OS or bovine retinal sections. Both ATP synthase and COX are catalytically active in OS. These are able to consume oxygen (O2) in the presence of pyruvate and malate. CLSM analyses showed that rhodopsin autofluorescence and MitoTracker Deep Red 633 fluorescence co-localise on rod OS. Data are confirmed by co-localisation studies of ATP synthase with Rh in rod OS by immunofluorescence and TEM in bovine retinal sections. CONCLUSIONS: Our data confirm the expression and activity of COX and ATP synthase in OS, suggestive of the presence of an extra-mitochondrial oxidative phosphorylation in rod OS, meant to supply ATP for the visual transduction. In this respect, the membrane rich OS environment would be meant to absorb both light and O2. The ability of OS to manipulate O2 may shed light on the pathogenesis of many retinal degenerative diseases ascribed to oxidative stress, as well as on the efficacy of the treatment with dietary supplements, presently utilised as supporting therapies.

A multicentre, double-masked, randomized, controlled trial assessing the effect of oral supplementation of omega-3 and omega-6 fatty acids on a conjunctival inflammatory marker in dry eye patients.

PURPOSE: To determine whether oral supplementation with omega-3 and omega-6 fatty acids can reduce conjunctival epithelium expression of the inflammatory marker human leucocyte antigen-DR (HLA-DR) in patients with dry eye syndrome (DES). METHODS: This 3-month, double-masked, parallel-group, controlled study was conducted in nine centres, in France and Italy. Eligible adult patients with mild to moderate DES were randomized to receive a placebo containing medium-chain triglycerides or treatment supplement containing omega-3 and omega-6 fatty acids, vitamins and zinc. Treatment regimen was three capsules daily. Impression cytology (IC) was performed at baseline and at month 3 to assess the percentage of cells expressing HLA-DR and to evaluate fluorescence intensity, an alternate measure of HLA-DR. Dry eye symptoms and objective signs were also evaluated. Analyses were performed on the full analysis set (FAS) and per-protocol set (PPS). RESULTS: In total, 138 patients were randomized; 121 patients with available IC were included in the FAS, and of these, 106 patients had no major protocol deviations (PPS). In the PPS, there was a significant reduction in the percentage of HLA-DR-positive cells in the fatty acids group (p = 0.021). Expression of HLA-DR as measured by fluorescence intensity quantification was also significantly reduced in the fatty acids group [FAS (p = 0.041); PPS (p = 0.017)]. No significant difference was found for the signs and symptoms, but there was a tendency for improvement in patients receiving the fatty acids treatment. CONCLUSION: This study demonstrates that supplementation with omega-3 and omega-6 fatty acids can reduce expression of HLA-DR conjunctival inflammatory marker and may help improve DES symptoms.