February 2016

 

INTERNATIONAL

 

Vitamin D and dry eye: Is there an association?


by Michelle Dalton EyeWorld Contributing Writer

 
 

Theres the possibility that its more than just the omega-3 thats helping patients. Having vitamin D probably helps people who are deficient but wont help people who are not vitamin D deficient and within the normal range. Alice Epitropoulos, MD

 
The TearLab Osmolarity System tests

The TearLab Osmolarity System tests for hyperosmolarity in the tear film, a hallmark of dry eye disease.

Source: Alice Epitropoulos, MD

New research from Turkey suggests there is

Vitamin D, a fat-soluble vitamin produced in the skin following exposure to sunlight, may be protective against the development of dry eye disease, according to a group of researchers from Turkey. Pelin Yildirim, MD, Kocaeli Derince Training and Research Hospital, Kocaeli, Turkey, and colleagues noted vitamin D deficiency (a serum 25-hydroxyvitamin D level of less than 20 ng/mL) has been linked to numerous health problems, including type 2 diabetes, hypertension, and cardiovascular disease, and optic neuritis and myopia. But to date, there is no data about the relationship, if any, between vitamin D deficiency and dry eye and the clinical parameters of both pathologies, Dr. Yildirim and co-authors said.1 Numerous studies have correlated vitamin D3 deficiency and other inflammatory diseases, including dry eye studies, said Alice Epitropoulos, MD, clinical assistant professor, Ohio State University, Columbus, and cofounder, the Eye Center of Columbus. This was the first study (while smallthere was only 50 healthy women enrolled) that made no other inflammatory correlation within the study group and specifically measured clinical signs of dry eye in a deficient population against a non-deficient control, she said. Other studies have evaluated the immunomodulatory role of vitamin D; in vivo studies (animal models) have shown vitamin D to be anti-inflammatory at the ocular surface, and in vitro vitamin D can lessen the inflammatory response to infection.

Since the underlying cause of dry eye is inflammation, it makes sense that there could be an association between vitamin D deficiency and the disease, Dr. Epitropoulos said. Other studies have reported that vitamin D3 induces production of IL-10, which inhibits production of other pro-inflammatory cytokines, including IL-1, IL-6 and TNF-alpha. It makes physiological sense that vitamin D3 would also play a role in assisting with the inflammatory mediators in the tear film in patients suffering with dry eye, Dr. Epitropoulos said.

Study details

Fifty premenopausal women with vitamin D deficiency and 48 controls were included. Participants were assessed by Schirmers test, tear break-up time test (TBUT), Ocular Surface Disease Index (OSDI), Stanford Health Assessment Questionnaire (HAQ), fatigue severity scale (FSS), and visual analogue scale-pain (VAS-pain).

Of the women with vitamin D deficiency, 52% (26 patients), 74% (37 patients), and 70% (35 patients) had dry eye according to the results of Schirmers test, TBUT, and OSDI, respectively. Lower scores in Schirmers test and TBUT and higher scores in OSDI were detected in patients with vitamin D deficiency than in controls (P<0.05). FSS was negatively correlated with Schirmers test (P=0.038) and TBUT scores (P=0.002); VAS-pain was negatively correlated with TBUT scores (P=0.023). HAQ scores showed no significant correlation with dry eye parameters (P>0.05). Vitamin D level was negatively correlated with OSDI (P<0.001) and positively with Schirmers test (P=0.001) and TBUT scores (P=0.029).

Impaired tear function tests may indicate a pathophysiological association between vitamin D deficiency and dry eye, the authors wrote.

Not a bullseye

Serum 25 D3 levels were not found to be associated with the severity of dry eye in a recent cross-sectional study on males with dry eye disease.2 Because the current study included only premenopausal women, that may be seen as a deficit, or simply due to patient selection criteria, Dr. Yildirim said, as the effects of aging and postmenopausal hormonal changes were eliminated.

Using Schirmers test (especially since this study did not specify if it was with or without anesthesia) has its limitations and is not a preferred method in testing for dry eye, Dr. Epitropoulos said. Schirmers test for aqueous deficiency does not test for evaporative dry eye disease, and its relatively insensitive for early forms of dry eye disease. Youre going to miss a lot of patients that have dry eye disease by using Schirmers, she said. Additionally, future studies evaluating the hypothesis should have a much larger sample size, along with more specific point of care testing such as tear osmolarity or inflammatory markers, such as the MMP-9 InflammaDry test [Rapid Pathogen Screening, Sarasota, Fla.]. The study authors also noted a limitation with the small study sample size. However, as the main symptoms of vitamin D deficiency are fatigue, pain, and functional impairment, this study is the first to demonstrate an association between dry eye and the clinical parameters of hypovitaminosis D, the authors wrote. In our study, fatigue was found to be correlated with dry eye parameters, including amount of tears and the stability of the tear film layer, they wrote. They also found pain to be associated with the tear film layer stability. There was not, however, an association between dry eye parameters with functional status.

An upside is that the study did employ TBUT analysis, which tests for tear instability, one of the hallmarks in the development of dry eye disease, Dr. Epitropoulos said. But the problem with TBUT is that its variable in mild to moderate dry eye disease. In severe form its not quite as variable, she said. Tear film breaks up almost instantaneously with more advanced forms of dry eye disease. For those who treat patients with dry eye, Dr. Epitropoulos said vitamin D is found in some sources of fish and many omega-3 preparations. Many anterior segment surgeons already prescribe re-esterified omega-3 preparations, and Dr. Epitropoulos currently prescribes re-esterified omega-3 supplements that have a vitamin D component (Dry Eye Omega Benefits, Physician Recommended Nutriceuticals, Plymouth Meeting, Pa.). Theres the possibility that its more than just the omega-3 thats helping patients, she said. Having vitamin D probably helps people who are deficient but wont help people who are not vitamin D deficient and within the normal range. The definition of dry eye is still evolvingthe Dry Eye WorkShop (DEWS) group is currently working on a revision to its landmark 2007 publicationand the next iteration may need to include vitamin D deficiency as a more prominent risk factor.

References

1. Yildirim P, et al. Dry eye in vitamin D deficiency: more than an incidental association. Int J Rheum Dis. 2015 Aug 13. [Epub ahead of print] 2. Galor A, et al. Effect of a Mediterranean dietary pattern and vitamin D levels on dry eye syndrome. Cornea. 2014;33:437441.

Editors note: The physicians have no financial interests related to this article.

Contact information

Epitropoulos
: aepitrop@columbus.rr.com
Yildirim: drpeliny@gmail.com

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