Research Review

Studies Examine Risk Factors for Dry Eye Disease

BY ERIC PAPAS, PHD, MCOPTOM, DIPCL, FAAO

You know the feeling...you spend hours waiting for a bus, and then three come along at once. Apparently, this observation also holds true for studies dealing with risk factors for dry eye disease, as there has been a small avalanche of publications on this topic recently. In fact, the last 18 months has seen seven different groups in five countries publish work in this area.

While it is great to have such a substantial body of work available, some may feel that it creates a degree of ambivalence. Large amounts of data—drawn from a range of geographical locations and covering different demographics—are attractive in terms of identifying what are truly relevant effects from among the noise. However, this very diversity, when coupled with the inevitable differences in methodology and disease definition that will exist among centers, can make it difficult for us to draw conclusions if our specific situation does not match those being explicitly dealt with in the study.

It would be wonderful if all of the produced risk factor lists agreed with one another; but, being human, researchers cannot cover every possibility, and so their individual and group biases come into play when deciding on study design. Their results reflect this “patchiness” of intention.

In fact, the absence of a particular risk factor from the “significant” list in a given study does not necessarily mean that it is of no fundamental importance. The reason may simply be that it wasn’t of special interest to the investigators at the time.

With that insight, there is an argument that says it is worth paying attention to any and all of the factors that emerge from the various studies; some clinical importance may be being signaled, even though only one group ever thought it was worth examining. We will return to this point later. For the moment, let’s start by looking at those areas in which there is general agreement.

Criteria Consensus

Contact Lens Use The most common significant risk factor across the seven studies was contact lens wear. Every group found that there was roughly a two- to three-times increased risk of dry eye when contact lenses were worn. This result probably comes as no surprise, given the well-known association between contact lens wear and symptoms of discomfort and dryness.

It might even seem reasonable to surmise that perhaps contact lenses are not really a direct cause of dry eye disease as such (with all of the attendant physiological changes that are implied by that designation), but that the risk factor data are simply reflecting that lenses often cause similar symptoms to those in dry eye disease.

Sorting through this requires some knowledge of the definitions used to designate individuals as dry-eyed or otherwise. While symptoms alone were the criterion in some cases, both signs and symptoms were deemed necessary elsewhere.

This confirms that, within the context of the multifactorial etiology of dry eye disease, contact lenses produce significant changes to the ocular environment that can and will push some individuals into manifesting a dry eyed state.

Gender and Age Next on the list are gender and age. Being female roughly doubles the risk of dry eye disease compared to being male (Ahn et al, 2014; Paulsen et al, 2014; Tan et al, 2015; Liu et al, 2014). This is also compounded for those who are menopausal and/or are undergoing hormone replacement therapy (Yang et al, 2015; Tan et al, 2015).

Age-related problems really start to become significant beyond 50 years of age, and geographical or ethnic factors may have relevance to the evident amount of excess risk. Studies conducted in mainland China, for example, report that the increased risk for 60-year-olds is around 3.5 times, while the figures for both the United Kingdom and the United States are smaller at 1.1 to 1.3 times (Liu et al, 2014; Vehof et al, 2014; Paulsen et al, 2014).

Mental Health It is interesting to note that the next most consistently reported risk factor revolved around mental health issues. Typical conditions mentioned were depression, post-traumatic stress disorder, and extreme stress; sufferers appeared to have up to twice the dry eye risk compared to their unaffected peers (Ahn et al, 2014; Vehof et al, 2014; Yang et al, 2015).

This is a complex area in which it is difficult to separate cause from effect. For example, as a treatment for their mental state, many individuals will be taking quite powerful anti-depressant or anti-anxiety medications, which can precipitate dry eye problems (Ahn et al, 2014). However, a patient’s emotional state can also be heightened by his ocular difficulties (Ahn et al, 2014).

An additional link is the potential for psychological pressures to act as the spark for autoimmune disease (Karaiskos et al, 2009), which is also one of the more prominent risk factors for dry eye. So, while a patient’s mental state is evidently an important factor, it is one for which clinical decision-making may be tricky.

Divergent Theories

The aforementioned factors form the bulk of the major risk factors for dry eye syndrome. But, there is still value in considering things that crop up less often.

One such item is increased sensitivity to pain, which has been newly identified in a study of female twins (Vehof et al, 2014). Before going further, it is important to understand that the phenomenon being referred to here is not corneal sensitivity, which has generally been found to decrease in dry eye (Bourcier et al, 2005; Wirth and Nepp, 2014), but thermal sensitivity of the forearm.

Vehof et al (2014) point out that because of this phenomenon, women who have dry eye disease may report symptoms earlier compared to others, and they are more likely to suffer from one of a series of chronic pain syndromes such as pelvic pain, irritable bowel syndrome, or chronic widespread pain syndrome (a.k.a., fibromyalgia). An intriguing suggestion is that pain syndromes and dry eye disease may be connected by sharing an etiological pathway, and they may even have genetic factors in common.

Disease Protection

It is useful to remember that risk factor studies can render good news, as well as bad, by identifying features that are protective against diseases. For dry eye, the regular use of vitamin supplements—including vitamins A, B6, B12, C, and E as well as beta-carotene and multivitamins—fall into that category; these have been found to offer a substantially reduced risk (Yang et al, 2015).

Even greater protection seems to accrue from consuming a diet rich in omega-3 fatty acids (Yang et al, 2015); the data indicate that the risk is almost halved for those in this group, presumably due to the general suppression of inflammatory elements that accompanies omega-3 supplementation.

These studies are vital to clarifying dry eye disease, and they offer vital clues that can assist in diagnosing and treating those affected. This latest batch shows that we can offer something good to eat while we await the arrival of the next risk factor bus. CLS

For references, please visit www.clspectrum.com/references and click on document #236.

Professor Eric Papas is executive director of Research & Development, Brien Holden Vision Institute and Vision Cooperative Research Centre, and professorial visiting fellow, School of Optometry & Vision Science, University of New South Wales, Sydney, Australia. The Brien Holden Vision Institute and Vision Cooperative Research Centre have received research funds from B+L, AMO, and Allergan and have proprietary interest in products from Alcon, CooperVision, and Carl Zeiss. You can reach him at e.papas@brienholdenvision.org.