The recent DEWS II report published in July 2017¹ has updated and refined our understanding of dry eye disease. This report serves as a timely reminder that we must continue to advance our understanding of the pathophysiology and clinical approaches to dry eye.

As the population ages, the number of people with glaucoma increases. The likelihood of ocular surface disease (OSD) also increases with age. And, as OSD may be an under-recognized co-morbid condition in patients with glaucoma, improved detection and treatment may lead to better clinical outcomes.

Understanding Dry Eye

There are multiple contributing causes for an abnormal tear film and ocular surface disease, including aging, environment, hormonal changes, meibomian gland disorders, and medication use. The complex interactions between the inciting events and the pathophysiologic responses are often referred to as a “vicious cycle.”

As our appreciation of OSD evolves to better understanding the factors interfering with homeostasis of the tear film, we can take a more targeted approach to improving the ocular health and comfort of our glaucoma patients, as well as our other patients who suffer with OSD or dry eye.

OSD in Glaucoma Patients

How prevalent is OSD in glaucoma patients? This question can best be interpreted by comparing studies in glaucoma patients to what we know about the general population.

In the Women’s Health Study,² nearly 40,000 female health professionals were asked about the symptoms of dry eye. Nearly 10% of women aged 75 or older reported symptomatic dry eye. In the Physicians’ Health Study, more than 25,000 men were surveyed about dry eye disease.³ The prevalence among men 80 years and older was reported as nearly 8%. A cross-sectional community study of more than 2,500 men and women aged 65 or older reported nearly 15% with one or more dry eye symptoms often or all the time.⁴

These studies serve as benchmarks, allowing us to expect to see dry eye in about 8% to 15% of our glaucoma patients. However, the reality is far different.

Several studies have evaluated the prevalence of OSD in treated glaucoma patients using the Ocular Surface Disease Index (OSDI).⁵ The OSDI consists of 12 questions that assess the functional impact of the symptoms of dry eye disease.

Leung and colleagues⁶ surveyed 101 glaucoma or ocular hypertension subjects and found mild, moderate, or severe symptoms in 59% in a single-center study. Fechtner and colleagues⁷ surveyed 630 treated subjects at 10 study sites and found similar results. In this study, 48.4% had mild, moderate, or severe symptoms. Slightly more than 27% of treated glaucoma patients had moderate to severe OSD symptoms.⁷

This prevalence is much greater than we would have predicted from population studies, but we now know that topical glaucoma treatments can negatively impact the health of the ocular surface.

OSD Detection

In the past, in many practices, detecting ocular surface disease wasn’t a high priority because there were few effective interventions. A patient who complained of ocular irritation might have been given a sample of lubricating drops and sent on her way. Now that there are more ways to address these complaints, it is well worth eliciting them. A detailed history and careful clinical examination can help detect signs and symptoms of OSD.

That said, it is important to note that the signs of OSD don’t always match the symptoms. For example, a patient may be miserable but have a relatively healthy-appearing ocular surface. Conversely, a terrible-looking ocular surface can be accompanied by dryness-induced nerve damage, which can decrease actual symptoms.

Multiple approaches have become available to evaluate the various contributing factors. It is important for clinicians to keep in mind that any new testing modality should be subjected to a meaningful validation process. Due to the complexity of OSD, no one test is best.

Patient questionnaires have been validated and accepted as a means of assessing symptoms of OSD. The OSDI was developed to study the impact of medical intervention for OSD, and has since been adapted more broadly to survey for OSD. It is worth noting that, while this is a validated tool, it has not been validated specifically for the glaucoma population. Other shorter surveys are also available.

We don’t need to overly complicate the detection or treatment of OSD. A few simple questions, such as “Are your eyes uncomfortable much of the time?” or “Do you find your vision gets worse late in the day?” can help to identify potential cases of OSD. A look at the medical history for diseases associated with dry eye, such as autoimmune disease or thyroid disease, may also identify patients at risk.

Diagnostic Testing

A slit lamp biomicroscopic examination provides many opportunities to detect the signs of OSD. Simple diagnostic maneuvers, such as examination of the meibomian glands or measuring tear breakup time using fluorescein stain, can easily be added to a routine examination. Tear meniscus height is an indicator of tear volume and can be assessed during slit lamp examination.

For symptomatic patients, aim to distinguish between a lipid deficiency leading to evaporative disease and an aqueous production deficiency. Schirmer’s testing can be useful in detecting aqueous production deficiency. This test does add to the examination time and the results can be variable, but it can be helpful in some cases.

Tear film osmolarity can be an indicator of tear health. Increased tear osmolarity suggests that the tears are not stable in composition. It may be the result of lipid layer dysfunction allowing for evaporation. Inflammation can also be a biomarker for OSD. A combination of history, physical examination, and supplemental testing remains are considered best practices for assessing OSD.

A Practical Approach to OSD

A rational approach to OSD in glaucoma patients will address underlying medical and environmental conditions, as well as interventions to improve tear film quality and overall ocular health. Treatment of dry eye is being shaped by new medical therapies and devices.

Restore tear film homeostasis

The concept of restoring tear film homeostasis seems rather straightforward, but in actual practice, it is often anything but that. There is a vicious cycle of changes in OSD. Interventions are available to influence the cycle at many points.

However, it is not always clear what the fundamental process is that initiated this vicious cycle. There is no single diagnostic test, and there is no single treatment that will provide all patients relief from their dry eye symptoms. Paradoxically, we can often achieve symptomatic relief without resolving the underlying cause. An example might be the patient who has mild meibomian gland disease and achieves relief from occasional ocular lubricants, such as drops. The symptoms might be addressed but the underlying cause is not. Restoring tear film homeostasis should remain the goal for long-term ocular health.

Improve meibomian gland function

OSD caused by meibomian gland dysfunction is likely far more prevalent than that caused by aqueous deficiency. It takes little more than a brief, careful look at the eyelid margin to identify gland plugging or scarring (Figure 1).

As mentioned above, deficiencies in the lipid layer lead to evaporative dry eye and can trigger a series of inflammatory responses. Restoring a healthy lipid layer should be one of the early considerations for patients with dry eye disease.

A simple regimen of hot compresses and meibomian gland expression may help to restore tear film homeostasis. Various lid scrub preparations are available to help clear secretions and may have other benefits. Supplementation of dietary omega-3 fatty acids found in fish oil, ground flaxseed, and proprietary preparations help some patients.

Off-label use of oral antibiotics, such as doxycycline or a topical antibiotic (e.g., azithromycin), can be considered for recalcitrant meibomian gland disease. It is rational to take a stepwise approach to manage this complicated and uncomfortable condition.

Utilize eye drops

Drops have long been the mainstay of dry eye treatment and remain a valuable tool. Often, occasional drop use may be all that is needed for mild dry eye disease. There are numerous formulations, including preservative-free options. It is often difficult to predict in advance which formulation will be most comfortable for a specific patient.

Reduce environmental irritants

The first fundamental principle for addressing environmental irritants is to remove the environmental factors, if possible. Most articles about OSD provide a long list of possible environmental factors. A few of them are of particular interest for our glaucoma patients.

In addition to ambient temperature and humidity, perhaps the most important environmental factor for the treated glaucoma patient is topical medication. It has been shown that the more eye drops a patient is administering, the greater the symptoms of OSD.

In one study,⁸ subjects taking 0 or 1 drop medication had similar prevalence of OSD symptoms. Subjects taking more than one drop medication had a substantial increase in symptoms. Most patients appeared able to tolerate their first medication.

Much attention has been paid to the preservative systems within drops. In particular, benzalkonium chloride is a common preservative that has been used for decades, but is implicated in OSD.¹ Now that alternative preservative systems and preservative-free medications have become available, these should be considered for glaucoma patients who are experiencing dry eye symptoms. Additionally, fixed combination medications can be used to simplify drug regimens and reduce the preservative burden.

These environmental factors are well within the physician’s control, although these potential benefits are not uniformly recognized by the decision-makers who control formulary access for patients.

Treat inflammation

Regardless of the inciting influence, inflammation can become a reinforcing factor in both aqueous deficient and evaporative dry eye disease. It may be necessary to break the inflammation cycle to restore ocular surface homeostasis. A mild steroid, such as lotoprednol, either alone or in combination with another medication, may help break the cycle.⁹ Topical cyclosporine ophthalmic emulsion (Restasis, Allergan) was the first FDA-approved medication for dry eye disease. Cyclosporine is an immunomodulatory drug with anti-inflammatory properties and has demonstrated benefit for dry eye disease; however, it usually requires prolonged therapy.

The most recently approved medication for dry eye is lifitegrast ophthalmic solution 5% (Xiidra, Shire). This medication aims to reduce inflammation by blocking the interaction between integrin lymphocyte function association antigen – one (LFA-1) and intracellular adhesion molecule – one (ICAM-1). This blocks T-cell migration and reduces cytokine release. Although it has been demonstrated to improve the signs and symptoms of dry eye disease, the role of this medication in improving OSD in treated glaucoma patients remains to be studied.

A Better Understanding

DEWS II emphasizes the continuing need for us to better understand the multifactorial nature of OSD and create individualized plans to restore tear homeostasis. A systematic approach to evaluation and treatment should result in more comfortable and happier glaucoma patients. GP

References

1. Willcox MDP, Arueso P, Georgiev GA, et al. TFOS DEWS II tear film report. Ocul Surf. 2017;15(3): 366-403.
2. Schaumberg DA, Sullivan DA, Buring JE, Dana MR. Prevalence of dry eye syndrome among US women. Am J Ophthalmol. 2003;136(2):318-326.
3. Schaumberg DA, Dana R, Buring JE, Sullivan DA. Prevalence of dry eye disease among US men: estimates from the Physicians’ Health Studies. Arch Ophthalmol. 2009;127(6):763-768.
4. Schein OD, Muñoz B, Tielsch JM, Bandeen-Roche K, West S. Prevalence of dry eye among the elderly. Am J Ophthalmol. 1997;124(6):723-728.
5. Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000;118(5):615-621.
6. Leung EW, Medeiros FA, Weinreb RN. Prevalence of ocular surface disease in glaucoma patients. J Glaucoma. 2008;17(5):350-355.
7. Fechtner RD, Godfrey DG, Budenz D, Stewart JA, Stewart WC, Jasek MC. Prevalence of ocular surface complaints in patients with glaucoma using topical intraocular pressure-lowering medications. Cornea. 2010;29(6):618-621.
8. Rossi GC, Tinelli C, Pasinetti GM, Milano G, Bianchi PE. Dry eye syndrome-related quality of life in glaucoma patients. Eur J Ophthalmol. 2009;19(4):572-579.
9. Sheppard JD, Donnenfeld ED, Holland EJ, Slonim CB, Solomon R, Solomon KD, et al. Effect of loteprednol etabonate 0.5% on initiation of dry eye treatment with topical cyclosporine 0.05%. Eye Contact Lens. 2014;40(5):289-296.

Dr. Fechtner is professor and chair of ophthalmology at SUNY Upstate Medical University in Syracuse, NY.