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Keeping an eye on dry eye

Our understanding and treatment of dry eye needs to become much more sophisticated because researchers are discovering that several systemic diseases can alter the composition of the tear film. Report by Mark Greener.

 

Learning Objective:

After reading this article you should:

Be able to describe the latest thinking regarding the link between dry eye and systemic disease.

 

Dry eye, which patients typically describe as a gritty, scratchy, irritating and uncomfortable sensation, is one of the commonest ocular ailments. Epidemiological estimates vary, depending on the definition and the patients included, but between 5 and 30 per cent of people aged 50 years and older experience dry eye1.

Pharmacists have long offered lifestyle advice, treatments and referrals to help patients cope with dry eye, but Anat Galor, staff physician at Miami Veterans Affairs medical center and a world authority on dry eye, told Pharmacy Magazine that pharmacists need to rethink this common condition.

“Even the term ‘dry eye’ is misleading,” says Professor Galor, who is also associate professor of clinical ophthalmology at the Bascom Palmer Eye Institute, University of Miami. “It implies that ocular dryness is a factor in the pathophysiology and that alleviating dryness is a practical solution. However, we know that many patients with dry eye symptoms do not have ocular dryness and that artificial tears do not alleviate dry eye symptoms in all patients.”

Tiny tear film

In humans, the tear film is just three microns thick (thinner than a red blood cell). Lacrimal glands produce tears, which protect and nourish the cornea, and enhance the turnover of cells on the eye’s surface. The down-stroke of each blink compresses and spreads the tear film, which ripples over the corneal surface.

Tears drain away through holes (called puncta) in the corners of the upper and lower eyelids. The tear film needs to remain stable between each blink – usually that is three or four seconds but you will be blinking less while you are reading this feature than when you are chatting to a customer or your staff.2 An unstable tear film can stress the surface, setting up a cycle of inflammation and pain that can trigger the symptoms of dry eye and, over time, potentially damage the cornea.3

Symptoms of dry eye can emerge at any age, but are especially common in older people as levels of the major tear proteins and tear production decline with age. Dry eye is more than twice as common in people aged over 80 years than in those under 60 years of age and women are 50 per cent more likely to experience it than men.4

The tear film is highly complex, containing lipids, electrolytes and water as well as hundreds of proteins. Several systemic diseases alter the composition of the tear film. These changes could act as ‘biomarkers’ that potentially indicate, for example, multiple sclerosis, diabetes, breast cancer and some other malignancies before symptoms emerge.5

“In the not-too-distant future, we will have apps on our smartphones that can diagnose a range of diseases using the non-invasive detection of biomarkers in, for example, our breath or tears,” says Ali Parsa, founder and CEO of digital health service babylon. “The technology is already being developed, although further studies need to determine the biomarkers’ accuracy and there are regulatory and logistical hurdles to overcome.”

Against this background, dry eye is more than the absence of a stable tear film. It isn’t even a single condition. Ophthalmologists have, for example, traditionally recognised two major classes of dry eye:

  • Aqueous-deficient dry eye arises from reduced tear flow and volume
  • Evaporative dry eye is when the lacrimal gland functions normally, but tear evaporation is increased.4 Evaporative dry eye seems to arise largely from a deficiency in the amount of lipid in the tear film.

In a study of 263 men aged, on average, 69 years, Professor Galor’s team found that 8 per cent had aqueous deficiency, 47 per cent showed lipid deficiency and 11 per cent a mixed pattern. Importantly, however, tear parameters only accounted for 8 per cent of the variability in dry eye symptoms.6

“We and others have demonstrated that dry eye symptoms do not correlate strongly with ocular surface signs,” Professor Galor says. “This shows that we need to move beyond thinking about dry eye as aqueous and evaporative.”

Complex picture

Numerous systemic diseases can cause dry eye, including primary Sjögren’s syndrome (an autoimmune disease that damages salivary and lacrimal glands), thyroid eye disease, rheumatoid arthritis and diabetes.4 Pharmacists should therefore refer any dry eye patient who presents with non-ocular pain or systemic symptoms to their GP. For instance, patients with Sjögren’s syndrome may also experience chronic oral symptoms including dry mouth, swollen salivary glands or the need to drink to help swallow food.4

Now a growing body of evidence paints an even more complex pathological picture of the relationship between dry eye symptoms and systemic disease. For example, Professor Galor’s team studied 136 patients aged, on average, 65 years. They found only weak correlations between symptoms of dry eye assessed using two widely used questionnaires and measures of the tear film, such as the time taken for the film to break up and tear production.

Non-ocular pain, depression and post-traumatic stress disorder (PTSD) showed a stronger association with dry eye symptoms. Indeed, nonocular pain and PTSD accounted for about 36-40 per cent of the variability in symptom scores.7

In another study, Professor Galor’s team examined the relationship between dry eye and other chronic pain syndromes (CPS), such as chronic widespread pain, irritable bowel syndrome and pelvic pain. They split 154 patients with dry eye into high and low CPS groups. The high CPS group reported worse nonocular pain, higher PTSD and depression scores, and more severe ocular pain. In contrast, objective corneal signs of dry eye did not differ in the two CPS groups.8

“We showed that if we look at patients with chronic overlapping pain conditions, the dry eye profile was different in terms of symptoms, but not of signs, compared to those without,” Professor Galor explains. “This suggests that dry eye symptoms, in some patients, may be one manifestation of a chronic pain condition.”

In other words, the research by Professor Galor’s team is part of a growing body of evidence suggesting that some dry eye patients have ‘somatosensory’ dysfunctions of sensory pathways innervating the eye’s surface. This leaves them hypersensitive to stimuli.

Professor Galor notes that in some patients a light wind is enough to evoke considerable pain. Indeed, people with dry eye often report spontaneous and persistent pain; pain triggered by normally innocuous stimuli (allodynia); excessive pain when faced with a noxious stimuli (hyperalgesia); and abnormalities in the nerves to the cornea. Patients with neuropathic pain elsewhere in their bodies typically report similar changes.7

Professor Galor argues that the research should change the way we think about dry eye. “Pharmacists and other clinicians need to move from thinking about ‘dry eye’ as a disease localised to the ocular surface to a disease that has eye symptoms, but in which central mechanisms probably play an important role,” she told Pharmacy Magazine.

“This doesn’t mean that dry eye symptoms are driven by central mechanisms in all patients, but it highlights the complexity of the disease we call dry eye and the importance of sub-categorising patients based on the underlying pathophysiology, which may be ocular surface dryness in some patients and a manifestation of a chronic overlapping pain disorder in others.”

Less responsive

Professor Galor notes that dry eye symptoms arising from somatosensory dysfunction are less responsive to artificial tears. “We need additional studies to be better able to identify ‘dry eye’ patients with underlying somatosensory dysfunction,” she says. “We also need studies to develop ways to modulate somatosensory function in patients whose dry eye symptoms persist with ‘traditional’ dry eye therapy.”

Such modulators are several years away. In the meantime, the findings by Professor Galor’s team highlight the importance of referring people with non-ocular pain and any other systemic symptoms to their GP. After all, while further studies are needed, it is clear our eyes aren’t just the windows into our souls – they are also windows into our bodies.

Advising about dry eye

Eye symptoms can be frightening but pharmacists can reassure patients that, in general, dry eye is ocularly benign. “Dry eye can make vision slightly blurry, although usually only for short periods,” says Matthew Athey, eye health information service manager at the Royal National Institute of Blind People. “However, dry eye doesn't usually cause any eye damage and doesn’t lead to permanent changes to vision.”

When advising on dry eye, consideration should be given to whether certain medicines might cause or exacerbate it. For example, HRT for the menopause, treatments that lower androgen levels, drugs with anticholinergic side-effects and some acne treatments (e.g. isotretinoin) can all cause dry eye.4 Patients with dry eye should also be reminded that central heating can make tears evaporate more quickly and that a humidifier may help slow down the evaporation.

Blinking more when reading or using a computer as well as using eye drops before spending a long time in front of a screen may also be useful. In one study, healthy people blinked, on average, 17 times a minute when resting quietly, compared to 26 times during conversation, but just 4.5 times while reading.2

“You cannot ‘cure’ dry eye but there are some treatments that can help your customers’ eyes feel more comfortable,” Athey adds. Most people with dry eye need to use eye drops, gels or ointments, which, among other actions, wash out pro-inflammatory chemicals and protect the cornea’s surface, he says.

However, people who apply artificial tears more than six times a day should be advised to use preservative-free eye drops, as preservatives used in large quantities or for a long time may damage the surface of the eye or trigger inflammation. Punctal occlusion can help some patients. This is when an ophthalmologist uses punctal plugs to seal the drainage holes in the lower eyelids.

 

References

  1. The Ocular Surface 2007; 5:93-107
  2. Mov Disord 1997; 12:1028-34
  3. Progress in Retinal and Eye Research 2015; 45132-164
  4. Optometry in Practice 2013; 14:137-146
  5. Proteomics Clin Appl 2015; 9:169-186
  6. Invest Ophthalmol Vis Sci. 2013; 54: 1426-1433
  7. Br J Ophthalmol 2015; 99:1126-1129
  8. The Journal of Pain

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