Feature, Report

Dry eye set to fuel eyecare explosion

Once thought of as a marginal sub-speciality of eyecare, dry eye is now a multibillion-dollar global industry. MATTHEW WOODLEY examines the seemingly growing prevalence of the disease and the potential impact it could have on eyecare.

Estimates vary, but dry eye is said to affect at least 344 million people worldwide.

Debate around its increasing prominence has focused on whether this is due to better diagnosis, environmental factors or a combination of both. However, what cannot be argued is that the greater understanding of the disease has changed the perception from it being a mild inconvenience restricted almost exclusively to ageing women, to something much more significant.

The current consensus amongst researchers and clinicians is that dry eye is a widespread disease that can have long-lasting and serious consequences, particularly with regard to quality of life. Complicating efforts to contain this disease is the fact that the nature of modern life, especially within developed nations, is likely to exacerbate the issue rather than help it.

Exposure to air conditioning, increased screen time, elevated levels of air pollution, and higher rates of contact lens use and laser eye surgery are all recent developments that are thought to increase the chance of contracting the disease. Because of this, UNSW researcher Professor Mark Willcox said it’s important for clinicians to embrace the increased emphasis that has been placed on treating the disease.

“The old concept that it’s a low-magnitude disease, or not even a disease, is outdated and it’s certainly becoming more obvious that it’s a significant condition,” he said.

“For example, children and youngsters are getting it much more commonly, and that’s probably to do with staring at computers or phones and not blinking enough and staring at the screen.

“It’s important to ask younger people when they come in about dry eye more, because you will find some patients who are affected by it but aren’t necessarily conscious of the fact that they have the disease.”

Diagnosis and management

Willcox chaired the Tear Film subcommittee for the Tear Film and Ocular Society (TFOS) DEWS II report, which overall involved 150 international clinical and basic research experts, who used an evidence-based approach to reach a global consensus on some of the main aspects of the disease. He said despite dry eye’s seemingly growing prevalence, the report, published in July last year, had helped simplify the way it is diagnosed and treated.

“The new DEWS II has probably made it easier to diagnose than it was before, and once you’ve gone through that diagnosis it actually makes it simpler to think about what type of treatment you might want,” he explained.

According to Professor Fiona Stapleton, head of the UNSW’s School of Optometry and Vision Science (SOVS), one of the ways the report helps clinicians diagnose dry eye is by providing a framework to help separate the disease into its major subtypes.

“We’ve learned to accept that for a dry eye to be diagnosed we need to have one sign and symptoms. These can be symptoms of discomfort or dryness, or visual symptoms,” Stapleton said.

“In terms of the pathophysiology there’s still quite a lot we don’t know, but in terms of the clinical diagnosis and management, I think we’ve got a nice paradigm to work within now.”

Stapleton chaired the DEWS II Epidemiology subcommittee and she said research conducted over the past 10 years had boosted efforts to quantify certain risk factors associated with the disease, which was also aiding diagnosis.

“Eyecare practitioners go to DEWS II if they have a problem. We’re able to put a label on it now and we’re understanding more about the risk factors and asking the right questions a little bit more, so we’re getting better at diagnosis and understanding the disease,” she said.

“Some of those things that we didn’t really have the evidence for, maybe like contact lens wear, have now become likely risk factors, so we have greater evidence.”

Another Australian who contributed to the DEWS II report, UniMelb’s Dr Laura Downie, agrees but said it is important to assess each case individually.

“We are seeing many more clinicians interested in engaging in best practice for dry eye, and trying to provide the best clinical care for their patients. It is a fairly hot topic in optometry, in particular many clinicians have a genuine interest in managing ocular surface disease,” Downie said.

“A key take home message is that there is no ‘recipe book’ answer for treating dry eye. The intent of DEWS II was to summarise the information in a way that allows clinicians to follow an evidence-based approach, without being prescriptive.

“The nature of the management is going to vary significantly for different patients. Trying to identify the relevant contribution of evaporative versus aqueous deficient dry eye is important, as is tailoring the therapy for the individual patient.”

   Quality of life

One of the reasons dry eye treatments, such as the ones offered at Auckland Eye, have proved popular can be found in the disease’s impact on quality of life. Professor Willcox thinks despite the growing mountain of evidence, the impact dry eye can have on a patient has been somewhat overlooked.

“People have done research on things like quality of life with dry eye and shown that it affects people as much as some other debilitating conditions, such as moderate angina. So it can have a very significant effect on people’s lives,” Willcox said.

“It’s not just a dry eye, it really does affect their whole life and often they get consumed by it.”

The symptoms can be so severe that one recent Korean study showed a patient diagnosed with dry eye exhibited an odds ratio (OR) of 1.32 for depression and 1.24 for suicidal ideation compared to those without the disease. The research, which was published in PLOS One, used data from the 16,408 participants who took part in the fifth Korea National Health and Nutrition Examination Survey, and applied logistic regression to examine the associations between dry eye, depression, and suicidal ideation.

A similar cross-sectional study undertaken by University of California researchers also found women with dry eye symptoms had higher odds of having depression than symptom-free patients. The research involved 3,514 patients who had enrolled in the Sjögren’s International Collaborative Clinical Alliance, of which 1,110 were diagnosed with moderate to severe depression.

According to medical new site Healio, participants who answered “yes” to the question “do your eyes feel dry?” had 1.82-fold greater odds of having depression compared with those who answered “no”. Furthermore, participants who reported a specific ocular sensation, such as light sensitivity or burning, had a 2.45-fold higher chance of depression compared to those with no symptoms.

Dr Downie warned that while it was less common today, there was still a potential tendency for the impact of dry eye to be underestimated.

“Certainly when you see patients that are severely affected by dry eye disease, it is not simply a matter of being able to prescribe an artificial tear to treat that condition,” Downie said.

“For people with severe dry eye, the burden of disease is similar to very significant health conditions. Those types of comparisons emphasise that dry eye disease can have major negative impacts on quality of life.”

   Industry response

Analysis conducted by ophthalmic marketplace researcher Market Scope estimates that dry eye products will generate US$4.5 billion (AU$6.06 b) annually by 2020, led by increases in procedure-based treatments for meibomian gland dysfunction. New dry eye Rx pharmaceuticals are also likely to enter markets by 2020, while other more experimental treatments are in the pipeline.

Currently, Allergan’s blockbuster drug Restasis (ciclosporin) is by far the largest income producer in the dry eye market, with sales upwards of US$1.47 billion (AU$1.99 b) in 2017, according to the company’s annual report. However, patent challenges and geographical barriers (it is still not available in the EU, Australia or New Zealand), mean its stranglehold on the market could soon be loosening.

Generic alternatives to the drug are expected to flood the US later this year, while multinational pharmaceutical company Shire is already generating hundreds of millions in sales annually from its own treatment – Xiidra (lifitegrast) – which was approved by the FDA in 2016 specifically for the treatment of dry eye.

Locally, one of the most recent additions to the selection of dry eye treatments is Novaliq’s NovaTears, which became available at the end of June. Registered in Australia via AFT Pharmaceuticals, the product is said to be the first and only water-free topical eye drop treatment specifically developed to treat patients with dry eye.

AFT CEO Dr Hartley Atkinson told Insight optometry practices, particularly independents, had an opportunity to stand out by adopting an overall treatment approach to dry eye, including eye heat masks, eye lid wipes and suitable lubricating eye drops to address the specific diagnosis.

“Developing a diagnosis and all-inclusive treatment program for dry eye is a way that independents can differentiate themselves and add value to their customers,” Atkinson said.

“In reality, if an optometrist manages their patients’ dry eye effectively then this will help to build the relationship with their customers, who will then interact with them on the whole range of their eye needs, including spectacles and contact lenses.”

The national product manager of the optometry segment of Designs For Vision, Mr William Robertson, was even more insistent that dry eye was of great important to independent optometrists. Robertson said offering a comprehensive dry eye treatment package was vital for independents to compete with large optometry chains, especially as it’s a highly skilled area of operation.

“The key to operating a successful dry eye practice is to build a complete system of accurate diagnosis, effective in-house treatment, at-home care regime, and follow-up review and management for patients,” he said.

“Having the right product range and equipment is essential to this strategy. It also requires a high level of patient trust and a solid foundation of knowledge and support for the provider.”

Meanwhile, France Medical director and national sales manager, Mr Gary Bosert explained that patients were looking for specialists that can both diagnose and treat conditions such as dry eye. Because of this, he suggested it was important for optometrists and ophthalmologists to continue to invest in and support new technologies, to help eyecare stay at the forefront of medical innovation.

Bosert also pointed to international markets, such as Europe, as evidence that more patients’ priorities were beginning to shift back to finding solutions that weren’t necessarily the most inexpensive, but provided long-term solutions to their eyecare issues.

“In a modern world, where technology and artificial intelligence anticipates our needs, patients are wanting the same from their specialists. They want them to act before it is ‘too late’: they are looking for early detection and preventive treatments,” Bosert said.

“Talking is not enough in 2018. Your patients need to visualise and want to be able to interpret the situation to consciously validate all options. This means that eyecare professionals need tools that can generate diagnostic reports but also involve their staff, when required, to speak with a unified voice.”

   New and unique services

An associated aspect of the improved understanding of dry eye is the increasing variety of treatments that are now available on the market. One clinic that has taken a unique approach to the disease is New Zealand’s Auckland Eye, which has established its own Oasis Spa for dry eye patients – the only one of its kind in the country.

Clinical optometrist Ms Surekha Parag runs the spa under the supervision of Dr Dean Corbett, and she told Insight the concept behind the new approach was to make the whole experience more attractive to long-term sufferers.

“Because dry eye is a chronic disease it’s not just going to go away with one or two treatments – but you’re also not going to go blind from it, or at least not from the usual dry eye condition. It’s something people choose to come do something about it, so we thought we might as well make the experience more pleasant,” she said.

“Instead of making it more clinical we decided to make it more like a spa experience. So we have nice artwork on the wall, diffusers and candles, whale music in the background and herbal teas.

“In the treatment room we have two options – the Optima IPL and LipiFlow. We have a large full-body massage chair as well, so while the patients are receiving the LipiFlow treatment they can also have a body massage done.”

The spa opened in March and has relied solely on referrals from in-house ophthalmologists rather than advertising, but Parag said it has already had to double the number of sessions it runs to meet demand. Another apparent drawcard has been the spa’s LipiFlow equipment, which is currently the only one available in New Zealand.

“With IPL, people need to come back for multiple sessions, so it’s quite time consuming and it also takes a while for the treatment to start having an effect.

Sometimes it can take up to 12 treatments, so that’s a lot to ask for someone to do that, especially during Summer months because it’s all skin type dependent as well – they can’t be tanning too much, they can’t go on holidays, all these considerations fall into that,” Parag said.

“With LipiFlow there are no such restrictions. It doesn’t matter if you’ve been sunbathing, plus you only need to do one in-office treatment, as outside of this it can be managed off-site with things like heatpacks to maintain the treatment effect.

“We will get patients who aren’t always willing to come here frequently as well and sometimes that’s what we base it on. If they don’t want to keep coming back then it will be LipiFlow.”

   Research snapshots

The continually increasing demand for new and improved dry eye treatments has prompted companies and researchers to work tirelessly to deliver the next breakthrough. One possible treatment that has shown promise but is yet to be approved involves boosting electrical activity in the eye to provide short-term relief from symptoms.

The University of Michigan’s Dr Donald Puro has been studying the bioelectrical responses of cells in the mucous membranes that line the eyelids (goblet cells), and he found that electrical activity in the goblet cells increases as hyperosmolarity (too much salt and not enough water) rises in the tear film.

According to Puro, the increased electrical activity allows the cells to produce more mucin. However, this boost is short-lived, which means even if the salt-to-water ratio of the tear film remains unbalanced in the long-term, the goblet cells’ electrical activity still returns to normal levels without producing additional mucin.

“Loss of this voltage increase during long-term dryness/hyperosmolarity may account for the clinical conundrum that goblet cells in chronically dry eyes can remain filled with mucin, even though the tear film is hyperosmotic and mucin-deficient,” Puro wrote in The American Journal of Physiology.

“Continued progress in elucidating the bioelectric mechanisms by which the ocular surface responds to dryness [and] hyperosmolarity should provide novel strategies for ameliorating the uncomfortable sight-impairing condition of dry eye.”

However, while Puro’s research has shown some promise, another high-profile study had a disappointing outcome for dry eye sufferers. A multi-centre clinical trial involving 535 patients found oral omega-3 was no better than a placebo in terms of relieving signs and symptoms of dry eye disease.

The patients in the Mount Sinai-led study received either a daily regimen of marine-derived omega-3 fatty acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), or a placebo of 5,000mg of olive oil.

According to the results, the mean change in symptom score was similar in both groups, while there were no significant differences between groups for changes in signs of dry eye, which were measured with conjunctival staining, corneal staining, tear break-up time, and the Schirmer test.

The Dry Eye Assessment and Management (DREAM) study was the first large-scale real-world, double-masked, randomised clinical trial to investigate the long-term efficacy and safety of omega-3 supplementation for symptomatic dry eye disease.

“DREAM results do not support omega-3 fatty acids supplementation for dry eye disease. There is a cost, and the money may be better spent on other treatments for dry eye disease,” study author Dr Penny Asbell said.

Closer to home, Australian and Israeli-based biotech startup Azura Ophthalmics has raised $US16 million ($20 million) to fund research into meibomian gland dysfunction, while next year the UNSW will begin research into trying to discover a reliable biomarker for dry eye.

The flurry of activity from both academia and industry indicates both the scale of the dry eye problem and the potential opportunities for eyecare professionals to help patients deal with this rising phenomenon. And while there is still much to learn about dry eye, one aspect of the disease is beyond debate: dry eye is here to stay.