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HomemieyecareSevere Dry Eye: Preparing for Inundation

Severe Dry Eye: Preparing for Inundation

Thought you were already inundated with patients seeking solutions for dry eye? Hold on to your hats – an ad campaign featuring actress Jennifer Aniston front and centre, talking about her experience with persistent dry eye and proclaiming that “there are too many beautiful things to see and do to let chronic dry eye get in your way” is bringing greater awareness to this debilitating disease. So what can you do to help?

We know dry eye disease (DED) is a multifactorial disease that can be difficult to diagnose, yet it affects nearly 337 million people worldwide1 and 20 per cent of the adult population in Australia2, numbers which are on the rise.

A study undertaken by Medcsape found that ophthalmologists estimated the percentage of their patients who are diagnosed with DED to be 38.44 per cent and for optometrists it was 35.11 per cent.3

On average, they estimated levels of severity of the disease among their patients as follows: mild (56.03 per cent), moderate (30.63 per cent) and severe (13.34 per cent).3

Most eye health professionals feel fairly comfortable making the diagnosis based on clinical examination

Factors contributing to the increase in prevalence of dry eye disease include longer life expectancies and extended careers; an expanding middle class in emerging markets with increased access to health care; increased visual demands related to smart phones, tablets, and computers; improved diagnostic technologies; dietary changes; and treatment regimens with enhanced effectiveness.

Two thirds of sufferers are women and post-menopausal women are at higher risk of DED. More severe dry eye affects 8 per cent of women and 4 per cent of men by age 50.4

Dry eye disease can have significant consequences. When mild to moderate, dry eye disease can be an uncomfortable annoyance. At the extreme end, it can limit a person’s ability to work, study, socialise and travel – quite simply, it’s a disease that can severely impact quality of life.

A recent study from Japan, that compared 100 women who suffer from the condition with 100 women who do not, found DED had a noticeable impact on sleep quality and a correlation with mood. The two cohorts were each split into three subgroups by age: 30-45; 46-55 and 56-69. The researchers measured ocular signs such as Schirmer test scores; sleep metrics such as the Pittsburgh Sleep Quality Index (PSQI) and mood; based on the Hospital Anxiety and Depression Scale (HADS). The study found that ocular signs were consistent across age groups however HADS scores were worse in the younger group with DED than they were in their equivalent control group while there was little difference between older women in both groups. PSQI scores were lower in the DED group than in the control group.5

Characteristics

In the May 2016 issue of mivision, Professor Mark Wilcox described the characteristics of DED or dry eye syndrome (DES); also known as keratoconjunctivitis sicca (KCS) or keratitis sicca as follows: a common, multifactorial disease of the tears and the ocular surface

  • Arises from a dysfunctional lacrimal functional unit (LFU)
  • Causes discomfort, visual disturbance and tear film instability
  • Is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface
  • Has the potential to cause damage to the ocular surface
  • Can be asymptomatic
  • Those living with the condition may not realise symptoms can be treated.

Professor Wilcox stated that “early detection and treatment can prevent the condition becoming ‘self-perpetuating’”.6

A Growing Therapeutics Market

Certainly, data on the dry eye therapeutics market would suggest this is exactly what is happening. According to sources, this market is one of the fastest growing indications in ophthalmology, predicted to grow to $4.6 billion by 2024.7 New treatments have been approved this year and more drugs, devices and diagnostics are in the pipeline in an effort to resolve this debilitating disease for almost 337 million people in the world who live with severe, moderate, or episodic dry eye syndrome.1

While the signs and symptoms of moderate dry eye can be reduced by one or a combination of over the counter artificial tear drops and ointments, chronic dry eye takes more effort.

However, because of the multiple factors underlying dry eye there is no silver bullet for this disease.

According to Dr. Reza Dana, Claes Dohlman Professor of Ophthalmology at Harvard Medical School, “topical cyclosporine cannot address all aspects of dry eye nor every patient who has dry eye.” He said the US Food and Drug administration was lessening its requirement for new compounds to demonstrate improvement to both signs and symptoms of dry eye. One reason for this was that “dry eye can be caused by aging, androgen deficiency, autoimmune disorders, or can be self-created by contact lens wear and/or refractive surgery”.8

Dr. Dana predicted that as more treatments for dry eye enter the market, they will be added to treatment provided by topical cyclosporine. “It’s unrealistic for any of us in this room to think we’re going to have one drug that will treat everyone with this disease,” said Dr. Dana. “When patients present with symptoms, the best way to guide therapy may very well be to re-evaluate how clinicians view the disease.”8

Xiidra a Game Changer

An exciting arrival on the market this year has been Xiidra (lifitegrast ophthalmic solution 0.5 per cent, Shire). When it was approved by the US Food and Drug Administration for the treatment of both signs and symptoms of dry eye in July, it was heralded by some as a ‘game changer’. The first new drug to be FDA approved for dry eye disease in 13 years, Xiidra is dosed twice per day, approximately 12 hours apart, in each eye.

The safety and efficacy of this new drug was studied in 1,181 patients (of which 1,067 patients received lifitegrast 5 per cent) in four placebo-controlled 12 week trials.

Patients were randomised to receive either Xiidra eye drops or placebo eye drops. The studies found that groups treated with Xiidra demonstrated more improvement in both the signs and symptoms of eye dryness than the groups treated with placebo.

The most common side effects of Xiidra include eye irritation, discomfort or blurred vision and an unusual taste sensation (dysgeusia).

Ophthalmologists, optometrists and general practitioners surveyed by Medscape in October 2015, prior to FDA approval of Xiidra indicated a willingness to prescribe the treatment for patients with moderate to severe DED rather than those with mild DED.3

Among the three groups who were aware of lifitegrast, GPs indicated they would be likely prescribe it within the first year for 43.61 per cent of their patients with moderate to severe DED, ophthalmologists answered 40.71 per cent, and optometrists answered 40 per cent. When asked about prescribing for patients with mild DED, on average, the three groups answered they would prescribe Xiidra for 22.86 per cent of patients.3

More recently, Dr. Christopher J. Rapuano and his practice partner, Dr. Parveen Nagra for the Cornea Service at Wills Eye Hospital in Philadelphia, Pennsylvania wrote in Medscape, “We have artificial tears, and we have an anti-inflammatory medicine, Restasis (cyclosporine ophthalmic emulsion). We can occasionally try different antibiotics or thicker lubricants and oral medications, but there are patients for whom we are not adequately treating dry eyes who remain symptomatic.” Dr. Rapuano added, “this will be a big game changer in the treatment of dry eye.”9

Interestingly, and echoing market discussion surrounding the pipeline of treatments, a week after the FDA approval of Xiidra patients, Allergan submitted a de novo FDA application for a new device called Oculeve intranasal tear neuro-stimulator. (The de novo application provides a pathway for medical devices for which general and/or special controls provide a reasonable assurance of safety and effectiveness, but for which there is no legally marketed predicate device.) This handheld stimulator has been investigated for temporarily increasing tear production upon activation in patients with dry eye disease due to decreased tear production and, according to Allergan, has performed with success. Speaking of the data released from trials, Allergan Chief R&D Officer David Nicholson, said, “This device is part of Allergan’s strong eye care development pipeline and will complement our leading dry eye treatment Restasis. This is a major step forward in providing a promising new option for eye care professionals and their patients with dry eye disease.”

The prescription eye drop FDA approved Restasis (cyclosporine 0.05 percent solution, Allergan) has long been used to reduce the signs and symptoms of DED. It works by reducing inflammation associated with dry eye disease and helping the body to produce more natural tears. However, Restasis takes 90 days for the treatment to kick in and some people have complained of a burning sensation in the first few weeks of treatment.10

Intense Pulsed Light Treatment

Intense Pulsed Light (IPL) treatment is an existing option for treating chronic dry eye disease that appears to be offering many patients some relief by stimulating and unblocking the meibomian glands in order for them to return to their normal functions. As a result, the dry lipid layer returns to a natural flow of lipid and tear evaporation is reduced.

Lumenis launched the first Food and Drug Administration approved IPL system in the late ’90s to treat various skin conditions. Dr. Rolando Toyos from the United States was one of the first to recognise that the device was beneficial for treating people with dry eye and has followed the evolution of the technology. Speaking of Lumenis’ current Optima M22 he said, “Most patients require multiple treatments to improve meibomian gland dysfunction (MGD) dry eye disease. Once the patient achieves a normal tear film then patients will undergo maintenance treatments to preserve normal gland and tear production.”11

It was the French based company E-Swin that designed the first IPL specifically to treat dry eye. The E-Eye Medical Grade IPL device was part of a study conducted at the Department of Ophthalmology, Auckland University, which found that “Intense pulsed light, with multiple sculpted pulses, shows therapeutic potential for meibomian gland dysfunction, improving tear film quality and reducing symptoms of dry eye”.12 The study authors noted that further larger studies were required.

According to the study, which was published in Investigative Ophthalmology and Visual Science, results were as follows: “Lipid layer grade improved significantly from BL to Day (D) 45 in the treated eye (P < 0.001), but not the control eye (P = 0.714), with 82 per cent of treated eyes improving by at least one LLG. Non-invasive tear break-up time also improved significantly from BL to D45 in the treated (P < 0.001) but not in the control eye (P = 0.056) and was significantly longer than in the treated eye at D45 (14.1 ± 9.8 seconds versus 8.6 ± 8.2 seconds, P < 0.001). The tear evaporation rate was not different in the treated eye compared with the control eye at any visit. Tear meniscus height did not change from BL in either eye (P > 0.05). Visual analog scale symptom scores improved from BL in the treated (P = 0.015), but not the control eye (P = 0.245), with 86 per cent of participants noting reduced symptoms in the treated eye by D45.”13

Omega Three Trials

As well as investigating new compounds and devices, researchers, like Australia’s own Dr. Laura Downie, are investigating new nutritional supplements. Dr. Downie recently presented results of a three-month trial comparing two forms of long-chain omega 3 supplements – phospholipid and triglyceride – for the treatment of dry eye. The paper was accepted by the journal Ophthalmology and is expected to be published online this month (December 2016).

The single-centre, double-masked, placebo-controlled randomised clinical trial involved 60 participants with dry eye disease over a period of 90 days (54 participants completed). On a randomised basis of 1:1:1, participants received placebo (olive oil 1500mg/day) or matched doses (1000mg/day eicosapentaenoic acid, EPA, + 500mg/day docosahexaenoic acid, DHA) of ω-3 EFAs in either predominantly phospholipid (krill oil) or triglyceride (fish oil) form.

Dr. Downie’s study aimed to measure the mean change from day 1–90 in tear osmolarity and DED symptoms (Ocular Surface Disease Index or OSDI), and, on a secondary level, the mean change in tear stability, tear production, ocular surface staining, bulbar redness, meibomian gland integrity, and tear inflammatory cytokines.

The study found that a moderate daily dose of both krill oil and fish oil reduced tear osmolarity and increased tear stability in people with dry eye disease. Additionally, omega-3 EFAs in a phospholipid (krill) form “may confer additional therapeutic benefit, with improvements in dry eye symptoms and lower basal tear levels of IL-17A, relative to placebo”.

Dr. Downie reported: At Day 90 tear osmolarity was reduced from baseline with ω-3 EFAs in predominantly phospholipid (-18.6 [SD:16.7] mOsmol/L, n=18, p<0.001) and triglyceride (-19.8 [SD:19.6] mOsmol/L, n=19, p<0.001) forms compared with placebo (-1.5 [SD:18.2] mOsmol/L, n=17). OSDI score was reduced at Day 90 relative to baseline in the phospholipid ω-3 EFA group only compared with placebo (-18.6 [SD:10.2] versus -10.5 [SD:13.5], p=0.02). At Day 90, there were also relative improvements in tear break-up time and ocular bulbar redness, compared with placebo, for both forms of ω-3 EFAs. Basal tear levels of the pro-inflammatory cytokine IL-17A were significantly reduced only in the phospholipid ω-3 EFA arm compared with placebo at Day 90 (-27.1 [SD:46.2] versus +46.5 [SD:125.5] pg/mL, p=0.02).

Conclusion

Although severe dry eye continues to have a devastating impact on the lives of people who live with the disease, existing treatments and the pipeline of new therapies, diagnostics and treatments on their way can reassure us there is hope for relief in years to come. To read more about dry eye treatment, it’s worth referring back to previous CPD articles in mivision, including Margaret Lam’s articles published in June 2015.

Jennifer Aniston Talks about Dry Eye

A partnership between pharmaceutical manufacturer Shire and actress Jennifer Aniston to create awareness of dry eye had an interesting beginning.

According to reports, Shire executives heard Aniston complain about her “addiction” to eye drops in an interview and approached her on the topic. She, in turn, went to see her ophthalmologist and was diagnosed with dry eye.1

Now Aniston is the star of an online and TV advertising campaign, in which she tells her story about how she has learnt to managing dry eye.

To see the eyelove ad campaign featuring Jennifer Aniston, visit myeyelove.com

Reference
1. www.fiercepharma.com/marketing/actress-jennifer-aniston-s-eye-drop-addiction-leads-to-gig-as-shire-spokeswoman

References
1. market-scope.com/pressrelease/dry-eye-products-market-expected-to-generate-4-5-billion-by-2020/
2. http://www.myvmc.com/diseases/dry-eye-syndrome-keratoconjunctivitis-sicca/
3. Marcia Frellick. Many Clinicians Take Wait-and-See Attitude to New Dry Eye Drug www.medcsape.com 5 August 2016
4. Melanie Kell. Stop the Itch: Managing Allergy and Dry Eye mivision, September 2016
5. www.hcplive.com/conference-coverage/aao-2016/does-dry-eye-disease-hinder-sleep-quality-and-mood
6. Professor Mark Wilcox. Dry Eye Disease – Looking After the Ocular Surface mivision May 2016
7. www.avizorex.com/
8. ois.net/2016-promises-to-disrupt-dry-eye
9. Christopher J. Rapuano, MD, Medscape July 26, 2016
10. www.allaboutvision.com/conditions/dryeye.htm#steroid
11. Dr. Rolando Toyos, Optima Intense Pulsed Light for Dry Eye mivision December 2016
12. www.dry-eyes.com.au/results/clinical_study
13. iovs.arvojournals.org/article.aspx?articleid=2277038

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