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A Complete Approach to Dry Eye

2T CPD in Australia | 1G in New Zealand | 1 November 2018

By Jason Holland

Dry eye is sometimes viewed as a simple condition, yet DEWS II has reminded us just how complex and multifactorial it is. There has been an explosion of interest in dry eye in recent years, along with a lot of opinions on how to best diagnose and manage the condition. While I am excited about optometrists’ enthusiasm to tackle the condition, I think it is important that we constantly review the literature to ensure our advice and methods remain current. This is where the DEWS II report is so important for any practitioner serious about making a difference for dry eye patients. The report allows us to look at our opinions and our current practice protocols to see if they correlate with what the evidence suggests is best practice.

LEARNING OBJECTIVES

  1. Understand the chemistry behind aqueous supplements and their role in dry eye disease (DED)
  2. Understand the chemistry behind lipid layer supplements and their role in DED
  3. Become familiar with different drop protocols to manage the varying severity of DED
  4. Understand clinical outcomes of Systane Complete in dry eye management and be able to apply its clinical use in practice.

Dry eye disease is a chronic condition and the treatments generally require a long time frame for maximum effect. Because of this, we as practitioners, need to be confident in our advice and methods, knowing that at first the patient may see little improvement. If we don’t stay strong and stand behind our advice, compliance will waver or treatments will be changed unnecessarily and ultimately we will mismanage the patient’s condition.

This article concentrates on the treatment of dry eye disease and assumes you have already made an accurate diagnosis of the type and severity of disease affecting your patient. To aid us in determining the appropriate treatment, DEWS II has a stepped management approach based on the severity of the diagnosed dry eye condition (Table 1).

Click on image to see larger version

Step 1 is possible for every practitioner; therapeutic endorsement is not required and this first step often involves long dry eye consultations with a lot of listening and education. Having said that, this is one of the reasons why I believe optometry is the best-placed profession to help these patients.

Before getting to the main elements of Step 1 treatments, I will spend a moment on one aspect of environmental modification which I do spend time discussing with every dry eye patient: blink rate.

Blink rate can be easily overlooked, yet can cause a patient to experience dry eye symptoms even when their tear film is perfect. Our world has changed since the launch of the iPhone and the way we embrace screen based technology has meant that our patients’ blink rate is now significantly less. Simply discussing the need to take conscious blinks and/or follow blink exercises can go a long way to promoting a healthier tear film.1

To ensure compliance, and keep my life simple, I have created four pillars of Step 1 management which I discuss with every dry eye patient. These are lid hygiene, warm compresses, dietary modifications and artificial tear substitutes.

Lid Hygiene

Apart from helping to manage anterior blepharitis, lid hygiene is an important element of managing dry eye disease. This is because obstruction of the meibomian glands can be due to hyperkeratinisation of the eyelid margin.2 Accumulated debris and keratinised cells on the lid margin need to be removed to promote better meibomian gland function. This can initially be done with a stainless steel golf spud, which has been shown in one study (n=16, test group) to improve symptoms in 22 per cent, and meibomian gland function in 46 per cent, one month post-treatment in patients presenting with dry eye symptoms and visible changes to the line of Marx.3 Additionally, dedicated eye lid cleansers should be used. DEWS II quotes a recent level 1 study (n=43) where the efficacy of diluted baby shampoo was compared to a lid cleanser. At 28 days the commercial lid cleanser was better tolerated, lipid layer quality improved and inflammatory markers reduced. The baby shampoo was found to have a negative effect on goblet cell function.4

In discussing lid hygiene, I must also mention the need to be mindful of Demodex. While it has not been shown to directly cause meibomian gland disease (MGD), its role in anterior blepharitis and symptomatic dry eye patients has been documented.5 Tea tree oil is toxic to Demodex.6 Pure tea tree oil can also be toxic to the eye, so diluted commercial preparations are advised.7,8 The key to success is treatment duration. The papers assessed in DEWS II suggest four to eight weeks of twice daily treatment.9 Compliance is often poor – it is suggested that only 55 per cent of patients were compliant after six weeks – hence periodical review is important with these patients.10

Warm Compresses

There is strong evidence on the efficacy of warm compresses, but in reality, a lack of sufficient heat, sufficient time or sufficient longevity of treatment hinders results.10-15 DEWS II evidence shows that a warm compress can soften and liquefy meibum but what is not definitive is the temperature and time required to be successful.16-20 The meibomian gland material that causes more severe obstruction has a higher melting point.16,18,21 Evidence suggests that heating the meibomian glands to at least 40oC is required for optimal results.18,22,23 Further to this, application of the device for at least five minutes twice a day is required for a treatment period of between two to four weeks.24

The time involved to make a hot washer therapeutic invariably leads to non-compliance, so even if you think you are helping by saving the patient money, ultimately the result will be suboptimal. I strongly suggest that if you are going to discuss warm compresses with your patient, you recommend one of the commercial heat packs. There are a number on the market now and a small study found they were all more effective than a hot washer in achieving 40oC for at least five minutes.25

For those wanting to use heat to perform more potent in-house treatment of MGD, the Blephasteam (Thea Pharmaceuticals) is an ideal tool. The device uses latent heat without pressure to the eyelids to warm the meibomian glands. Patients find it a pleasant experience, which is excellent given that serial treatments are required. Research has shown it to be the most efficient method to heat eyelids compared to warm compresses.12,26,27 The treatment takes 10 minutes and the patient can sit in a different room during treatment. For those wanting to create a point of difference, take this treatment to the next level – think ‘day spa for the eyes’… warm light, scented candles, soft orchestral music…

Unfortunately for my patients, pleasure follows pain and in this case it is in the form of lid expression (Figure 1). Lid expression has been advocated in MGD by multiple papers and while effective, a limiting factor to success is the patient’s pain threshold.28-32 A recent study investigated the outcome of four in-office expressions a week apart, and found significant improvement in gland secretion, lipid layer thickness and the number of expressible glands. The patient’s symptoms also improved.9 While I use paddle style forceps in-office, it is important to caution patients attempting expression at home. DEWS II mentions that the cornea can rise in temperature from 36 to 39.4oC after eight minutes of a warm compress. If the cornea is then rubbed or the meibomian glands are massaged against it, there is a risk of corneal deformation and visual blur.33-35 To ensure this is avoided, once the heating device is removed I demonstrate how to pull the eyelid away from the eye in a pinch like fashion with clean hands. The eyelid should then be squeezed for a count of three. Repeat this for each eyelid. This technique ensures no pressure is exerted on the cornea immediately after the warm compress. In America practitioners are so concerned by the risk of corneal deformation and visual blur that most either don’t express or they use the LipiFlow (Tear Science).

Figure 1. Lower lid after expression using paddle forceps. Image supplied by Megan Zabell B.Optom

 

The LipiFlow heats the meibomian glands to 42.5oC internally while simultaneously evacuating the gland contents using rubber balloons that inflate and deflate over the 12 minute treatment. The effect can be sustained for beyond three months.36 A recent study (n=26) compared a single LipiFlow treatment to three months of twice daily warm compresses combined with lid massage and lid hygiene. At six months, the single treatment was as effective as the three month intense traditional treatment group.37

Dietary Modifications

The DEWS II report provides considerable evidence about the role of nutritional supplementation and dry eye, and it is nicely tabled on page 609.9 Apart from discussing general hydration with our patients,38-40 the evidence suggests we should also be discussing essential fatty acids (EFAs).41 Patients can source EFAs through their diets. Important in DED are long chain Omega-3 EFAs, which exist as EPA and DHA. These are found in high concentrations in oily fish such as salmon, tuna, mackerel, trout and sardines.42 Omega-3 and Omega-6 EFAs compete for enzymes within the body and ultimately regulate systemic inflammation. The ratio of consumed Omega-3 to Omega-6 is important in balancing inflammatory cytokines.43 Our current Western diet has an elevated Omega-6 intake and so to restore the balance, nutritional intervention in the form of Omega-3 supplements is required.44 We could reduce our Omega-6 intake but who wants to tell their patients to order a Big Mac without the bun or side of fries! Go there if you dare.

Want more evidence? The Women’s Health Study, involving over 32,000 subjects, reported a 30 per cent reduction in the risk of DED for every additional gram of Omega-3 consumed per day.45

So, the common question asked is how much and for how long?

Based on the summarised DEWS II papers, most researchers assess performance at three months. Most used samples of over 1,000mg of Omega-3 up to 2240mg.9 A recent pilot study also suggested that 1,500mg of Omega-3 per day can have a central corneal neuroprotective effect.46

There are two important things to note when suggesting dietary modification. Firstly, the capsule size does not reflect the actual Omega-3 content and close examination of the nutritional label is important to ensure a therapeutic dose is being taken. Cheaper options are invariably full of other ingredients.

Second, high dose Omega-3 supplements can have systemic side effects so best practice is always to advise the patient’s GP of the dosage you are recommending. Be aware of patients with liver disease, bleeding disorders and atrial fibrillation.9,47

Role of Anti-inflammatory Therapy

Before we move on to artificial tears, let's discuss the other drops which many dry eye patients require. We know from DEWS that dry eye is a self-perpetuating inflammatory cycle. We also know that there is a cascade of events starting with an unstable tear film, leading to hyper-osmolarity, which then promotes inflammation which can lead to cell damage. Because of the above, many of our dry eye patients will require anti-inflammatory therapy as part of their treatment.

DEWS II also identified that inflammation can cause changes to the neurobiology of the ocular surface and this helps explain those patients who still report discomfort/irritation despite their ocular surface appearing normal.48

Animal studies have found that topical corticosteroids are effective in breaking the cyclical immune response in Dry Eye Disease.49,50 In my experience this is one area of management of dry eye disease where many of us either avoid, manage at a sub-therapeutic level or fail to ensure adequate compliance over the required time period. Remember that a 5ml bottle of eyedrops used four times a day in both eyes is likely to last two weeks, so, if you set a review in a month because that patient required corticosteroids for a month, you will not be optimally managing their condition as their drops will run out before their review. To minimise potential complications of topical corticosteroids, repeated short term pulse therapy has been found to be effective. One paper looked at this51 and found that after an initial pulse of two weeks, if disease free, the drops were tapered and the patient remained in a disease free state for 57 weeks. In this cohort, 21 per cent had a return of their dry eye disease and underwent a second pulse treatment. After the second course, all bar 1.9 per cent of patients were disease free for a period of 72 weeks. No complications were encountered during the entire study period.

DEWS II tables clinical studies that report benefits following the use of topical corticosteroids including improved symptoms of dry eye, reduced staining, improved goblet cell appearance, reduced inflammatory cells, improved Schirmer score, increased tear film breakup time and reduced conjunctival hyperaemia.52-61 The most commonly available agent used in these studies was FML 0.1 per cent, dosage was four times a day over one month.

Artificial Tear Substitutes

While historically, tear replacement products have been the common solution for patients with dry eye, generally these over the counter products were never intended to treat the underlying condition.62 The number of available treatment options, as discussed above, will ensure we can help our patients better than ever before, however we still need to manage our patient’s symptoms. As mentioned before, many of the dry eye treatment options take time to be effective. This makes it imperative to give attention to the best artificial tear supplement to keep our patients happy while we wait for the results.

Australian drinking habits have changed over the past 50 years. In the 1970s 75 per cent of us chose to drink beer. Now only 30 per cent of us choose the golden liquid with 40 per cent choosing wine, 30 per cent choose spirits and those highly educated individuals choose cider. In this vein, I am also expecting to see a change in our recommendations in relation to artificial tears. Traditionally we have focused on aqueous supplements and indeed the market has many for us to choose from. Given however, that DEWS II reports that evaporative dry eye is the most common type of dry eye,1,63,64 I suspect the use of lipid containing tear supplements should rise.

Aqueous supplements generally work by enhancing the natural tear volume and viscosity. Many agents exist including, but not limited to, carbomer, carboxymethyl cellulose (CMC), hyaluronic acid (HA), HP-Guar, hydroxypropyl methylcellulose (HPMC), polyvinyl alcohol (PVA) and polyethylene glycol. To help you navigate through all the reported benefits to ultimately make the right selection for the individual patient, DEWS II highlighted a few points.9

CMC based products have been shown to bind to corneal epithelial cells and promote healing.65,66 HPMC is found in a wide range of products and has been shown to be a safe and effective lubricant.62 HA has also been found to be able to bind to ocular surface cells and aid healing.67-72 One advantage HA has over cellulose derivatives is that they exhibit non-Newtonian properties. This exciting property means the viscosity of the lubricant will vary depending on the shear forces occurring. In the real world, this means the lubricant will thin while the patient is blinking, then thicken once the blink is finished.73 This ultimately helps ocular retention, which has been a challenge for cellulose products because they have needed to rely on increased viscosity to aid ocular retention, however, if too viscous, will cause blurred vision.

Some agents work better together. This is the case with HA and CMC. A three month study involving 305 subjects found that symptoms and signs of dry eye improved more in the group using a CMC+HA product compared with the group using a CMC product alone.74

Another novel approach to improving ocular retention is found in the Systane family of lubricants which use HP-Guar and Borate to create a cross-linked low viscosity gel (Figure 2).75 HP-Guar based products have reported benefits of improving dry eye symptoms, increasing mucous layer thickness, reducing inflammation and providing protection to the ocular surface.76-82

Figure 2

One final point to note is the role of electrolytes in restoring homeostasis to the tear film. Examples of these lubricants are Bion Tears (Alcon) and TheraTears (Akorn). Reported benefits include increasing conjunctival goblet cell density, corneal glycogen content, improved cell recovery and maintaining tear film structure after exposure to BAK.83-87

Lipid Supplements

Despite only being discussed on a single page in DEWS II, I believe we need, and will see, future innovation in lipid supplements. Multiple studies have already shown that lipid-based eye drops and liposomal sprays improve the symptoms, and in some cases signs, of dry eye disease.88-96

Lipid-based eye drops are formed as emulsions. They are more difficult to formulate than aqueous supplements.97 Emulsions can be categorised based on the droplet size. Products such as Systane Balance (Alcon) and Optive Advanced (Allergan) are macroemulsions with droplet sizes larger than 100nm.9

Systane Balance incorporates the LipiTech molecule, which is mineral oil surrounded by anionic phospholipids. It has been suggested that anionic polar phospholipids have a greater ability to increase the lipid layer thickness.98,99 The mechanism suggested is that they form a stable lipid film by binding to the non-polar lipids at the surface of the aqueous layer.100 Optive Advanced uses polysorbate80,101 which is a non-ionic surfactant and oil in water emulsifier. The drop is biphasic and when applied to the salty tear film, divides into polysorbate80 to complement the lipid layer, and CMC and glycerin to complement the aqueous layer.

Other options to complement the lipid layer are liposomal sprays and the semi-fluorinated alkane, NovaTears. While both these products work well on the lipid layer, best results can be achieved when they are used as chasers after the preferred aqueous supplement is instilled. The sprays contain phospholipid liposomes which are microscopic droplets of oil with an aqueous core. NovaTears is a water free wetting agent with a very low surface tension. It is a nanoemulsion with the droplet size being between 10–100nm. The very small droplet size allows improved spreading across the ocular surface and avoids the light scatter and initial blur which can occur with macroemulsions.9

One drop with the best of all ingredients would certainly make our life easier and the patient’s life less complicated. Alcon is about to release a new product called Systane Complete.

Systane Complete builds on the known science and performance of previous products, acknowledges changing demands of practitioners, and recognises the need to offer relief for our evaporate dry eye patient. This lipid-based evaporative artificial tear contains previously seen elements and new elements to further enhance effectivity. The HP-Guar platform has been maintained, however the concentration has increased compared to Systane Balance to more closely match that found in Systane Ultra. This ensures greater retention of the demulcents and further enhancement of the mucin layer.

Instead of the macroemulsion LipiTech droplets in Systane Balance, Systane Complete has nano-sized lipid droplets. As discussed previously, this allows improved spreading of the mineral oil over the ocular surface upon instillation, reduces the amount of scatter from the oil droplet and minimises visual disturbance (Figure 3).9

Figure 3:  a. Systane Complete has an increased concentration of HP-Guar.  b. An enhanced meshwork allows better retention of demulcents and a slow release of nano-sized lipid droplets. c. Nano sized droplets migrate to the top of the tear film.

 

In terms of drop evolution, I believe this product is the first to complement all layers of the tear film, have increased ocular retention without the need for high viscosity and display excellent spreading and visual performance due to non-Newtonian and nanoemulsion chemistry.

   

Jason Holland B.App.Sci (Hons) (Optom), PGOT, CASA CO runs a glaucoma and advanced dry eye clinic in Brisbane. He is the national director of optometry for the Optical Superstore Group and he served as the director and treasurer for Optometry Australia, Queensland and Northern Territory for nine years until 2017. He served on the Optometry Australia National Board for three years and currently sits on the Deakin Optometry Advisory Board.

Jason Holland wrote this article on behalf
of Alcon. The views expressed are those of the author and do not necessarily represent the views of Alcon.

Contact Alcon Laboratories (Australia) Pty Ltd: 1800 224 153, New Zealand: c\o PharmaCo, Auckland, NZ: 0800 101 106

NP4 Number # :A21809882206

  

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