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Dry Eye, do I have time to investigate, discuss management, and then review? Is my hard work going to make any difference for the patient? Is it financially viable?
The above are questions I commonly get asked when meeting with colleagues around Australia and in some cases, the answer can be no! However, the aim of this article is to engage you to help your Dry Eye patients with minimal chair time and to also learn when to put up the white flag and refer the patient to crazy people like myself who spend hours trying to improve the quality of life for the more severe dry eye patients.
DEWS 2 has reminded us just how complex and multifactorial Dry Eye is. I have seen the interest in Dry Eye explode in recent years and I have heard a lot of opinions on how to best diagnose and manage the condition. While I am excited about the enthusiasm of Optometrists 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 2 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.
It is important to remember that Dry Eye is a chronic condition and that treatments generally take a long time 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 waiver or treatments will be changed unnecessarily, and ultimately, we will mismanage the patient’s condition. Donald Korb suggested that a review at three months will ensure you assess treatments at their maximum effect. 
An accurate diagnosis of the type and severity of Dry Eye Disease affecting your patient is critical to successful management and does not need to be an expensive process or consume considerable chair time. To aid us, DEWS 2 has done all of the hard work. [Fig 5]
From the above diagram, the critical tests are an accurate symptom assessment and vital stains. I recommend using NaFl stain and Lissamine Green stain to assess tear stability, quantity, and surface staining. If time permits, expression of the Meibomian glands with gentle pressure is also a valuable test. The above should take less than five minutes and is inexpensive. Key points:
· NaFl good to assess Tear Meniscus height and FBUT (<6.5 sec abnormal) 
· Lissamine Green best to assess cell health, conjunctival stain often precedes corneal
· Number of glands expressing, and the quality of the expression can help tailor treatment
For every Dry Eye patient attending my clinic, they all leave with similar basic advice prior to returning for more advanced treatments. Part of the initial consultation is to educate the patient about their Dry Eye disease, set expectations and discuss all management options. For many, the cheaper more labour intensive is their first preference, and this is what I will discuss next.
I discuss four key elements with every Dry Eye patient. Drops, Lid Hygiene, Hot Compresses and Omega-3 intake.
These four elements appear in Steps 1 and 2 of the DEWS II recommendations.
Now I will admit here that Dry Eye consultations are never easy, the long case history can mean your coffee break evaporates and by the end of the consultation you are tempted to have a quick nip of the Christmas Scotch hiding in your top draw! 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. This is an environmental aspect which can be easily overlooked, yet can cause a patient 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 the blink rate of our patients is now significantly less. Simply discussing with patients, the need to take conscious blinks and/or follow blink exercises can go a long way to promoting a healthier tear film. 
Apart from treating Anterior Blepharitis, Lid Hygiene is an important element of managing Dry Eye disease as obstruction of the Meibomian Glands can be due to hyperkeratinisation of the eyelid margin.  Accumulated debris and keratinised cells on the lid margin need to be removed to promote better Meibomian Gland function. This can be done initially with a stainless-steel golf spud which has been shown in one study to improve patient symptoms in 22% and MG function in 46% of subjects.  In addition to this, dedicated eye lid cleansers should be utilised. DEWS 2 quotes a recent study where the efficacy of diluted baby shampoo was compared to a lid cleanser. The commercial lid cleanser was better tolerated, improved lipid layer quality and reduced inflammatory markers while the baby shampoo was also found to have a negative effect on goblet cell function. 
In discussing lid hygiene, I must also mention the need to be mindful of Demodex. While it has not been shown to directly cause MGD, its role in Anterior Blepharitis and symptomatic dry eye patients has been documented.  Tea Tree Oil is toxic to Demodex.  Pure Tea Tree Oil can be toxic to the eye so diluted commercial preparations are advised. [418,419] The key to success is treatment duration. The papers assessed in DEWS 2 suggest 4-8 weeks of twice daily treatment. [Table 6] What was also mentioned is that compliance is often poor with a suggestion that only 55% of patients were compliant after six weeks, hence periodical review is important with these patients. 
My go-to products are Oust Demodex or Occusoft Plus Platinum. The addition of Hypochloric Acid in Platinum plus ensures excellent results in even advanced cases of Anterior Blepharitis.
This is an area where I see a lot of sub-therapeutic techniques and a lot of non-compliance due to a lack of education. 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. [389,390,429-432] So, let’s move forward and upgrade to a newer better version of hot compresses! DEWS 2 evidence shows that a warm compress can soften and liquify Meibum but what is not definitive is the temperature and time required to be successful. [434,435,437-439] The more obstructed the glands, the higher the melting point of the Meibum. [434,437,440] Evidence suggests that heating the Meibomian glands to at least 40oC is required for optimal results. [433,437,441] Further to this, application of the device for at least 5 minutes twice a day is required for a treatment period of between 2-4 weeks.  Of note is the statement that a hot washer is only effective when used multiple times from a bundle of hot washers. 
The time involved to make the 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 would strongly suggest that if you are going to discuss warm compresses with your patient that you recommend one of the commercial heat packs. There are a number on the market now and a small study found that they were all more effective than a hot washer in achieving 40oC for at least five minutes. 
The Eye Doctor mask is an excellent choice and was shown to have the most stable heat over the 9-minute testing protocol. It can also be used cold which is an excellent adjunct therapy for your patients suffering ocular allergy.
Lid expression has been advocated in MGD by multiple papers and while effective, the limiting factor to success is either the patient’s pain threshold or the practitioner’s confidence level. [460-464] 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.  While in-office I use a paddle style forceps, it is important to mention here a caution for patients attempting expression at home. DEWS 2 mentions that the Cornea can rise in temperature from 36 to 39.4oC after 8 minutes of a warm compress. If rubbing of the Cornea then occurs or advice to massage the Meibomian glands against the Cornea is actioned, there is a risk of corneal deformation and visual blur. [448-450] As such, my advice and something that I demonstrate, is after the heating device is removed, with clean hands, pull the eyelid away from the eye in a pinch like fashion and squeeze for a count of three. Repeat this for each eyelid. This technique ensures that no pressure is exerted on the Cornea immediately after the warm compress.
For those who are still unsure of the role of nutritional supplementation and Dry Eye I would suggest you peruse the considerable evidence nicely tabled on page 609 of the DEWS 2 report. [Table 13] Apart from discussing general hydration with our patients [819-821], the evidence suggests that we should also be discussing essential fatty acids (EFAs) . Humans must source EFAs through food. Important in DED are long chain Omega3 EFAs which exist as EPA and DHA. These are found in high concentrations in oily fish such as Salmon, Tuna, Mackerel, Trout and Sardines.  Within the body Omega3 and Omega6 EFA’s compete for enzymes and ultimately regulate systemic inflammation. The ratio of consumed Omega3 to Omega6 is important in balancing inflammatory cytokines.  Our current Western diet has an elevated Omega6 intake and so to restore the balance, nutritional intervention in the form of Omega3 supplements is required.  We could reduce our Omega6 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 Woman’s Health Study involving over 32,000 subjects reported a 30% reduction in the risk of DED for every additional gram of Omega3 consumed/day. 
So, the common question asked is how much and for how long?
Based on the summarised DEWS 2 papers, most researchers assess performance at 3 months. Most used samples of over 1000mg of Omega3 up to 2240mmg. [Table 13] A recent pilot study also suggested that 1500mg of Omega3/day can have a central corneal neuroprotective effect.  This is exciting!
Two important things to note when suggesting Dietary modification. Firstly, the capsule size does not reflect the actual Omega3 content and close examination of the nutritional label is important to ensure a therapeutic dose is being taken. Often the patient chosen, may I say it “cheaper” option, is invariably full of other ingredients. Think fillers, stimulants, grass clippings etc Sounds like a good night out on the Gold Coast!!
Second, high-dose Omega3 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. 
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 hyperosmolarity 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. 
Studies have found that topical corticosteroids are effective in breaking the cyclical immune response in Dry Eye Disease. [541,542] 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 this  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% had a return of their dry eye disease and underwent a second pulse treatment. After the second course, all bar 1.9% 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 reporting benefits following the use of topical corticosteroids including improved symptoms, reduced staining, improved goblet cell appearance, reduced inflammatory cells, improved Schirmer score, increased tear film breakup time and reduced conjunctival hyperaemia. [547-557] Some points to note to guide practitioners are the most common available agent used was FML 0.1%, dosage was four times a day over one month. Other findings were that topical corticosteroids were more effective than topical NSAID (flurbiprofen) , more effective than HA drops alone  and more effective than CsA 0.5% .
Artificial tear substitutes
For those of you still reading, we are now on the home straight. Recharge your hot beverage and settle in for the final chapter.
While historically tear replacement, products have been the common solution for patients with Dry Eye, these generally over-the-counter products, were never intended to treat the underlying condition.  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 so it is imperative to also give attention to the best artificial tear supplement to keep our patients happy while we wait for the results.
Traditionally we have focused on aqueous supplements and indeed the market has many for us to choose from. Given however that we now know that approximately 85% of our Dry Eye patients have an element of Evaporative Dry Eye [139,140], I would suspect that 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 2 highlighted a few points.
CMC based products have been shown to bind to corneal epithelial cells and promote healing. [22,23] HPMC is found in a wide range of products and has been shown to be a safe and effective lubricant.  HA has also been found to be able to bind to ocular surface cells and aid healing. [28-33] One advantage HA and HP-Guar have over Cellulose derivatives is that they exhibit Non-Newtonian properties. This exciting property means that the viscosity of the lubricant will vary depending on the shear forces occurring, so in the real world this means that the lubricant will thin while the patient is blinking and then thicken once the blink is finished.  This ultimately helps ocular retention which has been a challenge for cellulose products where they have needed to rely on increased viscosity to aid ocular retention, however, if too viscous, will cause blurred vision.
Hylofresh and Hyloforte (0.1%) and (0.2%) respectively are pure HA products which are dispensed from the very clever COMED bottle which enables sterile preservative multi-dose instillations from a multidose bottle.
Like a good Shiraz and Eye Fillet, some things work better together. This is the case with HA and CMC. A study involving 305 subjects found that symptoms and signs improved more in the group using a CMC+HA product compared with the group using a CMC product alone.  I have also found combining Hylo products with Novatears a synergistic solution for more holistic tear film supplementation.
And now for the top-shelf products, the Lipid supplements. Despite only being discussed for a single page in DEWS 2, I really feel this is where we need, and will see, future innovation. Multiple studies have already shown that lipid-based eyedrops and liposomal sprays improve the symptoms and in some cases signs of Dry Eye disease. [65,141,142,177-182] Lipid-based eyedrops are formed as emulsions. They are more difficult to formulate than aqueous supplements . 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 100 nm.
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 [46,173]. 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 . Optive Advanced utilises Polysorbate 80 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 Polysorbate 80 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 semifluorinated alkane, Nova Tears. While both these products work well on the lipid layer, best results can be achieved when these products are used as “chasers” after the preferred aqueous supplement is instilled. Like the Tequila tastes better after the salt and lemon! The sprays contain phospholipid liposomes which are microscopic droplets of oil with an aqueous core. Nova tears 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 rapid spreading across the ocular surface and avoids the light scatter and initial blur which can occur with macroemulsions.
So, when do you decide to refer patients on? For busy practitioners, if you have allowed three months for a good management plan including lid hygiene, Omega-3 advice, warm compresses with expression and appropriate topical therapy to work and the patient returns unhappy, that is the point where I would suggest phoning a dedicated Dry Eye clinic. For some patients you may decide to review them after each month to ensure compliance and potentially change your topical therapy, but ultimately for some Dry Eye patients, relief may require more invasive procedures including IPL, LipiFlow and RexonEye
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