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Dry Eye Fails: Why Some Treatments Don’t Work

2 CPD in Australia | 0.25CD + 0.25G in New Zealand | 23 June 2017

By Dr. Colin Chan

Dry eye continues to be a giant and growing problem of optometry and ophthalmology. Despite new treatments developed as a result of extensive research and our efforts as practitioners to treat individual patients, many continue to complain that their dry eye treatment is not working. I’d like to share with you my thoughts, my conversations with patients and what I think can help to reduce dry eye treatment failures.

DEWS II recently reported that over 30 million people suffer from dry eye disease (DED) in the USA alone i.e. nearly 10 per cent of the population. We know this is probably a conservative figure as dry eye can be asymptomatic and therefore underdiagnosed. Yet for such a common problem, simple effective treatment still eludes many patients. It can be a very frustrating condition to treat, both for the patient and eye care practitioner.

As a so-called ‘dry eye specialist’, I am often not the first eye care practitioner the patient has seen. Usually she/he has tried self-treatment or seen other optometrists and ophthalmologists. This has given me a unique opportunity to observe and compare both other practitioners’ actions and my own and slowly develop an idea of what works and what doesn’t.

The key, as always, is communication. For some of my patients, I almost don’t need to say anything as they are so well researched and knowledgeable. But it is better not to assume this.

Would you water a plant regularly if you wanted it to be healthy? Do the same for your eye! 

Fail #1: Failure to Lubricate

We all know that dry eye management is a pyramid of treatments. Initially simpler measures such as lubricants, omega 3 supplements, warm compresses and environmental modifications should be recommended with mild dry eye according to DEWs and the Meibomian Gland Dysfunction (MGD) executive summary.1,2 With more severe dry eye, prescriptive medications such as topical corticosteroids or oral azithromycin constitute the next level up of the pyramid of treatments. As per the MGD executive summary (Table 1 on following page), these prescriptive medications are meant to be in addition to the simpler measures. However, so many of my patients ‘forget’ to keep going with the simpler measures once prescribed prescriptive medications. Or sometimes we presume that they should know to do that.

The conversation usually goes like this:

Me: “So have you been taking the FML eye drops?”

Patient: “Yes.”

Me: “Three times a day?”

Patient: “Well yes, well no… to be honest, most of the time I do three times but sometimes it’s twice or occasionally once.”

(Non-compliance is also often an issue.)

Me: “Ok...” Said with questioning tone to suggest gentle disapproval.

I think OK is one of the great words of the English language; said with different tones, it can mean anything; from actually meaning things really are OK to meaning things are really not OK...  But I digress.

Patient: Guilty look.

Me: “So have you been using your tear drops as well?”

Patient: “Uh no… I didn’t think I had to, since I was on the FML and especially once I started feeling better – I didn’t feel I needed to.”

Me: “Ok…”

It is important therefore, to emphasise to patients the need for ongoing lubricants in addition to their prescriptive medication. Patients typically only remember 14 per cent of any given consultation so repetition within a consultation and across consultations or even writing down how the drops should be taken may be helpful.3,4

Table 1: Treatment Algorithm for MGD. Copyright. Association for Research in Vision and Ophthalmology

 An analogy I often use which seems to help patients understand the importance of ongoing lubricants is to think of their eye like a plant. Their plant is not doing so well at this point in time, it’s brown, the leaves are falling off and watering it is not working. So they need fertiliser. But even with the fertiliser, it is still important to keep watering it. Patients get this. Sometimes they have given up on lubricants because they feel it makes no difference or even makes their eyes feel worse. I suspect that in patients with severe dry eye disease, very low level tear volume leads to poor spreadability of lubricants, which then causes more irritation.

Often patients are also confused as to how long after the prescriptive drop they should take the lubricant. I usually say two minutes as I think this is realistically the longest any human could stand to wait, still remember and not get distracted by children, the phone or some other task. Tradition dictates five minutes and other guidelines may say three.5,6

Fail #2: Failure to Maintain

Related to this is a common complaint by patients that their dry eye comes back. Again this is about understanding and accepting the nature of dry eye. The DEWS definition of MGD, the most common version of dry eye,2  states: “Meibomian gland dysfunction (MGD) is a chronic, diffuse abnormality of the meibomian glands, commonly characterised by terminal duct obstruction and/or qualitative/quantitative changes in the glandular secretion. It may result in alteration of the tear film, symptoms of eye irritation, clinically apparent inflammation, and ocular surface disease.

The key word here is chronic. Dry eye is a chronic disease. It doesn’t go away and it can’t be cured. It can only be controlled as best as possible. This is important to explain to patients so they understand that ongoing treatment such as regular lubricants, warm compresses, omega 3 supplements and lid hygiene is required. Initially this may be a hard thing for patients to accept. I find again that analogies work for example:

Me: “I know it’s hard to accept but dry eye is something that can’t be cured. You are always going to have dry eye and it will flare up from time to time, sometimes for no apparent reason. The best you can do is to control it but this means you have to be regular with what you do, like regular tear drops, or warm compresses.”

Patient: “Really?”

Me: “Yes unfortunately. Think of it this way, as we get older, we get more and more problems with our body right? For example, problems with our teeth and gums.”

Patient: “Yes, don’t get old doc, it’s no good.” Usually laughs.

Me: “Don’t worry, I am older than I look so I know… if we have unhealthy teeth and gums we need to brush and floss more and drink more water, right? And it’s not like you can do that for a few months and go, hey I feel better, now I can stop brushing and flossing right?”

Fail #3: Failure to Persist

Another common reason for failure of dry eye treatment is that either the patient or eye care practitioner did not persist with the proposed therapy for long enough. This may occur due to impatience or pressure for a ‘quick’ fix. In my experience it’s most commonly because either the patient didn’t understand or wasn’t explained the expected timeline for symptom relief or because the practitioner didn’t understand this either. This is particularly important for moderate to severe dry eye disease, which takes longer to resolve. Clinical drug trials usually use three to six months as the primary endpoint for patients who have moderate to severe dry eye disease.7,8

The other reason for lack of persistence with treatment is concern over side effects. Topical steroids seem to cause the most concern. This is despite studies which demonstrate even with strong penetrating steroids, side effects such as cataract or systemic side effects such as adrenal suppression are not typically seen even after one year of continuous use. The main issue with weakly penetrating steroids such as FML and flarex is the risk of intraocular pressure (IOP) rise. The risk of this happening over the first several weeks is low.9,10 Addressing this concern directly may often alleviate anxiety, particularly if the patient is counselled by other health practitioners, such as pharmacists or their GPs, about the risk of steroids. Also asking specifically for a family history of glaucoma is important as patients with a family history are more likely to be a steroid responder and are also more concerned in general regarding glaucoma risk.

The conversation may go like this:

Me: “The drop is actually a form of mild cortisone or steroid. Some people get worried when they hear this. It’s not at all like taking cortisone tablets – you are not going to get fat or grow extra hair.”

Patient: Usually laughs.

Me: “The main short term risk is the risk of the eye pressure going up. The risk of this happening over the next few months is low. You may be told by your pharmacist or GP that these drops cause glaucoma and are dangerous. Have you heard of glaucoma?”

Patient: “Yes.” Usually.

Me: “Glaucoma only occurs if the pressure goes up, and if it goes up high enough and for long enough… and if you don’t go to your optometrist or to me to check it, and if you keep using drop without telling us… and if we don’t do anything about it. So you can see, it’s unlikely to happen if we both do the right thing .” Said with a smile.

Patients should be encouraged to view dry maintenance treatment as similar to the need to brush ones teeth

Fail #4: Failure to Diagnose

Sometimes it isn’t dry eye… and it’s important to keep your mind open to the possibility of masquerade syndromes such as map dot finger print (MDF) dystrophy, (Figure 1 on following page) allergy and superior limbic keratoconjunctivitis (SLK). I was reminded of this recently when I reviewed a patient I had started treating for severe dry eye. Her initial presentation was typical of chronic severe dry eye: irritation and dryness and large clumps punctate epitheliopathy over the lower half of the cornea. I commenced her on FML three times daily and reviewed her six weeks later. Her optometrist had reviewed her at three weeks to check the IOP. She complained that her symptoms had only slightly improved before flaring a few days ago. Once I had seen her cornea, I knew why: the clumps of punctate erosions had gone, revealing underlying map dot fingerprint dystrophy. Beforehand, I had not been able to see it because of the erosions, but now it stood revealed.

Figure 1

Figure 2

MDF dystrophy is the most common corneal dystrophy. It may affect as many as 42 per cent of all ages worldwide, and about 76 per cent over the age of 50.11,12 In some patients the symptoms are classic – tearing sensations upon awakening in the morning or during sleep – but some people complain of symptoms more typical of dry eye: grittiness, dryness and fluctuating vision. The treatment paradigm for map dot is quite different from dry eye and includes treatments such as hypertonic saline 5 per cent and phototherapeutic keratectomy laser (PTK) which may worsen dry eye, hence differentiation of the two is important.

One of the principles we are taught at medical school is Occam’s razor: that a range of symptoms and signs occurring together should always, if possible, be attributed to a single disease rather than to several different diseases occurring simultaneously. This can be useful in many clinical situations. However, a counter principle, which is equally useful, is Hickam’s dictum. This is often stated as ‘Patients can have as many diseases as they damn well please’. The fact is, that as we get older, we often accumulate conditions and diseases and the eye is no exception. A patient with dry eye symptoms may have blepharitis, Sjögrens and MDF dystrophy. Blepharitis is a very common co-existent condition with any version of dry eye disease.13 If this patient goes on to have cataract surgery, then we can add in post cataract surgery neuropathy and preservative toxicity to this patient’s multifactorial dry eye disease. Maybe the patient is a breast cancer survivor and is also on tamoxifen and therefore has aromatase inhibitor dry eye as well. It becomes complex, doesn’t it?

That’s why I often have the following conversation with a patients:

Patient: “So what’s the cause of my dry eye?”

Me: “Well I can’t tell you the exact cause. No one knows what causes dry eye... If we knew, then we could cure it. What I can tell you is what your risk factors for dry eye are.”

Patient: “So what are mine?”

Me: “Firstly, dry eye is more common in females over the age of 40 as hormones play a part. Secondly you have a history of thyroid disease, so that may play a role. Also, you work in front a computer all day in an air-conditioned office. If you took a holiday for three months in a nice, moist tropical Asian island, I am sure your dry eye would be better.”

Patient: Laughing. “Can you write me a prescription for that?”

Me: “I wish.” Smiling. “So you can see why dry eye can be difficult – there are a lot of factors that we can’t change or control.”

Having said this, if possible it can be helpful to put some sort of label on the dry eye as this may guide more effective treatment. Sjögrens is a good example. I routinely test for Sjögrens in anyone with suggestive symptoms such as dry mouth or if the dry eye seems more difficult to treat and I am not having success after six months. Patients with Sjögrens typically require more intensive and more prolonged topical anti-inflammatory treatment. Punctal plugging is also more effective in Sjögrens syndrome, and in severe aqueous deficiency often punctal plugging is not effective unless the upper tear ducts are occluded as well as the lower tear ducts. Often these patients go on to punctal cauterisation.14,15,16

Rosacea patients are similar in that prolonged anti-inflammatory therapy is often required. However, these are often the patients I direct more towards meibomian gland treatments such as azithromycin or doxycycline and towards blephasteam or IPL.17,18

Fail #5: Failure to Treat the Whole Person

As much as eye care practitioners would like to simplify matters, patients’ eyeballs are still attached to the rest of the body and what happens to the rest of them, often affects their eye. Sometimes an eye problem may represent the first sign of a systemic disorder and we may be the first health practitioners to guide patients towards discovering it.

For example, a patient that presents with severe dry eye and severe filamentary keratopathy must be suspected to have rheumatoid arthritis or Sjögrens syndrome. In this scenario, I will suggest the patient go and see their GP and have blood tests such as rheumatoid factor and Sjögrens antibodies. From there, a rheumatologist will often become involved and medications such as plaquenil may be prescribed. Sometimes oral prednisolone may also be given and this can help settle the dry eye in addition to the topical prednisolone. This always needs to be kept in mind as, for example, if a patient is on a tapering dose of oral prednisolone, I usually do not taper my topical dose at the same time or I do it at a slower rate so the patient doesn’t get a double withdrawal effect and risk having a rebound of their dry eye keratopathy. Sometimes the dry eye will not settle without the addition of systemic medications and you may wish to write to the GP or physician and ask whether an oral medication may be considered or increased.19,20

Fail #6: Failure to Calm the Nerves

The freshly updated definition of dry eye released by DEWS at ARVO this year contained one very significant change. Dr. Jennifer P. Craig, the Workshop Vice-Chair stated, “Dry eye is a multifactorial disease of the ocular surface characterised by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles.”

This new definition now gives added weight to the concept that dry eye symptoms and signs are affected by changes to or abnormalities of corneal sensation and corneal nerves. We have all seen patients where the dry eye signs are minimal and do not explain the degree of symptoms. We have also all seen cases where the signs improve but the patient’s symptoms do not. There is evidence that this is because there is a significant neuropathic pain component to dry eye. Corneal and conjunctival nerves may undergo upregulation in terms of neural sensitivity over time and hence continue to send pain signals even with minimal stimuli.21-23

In patients where the signs of their dry eye improve yet their symptoms do not, I will often have this conversation:

Me: “Over the past few visits, I have actually seen your eye getting better. The ulcerations are gone and the tear layer looks a lot better. But you told me you don’t feel any better.”

Patient: “So what does that mean? Am I imagining it?”

Me: “No, not at all. Sometimes the nerves in the eye can become over sensitised if dry eye is chronic. It’s like being punched on the arm, even if each punch is the same after a few it would hurt more and more right? So sometimes the eye nerves get so sensitised that even when irritation stops, they still keep firing.”

Another analogy I often use is chronic back pain where often the disease e.g. slipped disc, does not worsen but maladaptive changes in posture, muscle reaction and upregulation of nerve sensitivity means pain worsens over time and treatment is difficult. Neuroscientists often quote the phrase “Nerves that fire… rewire” meaning that pain can become built into our system by repetition and chronicity.

A number of studies have examined the role of neurostabilisers and other medications in the treatment of dry
eye.16-17 These options are usually best explored with the patient’s general practitioner as multiple drug interactions and systemic side effects are possible, which may be outside the scope of practice of ophthalmologists and optometrists. However, often the suggestion to explore pain management options may need to come from the primary eye carepractitioner, as the general practitioner may not have the same appreciation of the impact of dry eye on the patient.

I personally have found referral to an optometrist for a bandage contact lens can be very useful in these cases as well (Figure 2). There are a few possible reasons I think this may work. One may be neural downregulation that comes with chronic contact lens wear, which is well documented. The other possibilities may be a barrier effect or trapping of a well of tears onto the cornea. The concept was initially alien to me as an ophthalmologist, but I was pleasantly surprised to find there is published literature as far as back as 1985 supporting this as an alternative in patients with recalcitrant dry eye disease or symptoms.24,25

Conclusion

Michael Jordon, arguably the greatest NBA player in history said: “I've missed more than 9,000 shots in my career. I've lost almost 300 games. Twenty-six times, I've been trusted to take the game winning shot and missed. I've failed over and over and over again in my life. And that is why I succeed.” I remember hearing that quote as a teenager and it made a big impression. Understanding why things fail and how to adjust what you do is a key to life and medical success.

Dry eye is an area of medicine where we still know so little and there is still so much variability in treatment success. I hope by sharing some of my experiences and thoughts with you, you will have greater success with your dry eye patients in the future. 

 
 

Dr. Colin Chan is a refractive, corneal and cataract surgeon at Southern Ophthalmology and Vision Eye Institute Sydney. He is a Senior Clinical Lecturer at the University of Sydney and was an Associate Professor at UNSW. He is a recipient of an Achievement Award from the Asia Pacific Academy of Ophthalmology for scientific contributions and teaching and the Supervisor for registrar training at Vision Eye Institute. He is also a Director of the Refractive Surgery Degree at University of Sydney, on the Curriculum committee for Ocular Therapeutics at the Australian College of Optometry and recently published a textbook on dry eye through Springer publications.   

 

References
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25. Segal O, Barkana Y, Hourovitz D, Behrman S, Kamun Y, Avni I, Zadok D. Scleral contact lenses may help where other modalities fail. Cornea. 2003 May;22(4):308-10.
26. Nichols KK, Foulks GN, Bron AJ, Glasgow BJ, Dogru M, Tsubota K, Lemp MA, Sullivan DA. The international workshop on meibomian gland dysfunction: executive summary. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1922-9. doi: 10.1167/iovs.10-6997a. 
Note: table has been modified. 
Novartis Pharmaceuticals Australia Pty Ltd, Ph:1 800 671 203. AU-2023 May 2017. © 2017 Novartis

' Dry eye is a chronic disease. It doesn’t go away and it can’t be cured… This is important to explain to patients so they understand that ongoing treatment… is required '