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Ocular surface disease: One physician’s approach to treatment
It has been a busy 2 weeks in the clinic since I wrote my last commentary on dry eye syndrome, focusing on the screening diagnostics I use in my practice. First, a few more thoughts on the diagnosis side, and then on to therapy. I will compare what I do today vs. what I did in the past and focus on what I am really doing in my clinical practice today.
In disclosure, I have practiced as a consultative corneal specialist for 38 years, so I may see a different mix of patients than other clinicians, and I consult widely in the field of ocular surface disease, including with companies that manufacture some of the products I will mention and/or their competitors. One could write a several hundred page book on the topic of ocular surface disease, and my comments are limited to a few paragraphs, so many topics are left out. The focus is on the horses, not the zebras. I have seen a few cases of ligneous conjunctivitis in my career and have had more ocular pemphigoid to treat than some, but these rarer cases are not the topic of today’s commentary.
In regard to symptom screening by my technicians, the symptom most frequently missed is fluctuating vision, which is quite common in meibomian gland dysfunction (MGD) with evaporative dry eye. I find tear film osmolarity useful in diagnosis and treatment, but the osmolarity numbers that I consider to be consistent with dry eye are different from those taught by many. In my patients who are screened for corneal refractive surgery with no symptoms, no MGD and no corneal staining, the tear film osmolarity is always under 300, actually usually around 290, and symmetrical within 2 milliosmoles to 3 milliosmoles. So for me, with the TearLab device, a reading higher than 300 milliosmoles and asymmetry of 4 milliosmoles or more is significant. If osmolarity is higher than 308 or asymmetric at the 8 milliosmole level, the patient has significant dry eye syndrome.
In regard to MGD or squamous blepharitis, which is my best ICD-10 code, I find it is pretty much present at least to a minor extent in everyone older than the age of 50 years. In most patients, it is mild and there are no symptoms, with a symmetric tear film osmolarity under 300 and no corneal/conjunctival staining with fluorescein or lissamine green. In these cases, I note it in the chart but do not treat unless I elicit symptoms of fluctuating vision or ocular fatigue associated with computer use or the like. A tear film breakup time less than 5 seconds is a useful sign here and can be objectively documented using the Visiometrics/AcuFocus AcuTarget HD. An irregularly irregular topography is also common and a useful sign. In these patients, treatment of their dry eye is critical before surgery, especially if corneal refractive surgery or a premium IOL is planned or errors in spherical and toric power will be made and patient satisfaction reduced. In addition, I am finding the LipiView II from TearScience a more useful tool than LipiView I for diagnosis and patient education in patients with significant MGD.
Michael Lemp, MD, has published that so-called evaporative dry eye is 86% of cases and aqueous deficient dry eye only represents 14%. In my practice, nearly all senior patients have either evaporative or combined evaporative/aqueous deficient dry eye. Pure aqueous deficient dry eye is rare, usually present in patients younger than 50 years, and when present, leads me to look carefully for associated systemic disease and Sjögren’s syndrome, especially in the young to middle-aged female patient. Just like acne rosacea needs to be looked for in all patients with MGD, a pure aqueous deficient dry eye with a Schirmer’s test with anesthesia less than 5 mm deserves a Sjö test (Bausch + Lomb) or a referral to the primary care physician or a rheumatologist for a work-up. I do not do many Schirmer’s tests compared with decades ago (none in the last 2 weeks), simply looking for a decreased tear meniscus as a sign of aqueous deficiency. There are, of course, a lot of other findings to note, and the most common I observed in the last 2 weeks were lid laxity, nocturnal lagophthalmos, conjunctivochalasis, nasal ectropion, punctal atresia, anterior basement membrane dystrophy, pingueculae, pterygium and floppy lids associated with obesity, to mention a few.
Now on to a few comments on treatment. In my practice, most, if not all, patients have an evaporative component to their dry eye. I therefore prescribe a lot of omega-3 supplements and find them very effective. I find the omega-3s extracted from pelagic fish the most helpful, preferring PRN or Nordic Naturals. Many patients are on ineffective OTC omega-3s that are not well absorbed, and many are using a sub-therapeutic dose. I recommend 2,000 mg per day. In addition, I find many patients cannot swallow the larger capsules and prefer the liquid omega-3 in a bottle as a preferred alternative.
In regard to tear supplements, I am a fan of those containing sodium hyaluronate, which is increasingly supported in the literature. If a patient is taking a topical lubricant more than four times a day or is on other preserved drops such as preserved generic glaucoma medications, I recommend non-preserved tears. Heat can be helpful, and the best way I have found to apply it at home is the Bruder mask, which uses a microwave and applies safe moist heat. I believe bacteria and in some cases Demodex play a role in the pathology of MGD. I used to prescribe a lot of erythromycin ointment and in some cases metronidazole or tea tree oil, but patients did not like the mess or stinging. I prefer drops over ointments, using a drop and massage approach when a medication is needed, and find AzaSite (azithromycin ophthalmic solution 1%, Akorn) and Polytrim (trimethoprim sulfate and polymyxin B sulfate, Allergan) quite useful.
However, for me and my patients, Avenova (NovaBay) sprayed on the eye, lids, and when acne rosacea is present, eyebrows, nose and cheeks works better than topical antibiotics. In women it can be applied in the morning before makeup is placed and in the evening after it is removed. It pretty much kills all microbes and on a glass slide is death to Demodex as well. It is also an anti-inflammatory. I use a lot of it, and it can be safely applied frequently, if needed four or more times a day. In the clinic, I demonstrate its use to my patients and have used it 10 or more times a day without toxicity. For many of my patients who can use it frequently because they do not wear makeup, it has replaced drops.
In moderate to severe disease with significant signs, especially corneal staining, I will usually initiate therapy with an antibiotic/steroid or steroid drop. Both symptoms and signs respond rapidly to steroid drops, usually in 1 week, and therapy past 2 weeks or at most 4 weeks is rarely indicated. Initiation of therapy with a steroid four times a day for 2 weeks, then tapering to twice a day for a second 2 weeks and adding Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan) twice a day on the third week of therapy is a good way to initiate anti-inflammatory therapy. I suspect this will work well with lifitegrast (Shire) if and when approved as well.
In very difficult chronic dry eye patients, low-dose non-preserved steroids such as compounded 0.01% dexamethasone or 0.25% prednisolone in balanced salt solution along with sodium hyaluronate is a useful treatment. Alrex (loteprednol etabonate ophthalmic suspension 0.2%, Bausch + Lomb) is a reasonable alternative as a prescription drop used off label, but it contains a preservative. Doxycycline at 20 mg to a maximum of 50 mg by mouth helps in acne rosacea. I reserve punctal plugs for confirmed aqueous deficient dry eye, so for me they are used infrequently.
We have two office treatments that we find useful in patients with MGD. The first is LipiFlow (TearScience), and I am using it more now that the price has been reduced. A less expensive but more labor-intensive treatment combines warming the lids with a Bruder mask, treating the lid margin with mechanical scraping and debridement with the BlephEx device, followed by manual meibomian gland expression. In our practice, we have found that we frequently delegate these treatments to an optometrist, and in some practices, a COT/COMT or physician assistant is delegated the responsibility for these treatments. After these treatments, long-term maintenance therapy is continued, and the LipiFlow or BlephEx treatment may need to be repeated every 6 to 12 months. Patients with disease requiring this level of therapy are very time consuming, and we have two full-time optometrists in our practice who specialize in caring for these patients.
In summary, my most frequently utilized treatment modalities now include an omega-3 by mouth, a tear containing sodium hyaluronate, Avenova, AzaSite or Polytrim topical antibiotics in drop and massage technique, heat with a Bruder mask, a topical steroid alone or in combination with an antibiotic for a short course of therapy, Restasis, low-dose doxycycline, punctal plugs, and BlephEx plus mechanical debridement and lid expression or LipiFlow treatment. I am excited to access lifitegrast, low-dose sustained-release dexamethasone in a punctal plug (Dextenza from Ocular Therapeutix) and the Oculeve lacrimal stimulation device (Allergan).
After being pretty stagnant for decades, my primary diagnostic and therapeutic recommendations have changed immensely in the past several years. With the increased realization that dry eye syndrome is frequent, causes significant patient suffering and reduced visual performance, negatively impacts subjective and objective outcomes in cataract and refractive surgery, and can be effectively treated, clinicians and industry have responded by developing ever better diagnostic and therapeutic agents. Fortunately, there are many more advances in the pipeline.
Disclosure: Lindstrom reports he is a consultant and investor in AcuFocus, Bausch + Lomb, OcularTherapeutix and TearLab.