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Issue: December 2008 Managing Concomitant Glaucoma and Ocular Surface Disease
EXPLORING The Latest Techniques and Treatments for Glaucoma

Managing Concomitant Glaucoma and Ocular Surface Disease

Always an important topic in the anterior segment world, ocular surface disease is changing how we treat glaucoma.

By J. James Thimons, OD, FAAO

Topical glaucoma therapy, which most patients use every day for many years, may compromise the ocular surface. Ocular surface disease (OSD) impairs vision and causes discomfort and redness. What's more, we're initiating glaucoma therapy earlier in a person's life than we did 10 years ago due to advances in diagnostic technology and clinical trials that demonstrate an evidence-based need for earlier intervention. With further research and advances in disease detection, we soon may be treating patients 30 years or more.

With this in mind, our goals for treating glaucoma are to prescribe topical therapies that lower IOPs effectively and support a comfortable, highly functioning ocular surface.

In this article, I'll discuss some new research in this area and some practical strategies for keeping the ocular surface healthy in your glaucoma patients.

Emerging Research

At this year's meeting of the American Glaucoma Society, Fechtner and colleagues1 reported on a multicenter study in which 630 glaucoma patients taking IOP-lowering medications completed an Ocular Surface Disease Index (OSDI) survey. About 48% of the patients reported mild to severe symptoms (about 35% mild). Researchers concluded that glaucoma patients were twice as likely to experience ocular surface disease, compared to people without glaucoma. This may be attributed to the ocular drying effects of some systemic medications and changes to the ocular surface that are induced or exacerbated by certain preservatives in topical medications. Researchers also found that the incidence and severity of ocular surface disease increases with the number of topical medications patients are using.

These data support and quantify what we see in practice. If we can't keep patients comfortable and functioning at a high level, they won't continue therapy. The effect of combined glaucoma and ocular surface treatment on compliance is the subject of a future study.

Benzalkonium chloride (BAK) is a preservative used in many glaucoma medications. Studies have shown that BAK has detrimental effects on the ocular surface.2,3 One study4 found that about 70% of the inflammation in the eye was caused by BAK.

Another study5 evaluated the safety and tolerability of bimatoprost (Lumigan, Allergan Inc.), latanoprost (Xalatan, Pfizer Inc.) and travoprost (Travatan Z, Alcon Laboratories Inc.) in 690 patients with ocular hypertension. When patients were switched from bimatoprost or latanoprost to BAK-free travoprost for 12 weeks, ocular surface disease improved from severe to moderate, from moderate to mild and from mild to normal. Travoprost without BAK contains an ionic-buffered preservative system that was specifically developed to be gentler than BAK on the ocular surface. In fact, about 72% of patients preferred travoprost without BAK.5

Multiple Diagnoses

Clearly, ocular surface problems, which are sometimes caused by blepharitis, present a unique challenge in the treatment of glaucoma. When patients have significant lid disease, it's challenging to find a glaucoma drop that won't exacerbate symptoms. My patients with only mild to moderate signs of ocular surface problems might call me the day after they start therapy to tell me, "That drug stings!" or "My eyes are really red this morning." Upon reviewing these cases, I often find that we started therapy before the anterior segment was clear. The smart way to turn this around is to treat the glaucoma and the anterior segment problem at the same time.

One of the most important tests I perform before initiating glaucoma therapy is lissamine green staining, which gives me a global look at the ocular surface (Figures 1 and 2). I look at the conjunctiva in particular to see if inflammatory disease is present.

Figures 1 and 2. Lissamine green is a dye used for staining cells, which are devitalized or have lost their normal mucin surface, to evaluate abnormal epithelial cells and ocular surface changes associated with insufficient tear-film protection.

I also ask the right questions. I pull back from focusing solely on the optic nerve, pressure and visual fields to look for signs and ask about symptoms of ocular surface disease. I'm always aware that visual function difficulties may stem from a problem on the ocular surface.

Management strategies for these patients may be complex, and I've become increasingly aware that if a patient is taking systemic medications or drops for other conditions, I can almost count on those drugs playing some role in ocular surface disease. I have to balance the right medications for better results.

Multifaceted Therapy

I follow the Delphi panel's6 recommendations for diagnosing and treating ocular surface disease in my glaucoma patients. I may instruct patients to stop using prostaglandins for 2 to 4 weeks to give us time to clear up their anterior segment, and then resume therapy.

I begin by aggressively treating lid disease. I recommend lid hygiene products, such as OcuSoft or SteriLid, for a week or two, and I instruct patients to exfoliate with a clean, warm washcloth thereafter. Heating the lid margins to help break down the oils also is an option. I tell patients to microwave a potato or boil an egg, wrap it with a wet paper towel and hold it on the closed lid for 10 minutes. They can refrigerate, microwave and reuse the same potato or egg for a week or make a new one every day.

If symptoms reach Level 2, I prescribe cyclosporine ophthalmic emulsion 0.05% (Restasis, Allergan Inc.), which treats chronic inflammatory marginal disease better than steroids over long periods and avoids the issue of IOP spikes in at-risk patient populations.7

At Level 3, I may refer patients for selective laser trabeculoplasty to reduce the number of drops they're using, which improves ocular surface quality and appearance. For frustrated patients, a short hiatus from glaucoma therapy is welcome, and then we continue with long-term management. In patients with well-controlled IOP and significant complaints, I occasionally will use an every-other-day regimen to decrease symptoms while maintaining IOP control.

In Level 4 cases, I include doxycycline in the regimen to improve lid hygiene and ensure good long-term results.

For all patients, nutrition and omega-3 fatty acid supplements that combine fish oil and flaxseed oil will help in the long term.8

When I instruct patients to resume glaucoma therapy, I have them continue exfoliation and nutritional supplements. In some cases, patients continue using cyclosporine long-term. In cases where inflammation or OSD may be present, I prescribe a prostaglandin analogue that's not preserved with BAK to help control the patient's IOP without causing increased discomfort and ocular surface irritation.

New Developments

Recently, several authors have evaluated the use of azithromycin (AzaSite, Inspire Pharmaceuticals) in patients with blepharitis. We've known for a long time that macrolides are inflammatory management drugs for a long time, but we haven't used them on the ocular surface because there was never a delivery vehicle that allowed the agent to be accurately dosed.

With DuraSite, patients can apply a single drop before bedtime and massage it into the lid each night for 4 weeks. Data show that the drug penetrates the skin at about 60 times the level of any other topical antibiotic, and it resides in the skin in much the same way azithromycin does — in every tissue — so we get a persistent effect.

The effect on patients with recalcitrant blepharitis can be remarkable, with many having significant improvement within several days to weeks. It ameliorates MMP-9 induced inflammation at about the same level as oral doxycycline, and the antibacterial capacity against gram-positive bacteria is very good.

This requires further study, but azithromycin may be another alternative to cyclosporine in helping us manage concurrent glaucoma and ocular surface disease in the future. OM

Dr. Thimons is medical director of Ophthalmic Consultants of Connecticut, clinical professor at the Pennsylvania College of Optometry and chairman of the National Glaucoma Society.

  1. Fechtner RD, Budenz DI, Godfrey DG, Obstbaum S, Stewart WC, Jasek MC. Prevalence of ocular surface disease symptoms in glaucoma patients on IOP-lowering medications. Paper presented at the meeting of the American Glaucoma Society, March 8, 2008, Washington, DC.
  2. Baudouin C, de Lunardo C. Short-term comparative study of topical 2% carteolol with and without benzalkonium chloride in healthy volunteers. Br J Ophthalmol. 1998;82:39–42.
  3. Baudouin C, Pisella PJ, Fillacier K et al. Ocular surface inflammatory changes induced by topical antiglaucoma drugs: human and animal studies. Ophthalmology. 1999;106:556–563.
  4. Epstein SP, Chen D, Asbell PA. Inflammatory response by ocular surface epithelia upon exposure to prostaglandin analogs. Poster presented at the annual meeting of the Association for Research in Vision and Ophthalmology, April 30, 2008.
  5. Peace JH, Henry JC, Stewart JA, et al. Ocular surface benefits of using travoprost BAK free compared to prior prostaglandin therapy. Poster presented at the annual meeting of the Association for Research in Vision and Ophthalmology, April 29, 2008, Fort Lauderdale, Fla.
  6. Behrens A, Doyle JJ, Stern L, et al. Dysfunctional tear syndrome: a Delphi approach to treatment recommendations. Cornea. 2006;25:900-907.
  7. Wilson SE, Perry HD. Long-term resolution of chronic dry eye symptoms and signs after topical cyclosporine treatment. Ophthalmology. 2007;114:76-79.
  8. Brown NA, Bron AJ, Harding JJ, Dewar HM. Nutrition supplements and the eye. Eye. 1998;12:127-133.
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