Article Date: 11/1/2008

Concurrent Treatment for Glaucoma And Ocular Surface Disease
CONTINUING EDUCATION

Concurrent Treatment for Glaucoma And Ocular Surface Disease

Addressing both conditions fosters corneal health, patient comfort and compliance with IOP-lowering therapy.

By Robert P. Wooldridge, OD, FAAO

This continuing education activity is the second in a series of case studies addressing ocular surface disease (OSD) in glaucoma patients. OSD is believed to be more prevalent in patients who have glaucoma than in the general population.1 This may be attributed to many factors, including age, use of systemic medications that have ocular drying effects, and changes to the ocular surface induced or exacerbated by certain preservatives in topical medications. Women, in particular, tend to have increased dryness due to hormonal changes associated with menopause.

The following case involves a 70-year-old woman who had significant dry eye symptoms and also required treatment for elevated IOP. The case highlights the importance of managing the two conditions concurrently and how to do it successfully.

The Patient

A 70-year-old Caucasian woman had a chief complaint of a "pulling sensation" in her eyes. She was being monitored for dry eye and was using artificial tears 2 to 4 times daily. Her medical history included arthritis and dyslipidemia, although she wasn't taking any systemic medications that contributed to her ocular discomfort.

A slit lamp examination showed relatively quiet eyes with no significant hyperemia. However, definite lissamine green staining was present OU. Both eyes showed mild punctate epithelial keratopathy consistent with keratitis sicca.

IOP measurements over the course of a few years had been borderline high, and recently had increased to 25 mmHg in the right eye and 17 mmHg in the left. Central corneal thickness measured 540 μm in the right eye and 536 μm in the left eye. Fundus examination showed healthy optic nerves in each eye despite the elevated pressure (Figures 1 and 2). Visual fields and optical coherence tomography (OCT) scans of the retinal nerve fiber layer (RNFL) were normal OU (Figures 3 and 4).

Figures 1 and 2. Throughout the course of treatment, fundus examinations showed healthy optic nerves in each eye despite elevated IOP.

Figures 3 and 4. Throughout the course of treatment, visual fields and the retinal nerve fiber layer remained normal OU.

Comfort Fosters Compliance

After reviewing the benefits and risks of treatment and no treatment, I decided to initiate topical therapy, beginning with the right eye, to prevent glaucomatous damage. The patient had blue irides and had expressed concern about hyperemia in the past; therefore, I didn't think she would tolerate hyperemia or a change in iris color. My goal was to prescribe the least offensive agent in this regard. Based on FDA labeling for the medications available at the time of this visit, I expected the alpha-2 adrenergic agonist, brimonidine tartrate (Alphagan P, Allergan Inc.), would be the best choice. I prescribed brimonidine b.i.d. for the right eye. I also prescribed topical cyclosporine (Restasis, Allergan Inc.) in an attempt to decrease the patient's dry eye complaints and increase the likelihood of compliance with the glaucoma drops.

When managing patients with glaucoma, lowering IOP is the obvious goal. However, therapy won't be effective if it's not used. Patients with glaucoma fail to comply with therapy recommendations for many reasons, including side effects.2 This makes keeping patients' eyes comfortable an equally desirable goal. I want to avoid prescribing drops and learning later that the patient stopped using them because of irritated and/or red eyes. A healthy ocular surface is a comfortable ocular surface, so staying alert to signs and symptoms of OSD and managing them concurrently with the glaucoma is very important.

Stay Alert to OSD Signs, Symptoms

Clinicians should ask patients at each visit about their comfort level and if they're having any problems with their glaucoma medications. Doctors should conduct an examination with an awareness of the clinical signs of OSD (Figure 5).

Figure 5. Ocular surface disease is common among glaucoma patients.

Because of the complex constellation of disease triggers and variable manifestations at different stages of OSD, clinicians can use multiple tests to diagnose an individual patient. Schirmer testing measures tear production, but it's not a reliable indicator of the severity of OSD. Tear film break-up time (TBUT) is a functional measure of tear stability. If stability is disturbed (as in lipid or mucin deficiency), TBUT can be reduced.

Fluorescein and other dyes, such as rose bengal and lissamine green3,4 are helpful for assessing the health of the ocular surface at the cellular level. Lissamine green is used to evaluate abnormal epithelial cells and ocular surface changes associated with insufficient tear-film protection. It stains cells that are devitalized or have lost their normal mucin surface. Rose bengal and lissamine green are both efficacious, although rose bengal tends to sting more and causes more staining of the lids. Adequate diagnostic testing needs to be part of detecting and monitoring OSD, because signs and symptoms often don't correlate. Staining patterns vary greatly; eyes may stain despite a lack of hyperemia or significant complaints of discomfort. Some patients with OSD exhibit staining only with fluorescein, others with lissamine green alone, while others stain with both. Lissamine green tends to stain the conjunctiva more than the cornea, though this too can vary.

In addition to the diagnostic tests mentioned above, clinicians should examine the eyelids and eyelashes for signs of anterior and posterior blepharitis. Both conditions can cause or contribute to OSD. A range of factors, including environmental triggers and coexisting conditions, such as ocular allergy, can impact each case. Acne rosacea is another condition that can affect ocular adnexa and contribute to blepharitis and dry eye.

Medications That May Contribute to Dry Eye and Ocular Surface Disease
Systemic
Antihypertensives
Antiandrogens
Anticholinergics
Antidepressants
Cardiac antiarrhythmic drugs
Parkinson's disease agents
Antihistamines

Topical
Preservatives in artificial tears and other drops

As in the case described here, patients often have somewhat vague symptoms of ocular discomfort. Asking the patients to more thoroughly describe their irritation may be helpful. Red, watery and itchy eyes that worsen in the spring and summer and are accompanied by nasal symptoms tend to be indicative of allergy. Ocular symptoms, such as dryness, and a sandy, scratchy or burning sensation that worsen in the winter tend to be indicative of dry eye.

All factors that can contribute to the status of the ocular surface should be considered, discussed with the patient and managed. While prevention of vision loss is of paramount importance, controlling OSD before initiating topical glaucoma therapy is ideal when safe to do so. This is reasonable when the OSD is severe and the patient isn't at risk for glaucoma progression in the short term.

How Patients Describe Symptoms Of Ocular Surface Disease
Patients may describe the symptoms of ocular surface disease (OSD) in a variety of ways. Clinicians must recognize the various descriptions as potential symptoms of OSD.

■ Dryness
■ Burning
■ Sandy, gritty sensation
■ Excessive tearing
■ Intermittent blurred vision
■ General ocular discomfort
■ Mild redness

Also note that OSD often is mild to moderate, but can be chronic and vary in severity. It may worsen late in the day or with contact lens wear.

Many treatments are available and should be employed starting with the least burdensome. Depending on the nature of the OSD, preservative-free artificial tears, topical cyclosporine, punctal plugs, doxycycline, lid scrubs or a short course of the esterbased topical steroid loteprednol etabonate 0.5% (Lotemax, Bausch & Lomb) can be effective.5 Use of a humidifier and oral supplements, such as flaxseed and fish oil and vitamin E, also may be helpful.

Balancing Act

The brimonidine I prescribed in this case didn't lower the patient's IOP. By the follow-up visit, her pressures had increased to 28 mmHg in the right eye, while being treated, and 23 mmHg in the left eye on no treatment. The RNFL and visual fields were still normal in both eyes. The patient had continued to use the topical cyclosporine bid. She reported using artificial tears four or more times a day but that her eyes felt drier than ever. At this point, we discontinued brimonidine and prescribed latanoprost (Xalatan, Pfizer Inc.) for the right eye as a monocular trial.

The latanoprost didn't lower the patient's IOP sufficiently. Therefore, rather than adding an additional topical medication, I decided to switch the patient to another prostaglandin analogue, travoprost 0.004% (Travatan, Alcon Laboratories Inc.). At this point, I also decided to initiate treatment in her left eye.

After some time had passed, the patient continued to use non-preserved artificial tears approximately five times a day, travoprost OU and topical cyclosporine, but she continued to suffer with dry, irritated eyes. Lissamine green staining was still evident.

When we talked about her therapies and discomfort, she said she'd been washing her eyes with tap water 8 to 10 times every day in an attempt to make them feel more comfortable. She was advised not to do this, and we discussed a new IOP-lowering option: travoprost with sofZia, (Travatan Z, Alcon Laboratories Inc.), which the FDA recently had approved.

Assessments Currently Used to Diagnose Ocular Surface Disease
■ Aqueous tear production
- Schirmer strip testing
■ Tear stability
- Tear film break-up time
■ Ocular surface
- Clinical examination
- Dye staining
■ Patient reports of severity and impact of symptoms.

Advanced Therapeutic Options

The new formulation doesn't contain the detergent-type preservative benzalkonium chloride (BAK) found in the original formulation and in most other glaucoma drops. Instead, it contains an ionic-buffered preservative system developed to be gentler than BAK on the ocular surface. Ample evidence exists in the literature that BAK has detrimental effects on the ocular surface. The evidence includes in vitro studies,6–8 rabbit eye models9,10 and clinical trials in humans.11,12

Adverse effects can be short- or long-term and include a decrease in TBUT, decrease in epithelial cell integrity, loss of goblet cells and an increase in conjunctival inflammatory cells. All of these changes are steps on a final common pathway that leads to OSD. Furthermore, positive effects on the ocular surface have been shown when there's a decrease in exposure to BAK.13,14 Peace et al showed that clinically and statistically significant reductions in OSD signs and symptoms may occur when BAK is eliminated or reduced.13

Since the efficacy of BAK-free travoprost has been proven to be equivalent to the original formulation in a randomized clinical trial,15 and because it potentially could be less toxic to the ocular surface, Travatan Z was substituted for Travatan.

At her last visit, although lissamine green staining was still present in both eyes, the patient said she was far more comfortable. Her IOPs had decreased to 15 mmHg in the left eye and 18 mmHg in the right eye. Visual fields and RNFL scans remained normal. I advised the patient to continue using Travatan Z as prescribed, as well as topical cyclosporine b.i.d. and non-preserved artificial tears as needed.

Bottom Line

We do our patients a disservice if we try to preserve their quality of life by lowering their IOPs and preventing the progression of glaucoma, only to make their eyes uncomfortable.

Serving our glaucoma patients best means preventing OSD when we can, staying alert to its signs and symptoms and managing it aggressively if it develops. The tools and techniques at our disposal today make this more possible than ever before. OM


Dr. Wooldridge is director of Eye Foundation of Utah, an optometric comanagement center in Salt Lake City. He's the education director/past president of the Mountain West Council of Optometrists and an adjunct clinical professor at several schools and colleges of optometry. Dr. Wooldridge is also a founding member of the Optometric Glaucoma Society.

References
  1. Fechtner RD, Budenz DL, Godfrey DG, Obstbaum S, Stewart WC, Jasek MC. Prevalence of ocular surface disease symptoms in glaucoma patients on IOP-lowering medications. Poster presented at the annual meeting of the American Glaucoma Society, March 8, 2008, Washington, DC.
  2. Tsai JC, McClure CA, Ramos SE, Schlundt DG, Pichert JW. Compliance barriers in glaucoma: a systematic classification. J Glaucoma. 2003;12:393–398.
  3. Sutphin JE. 2006-2007 External disease and cornea. Basic and clinical science course section 8. American Academy of Ophthalmology:20–22.
  4. Allen LV. Lissamine green 0.5% ophthalmic solution. Intl J Pharmaceutical Compounding. 1998;2:233.
  5. 2007 Report of the International Dry Eye WorkShop (DEWS). Ocul Surf. 2007;5:65–204.
  6. Baudouin C, Riancho L, Warnet J-M, Brignole F. In vitro studies of antiglaucomatous prostaglandin analogues: travoprost with and without benzalkonium chloride and preserved latanoprost. Invest Ophthalmol Vis Sci. 2007;48:4123–4128.
  7. Yee RW, Norcom EG, Zhao XC. Comparison of the relative toxicity of travoprost 0.004% without benzalkonium chloride and latanoprost 0.005% in an immortalized human cornea epithelial cell culture system. Adv Ther. 2006;23:511–518.
  8. Whitson JT, Cavanagh HD, Lakshman N, Petroll WM. Assessment of corneal epithelial integrity after acute exposure to ocular hypotensive agents preserved with and without benzalkonium chloride. Adv Ther. 2006;23:663–671.
  9. Kahook MY, Noecker RJ. Comparison of corneal and conjunctival changes after dosing of travoprost preserved with sofzia, latanoprost with 0.02% benzalkonium chloride, and preservative-free artificial tears. Cornea. 2008;27:339–343.
  10. Kahook MY, Noecker RJ. Quantitative analysis of conjunctival goblet cells after chronic application of topical drops. Adv Ther. 2008;25:743–751.
  11. 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.
  12. 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.
  13. Peace JH, Henry JC, Stewart JA, Stewart WC, Jasek MC. 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.
  14. Horsley MB, Kahook MY. Changes in tear break-up time and ocular surface disease index after initiation of travoprost with sofzia in patients previously using latanoprost with benzalkonium chloride. Poster presented at the Annual Meeting of the American Glaucoma Society, March 8, 2008, Washington, DC.
  15. Lewis RA, Katz GJ, Weiss MJ, et al. Travoprost 0.004% with and without benzalkonium chloride: a comparison of safety and efficacy. J Glaucoma. 2007;16:98–103.


Optometric Management, Issue: November 2008