Targeting dry eye in glaucoma patients

August 25, 2017

A poor ocular surface is a common condition in glaucoma patients due to the incidence of dry eye, age, and use of benzalkonium chloride (BAK). Poor compliance with glaucoma therapy can result. Use of point-of-care testing can help identify patients with a poor ocular surface and drive treatment decisions. Treatment options, including surgical, are discussed.


Due to the nature of the medications optometrists use and the typical age of glaucoma patients, these patients have the potential to become dry eye patients. Given that the data regarding the incidence of dry eye in the overall population is estimated to be 25 percent,1 it is not surprising that our glaucoma patients show rates of ocular surface dysfunction that may surpass the general population.

Age is a factor because most patients with glaucoma are age 60 or older and have lower baseline tear quality. Commonly, elderly patients can have meibomian gland dysfunction (MGD), which results in evaporative loss and dry eye discomfort.

Add a glaucoma drug to this environment, and the insufficient buffer of tears will leave the ocular surface stinging, red, and potentially damaged.

Related: How ODs can do better with dry eye

Even if patients are younger and exhibit no pre-existing ocular surface problems, in my experience long-term glaucoma therapy is likely to cause dry eye symptoms eventually, due in large part due to the cumulative toxicity of BAK preservative and the primary molecule on the ocular surface.

This is especially common with chronic prostaglandin analog use. Even low levels of BAK can cause patients to develop irritation, foreign body sensation, and other common symptoms of dry eye.

I attempt to continually balance the imperative to reduce intraocular pressure (IOP) in glaucoma patients with the need to keep the ocular surface healthy and comfortable in the presence of chronic disease therapy. Quality of life is important.

Equally pressing is the role of comfort in compliance with glaucoma medication. Patients will not put stinging eyedrops into red, irritated eyes, so dry eye disease becomes an impediment to controlling glaucoma and its potential for damage and vision loss. Before and during glaucoma treatment, proactive, accurate diagnosis of dry eye disease is essential.

Point-of-care testing

In my practice, when we identify symptomatic patients on the check-in questionnaire, we perform a sidebar series of tests directed at identifying ocular surface concerns. Our selection of point-of-care diagnostic systems includes only technologies that have been proven by trials published in the peer-reviewed literature. Tests tell us different things about the ocular surface and are used in a complementary way.

Related: How patients perceive their glaucoma matters

Two key tests, tear osmolarity and MMP-9, are used to identify ocular surface dysfunction with baseline results and trend lines based on multiple measurements over time.

 

Tear osmolarity measures the relative saltiness of tears. I place importance on osmolarity testing because it has the highest predictive value of any diagnostic technique for dry eye at 87 perdent.2

Our osmolarity device is the TearLab Osmolarity System (TearLab). A recent randomized, masked, in vitro study showed that the TearLab system has the highest level of accuracy available in a device for individualized use, with a correlation with known solutions of r2=0.96 (coefficients of variation were 1.2 percent , 2.3 percent, and 1.4 percent, respectively, for solutions simulating normal eyes, moderately dry eyes, and severe dry eyes).3

In comparison, the Wescor 55110 Vapro Pressure Osmometer, the FDA gold standard for laboratory osmometers, demonstrated a correlation of r2=0.98, while the i-Med Pharma i-Pen (not available in the U.S.) had a correlation of r2=0.03.3

Related: How to use tear osmolarity to help treat dry eye disease

Strength of correlation with anticipated results is an important indicator of a device’s ability to measure accurately and precisely (see Table 1).

Table 1: Strength of correlation

0.90 to 1.00Very high correlation
0.70 to 0.89High correlation
0.50 to 0.69Moderate correlation
0.30 to 0.49Low correlation
0.00 to 0.29Little if any correlation

Source: Westgard QC; available at https://buff.ly/2vwc1kw

If my patient’s result is ≥308 mOsm/L or there is an intereye difference ≥8 mOsm/L, then I know aqueous tears are deficient, indicating dry eye disease. Even mild cases are accurate with osmolarity testing.

Because dry eye is an inflammatory disease, direct chemical analysis for the inflammatory marker enzyme matrix metallopeptidase 9 (MMP-9) is informative. In my practice, we use InflammaDry (Quidel), its positive results (MMP-9 levels ≥ 40ng/ml) have statistically significant correlation to dry eye disease,4 even in asymptomatic patients.5

When MMP-9 is elevated, indicating an active inflammatory process, I know that ocular surface disease is the likely cause, particularly when this result occurs alongside abnormal osmolarity testing. I can also discern that the inflammation is having a daily effect on the patient’s compliance with glaucoma therapy.

In addition to tear osmolarity and MMP-9 testing, I perform supervital dye assessment with lissamine green to visualize damage to the ocular surface and test tear break-up time (TBUT).

Examining the posterior meibomian glands is initially accomplished at the microscope with direct pressure and grading of the oils status. Once MGD is established, I use LipiView meibography (TearScience) to see the extent of the blocked or atrophied glands.

It is important for clinicians to remember to avoid manipulation of the lids, instillation of topical agents, or the use of increased illumination before point-of-care testing to avoid adulterating the outcomes.

Pre-existing dry eye

If a patient has dry eye disease before glaucoma treatment, I know that noncompliance with glaucoma medication is a distinct possibility unless I begin dry eye treatment concurrently. If the patient has severe dry eye, I may consider surgical options earlier, but generally I begin with a non-preserved prostaglandin (frequently tafluprost 0.0015% [Zioptan, Akorn]) and dry eye treatment.

Related: Managing glaucoma in women

Prescription medications are limited in part by glaucoma. Because steroids such as loteprednol (Lotemax, Alrex, Bausch + Lomb) and standard ketone steroids like difluprednate (Durezol, Novartis) are capable of raising IOP or blocking IOP reduction, they are generally avoided or used in limited duration for patients with glaucoma.

Cyclosporine (Restasis, Allergan) produces gratifying results over time. Because this medication is not inexpensive, affordability is a factor for patients, but those who are comfortable with the cost typically comply very readily. In my experience, it takes about eight to 12 weeks to see results.

 

With the release of  lifitegrast (Xiidra, Shire), I have initiated therapy in a significant number of patients and have experienced results consistent with the clinical trials, with patients showing symptomatic improvement in as little as two weeks.6

I recommend my glaucoma patients with dry eye use 2,500 mg per day of a re-esterified triglyceride omega 3 supplement (PRN), which promotes natural anti-inflammatory processes and produces significant improvement over time. A good omega 3 supplement enables the meibomian glands to develop thinner, healthier oils that reduce evaporation on the ocular surface.

Related: Combating dry eye with punctal plugs

 In a double-masked, placebo-controlled study of a re-esterified triglyceride omega 3 vs. an ethyl esters product, the former had a remarkable impact on symptoms, tear osmolarity, MMP-9, and TBUT.7 Additionally, the re-esterified omega 3 demonstrated significant increases in serum levels in the 12 weeks of the trial while the ethyl-ester version showed no increases from baseline serum levels. The impact of omega 3 supplementation is typically 8 to 12 weeks after onset of treatment.

Finally, I am very much in favor of proscriptive therapy for artificial tears. I give patients a sample of Systane Balance (Alcon), Blink (Abbott), or Soothe XP (Bausch + Lomb), which are long-acting on the corneal surface and compatible with good visual activity. Making sure patients understand that not all products are the same, I endorse these specific agents, giving my patients confidence to navigate the overwhelming eyecare aisle and select the doctor-recommended product differentiates itself clinically from the rest.

Medication effects

In most cases, primary therapy for glaucoma is a prostaglandin once daily. Uncomfortable patients inevitably skip doses or stop using their drops, raising the average IOP and causing damage over time. Standard dry eye treatments are helpful for these patients, but I also adjust therapy to change, reduce or, if possible, stop medication.

Related: How oral and dental hygiene plays a role in glaucoma

Depending on the patient’s specific situation, we can change to a BAK-free drug or one with less BAK. Although BAK may not be the only source of toxicity in glaucoma medications, it has been clear in my experience that medications with lower levels of BAK or no BAK have less impact on the ocular surface.

However, long-term, it may be appropriate to switch glaucoma patients with dry eye to preservative-free medications such as dorzolamide-timolol 2%/0.5% (Cosopt PF, Akorn), tafluprost 0.0015%, or timolol maleate 0.25% or 0.5% (Timoptic, multiple manufacturers) to calm the ocular surface. While these medications are effective, they can be expensive when not covered by prescription plans, and storage can be a concern due to the lack of preservative.

 

Surgical options

In addition to changing medications, we also can reduce or sometimes eliminate ocular surface disease signs and symptoms with surgery. Once patients have struggled with topical therapy and had the opportunity to demonstrate that there are detrimental side effects, selective laser trabeculoplasty (SLT) is a logical step. SLT’s only significant drawback is the fact that it does not have a permanent effect and may need to be re-applied in the future. But for patients who have ocular surface problems from drops, the time without therapy can be a welcome change.

The growing number of micro-invasive glaucoma surgery (MIGS) options presents new opportunities for glaucoma patients with dry eye. Because MIGS procedures are relatively less invasive than trabeculectomy, their efficacy in reducing pressure has lower long-term complications. This is a new opportunity that has changed the decision-making process for treatment.

iStent (Glaukos) is an FDA-approved IOP-lowering MIGS device that is implanted during cataract surgery. Typically, iStent is utilized for patients on single-medication therapy. Along with cataract surgery, it has been shown to eliminate medical treatment in approximately 80 percent of patients at the two-year assessment. 

Related: New products, advancements in dry eye

When a patient needs or is close to needing cataract surgery, we frequently plan to use cataract surgery as an opportunity to lower pressure with a MIGS device such as iStent or CyPass (Alcon) and eliminate drops, reduce their use, or switch to a less potent, more tolerable medication after surgery that was not adequate before surgery. My patients have had good results with the Xen Gel Stent (Allergan), which has outcomes similar to but not as profound as trabeculectomy with a much less invasive procedure.

Dry eye and glaucoma

To treat glaucoma effectively, we have to diagnose dry eye early and address the problem through conventional dry eye treatment and IOP control that spares the ocular surface. If I see a tear osmolarity of 310 mOsm/L in the left eye and 325 mOsm/L in the right along with positive MMP-9 testing, a TBUT of <7 seconds, staining and blocked meibomian glands, I know my patient needs a comprehensive approach and close monitoring.

If another patient’s tear osmolarity is a much milder 295 mOsm/L left and 310 mOsm/L right, with a negative MMP-9 test, a TBUT of 10 seconds, no staining, and no visible meibomian gland problems, dry eye treatment with medication, omega 3s and artificial tears is still required because chronic use of topical glaucoma medication will likely cause dry eye discomfort and noncompliance. By treating both problems, we can ensure that the patient is comfortable and the glaucoma is controlled.

About the author

J. James Thimons, OD, FAAO, ABO, is ophthalmic medical director at Ophthalmic Consultants of Connecticut.
Dr. Thimons is adjunct clinical professor at the Pennsylvania College of Optometry at Salus University. He serves as a consultant for TearLab.
jimthimons@gmail.com

 

References:

1. O'Brien PD, Collum LM. Dry eye: diagnosis and current treatment strategies. Curr Allergy Asthma Rep. 2004 Jul;4(4):314-9.

2. Jacobi C, Jacobi A, Kruse FE, Cursiefen C. Tear film osmolarity measurements in dry eye disease using electrical impedance technology. Cornea. 2011 Dec;30(12):1289-92.

3. Rocha G, Gulliver E, Borovik A, Chan CC. Randomized, masked, in vitro comparison of three commercially available tear film osmometers. Clin Ophthalmol. Jan 27;11:243-248

4. Messmer EM, von Lindenfels V, Garbe A, Kampik A. Matrix Metalloproteinase 9 Testing in Dry Eye Disease Using a Commercially Available Point-of-Care Immunoassay. Ophthalmology. 2016 Nov;123(11):2300-2308

5. Lanza NL, McClellan AL, Batawi H, Felix ER, Sarantopoulos KD, Levitt RC, Galor A. Dry Eye Profiles in Patients with a Positive Elevated Surface Matrix Metalloproteinase 9 Point-of-Care Test Versus Negative Patients. Ocul Surf. 2016 Apr;14(2):216-23.

6. Semba CP, Gadek TR. Development of lifitegrast: a novel T-cell inhibitor for the treatment of dry eye disease. Clin Ophthalmol. 2016 Jun;10:1083-1094.

7. Epitropoulos AT, Donnenfeld ED, Shah ZA, Holland EJ, Gross M, Faulkner WJ, Matossian C, Lane SS, Toyos M, Bucci FA Jr, Perry HD. Effect of Oral Re-esterified Omega-3 Nutritional Supplementation on Dry Eyes. Cornea. 2016 Sep;35(9):1185-1191.