Ocular surface disease and glaucoma may occur together and can be a real problem for patients. In these patients, it’s important to carefully choose medications and a surgical plan.
Source: Robert Fechtner, MD
Experts discuss how ocular surface disease may be a factor when choosing a treatment plan in glaucoma patients
Treating the ocular surface is extremely important, but for those patients with both ocular surface problems and glaucoma, it becomes even more important to consider how the ocular surface may be impacted by glaucoma medications and surgery. Dana Wallace, MD, Thomas Eye Group, Sandy Springs, Georgia; Heather Weissman, MD, Atlanta Ophthalmology Associates, Atlanta; Jeffrey Kammer, MD, Vanderbilt Eye Institute, Nashville, Tennessee; and Tony Realini, MD, associate professor of ophthalmology, West Virginia University, Morgantown, West Virginia, discussed approaches to glaucoma management in patients with ocular surface disease (OSD).
First, Dr. Kammer said, physicians must acknowledge that ocular surface disease is a real problem in glaucoma patients. “In the United States, it is estimated that roughly 15% of all individuals over the age of 65 have some form of OSD,” he said. It’s also important to be aware of the population. “Many of our glaucoma patients are elderly, so they are at a higher risk of dry eyes to begin with, secondary to decreased age-related tear secretion, a decrease in goblet cells, and a dropout of the meibomian glands,” he said. “Glaucoma is another disease that becomes more common with advanced age, so it is not surprising that there is a high comorbidity rate between these two processes.”
When patients suffer from OSD, any medication that they place in their eye can cause discomfort, Dr. Kammer said. The patients also have the most difficulty tolerating drops that contain preservatives, particularly benzalkonium chloride (BAK), which is a quaternary ammonium compound whose antimicrobial activity stems from its ability to disrupt cell membranes, thereby potentiating the cell death process, he said. “Multiple studies have reported on the deleterious effects that BAK has on conjunctival epithelium, corneal epithelium and the corneal stroma,” Dr. Kammer said. “It can also elicit a significant pro-inflammatory response on the ocular surface, which can further exacerbate the health of the ocular surface.”
The more BAK that you use, the more ocular surface toxicity will develop, he said. This is seen in many glaucoma patients who use multiple glaucoma drops that contain BAK. “Fortunately, studies have found that reducing the BAK load can have a beneficial effect on the health of the ocular surface and tolerance of topical glaucoma medications,” he said.
Preservative-free eye drops are the best tolerated, Dr. Wallace said, although even these are not free of side effects for people with ocular surface disease.
The majority of the time, all glaucoma medications cause a form of dry eye, Dr. Weissman said, especially if you add multiple medications. She added that brimonidine seems to have more of a reaction than other medications.
Dr. Weissman agreed that preservative-free glaucoma medications are better tolerated. However, they’re more difficult for patients because they usually need to be refrigerated and often come in vials that can be hard to open for some.
Many therapeutic choices made are contributory to patients’ symptoms, Dr. Realini said, and almost any drop has something in it that can be irritating. Many drops are irritating that have nothing to do with preservatives, he added. For example, dorzolamide is only soluble at a pH of 5.6, Dr. Realini said, which is like lemon juice, so it will sting when you put it into the eye.
Glaucoma management in patients with OSD
Dr. Wallace recommends laser trabeculoplasty at an early stage to all patients with OSD. “With the rise of microinvasive glaucoma surgeries, we have more surgical options for patients with mild to moderate glaucoma that I may offer to patients who are poorly tolerating drops and who are appropriate candidates,” she said.
Eliminating or decreasing the drop burden on patients with OSD is critical, she said. “I always start with selective laser trabeculoplasty (SLT) but also consider glaucoma surgeries (particularly MIGS), as the addition of further drops usually exacerbates the OSD problem,” Dr. Wallace added.
“In general, I think glaucoma specialists aren’t as attentive to ocular surface effects that the drugs we use everyday have,” Dr. Realini said. “We prescribe them based on efficacy and safety, as well as cost and convenience.”
Dr. Realini added that it can be hard to factor ocular surface issues into the treatment process, as sometimes patients don’t complain about their symptoms. That doesn’t mean that it’s not relevant even if it’s invisible to the doctor, he said. But it’s important to realize that if the drops are making the eyes feel bad, patients may stop taking them.
Dr. Realini thinks SLT is a good option, particularly for primary open angle glaucoma (POAG). The efficacy is comparable to prostaglandins on average, he said, and it eliminates the need for daily compliance and chronic tolerability issues. SLT has cost effectiveness comparable to prostaglandins and can be done once a year or less for most people.
“I am surprised that SLT has not become the first line therapy for POAG in most patients,” he said. “It has significant advantages over drops with no significant disadvantages.”
Although some physicians may argue that it wears off, he said prostaglandins wear off every day. Some may argue that it’s expensive, but it’s expensive up front and not compared to the month-to-month cost of years of drop therapy. There may also be those who say that not everyone gets a great response, but he noted that the close to 85% response is consistent with what one would see with a prostaglandin.
Dr. Realini has modified his SLT technique to minimize ocular surface complications. He uses a low concentration hydroxyethylcellulose gel, a nighttime artificial tear gel, rather than higher concentration coupling agents to keep the lens on the eye. This helps it move more freely and come off more freely, with less chance of epithelial injury during lens removal and afterward.
When removing the lens, Dr. Realini likes to use his finger on the lower lid to break suction between the cornea and lens rather than pulling it off the eye to minimize traction and trauma on the epithelium.
Surgery is always less successful when performed on an inflamed eye, he said. In these cases, you could wait a short time. The pressure will go up, but if glaucoma is not advanced, this could be well tolerated.
Dr. Realini said to consider bleb-less procedures, like one of the MIGS procedures, so you’re not reliant on healthy conjunctiva for the success of the glaucoma procedure. The MIGS procedures don’t have any significant effect on the ocular surface, he said, and there is little additional trauma associated with them.
Dr. Kammer said his goal for patients with concomitant glaucoma and ocular surface disease is twofold: (1) optimize the ocular surface and (2) minimize the exposure to BAK.
“The first thing we can do for our patients is to recognize the signs of OSD and acknowledge that there is a problem,” he said. “Diagnosing ocular surface disease is easier than it has ever been.”
Besides the traditional use of lissamine green/rose bengal staining, Schirmer’s test and evaluating tear break-up time, there are objective tests, like tear osmolarity analysis and matrix metalloproteinase-9 analysis, to help confirm the diagnosis. “At that point, we have to treat the patient aggressively, particularly by addressing the aqueous deficiency and meibomian gland dysfunction,” he said. Preservative-free artificial tears and lid hygiene play a fundamental role in restoring the integrity of the ocular surface.
Dr. Kammer also likes to incorporate immunomodulatory agents. “Patients with meibomian gland dysfunction benefit significantly by including oral omega-3 fatty acid supplements in their diet,” he said. It is also important to consider incorporating newer treatment modalities into the treatment regimen. There are several dry eye devices that are commercially available that can improve the ocular surface, and these should be seriously considered, he added.
Punctal plugs and topical steroids may be considered more controversial in patients with both OSD and glaucoma. “While steroids can be beneficial, they have the chance of increasing IOP, which is counterproductive for glaucoma patients,” he said. “If they need to be used, I would only recommend using loteprednol BID for a week or two, as a bridge to one of the immunomodulatory agents.” Meanwhile, punctal plugs help maintain lubrication, but they also keep any preservative around longer and can potentiate the negative effects of the BAK on the ocular surface, Dr. Kammer said.
The second goal in patients with both OSD and glaucoma is to reduce exposure to preservatives, and there are several strategies to do this.
First, Dr. Kammer said to reduce the total number of drops. “This can be achieved by preferentially prescribing glaucoma drops that can be dosed once daily, like beta blockers and prostaglandin analogues,” he said. The use of fixed-combination preparations can also be increased. “There is strong clinical data that suggests that fixed combination glaucoma drops have a better safety profile and tolerability compared to when the medications are used separately,” he said.
Dr. Kammer stressed the need for early use SLT, which can produce a drop in IOP that is comparable to pharmacologic treatment while avoiding the preservative-induced toxicity to the ocular surface.
“I also consider using oral carbonic anhydrase inhibitors (CAIs) in selected individuals,” he said. “This is a bit controversial because oral CAIs have been documented to occasionally exacerbate dry eyes, particularly in elderly patients, whose body water content is lower compared to younger individuals.” However, for younger patients, those with significant sensitivity or intolerance to preservatives, and those who don’t have the dexterity to instill eye drops, this is a reasonable option, he said. “In many individuals, the benefits of a reduced BAK load outweigh the mild dehydration caused by the oral CAI.”
Another option, Dr. Kammer said, is to use eye drops that are either preservative-free or utilize non-BAK preservatives. From a clinical perspective, the glaucoma medications that use less toxic preservatives are well tolerated and often result in an improvement in symptomatology, particularly if these patients have pre-existing ocular surface issues, he said.
Another way to minimize the BAK burden is to use a preservative-free formulation. “Due to the significant risk for contamination in multidose bottles, the only practical way to accomplish this is with the use of single-dose units,” Dr. Kammer said. “While the lack of any irritating preservative is a boon for patients, this option tends to be much more expensive, and some patients (particularly the elderly) have difficulty handling the small vials.”
Many patients will be fine with preserved glaucoma medications. But a certain segment of the population benefits particularly from minimizing BAK exposure including those with a pre-existing dry eye or ocular surface disease; a documented intolerance to preservatives; an existing multidrug treatment regimen; and treatment that is expected to last many years.
Tests to perform
Dr. Weissman said many of the tests used for dry eye disease are important for these patients as well, including tear break-up time, Schirmer’s test, topography looking at the corneal surface, and tear osmolarity.
“The most important thing is adding one drop at a time,” she said. If the patient has a very high pressure, you may have to add more than one. By adding one at a time, you can see what the corneal surface does, Dr. Weissman said. If there is more dryness after one, switch to preservative-free, she suggested. It’s also important to make sure the patient is lubricating the eyes frequently with preservative-free artificial tears.
Topography is important to have readily available to look for distortion on the corneal surface, Dr. Weissman said. Staining is also helpful to see if there’s keratopathy on the exam that can show how dry the eyes are.
Dr. Weissman added that serum tears are a useful option. With these, the patient’s blood is drawn, spun down, and teardrops are formulated from the blood. They have an anti-inflammatory effect and can be helpful in patients with both glaucoma and severe dry eye, she said.
Impact of OSD on astigmatism measurements
There may be a concern that ocular surface problems can make astigmatism measurements less accurate in glaucoma patients. Dr. Wallace said that in order to get the best visual outcomes after cataract surgery, she brings the patient back in for IOL calculations on a separate preop visit where measurements are performed before any drops are placed in the eye. “We also may start a prescription medicine to treat the dry eye about a month before surgery,” she said.
Dr. Weissman uses topography to help account for these potentially inaccurate measurements, as it helps her to evaluate the patient better.
Editors’ note: Dr. Kammer has financial interests with Allergan (Dublin, Ireland). Dr. Realini has financial interests with Allergan, Bausch + Lomb (Bridgewater, New Jersey), and Alcon (Fort Worth, Texas). Dr. Wallace has financial interests with Allergan. Dr. Weissman has no financial interests related to her comments.