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Ophthalmology Management

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Glaucoma plus OSD equals double trouble

Corneal irritation, lid and orbital changes may be due to drops — but these patients often have distinct co-existing ocular surface disease as well.

By: Conni Koury, contributing editor
Ophthalmology Management March 1, 2021 Vol 25, Issue March 2021 Page(s): 40, 42, 44

Glaucoma specialists have their hands full. A recent review suggests that 11% of the 5 million Americans older than 50 who have ocular surface disease (OSD) also have glaucoma; and OSD is present in half of glaucoma patients on topical IOP-lowering therapy.1-7 Age is one of the main factors at work in this overlap as are the drops themselves, in particular those that contain the preservative benzalkonium chloride (BAK). This ingredient has been shown to cause cell damage on the ocular surface.8

Leung EW et al found that 59% of patients using eyedrops with BAK reported dry eye disease (DED) symptoms in at least one eye, and 27% of those patients reported severe symptoms.6 Schirmer testing determined that 61% of patients had a decrease in tear production in at least one eye, with 78% of patients showing abnormal tear breakup time.6

Preserving glaucoma patients’ sight is paramount, but maintaining a healthy ocular surface at the same time is critical to quality of life as well as medication adherence, which leads to better outcomes. Glaucoma and cornea specialists should collaborate in order to achieve the best balance.

SORTING IT OUT

When glaucoma patients have concomitant OSD, clinicians need to play detective and start by investigating if medications are the culprit. In a recent review, Osamah J. Saeedi, MD, and colleagues noted that all of the current glaucoma therapies — prostaglandin analogs, beta-adrenergic antagonists, alpha-adrenergic agonists and topical carbonic anhydrase inhibitors — can cause or worsen OSD either because of the medication itself or the added preservative.9 Dry eye risk increases along with the number of drops as well as the longevity of their use.

“The first potential issue with glaucoma drops is that of pure allergy,” says Dr. Saeedi. “Patients can be allergic to the active ingredient — brimonidine is the biggest offender — or the preservative — BAK is the most common. Typical presentation is red, irritated eyes and/or scaly eyelid skin. If the patient is on one drug it’s easy, but if they are on several, it’s trickier. At that point we would do a full drop holiday or eliminate them one at a time starting with the most likely offender.” Dr. Saeedi is associate professor of ophthalmology and visual sciences and director of the glaucoma division and director of clinical research at the University of Maryland School of Medicine, College Park.

Beeran Meghpara, MD, agrees that when a patient has concomitant OSD and glaucoma, the first step is to get them off preservative-containing medications. “It’s not always practical, however, as these preservative-free formulations may be cost-prohibitive for some patients.” These drugs also have to be refrigerated, adds Dr. Meghpara, codirector of refractive surgery, Wills Eye Hospital and clinical assistant professor of ophthalmology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia.

Also, each class of medication has products that use preservatives other than BAK, says Dr. Saeedi. For example, Travatan Z has SofZia in the United States and Polyquad in other countries (Alcon). Purite (Bio-Cide International Inc.) is found in Alphagan P (Allergan), and both products have fewer toxic effects on the ocular surface.10

Some advocate starting glaucoma patients on preservative-free formulations. Dr. Saeedi shares this preference, though he stresses that patients must be made aware of the additional cost associated with preservative-free options. He points out that products such as contact lens solutions and artificial tears also contain preservatives, “so patients may be getting them in other sources as well.”

PROSTAGLANDINS AND ARCHITECTURAL CHANGES

Another factor complicating medical treatment of glaucoma is prostaglandin-associated periorbitopathy (PAP). Fat cells shrink with exposure to prostaglandins, resulting in a constellation of effects that may include upper lid ptosis, upper lid retraction, redness and irritation, deepening and hollowing of the upper lid sulcus, involution of dermatochalasis, periorbital fat atrophy, mild enophthalmos, inferior scleral show and increased prominence of lid vessels. Additional well-known side effects are lengthening of lashes and increased pigmentation of the iris and periorbital skin.11-17

It is not just prostaglandins, however. “A variety of topical drops are a causative factor for lid changes,” says to Michael P. Rabinowitz, MD. “How to best treat these patients depends on the nature of the changes — what part is related to the medication, and which is a product of aging?” Dr. Rabinowitz is a member of the oculoplastics and orbital surgery department at the Wills Eye Hospital and instructor, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia.

He and some colleagues investigated this question by looking at patients who were using prostaglandin analogue drops in just one eye as the original studies on PAP were all bilateral disease.18

“Ptosis was one of the original signs of prostaglandin periorbitopathy,” Dr. Rabinowitz says. “But we found that early in the disease the treated eye was actually retracted. We surmised original studies of bilateral periorbitopathy revealed ptosis not from the drop, but from age. This is logical, as most glaucoma patients are older, the same population as age-related ptosis patients. But, as the periorbitopathy got severe, the muscle became weaker and then they would get ptosis at higher rates as compared to the normal aging population.”

Both patients with age-related ptosis as well as those with PAP and ptosis may have high lid creases and some lid hollowing. However, this is oftentimes more dramatic in the drop-related patients, as prostaglandins cause fat wasting, Dr. Rabinowitz notes. “While the lid crease might be high in both an age-related ptosis and a drop-related ptosis, in the drop-related ptosis there is often more redness, more hollowing and less fat.”

Dr. Rabinowitz does not rush to surgery for glaucoma patients with PAP. First, he would consider working with the glaucoma specialist to switch drops. “It might get better, although studies are not conclusive regarding if and when its course will reverse. It likely depends on the severity clinically and cell death on a molecular level. If it’s early in the course of their periorbitopathy, if they’re not terribly bothered by the droop and if it’s actively inflamed, I’d say, ‘Let’s switch your drops and see what happens.’”

On the other hand, if the glaucoma cannot be controlled in other ways and they are bothered by the structural change, he will proceed with surgery. “But I do let them know that even after we do surgery to raise the lids, they might continue to droop more in the future as they are still on the drop.”

AVOID OR REDUCE THE DROPS

Clinicians can consider avoiding drops altogether and go with a different strategy.

“Many of my colleagues, myself included, advocate for SLT (selective laser trabeculoplasty) first,” notes Dr. Saeedi. “I always present it as a good option at the start. The recently approved bimatoprost implant (Durysta, Allergan) may also be an option as it can reduce ocular surface symptoms associated with daily drops.”

Minimally invasive glaucoma surgeries (MIGS) are an excellent option to reduce or even eliminate medications for patients with severe ocular surface disease. “Often MIGS is done in conjunction with cataract surgery, and in those cases it is a slam-dunk decision,” says Dr. Saeedi. Some MIGS can be done as stand-alone procedures as well.

The paradigm is shifting toward earlier procedural intervention, and that will continue as more and increasingly effective MIGS devices are developed. “We have a lot of options at our fingertips for these people with severe ocular surface disease, but it still can present challenges,” he says.

Dr. Meghpara notes, “Any time we can reduce the drop burden it is certainly going to be helpful in these patients, but it is not always a practical option.” For some patients cost or efficacy limit the use of medications with alternative or no preservatives, and some need two, three or even four classes of medications to achieve their pressure goals.

When it is not possible to switch or eliminate drops and the other choices are off the table, then specialists turn to OSD management.

TREATING THE OSD

To optimize the ocular surface, Dr. Meghpara incorporates preservative-free tears, ointments at night and topical prescription anti-inflammatories (cyclosporine or lifitegrast). He notes that topical steroid use in glaucoma patients does require caution. “Although they are not out of the toolkit completely, we have to watch the patient closely,” he explains. “It is an individualized decision based on the severity of glaucoma and the health of the optic nerve. Newly approved Eysuvis (loteprednol etabonate ophthalmic suspension, Kala Pharmaceuticals), for example, is meant to be dosed for a few weeks as needed.”

Treating concurrent DED with an anti-inflammatory acknowledges that glaucoma drops cause an increase in inflammation on the surface of the eye. Dr. Saeedi prescribes cyclosporine (Restasis [Allergan], or Cequa [Sun Ophthalmics]) b.i.d. to mitigate that inflammation.

When glaucoma patients have mild OSD symptoms, the treatment is essentially the same as it would be in a nonglaucoma patient, starting with nonpreserved artificial tears and moving from there. “I’ll tell people to use the artificial tears 5 or 10 minutes before the glaucoma drops. This also helps decreases the sting,” he says.

Dr. Meghpara is an advocate of preservative-free tears for glaucoma patients. “They are an underrated treatment,” he says. “They can potentially dilute some of the toxicity from the drops as well as treat the ocular surface. I would say virtually all of these patients should be on preservative-free tears,” he says.

Prostaglandins and the rho kinase inhibitor Rhopressa (netarsudil, Aerie) may be associated with a bit more redness.9 “Some people like to use Lumify (brimonidine 0.025%, Bausch + Lomb), assuming no allergy, which is really nice because it’s one of the few safe options to reduce redness,” notes Dr. Saeedi.

Prostaglandins also appear to exacerbate meibomian gland disease, says Dr. Meghpara, who adds that he is aggressive when it comes to treating lid disease. “I start with lid scrubs but have a low threshold to escalate treatment with thermal pulsation, for example, if the patient has functioning glands. I will often put these patients on doxycycline to reduce eyelid inflammation.”

COOPERATION IS ESSENTIAL

“Ultimately, the glaucoma trumps DED; we have to preserve the patient’s vision first,” Dr. Meghpara emphasizes. “We have to sympathize with our glaucoma colleagues and not overstep our boundaries” when it comes to achieving the right balance between treating the two diseases. “I will talk through the situation with the glaucoma specialist, especially if I feel strongly that a patient could really benefit from a decreased drop regimen,” he notes. “The ocular surface is very important to the patient’s quality of life. But, in the end, the goal is to protect that optic nerve.” OM

REFERENCES

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