November 2018


Improving the ocular surface for cataract and refractive surgeons
Managing ocular surface issues caused by vision-preserving glaucoma drops

by Liz Hillman EyeWorld Senior Staff Writer

Toxic ocular surface disease brought on by glaucoma medication
Source: Marjan Farid, MD


Drops that help protect the optic nerve can be toxic to the ocular surface; experts discuss how to handle this situation

Friends don’t let friends be on four glaucoma medications,” said Steve Sarkisian, MD, glaucoma fellowship director, Dean McGee Eye Institute, and clinical professor, University of Oklahoma College of Medicine, Oklahoma City. Part of this, he continued, is because compliance is “abysmal” for patients on complicated pharmaceutical regimens and also because “the daily assault on the ocular surface by these medications will definitely catch up to you and the patient.”
Patients who have this level of topical poly-pharmacy have what Dr. Sarkisian calls “the look.” Their eyes are bloodshot, the lids are crusty, and there is the vacuous stare caused by atrophy of the periorbital fat pads.
“It’s not just the cornea, it’s the whole ocular surface, it’s the conjunctival, it’s the sclera, it’s the eye lids,” Dr. Sarkisian said.
Dry eye and ocular surface disease is multifactorial, said Marjan Farid, MD, associate clinical professor, Department of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, but there is a strong correlation with the number of glaucoma drops and years of exposure. All glaucoma drops, said Ali Djalilian, MD, professor of ophthalmology, University of Illinois College of Medicine, Chicago, will have some effect on the ocular surface; whether it’s significant enough for the patient to notice varies. In addition to the number of drops they’re on and for how long, age and preexisting dry eye are all factors that influence the effect of these medications on the ocular surface.
What’s more, different drops can have different effects. Brimonidine, Dr. Djalilian said, seems to have the most allergic reactions on the surface. Prostaglandins, on the other hand, seem to be more inflammation inducing and associated with higher rates of meibomian gland dysfunction. Beta blockers are detrimental to the surface as well, though the effect is harder to describe, he continued.
“Each is bad in its own way,” Dr. Djalilian said.
What most drops have in common is preservatives, which almost always have a negative effect on the ocular surface. Frequently, this preservative is benzalkonium chloride, the negative ocular surface effects from which have been well documented.1 Preservative-free glaucoma drops do exist—timolol, dorzolamide/timolol, and tafluprost—but Dr. Sarkisian said these options are limited. Dr. Djalilian said preservatives are almost always in generic versions of drops, and most patients, he added, are on generics.
Long exposure to preservatives and other agents in glaucoma drops can result in a slow loss of limbal stem cell function, Dr. Farid said. In glaucoma patients who are referred to her for ocular surface disease, Dr. Farid said she will look at their limbal architecture.
“The epithelium often looks very beat up and irregular. The epithelium can develop a whorled pattern keratopathy, which is an indication that the limbal stem cells are not working well. It’s beyond your dry eye punctate spots; there is more of a coarse punctate keratitis associated with loss of limbal architecture,” she said.
These patients will also often exhibit significant conjunctival hyperemia and/or chronic follicular conjunctivitis, Dr. Farid said, which are “signs that the ocular surface is really in distress.” Dr. Djalilian mentioned cicatricial conjunctivitis as well.
“[Limbal stem cell deficiency and cicatricial conjunctivitis] are two blinding conditions that cannot be treated easily once they get to advanced stages,” he said.
How to tell whether a patient’s ocular surface issues are a result of their medical glaucoma therapy, Dr. Djalilian explained, can involve taking them off that drop and watching the effect.
“My first choice is to try to change their drops around and get them on a regimen that’s gentler on the surface and lets them keep their pressure controlled,” Dr. Djalilian said, emphasizing that any change of glaucoma medication has to be done in consultation with the glaucoma specialist. “Obviously glaucoma takes precedence, except there are some situations where the surface disease can be vision threatening. In those cases, I will push the glaucoma specialist to make the change because this patient is going to go blind because of surface disease if we don’t do anything for them.”
Dr. Farid agreed. “First thing is the optic nerve, and the health of the optic nerve trumps the ocular surface,” she said. “We do everything we can from our cornea standpoint to maximize the tear film health, optimizing the lipid layer, putting them on anti-inflammatory drops or autologous serum, if that’s what they need.
“If it’s getting to the point where they’re having a lot of ocular surface distress, I’ll talk to my glaucoma colleague and suggest surgical intervention because we cannot keep these patients on the drops that are causing the ocular surface toxicity. That’s where the threshold for surgery gets lowered,” Dr. Farid said.
Dr. Sarkisian said he offers selective laser trabeculoplasty (SLT) as a first-line therapy, in order to avoid ocular surface issues and because it doesn’t alter or damage the tissue. He said he is among a growing number of surgeons offering SLT even before medical therapy.
“Invariably, people with moderate to severe glaucoma are going to need more than just laser trabeculoplasty to control their pressure, but if post-laser the patient can be on one or two drops instead of three or four drops, that’s an excellent move,” he said.
The treatment for ocular surface disease caused by glaucoma medication is to be on less medicine, Dr. Sarkisian quipped.
“In the MIGS era, that’s now reasonable,” Dr. Sarkisian said. MIGS, though it might have less risk due to it being minimally invasive surgery, however, can also come with less efficacy. Dr. Sarkisian projected that the combination of MIGS with sustained-release medications in the pipeline are going to change the conversation about glaucoma therapy as it pertains to the ocular surface. “These are such exciting times to be having this discussion about dry eye and ocular surface disease in glaucoma,” he said.
If a patient does not want to do a procedure to get off some or all of their medications, Dr. Sarkisian said ophthalmologists need to be more aggressive than just prescribing tears. Punctal plugs, anti-inflammatory medications, and more need to come into play. If the glaucoma specialist wishes to offer the patient dry eye management, he said it is worth scheduling a separate office visit to address that issue alone.
“It’s a good idea to spend some time coming up with a long-term strategy to help manage this and have a separate visit to address that. I think that will tell the patient that this is serious,” he said. “Usually, I refer them to one of my optometrists or if severe, a cornea specialist to manage.”
Dr. Djalilian said the ideal would be for every glaucoma specialist to be checking their patients for surface disease, to help avoid progression to more advanced, difficult to treat stages, but, he acknowledged, this is time consuming and might not be realistic.
“The real message is to be aware that chronic glaucoma medications can both exacerbate and induce ocular surface disease, which occasionally can be vision threatening and not just symptomatically bothersome to the patient. Being aware of these and intervening earlier makes a difference in the long-term outcomes,” Dr. Djalilian said.


1. Baudouin C, et al. Preservatives in eyedrops: the good, the bad and the ugly. Prog Retin Eye Res. 2010;29:312–34.

Editors’ note: Dr. Sarkisian has financial interests with Allergan (Dublin, Ireland), Beaver-Visitec International (Waltham, Massachusetts), Alcon (Fort Worth, Texas), Glaukos (San Clemente, California), Katena (Denville, New Jersey), New World Medical (Rancho Cucamonga, California), Omeros (Seattle), Santen (Osaka, Japan), and Sight Sciences (Menlo Park, California). Dr. Farid has financial interests with Allergan, Shire (Lexington, Massachusetts), Johnson & Johnson Vision (Santa Ana, California), CorneaGen (Seattle), and Bio-Tissue (Miami). Dr. Djalilian has no financial interests related to his comments.

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Managing ocular surface issues caused by vision-preserving glaucoma drops Managing ocular surface issues caused by vision-preserving glaucoma drops
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