Source/Disclosures
Disclosures: White reports he is a consultant to Allergan, Bruder, EyePoint, Eyevance, Kala, Novartis, Ocular Therapeutix, Omeros, Rendia, Sun and TearLab; is a speaker for Allergan, Eyevance, Kala, Novartis, Omeros and Sun; and has ownership in Ocular Science.
November 17, 2020
5 min read
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Dry eye and the glaucoma patient

Treatment of glaucoma can make dry eye worse.

Source/Disclosures
Disclosures: White reports he is a consultant to Allergan, Bruder, EyePoint, Eyevance, Kala, Novartis, Ocular Therapeutix, Omeros, Rendia, Sun and TearLab; is a speaker for Allergan, Eyevance, Kala, Novartis, Omeros and Sun; and has ownership in Ocular Science.
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Not a day goes by at SkyVision without a referral from a colleague who has come to wits’ end trying to manage the care of a patient who has dry eye disease.

It is surprising how many of these physician referrals are patients who had glaucoma first. The majority of these individuals have glaucoma that is well managed with stable visual fields, no evidence of progressive nerve fiber loss on OCT and IOP that is well within target range. Despite this favorable scenario, our office welcomes a patient who is miserable, sent by a doctor who is frustrated. Superlative care feels like a failure because their patient feels lousy.

Darrell E. White, MD
Darrell E. White

Our long-standing best practices for glaucoma often turn well-controlled glaucoma into symptomatic DED.

For the last 40 years or so, glaucoma care in the U.S. has been driven by one simple goal: do not operate. Comprehensive ophthalmologists and fellowship-trained glaucoma specialists alike worked hard to achieve adequate IOP control without having to resort to incisional glaucoma surgery. With the introduction of Timoptic (timolol, Bausch + Lomb) in the early 1980s, scores of patients who would have had glaucoma surgery were able to avoid the knife. Subsequent progress came from a pitched battle between pharmaceutical companies that introduced true breakthrough medications and their competitors that piled on with “me too” copycats.

Timoptic was shortly followed by several other branded beta-blockers. Thus began 30+ years of pharmaceutical innovation in glaucoma. Like Timoptic, the next big discovery was pretty friendly to the ocular surface. Xalatan (latanoprost, Pfizer) never seemed to cause all that much trouble from a dry eye standpoint. Xalatan’s relative lack of systemic side effects rapidly made it first-line treatment. Xalatan was followed by Alphagan (brimonidine tartrate, Allergan), and Alphagan drove Timoptic out of its slot as second-line treatment in many practices. Sadly, Alphagan and the follow-on prostaglandin analogs Lumigan (bimatoprost, Allergan) and Travatan (travoprost, Alcon) introduced ophthalmology to a host of ocular surface side effects that sullied the otherwise successful topical management of IOP.

Were the active ingredients the culprits in these new products, or was it something else? Yes. In retrospect, all of the prostaglandin analogs, even latanoprost, seem to cause a darkening of the periocular skin, especially below the lower lid. There is clearly something about bimatoprost, travoprost and brimonidine that is toxic to both corneal and conjunctival epithelial cells. A significant percentage of patients taking these medications have redness and irritation. Their eyes are indistinguishable at the slit lamp from those of our typical, non-glaucomatous patients with DED. The most striking finding of all, at least for me, is the dramatic increase in both the incidence and severity of meibomian gland disease in these patients. Their lids are so inflamed that they glow.

It is tempting to ascribe all, or at least most, of these side effects to the preservative found in essentially all traditional glaucoma drops. Benzalkonium chloride (BAK) as a preservative is ubiquitous in our medications. Indeed, BAK has been treated as an integral part of the mechanism of action in at least one category of drops, the prostaglandin analogs. Early marketing campaigns openly discussed the increased penetration of medications when BAK was included in the vehicle. We now know that BAK is proinflammatory. It seems as if it not really a question of if but when it will become a problem.

How do we address it when a patient with well-controlled glaucoma arrives at our office with severe DED issues? Our first dictum comes straight from our sacred oath to do no harm: take away as much of a potentially harmful element as possible. Why do we persist in using medications that contain an element that causes inflammation? Removing preservatives seems like it should be automatic. Heck, why do we even prescribe them in the first place? We have at our disposal preservative-free prostaglandin analogs, as well as a timolol-dorzolamide formulation. Sadly, we all know that the answer to this question lies in the maddeningly complex and punitive third-party payment system under which we labor. Still, if we wish to keep our patients out of the OR, changing them to preservative-free glaucoma drops is the logical first choice.

Stepping back at this point and looking at the state of glaucoma care in the U.S., I think we can see an even more direct route to solving the medication-induced DED epidemic: do whatever it takes to stop as many topical medications as possible. Indeed, with newer technologies available and a better understanding of how existing non-pharmacologic treatment options can be used earlier in our therapeutic paradigms, it is entirely reasonable for us to ask ourselves if we shouldn’t be trying as hard to avoid topical treatment as we have heretofore been trying to avoid traditional incisional glaucoma surgeries.

Looking at glaucoma care through the eyes of a DED doctor, the closest thing to a slam dunk is either starting our glaucoma patient’s care with selective laser trabeculoplasty or using SLT to remove one or more drops from their regimen. Data from the LiGHT study continue to come out showing that SLT is more than just “noninferior.” Most recently we have learned that, even in the face of similar IOP measurements in the office, at the 3-year point patients treated with SLT have less progression than those treated with drops. The investigators opine that this is likely due to nonadherence to the proper drop regimen. Those of us who see patients with DED caused by glaucoma drops have no trouble understanding this.

I think it is time for us to think of MIGS procedures as DED therapy as well. Why must our patients with glaucoma continue to have DED and MGD when we now have surgical options that have a better safety profile than trabeculectomy or tube shunts? For goodness sake, the ultimate MIGS procedure is lensectomy. Thousands of glaucoma patients have lower IOP after cataract surgery. If you add a micro-shunt, goniotomy or gonioplasty, the effect of removing the crystalline lens is amplified.

Our decades-long overarching quest to avoid glaucoma surgery is leading to the greater patient burden of DED and is now counterproductive. Glaucoma should become a more surgical disease. SLT should be first-line treatment. Lensectomy for glaucoma should be viewed as medically necessary and should be covered by insurance as such. MIGS procedures of all sorts should be decoupled from lens-based surgeries. For example, inserting iStents (Glaukos) in a pseudophakic patient should also be treated and covered as medically necessary. Big pharma is also doing its part. If we must use glaucoma medication to treat our patients, we should be putting it inside the eye, not on the eye; the next great leap in medical treatment for glaucoma is Durysta (Allergan), an injectable form of bimatoprost that Nathan Radcliffe has called the fourth pillar of care. It appears to last at least 6 months. And if we absolutely gotta musta hafta use eye drops, when they hit the eye, they should be free of preservatives (hurry up, TearClear).

Glaucoma treatment should no longer be a risk factor for symptomatic DED.