Dry eye disease (DED) and primary open-angle glaucoma (POAG) are two common, chronic and serious eye conditions that interact iatrogenically when glaucoma medications, surgery and, in rare cases, laser cause DED. As this interaction can result in patient discomfort, this article addresses how to diagnose DED in our glaucoma patients and effectively treat it.

Diagnosing DED

While DED is often sufficiently symptomatic to elicit complaints from patients, diagnostics can be helpful in clarifying the diagnosis. These diagnostics are corneal topographers (devices from AIT Industries, Bausch + Lomb, EasyScan, Marco, Oculus, Topcon, Zeiss, and Ziemer); inflammatory and osmolarity assessments (InflammaDry, TearLab Osmolarity System, I-PEN Tear Osmolarity System); meibography (LipiScan, Meibox, Oculus Keratograph 5M); and meibomian gland expression devices (Flexx MG Expressors, Mastrota Paddle, Meibomian Gland Evaluator). These tests may help the clinician decide whether to primarily address inflammation or other aspects of DED, such as meibomian gland dysfunction (MGD), which could drive decisions, such as instituting anti-inflammatory therapy vs discontinuing a prostaglandin analog.

Effective Treatment

There are four ways to combat DED caused by topical glaucoma pharmacotherapies:

1. Selective laser trabeculoplasty (SLT). In the prospective Laser in Glaucoma and Ocular Hypertension (LiGHT) trial,¹ 718 patients were randomized to receive laser or topical therapy (a prostaglandin analogue) as an initial treatment for ocular hypertension or glaucoma. At 3 years, there was better pressure control (93.0% vs 91.3%) and fewer surgical interventions (0 vs 11 patients) in patients who underwent SLT. Additionally, the laser was successful in controlling the disease without drops 75% of the time. This result has led many practitioners to begin recommending SLT as an initial therapy.

For patients already using topical agents who develop DED, SLT is an ideal replacement therapy that will likely result in symptomatic improvement. For example, a smaller study examined 143 glaucoma patients to see whether switching to SLT could reduce punctate keratitis and resolve other side effects, such as ocular discomfort, and SLT demonstrated less punctate keratitis and improved side effects. Topical medications were stopped.²

2. Carefully chosen eye drop formulations. For many patients, preserved once daily eye drops are well tolerated. A once daily, preserved prostaglandin analog is reasonable therapy for many, but not all glaucoma patients. Preservatives are included to maintain the sterility of multidose ophthalmic medications, with benzalkonium chloride (BAK) being the most commonly used. BAK can disrupt the stability of the precorneal tear film, induce corneal epithelial dysfunction and cause cell damage.^3-5 In addition to glaucoma drops themselves, a daily dose of BAK greater than 3 is associated with a higher ocular surface disease index score.⁶ The commercially available preservative-free drops are latanoprost ophthalmic emulsion 0.005% (Xelpros; Sun Pharma) timolol maleate 0.25% and 0.5% (Timoptic and in Ocudose, Bausch & Lomb); dorzolamide HCL 2%/timolol maleate 0.5% fixed-dose combination (Cosopt PF, Akorn) and tafluprost (Zioptan, Akorn).

Additionally, several formulations with alternative (non-BAK) preservatives are available: brimonidine tartrate 0.1% or 0.15% (Alphagan-P, Allergan) bottled with Purite, a preservative with oxidative properties; and travoprost 0.004% preserved with the oxidative preservative SofZia (Travatan Z, Alcon). In this author’s experience, one can judiciously use preservative-free and alternatively preserved agents to combat epithelial toxicity associated with BAK; however, it is important to also consider the toxicity of the active ingredients in these formulations themselves.

3. Microincisional glaucoma surgery, or MIGS. MIGS can be achieved with a variety of surgical approaches and implants aiming to reduce intraocular pressure (IOP) and medication use via a safe, ab interno procedure performed at the time of cataract surgery or as a stand-alone procedure. For example, in one prospective study of MIGS as a standalone procedure, both the iStent (Glaukos) and Hydrus (Ivantis) reduced medication use, and 46.6% of Hydrus patients and 24.0% of two iStent patients were medication free at 1 year.⁷ While there are no specific data on DED improvement after MIGS, it is expected that medication reduction would be beneficial. My clinical experience has been positive, in terms of DED after MIGS. That said, one needs to balance the severity of the cataract and glaucoma, the IOP and medication burden (as well as the DED effects of cataract surgery itself) in the decision-making process for offering MIGS in the POAG patient with DED.

4. Traditional DED treatments. Traditional treatments may be beneficial in POAG patients who have DED.⁸ Traditional treatments on the market: antibiotics, artificial tears, cyclosporine (Restasis from Allergan or Cequa from Sun Pharmaceuticals), lifitegrast (Xiidra, Novartis), topical corticosteroids, and lid hygiene products. Glaucoma care providers may be hesitant to treat with additional DED topical therapies, due to concerns of these therapies interfering with glaucoma medication patient compliance, however these therapies can be effectively implemented in POAG patients who have DED.

Traditional treatments for MGD are tetracycline antibiotics, omega-3 fatty acids or mechanical gland expression, and can be employed in glaucoma patients. Thermal pulsation systems, offered by Alcon, Johnson & Johnson Vision, and SightSciences, utilize heat and compression/expression to relieve obstruction of the meibomian glands. Alternatively, intense pulsed light (IPL) therapy, offered by Hologic and Lumenis, can be used to treat both DED and rosacea by applying broad spectrum light periocularly in a band from ear to ear that goes below the lid margin of the lower eyelid. Because these approaches do not involve the use of additional medications, which may compromise patient compliance, they may be ideal for glaucoma patients who have MGD.

5. Sustained delivery. One option that could become helpful for DED and glaucoma patients is the sustained delivery of glaucoma medications. The two most promising benefits of sustained delivery are guaranteed compliance and improved ocular surface tolerability. Some therapies will be delivered to the ocular surface, while others will be intracameral. The FDA recently approved bimatoprost implant, 10mcg (Durysta, Allergan), which is an intracameral, sustained-release implant approved to reduce IOP in POAG and ocular hypertension.

Several Choices

While several factors contribute to DED in POAG patients, traditional topical pharmacotherapy is the main culprit. The first step to managing DED is a definitive diagnosis. The next step is to match the treatment choice with the cause and type of DED, as well as the patient’s personal circumstances, such as poor compliance with their drop regimen. SLT is a helpful primary or replacement therapy, while the thoughtful use of alternative or preservative-free therapies and traditional treatments can be beneficial. Additionally, sustained delivery is promising. Ultimately, the clinician can use some or all of the tools in this toolbox to limit the impact of DED in glaucoma. CP

References

1. Gazzard G, Konstantakopoulou E, Garway-Heath D, et al. Selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma (LiGHT): a multicentre randomised controlled trial. Lancet Lond Engl. 2019;393(10180):1505-1516. doi:10.1016/S0140-6736(18)32213-X
2. De Keyser M, De Belder M, De Groot V. Quality of life in glaucoma patients after selective laser trabeculoplasty. Int J Ophthalmol. 2017;10(5):742-748. doi:10.18240/ijo.2017.05.14
3. Wilson WS, Duncan AJ, Jay JL. Effect of benzalkonium chloride on the stability of the precorneal tear film in rabbit and man. Br J Ophthalmol. 1975;59(11):667-669. doi:10.1136/bjo.59.11.667
4. Cha SH, Lee JS, Oum BS, Kim CD. Corneal epithelial cellular dysfunction from benzalkonium chloride (BAC) in vitro. Clin Exp Ophthalmol. 2004;32(2):180-184. doi:10.1111/j.1442-9071.2004.00782.x
5. Takahashi N. Quantitative cytotoxicity of preservatives evaluated in cell culture with Chang’s human conjunctival cells--effect of temperature on cytotoxicity. Jpn J Ophthalmol. 1982;26(2):234-238.
6. Skalicky SE, Goldberg I, McCluskey P. Ocular surface disease and quality of life in patients with glaucoma. Am J Ophthalmol. 2012;153(1):1-9.e2. doi:10.1016/j.ajo.2011.05.033
7. Ahmed IIK, Fea A, Au L, et al. A prospective randomized trial comparing Hydrus and iStent microinvasive glaucoma surgery implants for standalone treatment of open-angle glaucoma: the COMPARE study. Ophthalmology. 2020;127(1):52-61.
8. Boso ALM, Gasperi E, Fernandes L, et al. Impact of ocular surface disease treatment in patients with glaucoma. Clin Ophthalmol. 2020;14(14):103-111.

DR. RADCLIFFE is a clinical associate professor of ophthalmology at New York Eye and Ear Infirmary and is a cataract and glaucoma surgeon at the New York Eye Surgery Center. Additionally, he is the editor of Glaucoma Physician, a sister publication of Corneal Physician.