Ocular surface disease, namely dry eye disease (DED), is a prevalent potential adverse ocular effect of glaucoma medication that is linked with patient noncompliance to prescribed medication(s).^1,2 In fact, it is estimated that 18% to 54% of glaucoma patients using glaucoma medication(s) have superficial punctate keratopathy on their corneal and conjunctival surface, and reduced tear break-up time in these patients may be as high as 60%.^3-7 Because patient medication noncompliance is one of our greatest challenges in managing glaucoma effectively, and medication-induced DED has been implicated as a common cause, it makes sense to review how to alleviate DED-related symptoms, such as burning, so patients can stick with their prescribed glaucoma medication(s) and, therefore, maintain their current sight.

This article aims to provide that review via a discussion of three action steps: (1) Prescribing anti-DED treatments, (2) Switching medications, and (3) Considering a surgical consult.

1. Prescribing anti-DED treatments
Several anti-DED interventions are available to enable our patients to decrease and, therefore, often tolerate their glaucoma medication-induced DED symptoms, so they can remain on the treatments that are best managing their disease. These interventions:

• Preservative-free artificial tears. When traditional OTC artificial tears do not address the patient’s DED sufficiently, preservative-free artificial tears are shown to provide significant relief of OSD signs and symptoms.⁷ I have found that this intervention is ideal for patients who are open and able to instilling the tears multiple times of day to achieve symptomatic relief.
• Lid hygiene. As most DED is evaporative vs. aqueous deficient, prescribing lid hygiene, or the use of lid scrubs, wipes, masks, sprays, warm compresses, warm goggles, etc., can facilitate meibomian gland secretion. What’s more, if Demodex blepharitis is present, lotilaner ophthalmic solution 0.25% (Xdemvy, Tarsus Pharmaceuticals) should be prescribed to eradicate the infestation, allowing for meibum secretion.
• Tetracycline analogue. Use of these agents results in minor (4%) to significant (89%) decreases in the abnormal appearance of the meibomian glands, and is shown to boost the stability of the tear film from 21% to 273%.⁸ For example, a three-month course of 50 mg oral doxycycline once daily, used with artificial tears and lid hygiene, alleviated DED symptoms and decreased IOP.⁹
• Immunomodulators. Cyclosporine ophthalmic solution 0.1% (Vevye, Harrow), cyclosporine ophthalmic solution 0.09% (Cequa, Sun Pharma), and cyclosporine 0.05% (Restasis, Allergan) increase tear production in patients who have aqueous-deficient DED via blocking T cell infiltration and activation, which release inflammatory cytokines.¹⁰ I, personally, prescribe topical corticosteroids as an adjunct to cyclosporine to “kick start” the immunomodulator. Also, I check IOP carefully, as many glaucoma patients are steroid responders.

Additionally, the lymphocyte function-associated antigen-1 antagonist, lifitegrast 5% ophthalmic solution (Xiidra, Novartis) works as an immunomodulator for DED patients. Specifically, it prevents LFA-1 on T cells from binding with ICAM-1, which might be overexpressed in DED, precluding immunologic synapse formation. In vitro studies show that this prevention may inhibit T cell activation, migration of activated T cells to the ocular surface, and reduce cytokine release, according to the manufacturer.

• In-office therapies. These include: a hydroxypropyl cellu-lose ophthalmic insert (Lacrisert, Bausch + Lomb, continuously bathing the ocular surface); intense pulsed light (OptiLight, from Lumenis, and the Quadra Q4 Platinum Series IPL, from Dermamed, heating the meibum); low level light therapy (Marco’s Equinox), microblepharoexfoliation (BlephEx, from Alcon, and NuLids, from NuSight Medical, unblocking the meibomian glands); and thermal treatment (LipiFlow, from Johnson & Johnson, Mibo Thermoflo, from Mibo Medical Group, Systane iLux, from Alcon, and TearCare, from Sight Sciences), heating the meibum prior to meibomian gland expression.
• Neurostimulation. Neurostimulation is designed to increase basal tear component production in patients who have aqueous-deficient DED via activating the nerves that produce the various tear components. This treatment is offered via the iTear 100 device (Olympic Ophthalmics) and varenicline solution nasal spray 0.03 mg, or Tyrvaya, from Viatris.
• Ocular nutritional supplementation. Omega-3 and
  Omega-6 supplementation is shown to decrease inflammation, which reduces the symptoms of DED, and is shown beneficial when used in conjunction with other DED treatments.¹¹ Regarding the former, pooled data from randomized controlled trials show when patients received 1,000 mg/day eicosapentaenoic acid, with 500 mg/day docosahexaenoic acid and 900 mg/day alpha-linolenic acid, IOP also decreased by 8%.¹² In relation to the former, a combination of omega-3 and omega-6 supplementation resulted, “in a significant and clinically meaningful improvement of dry eye symptoms in extremely symptomatic participants with DED (OSDI ≥52).”¹³ The offerings: Dry Eye Omega Benefits (PRN), EZ tears (Eye Promise), TG Omega-3 (MacuHealth), Tozal (Focus Laboratories), Focus Relief Plus (Covalent Medical), HydroEye (ScienceBased Health), and Pro Omega 2000 (Nordic Naturals).
• More interventions. The OD can also prescribe amniotic membranes to promote ocular surface healing (AmbioDisk [Katena], Amniograft, Prokera [BioTissue], Aril [Seed Biotech], BioDOptix [Integra], AcellFX [Akorn], and SurGraft [Surgenix]); autologous serum tears (see p.30), therapeutic contact lenses to protect the ocular surface from the mechanical effect of the lids (Acuvue Oasys [Johnson & Johnson Vision], Air Optix Night & Day Aqua [Alcon], PureVision [Bausch + Lomb], and Sof-Form 55 EW [Unilens Vision]); scleral contact lenses, which bathe the ocular surface due to their design (ABB Optical, AccuLens, Art Optical, Bausch + Lomb, Blanchard Contact Lenses, X-Cel, etc.); and punctal occlusion, which precludes tear drainage.

2. Switching medications
As the preservatives, such as benzalkonium chloride (BAK), in glaucoma medications can cause superficial punctate keratitis, corneal erosion, conjunctival injection, and anterior chamber inflammation, by virtue of their bacteriostatic properties that help extend their shelf life,^14-19 another action step optometrists can take to alleviate DED symptoms is to consider switching the patient to a combination glaucoma medication and/or a preservative-free glaucoma medication.

The fixed-combination glaucoma medications tend to require less drop instillation, limiting preservative exposure. These medications: Brinzolamide/brimonidine tartrate ophthalmic suspension 1%/0.2% (Simbrinza; Alcon), brimonidine 0.2%-timolol 0.5% (Combigan; Allergan), and dorzolamide 2%-timolol 0.5% (Cosopt [Thea]).

The preservative-free glaucoma medications are dorzolamide HCl-timolol maleate ophthalmic solution 2%/0.5% (Cosopt PF), latanoprost ophthalmic solution 0.005% (Iyuzeh, Théa Group), tafluprost ophthalmic solution 0.0015% (Zioptan, Théa Group), and 0.25% and 0.5% timolol maleate ophthalmic solution in Ocudose (Timoptic in Ocudose, Merck). Compounding pharmacies are an option for either combination or preservative-free medications.

Patient financial assistance programs are offered for both combination and preservative-free glaucoma medications, if needed. Additionally, financial support services are available through the Glaucoma Research Foundation, Prevent Blindness, and Bright Focus Foundation.

We may want to consider prescribing the generic alternatives of these drugs, as they cost less than the branded formulations. That said, because there is significant variability among generic medications in ease of use, efficacy, formulation and tolerability, and switching to a generic glaucoma medication due to side effects (with associated less patient adherence) and formulation differences may result in a loss of IOP control, these limitations must be understood and addressed with patients.¹⁹                 

3. Considering a surgical consult
As glaucoma drainage devices, microincisional glaucoma surgery, selective laser trabeculoplasty, and trabeculectomies can decrease or eliminate the requirement of glaucoma medication, thereby reducing or terminating glaucoma medication-induced DED symptoms, these are options worth discussing with our glaucoma patients as well.

Conquering a continuous nemesis
Mitigating glaucoma medication-induced DED is essential for improving medication compliance and patient quality of life. When adverse reactions of the medication start outweighing the benefits, we must consider other therapeutic options. We often must employ trial and error to arrive at the best solution for each patient who has glaucoma medication-induced DED, as one size does not fit all. OM

References

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Dr. Gottehrer currently practices at VA Finger Lakes Healthcare System, in Rochester, N.Y. She is a fellow of the American Academy of Optometry, and recipient of the 2023 national Hero award. She has no disclosures or financial interests.