Recently in our dry eye clinic, I (Dr. Chaglasian) saw an 83-year-old female with significant subjective and objective signs and symptoms of ocular surface disease (OSD), including redness, burning, itching, watering, foreign body sensation, corneal and conjunctival staining, increased tear osmolarity and decreased tear production. 

The Complication
This is not an unusual presentation in our clinic, but she was also being treated for moderate primary open-angle glaucoma. She reported side effects, such as irritation and redness, to hypotensive drops including prostaglandins, carbonic anhydrase inhibitors and alpha agonists. 

At the time, she was using Restasis (cyclosporine, Allergan), preservative-free artificial tears and nighttime gel. She had tried bandage contact lenses with minimal success. She had also undergone selective laser trabeculoplasty to reduce some of her topical medication usage and was only using Simbrinza (brinzolamide/brimonidine, Alcon) at the time of initial presentation. She admitted that she sometimes purposely skipped taking her glaucoma medication because of the irritation.

This serves as a reminder that as our population ages, there will be greater overlap between the dry eye and glaucoma populations we see in our practices.1 We need to be cognizant to not exacerbate one condition while treating the other. Although multidose, preserved, topical eyedrops are the mainstay of glaucoma management, other available options need to be considered, including “softer” preservatives and preservative-free preparations.

While there is no disputing the benefits of reducing microbial contamination with preservatives, significant negative side effects to the ocular surface exist and cannot be ignored in vulnerable eyes, such as destabilization of the pre-corneal tear film, increase in evaporation of the lipid layer, corneal neurotoxicity, inflammation and reduction in aqueous tear production. 

The Culprit
Often, the problem is benzalkonium chloride, a cationic surfactant, which can damage the corneal and conjunctival tissues, even in small concentrations.2-4 Other preservatives, such as Purite and Sofzia, offer antimicrobial properties while minimizing (though not eliminating) ocular surface compromise. Purite, found in Alphagan P (brimonidine, Allergan), is a stabilized oxychloro complex that destabilizes into non-toxic components upon instillation. Sofzia, found in Travatan Z (travoprost, Alcon) contains borate, zinc and sorbitol. Upon instillation, it is inactivated via tear enzymes.5 

In patients with concurrent OSD and glaucoma, preservative-free medications have been effective in treating intraocular pressure (IOP) while also improving patient compliance and symptoms and reducing inflammation, osmolarity and clinical signs.6,7 

The Downsides
Without the antimicrobial benefit afforded by preservatives, these medications need to be packaged in individual, single-use containers. These can be difficult for patients to open. Another downside is cost, as these medications tend to be more expensive than multiuse bottles. A bottle of latanoprost can cost as little as $12, while a 30-vial package of preservative-free Zioptan (tafluprost, Akorn) is $195 on GoodRx.

Getting back to our patient: After consultation with a colleague who was managing the patient’s glaucoma, we switched her to Zioptan. At her last dry eye follow-up one year later, she reported full compliance with its use and improved comfort with stable IOP. Her osmolarity and clinical signs had also improved. 

Glaucoma and OSD are chronic diseases that need long-term therapies. Individualized treatment plans to maximize outcomes are essential, and alternative preservative or preservative-free solutions need to be in the forefront of our minds.   

1. Aptel F, Choudhry, Stalmans I. Preservative-free versus preserved latanoprost eye drops in patients with open-angle glaucoma or ocular hypertension. Curr Med Res Opin. 2016;32(8):1457-63. 
2. Cha Sh, Lee JS, Oum BS, Kim CD. Corneal epithelial cellular dysfunction from benzalkonium chloride(BAC) in vitro. Clin Experiment Ophthalmol. 2004:32(2):180-4.
3. De Saint Jean M, Brignole F, Bringuier AF, et al. Effects of benzalkonium chloride on growth and survival of Chang conjunctival cells. Invest Ophthalmol Vis Sci. 1999;40(3):619-30.
4. Janulevi I, Derkač I, Grybauskiene L, et al. Effects of preservative-free tafluprost on tear film osmolarity, tolerability, and intraocular pressure in previously treated patients with open-angle glaucoma. Clin Ophthalmol. 2012;6:103-9.
5. Leung EW, Medeiros FA, Weinreb RN. Prevalence of ocular surface disease in glaucoma patients. J Glaucoma. 2008;17(5):350-5.
6. Sarkar J, Chaudhary S, Namavari A et al. Corneal neurotoxicity due to benzalkonium chloride. Invest Ophthalmol Vis Sci. 2012;53:1792-1802.
7. Yadgarov A, Garg RA. Preservative free alternatives. Glaucoma Today. Nov/Dec 2016.