Understanding the Dual Dilemma of Dry Eye and Glaucoma: An International Review

Abstract

Glaucoma-related ocular surface disease (G-OSD) is a significant, yet often underdiagnosed, ocular co-morbidity affecting 40% to 59% of glaucoma patients worldwide. Although the use of topical glaucoma medications represents a proven strategy to control the untoward effects of high intraocular pressure, this treatment can profoundly disrupt the homeostasis of the tear film. The cumulative effect of medications, preservatives, and excipients alter underlying cellular structures which results in tear film abnormalities and instability of the ocular surface. Furthermore, these chronic inflammatory changes have been shown to impact efficacy of glaucoma treatment, patient compliance with therapy and overall quality of life. The pathogenesis of G-OSD is multifactorial and involves a vicious self-perpetuating cycle of inflammatory cytokines and proteins. The diagnosis of such disease is based on similar tests used in assessing traditional dry eye, taking into consideration findings specific to this patient population. The hallmark of treatment for these patients is to minimize the ocular surface inflammatory response by choosing glaucoma therapies that spare the ocular surface such as preservative free formulations and initiating dry eye treatment early in the course of care. In summary, glaucoma affects millions of patients around the world and chronic use of topical glaucoma medications may negatively impact the patient's ocular surface, symptoms, and vision. Understanding the pathogenesis of G-OSD, recognizing its risk factors and incorporating diagnostic and therapeutic strategies that restore and maintain ocular surface homeostasis will result in improved care for our patients.

Efficacy, Safety and Patient-Reported Outcomes with Preservative-Free (PF) Tafluprost or PF-Dorzolamide/Timolol Compared with Preserved Latanoprost: A Prospective Multicenter Study in Korean Glaucoma Patients with Ocular Surface Disease

“…Ocular surface toxicity associated with the long-term use of topical anti-glaucoma medication can result from the active ingredient(s), especially for patients with pre-existing OSD, and/or from preservatives and excipients [13][14][15][16][17][18]. Most eye drops contain preservatives, commonly benzalkonium chloride (BAK), which can cause corneal, conjunctival, and trabecular meshwork toxicities resulting in OSD [15][16][17][18][19][20][21].…”

“…Ocular surface toxicity associated with the long-term use of topical anti-glaucoma medication can result from the active ingredient(s), especially for patients with pre-existing OSD, and/or from preservatives and excipients [13][14][15][16][17][18]. Most eye drops contain preservatives, commonly benzalkonium chloride (BAK), which can cause corneal, conjunctival, and trabecular meshwork toxicities resulting in OSD [15][16][17][18][19][20][21]. A range of deleterious effects in these tissues has been reported for BAK including apoptosis, oxidative stress, disruption of tight junctions, cytoskeleton changes, and induction of inflammatory chemokines [19,22,23].…”

“…A range of deleterious effects in these tissues has been reported for BAK including apoptosis, oxidative stress, disruption of tight junctions, cytoskeleton changes, and induction of inflammatory chemokines [19,22,23]. There has also been a report of severe impairment of corneal sensitivity owing to chronic use of preserved glaucoma medication containing BAK, which indicates the wide-ranging impact of BAK in changing the ocular surface structure [18].…”

Treatment of open-angle glaucoma and ocular hypertension with preservative-free tafluprost/timolol fixed-dose combination therapy: 6 case reports and clinical outcomes

“…Ideally, topical glaucoma treatments, should provide a balance of powerful efficacy alongside an acceptable tolerability profile [ 9 ]. Recent data indicate that treatments that are better tolerated at the ocular surface and result in less OSD may be associated with further reductions in IOP among people with glaucoma, possibly as a result of improved treatment adherence and reduced inflammation at the site of instillation, which allows IOP-lowering medications to act more effectively [ 5 , 7 , 9 – 14 ]. The European Glaucoma Society (EGS) guidelines emphasize that treatment should consider patient QoL from the outset [ 2 ].…”

In Silico Screening and In Vivo Evaluation of Potential CACNA2D1 Antagonists as Intraocular Pressure-Reducing Agents in Glaucoma Therapy

“…Examples of the side effects of recently approved products are Vyzulta (latanoprostene bunod, 0.024%), which is associated with a permanent pigmentation of the eyelids, lashes and iris [ 6 ]; and Rhopressa (netasudil, 0.02%), which causes conjunctival hyperemia and hemorrhage, eye pain upon instillation and cornea verticillate [ 7 ]. In addition to the previously mentioned side effects, the chronic use of topically applied anti-glaucoma medication may result in a disturbance of the tear film that impacts the health of the patient’s ocular surface and results in a glaucoma-related ocular surface disease and dry eye condition [ 8 ]. Therefore, identification of safe, effective and long-acting drug molecules that can selectively interact with a specific target site inside the eye and have the ability to control the IOP is still an urgent medical need.…”