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Exploring Topical Anti-Glaucoma Medication Effects on the Ocular Surface in the Context of the Current Understanding of Dry Eye

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Exploring Topical Anti-Glaucoma Medication Effects on the Ocular Surface in the Context of the Current Understanding of Dry Eye The Ocular Surface 16 (2018) 289e293 Contents lists available at ScienceDirect The Ocular Surface journal homepage: www.theocularsurface.com Original Research Exploring topical anti-glaucoma medication effects on the ocular surface in the context of the current understanding of dry eye Aaron B.C. Wong, Michael T.M. Wang, Kevin Liu, Zak J. Prime, Helen V. Danesh-Meyer, * Jennifer P. Craig Department of Ophthalmology, New Zealand National Eye Centre, The University of Auckland, New Zealand article info abstract Article history: Purpose: To assess tear film parameters, ocular surface characteristics, and dry eye symptomology in Received 11 November 2017 patients receiving topical anti-glaucoma medications. Received in revised form Methods: Thirty-three patients with a diagnosis of open angle glaucoma or ocular hypertension, 26 February 2018 receiving unilateral topical anti-glaucoma medication for at least 6 months, were recruited in a cross- Accepted 2 March 2018 sectional, investigator-masked, paired-eye comparison study. Tear film parameters, ocular surface characteristics, and dry eye symptomology of treated and fellow eyes were evaluated and compared. Keywords: Results: The mean ± SD age of the participants was 67 ± 12 years, and the mean ± SD treatment duration Glaucoma ± fi ¼ fi Prostaglandin analogue was 5.3 4.4 years. Treated eyes had poorer non-invasive tear lm breakup time (p 0.03), tear lm ¼ ¼ Tear film osmolarity (p 0.04), bulbar conjunctival hyperaemia (p 0.04), eyelid margin abnormality grade Ocular surface (p ¼ 0.01), tear meniscus height (p ¼ 0.03), and anaesthetised Schirmer value (p ¼ 0.04) than fellow eyes. Dry eye There were no significant differences in dry eye symptomology, meibomian gland assessments, and Meibomian gland ocular surface staining between treated and fellow eyes (all p > 0.05). Conclusions: Adverse changes in tear film stability, tear osmolarity, conjunctival hyperaemia, and eyelid margins were observed in treated eyes. This suggests that inflammatory mechanisms may be implicated in the development of dry eye in patients receiving long term topical anti-glaucoma therapy. © 2018 Elsevier Inc. All rights reserved. 1. Introduction a common preservative in ophthalmic preparations [9], has been identified to be an independent risk factor for the development of Glaucoma and ocular surface disease are common chronic ocular surface disease in glaucoma patients [4,8] Benzalkonium conditions, which frequently coexist in ophthalmic patients [1e5]. chloride is recognised to destabilise the tear film lipid layer through Over 60 million people are affected by glaucoma worldwide, and its detergent-like tensioactive effects, which may promote excessive the global burden is expected to rise with the ageing population [6]. evaporation of the aqueous tear film. Furthermore, the pro- The prevalence of ocular surface disease is greater in glaucoma inflammatory and toxic effects of benzalkonium chloride can also patients than in the normal adult population [1,3], and has been lead to chronic damage of the ocular surface, and disrupt tear film reported to be as high as 60% [5]. The associated tear film homeostasis [1e4,8,9]. dysfunction and dry eye symptoms can contribute towards further Recent studies have explored the potential association between deterioration in ocular comfort, vision and quality of life [1e3,7]. topical anti-glaucoma medications and meibomian gland Although the propensity for dry eye development in glaucoma dysfunction [10e13]. Through its adverse effects on lipid layer patients is not fully understood, it is thought to be multifactorial integrity and tear film stability, meibomian gland dysfunction is a [1e3]. Clinical and laboratory studies have suggested that the long leading cause of evaporative dry eye disease [7,14e16]. Poorer tear term use of topical anti-glaucoma medications may contribute film quality and meibomian gland function have been observed [1e4,8]. In particular, increased exposure to benzalkonium chloride, with topical anti-glaucoma medication use in both paired-eye comparison and case control studies [10e13]. * Corresponding author. Department of Ophthalmology, New Zealand National This cross-sectional paired-eye comparison study sought to Eye Centre, The University of Auckland, New Zealand, Private Bag 92019, Auckland, investigate the effect of topical anti-glaucoma medication use on 1142, New Zealand. ocular surface characteristics, tear film quality, aqueous tear E-mail address: [email protected] (J.P. Craig). https://doi.org/10.1016/j.jtos.2018.03.002 1542-0124/© 2018 Elsevier Inc. All rights reserved. 290 A.B.C. Wong et al. / The Ocular Surface 16 (2018) 289e293 production, meibomian gland function, and dry eye symptomology. eye and the higher reading recorded. Lid margin abnormalities (lid margin irregularity, telangiectasia, plugged orifices of meibomian 2. Materials and methods glands, and anterior or posterior replacement of the mucocuta- neous junction) were assessed by slit lamp examination, and scored 2.1. Subjects from 0 to 4, according to the number of abnormalities present in each eye [10]. This cross-sectional, investigator-masked, paired-eye compari- Sodium fluorescein and lissamine green dyes were applied, in son study adhered to the tenets of the Declaration of Helsinki, and turn, to the bulbar conjunctiva in order to evaluate localised corneal was approved by the institutional ethics committee. Participants and conjunctival areas of epithelial dessciation, and recorded using were required to be at least 18 years of age, with a diagnosis of open the Oxford grading scheme for ocular staining [22]. Lid wiper epi- angle glaucoma or ocular hypertension, and topical anti-glaucoma theliopathy (LWE) was also assessed following lissamine green medication use in only one eye. Furthermore, eligibility required application [23]. participants to report no changes in anti-glaucoma medications Meibomian gland function assessment was conducted in within the preceding 6 months, no contact lens wear, no use of accordance with the recommendations of the International Work- other topical or systemic medications known to affect the eye, no shop on Meibomian Gland Dysfunction and TFOS DEWS II [19,24]. history of Sjogren's€ syndrome, and no previous ocular surgery Expressibility of the inferior eyelid meibomian glands was assessed ® (other than phacoemulsification, childhood strabismus surgery, or with the Korb Meibomian Gland Evaluator™ (TearScience , North epiretinal membrane surgery, more than 6 months before study Carolina, USA). The number of meibomian orifices yielding lipid enrolment) [17]. Eligible participants were enrolled after providing secretion was evaluated at each of the nasal, central and temporal written informed consent. aspects of the lower lid [25]. The meibum viscosity and expressi- A total of 33 eligible participants were recruited, exceeding bility was graded as: grade 0, clear fluid; grade 1, slightly turbid; sample size requirements. Non-paramateric adjusted power cal- grade 2, thick opaque; grade 3, toothpaste-like; grade 4, complete culations were conducted using NCSS PASS 2002 (Utah, USA), with orifice blockage [21]. Infrared meibography was imaged with the non-invasive tear film breakup time as the designated outcome Oculus Keratograph 5 M, with the superior and inferior eyelids (due to yielding the most stringent sample size requirements of all everted in turn. From the captured image, the proportion of mei- outcome measures), and the normal SD estimated to be 6 s [18]. A bomian glands visible within the tarsal area were graded according minimum of 26 participants was required to detect a clinically to the Meiboscale [26]. significant difference of 5 s, with 80% power (b ¼ 0.2), at a two- The Schirmer I test was then performed, as the final assessment, sided statistical significance level of 5% (a ¼ 0.05). under topical anaesthesia (0.4% oxbuprocaine) [27]. 2.2. Measurements 2.3. Statistics Participants were instructed to refrain from taking the morning Statistical analyses were performed using IBM SPSS Statistics dose of topical anti-glaucoma medications before clinical assess- version 22 (New York, USA) and Graph Pad Prism version 6.02 ment. Tear film parameters, ocular surface characteristics and dry (California, USA). Comparisons of continuous variables were per- eye symptomatology were evaluated in both treated and untreated formed using paired t-tests, where normal distributions had been eyes of each participant, within a single clinical session. The in- confirmed by Kolmogorov-Smirnov testing (p > 0.05). Non- vestigators conducting measurements were masked to the treat- normally distributed continuous and ordinal data were analysed ment status of each eye. Assessments were conducted in ascending using Wilcoxon signed-rank test. All tests were two-tailed and order of invasiveness to minimise the impact on tear film physi- p < 0.05 was considered significant. All normally distributed ology for subsequent measurements: tear meniscus height, non- continuous data are presented as mean ± SD, non-normally invasive tear film breakup time, tear film lipid layer grade, bulbar distributed continuous data or ordinal data as median (IQR), and conjunctival hyperaemia, tear osmolarity, slit lamp examination, categorical data as number of participants (% of participants), un- ocular surface staining, meibomian gland expression, infrared less otherwise stated. meibography, Schirmer I test. All participants were assessed in the same location, with a mean ± SD room temperature
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