The influence of glaucoma medications on ocular surface disease in primary open-angle glaucoma patients with and without conjunctivochalasis.

Abstract

Ocular surface disease (OSD), one of the major side-effects of long-term use of antiglaucoma drugs, is thought to develop secondary to reduced tear production, corneal epithelial damage, decreased number of subbasal nerves and corneal sensitivity, reduced number of goblet cells and damage to the mucous layer of the tear film resulting in tear film instability (Pisella et al. 2002). OSD in elderly is also associated with several conditions including conjunctivochalasis (CCh), a frequently overlooked ocular surface problem of the ageing population characterized by looseness and redundancy of inferior bulbar conjunctiva between the globe and the eyelid, which causes OSD symptoms by inducing tear film instability, delayed tear clearance and ocular surface inflammation (Liu 1986; Di Pascuale et al. 2004). The aim of this study was to evaluate whether the effect of CCh on ocular surface parameters differs according to the type of topical antiglaucoma medication in primary open-angle glaucoma patients. A total of 190 eyes of 190 subjects with or without CCh were included in this prospective study. Participants were divided into three groups: Group I was composed of patients treated with prostaglandin (PG) analogues (n = 46); Group II was composed of patients treated with beta-adrenergic antagonists (n = 45); Group III (control group) was composed of healthy subjects (n = 99). The subjects were categorized into two subgroups according to the presence or the absence of CCh. The tear break-up time (BUT), lissamine green (LG) staining and Schirmer test were performed and ocular surface disease index (OSDI) questionnaire scores were noted for each subject. Mann–Whitney U test, Kruskal–Wallis test and one-way anova were used for statistical analysis. All ocular surface parameters were found worse in each group with CCh. Patients with CCh in Group I had significantly lower Schirmer test values and higher LG grading and OSDI scores than those of patients with CCh in Group II and Group III (p < 0.05; Table 1). Ocular surface parameters of patients with grade 2 CCh were significantly different than those of grade 1 CCh in all groups (p < 0.05). Both beta-blockers and PG analogues increase the inflammatory marker expression and decrease MUC5AC-related mucin production in epithelial cells compared with normal subjects (Pisella et al. 2004). These factors may be crucial in development of ocular surface changes in patients without CCh who are on PG analogue therapy or beta-adrenergic antagonists. In addition, it is also known that preservatives have adverse effects on ocular surface (Pisella et al. 2002). Thus, we cannot rule out BAK as a co-pathogenic factor for the observed ocular surface alterations detected in our study. We found that ocular surface parameters were adversely affected in the presence of CCh in medically treated glaucoma patients compared with healthy control subjects. In addition, grade 2 CCh had evidence of more profound alterations in ocular surface testing than those of grade 1 CCh in both glaucoma patients and control subjects. Patients who were on PG analogue therapy and had coexistent CCh showed evidence of a more severe ocular surface disease compared with patients who were on beta-adrenergic antagonists. This could be due to the contribution of both PG use and CCh separately to ocular surface disease, as both PG use and CCh are known to be associated with ocular surface inflammation (Fodor et al. 2012). In conclusion, long-term monotherapy with topical antiglaucoma therapy is associated with OSD in patients with and without CCh. The severity of CCh is associated with both objective and subjective alterations. It seems reasonable to evaluate and follow-up glaucoma patients treated with a long-term antiglaucoma drug for the presence of CCh and the ocular surface disease.