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Year : 2021  |  Volume : 29  |  Issue : 1  |  Page : 28-33

Prevalence of Ocular Surface Disease in Glaucoma Patients on Long-Term Antiglaucoma Medications

Department of Ophthalmology, University of Uyo Teaching Hospital, Uyo, Nigeria

Date of Submission22-Jun-2020
Date of Decision29-Dec-2020
Date of Acceptance01-Feb-2021
Date of Web Publication16-Jul-2021

Correspondence Address:
Emem G Abraham
Department of Ophthalmology, University of Uyo Teaching Hospital, Uyo
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/njo.njo_25_20

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Objective: Long term use of preservative-containing medications has been associated with the development or worsening of ocular surface disease (OSD). This study aimed to determine the prevalence of OSD in glaucoma patients on long-term antiglaucoma medications. Methods: A cross-sectional hospital-based study was carried out on 208 respondents using Ocular Surface Disease Index (OSDI) questionnaire, tear break-up time (TBUT), and Schirmer 1 test. Data analysis was done using Statistical Package for Social Science version 22.0 (SPSS Inc, Chicago, Illinois, USA). Results: The prevalence of OSD was higher in those on antiglaucoma medication using all modalities of assessment. Prevalence of OSD in glaucoma patients on antiglaucoma drugs was highest using TBUT- 69.2% (P = 0.031), with OSDI questionnaire it was 62.5% (P = 0.005), and it was lowest for Schirmer 1 test - 59.6%. For those nonglaucoma cases/not on any antiglaucoma medication, the prevalence using TBUT was 42.3%, using OSDI it was 16.3%, and with Schirmer 1 test it was 25.9%. Prevalence also increased with the increase in the number of eye drops from 1 to 2 drops/day using all modalities of assessment (P = 0.004). Using multivariate analysis, adjusting for sex and age, subjects who instilled 2 drops/day had four to five times the odds of having OSD. Conclusion: The prevalence of OSD is higher in patients with glaucoma on topical antiglaucoma medication than the nonglaucoma population studied and this increased with the increase in number of drops per day.

Keywords: Antiglaucoma medications, preservative, ocular surface disease

How to cite this article:
Abraham EG, Udofia IE. Prevalence of Ocular Surface Disease in Glaucoma Patients on Long-Term Antiglaucoma Medications. Niger J Ophthalmol 2021;29:28-33

How to cite this URL:
Abraham EG, Udofia IE. Prevalence of Ocular Surface Disease in Glaucoma Patients on Long-Term Antiglaucoma Medications. Niger J Ophthalmol [serial online] 2021 [cited 2022 Jan 22];29:28-33. Available from:

  Introduction Top

Glaucoma, the second leading cause of blindness globally, accounts for 8% of blindness among the 39 million blind people worldwide.[1] It can be treated with topical antiglaucoma medications, lasers, or surgery, for example trabeculectomy, and the treatment is aimed at reducing the intraocular pressure (IOP) which is the only modifiable risk factor for progressive optic nerve damage. Most topical antiglaucoma medications used in our environment contain the preservative benzalkonium chloride (BAK). This preservative inhibits microbial growth in the medication and thus minimizes the risk of ocular infection. The benefits of reducing the microbial contamination is counteracted by its side effects.[2] Preservatives are shown to be toxic to the ocular surface by decreasing the stability of the precorneal tear film,[3],[4] reducing the goblet cells density in the conjunctival epithelium, and increasing evaporation of tears by causing a detergent effect in the lipid layer of precorneal tear film.[5],[6]

A high prevalence of ocular surface disease (OSD) symptoms in patients treated for glaucoma with topical antiglaucoma has been observed in many studies. Barisic et al.[7] in a prospective, multicenter, observational study observed a 75% prevalence in the studied population. Fechtner et al.[8] concluded that OSD is prevalent among glaucoma patients who are medically treated and that the severity of OSD symptoms is positively correlated to the number of IOP-lowering medications used. The use of preservative-containing medications has been associated with the development or worsening of OSD.[3],[9]

The investigator observed during the course of the 3 months rural posting that many glaucoma patients on antiglaucoma medications presented with nonspecific complaints of ocular discomfort such as itching, tearing, sandy sensation, or dryness which either developed or worsened following commencement of antiglaucoma medications. These symptoms were a source of distress to the patients and in severe cases, added to their ocular morbidity. Even though there have been numerous studies on dry eye in our environment, there is a paucity of published studies on the effect of topical antiglaucoma drugs on the ocular surface in the study area.

The aim of this study is to determine the prevalence of OSD in glaucoma patients on long-term antiglaucoma medications using subjective methods (Ocular Surface Disease Index [OSDI] questionnaire) and objective methods (tear break-up time [TBUT] and Schirmer 1). The study will also look at the relationship between frequency of instillation of eye drop, the number of eye drops used, and OSD.

  Materials and Methods Top

The study was a hospital-based cross-sectional study evaluating the prevalence of OSD in glaucoma patients on long-term topical drugs and nonglaucoma patients not on any topical medication. All 208 eligible participants who met the inclusion criteria were consecutively recruited into the study during a routine clinic appointment. The inclusion criteria were: patients aged 18 years and above, male or female with a clinical diagnosis of primary open-angle glaucoma in one or both eyes who had been on one or more topical antiglaucoma medications for not less than 6 months before enrolment into the study. Additionally, subjects aged 18 years and above who had neither used any topical medication in the last 6 months nor were known glaucoma patients were included. Excluded were: those with a history of any ocular surgery including trabeculectomy, patients with dry eye disease, allergic conjunctivitis, atopy, or known diabetics. Also excluded were patients using contact lenses, presence of blepharitis, cicatrizing lid, or conjunctival disease. Uses of systemic medications that can alter tear film, for example diuretics, atropine, diazepam, antihistamines, and phenothiazines were the other exclusion criteria.

Study procedure

Eligible subjects were identified at each clinic visit and informed consent was obtained before enrolment into the study. Interviewer-administered pretested questionnaire which included sociodemographics, date first diagnosed with glaucoma (documented evidence of diagnosis by managing consultant obtained from patient’s records), date of commencement of topical antiglaucoma medication(s), name and number of medications used, the concentration and type of preservative in each of the topical medications. Primary open-angle glaucoma was diagnosed based on the presence of glaucomatous optic neuropathy in at least one eye with a corresponding visual field loss and gonioscopically open-angle of the anterior chamber with no identifiable cause of secondary glaucoma. IOP was not considered in the criteria for diagnosis in this study.

The questionnaires were pilot tested among 20 glaucoma patients on topical medications and two patients not using antiglaucoma medication selected from the University of Uyo Teaching Hospital which is about 15 km away from Mercy Eye Hospital, Abak (where the study was done). The patients recruited for the pilot were not included in the final analysis of the data collected in this study. The OSDI questionnaire was interviewer-administered to all participants selected for the study. For illiterate patients, the contents of the questionnaire were clearly explained in the patient’s language using an interpreter. OSDI score was interpreted as follows: zero to 10 (no symptoms), 11 to 15 (mild), 16 to 32 (moderate symptoms), and 33 to 100 (severe symptoms). Patients then had their TBUT done, followed by Schirmer 1 tests (in that order) measured by only one investigator.

Assessment of TBUT was done with the subject properly seated on the slit lamp, fluorescein impregnated paper strip was moistened with preservative free normal saline and the wet end gently applied to the inferior cul-de-sac, fisrt for the right eye, then the left. Care was taken not to induce reflex tearing in the process. The slit lamp biomicroscope was adjusted for diffuse illumination through a cobalt blue filter with magnification set at ×12. The patient was asked to look ahead and blink severally, then to stop. A stop watch (Samsung S4 phone) was used to count the number of seconds that elapsed between the last blink and the appearance of the first dry spot. The procedure was then repeated for the left eye.

In doing Schirmer 1 test (without anesthesia), subjects were well seated in a dimmed room and excess moisture from eyelid margin removed with cotton tipped applicator. A sterile filter paper (Whatman no. 41) was folded at the indentation mark and gently placed into the inferior fornix at the junction between the medial two-thirds and lateral third. Subjects were asked to keep eyes open and blink normally but were permitted to close eyes if they wanted but avoid squeezing. This was done for both eyes. The strips were removed after 5 minutes. The distance between the indentation mark and the farthest extent of wetting was measured.

Dry eye disease was assessed subjectively using an interviewer-administered OSDI questionnaire and objectively using the Schirmer 1 test and TBUT. TBUT average of two consecutive readings of ≤9 seconds or Schirmer 1 test reading of less than 10 mm were considered diagnostic.

Data Analysis

Data analysis was carried out with Statistical Package for Social Sciences program version 22.0 (SPSS Inc, Chicago, Illinois, USA). Only variables of the right eye, for convenience, were analyzed. For descriptive statistics, frequencies and percentages were used for categorical variables in univariate analyses. In bivariate analyses, Pearson’s chi-square test was used to test for significant relationship between variables. A P-value of <0.05 at 95% confidence interval was considered statistically significant. Multivariate logistic regression analysis was used to identify the association between the subject’s characteristics and OSD.

Ethical Consideration

Ethical approval was sought and obtained from the Research and Ethics committee of the National Eye Center, Kaduna. Permission was sought from the Administrator of Mercy Eye Hospital. This study conforms to Declaration of Helsinki. Written and verbal consent to participate in the research was obtained from the participants following an explanation of the purpose of the study and the procedures to be carried out. Participants with diagnosed dry eye disease were treated appropriately.

  Results Top

A total of 208 eligible participants were studied, 104 with glaucoma and 104 without glaucoma. The mean age for those using antiglaucoma medication was 64.1 ± 5.3 (range 33–79 years) while those without was 68.3 ± 11.7 (range 33–79 years) [Table 1]. There was no statistically significant age difference between the two groups and the male:female ratio was 1:1. BAK was the most common preservative in the antiglaucoma medications used by patients in this study.
Table 1 Age and sex distribution of study population

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The prevalence of OSD was higher in participants on antiglaucoma assessed using all the three methods (TBUT 69.2%, OSDI questionnaire 62.5%, and Schirmer 59.6%) compared to those who were not on any antiglaucoma medication (TBUT 42.3%, OSDI questionnaire 16.3%, and Schirmer 25.9%) [Table 2]. Furthermore, prevalence also increased with the increase in the number of drops from 1 to 2 drops/day using all modalities of assessment (P = 0.004) but an increase from 2 to 3 drops/day was not associated with an increasing prevalence of OSD using the Schirmer 1 test (P = 0.009) [Table 3]. With multivariate analysis adjusting for age and sex, subjects who instilled 2 drops/day had four to five times odds of having an OSD [Table 4]. The most commonly used topical antiglaucoma medication in this study was timolol (21.1%) either used singly or in combination with latanoprost (20.2%) and dorzolamide (15.4%). The least used medication was pilocarpine (3.8%) [Figure 1] and [Figure 2]. Sixteen subjects (15%) were on three medications, 49 subjects (47%) used two medications while 39 subjects (38%) used only one medication.
Table 2 Prevalence of OSD among participants

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Table 3 Prevalence of ocular surface disease by frequency of drug instillation in patients on long-term antiglaucoma drugs

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Table 4 Multivariate regression models for association between frequency of instillation of topical medication and OSD in patients on long-term antiglaucoma drugs

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Figure 1 Distribution of types of antiglaucoma medications used by subjects on long-term antiglaucoma medication. For all the types of antiglaucoma medications used by patients in this study, benzalkonium chloride was the preservative used. The most commonly used topical antiglaucoma medication in this study was timolol (21.1%) either used singly or in combination with latanoprost (20.19%) and dorzolamide (15.3%). The least used medication was pilocarpine (3.8%). Source: Original.

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Figure 2 Distribution of number of topical antiglaucoma medications used by subjects on antiglaucoma medications. Sixteen subjects (15%) were on three medications, 49 subjects (47%) used two medications while 39 subjects (38%) used only one medication of which a majority was timolol followed by latanoprost. Source: Original.

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  Discussion Top

All the three parameters showed higher prevalence of OSD among the glaucoma cases (69.2%, 59.6%, and 62.5%) as against (42.3%, 25.9%, and 16.3%) of those who were not using any antiglaucoma drugs using TBUT, Schirmer 1, and OSDI and this was statistically significant (P = 0.031, P = 0.009, and P = 0.005, respectively). This corroborates earlier studies by Barisic et al.[7] in a multicenter study, Pai[10] and Sarimiye et al.[11] in Ibadan, Nigeria. The prevalence of OSD in subjects on topical antiglaucoma medications varied according to the modality of test used to assess OSD. Results from this survey showed a high prevalence of OSD of 59% using OSDI, 61% using Schirmer 1, and 78% using TBUT tests. Similar findings were observed from the study in the USA by Leung et al.[11] who reported a frequency of 59% using OSDI but higher values 75% (using OSDI) was obtained by Barisic et al.[7] The difference could be because Gracia-Fejioo et al.[14] carried out a multicentre study involving four different hospitals across two different countries with different ethnic groups but this study was done in one location involving the same nationals. Also, the patients had a higher age range 37 to 92 years compared to this study. The mean age of participants in this study was 64.1 ± 5.3 and 68.3 ± 11.7 [Table 1]. Studies by Leung et al.[12] and Gracia-Fejioo et al.[14] which also evaluated OSD in glaucoma patients reported similar findings. Other studies have also demonstrated an increase in the prevalence of glaucoma and OSD with increasing age.[15],[16] A multicentre study reported a higher mean age of 72 years.[7] Population-based prevalence studies have reported a lower prevalence of OSD than clinic-based studies probably because they also include subjects who do not have glaucoma.[13],[14],[17] When comparing the different modalities of assessing OSD, the prevalence was highest using TBUT as corroborated by earlier studies.[12] TBUT evaluates abnormality in the quality of tears while OSDI is a subjective test that evaluates symptoms. It is possible that subjects may have tear film instability and alterations in ocular surface (measured by TBUT) ongoing, long before becoming symptomatic. Also, results of Schirmer 1 test have been shown to have high variability and low sensitivity in detecting OSD than TBUT.[18],[19] The prevalence of OSD increased significantly with an increase in the number of daily drops of antiglaucoma medications. This was statistically significant for TBUT and Schirmer 1 tests. The prevalence of OSD in subjects instilling 2 drops/day was three times higher than subjects on 1 drop/day regimen using TBUT and OSDI, and two times higher using Schirmer 1 test. There was a further increase with subjects using ≥3 drops/day using TBUT. However, with Schirmer 1 and OSDI, there was no increase in the prevalence of OSD with an increment to ≥3 drops. Multivariate logistic regression models showed the association between frequency of daily drug instillation and the prevalence of OSD to be statistically significant. Subjects on 2 drops/day had four and five times higher odds (TBUT and OSDI, respectively) of having symptomatic OSD when compared to subjects on 1 drop/day. The odds increased by 14 times (OSDI) with subjects using 3 drops/day. The findings of this study corroborate earlier findings[12],[13],[14] which revealed an increase in OSD symptoms with an increasing number of drops applied. Most of the subjects (those who came with their drugs to the clinic) in this study were using benzalkonium-preserved topical antiglaucoma medications. The results from this study are believed to be related to the preservative component of the antiglaucoma medication used by the subjects.

Topical medications containing preservatives (especially BAK) have been implicated in causing OSD in patients in some studies[20],[21] compared to the less toxic preservatives.[22],[23] It could also be deduced that the high prevalence of OSD seen in this study may have resulted from the role of the active ingredient. Timolol has been associated with reduced goblet cell density, and tear production,[24],[25] while prostaglandin analogs have been demonstrated to cause inflammatory damage and toxicity to the ocular surface.[26],[27] Majority of the glaucoma patients in this study were on Timolol and prostaglandin analogs.

  Conclusion Top

This study has shown that patients on topical antiglaucoma medication have a higher prevalence of OSD than nonglaucoma patients who are not on any antiglaucoma medications and this was strongly related to the number of drops instilled. We recommended that all glaucoma patients should have detailed OSD assessment as part of routine follow-up evaluation and preservative-free antiglaucoma drugs should be used; where more than one drug is required, a fixed drug combination is advocated as this will reduce the number of drops needed.

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Conflicts of interest

The authors report no conflicts of interest.

  References Top

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  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3], [Table 4]


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