Effect of Chronic Anti-glaucoma Medications and Trabeculectomy on Tear Osmolarity

S-Y Lee; T T Wong; J Chua; C Boo; Y F Soh; L Tong


Eye. 2013;27(10):1142-1150. 

In This Article

Abstract and Introduction


Purpose To evaluate the tear film osmolarity (TFO) and ocular surface clinical signs and symptoms in chronically medicated glaucoma patients and post-trabeculectomy patients.

Methods This is a single-center, prospective case-controlled study. One-hundred and thirty eyes of 130 participants aged ≥45 years were included (49 normal controls, 50 glaucoma patients on chronic preserved anti-glaucoma medication ≥6 months, and 31 post-trabeculectomy patients not on medication ≥6 months). TFO, tear break-up time (TBUT), Schirmer's test I and dry eye symptoms were evaluated. Data from both groups of glaucoma patients were compared with age and sex-matched controls. Logistic regression was performed to calculate the odds ratios.

Results Mean TFO in the three groups were 301.4±7.7, 307.0±9.3, and 307.4±11.6 mOsm/l, respectively. Compared with normal controls, chronically medicated glaucoma patients and post-trabeculectomy patients were more likely to have a raised TFO, with odds ratios (95% CI) of 4.43 (1.74–11.32) and 2.76 (1.02–7.94), respectively. Both groups of glaucoma patients were also more likely to experience dry eye symptoms, with ORs of 4.72 (1.92–11.59) and 4.24 (1.54–11.72). There was no significant difference in TFO and symptoms between both groups of glaucoma patients, and in TBUT and Schirmer's test across all three groups.

Conclusions Patients on chronic topical anti-glaucoma medication and post-trabeculectomy patients were more likely to have raised TFO and dry eye symptoms, suggesting significant ocular surface disease. Glaucoma practitioners should be aware that dry eye symptoms and raised TFO may occur in the absence of TBUT and Schirmer's test abnormality.


Glaucoma is a major cause of blindness worldwide, second only to cataract.[1,2] The estimated prevalence of 0.8–7.0% globally[3,4,5,6] is predicted to increase by up to 50% by the year 2020,[2] with 11.2 million of these patients projected to suffer from bilateral blindness.[2] Treatment for glaucoma is usually targeted at reducing the intraocular pressure (IOP), which, when increased, is the main cause of irreversible optic nerve damage. This is usually achieved by topical medications.[7]

Unfortunately, ocular surface disease (OSD) is common in patients chronically treated for glaucoma.[8] One of the reasons for this adverse effect is the presence of preservatives in the medication. The detrimental effects on the ocular surface could even decrease quality of life.[9,10] These preservatives, the most common being benzalkonium chloride (BAK), inhibit microbial growth in the medication and minimize the risk of ocular infection. In the form of cationic surfactants, preservatives cause microbial cell destruction by disrupting the cell membrane lipids and cytoplasmic contents.[11] The lipid-destruction properties in BAK extend to the lipids in the tear film, which solubilizes during interaction with BAK.[12] Tear lipids are responsible for the stabilization and evaporation control of the tear film. Its disturbance is a major cause of dry eye[13] —a common condition among patients being treated for glaucoma.[14] The International Dry Eye Workshop has classified the use of anti-glaucoma medication as an extrinsic cause of evaporative dry eye.[13]

Surgical intervention is warranted when topical medications are inadequate in achieving the target IOP (eg, in advanced glaucoma), or there are significant contraindications for medication use (eg, medical side effects such as arrhythmia or allergic response).[7] The current first line surgical procedure for glaucoma treatment is trabeculectomy with antimetabolites. After trabeculectomy, approximately 40% patients no longer require the use of anti-glaucoma medication.[15] The prospect of anti-glaucoma medication cessation after surgery may be an advantageous outcome because the eye will no longer be subjected to the side effects of the contained preservatives. It is not known if the dry eye effect induced by previously instilled preservative containing medications can be reversed after their cessation. On the other hand, trabeculectomy has been suggested to have deleterious effects on the ocular surface, for example, conjunctival epithelial spongiosis and reduced number of conjunctival goblet cells.[16]

Previous researchers have analyzed the tear function in patients using topical anti-glaucoma medications. Tear break-up time (TBUT) and Schirmer's test are examples of the common tests used. Another parameter that can be used to evaluate dry eye is tear film osmolarity (TFO). Measurements of TFO have been demonstrated to be suitable, and even superior to other forms of tests, in terms of dry eye diagnosis.[17,18,19] Sullivan et al.[20] found that TFO measurements are the best indication of dry eye severity, with a correlation coefficient of 0.55, as compared with other clinical tests.

In dry eye patients, TFO is increased. This moreover causes osmolarity of the ocular surface epithelial cells to elevate. The hyperosmolarity of the cells prompts the production of a cascade of proinflammatory cytokines.[21] Conjunctival hyperemia, superficial punctate keratitis and symptoms of ocular discomfort are just a few of the clinical manifestations of tear cytokine upregulation.[21] In patients topically medicated for glaucoma, TFO have been demonstrated to be elevated compared with normal values.[22,23] However, the previous studies did not compare these TFO values to a group of normal patients as controls. Januleviciene et al[23] evaluated the change in TFO as patients switched from preserved anti-glaucoma medications to its preservative-free variants, whereas Labbe et al[22] did a cross-sectional study to evaluate the effect of preserved topical anti-glaucoma medications on TFO.

Despite the numerous studies conducted on anti-glaucoma medication and OSD, the tear function test (TBUT and Schirmer's test) profiles of these patients have not been well reported. The far majority of studies only reported symptoms[24] or the tear function tests with preset thresholds.[22,25,26] Another study reported that only 4.8% and 33.8% of patients on anti-glaucoma medications had TBUT and Schirmer's test values of >10 s and >10 mm, respectively, as compared with a healthy population of 100% above these thresholds.[27]

We hypothesize that TFO may be raised in glaucoma patients, both on topical therapy and post trabeculectomy, compared with normal controls. This study is therefore aimed to compare TFO in chronically medicated glaucoma patients and post-trabeculectomy patients to controls without glaucoma or dry eyes.

As a secondary aim, we will compare clinical tear function tests between glaucoma patients and controls and explore the relationships between these dry eye test results and glaucoma treatment variables (ie, duration and number of topical anti-glaucoma medications).