In this study we have observed a high prevalence of OSD symptoms in patients treated for glaucoma -3/4 (75%) of glaucoma patients on hypotensive medications have symptoms of OSD. Of those, 17% had scores in accordance with mild OSD, 11% with moderate OSD and 47% with severe OSD. Our results show that glaucoma patients were twice as likely to experience OSD symptoms, compared to control group without glaucoma. Local antiglaucoma therapy, which patients use every day for many years, may compromise the ocular surface. The impact of OSD on quality of life is best shown by the utility study performed by Schiffman et al. [14
] who demonstrated how patients viewed their dry eye disease in terms of quality of life compared with angina pectoris. The study found that patients with severe OSD were in the same range in terms of quality of life as those with severe angina. The impact of OSD on visual function is also important. Miljanovic et al. [15
] showed that crucial daily activities of modern living such as reading, computer use, professional work, driving and watching television are all negatively impacted by OSD.
In this multicentre study 110 glaucoma patients and 50 control subjects completed the OSDI survey. The OSDI is a valid and reliable instrument for measuring the severity of dry eye disease, and it possesses the necessary psychometric properties to be used as an end point in clinical trials as proved by several clinical studies [10
Fechtner et al. [8
] also used OSDI to describe the prevalence of OSD among glaucoma treated patients. In their study which enrolled 630 glaucoma patients, 48.4% of the patients reported mild to severe symptoms which is significantly less compared to our results in which 3/4 of glaucoma patients had mild to severe OSD (47% with severe OSD). The higher prevalence of OSD in our study may have several explanations. This difference could be explained by the differences in the selection of patients (more severe disease, differences in age, duration of therapy and the type and number of medications used). Patients enrolled in this study are all treated in the specialized glaucoma departments for severe form of disease and most of them have used multiple antiglaucoma eye drops for a long time period (70,4% patients were treated for more than 7 years).
Previous studies are showing a strong correlation between the number of IOP-lowering medications used and the presence of dry eye [8
]. Study by Rossi et al. [16
] described the prevalence of OSD and they wanted to assess quality of life in subjects with glaucoma. In this study 40% of patients using 2 or 3 antiglaucoma medications had symptoms of OSD, which is in line with our findings. Patients on a single medication had the lowest median of OSDI score followed by patients on 2 medications and the highest median was on 3 or more medications. This difference was significant (P=0.048) (Figure 3).
In an international study published by Garcia-Feijoo et al. [18
], patients who had a glaucoma diagnosis of less than 6 years had a mean OSDI score of 18 units, which is indicative of mild OSD, while patients who had a glaucoma diagnosis of 6 years or longer had a mean OSDI score that was significantly worse (P=0.03), indicating moderate OSD. This is in accordance with our findings where OSDI score increases with the duration of glaucoma disease and glaucoma therapy (P=0.042) (Figure 4).
Figure 4 also shows that OSDI score tend to slightly fallin patients that are on therapy for >10 years. This can be explained by another factor that may complicate the assessment of OSD using OSDI and it is corneal hypoesthesia. Corneal sensitivity tends to decrease with age but it is also a consequence of long-term effect of preservative-containing antiglaucoma eye drops on corneal surface [19
]. The chronic patients have less innervation of the ocular surface and as a consequence experience less pain and discomfort which can result in slightly better OSDI score.
We found that the OSD symptoms have been reported in 30% of the normal subjects and in up to 75% of glaucoma subjects. Gosh et al. [21
] has also found similar results. A significant increase in the prevalence of OSD signs was observed in the glaucoma population, 70.3%, compared to controls, 33% [21
]. Studies have demonstrated the possibility that interaction between glaucoma and OSD syndrome increases because of topical ocular medications [5
]. Once applied, any topical medication exerts toxicity on ocular surface from the active compound. The majority of medications used by our patients have varying concentrations of benzalkonium chloride (BAK). Even in low concentrations BAK can trigger apoptosis in human corneal and conjunctival epithelial cells and it can cause chronic stromal inflammation [23
]. As a detergent, it disrupts the tear film after only a single drop [26
] and with the chronic use decreases the density of goblet cells in the conjunctival epithelium [27
] which are producing mucous layer of the tear film. In addition, it has a detergent effect on corneal barrier function by breaking down the intercellular adhesion which makes the tear film unstable and unable to maintain the healthy ocular surface [28
]. When patients are using multiple medications there is a cumulative effect of BAK which may explain our finding that OSDI scores increased with the number of IOP-lowering medications used. Leung et al. reported that the use of more BAK-containing eye drops was significantly associated with higher prevalence of abnormal results in lissamine green test [9
]. Another study evaluated the efficacy, safety and tolerability of changing to travoprost BAK-free from prior prostaglandin therapy in 691 patients with primary open-angle glaucoma or ocular hypertension. All patients were switched from latanoprost or bimatoprost to BAK-free travoprost for 12 weeks. OSD scores improved from severe to moderate, from moderate to mild and from mild to normal. There was also significant decrease in hyperemia with travoprost BAK-free and equal or better IOP control. As for patient preference, 72% of patients preferred travoprost without BAK [29
]. Those results agree with study of Pisella et al. [30
] who showed that symptoms and signs of OSD are more prevalent in glaucoma patients using preservative –containing eyedrops compared with patients using preservative -free eyedrops.
Our study included patients form four different Departments in Croatia and Bosnia and Herzegovina in order to avoid selection biases and have the representative sample for our region. To our knowledge this is the first study that established the prevalence of OSD in glaucoma patients using topical IOP therapy in our region. The identical results were reported in different regions of Croatia and Bosnia and Herzegovina in spite of climate and demographic differences (inland and Mediterranean parts). We wanted to compare our results on OSDI score in patients treated for open-angle glaucoma with the published studies from other regions.
Our study has some limitations. Although OSDI questionnaire is written in Croatian, questions 6-9 that concerne visual symptomatology are not objective because patient cannot see because of other ocular pathology, other than OSD symptoms. The OSDI questionnaire is a subjective tool and it would be useful to have an objective clinical test to assess the ocular surface, although the correlation between OSDI scores and severity of clinical presentation has been reported to be poor [9
]. Furthermore we have not evaluated the relationship between the type of medication used with OSDI score. Many patients used different types of medications for different periods of time, or were switched from one to another or to multiple medications. Considering this it was difficult to evaluate the relationship between the type of the medication and OSDI score. The most frequent complaints of glaucoma patients using hypotensive therapy in our sample were sensitivity to light, poor vision and discomfort in windy conditions. In conclusion, despite its various limitations, this study shows that OSD is a very serious problem in patients treated for glaucoma. Three quarters of glaucoma patients on hypotensive medications in Croatia and Bosnia and Herzegovina have symptoms of OSD. Severity of symptoms correlated with the number of IOP medications used and duration of hypotensive therapy.
The adverse effects of antiglaucoma medications can influence compliance, success of treatment and can ultimately greatly influence the quality of life of the glaucoma patients. We can provide a better ocular surface for our patients by recommending to avoid environmental circumstances such as dry air, long working hours in front of computer and by switching from BAK preserved medication to a medication with a smaller percentage of BAK, or BAK free. To verify the beneficial influence of BAC free agents on OSD, further studies that would include comparison of BAK and BAK free agents are needed.