The results in our study demonstrate that the glaucomatous population treated with topical medication show significantly increased OSD signs and symptoms compared to non-glaucomatous population. These findings are consistent with previous studies that have showed association between glaucoma medication and OSD [8, 21–22]. Furthermore, a long-term exposure to glaucoma eye drops has been associated with changes in the ocular surface, conjunctiva, and trabecular meshwork [23–25]. During the recent years, special attention has been paid on the role of preservatives in glaucoma eye drops. Preserved topical glaucoma medication has been shown to cause OSD signs and symptoms, whereas preservative-free medications have showed significantly less ocular toxicity [7, 9, 13, 23, 26]. In the presence study, we found similar relation to preservative-free compounds.
BAC is the most used preservative in ocular drugs. It is effectively penetrating to the eye tissues and has long-term effects on them [16]. In addition to its effects on the ocular surface that causes ocular signs and symptoms, the use of BAC-containing drugs has been directly linked to the failure of glaucoma surgery [17–19]. A recent glaucoma guideline recommends the use of preservative-free medication in patients suffering from OSD [27].
According to glaucoma guidelines, monotherapy is the preferred type of medication in glaucoma care. In our study, 42.7% of all glaucoma patients were using only one active compound. More than half of the glaucoma patients were using combined medications with multiple active compounds and daily eye drops. Furthermore, European Glaucoma Society Guidelines recommend the maximum use of three active compounds and three–four eye drops per day [27]. In our study, 2.5% of the glaucoma patients had more than three active compounds in their medication and 20.7% used more than four eye drops per day. Similar reports have been shown previously [28–29]. In this respect, it is important to recognize that the increasing number of active compounds and administered eye drops per day is associated with increasing severity of OSD signs, as shown in this study.
Most of the glaucoma patients in this study suffered from the symptoms of OSD. This was most significant in those who were medicated with three active compounds (fixed combination with beta-blocker and other (than prostaglandin) plus prostaglandin) or combinations with brimonidine. The symptoms of dry eye correlated with the increasing number of active compounds and/or eye drops of the used medication.
The strengths of this study include the robust, prospective nature of it. All data was obtained collectively from private clinics outpatients. Study subjects that were willing to participate in the study were enrolled consecutively at each center avoiding selection bias. As the study was multicenter-based with a large number of patients, the study represents well private clinics, where a significant proportion of glaucoma patients are treated by private ophthalmologists in Finland. To our knowledge, this is the first study to do so with standardized methods that include reference images for the OSD signs and a single, independent study nurse with a fixed protocol regarding the OSD symptom questionnaire.
Our study has also some limitations. Although this study was prospective, it was blinded only for recording the OSD symptoms by a single, independent study nurse. The study was cross-sectional and assessed only patients attending private ophthalmologist clinics in Finland. Therefore, even though these results can represent outpatient patient in general, they cannot be directly compared to those obtained from public eye hospitals.
Our results demonstrate that multi-therapy is common among glaucoma outpatients. Also, the prevalence of OSD signs and symptoms among these patients is related to the number of active compounds and administered eye drops per day. There are significant differences between glaucoma medications. Beta-blockers and preservative-free prostaglandin show the least effect on both ocular signs and symptoms. Therefore, BAC likely contributes to the ocular surface problems. These findings suggest that the use of preservative-free glaucoma medication is highly recommended. Special attention should be paid on patients having OSD signs and symptoms on what type of medicine is prescript, and in case of multi-therapy, to select laser or surgical treatment instead of increasing topical medication.