Do antiglaucoma drugs induce inflammation and irritation on the eye surface? Results of a 2-year randomized study

Methodology and Study Progress

This prospective randomized controlled study conducted at a university hospital in Nottingham, UK, included 36 previously untreated adult patients with glaucoma or elevated intraocular pressure (IOP). At study entry, patients could not have any eye surface diseases (other than dry eye syndrome or blepharitis) and were not allowed to use any other eye drops except artificial tears during the study.

Patients were randomized into 3 groups of 12 subjects each based on the treatment regimen:

1. latanoprost 0.005% preservative-free (PF)
2. travoprost 0.004% with polyquadium chloride (PQ) preservative
3. bimatoprost 0.01% with benzalkonium chloride (BAK) preservative

Before starting the treatment and subsequently after 1, 3, 6, 12, and 24 months of use, patients filled out the OSDI (Ocular Surface Disease Index) questionnaire to evaluate dry eye syndrome symptoms in the past week. Conjunctival impression cytology and tear film sample analysis were performed to determine the profile (mRNA expression, proteins) of inflammatory cytokines (IL-6, IL-8, IL-10, IL-12A, IL-12B, IL-17A, IL-1β, TNF-α). If the reduction in IOP was insufficient, additional drops with the same preservative were added, and artificial tears were used if necessary.

Results

The baseline profile of inflammatory cytokines and OSDI scores were comparable for all patients. A reduction in IOP was evident in all patients after 24 months of treatment. According to the OSDI questionnaires, irritation and dry eye syndrome were primarily experienced by patients using bimatoprost with benzalkonium chloride.

A significant increase in the expression of mRNA and proteins IL-6, IL-8, and IL-1β was observed only in patients using bimatoprost with BAK preservative. This was evident after 3 months and persisted even after 2 years of use. No significant increase was detected in other cytokines. In this group, a correlation was observed between the OSDI scores and the expression of mRNA IL-1β (r = 0.832; R² = 0.692; p = 0.040) and IL-10 (r = 0.925; R² = 0.856; p = 0.008), as well as IL-1β protein (r = 0.899; R² = 0.808; p = 0.014).

Discussion and Conclusion

Preservatives (especially benzalkonium chloride) in eye drops can cause irritation and chronic sterile inflammation of the eye surface, even after 3 months of treatment. In patients using preservative-free antiglaucoma drugs or those containing polyquadium chloride, inflammatory cytokines in the tear film and conjunctival epithelium were not significantly elevated. These patients also did not report dry eye syndrome. However, long-term use of eye drops containing PQ might induce late subclinical inflammation.

The study is limited by the relatively small number of participants. The pro-inflammatory effect could theoretically also be caused by bimatoprost itself. Therefore, larger clinical studies comparing the effects of latanoprost, travoprost, and bimatoprost with and without preservatives are desirable in the future.

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Source: Mohammed I., Kulkarni B., Faraj L. A. et al. Profiling ocular surface responses to preserved and non-preserved topical glaucoma medications: a 2-year randomised evaluation study. Clin Exp Ophthalmol 2020 Sep; 48 (7): 973−982, doi: 10.1111/ceo.13814.