Profiling ocular surface responses to preserved and non‐preserved topical glaucoma medications: a two‐year randomised evaluation study

Mohammed, Imran; Kulkarni, Bina; Faraj, Lana A.; Abbas, Ali; Dua, Harminder S.; King, Anthony J.

Abstract

Background
Use of topical glaucoma medications has been reported to cause ocular surface (OS) discomfort and inflammation. This study explores the profile of inflammatory cytokines and OS symptoms induced in response to preserved and non‐preserved drops.

Methods
Prospective, randomized evaluation on thirty‐six treatment‐naïve patients over 24 months of three differently preserved glaucoma drop preparations: Preservative‐free (PF), Polyquad (PQ), and Benzalkonium chloride (BAK). Study participants were evaluated at baseline and then at 1, 3, 6, 12 and 24 months whilst on medication. At each visit, participants completed the Ocular Surface disease index (OSDI) questionnaire, had basal tear sampling and impression cytology (IC) of the conjunctival epithelium. Quantitative polymerase chain reaction was performed to measure the gene expression of inflammatory cytokines (Interleukin (IL)‐6, IL‐8, IL‐10, IL‐12A, IL‐12B, IL‐17A, IL‐1β, and tumour necrosis factor (TNF)‐α) in the IC samples. Corresponding protein expression of cytokines in tear samples was assessed by the Becton‐Dickinson cytometric bead arrays.

Results
Compared to PF and PQ groups, mRNA and protein expression of IL‐6, IL‐8, and IL‐1β increased in samples from the BAK group in a time‐dependent fashion, whereas all other cytokines showed a non‐significant increase. In the BAK group, there was a strong correlation between OSDI and the levels of IC/IL‐1β (r=0.832, R squared=0.692 and p=0.040 ); IC/IL‐10 (r=0.925, R squared=0.856 and p=0.008) and tear/IL‐1β (r=0.899, R squared=0.808 and p=0.014 ).

Conclusion
BAK‐preserved topical drops stimulate a sterile inflammatory response on the OS within 3‐months which is maintained thereafter. Whereas PF‐drops and PQ‐preserved drops showed no significant OS inflammation.

Citation

Mohammed, I., Kulkarni, B., Faraj, L. A., Abbas, A., Dua, H. S., & King, A. J. (2020). Profiling ocular surface responses to preserved and non‐preserved topical glaucoma medications: a two‐year randomised evaluation study. Clinical and Experimental Ophthalmology, 48(7), 973-982. https://doi.org/10.1111/ceo.13814

• Journal Article Type: Article
• Acceptance Date: Jun 18, 2020
• Online Publication Date: Jun 21, 2020
• Publication Date: 2020-09
• Deposit Date: Jul 21, 2020
• Publicly Available Date: Jun 22, 2021
• Journal: Clinical & Experimental Ophthalmology
• Print ISSN: 1442-6404
• Electronic ISSN: 1442-9071
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 48
• Issue: 7
• Pages: 973-982
• DOI: https://doi.org/10.1111/ceo.13814
• Keywords: Ophthalmology
• Public URL: https://nottingham-repository.worktribe.com/output/4781015
• Publisher URL: https://onlinelibrary.wiley.com/doi/abs/10.1111/ceo.13814
• Additional Information: This is the peer reviewed version of the following article: Mohammed, I., Kulkarni, B., Faraj, L.A., Abbas, A., Dua, H.S. and King, A.J. (2020), Profiling ocular surface responses to preserved and non‐preserved topical glaucoma medications: a two‐year randomised evaluation study. Clin Experiment Ophthalmol., which has been published in final form at https://onlinelibrary.wiley.com/doi/abs/10.1111/ceo.13814 . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions