Abstract
Objective
Halting and reversing glaucoma therapy-related ocular surface disease (GTR-OSD) will improve the success of long-term medical therapy, impacting millions of patients worldwide.
Methods
A single-centre, masked, prospective, placebo-controlled, crossover trial of 41 well-controlled open-angle glaucoma subjects with moderate to severe GTR-OSD on preserved latanoprost and dorzolamide/timolol fixed combination (DTFC) therapy was conducted. Subjects were randomized to preservative-free (PF) tafluprost and DTFC with either placebo or cyclosporine 0.1% drops for 6 months and were then crossed over to the opposite therapy. Oxford score of ocular staining was the primary outcome; osmolarity, matrix-metalloproteinase-9 (MMP-9) testing, tear film break-up time (TFBUT), meibomian gland dysfunction (MGD), punctum evaluation, adverse events and diurnal intraocular pressure (IOP) comprised secondary outcomes.
Results
GTR-OSD findings improved with PF therapy. At 6 months the triple PF with placebo group showed improvement compared to baseline in mean Oxford score (mean difference [MD]:−3.76; 95% confidence interval [CI]:−4.74 to −2.77; p < 0.001), osmolarity (MD:−21.93; 95%CI:−27.61 to −16.24 mOsm/l; p < 0.001), punctum stenosis (p = 0.008) and conjunctival hyperaemia (p < 0.001). Similar improvements occurred in the cyclosporine enhanced period, which also provided greater improvement in MMP-9 positivity (24 vs 66%; p < 0.001) and TFBUT (p = 0.022). The cyclosporine group was superior vs placebo in mean Oxford score (MD:−0.78; 95%CI:−1.40 to −0.15); p < 0.001), itchiness and objective adverse events (p = 0.034). Cyclosporine elicited more stinging vs placebo (63 vs 24%; p < 0.001). Both PF regimens reduced mean diurnal IOP more than preserved therapy (14.7 vs 15.9 mmHg; p < 0.001).
Conclusions
Changing from preserved to PF glaucoma medications improves ocular surface health and IOP control. Topical cyclosporine 0.1% further reverses GTR-OSD.
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Data availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
The authors would like to thank all medical staff of the 1st University Department of Ophthalmology and the patients who participated in this study.
Funding
This study was supported in part by Santen. The sponsor had no involvement in the design of the trial, the analysis or interpretation of results, or the publication of the paper.
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AGK and KGB contributed to the conception of the study, the examination of patients, and the preparation of the manuscript. GPA, ICV and EP contributed to the examination of patients and drafting parts of the manuscript. ABH contributed to the conception of the study, the statistical analysis and the preparation of the manuscript. AK contributed to the interpretation of results and the preparation of the manuscript. LJK contributed to the conception of the study, the interpretation of results and the preparation of the manuscript. All authors approved the submitted version of the manuscript and agree to be accountable for all aspects of the work.
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Competing interests
AGK: Research funding from Allergan, Bayer, Omni Vision, Pharmaten and Santen; travel support and congress expenses from Vianex and Zwitter; honoraria from Allergan, Esteve Pharmaceuticals, Santen and Vianex. KGB: Honoraria from Laboratoires Théa, Bausch & Lomb, Santen and Novartis. GPA, ABH, ICV and EP: No conflicts of interest. AK: Honoraria and congress expenses from Cooper SA, Santen, Vianex, Zwitter; research funding from Laboratoires Théa. LJK: Grants and research support from Allergan, Diopsys, Heidelberg Engineering, Alcon, Zeiss, Olleyes; consultant/advisory board: Olleyes (stock options); honoraria from Allergan, Glaukos, Bausch & Lomb; Stock shareholder: Glaukos, Mati Therapeutics, Aerie, Olleyes; employment (salary): Glaukos (Chief Medical Officer).
Ethics approval
The research protocol was approved by the Institutional Review Board of the Medical School of Aristotle University and was registered with ClinicalTrials.gov (NCT04673604). The study was conducted in accordance with the tenets of the Declaration of Helsinki.
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Konstas, AG., Boboridis, K.G., Athanasopoulos, G.P. et al. Changing from preserved, to preservative-free cyclosporine 0.1% enhanced triple glaucoma therapy: impact on ocular surface disease—a randomized controlled trial. Eye 37, 3666–3674 (2023). https://doi.org/10.1038/s41433-023-02578-w
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DOI: https://doi.org/10.1038/s41433-023-02578-w