Comparison of the clinical effects of two different doses (0.05% and 0.1%) of topical cyclosporine A in dry eyes with meibomian gland dysfunction

Objective: To compare the clinical efficacy of two different doses of topical cyclosporine A used in addition to artificial tears in the treatment of patients with meibomian dysfunction and secondary dry eye. Methods: Fifty patients aged 18 to 40 years, who presented to our clinic between June 2020 and June 2021 were included in our study. Patients were divided into two groups as Group A (topical cyclosporine A 0.05%)


INTRODUCTION
Dry eye is becoming more and more common around the world due to the rapid evaporation of tears from increased exposure to digital screens and other causes. Dry eye syndrome, a multifactorial disease of the ocular surface that can cause eye discomfort and visual impairment, may occur as a result of lack of aqueous tears or impaired evaporation of tears. (1,2) The most common cause of tear evaporation disorder is meibomian gland dysfunction (MGD), which results in the instability of the tear film layer, increased tear evaporation, and dry eye disease. The meibomian glands, located in the tarsal plate of the upper and lower eyelids, are responsible for the formation of the lipid component of the tear film layer. (3,4) The diagnosis of MGD is made by determining the symptoms of patients with questionnaires, biomicroscopic examination of lid morphology and ocular surface, measurement of tear osmolarity, measurement of tear secretion, staining of the ocular surface, and determination of tear film stability using tear break-up time (TBUT). (5) In the treatment of MGD, hot compress, lid cleaning, and drop therapy are recommended. Artificial tears are primarily used in the treatment of dry eye, (6) but this is not sufficient in most patients; therefore, topical cyclosporine A is additionally applied. Topical cyclosporin A reduces T-cell mediated inflammation of the lacrimal tissue, resulting in an increase in the number of goblet cells and reversal of the squamous metaplasia of the conjunctiva. Currently, two different topical doses of cyclosporine A are used in therapy: 0.05% and 0.1%. (7) In this study, we aimed to compare the clinical efficacy of two different doses of topical cyclosporine A used in addition to artificial tears in the treatment of patients with MGD and secondary dry eye based on the Ocular Surface Disease Index (OSDI) and TBUT test results.

METHODS
The study was designed as observational at the Department of Ophthalmology of Erzincan Binali Yildirim University Faculty of Medicine. Ethical approval was obtained from the local ethics committee, and the principles of the Declaration of Helsinki were adhered to throughout the study (decision no: 10/05). Signed consent was not required for participation because the study involved only observation of clinical practice, and no patient identifying data were collected.
Fifty patients aged 18 to 40 years, who presented to our clinic between June 2020 and June 2021 with chronic blepharitis and related MGD and had no ocular or systemic disease other than meibomitis were included in our study. At the time of admission, all the patients underwent a detailed ophthalmological examination and basal OSDI and TBUT tests.
Ocular Surface Disease Index, a 12-item questionnaire, was used to determine the patient's complaints about dry eye within the last two weeks. The results were evaluated on a scale of zero to one hundred, and a higher score was interpreted to indicate greater severity of dry eye. (8) Tear break-up time was measured in seconds by applying fluorescein paper to the lower fornix without anesthesia.
In addition to artificial tears, 25 patients were started on topical cyclosporine A 0.05% (Depores, DEVA, Turkey) twice a day and constituted Group A. Other 25 patients who were given topical cyclosporine A 0.1% (Depores X, DEVA, Turkey) once a day and were evaluated as Group B. Routine ophthalmological examinations were performed at the first-and third-month controls in both groups, and the OSDI and tear break-up time tests were repeated.
The Statistical Package for the Social Sciences (SPSS, IBM), version 23, was used for the statistical analyses. The normality of the distribution of continuous variables was determined with the Kolmogorov-Smirnov test. Descriptive statistics for continuous variables were expressed as mean ± standard deviation values with ranges or medians (25 th -75 th percentile), where applicable. Categorical data were expressed as the number and percentage of cases. The independent t-test and analysis of variance (ANOVA) were used as parametric tests to compare normally distributed data. Post-hoc multiple comparisons were adjusted using the Bonferroni correction. The Mann Whitney-U test was used as a non-parametric method. The repeated-measures ANOVA was used to analyze the repeating data, and the Friedman variance analysis was conducted when the data were not normally distributed. Differences were considered significant at p≤0.05.

DISCUSSION
The aim of the study was to evaluate the effects of two doses of cyclosporine A eye drops in patients with dry eye, which has an increasing incidence across the world. Many studies have shown that dry eye is an inflammatory disease that has many features in common with autoimmune disorders. (9) In recent studies, treatment with cyclosporine A 0.05% eyedrops twice a day have been shown to improve dry eye symptoms and reduce the use of artificial tears. (10)(11)(12)(13) In our study, we compared cyclosporine A 0.05% and 0.1% eyedrops and found that dry eye symptoms improved in both groups, with no significant difference between the two doses.
In the current study, improvement in the tear function tests and OSDI score was observed with the use of both 0.05% and 0.1% cyclosporine A eye drops in patients with dry eye. Similarly, Boboridis et al. suggested that topical cyclosporine A 0.1% presented as a novel promising medication for the management of dry eye disease and MGD. (14) The short follow-up time and low number of patients can be considered as a limitation of our study.

CONCLUSION
Cyclosporine A 0.05% and 0.1% eye drops were determined to be effective in managing dry eye disease in our study. There was no significant difference between the two different doses of topical cyclosporine A over the three-month use. Currently, there are limited published clinical data concerning the efficacy of these two different doses of topical cyclosporine A, and further studies with a higher number of patients and longer follow-up are needed.