Water-free topical cyclosporine may be a promising method of treating dry eye disease (DED) given results of several studies that confirm dryness scores improved in patients with when using the topical treatment. The meta-analysis published in the Journal of Ophthalmic Inflammation and Infection1 reported less promising results in the improvement of total and central corneal fluorescence staining score (tCFS and cCFS).
DED is characterized by 1 or both eyes having disruption in either the production or the function of tears.2 DED most commonly affects women and is highly prevalent among adults aged at least 40 years. Using treatment that targets inflammation has been successful in addressing DED in patients. Topical cyclosporine A is just 1 of the potential treatments, but results of the efficacy and safety of the medication have been mixed. This review assessed how safe and effective 0.1% water-free cyclosporine A was for treating DED in patients.
Water-free topical cyclosporine was able to improve dryness scores in patients with dry eye disease | Image credit: lenblr – stock.adobe.com
The researchers used PubMed, SCOPUS, Web of Science, and Cochrane Library to conduct their literature search. Patients who were diagnosed with moderate to severe dry eye were the primary population that were preferred for this analysis. Only randomized controlled trials that included patients with a confirmed diagnosis of moderate to severe dry eye who took water-free topical cyclosporine formulations and compared them against placebo with objective measures were included in the study. These objective measures included tCFS, cCFS, tear breakup time (TBUT), ocular surface disease index (OSDI) scores, and Schirmer’s test.
There were 4 studies with 1471 total participants included in the final review. The mean age of the participants who took cyclosporine 0.1% was 56.7 years and the control group had a mean age of 57 years; 75% of the participants were women.
Participants used the topical treatment for 29 days and a mean tCFS of 10.68 and mean cCFS of 1.97 at baseline. The 4 studies included found that the tCFS (MD, –1.08; 95% CI, –3.48 to 1.32) and cCFS(MD, –0.21; 95% CI, –0.50 to 0.08) did not show any significant improvement during the period of use. Both of these analyses had high heterogeneity. However, the dryness score of those who received water-free cyclosporine 0.1% was significantly improved across the studies (MD, –7.48; 95% CI, –14.5 to –0.82) with high heterogeneity.
The risk ratio for participants who reported adverse events related to the treatment was 1.13 (95% CI, 0.95-1.34) but a pooled analysis of safety outcomes had no statistically significant results. Patients who reported ocular treatment-emergent adverse events had a risk ratio of 1.19 (95% CI, 0.90-1.59) whereas the risk ratio for serious treatment-emergent adverse events was 0.55 (95% CI, 0.14-2.08).
There were some limitations to the study. There were only 4 studies included in the final analysis. There was also variability in the CFS scores that could limit the generalizability of the overall analysis. Most of the participants were women and may not adequately cover responses in men. Evaluation techniques and outcomes measured were different in each study, which may have caused inconsistency in the results.
The researchers concluded that, although the CFS scores did not improve significantly with use of 0.1% water-free cyclosporine A, the dryness scores improved overall, which was a sign that further research into the treatment should be conducted to assess the usefulness of the medication in DED.
“Future studies should strive for more comprehensive and diverse populations, longer follow-up periods, and standardized evaluation methodologies to better grasp the full potential and application of water-free cyclosporine in controlling dry eye disease,” the authors wrote.
References
- Rehan AH, El-Masry H, Abdultawab R, et al. Efficacy and safety of water-free topical cyclosporine for moderate to severe dry eye disease: a systematic review and meta-analysis. J Ophthalmic Inflamm Infect. 2025;15:20. doi:10.1186/s12348-025-00467-9
- Dry eye. National Eye Institute. Updated February 18, 2025. Accessed February 25, 2025. https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/dry-eye
