Comparative Efficacy of Cyclosporine, Tacrolimus, and Neurostimulatory Nasal Sprays for Moderate-to-Severe Dry Eye Disease: A Systematic Review and Network Meta-Analysis
In brief
Cyclosporine 0.09% and 0.1% ranked highest for corneal staining
In a review of 29 trials involving 8,453 people with moderate-to-severe dry eye, cyclosporine 0.09% and 0.1% ranked highest for improving corneal staining, a measure of surface damage. Tacrolimus showed early tear-related benefits, while nasal varenicline increased tear production; comparisons remain limited, and lubricating placebo vehicles may explain some results, underscoring the need for head-to-head trials.
- Journal
- Clinical ophthalmology (Auckland, N.Z.) (Q1)
- Published
- 12 September 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Asim Marwan Bogari, Nada Omar Taher, Reem Omar Nughays, Mohammed Albadri, Hind Mohammed Aljabri, Mohammed Abdulaziz Taha, et al.
- PMID
- 42788109
- DOI
- 10.2147/OPTH.S608369
Why clinicians should know about it
- Picked for Ophthalmology (top studies of the week, 27 September 2026): Network meta‑analysis of cyclosporine, tacrolimus, nasal sprays for dry eye
Abstract
AIM: To compare the efficacy and tolerability of topical cyclosporine A (CsA) 0.05%, 0.09%, and 0.1%; tacrolimus 0.03%; and neurostimulatory nasal sprays (varenicline and simpinicline) in moderate-to-severe dry eye disease (DED), focusing on tear production, ocular surface integrity, and tear film stability. CLINICAL RELEVANCE: DED management remains complex due to heterogeneous presentation and variable therapeutic responses. While immunomodulators like CsA and tacrolimus are widely used, novel neuromodulatory agents such as varenicline nasal spray are emerging. Comparative data across these treatment classes remain scarce. METHODS: A systematic search of MEDLINE, Embase, and CENTRAL was performed up to January 2025. Randomized controlled trials assessing CsA 0.05%, 0.09%, or 0.1%; tacrolimus 0.03%; or nicotinic acetylcholine receptor agonist nasal sprays in moderate-to-severe DED were included. Primary endpoints included Schirmer test score (STS), tear break-up time (TBUT), corneal fluorescein staining (CFS), and ocular surface disease index (OSDI). A Bayesian network meta-analysis estimated comparative efficacy using the surface under the cumulative ranking curve (SUCRA). RESULTS: Twenty-nine RCTs (n = 8453 patients) were included in the systematic review; fourteen qualified for network meta-analysis. CsA 0.09% and 0.1% ranked highest for CFS improvement at the evaluated time points. Tacrolimus 0.03% showed favorable early STS and TBUT trends but did not consistently improve longer-term ocular surface outcomes. Varenicline improved tear production but lacked CFS data. Placebo ranked favorably for STS and TBUT at 3 months and beyond, possibly because several vehicles had lubricating or tear-stabilizing effects. CsA 0.05% showed modest efficacy. CONCLUSION: CsA 0.09% and 0.1% showed the most favorable corneal healing outcomes, while tacrolimus 0.03% showed an early tear-stimulating effect. Varenicline offers a distinct neurostimulatory mechanism but requires further comparative validation. These findings support phenotype-guided therapy and future head-to-head trials.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.