Key messages
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Cyclosporine A (CsA) eye drops, including Restasis, Cequa, and other newer versions, may improve some signs and symptoms of dry eye compared with their "vehicle" (inactive eye drops containing no CsA) or artificial tears. However, we have only moderate or low confidence in these results.
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People who used CsA eye drops were slightly more likely to stop treatment due to unwanted effects, but overall, few people withdrew from studies for this reason.
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We need higher-quality, longer-lasting studies that look at the benefits and harms of CsA eye drops in people with dry eye disease of varying seriousness.
What is dry eye disease?
The eye's surface is moist and covered with a thin film of tears. When problems arise with the tear film, people can develop a common condition known as dry eye disease. People with dry eye may have eye discomfort (such as a feeling of grittiness), burning sensations, light sensitivity, and blurred or fluctuating vision, which can affect driving and reading and lower their quality of life.
Some people develop dry eye disease because of another health condition or as a result of eye treatment, while in others, the cause is unknown. Many cases of dry eye are linked to health conditions that cause inflammation (swelling and irritation) in and around the eyes.
What are cyclosporine A (CsA) eye drops?
CsA eye drops are anti-inflammatory medicines that aim to reduce eye surface inflammation, improve tear production, and prevent eye surface damage. CsA eye drops come in different strengths, typically ranging from 0.05% (lower strength) to 2% (higher strength).
What did we want to find out?
We wanted to find out whether CsA eye drops work better than eye drops containing all the same ingredients except cyclosporine ('vehicle eye drops' or just 'vehicle'), artificial tears, or another type or strength of CsA to improve:
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dry eye symptoms;
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eye surface health;
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tear production;
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how well tears stay on the eye (tear film stability).
We also wanted to find out whether people using CsA eye drops were more likely to stop using them because of unwanted effects than those using vehicle, artificial tears, or CsA drops of a different type or strength.
What did we do?
We searched for studies comparing CsA eye drops with vehicle, artificial tears, or another CsA formulation or strength. We compared and summarized the results of these studies and rated our confidence in the evidence based on factors such as study methods and the number of people in the studies.
What did we find?
We found 58 studies involving 10,225 people with dry eye disease. China, South Korea, and the USA contributed 35 of the 58 studies (60%). Participants were typically around 53 years old. Women made up about 80% of participants overall, though proportions varied across studies from 46% to 100%. Pharmaceutical companies funded or sponsored nearly half of the studies. Non-profit organizations supported 10 studies, six studies had no external funding, and 14 studies did not report funding sources.
We grouped the studies into six groups based on CsA strength and the comparison treatments. Here, we focus on three groups with the most data.
Main results
Comparison 1
Compared to vehicle, artificial tears, or both, using CsA 0.05% eye drops for three months may have slightly improved people's:
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dry eye symptoms (13 studies, 1396 people);
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eye surface health (7 studies, 1355 people).
Results for tear production and tear film stability were inconsistent, preventing us from drawing firm conclusions.
Comparison 2
People using CsA eye drops of different strengths and types may have had slightly better tear production than those using CsA 0.05% eye drops after three months, but the difference between groups was small (5 studies, 572 people). We are uncertain about the effects on:
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dry eye symptoms;
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eye surface health;
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tear film stability.
Comparison 3
Compared to vehicle, artificial tears, or both, using CsA 0.1% eye drops for three months:
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probably improved eye surface health slightly (7 studies, 2940 people);
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may have improved tear production slightly (3 studies, 735 people).
Results for dry eye symptoms were inconsistent, preventing us from drawing firm conclusions. We are uncertain about the effect of CsA 0.1% on tear film stability.
Stopping treatment due to unwanted effects
Compared with people using vehicle eye drops or artificial tears, those using CsA 0.05% or 0.1% were slightly more likely to stop treatment due to unwanted effects. Overall, only a few people stopped treatment because of unwanted effects.
What are the limitations of the evidence?
We have little confidence in the evidence for dry eye symptoms, eye surface health, tear production, and tear film stability because study results were often inconsistent or too uncertain to determine the true size of the effect. Many studies gave unclear or few details about their methods. However, we are moderately confident in the evidence about stopping treatment.
How up to date is this evidence?
The evidence is current to March 2026.
Read the full abstract
Topical cyclosporine A (also known as ciclosporin A) (CsA) is an anti-inflammatory that has been widely used to treat inflammatory ocular surface diseases. Two CsA eyedrops have been approved by US Food and Drug Administration for managing dry eye: Restasis (CsA 0.05%, Allergan Inc, Irvine, CA, USA), approved in 2002, and Cequa (CsA 0.09%, Sun Pharma, Cranbury, NJ, USA), approved in 2018. Numerous clinical trials have been performed to assess the effectiveness and safety of CsA for dry eye; however, there is no universal consensus with regard to its effect.
Objectives
To assess the benefits and harms of topical CsA in the treatment of dry eye disease.
Search strategy
We used CENTRAL, MEDLINE, Embase, two other databases, and two trial registers, together with reference checking, to identify studies included in the review. The latest search date was 17 March 2026.
Selection criteria
We included randomized controlled trials (RCTs) of people with dry eye regardless of age, sex, severity, etiology, or classification of dry eye. We included RCTs in which different concentrations of topical CsA were compared with one another or with artificial tears, placebo, or vehicle. We also included RCTs in which CsA in combination with artificial tears was compared to artificial tears alone.
Data collection and analysis
We followed the standard Cochrane methodology and assessed the certainty of the evidence using GRADE.
Main results
We included 30 RCTs (4009 participants) with follow-up periods ranging from 6 weeks to 12 months. We studied dry eye of various severity and underlying causes. The interventions investigated also varied across RCTs: CsA versus artificial tears; CsA with artificial tears versus artificial tears alone; and in some studies, more than one concentration of CsA. Artificial tears were used as adjunctive to study medication in all but five trials. Almost all trials had deficiencies in the reporting of results (e.g. reporting P values or direction only), precluding the calculation of between-group estimates of effect or meta-analysis.
Eighteen trials compared topical CsA 0.05% plus artificial tears versus vehicle plus artificial tears or artificial tears alone. One trial reported subjective symptoms of dry eye at 6 months and the results were in favor of CsA (mean difference (MD) -4.80, 95% confidence interval (CI) -6.41 to -3.19; low-certainty evidence). Two trials reported MD in ocular surface dye staining at 6 months, but the results were inconsistent in these two trials (MD −0.35, 95% CI −0.69 to −0.01 in one and MD 0.58, 95% CI 0.06 to 1.10 in the other; low-certainty evidence). Four trials reported MD in Schirmer test scores at 6 months and the estimates ranged from -4.05 (95% CI -6.67 to -1.73) to 3.26 (95% CI -1.52 to 5.00) (low-certainty evidence). Three trials reported risk ratio (RR) of improved Schirmer test scores at 6 months; estimates ranged from 0.98 (95% CI 0.83 to 1.17) to 3.50 (95% CI 2.09 to 5.85) (low-certainty evidence). Four trials reported MD in tear film stability measured by tear break-up time at 6 months and the estimates ranged from -1.98 (95% CI -3.59 to -0.37) to 1.90 (95% CI 1.44 to 2.36) (low-certainty evidence). Three trials reported RR of improved tear break-up time at 6 months and the estimates ranged from 0.90 (95% CI 0.77 to 1.04) to 4.00 (95% CI 2.25 to 7.12) (low-certainty evidence). Three trials reported frequency of artificial tear usage at 6 months without providing any estimates of effect; the direction of effect seem to be in favor of CsA (low-certainty evidence). Because of incomplete reporting of the results data or considerable statistical heterogeneity, we were only able to perform a meta-analysis on mean conjunctival goblet cell density. Mean conjunctival goblet cell density in the CsA treated group may be greater than that in the control group at the end of follow-up at four and 12 months (MD 22.5 cells per unit, 95% CI 16.3 to 28.8; low-certainty evidence). All but two trials reported adverse events that included burning and stinging. Participants treated with CsA may be more likely to have treatment-related adverse events than those who treated with vehicle (RR 1.33, 95% CI 1.00 to 1.78; low-certainty evidence).
Other comparisons evaluated were CsA 0.05% plus artificial tears versus higher concentrations of CsA plus artificial tears (4 trials); CsA 0.05% versus placebo or vehicle (4 trials); CsA 0.1% plus artificial tears versus placebo or vehicle plus artificial tears (2 trials);
CsA 0.1% cationic emulsion plus artificial tears versus vehicle plus artificial tears (2 trials); CsA 1% plus artificial tears versus placebo plus artificial tears (3 trials); and CsA 2% plus artificial tears versus placebo plus artificial tears (3 trials). Almost all of these trials reported P value or direction of effect only (mostly in favor of CsA), precluding calculation of between-group effect estimates or meta-analyses.
Authors' conclusions
Low-certainty evidence suggests that topical CsA may improve DED symptoms and certain clinical signs compared with vehicle or artificial tears. However, results for DED symptoms and tear parameters were inconsistent and highly heterogeneous. Higher CsA concentrations were associated with increased treatment discontinuation. Future studies should stratify DED by subtype and severity, compare formulations, and assess long-term benefit and harm.
Funding
The Cochrane Eyes and Vision US Project is supported by grant UG1EY020522, National Eye Institute, National Institutes of Health.
Registration
Original review (2019) DOI: 10.1002/14651858.CD010051.pub2
