Volume 13, Issue 3, Pages 213-225 (July 2015) Efficacy and Safety of Topical 0.05% Cyclosporine Eye Drops in the Treatment of Dry Eye Syndrome: A Systematic Review and Meta-analysis  Kelvin H. Wan, MBChB, Li Jia Chen, MRCSEd(Ophth), PhD, Alvin L. Young, MMedSc (Hons), FRCSIrel  The Ocular Surface  Volume 13, Issue 3, Pages 213-225 (July 2015) DOI: 10.1016/j.jtos.2014.12.006 Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 1 Flow chart showing selection of RCTs for inclusion in this meta-analysis. CENTRAL=Cochrane Central Register of Controlled Trials; WHO ICTRP=World Health Organization International Clinical Trials Registry Platform; RCT=randomized control trial; DES=dry eye syndrome. *Of these 808 studies, 457 were not related to dry eye human subjects (i.e., other ocular or non-ocular autoimmune diseases that were not DES where cyclosporine was used; conditions where DES can be part of the manifestation but were not the main objective of the studies, i.e., Sjögren syndrome, Stevens-Johnson syndrome; or animal studies); 139 involved DES where topical 0.05% cyclosporine was not the intervention; 124 were review articles on DES or the general role of cyclosporine on autoimmune diseases; 42 were case series or observational studies where no control group was used; 31 did not present outcomes relevant to this meta-analysis in the abstracts; and 15 were not RCTs. The Ocular Surface 2015 13, 213-225DOI: (10.1016/j.jtos.2014.12.006) Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 2 A. Risk of bias summary: authors' judgments about each risk of bias item for each included study. B. Risk of bias graph: authors' judgments about each risk of bias item presented as percentages across all included studies. The Ocular Surface 2015 13, 213-225DOI: (10.1016/j.jtos.2014.12.006) Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 3 Ocular surface disease index (OSDI) scores in cyclosporine A and control groups. CsA=cyclosporine; SD=standard deviation; IV=inverse variance; CI=confidence interval. The Ocular Surface 2015 13, 213-225DOI: (10.1016/j.jtos.2014.12.006) Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 4 Tear film break-up time (TFBUT) values in cyclosporine A and control groups. CsA=cyclosporine; SD=standard deviation; IV=inverse variance; CI=confidence interval. The Ocular Surface 2015 13, 213-225DOI: (10.1016/j.jtos.2014.12.006) Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 5 Schirmer test (without anesthesia) in cyclosporine A and control groups. CsA=cyclosporine; SD=standard deviation; IV=inverse variance; CI=confidence interval. The Ocular Surface 2015 13, 213-225DOI: (10.1016/j.jtos.2014.12.006) Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 6 Schirmer test (with anesthesia) in cyclosporine A and control groups. CsA=cyclosporine; SD=standard deviation; IV=inverse variance; CI=confidence interval. The Ocular Surface 2015 13, 213-225DOI: (10.1016/j.jtos.2014.12.006) Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 7 Goblet cell density in cyclosporine A and control groups. CsA=cyclosporine; SD=standard deviation; Std. Mean Difference=standardized mean difference; IV=inverse variance; CI=confidence interval. The Ocular Surface 2015 13, 213-225DOI: (10.1016/j.jtos.2014.12.006) Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 8 Corneal fluorescein staining in cyclosporine A and control groups. CsA=cyclosporine; SD=standard deviation; Std. Mean Difference=standardized mean difference; IV=inverse variance; CI=confidence interval. The Ocular Surface 2015 13, 213-225DOI: (10.1016/j.jtos.2014.12.006) Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 9 Treatment-related adverse effects in cyclosporine A and control groups. CsA=cyclosporine; SD=standard deviation; M-H=Mantel-Haenszel, CI=confidence interval. The Ocular Surface 2015 13, 213-225DOI: (10.1016/j.jtos.2014.12.006) Copyright © 2015 Elsevier Inc. Terms and Conditions