Topical corticosteroids with topical cyclosporine A versus topical corticosteroids alone for immunological corneal graft rejection. Issue 3 (May 2022)

• Record Type: Journal Article
• Authors: Marques, Raquel Esteves; Leal, Inês; Guerra, Paulo Silva; Barão, Rafael Correia; Quintas, Ana Miguel; Rodrigues, Walter
• Is Part Of: European journal of ophthalmology. Volume 32:Issue 3(2022)
• Page Start: 1469
• Page End: 1481
• Publication Date: 2022-05
• Subjects: Corneal transplantation -- graft rejection -- immunosuppression -- cyclosporine; Ophthalmology -- Periodicals; Eye -- Diseases -- Periodicals; 617.7005
• DOI: 10.1177/11206721211023320
• Languages: English
• ISSNs: 1120-6721

Abstract

Purpose: To assess the efficacy and safety of supplementing topical cyclosporine A (CsA) to topical corticosteroids (CS), in the prophylaxis and treatment of corneal graft rejection following penetrating keratoplasty (PK). Methods: Meta-analysis. Search was performed in PubMed, CENTRAL, ClinicalTrials.gov, reference lists of articles and conference proceedings. Primary outcomes: 1-year rejection-free survival rate (prophylaxis); resolution rate of rejection episodes (treatment). Secondary outcomes: 6- and 24-month rejection-free graft survival rate, number of rejection episodes during follow-up, time-to-resolution of rejection episode, 12- and 24-months graft survival rate, adverse events. Subgroup analyses were planned for high-risk grafts; primary vs. secondary prophylaxis of graft rejection episodes; and CsA concentrations of 0.05%, 1%, and 2%. Results: Five studies of moderate methodological quality were included (one retrospective, four RCT), assessing 459 eyes (CS + CsA 226, CS 233). In the prophylaxis setting, supplemental CsA was associated with a higher rejection-free survival rate at 12-months (RR 1.25, 95% CI: 1.00–1.56, p = 0.05) and 24-months post-PK (RR 1.56, 95% CI: 1.15–2.11, p < 0.01), though no differences were found at the 6-months timepoint ( p = 0.93). This effect was mostly verified using CsA 2% in the high-risk subset of patients. In the treatment setting, no differences were found in the resolution rate of rejection episodes ( p = 0.23). No differences existed on drug-related adverse events. Conclusion: In the prophylaxis of rejection episodes post-PK, the combined regimen of CS + CsA was associated with a higher 1- and 2-year rejection-free graft survival rate. Subgroup analysis mostly supported the use of CsA 2% for high-risk grafts. Further studies are needed to validate these results.