Topical Tacrolimus in the Management of High-Risk Keratoplasty: A Systematic Review and Meta-Analysis

Corneal transplantation is a frequently performed procedure for human eye transplants. In low-risk conditions such as keratoconus and Fuch's dystrophy, corneal transplantation has a high success rate due to the immune advantages in support of the cornea. Major risk factors for corneal graft rejection include: atopy, chemical burn, prolonged herpes infection, infectious leukoma, trauma, prior transplantation, active inflammation, and corneal neovascularization. Treatments against lymphangiogenic bacteria and anti-angiogenic bacteria are two strategies to reduce corneal graft rejection. The primary objective of this systematic review and meta-analysis was to assess topical tacrolimus's benefits for high-risk keratoplasty management. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, data was gathered by combining pertinent medical subject words in the literature of the complementing articles from the PubMed, Cochrane Library, Embase, Web of Science, Medline, and Google Scholar. The search was conducted using terms such as "tacrolimus," "keratoplasty," and other related synonymous terms. Prior to conducting a meta-analysis, Review Manager version 5.3.2 (www.revman.cochrane.org) was utilized to assess the risk of bias in the extracted data, and the literature was chosen according to pre-established inclusion and exclusion criteria. The meta-analysis employed both Forest plots and funnel plots to examine heterogeneity and assess the likelihood of publication bias. Eight studies were included in the analysis. The results indicated a moderate level of heterogeneity among the included studies, with Tau2 = 0.19 and I2 = 52%. Moreover, the overall findings suggested that topical tacrolimus treatment emerged as the most effective medication for high-risk keratoplasty, as evidenced by the diamond marker positioned slightly to the left side of the 95% confidence interval (0.67; 0.42-1.06), rather than the right side. Subgroup analysis further reinforced this notion, showing that topical tacrolimus was particularly efficacious in treating high-risk keratoplasty, with a 95% confidence interval of (0.16; -0.68-1.00). However, the difference observed was minimal, possibly due to certain studies comparing topical tacrolimus with mixed treatment doses, some of which included a combination of tacrolimus and other agents. Additionally, topical tacrolimus treatment was identified as the safest option for high-risk keratoplasty, with a confidence interval of (-0.35; -2.23-0.88). Nonetheless, the overall effect suggested that the medication did not significantly differ from other treatments. This study confirms that topical tacrolimus is both effective and the safest treatment for managing high-risk penetrating keratoplasty (PKP). However, future studies should focus on determining the appropriate dosage levels for the management of high-risk PKP.