The impact of tacrolimus therapy on the outcomes of vernal keratoconjunctivitis: a systematic review and meta-analysis

Abstract

Background: Various preparations of tacrolimus have been implemented for patients with vernal keratoconjunctivitis (VKC). However, there is a lack of evidence regarding the safety and effectiveness of different dosages and forms of tacrolimus for patients with VKC.

Objective: The present systematic review and meta-analysis evaluated the safety and effectiveness of various dosages and forms of tacrolimus for patients with VKC.

Methods: The literature review was performed through 12 databases on 15 June 2024. All clinical studies comparing the outcomes of different dosages and tacrolimus preparations for VKC were included. Subgroup analysis was performed based on the dosages and formulations of tacrolimus.

Results: The present meta-analysis included 17 articles, encompassing 832 patients with VKC. Of them, 421 patients received tacrolimus, while 411 patients were in the control group. Of the treated patients with tacrolimus, 66 were treated with tacrolimus ophthalmic suspension 0.1%, and 62 were treated with tacrolimus 0.1% ointment. Furthermore, 293 patients were treated with tacrolimus 0.03% ointment. There was a statistically significant (p = 0.02) difference between tacrolimus and the control group regarding the mean score for objective signs with SMD of -0.70 (95%CI:-1.28, -0.13). A statistically significant difference (p < 0.001) was observed between the tacrolimus ophthalmic suspension 0.1% and the control group with an SMD of -1.09 (95%CI:-1.59, -0.59). There was a significantly lower total subjective symptom score among patients treated with tacrolimus with an SMD of -0.86 (95%CI:-1.44, 0.28) and a probability value of 0.004. A statistically significant lower risk of treatment-related adverse events was revealed among patients treated with tacrolimus 0.03% ointment (p = 0.0002) with an RR of 0.16.

Conclusion: Tacrolimus is an effective and safe therapeutic intervention for patients with VKC. It remarkably reduced the total score for objective signs and total subjective symptom score of VKC, with a relatively lower risk of treatment-related adverse events. The improvement of clinical manifestations was significantly associated with tacrolimus ophthalmic suspension 0.1%, while tacrolimus 0.03% ointment was associated with the lowest risk of treatment-related adverse events.

Keywords: VKC; ointment; suspension; tacrolimus; vernal keratoconjunctivitis.

Figure 1

PRISMA flow chart showing the process of the literature search, title, abstract, and full text screening, systematic review, and meta-analysis.

Figure 2

(A) Risk of bias graph, (B) Risk of bias summary: review authors’ judgments about each risk of bias item presented as percentages across all included studies.

Figure 3

Forest plot of summary analysis of the (A) Standardized Mean Difference (SMD) and 95% CI of mean total score for objective signs between tacrolimus and control groups subgrouped by the dosages and formulations of tacrolimus. (B) Funnel plot showing the symmetrical distribution of the studies along the middle line. (C) Standardized Mean Difference (SMD) and 95% CI of the total objective symptom scores between tacrolimus and control groups. Size of the green squares is proportional to the statistical weight of each trial. The gray diamond represents the pooled point estimate. The positioning of both diamonds and squares (along with 95% CIs) beyond the vertical line (unit value) suggests a significant outcome (IV, inverse variance).

Figure 4

Forest plot of summary analysis of the (A) Standardized Mean Difference (SMD) and 95% CI of mean total subjective symptom score between tacrolimus and control groups subgrouped by the dosages and formulations of tacrolimus. (B) Standardized Mean Difference (SMD) and 95% CI of the mean intraocular pressure between tacrolimus and control groups. (C) Risk ratio and 95% CI of the risk of treatment failure between tacrolimus and control groups. (D) Risk ratio and 95% CI of the risk of treatment-related adverse events between tacrolimus and control groups. Size of the green or blue squares is proportional to the statistical weight of each trial. The gray diamond represents the pooled point estimate. The positioning of both diamonds and squares (along with 95% CIs) beyond the vertical line (unit value) suggests a significant outcome (IV, inverse variance).