Correlation between corneal concentration and minimum inhibitory concentration of antifungals in patients undergoing therapeutic keratoplasty for fungal keratitis.

Objectives: To correlate corneal concentration and minimum inhibitory concentration (MIC) of antifungal drugs in patients undergoing therapeutic penetrating keratoplasty (TPK) for fungal keratitis.

Methods: The study included 43 cases of culture- and smear-proven fungal keratitis that underwent TPK due to inadequate responses to topical natamycin (NTM) 5% and/or topical voriconazole (VCZ) 1%. Liquid chromatography mass spectrometry (LCMS) was used to analyze the host corneal tissue of the patients to measure the intracorneal concentrations of NTM and VCZ. Antifungal susceptibility testing was performed using the E-test method with standard-dose antifungal E-strips on the same corneal tissue.

Results: The mean age of study participants was 48.11 ± 15.22 years. Aspergillus sp. was the most commonly identified fungus. The study found that the mean intracorneal concentration of NTM was 80.76 ± 107.59 μg/gm (n = 30/43), while that of VCZ was 0.0962 ± 0.25 μg/gm (n = 32/43). Twenty-one cases had MIC-90 values for both antifungal drugs. Over 85% of cases had an intracorneal concentration lower than VCZ MIC-90, and 61.9% of cases showed NTM intracorneal concentration higher than its MIC-90.

Conclusion: Despite achieving corneal concentration higher than the MIC-90, cases with recalcitrant fungal keratitis had a poor clinical response to NTM, suggesting other possible reasons, such as poor drug penetration and drug resistance.