Clinical efficacy of intrastromal voriconazole injection in fungal keratitis involving different corneal stromal depths

To evaluate the clinical efficacy of intrastromal injection of 0.5% (5 mg/mL) voriconazole in fungal keratitis (FK) involving different corneal stromal depths. This was a non-randomized, retrospective study based on patient treatment preferences. A total of 53 patients (53 eyes) with confirmed fungal keratitis treated between March 2021 and December 2023 were enrolled. Based on anterior segment optical coherence tomography (AS-OCT) findings, lesions were stratified by depth into superficial stromal involvement (Group A, n = 29) and deep stromal involvement (Group B, n = 24). Each group was further subdivided according to treatment modality: non-injection group (conventional antifungal therapy) (subgroups A1 and B1) versus injection group (conventional antifungal therapy combined with intrastromal voriconazole injection) (subgroups A2 and B2). The following clinical parameters were compared among the four subgroups: reduction ratio of corneal epithelial staining area at 7 days post-treatment initiation, best-corrected visual acuity (BCVA), corneal epithelial healing time, clinical cure time, and final clinical outcomes. All groups demonstrated significant reduction in ulcer area after 7 days of treatment (P < 0.05). In superficial stromal fungal keratitis, ulcer improvement rates were comparable between groups A1 (37.19%) and A2 (36.11%) (P = 0.838). In deep stromal fungal keratitis, group B2 (41.30%) showed significantly greater improvement compared to B1 (14.95%) (P < 0.0001). Final BCVA improved significantly in all groups, with no significant intergroup differences. Epithelial healing time and clinical cure time showed no significant differences across groups. The overall clinical cure rate was 98.1%, achieved through the non-injection group in 79.2% of cases and the injection group in 18.9% of cases. Treatment failure occurred in one case (1.9%). Intrastromal voriconazole injection provides no additional benefit for superficial stromal fungal keratitis compared with conventional topical therapy and is therefore not recommended as routine treatment given its invasive nature. For deep stromal fungal keratitis, intrastromal injection demonstrates superior early lesion control but does not reduce overall disease duration or improve final visual outcomes. Further large-scale prospective studies are warranted to establish its optimal indications and clinical value. (1) Fungal keratitis is primarily managed with pharmacological therapy; however, the availability of antifungal agents for ocular use remains limited. These agents demonstrate poor tissue penetration and insufficient efficacy against deep corneal infections, frequently resulting in delayed ulcer healing, infection recurrence, and corneal perforation. (2) Voriconazole, a second-generation triazole antifungal agent, exhibits superior antifungal activity and corneal stromal penetration compared to conventional agents. However, its penetration into deep stromal layers remains limited, potentially leading to residual lesions or recurrence. (1) For patients with superficial stromal fungal keratitis, the addition of intrastromal voriconazole injection to conventional antifungal therapy demonstrated no significant therapeutic advantage. Given the invasive nature of this procedure, intrastromal voriconazole injection is not recommended for superficial stromal infections. (2) For patients with deep stromal fungal keratitis, combined therapy with intrastromal voriconazole injection and conventional antifungal agents resulted in more effective reduction of corneal epithelial staining area at 7 days post-treatment compared to conventional therapy alone. However, this approach did not significantly shorten clinical cure time or improve final clinical outcomes.