Refractory Polymicrobial Fungal Keratitis Leading To Corneal Perforation And Requiring Therapeutic Penetrating Keratoplasty In A Patient Receiving Glp-1 Receptor Agonists: A Case Report

To present the case of a 28-year-old female, a contact lens wearer on systemic treatment with GLP-1 receptor agonists (semaglutide), who developed fungal keratitis in the left eye. The objective is to analyze the torpid clinical course which, after an initial improvement, suffered a fulminant recurrence leading to corneal perforation and requiring urgent therapeutic penetrating keratoplasty (PKP) despite intensive management.

Anterior segment and cornea unit, Hospital Universitario 12 de Octubre (Madrid, Spain), a tertiary referral academic hospital.

A 28-year-old female, contact lens wearer and undergoing semaglutide treatment, presented with a grayish corneal infiltrate with feathery borders. Microbiological analysis of contact lenses and storage fluid confirmed a coinfection by Fusarium solani and Candida sp., sensitive to voriconazole and amphotericin B. Initial management consisted of an intensive hourly regimen of topical voriconazole, fortified vancomycin and ceftazidime. After one month of treatment, clinical resolution and epithelial closure were achieved. However, one week after discontinuing antibiotics and reducing voriconazole frequency, a sudden recurrence occurred, progressing to a large corneal abscess within five days. The patient was hospitalized for therapeutic escalation: systemic therapy (oral voriconazole, doxycycline and vitamin C) and multidrug topical therapy (voriconazole/natamycin 6h; moxifloxacin/dexamethasone/cycloplegic 8h; and chlorhexidine 3h). Despite intensive care, corneal perforation occurred 72 hours after admission, necessitating a therapeutic PKP. Post-surgical histopathology of the host cornea was negative for microorganisms. Two months later, the graft remains stable and transparent without signs of fungal recurrence. Current maintenance therapy includes topical and systemic voriconazole, topical natamycin and amphotericin B (6h), netilmicin gel, cyclosporine 0.1%, dexamethasone (8h), and nerve supplement (12h). Systemic voriconazole levels and hepato-renal function remain normal.

Fungal keratitis remains a major challenge due to its high recurrence rate, and even more when there is a fungal co-infection. This case highlights a fulminant progression to perforation despite early diagnosis and an initially successful aggressive therapy. Therapeutic PKP is the definitive emergency procedure to preserve globe integrity and control infection in refractory cases. It is essential to investigate the potential role of GLP-1 receptor agonists (semaglutide) in modulating ocular immune response and stromal repair, as they may act as a coadjuvant factor in fungal coinfection and clinical outcomes.