Intrastromal voriconazole injection shows promise for recalcitrant deep fungal keratitis

This small case series published in the December 2011 issue of the British Journal of Ophthalmology evaluated the efficacy of intrastromal injection of voriconazole for recalcitrant fungal keratitis. While the best dose and frequency of injections remain to be determined, the study’s authors conclude that judicious and timely use of this method as an adjunctive therapy may be undertaken in selected patients who are unresponsive to other forms of antifungal therapy.

This is the largest reported series of patients with fungal keratitis treated with intrastromal voriconazole injection. I find it intriguing that these injections helped despite the resistance of the ulcers to hourly topical voriconazole drops.

The 12 subjects all had smear and/or culture positive fungal keratitis that was nonresponsive to four weeks of topical natamycin (5%) and two weeks of topical voriconazole (1%) and oral voriconazole (200 mg twice daily). They were given one or more intrastromal injections of voriconazole (50 mg in 0.1 ml) at 72-hour intervals at the junction of clear cornea and infiltrates using a 30-gauge needle in five quadrants to form a barrage around the ulcer. The authors injected the drug around the abscess in each patient to form a deposit around the circumference of the lesion. They performed this so that a centripetally directed progressive wave of fluid appeared to encompass the abscess along each meridian. Patients also continued to receive topical and systemic antifungal therapy.

Aspergillus species was isolated from eight eyes, Fusarium species from three eyes and Curvularia from one. Ten of 12 eyes healed with scar formation after a mean of 39.75 ± 7.62 days. In the two patients who failed intrastromal injection treatment, their corneas perforated and required emergency penetrating keratoplasty.

BCVA was less than 20/1200 in all patients at the time of presentation, which improved to better than 20/400 in 10 eyes and 20/40 in the two eyes that underwent penetrating keratoplasty at the end of 24.75 ± 2.14 weeks of follow-up. None of the patients developed any toxic effects due to voriconazole injection.

The authors say that the major advantage of this modality is that it delivers the drug at the site of infection, achieving a high intracorneal concentration, which may not be possible with topical and systemic antifungal therapy.