FUNGAL KERATITIS

Targeted drug delivery might offer a solution for the treatment of recalcitrant fungal keratitis, given the limitations of topical antifungal therapy, Namrata Sharma MD told a session of the 7th International Congress on Ocular Infections in Barcelona, Spain.

“Topical antifungal therapy has poor ocular penetration and bioavailability, so we have looked into both intrastromal and intracameral drug injection for those infections non-responsive to conventional topical and systemic antifungal therapy for four weeks,” said Dr Sharma, All India Institute of Medical Sciences, New Delhi, India.

Indications for intrastromal injections include deep mycotic keratitis, non-perforated corneal ulcers and postoperative interface lamellar infection, a complication that is likely to become more prevalent with the increasing number of lamellar surgeries performed.

Drugs that have been tested include amphotericin B (5.0-7.5μg/0.1ml/5% dextrose), voriconazole (50-100μg/0.1ml) and fluconazole 0.2 per cent. A single intrastromal injection of 10μg amphotericin B achieves an effective drug level in corneas for up to seven days in a rabbit model. However, corneal oedema can occur at high doses, she said.

In a study published in 2011, Dr Sharma and her team injected intrastromal voriconazole in 12 eyes of 12 patients with recalcitrant fungal keratitis. Of these, 10 eyes healed with scar formation, while two eyes required therapeutic penetrating keratoplasty (PKP).

RECENT STUDY

In a more recent study of non-responders to topical two-hourly natamycin five per cent therapy for 14 days, 40 patients were randomised into treatment with either hourly topical voriconazole or at least three intrastromal voriconazole injections.

Both groups also received identical topical treatments, including natamycin, homatropine and ciprofloxacin. Baseline characteristics were comparable in both groups, including organism culture positivity rate of around 60 per cent.

There was no statistical difference in mean duration to healing between the two groups. Adverse events of perforation and posterior synechiae were similar, although pain was reported more frequently in the intrastromal group (p=0.05), reported Dr Sharma.

Dr Sharma suggested adding intracameral antifungals in cases in which hypopyon was present. Taking this concept to the next level, Dr Sharma reminded delegates of the 2014 study by Pallikaris et al in which the 150kHz Intralase iFS laser was used to create a corneal pocket into which antifungals can be deposited.

Another possibility for intrastromal delivery is Natamatrix, which is a tiny, dissolvable matrix that can be inserted into the stroma. “The pharmacokinetics of intrastromal drug injection need further study, but this is a treatment modality that might offer hope to those with recalcitrant fungal corneal infections,” she concluded.

Namrata Sharma: namrata.sharma@gmail.com