What are the contraindications for intrastromal antifungal injection in patients with fungal keratitis?

Contraindications for Intrastromal Antifungal Injection in Fungal Keratitis

There are no absolute contraindications specifically documented in current guidelines for intrastromal antifungal injection in fungal keratitis; however, the procedure should be avoided in cases of impending or frank corneal perforation, extremely thin cornea where injection could precipitate perforation, and when the integrity of the eye is already severely compromised. 1

Clinical Context and Evidence Base

The available evidence shows that intrastromal antifungal injection is actually used as a salvage therapy for the most severe cases, but this does not mean it is appropriate for all severe presentations:

Relative Contraindications Based on Corneal Integrity

• Impending or frank perforation represents the most critical contraindication, as the mechanical trauma of injection could complete a perforation in an already compromised cornea 1

• Extremely thin cornea poses similar risks, where the needle insertion itself could cause iatrogenic perforation during the injection procedure 1

• Active corneal melting with significant stromal loss may make the injection technically unsafe and potentially counterproductive 1

When Intrastromal Injection Is Actually Indicated

The evidence demonstrates that intrastromal antifungal injection is reserved for recalcitrant deep fungal keratitis that has failed to respond to maximal topical and systemic antifungal therapy 2, 3:

• A case series of 12 patients showed that intrastromal voriconazole (50 μg in 0.1 ml) achieved healing in 10 of 12 eyes with recalcitrant fungal keratitis, though 2 corneas perforated and required therapeutic penetrating keratoplasty 2

• The technique involves injection at the junction of clear cornea and infiltrates using a 30-gauge needle in five quadrants to form a barrage around the ulcer 2

• Intrastromal amphotericin B has also been successfully used for recurrent fungal keratitis, offering a less invasive alternative to repeat penetrating keratoplasty 4

Important Clinical Caveats

The variable evidence on efficacy of intrastromal antifungals noted in guidelines suggests this is not a first-line therapy but rather a salvage option 1:

• Fungal keratitis has inherently worse outcomes than bacterial keratitis, with larger infiltrate/scar, slower re-epithelialization, and higher perforation rates at 3 months 1

• The risk of perforation during or after intrastromal injection must be weighed against the risk of progressive disease without intervention 2

• Cases with impending perforation may be better served by immediate surgical intervention (tissue adhesive, amniotic membrane, or keratoplasty) rather than intrastromal injection 1

Practical Algorithm for Decision-Making

Before considering intrastromal antifungal injection, assess:

1. Corneal thickness and structural integrity - if less than approximately 200 microns or showing active melting, surgical options are safer 1

2. Response to maximal medical therapy - intrastromal injection is only indicated after failure of topical hourly antifungals plus systemic therapy 2, 3

3. Presence of deep stromal involvement - superficial infections do not require and should not receive intrastromal injection 2, 3

4. Risk-benefit in context of perforation risk - if perforation appears imminent within hours to days, proceed directly to surgical intervention rather than attempting injection 1