Is topical voriconazole more effective than topical natamycin in treating fungal keratitis?

Topical Natamycin is Superior to Voriconazole for Fungal Keratitis

For filamentous fungal keratitis, topical natamycin 5% should be used as first-line therapy rather than voriconazole, as it produces significantly better visual outcomes and reduces the risk of corneal perforation or need for therapeutic keratoplasty. 1, 2

Evidence-Based Treatment Algorithm

First-Line Therapy Selection

• Natamycin 5% ophthalmic suspension is the preferred initial treatment for fungal keratitis, applied hourly while awake until re-epithelialization, then four times daily for at least 3 weeks 1, 2

• The Infectious Diseases Society of America guidelines recommend either topical natamycin 5% or topical voriconazole for Aspergillus keratitis, but the most recent high-quality randomized trial demonstrates natamycin's superiority 1, 2

Comparative Efficacy Data

• In the landmark Mycotic Ulcer Treatment Trial (MUTT), natamycin-treated patients achieved significantly better 3-month visual acuity than voriconazole-treated patients (0.18 logMAR difference; P=0.006) 2

• Natamycin reduced the odds of corneal perforation or need for therapeutic penetrating keratoplasty by 58% compared to voriconazole (odds ratio=0.42; P=0.009) 2

• The benefit was most pronounced in Fusarium keratitis, where natamycin produced dramatically better outcomes (0.41 logMAR improvement; P<0.001) with 94% reduction in perforation risk (odds ratio=0.06; P<0.001) 2

Organism-Specific Considerations

• For Fusarium species (40% of filamentous fungal keratitis cases): natamycin is clearly superior and should always be used first-line 2

• For non-Fusarium filamentous fungi including Aspergillus (17% of cases) and other species (43% of cases): outcomes were similar between natamycin and voriconazole, but natamycin remains preferred given its overall safety profile 2

• For Candida species: consider oral fluconazole 400-800 mg daily for susceptible isolates 3

When to Consider Voriconazole

• Voriconazole should NOT be used as monotherapy in filamentous fungal keratitis based on the MUTT trial results 2

• Voriconazole may be added as adjunctive therapy to natamycin in recalcitrant cases not responding after 2 weeks of natamycin monotherapy 4

• In recalcitrant cases, topical voriconazole 1% added to natamycin produced better visual outcomes (1.295 logMAR) than intrastromal voriconazole injections (1.692 logMAR; P=0.008) 4

Critical Management Points

Diagnostic Workup Before Treatment

• Obtain corneal scrapings from the ulcer base and periphery using proparacaine 0.5% before initiating antifungal therapy, and inoculate directly onto fungal culture media 3

• Do not tap the hypopyon as it is typically sterile unless concurrent endophthalmitis from trauma or surgery is present 3

Adjunctive Therapies

• Use cycloplegics (atropine 1% or homatropine 5%) to reduce pain and prevent synechiae formation 3

• Consider oral doxycycline or minocycline 100 mg twice daily to inhibit matrix metalloproteinases and reduce corneal melting risk 3

• Avoid topical corticosteroids initially, as fungal keratitis has worse outcomes than bacterial keratitis with higher perforation rates 3

Monitoring Protocol

• Perform daily examinations until clear clinical improvement is documented 3

• Reassess at 3-4 days to evaluate treatment response 3

• Continue treatment for a minimum of 14-21 days even with clinical improvement to prevent relapse 3

Common Pitfalls to Avoid

• Do not assume voriconazole is equivalent or superior to natamycin - the highest quality evidence demonstrates natamycin's superiority for filamentous fungi 2, 5

• Delaying corneal scraping leads to incorrect differentiation between bacterial and fungal keratitis 3

• Starting corticosteroids early can cause rapid progression of fungal keratitis 3

• Using preserved anesthetics or cycloplegics before obtaining cultures reduces culture yield 3

Surgical Intervention Thresholds

• Consider surgery when progressive stromal thinning occurs despite maximal medical therapy, or with impending/frank corneal perforation 3

• Amniotic membrane transplantation may stabilize the ocular surface, though it does not reduce hypopyon size or duration 3

• Therapeutic penetrating keratoplasty may be necessary for large perforations or progressive disease 3