TST Protocol for Fungal Corneal Ulcer Management
The TST (Topical-Systemic-Targeted) protocol is a stepwise treatment algorithm that begins with topical natamycin 5%, escalates to add oral antifungals for larger/deeper ulcers, incorporates topical voriconazole for poor responders, and progresses to intrastromal/intracameral injections or keratoplasty for refractory cases. 1
Protocol Components
Initial Treatment (Topical Phase)
Start all treatment-naive fungal keratitis cases with topical natamycin 5% as first-line therapy 1. This forms the foundation of the TST protocol regardless of ulcer severity.
Escalation Criteria for Systemic Therapy
Add oral ketoconazole or voriconazole when any of these features are present 1:
- Ulcer size >5 mm
- Depth >50% of corneal thickness
- Impending perforation
Targeted Therapy for Non-Responders
If inadequate response occurs at 7-10 days of initial treatment 1:
- Add topical voriconazole 1% to the existing regimen
- This creates combination topical therapy alongside systemic agents if already initiated
Advanced Interventions
For cases showing poor response to combination topical and systemic therapy 1:
- Intrastromal antifungal injections - delivers steady-state drug levels directly into corneal tissue, preventing subtherapeutic intervals 2
- Intracameral antifungal injections - reserved for severe cases with deep stromal infiltration not responding to other treatments 2
Surgical Management
Penetrating keratoplasty is performed when medical management fails at any stage 1. This removes diseased tissue, decreases infectious load, and restores globe integrity 3.
Clinical Outcomes from TST Protocol
The protocol achieved a 79.8% treatment success rate in a cohort of 223 fungal keratitis cases 1. Key metrics included:
- Mean healing time: 41.5 ± 22.2 days
- Corneal perforation rate: 7%
- Keratoplasty required: 20.2% of cases
- Visual improvement: from 2.05 logMAR at presentation to 1.6 logMAR at 3 months
Critical Pitfalls to Avoid
Do not delay systemic therapy in ulcers meeting size/depth criteria - topical therapy alone may be insufficient for larger or deeper infiltrates. The protocol's strength lies in its proactive escalation rather than waiting for treatment failure.
Monitor closely at 7-10 days - this is the critical decision point for adding targeted topical voriconazole. Missing this window delays appropriate escalation.
Consider early surgical intervention - the 20.2% keratoplasty rate demonstrates that a significant minority will require surgery. Early therapeutic keratoplasty before limbal/scleral extension yields better outcomes 3.
Adjunctive Considerations
While not part of the original TST protocol, corneal cross-linking has emerging evidence as adjunctive therapy, though it may worsen visual outcomes through increased corneal scarring and astigmatism 4. Use judiciously only in refractory cases.
Temporary suture tarsorrhaphy can be considered for impending perforations in resource-limited settings, achieving 87.4% anatomical success and 26.9% functional success 5, though this represents salvage rather than definitive therapy.
Organism-Specific Notes
The protocol was validated primarily against Fusarium (42.2%) and Aspergillus (32.8%) 1, which are the most common fungal pathogens. Natamycin remains first-line for filamentous fungi, while voriconazole provides broader coverage when added.