A 28-year-old man with a history of recurrent corneal ulcers presents with pain, tearing, and a white infiltrate in the cornea. Slit-lamp examination shows a central corneal opacity with stromal edema and anterior chamber reaction. The patient is on topical acyclovir but symptoms persist. Which investigation would best differentiate between HSV stromal keratitis and bacterial superinfection?

Explanation

## Differential Diagnosis: HSV Stromal Keratitis vs. Bacterial Superinfection ### Clinical Scenario The patient has: - Recurrent HSV keratitis (stromal involvement) - Persistent symptoms despite acyclovir - Central corneal opacity with stromal edema - Anterior chamber reaction This raises concern for **bacterial superinfection**, which complicates ~5–10% of HSV keratitis cases. ### Investigation Strategy | Investigation | Detects | Sensitivity | Specificity | Turnaround | Clinical Value | |---|---|---|---|---|---| | **PCR (viral + bacterial)** | HSV + bacteria | 95–98% (both) | >95% | 2–4 hrs | **Simultaneous diagnosis** | | Gram stain + culture | Bacteria only | 60–80% | 100% | 2–7 days | Slow; misses HSV | | Confocal + immunofluorescence | Morphology + HSV | Variable | Variable | 1–2 hrs | Qualitative; not quantitative | | AS-OCT | Stromal thickness | N/A | N/A | Real-time | Structural; not diagnostic | ### Key Point: **Multiplex PCR (viral + bacterial panels)** is the investigation of choice because it simultaneously detects HSV and bacterial pathogens in a single test, enabling rapid differentiation and targeted therapy. ### High-Yield: Why multiplex PCR is superior: 1. **Simultaneous detection** of HSV and bacteria in one assay 2. **Rapid results** (2–4 hours) vs. culture (5–7 days) 3. **Higher sensitivity** for fastidious organisms (Pseudomonas, Staphylococcus) 4. **Guides therapy**: Continue acyclovir if HSV-positive; add antibiotics if bacteria detected ### Clinical Pearl: Bacterial superinfection in HSV keratitis is suggested by: - Purulent discharge - Rapid progression despite acyclovir - Hypopyon - Positive bacterial culture Multiplex PCR avoids the diagnostic delay of sequential testing (viral culture → bacterial culture). ### Warning: ~~Gram stain and culture alone~~ will miss HSV and delay diagnosis by 5–7 days. ~~Confocal microscopy~~ is qualitative and cannot definitively rule out bacteria. ~~AS-OCT~~ measures stromal thickness but does not identify the causative organism.