Investigations for suspected viral corneal ulcer (viral keratitis)

1. Clinical assessment

• Visual acuity in each eye, before treatment.
• History: previous similar episodes, fever, herpes labialis, shingles, contact-lens use, trauma, topical steroid use, immunosuppression.
• Slit-lamp biomicroscopy:
  • HSV: branching dendritic epithelial ulcer with terminal bulbs
  • VZV: raised pseudodendrites, generally without terminal bulbs
  • Adenovirus: punctate epithelial keratitis or subepithelial infiltrates
  • Look for stromal infiltrate/edema, anterior uveitis, keratic precipitates, and raised IOP.
• Fluorescein staining highlights the dendritic ulcer bed.
• Rose Bengal or lissamine green stains the swollen ulcer margins. Kanski describes fluorescein staining of the dendrite base and Rose Bengal staining at its edges. Kanski's Clinical Ophthalmology, p. 237.
• Test corneal sensation. It may be reduced in HSV and VZV keratitis, especially with neurotrophic disease.
• Examine eyelids and skin for herpetic vesicles or a zoster rash, and examine the fellow eye.

2. Microbiological confirmation

• PCR/NAAT for HSV-1, HSV-2, VZV, and where indicated adenovirus. This is the preferred confirmatory test because it is rapid and generally more sensitive than culture.
• Viral culture if PCR is unavailable, but it is slower and less sensitive.
• Direct immunofluorescence antigen detection, where available.
• Cytology smear using Giemsa/Papanicolaou stain may show multinucleated giant cells and intranuclear inclusions, but has limited sensitivity.

3. Tests to exclude other microbial keratitis

• Corneal scraping for Gram stain and bacterial culture/sensitivity
• KOH wet mount/calcofluor and fungal culture
• Testing/culture for Acanthamoeba when contact-lens related or pain is disproportionate to signs
• Consider corneal biopsy/superficial keratectomy if repeated scrapes are negative but the ulcer progresses.

4. Additional investigations in complicated disease

• Tonometry: HSV/VZV keratouveitis may cause elevated intraocular pressure.
• Anterior segment OCT: useful to document epithelial defect and stromal thinning, not to establish viral etiology.
• Corneal esthesiometry if neurotrophic keratopathy is suspected.
• Aqueous humor PCR for HSV/VZV/CMV in atypical endotheliitis, keratouveitis, or unexplained high IOP, under ophthalmology supervision.