Diagnosing HSV in the Eye
Diagnosis of HSV keratitis is primarily clinical based on characteristic findings of dendritic or geographic corneal ulcers on slit-lamp examination with fluorescein staining, supplemented by laboratory confirmation using immunofluorescence assay (IFA) or PCR when the diagnosis is uncertain. 1, 2
Clinical Diagnosis: The Foundation
The diagnosis starts with recognizing distinctive clinical features on examination:
- Corneal findings: Look for pleomorphic or excavated dendritic epithelial keratitis, which is pathognomonic for HSV 1
- Conjunctival signs: Unilateral bulbar conjunctival injection, watery discharge, and mild follicular reaction 1
- Eyelid involvement: Vesicular rash or ulceration of the eyelids strongly suggests HSV 1
- Lymphadenopathy: Palpable preauricular lymph node may be present 1
- Fluorescein staining: Essential to visualize dendritic ulcers that may not be apparent otherwise 3
Laboratory Confirmation: When and How
When clinical presentation is atypical or diagnosis uncertain, laboratory testing should be pursued:
Preferred Diagnostic Tests
- Immunofluorescence assay (IFA) combined with PCR provides optimal diagnostic accuracy for HSV-1 keratitis 4, 2
- IFA sensitivity is 78.6-85.7% with specificity of 85.3-95%, making it highly reliable 4, 2
- PCR sensitivity is 81.2-100% but specificity is lower at 67.9%, meaning it may detect non-pathogenic viral DNA 4, 2
- The combination of both tests maximizes diagnostic yield—if either is positive in a clinically suspected case, HSV is confirmed 4, 2
Alternative Diagnostic Method
- Giemsa staining for multinucleated giant cells has only 57.1% sensitivity but 85.9-100% specificity 4, 2
- This method can provide presumptive diagnosis in atypical cases when IFA/PCR are unavailable, but negative results do not rule out HSV 4, 2
Specimen Collection Technique
Corneal scrapings must be obtained properly for accurate testing:
- Firm corneal scraping or imprint to glass slides is required for IFA and Giemsa staining 2, 5
- Samples should be collected from the ulcer edge where viral replication is most active 2
- Fixation with cold acetone is necessary for immunofluorescence testing 5
Critical Diagnostic Pitfalls to Avoid
Several common errors can lead to missed or delayed diagnosis:
- Do not rely solely on Giemsa staining—its low sensitivity (57%) means many cases will be missed if used alone 4, 2
- Viral culture takes several days and is not practical for acute management decisions, though it remains the gold standard 4
- Bilateral presentation can occur in atopic, pediatric, or immunocompromised patients, so don't exclude HSV based on bilaterality alone 1
- Consider HSV reactivation in COVID-19 patients presenting with keratitis symptoms, as SARS-CoV-2 may trigger HSV reactivation 3
When to Suspect HSV Keratitis
Key clinical scenarios that should prompt consideration of HSV:
- History of prior HSV infection with triggers including stress, febrile illness, UV exposure, surgery, or trauma 1
- Primary HSV infection following exposure to an infected individual 1
- Unilateral presentation with photophobia, tearing, decreased vision, eye redness, and pain 1, 3
- Corneal anesthesia may be present in recurrent disease 1
Immediate Management Considerations
Once HSV is diagnosed or strongly suspected clinically, treatment should not be delayed for laboratory confirmation:
- Initiate combination therapy immediately with topical ganciclovir 0.15% gel 3-5 times daily AND oral antiviral (valacyclovir 500 mg 2-3 times daily or acyclovir 400 mg five times daily) 6, 7
- Never use topical corticosteroids in epithelial HSV keratitis as they potentiate viral replication 6, 7
- Schedule follow-up within 1 week with visual acuity and slit-lamp examination to monitor treatment response 6, 7