What is the difference between nummular epithelial keratitis due to adenoviral and Herpes Simplex Virus (HSV) infections?

Distinguishing Nummular Epithelial Keratitis: Adenoviral vs HSV

The key difference is that HSV produces excavated dendritic ulcers with terminal bulbs that stain with fluorescein, while adenoviral keratitis presents with multiple subepithelial infiltrates (nummular lesions) that develop after the acute follicular conjunctivitis phase and do not represent true epithelial ulceration.

Clinical Presentation Differences

HSV Epithelial Keratitis

• Usually unilateral presentation with bulbar conjunctival injection and watery discharge 1
• Distinctive excavated dendritic epithelial keratitis with branching patterns and terminal bulbs that stain brightly with fluorescein 1
• May present with vesicular rash or ulceration of eyelids as an accompanying sign 1
• Mild follicular conjunctival reaction with possible palpable preauricular lymphadenopathy 1
• In primary HSV infection, the cornea shows myriads of clear epithelial vesicles that progress to rounded limbal epithelial foci before forming typical dendrites 2
• Can be bilateral in atopic, pediatric, or immunocompromised patients 1

Adenoviral Keratitis

• Often sequentially bilateral with abrupt onset and varying severity 1
• Presents with prominent follicular reaction of inferior tarsal conjunctiva, marked chemosis, and eyelid swelling that can resemble orbital cellulitis 1
• Subepithelial corneal infiltrates (nummular lesions) develop as a sequela of epidemic keratoconjunctivitis, typically appearing after the acute phase 1
• Associated with membrane/pseudomembrane formation and punctate epithelial keratitis that evolves to anterior stromal involvement 1
• Clear history of exposure to infected individuals (especially school settings) or recent ocular testing 1

Morphological Distinctions

HSV Characteristics

• Excavated ulcers with true epithelial defects that penetrate Bowman's layer 1
• Pleomorphic dendritic pattern with characteristic branching and terminal bulbs 1
• Early vesicular changes precede dendritic formation in primary infection 2
• Ulceration can extend to the conjunctiva in severe cases 1

Adenoviral Characteristics

• Non-excavated punctate epithelial keratitis in the acute phase 1
• Subepithelial infiltrates (nummular lesions) represent immune-mediated inflammation beneath intact or minimally disrupted epithelium 1
• Multiple, scattered, coin-shaped (nummular) opacities that are subepithelial rather than epithelial ulcers 1

Natural History and Timeline

HSV Pattern

• Usually subsides without treatment within 4 to 7 days unless complications develop 1
• Requires topical antiviral therapy (ganciclovir 0.15% gel 3-5 times daily or trifluridine 1% solution 5-8 times daily) combined with oral antivirals 3
• Topical corticosteroids are absolutely contraindicated in HSV epithelial keratitis as they potentiate viral replication 3

Adenoviral Pattern

• Self-limited with improvement within 5 to 14 days in most cases 1
• Subepithelial infiltrates from epidemic keratoconjunctivitis can persist for weeks to months after acute infection resolves 1
• No specific antiviral treatment available; management is supportive 1

Critical Diagnostic Pitfalls

Common Misidentification Risks

• Do not confuse the non-excavated pseudodendritic pattern of varicella zoster virus with HSV's excavated dendrites or adenoviral punctate keratitis 1
• Adenoviral subepithelial infiltrates may be mistaken for HSV stromal disease, but the presence of preceding follicular conjunctivitis and bilateral involvement favors adenovirus 1
• HSV can present bilaterally in atopic patients, potentially mimicking adenoviral infection, but the excavated dendritic morphology remains distinctive 1

Key Distinguishing Features Summary

• Laterality: HSV typically unilateral; adenovirus often sequentially bilateral 1
• Ulcer morphology: HSV shows excavated dendrites; adenovirus shows non-excavated punctate keratitis or subepithelial infiltrates 1
• Conjunctival response: HSV has mild follicular reaction; adenovirus has prominent inferior tarsal follicles with chemosis 1
• Associated findings: HSV may have vesicular lid lesions; adenovirus associated with upper respiratory infection and epidemic exposure 1
• Treatment implications: HSV requires immediate antiviral therapy without steroids; adenovirus is self-limited with supportive care only 1, 3