A 32-year-old woman presents with a 5-day history of right eye pain, photophobia, and blurred vision. She reports a vesicular rash on the forehead and upper eyelid 2 days prior to eye symptoms. On examination, visual acuity is 6/9, and slit-lamp biomicroscopy reveals branching dendritic ulcers with terminal bulbs on the cornea. Corneal sensation is reduced. What is the most appropriate initial pharmacological management?

Explanation

## Clinical Diagnosis **Key Point:** The constellation of vesicular rash on V1 distribution (forehead/eyelid), dendritic ulcers with terminal bulbs, and reduced corneal sensation is pathognomonic for **Herpes Simplex Virus (HSV) keratitis**, specifically primary HSV-1 infection. ## Mechanism of Dendritic Ulcers Dendritic ulcers in HSV keratitis result from viral replication in corneal epithelial cells. The characteristic **branching pattern with terminal bulbs** represents: - Central area of infected epithelial cells (staining with rose bengal or lissamine green) - Lateral extensions of viral spread along nerve endings - Terminal bulbs at the tips of dendrites (areas of active viral replication) ## Management Algorithm ```mermaid flowchart TD A[HSV Keratitis - Dendritic Ulcer]:::outcome --> B{Epithelial Disease Only?}:::decision B -->|Yes| C[Topical Acyclovir 5x/day]:::action B -->|No - Stromal/Endothelial| D[Add Oral Acyclovir + Topical Steroid]:::action C --> E[Plus Oral Acyclovir 400mg 5x/day × 10 days]:::action E --> F[Healing in 7-10 days]:::outcome D --> G[Prevent recurrent scarring]:::outcome ``` ## Pharmacological Rationale | Agent | Indication | Mechanism | Notes | |-------|-----------|-----------|-------| | **Topical Acyclovir 5%** | Epithelial HSV keratitis (dendritic/geographic) | Viral DNA polymerase inhibitor; high corneal penetration | First-line for epithelial disease | | **Oral Acyclovir 400 mg 5×/day** | Systemic viral suppression | Achieves therapeutic aqueous humor levels | Reduces recurrence risk; essential in primary infection | | Topical Ganciclovir | CMV keratitis (rare in immunocompetent) | Broader spectrum; requires phosphorylation by viral kinase | Not first-line for HSV; reserved for acyclovir resistance | | Topical Cidofovir | Acyclovir-resistant HSV (immunocompromised) | Nucleotide analog; direct viral DNA inhibition | Expensive; reserved for resistant cases | | Interferon-alpha | Adjunctive in severe stromal disease | Antiviral + immunomodulatory | Rarely used as monotherapy; outdated | **High-Yield:** Combination of **topical acyclovir 5 times daily + oral acyclovir 400 mg 5 times daily** is the gold standard for primary HSV epithelial keratitis. Oral therapy reduces systemic viral load and prevents contralateral eye involvement and recurrences. ## Clinical Pearls **Clinical Pearl:** Reduced corneal sensation in HSV keratitis is due to viral invasion of trigeminal nerve terminals and is a hallmark finding that distinguishes HSV from bacterial keratitis. **Warning:** Do NOT use topical steroids in epithelial HSV keratitis — they promote geographic ulceration (coalescence of dendrites). Steroids are only indicated in stromal or endothelial disease, always with concurrent antiviral cover. **Key Point:** The dendritic ulcer typically heals within 7–10 days with appropriate antiviral therapy. Failure to heal suggests acyclovir resistance (rare in immunocompetent hosts) or incorrect diagnosis. ## Expected Course 1. Epithelial healing: 7–10 days with topical + oral acyclovir 2. Corneal sensation recovery: weeks to months 3. Recurrence rate: ~50% within 5 years (oral prophylaxis reduces to ~20%)