A 32-year-old woman presents with recurrent episodes of corneal ulceration preceded by vesicular rash on the eyelid. Slit-lamp examination shows a branching ulcer with reduced corneal sensation. Regarding the pathophysiology and management of this condition, all of the following are true EXCEPT:

Explanation

## Correct Answer Analysis **Key Point:** Viral DNA replication is NOT confined to the epithelium during primary infection. While epithelial HSV keratitis is the most common presentation, HSV can involve stromal and endothelial layers even in primary infection, particularly in immunocompromised patients. Stromal involvement indicates deeper viral penetration or immune-mediated inflammation. ## HSV Infection: Anatomical Levels & Pathophysiology | Level | Mechanism | Clinical Form | Viral Replication | |-------|-----------|---------------|-------------------| | **Epithelium** | Direct viral cytolysis | Dendritic/geographic ulcers | Active (primary & recurrent) | | **Stroma** | Immune-mediated inflammation ± viral antigen | Stromal keratitis, neovascularization | Minimal to absent (immune-driven) | | **Endothelium** | Viral invasion + immune response | Endotheliitis, Descemet's folds | Variable | **High-Yield:** In primary HSV infection, viral replication CAN extend beyond the epithelium into the stroma, especially in neonates or immunocompromised hosts. Stromal involvement in recurrent disease is predominantly **immune-mediated** (type IV hypersensitivity) rather than due to active viral replication. ## Latency & Reactivation 1. **Site of latency:** Trigeminal ganglion (sensory neuron nuclei) 2. **Reactivation triggers:** Stress, fever, UV exposure, immunosuppression, menstruation, trauma 3. **Axonal transport:** Virus travels along trigeminal nerve to cornea → epithelial reinfection 4. **Prodrome:** Lid vesicles, pain, photophobia, foreign body sensation (hours to days before ulcer) **Clinical Pearl:** Recurrent HSV keratitis is preceded by **prodromal symptoms** in ~50% of patients — lid vesicles, pain, or photophobia — which can help distinguish HSV from other causes of recurrent keratitis. ## Management Strategy ```mermaid flowchart TD A[HSV Keratitis Presentation]:::outcome --> B{Which layer involved?}:::decision B -->|Epithelial| C[Topical antivirals<br/>Acyclovir 5x daily]:::action B -->|Stromal| D[Topical antivirals +<br/>Topical corticosteroids]:::action B -->|Endothelial| E[Systemic acyclovir +<br/>Topical steroids]:::action C --> F{Healing?}:::decision F -->|Yes| G[Continue antivirals<br/>until epithelialization]:::action F -->|No| H[Add systemic acyclovir<br/>or switch antiviral]:::action D --> I[Steroids reduce stromal<br/>inflammation & neovascularization]:::outcome ``` **Warning:** Topical corticosteroids are CONTRAINDICATED in epithelial disease (risk of geographic ulcer) but are ESSENTIAL in stromal keratitis (immune-mediated). Always pair steroids with antivirals in stromal disease.