Herpes Simplex Keratitis - Initial Therapy

Key Points

• A classic dendritic epithelial lesion with terminal bulbs strongly suggests HSV epithelial keratitis.
• Epithelial HSV reflects active viral replication and is treated with antiviral therapy.
• Do not use topical corticosteroid monotherapy for active epithelial keratitis.
• Stromal keratitis is treated differently and often requires topical corticosteroid plus antiviral coverage under ophthalmology supervision.
• Check IOP when uveitis or trabeculitis is present and the globe is otherwise safe to examine.
• Oral acyclovir, valacyclovir, or famciclovir and topical ganciclovir or trifluridine are accepted antiviral options.
• Recurrent stromal disease can lead to permanent scarring and may justify suppressive oral antiviral therapy.
• Failure to improve should prompt reconsideration of Acanthamoeba, bacterial, fungal, zoster, neurotrophic, or toxic disease.

Algorithm

1. Assess unilateral red eye with pain or photophobia using visual acuity and slit-lamp fluorescein examination.
2. Identify whether disease is epithelial only or whether stromal haze, uveitis, endotheliitis, or elevated IOP is present.
3. For epithelial disease, start an accepted topical or oral antiviral regimen.
4. Avoid topical corticosteroid in isolated active epithelial disease.
5. If stromal or intraocular inflammation is present, obtain urgent ophthalmology guidance for corticosteroid plus antiviral therapy.
6. Stop contact-lens wear and avoid home topical anesthetic use.
7. Reassess healing and visual acuity; modify treatment if epithelial disease persists or deeper inflammation emerges.
8. Consider long-term suppressive antiviral therapy in recurrent high-risk disease.

Clinical Synopsis & Reasoning

Herpes simplex virus keratitis is a recurrent ocular infection that can involve the corneal epithelium, stroma, endothelium, iris, or multiple layers. Epithelial keratitis reflects active viral replication and classically produces a branching dendritic epithelial ulcer with terminal bulbs that stains with fluorescein and rose bengal or lissamine green. Symptoms include unilateral pain, photophobia, tearing, foreign-body sensation, redness, and blurred vision, although corneal sensation may be reduced. Recurrent episodes can leave scarring and neurotrophic surface disease.

The clinical subtype determines treatment. Epithelial disease is treated with antiviral therapy and generally should not receive topical corticosteroids because steroids can enhance viral replication and convert a dendrite into a larger geographic ulcer. Stromal keratitis is largely immune-mediated and may require topical corticosteroid to prevent scarring, but steroid is given with antiviral coverage and close ophthalmology monitoring. Endotheliitis and HSV anterior uveitis likewise often require corticosteroid plus antiviral therapy and IOP surveillance. The distinction is therefore not academic: a drug appropriate for stromal disease can worsen untreated epithelial viral disease.

Diagnosis is usually clinical by slit-lamp examination. PCR or viral culture is reserved for atypical cases, immunocompromised patients, refractory disease, or diagnostic uncertainty. Differential diagnosis includes herpes zoster, healing abrasion, recurrent corneal erosion, Acanthamoeba, toxic keratopathy, and bacterial or fungal infection. A history of prior cold sores is neither necessary nor sufficient for diagnosis. Bilateral disease is uncommon in immunocompetent adults and should prompt consideration of immune compromise or alternative diagnoses.

Treatment Strategy & Disposition

For epithelial keratitis, use topical or oral antiviral therapy. AAO guidance supports options such as oral acyclovir, valacyclovir, or famciclovir, or topical ganciclovir or trifluridine. Oral therapy avoids topical epithelial toxicity and is often convenient, while topical ganciclovir is well tolerated. Trifluridine is effective but frequent dosing and epithelial toxicity limit prolonged use. Debridement is not required in most modern treatment strategies but may be used selectively by ophthalmology.

Do not prescribe topical corticosteroid for an active epithelial dendrite unless an ophthalmologist identifies a separate steroid-responsive component and ensures adequate antiviral coverage. For stromal keratitis, HEDS data support topical corticosteroid with antiviral therapy, usually tapered slowly according to inflammation. IOP should be monitored because both HSV trabeculitis and corticosteroids can elevate pressure. Oral antiviral prophylaxis can reduce recurrences in patients with frequent episodes, prior stromal disease, or around certain ocular surgeries.

Urgent ophthalmology review is warranted for reduced vision, central lesions, stromal haze, anterior-chamber inflammation, elevated IOP, immunocompromise, uncertain diagnosis, or failure to improve. Patients with uncomplicated peripheral epithelial disease still require timely follow-up to confirm healing. Contact lenses should be stopped during active disease. Avoid topical anesthetic prescriptions for home use because they impair epithelial healing and mask progression.

Epidemiology / Risk Factors

• HSV-1 is the predominant cause of ocular herpes simplex disease in many populations.
• Reactivation from trigeminal latency causes recurrent episodes and cumulative corneal injury.
• Recurrent stromal keratitis is a major cause of infectious corneal scarring and visual impairment.
• Immunosuppressed patients can have atypical, bilateral, or more severe disease.

Investigations

Example Regimens

Pharmacology

Prognosis / Complications

• Uncomplicated epithelial keratitis usually heals with antiviral therapy and can leave little permanent visual loss if central scarring does not develop.
• Recurrent stromal inflammation carries a greater risk of scarring, neovascularization, thinning, and reduced vision.
• Neurotrophic keratopathy can complicate recurrent HSV because corneal sensation decreases over time.
• Long-term suppressive oral antiviral therapy reduces recurrence risk in selected patients with previous stromal disease.

Patient Education / Counseling

• Explain that the virus remains latent and future recurrences are possible even after the current ulcer heals.
• Advise against using leftover steroid eye drops because steroids can worsen active epithelial HSV.
• Stop contact lenses until the epithelium has healed and ophthalmology approves restarting them.
• Provide urgent return precautions for reduced vision, increasing pain, expanding white corneal opacity, or severe photophobia.
• Discuss suppressive antiviral therapy when recurrent disease or prior stromal involvement creates a high risk of visual damage.

Notes

The most dangerous prescribing error in HSV keratitis is treating every inflamed cornea with a steroid before defining whether active epithelial virus is present. Epithelial HSV and stromal HSV can coexist in the same disease family but have opposite implications for corticosteroid use. A reference article should make the subtype decision explicit before listing medications.

Modern oral antivirals make treatment simpler for many patients, but they do not eliminate the need for slit-lamp follow-up. Healing of the epithelial defect, development of stromal inflammation, IOP changes, and recurrent disease determine whether the plan should remain antiviral-only or transition to specialist-directed anti-inflammatory therapy.

References

1. American Academy of Ophthalmology HSV Keratitis Treatment Guideline — Link
2. AAO: Herpes Simplex Epithelial Keratitis — Link