Clinical Guide for Doctors | Ocular Herpes Simplex vs. Herpes Zoster Ophthalmicus

Herpetic eye disease remains one of the most important viral causes of corneal disease, anterior segment inflammation, and vision-threatening ocular morbidity. Two common entities encountered in clinical practice are ocular herpes simplex virus disease, most often HSV-1, and herpes zoster ophthalmicus, caused by reactivation of varicella-zoster virus in the ophthalmic division of the trigeminal nerve.

Although both conditions may present with redness, pain, photophobia, keratitis, uveitis, and reduced vision, the clinical patterns, recurrence behavior, corneal findings, and treatment considerations differ significantly.

HSV vs HZO infographic with eye photos, a doctor pointing, and clinic office decor.

Ocular Herpes Simplex Virus

Ocular HSV most commonly presents as epithelial keratitis, stromal keratitis, endotheliitis, or anterior uveitis. HSV-1 is the typical cause, although HSV-2 can occur.

Common Clinical Findings

HSV epithelial keratitis may present with:

• Unilateral red eye

• Foreign body sensation

• Tearing

• Photophobia

• Reduced corneal sensation

• Classic branching dendritic epithelial lesion

• Terminal bulbs with fluorescein staining

• Rose bengal or lissamine green staining of devitalized epithelial borders

The classic HSV dendrite is typically a true epithelial ulcer with branching morphology and terminal bulbs. Reduced corneal sensitivity can be an important clinical clue, especially in recurrent disease.

HSV Stromal Keratitis

HSV stromal keratitis may be immune-mediated, necrotizing, or associated with active viral replication. Findings may include:

• Stromal haze or infiltrate

• Corneal edema

• Keratic precipitates

• Anterior chamber reaction

• Neovascularization in recurrent disease

• Scarring or irregular astigmatism

The AAO HSV keratitis guideline notes that stromal keratitis often requires antiviral therapy, and topical corticosteroids may be used when indicated, especially for stromal inflammation, with antiviral coverage.

Typical HSV Treatment Patterns

Treatment depends on the layer involved.

HSV Epithelial Keratitis

Common treatment options include:

• Ganciclovir gel 0.15% 5 times daily until healed, then commonly reduced for several days

• Trifluridine 1% up to 9 times daily, though toxicity limits prolonged use

• Oral acyclovir 400 mg 5 times daily

• Oral valacyclovir 500 mg TID

• Oral famciclovir 250–500 mg TID

EyeWiki notes that HSV epithelial keratitis is commonly treated with oral acyclovir, valacyclovir, famciclovir, and/or topical antiviral therapy for approximately 10–14 days.

Topical steroids are generally avoided in active epithelial HSV keratitis unless there is a specific indication and adequate antiviral coverage.

HSV Stromal Keratitis / Endotheliitis / Uveitis

For stromal or endothelial disease, treatment often includes:

• Oral antiviral coverage

• Topical corticosteroid for stromal or anterior chamber inflammation

• Cycloplegia if significant iritis is present

• IOP monitoring and treatment if pressure rises

For stromal keratitis, the AAO guideline emphasizes antiviral therapy and appropriate corticosteroid use when stromal inflammation is present.

Herpes Zoster Ophthalmicus

Herpes zoster ophthalmicus occurs when varicella-zoster virus reactivates in the ophthalmic division of cranial nerve V. HZO may involve the eyelids, conjunctiva, cornea, sclera, uveal tract, trabecular meshwork, retina, optic nerve, and cranial nerves.

Unlike HSV, HZO often has a prominent dermatomal component.

Typical Clinical Presentation of HZO

Patients may present with:

• Unilateral forehead, scalp, or periocular pain

• Burning, tingling, or hyperesthesia before rash onset

• Vesicular rash in the V1 distribution

• Eyelid edema

• Conjunctivitis

• Episcleritis or scleritis

• Punctate epithelial keratitis

• Pseudodendrites

• Stromal keratitis

• Endotheliitis

• Anterior uveitis

• Elevated IOP

• Sectoral iris atrophy

• Neurotrophic keratopathy

• Post-herpetic neuralgia

The zoster pseudodendrite is usually more elevated, “stuck-on,” and often lacks the classic terminal bulbs seen in HSV epithelial dendrites.

Hutchinson’s Sign

Hutchinson’s sign refers to vesicular lesions on the tip, side, or root of the nose, reflecting involvement of the nasociliary branch of the ophthalmic division of the trigeminal nerve.

Clinically, Hutchinson’s sign is important because the nasociliary nerve also innervates ocular structures, so nasal involvement increases suspicion for ocular involvement.

Clinical Significance

Patients with Hutchinson’s sign have a higher risk of:

• Keratitis

• Anterior uveitis

• Corneal hypoesthesia

• Trabeculitis

• Elevated IOP

• Neurotrophic keratopathy

• Delayed ocular inflammation

A classic study found Hutchinson’s sign to be a strong predictor of ocular inflammation and corneal denervation in HZO.

However, the absence of Hutchinson’s sign does not rule out ocular disease. Patients with V1 shingles can still develop ocular complications without nasal lesions. Any patient with shingles involving the forehead, eyelid, or periocular region should be evaluated for ocular involvement.

Typical Oral Treatment for HZO

Systemic antiviral therapy is the mainstay of HZO treatment and is most effective when started early, ideally within 72 hours of rash onset. Treatment may still be appropriate beyond 72 hours if new lesions are developing, ocular involvement is present, or the patient is immunocompromised.

Typical oral regimens include:

Medication	Common Adult Dose
Acyclovir	800 mg PO 5 times daily for 7–10 days
Valacyclovir	1 g PO TID for 7 days
Famciclovir	500 mg PO TID for 7 days

StatPearls lists systemic antivirals, topical corticosteroids, cycloplegics, analgesics, and selected systemic corticosteroids or adjunctive therapy as part of HZO management depending on severity and ocular involvement.

For immunocompromised patients or severe orbital, retinal, neurologic, or disseminated disease, urgent ophthalmology involvement and possible IV acyclovir are often required.

Elevated IOP in HZO: Trabeculitis and Inflammatory Glaucoma

One of the important clinical complications of HZO is elevated intraocular pressure. The IOP spike may occur from inflammatory involvement of the trabecular meshwork, commonly described as trabeculitis, and may also be worsened by steroid response during treatment.

In HZO anterior uveitis, the trabecular meshwork can become inflamed, reducing aqueous outflow and causing secondary ocular hypertension. These patients may present with:

• Anterior chamber cell and flare

• Keratic precipitates

• Corneal edema if IOP is high

• Sectoral iris atrophy

• Pupil irregularity

• Eye pain or brow ache

• IOP elevation that may be disproportionate to the level of visible inflammation

AAO guidance emphasizes that IOP should be measured during HZO treatment because pressure spikes may be related to the ocular disease itself or to steroid use.

Treating HZO Trabeculitis and High IOP

When elevated IOP is due to active inflammatory trabeculitis, the treatment approach usually requires both controlling inflammation and lowering pressure.

Anti-inflammatory Treatment

Topical corticosteroids are often used when there is stromal keratitis, endotheliitis, trabeculitis, or anterior uveitis. A common approach may include:

• Prednisolone acetate 1% depending on severity, then slow taper

• Loteprednol or fluorometholone in milder cases or steroid responders

• Close monitoring of IOP and inflammation

• Continued systemic antiviral coverage

The key clinical point is that pressure may not normalize unless the underlying trabecular inflammation is treated. In this setting, topical steroid is not simply optional “comfort treatment”; it may be necessary to quiet the inflammatory mechanism driving the IOP elevation.

IOP-Lowering Treatment

Depending on IOP level and optic nerve risk, treatment may include:

• Topical beta-blocker

• Topical carbonic anhydrase inhibitor

• Alpha-agonist

• Oral acetazolamide in more significant spikes, if not contraindicated

Prostaglandin analogs are often used cautiously in active herpetic inflammation because of theoretical or clinical concern for worsening inflammation or viral recurrence in susceptible patients. Miotics are generally avoided in active uveitis.

Cycloplegia may also be used for ciliary spasm, posterior synechiae prevention, and patient comfort.

HSV vs. HZO: Clinical Differentiation

Feature	HSV	HZO
Virus	Herpes simplex virus, usually HSV-1	Varicella-zoster virus
Typical history	Recurrent unilateral keratitis, cold sore history possible	Prior chickenpox, shingles, older age or immunocompromise
Skin findings	Usually absent, unless periocular HSV lesions	Dermatomal V1 vesicular rash
Corneal lesion	True dendrite with terminal bulbs	Pseudodendrite, often elevated and without terminal bulbs
Corneal sensation	Often reduced	May be reduced, especially with neurotrophic disease
Uveitis	Can occur	Common and may be granulomatous
IOP elevation	Can occur with HSV trabeculitis/uveitis	Common concern with HZO trabeculitis/uveitis
Steroid role	Used for stromal disease/uveitis with antiviral coverage	Used for stromal keratitis, uveitis, trabeculitis with antiviral coverage
Antiviral dosing	HSV dosing generally lower than zoster dosing	Higher zoster dosing required

Practical Clinical Pearls

1. Do not confuse HSV dendrites with HZO pseudodendrites.

HSV dendrites typically stain as true epithelial defects with terminal bulbs. HZO pseudodendrites may appear elevated, mucous plaque-like, and less ulcerative.

2. Hutchinson’s sign increases concern, but absence is not reassuring enough.

Nasal tip, side, or root involvement should raise suspicion for ocular disease, but ocular involvement can still occur without nasal lesions.

3. Always check IOP.

HZO and HSV can both produce anterior uveitis and trabeculitis. IOP may rise from trabecular inflammation, steroid response, or both.

4. Treat inflammatory IOP by treating inflammation.

If IOP elevation is driven by active trabeculitis, pressure-lowering drops alone may not fully address the mechanism. Topical steroid therapy, with antiviral coverage, is often required.

5. Avoid steroid monotherapy in active herpetic disease.

Steroids may be necessary for stromal keratitis, endotheliitis, trabeculitis, or uveitis, but they should generally be used with appropriate antiviral coverage and close follow-up.

6. Watch for neurotrophic keratopathy.

Both HSV and HZO can reduce corneal sensation. Persistent epithelial defects, poor healing, and recurrent surface breakdown should prompt evaluation for neurotrophic disease.

Follow-Up Considerations

Follow-up frequency depends on severity, but clinicians should monitor:

• Visual acuity

• Corneal staining

• Stromal edema or infiltrate

• AC cell/flare

• IOP

• Corneal sensation

• Pupil/iris changes

• Steroid response

• Epithelial healing

• Development of neurotrophic keratopathy

Patients with HZO may develop delayed ocular inflammation even after the rash begins improving, so follow-up should not stop simply because the skin lesions are crusting.

Clinical Takeaway

Ocular HSV and HZO can both cause keratitis, uveitis, trabeculitis, elevated IOP, and vision-threatening inflammation, but their clinical patterns are distinct. HSV more often presents as recurrent corneal disease with classic dendritic epithelial lesions, while HZO is associated with V1 dermatomal shingles, pseudodendrites, Hutchinson’s sign, anterior uveitis, trabeculitis, and delayed inflammatory sequelae.

For HZO, oral antivirals such as valacyclovir 1 g TID, famciclovir 500 mg TID, or acyclovir 800 mg five times dailyare typical treatment choices. When high IOP is secondary to inflammatory trabeculitis, management often requires both IOP-lowering therapy and topical corticosteroids with antiviral coverage.