Necrotizing Stromal Keratitis (Herpes): Signs and Risks

Necrotizing stromal keratitis is the most destructive form of herpes simplex virus (HSV) disease in the corneal stroma.

It combines active viral replication with an intense immune reaction.

As a result, the stroma can melt, ulcerate and perforate within days.

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What Necrotizing Stromal Keratitis Is

In the Holland and Schwartz classification, HSV stromal keratitis has two forms.

The nonnecrotizing form is immune driven and usually responds to steroids under antiviral cover.

The necrotizing form, however, adds live virus and tissue destruction.

Therefore, the clinician must treat infection and inflammation at the same time.

Why the Stroma Breaks Down

Viral antigen in the stroma attracts neutrophils and other immune cells.

These cells then release proteases and collagenases.

In addition, replicating virus damages keratocytes directly.

Because both processes act together, collagen loss can progress quickly.

Symptoms of Necrotizing Stromal Keratitis

Patients report pain, redness, photophobia and blurred vision.

Many also describe earlier herpetic eye attacks.

However, corneal anesthesia from prior episodes may blunt pain.

Therefore, mild symptoms do not exclude deep destruction.

Slit Lamp Signs of Necrotizing Stromal Keratitis

The examiner sees a dense, cheesy white stromal infiltrate.

An overlying epithelial defect is common, and it stains with fluorescein.

Around the infiltrate, the stroma often looks thinned or excavated.

Also look for neovascularization, anterior chamber reaction and hypopyon in severe cases.

Exam Features to Record

• Infiltrate size and depth
• Epithelial defect dimensions
• Residual thickness at the thinnest point
• Corneal sensation compared with the fellow eye
• Intraocular pressure and anterior chamber cells

Necrotizing Stromal Keratitis vs Disciform Keratitis

Disciform keratitis is an endotheliitis with a round zone of stromal edema.

The epithelium stays intact, and keratic precipitates sit under the edema.

In contrast, the necrotizing form shows a dense infiltrate, ulceration and thinning.

Disciform disease rarely melts, so its threat is mainly scarring and endothelial damage (see herpetic disciform keratitis).

Nonnecrotizing immune stromal keratitis also keeps the epithelium intact, while it leaves haze and ghost vessels.

Necrotizing Stromal Keratitis Mimics

A white infiltrate with an epithelial defect is microbial keratitis until proven otherwise.

Therefore, keep the differential broad.

• Bacterial keratitis, especially in contact lens wearers
• Fungal keratitis after plant trauma
• Acanthamoeba keratitis
• Bacterial superinfection of a herpetic ulcer
• Peripheral ulcerative keratitis from systemic vasculitis

Tests in Necrotizing Stromal Keratitis

Corneal scraping for Gram stain and culture helps exclude bacterial and fungal infection.

HSV PCR on scrapings can support the diagnosis, although a negative result does not exclude stromal virus.

Anterior segment OCT measures residual thickness and tracks thinning.

In addition, reduced corneal sensation favors a herpetic cause (see fungal vs bacterial keratitis clues).

Antiviral Therapy

Antivirals target replicating virus and form the base of treatment.

Clinicians usually prescribe oral acyclovir or valacyclovir at treatment doses.

Topical ganciclovir gel or trifluridine may help when epithelial disease coexists.

However, antivirals cannot restore collagen already lost.

In the Herpetic Eye Disease Study (HEDS), adding oral acyclovir to topical steroid and trifluridine showed no significant benefit for stromal keratitis.

Also, oral acyclovir needs dose adjustment in renal impairment.

Steroid Logic in Necrotizing Stromal Keratitis

Topical steroids suppress the immune attack that drives melting.

HEDS showed that prednisolone with trifluridine speeds resolution of stromal keratitis.

However, steroids also slow epithelial healing and may favor viral replication.

Therefore, many corneal specialists start them only under full antiviral cover, at low frequency, and taper slowly.

Necrotizing cases were less well studied, so much management relies on expert consensus and the AAO guideline.

Managing Thinning and Perforation

Severe thinning needs close observation, sometimes daily.

Cyanoacrylate glue with a bandage contact lens can seal a small perforation.

Amniotic membrane may also support healing of persistent defects.

Larger perforations then require tectonic keratoplasty.

Surgery After Necrotizing Stromal Keratitis

Penetrating keratoplasty in an inflamed herpetic eye carries a high risk of rejection and recurrence.

Therefore, most surgeons wait until the eye has stayed quiet for several months.

Surgeons usually continue oral antiviral prophylaxis after grafting.

Preventing Recurrence

The HEDS prevention trial found that long-term oral acyclovir reduced recurrent stromal keratitis.

Patients with previous stromal disease showed a clear benefit.

As a result, many clinicians offer prophylaxis after a necrotizing episode.

Even so, recurrence can occur once prophylaxis stops.

Counseling Patients With Necrotizing Stromal Keratitis

Explain that infection and inflammation both need treatment.

Patients should never stop antivirals early or adjust steroid drops alone.

Also warn them to return at once if pain rises or vision drops suddenly.

Finally, discuss that scarring may limit vision after the infection settles (see herpes simplex keratitis).

Pitfalls to Avoid

• Starting steroids without antiviral cover
• Assuming every herpetic stromal lesion is purely immune
• Missing bacterial or fungal superinfection
• Ignoring reduced sensation as a clue
• Tapering steroids too quickly, which invites rebound inflammation

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References

1. Holland EJ, Schwartz GS. Classification of herpes simplex virus keratitis. Cornea. 1999;18:144-154.
2. Wilhelmus KR, Gee L, Hauck WW, et al. Herpetic Eye Disease Study: a controlled trial of topical corticosteroids for herpes simplex stromal keratitis. Ophthalmology. 1994;101:1883-1896.
3. Barron BA, Gee L, Hauck WW, et al. Herpetic Eye Disease Study: a controlled trial of oral acyclovir for herpes simplex stromal keratitis. Ophthalmology. 1994;101:1871-1882.
4. Herpetic Eye Disease Study Group. Acyclovir for the prevention of recurrent herpes simplex virus eye disease. N Engl J Med. 1998;339:300-306.
5. White ML, Chodosh J. Herpes simplex virus keratitis: a treatment guideline. American Academy of Ophthalmology. 2014.