HSV stromal keratitis is the most common cause of infectious corneal blindness in the United States, and it is the form of recurrent herpetic external disease associated with the greatest visual morbidity. Stromal involvement results from immunologic activity generated by the host against the virus. Each episode of active stromal keratitis increases the risk of future episodes.
CLINICAL PRESENTATION
Herpetic stromal keratitis can be nonnecrotizing (interstitial or disciform) or necrotizing, and different forms may present simultaneously. Herpetic interstitial keratitis presents as unifocal or multifocal interstitial haze or whitening of the stroma in the absence of epithelial ulceration (Fig 9-10). Mild stromal edema may accompany the haze, but epithelial edema is not typical. In the absence of significant extracorneal inflammatory signs such as conjunctival injection or anterior chamber cells, it may be difficult to identify active disease in an area of previous scarring and thinning. Long-standing or recurrent HSV interstitial keratitis may be associated with corneal vascularization. The differential diagnosis of herpetic interstitial keratitis includes
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VZV keratitis
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Acanthamoeba keratitis
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syphilis
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EBV keratitis
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mumps keratitis
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Lyme disease
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sarcoidosis
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Cogan syndrome
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atopic keratitis
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vernal keratitis
Herpetic disciform keratitis is a primary endotheliitis, which presents as corneal stromal and epithelial edema in a round or oval distribution, associated with keratic precipitates underlying the zone of edema (Fig 9-11). Iridocyclitis can be associated, and the disciform keratitis may be confused with uveitis with secondary corneal endothelial decompensation. However, in disciform keratitis, disc-shaped stromal edema and keratic precipitates appear out of proportion to the degree of anterior chamber reaction. Disciform keratitis due to HSV and that due to VZV are clinically indistinguishable.
Necrotizing herpetic keratitis appears as suppurative corneal inflammation (Fig 9-12). It may be severe, progress rapidly, and appear clinically indistinguishable from fulminant bacterial or fungal keratitis. Overlying epithelial ulceration is common, but the epithelial defect may occur somewhat eccentric to the infiltrate, and the edges of the epithelial ulcer do not stain with rose bengal dye. Corneal stromal vascularization is common. The differential diagnosis for necrotizing herpetic keratitis includes microbial keratitis due to bacteria, fungi, or acanthamoebae; retained foreign body; and topical anesthetic abuse.
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MANAGEMENT
Many past controversies regarding the optimal management of HSV stromal keratitis have been resolved by the landmark HEDS (Table 9-6). Most important, HEDS findings showed that topical corticosteroids given with a prophylactic antiviral reduce persistence or progression of stromal inflammation and shorten the duration of HSV stromal keratitis; in addition, long-term suppressive oral acyclovir therapy reduces the rate of recurrent HSV keratitis and helps preserve vision. Lifelong antiviral prophylaxis is recommended for patients with multiple recurrences of HSV stromal keratitis.
The experimental protocol applied by HEDS investigators for patients with herpetic stromal keratitis is a useful starting point for a treatment algorithm. Visually significant herpetic interstitial keratitis is treated initially with prednisolone 1% drops every 2 hours, accompanied by a prophylactic antiviral drug, either topical trifluridine 4 times daily or an oral agent such as acyclovir 400 mg twice daily or valacyclovir 500 mg once a day. The prednisolone drops are tapered every 1–2 weeks depending on the degree of clinical improvement. The antiviral is given to prevent severe epithelial keratitis should the patient shed HSV while using corticosteroid drops, and it is generally continued until the patient has completely stopped the corticosteroids or is using less than 1 drop of prednisolone 1% per day. The corticosteroid should be tapered to the lowest possible dosage that controls the patient’s inflammation.
Currently available topical antiviral medications are not absorbed by the cornea through an intact epithelium, but orally administered acyclovir penetrates an intact cornea and anterior chamber. In this context, anecdotal evidence suggests that oral acyclovir might benefit the deep corneal inflammation of disciform keratitis. The HEDS showed no additional benefit when acyclovir was added to trifluridine and prednisolone for the treatment of herpetic stromal keratitis, but disciform keratitis was not analyzed as a separate group. Some cornea specialists routinely substitute oral acyclovir for topical trifluridine in treating disciform keratitis.
Necrotizing stromal keratitis is probably the least common but most destructive form of herpetic keratitis. The diagnosis is frequently one of exclusion following negative cultures for fungal and bacterial pathogens, but it is suggested by a history of facial, conjunctival, and/or corneal HSV infection. The toxicity of topical antiviral agents may be undesirable in patients with necrotizing inflammation and can confuse the clinical picture. Therefore, an oral antiviral such as acyclovir is preferred. Fortunately, necrotizing herpetic keratitis seems to be very sensitive to topical corticosteroids, and twice-a-day dosing may be sufficient to control inflammation in many patients.