Diagnosis and Management of Herpetic Anterior Uveitis

Anterior uveitis is the most common form of intraocular inflammation, accounting for more than 90% of uveitis cases seen by community ophthalmologists 1 and from 30% to 60% of uveitis cases seen at tertiary referral centers. 1–3 Most cases of anterior uveitis are either idiopathic or associated with HLA-B27 positivity. Herpetic anterior uveitis due either to herpes simplex virus (HSV) or varicella-zoster virus (VZV) infection accounts for 5% to 10% of all uveitis cases seen at tertiary referral centers, however, and is the most common cause of infectious anterior uveitis. 4–6 Clinical Features Herpetic anterior uveitis can be caused by either HSV or VZV infection and may be accompanied by dermatitis, conjunctivitis, keratitis, scleritis, or retinitis. 7–11 It is virtually always unilateral, and patients most frequently complain of blurred vision accompanied by eye pain, redness, and photophobia. 12,13 Each episode of herpetic anterior uveitis can last from 1 week to several months, 9,12,13 and recurrences are common. Anterior chamber inflammation may be mild or severe and may even produce a hypopyon or hyphema. 13 Keratic precipitates may appear small, large, or stellate and collect frequently under areas of active keratitis. 4,13 Posterior synechiae are common. 4,13 Many patients also have decreased corneal sensation, 14 an acute rise in the intraocular pressure, 6,7,14,15 or patchy, sectoral, or diffuse iris atrophy, which may distort the pupil and which is best seen on transillumination. 6,9,10,16–18 The acute increase in intraocular pressure has been attributed by most authors to inflammation of the trabecular meshwork, 7 a notion supported by the observation that intraocular pressure typically normalizes in response to topical corticosteroid therapy. 7,15 Such hypertensive episodes resemble, in many ways, the attacks of Posner-Schlossman syndrome, which some investigators have suggested may be due to HSV infection. 14,19 Sectoral iris atrophy, which results from ischemic necrosis of the stroma, 18,20 is a very specific sign for the presence of herpetic anterior uveitis. Yamamoto and coworkers 17 collected aqueous humor from 6 patients with recurrent iridocyclitis and sectoral iris atrophy and demonstrated herpetic DNA in each case, including 5 cases with HSV DNA and one case with VZV DNA. Van der Lelij and colleagues 14 analyzed the aqueous humor of 24 patients with recurrent iridocyclitis and sectoral iris atrophy for herpesvirus DNA and herpesvirus-specific antibodies using polymerase chain reaction (PCR) and the Goldman-Witmer coefficient, respectively. Twenty patients (83.1%) were positive for HSV and 3 (12.5%) for VZV using one or both assays. Of note, VZV was identified more often in patients older than 60 years. Over time, such complications as cataract and glaucoma may develop. 7,9 Diagnosis The diagnosis of herpetic anterior uveitis usually is based on clinical findings. The presence of herpetic dermatitis or dendritic keratitis provides the strongest diagnostic support, but these findings are often absent. In such situations, the diagnosis usually remains presumptive and is based on the presence of corneal stromal scars or edema, decreased corneal sensation, acutely elevated intraocular pressure, or iris atrophy. One should always consider other uveitic conditions that can produce findings suggestive of herpetic anterior uveitis, however. Stromal keratitis, for example, can be seen in Epstein-Barr virus, 21 syphilis, 22,23 tuberculosis, 24 sarcoidosis, 25 leprosy, 26 or onchocerciasis. 27 Similarly, leprosy can cause decreased corneal sensation. 28 Anterior uveitis with an acute raise in intraocular pressure can be seen in syphilis, 29 sarcoidosis, 30 leprosy, 31 and the Posner-Schlossman syndrome. 32 Even more difficult than diagnosing herpetic anterior uveitis may be distinguishing between HSV and VZV as the cause of anterior uveitis, 4 as both viruses can present with similar findings. History and examination may suggest which virus is the more likely etiological agent in some patients. 4,6 HSV usually affects children and young adults, for example, whereas HZV is more commonly seen in elderly and immunocompromised patients. Skin lesions in HSV usually consist of grouped vesicles with diffuse edema. In VZV, in contrast the distribution of the vesicles follows a dermatomal distribution, usually on the region innervated by V 1 . A dermatomal distribution has also been reported in cases of HSV dermatitis (zosteriform herpes simplex), 33 however. The pattern of dendritic keratitis, when present, may also help to differentiate HSV from VZV uveitis. HSV dendrites are usually branching, with well-developed terminal end bulbs that tend to show fluorescein staining in the ulcer base and rose bengal staining at the border. VZV pseudodendrites, in contrast, are usually slightly elevated, broader, and polymorphous, with less regular branching, few terminal end bulbs, and central rose bengal staining with fluorescein pooling along the edge. 34 Both viral cultures and, more recently, PCR-based analysis of aqueous humor samples can be used to diagnose herpetic anterior uveitis more securely. Viral cultures, however, are difficult and time-consuming and have a low sensitivity. 13,35 The sensitivity of PCR-based analyses for HSV or VZV DNA in aqueous humor samples has ranged from 25% to 100% in various studies 14,17,35 but overall appears to be better than culture. Among authors, there are several explanations for this difference in PCR sensitivity. 17 First, the clinical criteria for the selection of patients with presumed herpetic anterior uveitis could have varied considerably between the different studies. Second, the primer sets used in each laboratory were different, and this could have altered the sensitivity of each test. Finally, PCR techniques can differ among laboratories. A less widely used method for the diagnosis of herpetic anterior uveitis is the Goldman-Witmer coefficient, which measures the intraocular production of antibodies directed against specific organisms. 14,36 This method is less specific than PCR or culture, however, because antibodies directed against HSV may cross-react with those for VZV. Moreover, the positivity of the Goldman-Witmer coefficient seems to vary with time from onset of the uveitis. 36 Management Management of herpetic anterior uveitis remains controversial. Topical corticosteroids and oral antivirals have become the mainstays of treatment, however. 4 Topical corticosteroids control the iridocyclitis 7,15,37 and also acutely decrease intraocular pressure owing to their antiinflammatory effects on the trabecular meshwork. 7 Corticosteroids should be tapered slowly once the inflammation is controlled, however, as a “rebound” effect can take place if they are withdrawn too rapidly. 7 Some patients may even require a very low dose of topical corticosteroid indefinitely to maintain long-term control of their inflammation. 4 Acyclovir ointment 3% four times daily can be used in place of oral acyclovir, as it provides good ocular penetration. 15 Oral acyclovir appears to provide some benefit over acyclovir ointment, however, because it does not blur vision and is not associated with corneal toxicity. The usual dosage of oral acyclovir is 400 mg five times daily for HSV and 800 mg five times daily for VZV. Oral acyclovir, 600 to 800 mg/day, has been shown to diminish the number of recurrences in patients with herpetic anterior uveitis when given on a long-term basis. 38 Oral acyclovir has been shown to reduce the incidence and severity of ocular complications, including anterior uveitis, when given for 10 days starting within 72 hours of onset of skin lesions in patients with herpes zoster ophthalmicus. 10 Similar effects have been shown with oral valacyclovir, a prodrug of acyclovir, 1 gm three times daily for 7 days. 39 Topical and oral ocular antihypertensive agents are often necessary to control the ocular hypertension, especially during the first days of treatment. The ocular hypertension may become chronic, however, owing to the inflammation or the chronic use of corticosteroids, and either long-term antihypertensive drops or a filtering procedure may be required. Latanoprost should probably be avoided because it may potentiate reactivation of herpesviruses. 40 Patients with herpetic anterior uveitis also typically require a topical cycloplegic-mydriatic agent, both to prevent posterior synechiae formation and for improved comfort. Summary Herpetic anterior uveitis is a relatively common condition. History of herpetic disease and the presence of characteristic findings on ocular examination suggest the diagnosis and help to differentiate between HSV and VZV as the cause of this condition. New diagnostic techniques have allowed a more specific diagnosis. Topical corticosteroids and oral antivirals have become the main standards for management. This work was supported in part by a Career Development Award to Dr. E. T. Cunningham, Jr., from Research to Prevent Blindness, Inc., New York, NY.