Part 4 • Infectious Uveitic Conditions

Chapter 13 Other Viral Diseases

HSV iridocyclitis were randomly assigned to receive a 10-week course of either oral aciclovir 400 mg five times daily or placebo in conjunction with topical trifluridine and a topical corticosteroid. The trial was stopped early because of slow recruitment after only 50 of the planned 104 patients were enrolled. Treatment failure, defined as persistence or worsening of ocular inflammation, withdrawal of medica­ tion because of toxicity, or withdrawal for any reason, occurred in 11 of 22 patients (50%) receiving aciclovir and in 19 of the 28 patients (68%) receiving placebo. Although the difference in failure rates was not statistically significant between the two groups, there was a trend toward a better outcome in the patients receiving oral aciclovir. Finally, oral aciclovir effectively prevents herpes-related recurrences after penetrating keratoplasty in herpetic eye disease, supporting the use of the drug.13

Valaciclovir and famciclovir are dosed less frequently than oral aciclovir and may be a useful alternative. In a small, prospective, randomized clincal trial of 52 immunocompe­ tent patients oral valaciclovir (500 mg daily was as effective and well tolerated as aciclovir (400 mg twice daily) in reduc­ ing the rate of recurrent ocular herpes simplex virus disease.14 In another small randomized clinical trial, oral valaciclovir had similar efficacy to topical aciclovir ointment in patients with herpes simplex keratitis.15 Wilhelmus16 compared the effects of various therapeutic interventions for dendritic or geographic HSV epithelial keratitis by searching the Cochrane Central Register of Controlled Trials. The conclu­ sion of the review was that currently available antiviral agents are effective and nearly equivalent. The author also noted that the combination of a nucleoside antiviral with either debridement or with interferon seemed to speed healing.

Work to develop a vaccine for HSV infection is ongoing. In a small randomized clinical trial, the use of a vaccination with heat shock-inactivated herpes simplex virus type 1 (HSV-1) seemed to reduce the number and duration of relapses in HSV-1-related keratitis or keratouveitis.17

Secondary glaucoma is associated with herpetic kerato­ uveitis and may be difficult to control, especially in patients with rubeosis. Glaucoma in these patients often requires surgical treatment with a drainage device. Nevertheless, vision loss related to glaucoma is common in these patients.

Herpes simplex retinitis is clearly caused by direct infec­ tion of the retina by the virus. As already stated, some cases of acute retinal necrosis may be caused by HSV infection (see Chapter 12). In addition, herpes simplex retinitis can occur in congenital HSV infection associated with herpes encepha­ litis.18 This infection is usually caused by herpes simplex type 2 (HSV-2) and may be acquired in utero rather than during birth. Many patients with congenital herpes simplex retinitis have corneal and anterior chamber involvement as well, obscuring a clear view of the retina. When retinal lesions are seen clinically or pathologically, they appear as large, white retinal infiltrates associated with vitritis and retinal vascular sheathing. After the lesions heal, there are large areas of atrophic and scarred retina. The systemic infection with herpes simplex is often overwhelming and fatal.

Herpes simplex retinitis has also been reported in patients who have undergone chemotherapeutic immunosuppres­ sion, and again a viral encephalitis often accompanies this ocular condition. Large areas of white retinitis with retinal

necrosis result from the viral infection. The disorder may also occur in patients without immunosuppression, and diagnosis in some patients has been made after chorioretinal biopsy.19 In some patients the disorder appears to respond to treatment with intravenous aciclovir.

Herpes zoster ophthalmicus

Varicella-zoster virus (VZV) causes two clinically distinct diseases. Primary infection causes varicella: chicken pox;20 recurrent infection is known as herpes zoster infection. Although uveitis has been reported with varicella, most cases occur with herpes zoster infection. In fact, uveitis associated with herpes zoster infection often occurs with herpes zoster ophthalmicus. Ocular involvement is noted in two-thirds of patients with herpes zoster involving the ophthalmic divi­ sion of the trigeminal nerve.21 VZV is a DNA herpes class virus and remains latent in the ganglia after the patient has had chickenpox. Although reactivation occurs frequently in elderly patients, reactivation may also occur in young and healthy persons with no known immunosuppression. Cuta­ neous herpes zoster has been associated with defects in cel­ lular immunity, and this disorder has been frequently seen with HIV infection.

Anterior uveitis can accompany herpes zoster ophthal­ micus and probably results from vascular occlusion and secondary ischemia. Intraocular inflammation occurs in one-third to one-half of patients.21,22 A severe glaucoma often arises in patients with severe inflammatory disease, and corneal disease manifested by dendritic keratitis, stromal keratitis, or exposure keratitis is a common finding. Large keratic precipitates and posterior synechiae accompany the anterior uveitis. Although the anterior uveitis may appear with the initial cutaneous lesions, it often develops 1–2 weeks after the onset of dermatologic disease. In a small number of patients, scleritis may be seen. The iris should be closely examined because it may be the key to correct diag­ nosis. Sector and patchy iris atrophy consistent with ischemic damage is characteristic of the disorder. Hyphema may occur, and some eyes develop phthisis because of severe ischemic destruction of the iris and ciliary body. Histologic study in severe disease reveals vascular inflammation and a granulomatous cellular infiltrate in the uvea.23 Occasionally a retinal vascular occlusive disease or severe choroiditis with associated vitreal inflammation can be seen.

Treatment

Treatment with oral aciclovir early in the course of herpes zoster infection, when the cutaneous lesions are still active, appears to reduce viral proliferation and the complications of the infection, including anterior uveitis.24–26 The usual dose of aciclovir is 800 mg five times daily. Famciclovir at a dose of 500 mg three times daily had efficacy similar to that of aciclovir for treating patients with ophthalmic zoster,27 and valaciclovir has also been used effectively to treat the severity and duration of zoster infection. In contrast, aciclo­ vir appears to have little effect on the development of post­ herpetic neuralgia. In addition, several weeks into the course of the disease the anterior uveitis is not caused by active viral replication but by ischemia. Therefore, antiviral therapy appears to be no longer useful. The anterior uveitis and