important to distinguish HSV retinitis from other causes of retinitis in a newborn such as TORCH diseases. Viral cultures and assay for IgM antibodies to HSV help to confirm the diagnosis.

16.3.3.2  Treatment of Congenital and Neonatal

HSV Retinitis

Systemic antiviral therapy must be administered urgently to achieve an optimal response. Acyclovir and vidarabine are the most commonly used agents. In neonates, the dose is the same for both drugs (IV 30 mg/kg/day given for 1–4 weeks). The major side effect of acyclovir is transient renal insufficiency, as the drug is excreted through the kidneys. Proper dose adjustment and hydration can minimize occurrence of this complication. Side effects of systemic vidarabine administration include hepatotoxicity and bone marrow suppression.

16.3.4  Acute Retinal Necrosis

Acute retinal necrosis is a well-known clinical entity first described in Japan by Urayoma and originally known as Kirisawa-type uveitis [212]. Herpes virus was confirmed as the etiological agent after histopathological and electron microscopic evaluation of an enucleated eye in 1982 [213]. Further reports and works using various investigational techniques including retinal biopsy specimens, serological analysis of serum or intraocular fluid, viral cultures, immunohistochemical

studies, and temporal relationship between acute retinal necrosis syndrome and herpetic dermatitis have further implicated varicella, zoster, and herpes simplex type 1 and 2 as the causes of this syndrome [214–218]. A few reports have implicated CMV [217, 220–222], and Ebstein barr virus has also been incriminated [223]. Accordingly, any of the herpes viruses, namely VZV, HSV, CMV, and EBV, is thought to be capable of causing ARN.

In recent report, aqueous and vitreous specimens were analyzed by PCR to determine the specific viral cause in each case of individual retinal necrosis. The data suggested that varicela-zoster virus or HSV 1 cause the syndrome in patients over 25 years of age whereas HSV 2 is the most likely cause below 25 years of age. CMV was the cause in only one case in this series [222]. A history of central nervous system involvement in patients with acute retinal necrosis suggests that herpes simplex virus is likely to be the cause [222]. In one study, around half of acute retinal necrosis cases caused by HSV 2 were children, and the overall incidence of children affected by acute retinal necrosis was around 25% [222].

16.3.4.1  Clinical Presentation

Diagnosis of acute retinal necrosis is based on the finding of well-demarcated areas of peripheral retinal necrosis, rapid circumferential progression, occlusive vasculitis (Fig. 16.10), and a prominent inflammatory reaction in the vitreous and anterior chamber [224]. Initially, patients may present with ocular pain with eye movements or may complain of floaters. Anterior

Fig. 16.10  Acute retinal necrosis (Photo courtesy of Peter Buch, University at Buffalo, Ross Eye Institute, Buffalo, NY, USA)

granulomatous uveitis is common, and increased intraocular pressure may occur. Retinitis typically starts in the postequatorial retina characterized by deep round or oval intraretinal lesions, typically sparing the macula. Arteritis may be seen affecting both the peripheral and central arterioles, and optic disc swelling may be present early in the disease course. Over a period ranging from days to a few weeks, patches of necrotizing retinitis begin to appear in the peripheral retina, rapidly spreading circumferentially. The area of retinitis remains mostly outside the major temporal arcades. The associated vitritis is sometimes severe enough to interfere with fundus visualization and may result in reduced vision. Retinal artery or vein occlusion is another potential cause of sudden vision loss, as is optic neuropathy. In the late stages of the disease, the retinitis begins to spontaneously regress. Regression is faster and may take as little as a few days if antiviral treatment has been instituted. Atrophic retina is left in its wake as active retinitis resolves, though vitreous haze may initially increase with sloughing of the necrotic retinal debris into the vitreous. Full thickness retinal necrosis prevents retinochoroidal scar formation, and retinal detachment is a frequent late sequel. Fine salt and pepper pigmentation often develops, in the area of atrophic retina [225].

The disease is bilateral in 25–80% of cases [225, 226]. Both eyes may be affected simultaneously or sequentially within a few days. The wide variation in the estimated incidence of bilaterality may be related to the fact that the second eye involvement sometimes does not occur for many years [227]. Recurrence of

acute retinal necrosis in the same eye has also been reported [228].

In acute retinal necrosis, the histopathological features of the acute phase is characterized by widespread full thickness retinal necrosis and hemorrhages. Inflammatory cells extend into the overlying vitreous. There is sharp demarcation between the necrotic and the normal retina. Other pathological features in the acute phase include occlusive vasculitis ranging from chronic perivascular inflammation to complete occlusion of the vessels by endothelial cells, optic neuritis with necrosis of the optic nerve and heavy infiltration with plasma cells, and chronic panuveitis characterized by dense plasmocytic infiltration [213, 214, 229–231]. In older lesions, pathological features include extensive glial scarring, epiretinal gliosis, granulomatous choroiditis, perivascular infiltration of the retinal arterioles with plasma cells, and lymphocytes [232].

16.3.4.2  Diagnosis

A variety of investigational techniques have been used for identification of the viral causes of ARN and PORN, including retinal biopsy, serological analysis of serum or intraocular fluid, viral cultures, immunohistochemical studies and the temporal relationship between acute retinal necrosis syndrome and herpetic dermatitis [214–219], and most recently PCR-based assay [215, 216, 222, 233]. PCR is a highly sensitive, specific, and rapid means of detecting small amounts of viral DNA in intraocular fluid samples. It is effective both for the diagnosis and in determination of the specific etiologic virus.

16.3.4.3  Treatment

Intravenous acyclovir is the mainstay of treatment for ARN [215, 234, 235]. Intravitreal administration at the time of vitrectomy has also been reported [228, 236]. Adjunctive intravitreal injection of ganciclovir and foscarnet has been reported [237]. Famciclovir has also been used in treatment of ARN [238]. Interferon alpha and beta have been recommended as synergistic adjunctive therapy to acyclovir, especially those cases caused by the Herpes zoster virus [239]. Interferon alpha may be a safe adjunct in children as they have been used successfully in the treatment of infants with