varicella occurring as zoster during some period of life [169]. Zoster is rare in childhood, and patients with zoster are less contagious than patients with varicella because of the absence of respiratory infection.

The occurrence of zoster is influenced mostly by the host and is independent of the prevalence of varicella. The risk of zoster infection increases with development of malignancies, use of chemotherapy, bone marrow transplantation, and trauma [170, 171]. Humoral immunity appears to play no role in varicella-zoster reactivation [172].

The mode of entry of the virus into the host in varicella is not fully understood but is thought to occur through the mucous membrane contact in the oropharynx, upper respiratory tract, conjunctiva, and skin. During the primary infection, the virus spreads centripetally by neuronal routes from the skin and the mucosal lesions to the corresponding sensory ganglia via contagious sensory nerve endings and sensory nerve fibers. In the ganglia, the virus establishes a latent infection probably in the satellite cells that surround the neurons [167, 173]. Later in life, reactivated virus may travel centrifugally down the sensory nerves to the skin and produce vesicles along associated dermatome, which is the hallmark of zoster.

Maternal varicella infection during pregnancy has been associated with the congenital varicella syndrome [174–178]. This syndrome, although rare, is associated with a mortality rate as high as 30% when mothers contact varicella in the last few days of pregnancy or in the first few days postpartum [179]. The disease has also been reported to occur in infants born to mothers who had cutaneous zoster during pregnancy [180]. Because the newborn does not receive protective transplacental maternal antibodies and has an immature immune system, illness is often severe.

Systemic manifestations of prenatal infection are protean and include atrophic limbs, cicatricial skin lesions, cerebral atrophy, seizures, intrauterine growth retardation, and developmental delay, among others.

16.3.2.1  Ocular Manifestations

Development of retinitis during the course of the primary systemic infection either in congenital VZV infection or following chickenpox is rare. VZV retinitis does occasionally develop as a reactivation of infection in adults. Ocular manifestations of congenital

Varicella infection include microphthalmos, cataract, Horner’s syndrome, Chorioretinitis, chorioretinal scars, and optic atrophy. Chorioretinal scars are typically small or large with a gliotic center surrounded by black pigmentation mimicking the scar of congenital toxoplasmosis. The remaining retina appears normal, with frequent sparing of the macula and retinal vessels. Serological studies may be required to differentiate this clinical picture from other causes of TORCH syndrome, particularly toxoplasmosis.

In primary acquired varicella infection, a variety of chorioretinal lesions may be seen occur in children and adults [181]. A mild form of necrotizing retinitis has been reported rarely [182–186]. Thirty percent of reported cases occurred in children, and a few cases were associated with mild immunosuppression. The disease is unilateral in most cases, and the typical lesion is peripheral, localized, and mild. Vitritis may be present, which produces symptomatic floaters. Vitritis typically develops as the skin lesions are fading. Vasculitis, when present, is localized to the area of retinitis. The retinitis is typically self-limited and fades within 2–3 weeks from the onset, usually with no adverse effect on the vision. Because of the self-limited nature of the condition, treatment is usually not required.

HZV is among the viral etiologies of acute retinal necrosis syndrome and is the major virus causing ­progressive outer retinal necrosis syndrome (See Pro­ gressive outer retinal necrosis below). Unifocal choroiditis has rarely been reported to occur with primary VZV infection (Chickenpox). In one patient, unilateral choroiditis with overlying serous detachment developed [187]. Multifocal choroiditis has also been reported in a few cases following Herpes zoster ophthalmicus [188, 189]. Multiple yellow-white lesions, which resemble those of birdshot’s retinopathy, can develop and may be associated with vitritis and anterior uveitis. These lesions may represent either choroidal granulomatous inflammation or choroidal infarcts caused by occlusion of the posterior ciliary arteries [190]. Vitreous hemorrhage has rarely been the presenting sign of ocular disease [191].

16.3.3  Herpes Simplex Virus

Herpes simplex Virus (HSV) is one of the most common infectious agents to inflict humans. Type 1 (HSV 1)

is transmitted by direct contact with skin surfaces, typically affecting areas above the waist, while Type 2 (HSV 2) is most commonly transmitted via genital infection and typically affects regions below the waist.

Primary infection with HSV occurs in the susceptible host with no HSV antibodies. HSV 1 is the most common serotype responsible for the initial infections in children and produces the majority of herpetic eye disease in all age groups [192]. Infrequently, HSV 2 is blamed for the ocular disease in children [193–196]. Neonates, children, and immunocompromised adults are at greatest risk of the disease. The disease is most commonly unilateral [192] and predominantly affects the cornea and the conjunctiva, rarely causing retinochoroiditis and chorioretinal scarring [195].

Like other members of herpes viruses, the organism consists of a linear double stranded DNA surrounded by a capsid and covered by a lipid containing membrane [197]. It can be transmitted intrapartum (neonatal infection) from contact with infected genital secretions in the maternal birth canal or uncommonly via the placental (congenital infection) to an unborn fetus. Congenital infection (transplacental) usually occurs with mothers who have a history of new onset HSV disease, typically during the second trimester.

When transmitted transplacentally, disseminated infection of the fetus can occur, leading to severe systemic and ocular sequences. The disease is fatal for most congenitally infected neonates. Seventy percent of neonatal HSV is caused by HSV 2. HSV 1 can be acquired postnatally through contact with persons who have symptomatic or asymptomatic orolabial HSV 1 infection [198].

Only around 30% of mothers of infants who develop neonatal disease have signs and symptoms of HSV genital infection at the time of delivery [199]. Neonatal ocular infection occurs in around 20% of HSV infected neonates, of whom 5% develop HSV retinitis. In neonates with HSV encephalitis, the incidence of ocular disease is as high as 60% with retinal disease occurring in up to 25% [195].

Infections transmitted transplacentally during the first and the second trimester are associated with a variable degree of fetal anomalies namely, congenital heart disease, intrauterine growth retardation, short digits, skin pigmentation, and CNS abnormalities [200]. Systemic features of both congenital and neonatal HSV disease include encephalitis, gastrointestinal

tract inflammation, hepatitis, hepatosplenomegaly, thrombocytopenia, lymphadenopathy, and adrenal necrosis [198, 201]. Untreated neonatal HSV infection has an extremely high mortality rate.

16.3.3.1  Ocular Disease

HSV ocular involvement is often misdiagnosed, particularly if only conjunctivitis is present and if skin and oral lesions are absent. Skin involvement is never seen in 20% of infected neonates, so absence of skin lesions does not exclude neonatal HSV infection.

In transplacentally acquired infections, there is no typical pattern of ocular or retinal lesions. These features may be dependent on the size of the viral inoculum and the stage of development of the affected fetus. The following is a list of ocular lesions reported to occur in congenital and presumably congenital HSV infection; optic atrophy, vitreous masses, microcornea, microphthalmos, and nystagmus [202, 203]. A case of bilateral persistent fetal vasculature has been reported in an infant infected with HSV transplacentally [204]. Reported retinal lesions in congenital HSV-infected infants are scarce, as the disease is uncommon and usually fatal. Retinal lesions were in the form of healed chorioretinal scars [202, 203] (Fig. 16.9a, b).

Ocular manifestations of neonatally acquired infection include conjunctivitis, the commonest ocular finding, followed in frequency by keratitis. Ocular surface involvement is usually unilateral and rarely isolated [205]. Other reported anterior segment findings include cataract and corneal scarring [206].

Posterior segment manifestations include bilateral atrophic and nonpigmented scars, active retinal vasculitis, vitritis, retinal hemorrhages, optic atrophy, vascular tortuosity, and rarely exudative retinal detachment and retinal necrosis [194, 202, 207, 208].

Retinal lesions in congenital and neonatal HSV infection are characterized by bilateral retinal destruction with gliosis, proliferative metaplasia of the retinal pigment epithelium, scarce inflammatory cells, and relative sparing of the anterior segment and the choroid. Inclusions consistent with HSV have been noted within all layers of the involved retina and particularly at the junction between the healthy and unhealthy retina [209–211].

Because of the variability of ocular findings associated with congenital and neonatal HSV infection, it is