Case report

A 9 day old baby was referred to the eye clinic after having been diagnosed with congenital symptomatic CMV infection.

During pregnancy, at 34 weeks, poor growth and ventriculomegaly were noted and a scan at 35 weeks showed bilateral cysts in the occipital horn of the lateral ventricles. He was born at 40 weeks by emergency caesarean section. The mother was a healthy 18 year old woman. His birth weight was 2.1 kg and his head circumference 31.5 cm, both of which were below the 0.4th centile. Brain magnetic resonance imaging confirmed the presence of bilateral occipital cysts and periventricular calcification. Serology and urine tests showed congenital CMV infection. The child had a normal immune system for his age.

Eye examination revealed sheathing of the retinal vessels and haemorrhages, which involved the arcades and were more marked in the left eye (Fig 1A, B, C). Exudates were present in both eyes superior to the disc (Fig 1A). The following day the vasculitis in the left eye had progressed and was involving the macula. Treatment with ganciclovir 5 mg/kg/day intravenously was started in view of the active retinitis. One week after treatment the haemorrhages and exudation in both eyes were resolving and 2 weeks after treatment complete resolution of the ocular infection occurred (Fig 1D). The macula of the right eye remained unaffected, but scarring occurred in the periphery of both eyes and the left macula. Ganciclovir was stopped 3 weeks after initiation.

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Figure 1

(A, B) Fundus photographs of the left eye showing active CMV retinitis, with a necrotic area over the disc and several haemorrhages and sheathing on the superotemporal and inferotemporal arcade. (C) Fundus photograph of the right eye showing active CMV retinitis with sheathing and exudation on the inferotemporal arcade of the right eye. (D) Same area of the fundus of the right eye showing improvement of the picture after 1 week of treatment.

Electrodiagnostic tests were performed at 4 months and suggested moderate vision in the right eye and poor vision in the left.

On last examination at 5 months the baby would not fixate with the left eye and had developed a divergent squint while he was fixing on bright objects with his right eye. Fundus examination revealed a pale optic disc on the left, vascular attenuation in the left eye, pigmented scars superiorly in both eyes, and right macular gliosis. There was no gross refractive error.

His growth followed a centile just below the 0.4th with delayed development and microcephaly.

Comment

Cytomegalovirus is the most common cause of congenital and perinatal viral infections throughout the world.¹ The incidence of congenital infection ranges from 0.2–2.4% of all live births, with higher rates in populations with a lower standard of living. The fetus may become infected as a consequence of primary and recurrent maternal infection. The risk of fetal infection is greatest with maternal primary CMV infection (40%) and much less likely with recurrent infection (1%). Only 5% of all congenitally infected children have severe disease, another 5% have mild involvement, and 90% are born with subclinical but chronic CMV infection.² The most characteristic signs include intrauterine growth retardation, prematurity, hepatosplenomegaly and jaundice, thrombocytopenia and purpura, and microcephaly and intracranial calcifications. Neurological problems include mild increase in cerebrospinal fluid protein, sensorineural hearing loss, and chorioretinitis. Among the most severely affected infants, mortality may be as high as 30% and death may occur in the neonatal period or months later.² The likelihood that infants who survive symptomatic congenital CMV infection will have normal hearing and intellectual development is small.³ In infants with subclinical infection, the outlook is much better.⁴

Active CMV infection is best demonstrated by virus isolation from urine, saliva, broncheoalveolar washings, breast milk, cervical secretions, and tissues obtained with biopsy. The definitive method for diagnosis of congenital CMV infection is isolation of the virus in urine or saliva. This must be done shortly after birth. Intrauterine, perinatal, or early postnatal acquisition of CMV characteristically causes a more chronic infection with regard to virus excretion than does infection acquired later in life. Virus is shed into the urine for approximately 5 years and frequently into the nasopharynx for 2–4 years. The quantity of virus excreted in these sites is much greater than that found in infected older children and adults. Immaturity of the immune response of the fetus and of young infants is believed to be the major determinant of virulence of the congenital and early postnatally acquired infections. Still, the extent and exact nature of the immune defect in congenitally infected infants have yet to be resolved.⁵ CMV can also be diagnosed in utero by isolation of the virus in the amniotic fluid.

CMV retinitis is known to occur in immunosuppressed adults and its incidence has increased in the last years as a result of acquired immunodeficiency syndrome (AIDS).⁶ However, the occurrence of CMV retinitis in immunocompromised children is unusual and only few cases have been reported in the literature.⁷

Congenital CMV infection may also be associated with retinitis. The precise incidence of CMV retinitis has been reported to be up to 25% of infants with severely symptomatic congenital CMV and in approximately 1% of infants who are asymptomatic and congenitally infected.^8,9 The retinitis in congenitally infected children differs from that described in immunocompromised subjects because it usually does not progress after birth if the child is otherwise immunocompetent.^7,10

Delayed onset and reactivation of chorioretinitis in children with congenital CMV infection has been described in a series of seven patients. Progression occurred later in life, the age ranging from 3 to 11 years. Only one child had a positive urine culture for CMV and no treatment was administered.¹¹

The baby we treated presented to us at 9 days of age with active progressive bilateral CMV retinitis and congenital symptomatic CMV infection. He was not immunosuppressed. Diagnosis was made by the clinical picture and blood and urine cultures, from which the virus was isolated. The optimal treatment for CMV retinitis in children has not yet been established. There are limited data regarding ganciclovir treatment in infants with symptomatic congenital CMV infection and it is not known whether antiviral drugs alter the prognosis. We prescribed the currently recommended therapeutic regimens of ganciclovir which are identical to those used in adults, with drug doses adjusted for body weight.¹² In our case dramatic improvement of the retinitis occurred within 1 week of treatment and ganciclovir was stopped after 3 weeks, as the child was otherwise immunocompetent. We cannot be sure to what extent the treatment contributed to the resolution of the retinitis as the natural history of the disease is not known. However, despite the rapid resolution of the retinitis, the visual outcome was not ideal. Based on current evidence it would seem appropriate to recommend early treatment of active retinitis.

It is important to be aware that active and progressive CMV retinitis can occur in children with symptomatic congenital CMV infection who are not otherwise immunocompromised. The associated retinal vasculitis can result in significant visual impairment. Urgent assessment and prompt initiation of treatment is recommended as it is likely to improve the visual prognosis by arresting the necrotising retinitis from spreading to the posterior pole, or the contralateral eye.

Reporting such rare cases should raise awareness of this serious condition with potentially devastating ocular sequelae. It may in time clarify the spectrum of the disease and help in establishing the best way to manage its complications.