INTRAUTERINE INFECTION AND THE EYE ISABELLE RUSSELL-EGGITT' and SUSAN LIGHTMAN2 London SUMMARY similar with considerable overlap in the cross-reactivity. This paper reviews the manifestations of intrauterine Primary infection with herpes simplex is uncommon in infection with toxoplasma gondii, rubella, cytomegalovi­ pregnancy and may be asymptomatic or limited to a mild rus, herpes simplex, varicella-zoster and syphilis with pharyngitis with a cutaneous vesicular eruption. Fetal particular emphasis on the ocular findings. infection with herpes simplex is often fatal usually result­ ing in abortion, but if the fetus survives and is born, skin Intrauterine infection is a major cause of inflammation in vesicles or scarring, microcephaly or hydrancephaly, the neonatal eye. Infection in utero can result in resorption encephalitis, chorioretinitis and hepatitis can occur. of the embryo, abortion or stillbirth. If the infant survives Severe disease can result from fetal infection at any time it may be born prematurely, suffer from intrauterine during gestation. growth retardation, be malformed, scarred and the infec­ Like other herpes viruses immunosuppression lights up tion may be still active. Microorganisms may be ter­ latent infection. Most maternalherpes simplex infection is atogenic by causing cell death, alteration in cell growth or a localised recurrent genital vesicular eruption. Herpes chromosomal damage. The varicella-zoster virus, CMV simplex infection in neonates is therefore mostly acquired and rubella probably act in a combination of these ways. by infection at delivery and type 2 is most commonly Inflammationwith subsequent tissue destruction are prob­ responsible. The mortality of newborn infants infected ably the major causes of structural abnormalities in con­ with herpes simplex is high and for this reason caesarean genital syphilis and toxoplasma infection. The infection sections are now often performed in women with active may persist after birth continuing to cause damage in genital lesions. Many of the mothers howerver, may be development and risking infection of other infants. asymptomatic at the time of delivery, leading to infection Certain infective agents such as toxoplasma, rubella, of the newborn infant and a delay in making the diagnosis. cytomegalovirus and herpes simplex often produce a Neonatal herpes simplex mostly manifests as a cutane­ similar clinical picture of congenital infection.' Common ous vesicular eruption progressing to generalised infection features are purpura, jaundice, anaemia, microcephaly/ in 50% of cases, with hepatitis, pneumonia and dissemi­ hydrocephaly, cerebral calcification, pneumonitis, micro­ nated intravascular coagulation. However, not all infants phthalmia, cataract and chorioretinitis. Whilst any of these have skin lesions and the ophthalmologist may be the first abnormalities may occur some are commoner in one con­ to suggest the diagnosis if the typical retinitis is seen. If the dition than another; for instance, cataracts are common in infection is acquired at birth the retinitis may not be seen rubella, but are rare in toxoplasmosis and then often in until at least one month of age. association with retinal detachment. The ophthalmologist In acute ocular involvement there usually are epithelial plays a role in diagnosis of the systemic illness as well as lesions of the lids, conjunctiva and cornea. In the neonate management of ocular problems. herpes conjunctivitis is not accompanied by follicles and It is usually a primary infection of the mother that harms there is often only mild injection. Stromal keratitis occurs the fetus. However recurrent disease in spite of some without antiviral therapy of the dendritic lesions. Catar­ maternal immunity may be a cause of congenital acts may also occur and virus could be cultured from the 18 infection. lens aspirate in an month old child who also had oval pigmented chorioretinal scars at both temporal equators.2 HERPES SIMPLEX Retinitis with vitritis rarely occurs, but then is often severe, and uveitis may result in secondary cataract forma­ The DNA of types 1 and 2 of herpes simplex are very tion. Treatment is with intravenous acyclovir and topical 'Hospitals for Sick Children, Great Ormond Street, London WCI. therapy for keratitis. 2Moorfields Eye Hosptial, City Road, London ECIV 2PD. Correspondence to: I. M. Russell-Eggitt FRCS, FCOphth, Hospitals The late neurological sequelae of neonatal herpes for Sick Children, Great Ormond Street, London WCI. simplex infection includes: spasticity, microcephaly, psy- Eye (1992) 6,205-210 206 ISABELLE RUSSELL-EGGITT AND SUSAN LIGHTMAN chomotor retardation, learning difficulties, cortical blind­ culitis with arterial sheathing and perivascular exudates. ness and sensorineural hearing loss.3 El Azazi reviewed The pigmentation of scars is less than in toxoplasmosislO the late ocular manifestations of neonatal herpes simplex (see Fig. 1). CMV chorioiretinitishas not been reported to in 32 children.4 Findings included: cortical visual loss, reactivate. squint, chorioretinal scars, optic atrophy, corneal scarring Other less common findings are optic atrophy, II optic and cataract. Typically the fundus lesions are less pig­ disc malformations,12 microphthalmos, keratitis, cataracts mented thanin toxoplasmosis as the primary pathology is and anterior chamber malformations with glaucoma.13 As in the retina, which atrophies with pigmentation of the sur­ CMV is such a common intrauterine infection some of rounding and underlying choroid. The majority of those these findings may be just chance associations. with eye lesions are also neurologically impaired. VARICELLA/CHICKENPOX CYTOMEGALOVIRUS (CMV) Chickenpox (varicella) is common in childhood only The CMV viruses are the largest members of the herpes about 10% of women of childbearing age are seronega­ virus family. The human CMV appears to be species tive.14 Chickenpox is the manifestation of primary infec­ specific, and replicates much slower than herpes simplex. tion with the varicella-zoster virus (V-Z). Zoster is caused Antibodies to CMV are present in just over 50% of women by the same virus. Like other herpes virusesV-Z may per­ of childbearing age in Europe, but in up to 90% in more sist in a latent form. Zoster is the reactivation of virus pre­ densely populated regions of the world.5 viously dormant in a dorsal root ganglion nerve cell. Most infections with CMV are subclinical including Zoster is only thought to be accompanied by a viremia and those acquired in utero and perinatally. CMV is probably generalised rash in patients with reduced cell-mediated the commonest cause of intrauterine infection in the devel­ immunity. oped world, with approximately 1 % of newborn infants The V-Z virus has been shown to induce chromosomal excreting live virus at birth. In utero infection with CMV abnormalities in vitro and in vivo. Chromosomal defects can occur both from primary and from recurrent CMV and have not been reported in babies bornto infected mothers, therefore can occur in consecutive pregnancies. However, but there is some evidence that there may be increased risk infants born to mothers with a recurrent CMV infection of childhood leukaemia. The V-Z virus may be trans­ veryrarely ( < 1 %) have clinically apparent disease. About mitted across the placenta, although most infants of half the mothers with a primary CMV infection (when women with gestational varicella are bornhealthy . 15 There maternalIgM antibody to CMV is found) transmit virusto is preference for skin, lung and liver involvement. A pat­ their fetus, but only 10-15% of these are born with clini­ tern of skin scarring, limb hypoplasia brain and eye dam­ cally apparent disease.5 age is related to intrauterine V-Z infection. This has been It is not understood why only some infants have mani­ called 'The congenital varicella syndrome' , first described fest disease and infants with congenital CMV have been by Laforet and Lynch.16 This syndrome is seen both in used as a model for understanding virus latency. These infants bornto mothers with chickenpox and zoster during infants seem to have a specific defect in CMV-induced pregnancy. However, it is more rare in gestational zoster lymphocyte proliferation.6 CMV is probably the common­ est intrauterine infection in the westernworld, but uncom­ monly causes morbidity. However infants born to HIV seropositive mothers may succumb to CMV encephalitis.7 Stagno summarised the acute findings in 34 newborns with congenital CMV infection.8 Petechiae were apparent in the majority by two weeks of age. The liver was the most common organ involved and they tended to be born small and prematurely. Half were microcephalic, but only four had chorioretinitis. This is similar to Ramsay's find­ igns in 65 infants who were bornwith symptomatic CMV and were reviewed at more than three years of age.9 Only 29 (45%) had neurological impairment and just under a quarter of these had isolated sensorineural deafness. Only seven (11%) were known to have ocular morbidity (three chorioretinitis andfour cortical blindness), but not all had full assessment. The appearance of the chorioretinitis usually differs fromthat in toxoplasmosis as in CMV the retina is primar­ ily involved and it is more truly a retinitis which usually becomes inactive in early infancy. An acute retinitis appears as scattered white dots which coalesce and Fig. 1 Fundus photograph showing retinal atrophy and become haemorrhagic and there is often a retinal vas- scarring after