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ORIGINAL ARTICLE
Year : 2002  |  Volume : 50  |  Issue : 4  |  Page : 307-311
 

Ocular manifestations of congenital rubella syndrome in a developing country.


Department of Paediatric Ophthalmology and Strabismus, Aravind Eye Hospitals, Madurai, India

Correspondence Address:
P Vijayalakshmi
Department of Paediatric Ophthalmology and Strabismus, Aravind Eye Hospitals, Madurai
India
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PMID: 12532496

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  Abstract 

PURPOSE: To describe the ocular manifestations of congenital rubella syndrome (CRS), a common cause of congenital cataracts in developing countries. METHODS: Retrospective analysis of case records of 46 sero-positive infants under 12 months of age who presented at Aravind Eye Hospital, Madurai between July 1993 and February 2001. The ocular and systemic examination details were recorded. RESULTS: Both eyes were affected in 41 (89%) patients. Cataract was present in 81 (93.1%) eyes; most of them were nuclear cataract (79, 97.5%). Other common ocular presentations included microphthalmos in 74 (85.1%) eyes, iris abnormalities in 51 (58.6%) eyes, and pigmentary retinopathy in 33 (37.9%) eyes. Cataract, microphthalmos and iris hypoplasia was a common combination present in 49 (56.3%) eyes. Systemic manifestations included cardiac anomalies in 23 (50%) and neurological anomalies in 16 (34%) children. Multi-system involvement was present in 32 (70%) children. Low birth weight (below 2 kg) was seen in 30% infants. CONCLUSION: CRS may present with a wide spectrum of ocular and systemic findings and requires a high index of suspicion for diagnosis. Any sick infant with unilateral or bilateral congenital cataract should be investigated thoroughly for CRS.


Keywords: Congenital rubella syndrome, rubella cataract, microphthalmos, rubella retinopathy, congenital cataract


How to cite this article:
Vijayalakshmi P, Kakkar G, Samprathi A, Banushree R. Ocular manifestations of congenital rubella syndrome in a developing country. Indian J Ophthalmol 2002;50:307-11

How to cite this URL:
Vijayalakshmi P, Kakkar G, Samprathi A, Banushree R. Ocular manifestations of congenital rubella syndrome in a developing country. Indian J Ophthalmol [serial online] 2002 [cited 2014 Jul 23];50:307-11. Available from: http://www.ijo.in/text.asp?2002/50/4/307/14761


The consequences of rubella infection in-utero are referred to as the congenital rubella syndrome (CRS). Rubella is a mild exanthematous disease of viral aetiology that afffects all ages.[1],[2] When contracted by the mother during the first three months of pregnancy, it may result in abortion, stillbirth or an infant born with CRS. Congenital malformations including congenital cataract among 78 infants born following maternal rubella infection, acquired during the 1940 epidemic of rubella in Australia have been described.[3] More clinical findings were added later to the spectrum of CRS, which includes deaf-mutism and microcephlaly,[4] pigmentary retinopathy[5] and dacryostenosis.[6]

An estimated 238,000 children are born worldwide with CRS each year, a majority in the developing countries. In India, it is estimated that about 50,000 children are born blind from congenital cataract every year, of which at least 25% are due to maternal rubella.[7] The reported overall incidence of rubella immunity among females in the reproductive age group in India is 55%, and nearly 45% of women were susceptible to this infection during pregnancy.[8] The lack of serological confirmation is a limitation of previous reports of CRS from India.[9],[10] This paper reports the clinical spectrum in serologically confirmed cases of CRS in South India.


  Materials and Methods Top


Medical records of all patients with a diagnosis of CRS (clinically diagnosed and serologically confirmed) in the Paediatric Ophthalmology department of Aravind Eye Hospital, Madurai between 1993-2001 were reviewed. History included fever with rash in the mother during the early months of gestation. The details in infants included birth weight, age at presentation, gender, significant neonatal problems and the, ocular findings at presentation and in the one year follow-up period. Ocular examination included a detailed anterior segment evaluation consisting of corneal diameter measurement (Castroviejo Caliper), tonometry using either the Pulsair 2000 (Keeler Ltd., Berkshire, London) or Tono-pen XL (Mentor Inc., Jacksonvile, USA), structure of the iris, status of the pupil, description of the cataract and fundus examination (done postoperatively). While the corneal diameter was measured under the microscope during anaesthesia, the intraocular pressure (IOP) was measured as an outpatient procedure.

All these children also underwent a detailed systemic evaluation by a paediatrician and cardiologist (when necessary). Clinical diagnosis was based on WHO criteria.[11] Rubella IgM titres in the serum were estimated using the Human ELISA kit (Human Gesellschaft fur Biochemica and Diagnostica mbH, Wiesbaden, Germany). Two ml of blood was collected in a Vacutainer tube (Greiner bio-one GmbH, Austria), centrifuged and separated serum was stored at - 20 C before subjecting it to the ELISA. Twenty-five cases were confirmed at the Central Public Health Laboratory, London and 21 at Aravind Eye Hospital, Madurai.


  Results Top


Eighty seven eyes of 46 infants were analysed. Forty-one (89%) children had bilateral ocular involvement; 23 (50%) children were males. Age at diagnosis ranged from 1 day to 12 months. Thirty-one (67%) infants were diagnosed within five months of life. The birth weight distribution was as follows: less than 1.50 kg in five infants; 1.50-2.0 kg in 25 infants; 2.0-2.50 kg in six and more than 2.5 kg in four infants. Birth weight was not available for six infants. Two infants weighing 1.47 kg and 1.25 kg respectively were premature by 6-8 weeks. Significant neonatal problems included seizures in six infants, jaundice in two, septicaemia with acute renal failure in one, rash after birth in one and hepato-spleenomegaly in one infant. Nineteen (41.3%) mothers gave a positive history of fever with rashes during the early months of pregnancy.

[Table - 1] shows the ocular abnormalities in children with CRS. Cataract was the commonest finding seen in 81 (93.1%) eyes, which included all the five cases with unilateral ocular involvement. The type of cataract was nuclear in 79 (97.5%) eyes including all the five from the unilateral group [Figure - 1]. Others included bilateral 34 (92%) and unilateral 6 (8%) microphthalmos, iris hypoplasia 51 (58.6%), cloudy cornea of variable intensity 16 (18%), Rubella retinopathy 33 (38%), nystagmus 23 (50%), concomitant strabismus 12 (26%), primary optic atrophy 2 (4.3%), and bilateral dacryostenosis 1 (2.1%). All 40 patients with microphthalmos also had cataract. The corneal diameter in our patients ranged from 8-10 mm. In 11 eyes with corneal oedema IOP was within normal limits (<20 mm Hg). Five eyes with corneal oedema had associated glaucoma. Four eyes with glaucoma were microphthalmic and had cataract. Only one eye with glaucoma had megalocornea with clear lens.

Systemic abnormalities were present in 32 (70%) children. Cardiovascular anomalies were found in 23 (50%) children. Developmental and neurological defects were seen in 16 (34.8%), which included microcephaly, psychomotor retardation and seizure disorder. Hearing abnormality was detected in two patients.


  Discussion Top


Rubella infection, affecting children and young adults, has no consequence and often goes undetected. Over 50% mothers in our study denied any history of fever or rash during pregnancy, which may be due to the subclinical nature of infection.[12] When contracted during the early weeks of pregnancy, the virus transplacentally infects the developing foetus. The virus gets disseminated throughout the body, mostly in the blood stream, thereby inhibiting cell growth. The foetus is susceptible to this infection due to the rapid organogenesis and undeveloped specific immunity against the virus in the first two trimesters. The severity of the damage to the foetus depends upon the virulence of the organism and the timing of the foetal infection. The earlier in pregnancy the infection occurs, the greater is the damage to the foetus.[13] Incidence of birth defects is reported to be 90% when infection occurs within the first 10 weeks of pregnancy.[12],[13] In CRS, the foetus synthesises its own immunoglobulin (IgM antibodies) persisting for 18 months postnatally. However, the sensitivity of IgM estimation for the diagnosis of CRS reduces from 100% before five months, 60% up to 12 months and 40% by 18 months.[14] In the present analysis 31 (67%) infants were diagnosed by five months of age when the sensitivity of the test is expected to be the highest.

CRS affects almost all ocular structures, either in isolation or in combination. Rubella cataract is the most common ocular sign. The virus enters the lens before the development of the lens capsule that would otherwise act as barrier to the virus.[15],[16] This may be the reason why rubella cataract is always at the foetal nuclear level and is frequently bilateral. Microphthalmos is probably due to generalised slowing of replication, a sort of ocular failure to thrive, seen with simultaneous diffuse ocular involvement also causing cataract and glaucoma in many.[17] The virus is assumed to invade the developing corneal endothelium and cause transient clouding.[18] Congenital glaucoma is an infrequent finding following maternal rubella.[4],[19] Glaucoma may be caused either by failure of absorption of the mesoderm of the angle or by failure of the canal of Schlemm to differentiate.[20] The retinopathy in CRS is variably reported from 13.3% to 61%.[5],[17],[21],[22] The pigment deposits may vary from fine powdery, sprinkled or granular shapes throughout the retina, especially the posterior pole, or discrete patchy black lesions varying in size and location resembling retinitis pigmentosa.[21] The pigment changes may involve one or more quadrants but characteristically are more prominent in the posterior pole. The visual acuity is unaffected by these pigmentary changes and the retinopathy does not progress.[3],[5] Disorders of motility (strabismus and nystagmus) are frequent and likely to be the result of organic lesions of the eye.[23]

Cataract was present in 81 (93.1%) eyes in our series. This is much higher than the 27% incidence reported by Givens et al.[17] Additionally, bilateral cataract in our series at 88% was much higher than their reported incidence of 61.8%. Predominance of nuclear cataract is another interesting observation.[3],[7],[24],[25]

A study conducted at our institute on aetiology of congenital cataract in 1994 showed that 25% were due to rubella infection in infants below one year of age and all of them were of the nuclear type.[7] Nuclear cataract in this group of children had a positive predictive value of 75% for CRS. Postnatally the lens acts as a reservoir for the virus, causing a persistent infection owing to which the nuclear cataract progresses into a total form.[3] Incidence of cataract with microphthalmos is reported to be as high as 90%[17] to 100%.[22] In our study all 40 patients (100%) with microphthalmos also had cataract, conforming to the notion that the infecting virus retards the growth of all ocular tissues during organogenesis. Fifty-one (58.6%) eyes in our series had iris hypoplasia evidenced by absence of iris crypts, an atrophic smooth appearance, underdevelopment of the sphincter muscle characterised by pinpoint pupil with poor response to mydriatics. Variable pigmentary distribution on the anterior surface was also noticed. The iris abnormalities include iris coloboma, anisocoria, posterior synechiae, persistent pupillary membrane, and mesodermal dysgenesis,[24] which were not observed in our study. Primary involvement of the cornea, though infrequent, does exist where transient or permanent oedema in the absence of elevated IOP is found. [26,27] A few authors believe that corneal oedema in CRS could be more a consequence of secondary glaucoma.[28],[29] Corneal clouding is usually central and in most reported cases resolves spontaneously over a period of 3-6 months.[26],[27] Deliuse[26] reports persistent corneal oedema in two eyes that on histopathology demonstrated corneal stromal swelling and interstitial keratitis accompanied by an absence of Descemet's membrane and severely deranged endothelial cell ultrastructure. In our series, cloudy cornea of variable intensity resembling corneal opacitites was seen in 16 (18.4%) eyes. This spontaneously cleared to a certain extent initially, but a persistent oedema was evident in all. The corneal opacity was central in all the patients [Figure - 2]. In our series, rubella retinopathy was seen in 33 (37.9%) eyes. Except in three eyes this was associated with cataract and microphthalmos. In general it had a salt-and-pepper appearance (in 29 eyes) with the variable-sized pigmentation distributed throughout the retina. Optic atrophy in CRS may occur as a sequel of meningitis or encephalitis.[22] Two patients in our series had primary optic atrophy. One patient had an associated pigmentary retinopathy. The other patient had cerebral palsy. The incidence of nystagmus at 50% in this series was two times that of Givens et al, and the strabismus incidence at 26% was similar.[17]


  Systemic manifestations Top


Though almost all systems can be affected in CRS, the defects of hearing, cardiovascular system and central nervous system have been well documented.

Cooper et al[25] in his series of 271 patients described heart diseases in 142 (52%), hearing loss in 140 (52%), and psychomotor retardation in 109 (40%). Incidence of cardiac defects in CRS with eye involvement could be as high as 95%.[6] Cardiovascular anomalies in our series were present in 23 (50%) patients. The low incidence of cardiac anomalies in our series can be attributed to the fact that our cases were detected mainly during pre-anaesthetic checkup. In total 14 (61%) children had patent ductus arteriosus either as an isolated defect or in combination with other cardiac defects. The other anomalies included atrial septal defect, pulmonary stenosis and ventricular septal defect.

Developmental and neurological defects were seen in 16 (34.8%) children, which included microcephaly with mental retardation, seizure disorder and delayed milestones, emphasising the need for multi-speciality management in these infants.

In summary, foetal infection with rubella virus causes serious multisystemic malformations, resulting in severe morbidity and mortality. It continues to represent a challenge, with its wide range of ophthalmic and systemic disorders. By recognising and treating this disease early, the quality of life can be improved for these infants. Ophthalmologists can play a major role in the early diagnosis of this multisystem disease because the ocular findings can be detected at birth unlike most of the systemic manifestations such as hearing loss and neurological abnormalities. Proper immunisation nearly always prevents the disease. The combined effort of ophthalmologists and other health care personnel working in this field is required to achieve optimal results. A greater awareness of various aspects of CRS in our country is the need of the hour.[29]

 
  References Top

1.Ballal M, Shivananda PG. Prevalence of rubella virus in suspected cases of congenital infections. Indian J Pediatr 1997;64:231-35.  Back to cited text no. 1  [PUBMED]  
2.Banatvala JE, Best RM. Rubella. In: Brown and Wilson, editors, Principles of Bacteriology, Virology and Immunity. 7th ed., London: Edward Arnold; 1984. pp 271-302.  Back to cited text no. 2    
3.Gregg NM. Congenital cataract following German measles in the mother. Trans Ophthal Soc Aust 1941;3:35-46.  Back to cited text no. 3    
4.Swan C. Congenital malformations in infants following maternal rubella in pregnancy. Trans Ophthal Soc Aust 1944;4:182-49.  Back to cited text no. 4    
5.Morlet C. Rubella retinitis in Western Australia. Trans Ophthal Soc Aust 1949;9:212-14.  Back to cited text no. 5    
6.Geltzer Al. Ocular manifestations of the 1964-65 rubella epidemic. Am J Ophthalmol 1967;63:221-29.  Back to cited text no. 6    
7.Eckstein M, Vijayalakshmi P, Killeder M, Gilbert C, Foster A. Aetiology of childhood cataract in south India. Br J Ophthalmol 1996;80:628-32.  Back to cited text no. 7    
8.Yadav S, Gupta S, Kumari S. Seroprevalence of rubella in women of reproductive age. Indian J Pathol Microbiol 1995;38:139-42.  Back to cited text no. 8  [PUBMED]  
9.Rao VA, Arthanariswaran. Rubella syndrome with ectopia lentis. J M.S.O.A. 1982;19:17.  Back to cited text no. 9    
10.Angra SK, Madan M. Rubella cataract. Indian J Ophthalmol 1982;30:445-48.  Back to cited text no. 10    
11.Felicity TC, Jennifer B, Merilda MS, Kristina E, Susan ER. Guidelines for surveillance of congenital rubella syndrome and rubella. Field test version, May 1999. Bull World Health Organ 1999;22:12.  Back to cited text no. 11    
12.Prendercast, John J. Congenital cataract and other anomalies following rubella in mother during pregnancy. A California survey. Arch Ophthalmol 1946;35:39-41.  Back to cited text no. 12    
13.Elizabeth M, John EC, Watson, Thomas M. Consequences of confirmed maternal rubella at successive stages of pregnancy. Lancet 1982;2:781-84.  Back to cited text no. 13    
14.Thomas HI, Morgan-Capner P, Cradock-Watson JE, Enders G, Best JM, et al. Slow maturation of IgG1 avidity and persistence of specific IgM in congenital rubella: implications for diagnosis and immunopathology. J Med Virol 1993;41:196-200.  Back to cited text no. 14  [PUBMED]  
15.Zimmerman L E. Pathogenesis of rubella cataract. Arch Ophthalmol 1965;73:761.  Back to cited text no. 15    
16.Alfano J E. Ocular aspects of maternal rubella syndrome. Trans Amer Acad Ophthal Otolaryng 1996;70:235-66.  Back to cited text no. 16    
17.Givens KT, Lee DA, Jones T, Ilstrup DM. Ophthalmic manifestations and associated systemic disorder. Br J Ophthalmol 1993;77:358-86.  Back to cited text no. 17  [PUBMED]  
18.Zimmerman LE. Histopathologic basis for ocular manifestations of congenital rubella syndrome. Am J Ophthalmol 1968;65:837-62.  Back to cited text no. 18  [PUBMED]  
19.Long JC, Danelson RW. Cataract and other congenital defects in infants following rubella in the mother. Arch Ophthalmol 1945;34:24-27.  Back to cited text no. 19    
20.Mann I. Developmental Abnormalities of the Eye. Philadelphia; J B Lippincot; 1957.  Back to cited text no. 20    
21.Marks EO. Pigmentary abnormalities in children congenitally deaf following maternal German measles. Br J Ophthalmol 1947;31:119.  Back to cited text no. 21    
22.Hamilton JB, Philips F, Palfreyman CR. Rubella retinitis in Tasmania. Trans Ophthal Soc Aust 1948;8:114-18.  Back to cited text no. 22    
23.O'Neill JF. Strabismus in congenital rubella. Arch Ophthalmol 1967;77:450-54.  Back to cited text no. 23    
24.Roy FH. Ocular manifestations of CRS. Arch Ophthalmol 1966;75:601-7.  Back to cited text no. 24    
25.Cooper LZ, Ziring PR, Ockerse AB, Fedun BA, Kiely B, Krugman S. Rubella clinical manifestations and management. Am J Dis Child 1969;118:18-19.  Back to cited text no. 25    
26.Deluise VP, Cobo M, Chandler D. Persistent corneal oedema in the congenital rubella syndrome. Ophthalmology 1983;90:835-39.  Back to cited text no. 26    
27.Chandla PA, Grantiom. Glacuoma 2nd ed. Philadelphia: Lea and Jebiger; 1979. p 388.  Back to cited text no. 27    
28.Wolff SM. The ocular manifestations of congenital rubella. Trans Am Ophthalmol Soc 1972;70:577-614.  Back to cited text no. 28    
29.Zoniss ME, Zelter M. Clinical and pathological manifestations in a case of congenital rubella syndrome. J Pediatr Ophthalmol 1975;12:184-88.  Back to cited text no. 29    


    Figures

[Figure - 1], [Figure - 2]

    Tables

[Table - 1], [Table - 2]


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