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Vijayalakshmi et al Ocular Manifestations of Congenital Rubella Syndrome

December 2002

Original Article

307

Ocular Manifestations of Congenital Rubella Syndrome

in a Developing Country

P Vijayalakshmi, MS; Gaurav Kakkar, MS; Arun Samprathi, MS; R Banushree, MD

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.
Key Words: Congenital rubella syndrome, rubella cataract, microphthalmos, rubella retinopathy,
congenital cataract
Indian J Ophthalmol 2002;50:307-11

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 retinopathy5 and dacryostenosis.6
An estimated 238,000 children are born worldwide
with CRS each year, a majority in the developing

Department of Paediatric Ophthalmology and Strabismus,

Aravind Eye Hospitals, Madurai (PV, GK, RB) and Aravind Eye
Hospitals, Coimbatore (AS), India.
Correspondence to Dr. P Vijayalakshmi, Pediatric
Ophthalmology and Strabismus Services, Aravind Eye Hospital
and PG Institute of Ophthalmology, 1, Anna Nagar, Madurai
625 020, India. E-mail: <p.vijayalakshmi@aravind.org>
This study was supported by Aravind Medical Research
Foundation, Madurai, India.
Manuscript received: 18.6.2001; Revision accepted: 13.5.2002

Original_Article_5F.p65

307

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

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

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INDIAN JOURNAL OF OPHTHALMOLOGY

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
200 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
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
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

Table 2. Systemic features of congenital rubella

syndrome in 46 infants
Systemic anomalies

Table 1. Ocular manifestations of congenital rubella

syndrome in 46 infants (87 eyes)
Ocular anomalies

No. of eyes (%)

Microphthalmos + Cataract +
Iris hypoplasia
Rubella retinopathy
Corneal opacity
Glaucoma
Congenital dacryostenosis
Optic atrophy
Strabismus
Nystagmus

Original_Article_5F.p65

49 (56)
31 (36)
16 (18)
15 1(6)
12 (2.3)
14 (4.6)
12 patients (26)
23 patients (50)

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Vol. 50 No. 4

No. of patients 46 (100)

Cardiac anomalies
Patent ductus arteriosus
Patent ductus arteriosus +
pulmonary stenosis
Patent ductus arteriosus +
ventricular septal defect
Ventricular septal defect
Atrial septal defect
Atrial septal defect +
pulmonary stenosis
Pulmonary stenosis

23 (50)
10 (21.7)

Central nervous system anomalies

Isolated microcephaly
Isolated psychomotor retardation
Multiple neurological deficits + seizures

16 (34.7)
02 (4.5)
08 (17.4)
06 (13)

Hearing defects

02 (4.34)

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03 (6.5)
01 (2.1)
05 (9.2)
02 (4.3)
01 (2.1)
01 (2.1)

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Vijayalakshmi et al Ocular Manifestations of Congenital Rubella Syndrome

December 2002

309

Figure 1. Unequally dense cataract in an infant with CRS; Figure 2. Bilateral central corneal opacities in a case of CRS (A small
subconjunctival haemorrhage is due to surgical trauma optical iridectomy)

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

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309

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
Deliuse26 reports persistent corneal oedema in two eyes
that on histopathology demonstrated corneal stromal
swelling and interstitial keratitis accompanied by an
absence of Descemets membrane and severely

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INDIAN JOURNAL OF OPHTHALMOLOGY

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
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 al25 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

Vol. 50 No. 4

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.

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