A Nationwide Danish Study of 1027 Cases

of Congenital/Infantile Cataracts
Etiological and Clinical Classifications
Birgitte Haargaard, MD,1 Jan Wohlfahrt, MSc,1 Hans C. Fledelius, MD, PhD,2 Thomas Rosenberg, MD,3
Mads Melbye, MD, PhD1
Objective: To study the distribution of congenital/infantile cataract in the entire population of Denmark
according to etiological and clinical classifications.
Design: Population-based cohort study with retrospective chart review.
Participants: All children (0 to 17 years old) who were born between 1959 and 2001 and registered with
congenital/infantile cataract in Denmark during the period 1977 to 2001. Cases were ascertained from the
mandatory Danish National Register of Patients, and all medical records were reviewed.
Methods: Etiological and clinical classifications of the cataract cases were based on information from the
medical records.
Main Outcome Measures: Classification of congenital/infantile cataract according to presumed etiology;
gender; clinical appearance, including laterality and morphology; and the time trends according to etiology and
laterality.
Results: A total of 1027 children with congenital/infantile cataract, 529 boys and 498 girls, were included, of
whom 64% were bilateral. Males predominated with bilateral cataract, whereas females predominated with
unilateral cases. Isolated cataract was the most frequent clinical presentation (71% of all cases), followed by an
even proportion of cataract associated with additional ocular dysmorphology and cataract associated with
systemic anomalies. Almost two thirds of all cases had an unknown etiology (idiopathic). Idiopathic cases
showed a higher proportion of unilateral cataract and of additional ocular dysmorphology compared with cases
of known etiology. The etiology was unknown in 87% of unilateral cases and in 50% of bilateral cases. The
distribution by presumed etiology was stable during the study period, except for cataract caused by maternal
infections, which decreased mainly due to the elimination of congenital rubella.
Conclusions: With the exception of the decline of congenital rubella, the proportion of congenital/infantile
cataract cases of unknown, genetic, and infectious origins has been stable since the late 1970s. The causes of
87% of unilateral cataracts and 50% of bilateral congenital/infantile cataracts remain unknown, making the
prevention of the disease a continuing challenge. Ophthalmology 2004;111:2292–2298 © 2004 by the American
Academy of Ophthalmology.

Congenital/infantile cataract is the most serious type of

Originally received: February 19, 2004.
Accepted: June 22, 2004. Manuscript no. 240122.
1
Department of Epidemiology Research, Danish Epidemiology Science
Centre, Statens Serum Institut, Copenhagen, Denmark.
2
Rigshospitalet, Copenhagen University Eye Clinic, Copenhagen, Denmark.
3
Gordon Norrie Centre for Genetic Eye Diseases, National Eye Clinic for
the Visually Impaired, Hellerup, Denmark.
Presented at: XIth Nordiska Barnoftalmogiska Kongressen, September,
2003; Uppsala, Sweden.
Financial support: Augustinus Foundation, Copenhagen, Denmark (grant
no.: 1-293); Danish Eye Research Foundation, Copenhagen, Denmark;
Einar Willumsen’s Memorial Foundation, Brondby, Denmark; Carl and
Nicoline Larsen Foundation, Copenhagen, Denmark; Family Hede Nielsen
Foundation, Horsens, Denmark; Aase and Ejnar Danielsen Foundation,
Lyngby, Denmark (grant no.: 103319); Dagmar Marshall Foundation,
Copenhagen, Denmark; and Simon Spies Foundation, Copenhagen, Denmark.
Correspondence to Dr Birgitte Haargaard, Department of Epidemiology
Research, Statens Serum Institut, 5 Artillerivej, DK-2300 Copenhagen S,
Denmark. E-mail: bgd@ssi.dk.
childhood cataract because of its potential for inhibiting or
restricting early visual development. In developed coun-
tries, congenital cataract is responsible for 3% to 12% of
severe childhood visual impairment,1– 4corresponding to ap-
proximately 6/100 000 children.5
In the developed world, the etiological distribution of
congenital/infantile cataract has changed over time, mainly
because of the introduction of vaccination against rubella.
Until today, most of the reported studies on the etiology of
congenital/infantile cataract have been performed at loca-
tions where rubella has remained a significant cause of the
disease6,7 or were from a time when rubella was fre-
quent.8 –11 Others are based on selected populations1,12 or
on a limited time.13 In more recent studies, the percentage of
cases of unknown origin is generally reported to be at least
50%, and the percentage of genetically based cataracts
varies from 27% to 39%.13–15
In a search for clues to understand the possible factors
underlying the development of congenital/infantile cataract

2292 © 2004 by the American Academy of Ophthalmology ISSN 0161-6420/04/$–see front matter
Published by Elsevier Inc. doi:10.1016/j.ophtha.2004.06.024
 Haargaard et al 䡠 Nationwide Danish Study of Congenital/Infantile Cataracts
better, detailed population-based investigations of the dis-
tribution and time trends are needed. Therefore, we under-
took a study comprising cases ascertained from national
registries in Denmark during 1977 to 2001 to characterize
the etiological and clinical classifications of congenital/
infantile cataract, including laterality, gender, and morphol-
ogy, and further to report trends in their distribution over
time.
Materials and Methods
All children (0 to 17 years old) with a hospital discharge diagnosis
code of congenital or infantile cataract recorded in the Danish
National Register of Patients (NRP) during the period 1977 to
2001 were selected. Thus, our study population included birth
cohort years from 1959 to 2001. Children born abroad but regis-
tered with cataract in Denmark were included (4%). The NRP was
established in 1977 and contains all discharge diagnoses of pa-
tients admitted to public hospitals (inpatients). Since 1995, the
registration has also included outpatients. Less than 1% of Danish
children are born at home, but these are also registered in the NRP.
Even fewer are born at private hospitals, and information on these
children is not available in the NRP. Surgery on children for
cataract at private hospitals is virtually nonexistent, and thus, the
NRP registers close to all children with congenital or infantile
cataract seen at hospitals in Denmark.
All medical records of children registered with congenital or
infantile cataract (codes 74439, 37400, and 37401 in International
Classification of Diseases 8 [1977–1993] and codes Q12.0 and
H26.0 in International Classification of Diseases 10 [1994 –2001])
were reviewed to classify the cases according to etiology and
clinical appearance, including laterality and morphology. In addi-
tion, to look for possibly late or misclassified congenital/infantile
cases, we reviewed medical records of children registered with a
diagnosis of cataract not being congenital/infantile and not unan-
imously classified as acquired.16 For the present analysis, cataracts
with traumatic, acquired systemic (e.g., diabetes), or acquired
ocular etiology (e.g., uveitis) were not included (724 cases in all).
Both visually impairing and visually less significant cataracts
among cases were included. From the Danish Health Security
System’s register, which since 1990 has registered all consulta-
tions at private specialists, we collected and reviewed the medical
records from private ophthalmologists who were registered with a
contact with ⱖ1 of the identified cases under study. These records
supplemented the information gathered from the hospital charts.
Although information on hereditary cases was obtained from the
medical records, we also cross-referenced all cases with the Danish
Family Archive for Hereditary Eye Disorders at the National Eye
Clinic for the Visually Impaired to obtain any additional informa-
tion on hereditary cases (e.g., on inheritance pattern).
The study was approved by the scientific– ethical committees
for Copenhagen and Frederiksberg (reference no. [KF] 01-253/00),
and permission to receive data from the national registries was
obtained from the Danish Data Protection Agency (reference no.
2000-41-0285).
The cases of congenital/infantile cataract were classified ac-
cording to their most likely etiology: (1) unknown/idiopathic, (2)
genetic, (3) intrauterine infection, (4) exposure to chemical sub-
stances during embryogenesis, and (5) classification not possible.
The genetic group was subdivided into cases of congenital/infan-
tile cataract among first-degree relatives (i.e., siblings, parents, or
children) (hereditary cataract) and cases in which patients did not
necessarily have family members with congenital/infantile cata-
ract. Cases of inherited aniridia or inherited congenital ectopia
lentis with no family members with congenital/infantile cataract
were thus grouped as hereditary other ocular dysmorphology, and
cases associated with syndromes/chromosomal anomalies as syn-
dromes/chromosomal anomalies. In the intrauterine infection
group, we included cases of cataract probably caused by a maternal
infection during pregnancy, and the etiological group chemical
substances during embryogenesis comprised cataract probably
caused by teratogenic drugs.
After the etiological subdivision, the patients were further
divided into clinically defined groups of (1) isolated cataract, (2)
nonsystemic cataract associated with additional ocular dysmor-
phology, and (3) cataract with systemic anomalies regardless of
additional ocular dysmorphology. Finally, the cases were distrib-
uted according to unilateralism or bilateralism.
Ocular dysmorphology was defined as coloboma of the iris/
choroid/lens/optic nerve; microcornea (defined as 2 standard de-
viations [SDs] below the mean corneal diameter according to
postconceptional age17 and otherwise as ⬍10 mm in diameter);
microphthalmos (defined as an axial length 2 SDs below the mean
according to postconceptional age17,18); anterior segment dysgen-
esis; persistent fetal vasculature (PFV),19 including persistent hy-
aloid artery and persistent hyperplastic primary vitreous; optic
atrophy; or retinal dystrophy. Some patients had cases of PFV and
microcornea/microphthalmos, and these were classified as PFV.
Eye pathology considered secondary to an acquired disease (e.g.,
chorioretinitis in a child with cytomegalovirus) was not catego-
rized as an ocular dysmorphology.
Systemic disease was defined as hydrocephalus, microcepha-
lus, other malformations of the brain, multisystem defects (involv-
ing malformations in ⱖ2 different organs apart from the eye), or
mental retardation not related to asphyxia.
The classification not possible group (n ⫽ 43) included cases
not belonging to the above groups and cases for which lack of
information on the presence or absence of congenital/infantile
cataract or other ocular dysmorphology among family members
prevented classifying the case as either unknown or genetic.
Among these, 9 children were adopted (7 had isolated cataract and
2 had cataract with systemic anomalies), and 3 were refugees
and/or brought up abroad (all 3 had isolated cataract). Of the
remaining 31 cases, 26 had isolated cataract, and 5 had cataract
with additional ocular dysmorphology.
The clinicians’ description of the cataract morphology was
extracted from the medical records. The Danish definition of
zonular cataract coincides with the American description of nu-
clear cataract (one of the subdivisions of zonular cataracts),20 and
accordingly, these morphologies are grouped together. The mor-
phology groups were nuclear/zonular, posterior cortical/subcapsu-
lar, posterior polar, anterior polar, mixed, dense, other, and a small
one for which a description of the morphology was missing. The
group of mixed cataracts consisted mainly of cataracts with both
nuclear and posterior cortical opacities. Some descriptions of the
cataract morphology in the medical records were less specific (e.g.,
described merely as dense), and they were categorized as such.
Some of the cataracts with a specific morphology were (or be-
came) dense too, but the specific morphology was stated whenever
available.
Statistical Analyses
The overall/gender-specific cumulative risk of congenital/infantile
cataract during childhood with a specific etiology or laterality was
estimated as 1⫺exp (⫺␭), where ␭ was the overall/gender-specific
cumulative incidence rate of cataract with the specific etiology or
laterality. The cumulative incidence rate was determined as a
weighted sum of age-specific incidence rates (8 age categories)
with weights equal to the number of years in the age categories.
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 Ophthalmology Volume 111, Number 12, December 2004

Table 1. Etiological and Clinical Classifications of Congenital/Infantile Cataract Cases Registered in Denmark from 1977 to 2001
among Children (0 –17 Years Old) by Laterality

No. of Cases
Etiological and Clinical Classification Unilateral Bilateral Total
Unknown/idiopathic (63%)
Isolated cataract 231 244 475
Additional ocular dysmorphology, nonsystemic 91 31 122
Systemic anomalies 4 44 48
Genetic (29%)
Hereditary cataract (23%)*
Isolated cataract 4 211 215
Additional ocular dysmorphology, nonsystemic 2 14 16
Systemic anomalies 9 9
Hereditary other ocular dysmorphology (⬍1%)†
Additional ocular dysmorphology, nonsystemic 4 4
Syndromes/chromosomal anomalies (6%)
Systemic anomalies 6 54 60
Intrauterine infection (3%)‡
Isolated cataract 2 1 3
Additional ocular dysmorphology, nonsystemic 1 1
Systemic anomalies 6 24 30
Chemical substances during embryogenesis (⬍1%)
Thalidomide, ocular dysmorphology, nonsystemic 1 1
Classification not possible (4%)
Isolated cataract 21 15 36
Additional ocular dysmorphology, nonsystemic 5 5
Systemic anomalies 1 1 2
Total§ 374 653 1027

*Family members with congenital/infantile cataract.

†
No family members with congenital/infantile cataract.
‡
The measles, mumps, and rubella vaccination was introduced in 1987. Of the patients with 34 cases caused by intrauterine infection, 27 with congenital
rubella were born before 1987.
§
The 374 unilateral cases in 162 males and 212 females, and the 653 bilateral cases in 367 males and 286 females.

The age-specific incidence rates were estimated as the number of
cases divided by the number of person-years at risk in each age
category. Person-years at risk were calculated by assuming that
children were at risk from January 1, 1995 or from the day of birth,
whichever occurred later, until the first diagnosis of cataract or
until death, emigration, 18th birthday, or December 31, 2000,
whichever occurred first. Estimation of cumulative risks was based
on children born in Denmark and diagnosed in 1995 to 2000. This
restriction was used because a complete disease history was avail-
able only for children born in Denmark, registration after 1995
included both inpatients and outpatients, and registration in 2001
was incomplete at the time of the study. The cumulative risks
correspond to the cumulative incidences because the disease is
rare. Confidence intervals (CIs) for cumulative risks were esti-
mated by standard errors (SEs). The SEs were estimated as the
square root of the weighted sum of squared SEs of the 8 age-
specific incidence rates, with weights equal to the square of the
weights used to estimate the cumulative risk. Gender differences in
incidence were evaluated using log-linear Poisson regression.
Time trends were evaluated using the Mantel–Haenszel chi-square
test. Confidence intervals for proportions and P values for differ-
ences were determined by log-linear binomial regression.
Results
Ascertainment and Validation of Cases
Overall, 1093 children (0 to 17 years old) were registered with a
diagnosis of congenital or infantile cataract in the Danish NRP
during 1977 to 2001. We excluded 132 of these cases, 30 because
the medical records were not available for evaluation and 102
because of erroneous diagnosis (no cataract at all [n ⫽ 60] or not
congenital/infantile cataract according to our definition [n ⫽ 42]).
However, among the additionally reviewed medical records of
confirmed cataract cases originally coded as another type of cata-
ract, as described in detail elsewhere,16 we found 66 cases of 283
that could be reclassified as congenital/infantile cataract according
to our definition.
In total, 1027 cases of congenital/infantile cataract, 529 boys
and 498 girls, were included in the study. The median age at
diagnosis was 3 years, and in 3.5% of the cases both parents were
born outside Europe or North America.
Etiological and Clinical Classifications, 1977 to
2001
Table 1 shows the etiological and clinical classification of regis-
tered congenital/infantile cataract cases in the entire period accord-
ing to laterality. Overall, 36% (95% CI, 34%–39%) were unilateral
and 64% (95% CI, 61%– 67%) were bilateral. The ratio of unilat-
eral/bilateral cataract was 1:1.7. Among all unilateral cataract
cases there was a female predominance (57% [95% CI, 51%–
61%], P ⫽ 0.01), whereas boys predominated in the bilateral group
(56% [95% CI, 52%– 60%], P ⫽ 0.002).
Idiopathic cataract constituted by far the largest group, making
up 63% of all 1027 cases. Genetically based cataract ranked
second, with 304 cases (29%), the majority of these being hered-
itary cataract (240/304). Although the vast majority of cataract
cases with known etiology were bilateral, there was no significant

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 Haargaard et al 䡠 Nationwide Danish Study of Congenital/Infantile Cataracts

Table 2. Additional Ocular Dysmorphology among Unknown/Idiopathic and Genetic, Hereditary Nonsystemic Congenital/Infantile
Cataract Cases Registered in Denmark from 1977 to 2001 among Children (0 –17 years Old) by Laterality

No. of Cases (Unilateral/Bilateral)

Ocular Dysmorphology Unknown/idiopathic Hereditary cataract Others* Total
PFV 52/3 2/0 2/0 56/3
Microcornea and/or microphthalmos 21/11 0/7 1/0 22/18
Colobomas 7/1 0/4 1/0 8/5
Aniridia 0/6 0/3 0/3 0/12
Lenticonus 5/2 2/0 7/2
Ectopia lentis 1/6 0/1 1/7
Other 5/2 0/1 5/3
Total 91/31 2/14 6/5 99/50

PFV ⫽ persistent fetal vasculature.

*Includes 4 hereditary ocular dysmorphology (3 aniridia and 1 ectopia lentis), 1 intrauterine infection (microcornea), 1 thalidomide (other), and 5
classification not possible (2 PFV, 1 coloboma, and 2 lenticonus) (Table 1).

difference between the numbers of unilateral and bilateral cases in cases were associated with a deletion of chromosome 11p, includ-
the idiopathic group. Overall, the label idiopathic applied to 87% ing 3 patients with the WAGR (Wilm’s tumor, aniridia, genital
of the unilateral and almost 50% of the bilateral cataract cases. anomalies, and mental retardation) syndrome (Tables 2, 3).
Isolated cataract was the predominant clinical appearance (71% Table 4 presents the clinical classification in congenital/infan-
of all cases), whereas cataract associated with additional ocular tile cataract cases caused by intrauterine infections. Rubella was
dysmorphology and cataract associated with systemic anomalies the intrauterine infection most often associated with cataract and
each accounted for 14.5%. Cataract cases with additional ocular the only one causing unilateral cataract.
dysmorphology were predominantly unilateral (66%), whereas In Table 5, the morphology of the cataract cases is presented
cataract cases with systemic anomalies were mainly bilateral according to etiological classification and laterality. Nuclear/zonu-
(89%). Cataracts with systemic anomalies were obviously more lar cataract accounted for 34% of all cases and was the most
frequent among cases of known etiology (29%), compared with common morphology in all major etiological groups. Posterior
cases of unknown etiology (7%). The proportion of cataract with polar cataract and posterior cortical/subcapsular cataract were
additional ocular dysmorphology was significantly higher among most frequent among idiopathic cases.
nonsystemic idiopathic cases (20%) than among nonsystemic
cases of known etiology (9%). Table 3. Syndromes/Chromosomal Anomalies Associated with
Among the 240 cases of hereditary cataract, 89% were auto- Congenital/Infantile Cataract Cases Registered in Denmark
somal dominant, 7% were autosomal recessive, 2% were X-linked, from 1977 to 2001 among Children (0 –17 Years)
and another 2% could not be classified. With regard to the clinical
classification, autosomal dominant inheritance was highly repre- Incidence per
sented in cases of isolated cataract (91%) and in those associated No. of Cases 1 000 000
with additional ocular dysmorphology (81%). Regarding the pa- Disease (n ⴝ 60) Children*
tients with systemic anomalies, 5 of the 9 cases were dominantly Trisomy 21 (Down syndrome) 29 13.5†
inherited, and 4 were recessively inherited; all 9 patients were Rhizomelic chondrodysplasia 6 2.6†
mentally retarded. punctata (Conradi’s syndrome)
Four cases had inherited the associated ocular dysmorphology Lowe’s syndrome 4 0.6†
(genetic, hereditary other ocular dysmorphology) but did not have WAGR syndrome 3 1.9
family members registered with congenital/infantile cataract. Deletion 11p13 (no Wilm’s tumor) 2 0.6†
Three of these patients had autosomal dominant aniridia, and 1 had Nance–Horan syndrome 2 1.3
autosomal recessive ectopia lentis. COFS syndrome 2 —†
Galactosemia 2 1.3
As shown in Table 2, nonsystemic cataract with additional Walker–Warburg syndrome 2 1.3
ocular dysmorphology was recorded in a total of 149 of the 1027 (HARD ⫾ E)
cases (14.5%) and appeared mainly in the idiopathic group (n ⫽ Cockayne’s syndrome 1 0.6
122). Two of 3 patients had unilateral cataract, and PFV (n ⫽ 59) Hallermann–Streiff syndrome 1 0.6
was the most frequent single ocular malformation in the series, Wolf–Hirschhorn syndrome 1 0.6
followed by microcornea and/or microphthalmos (n ⫽ 40). Micro- Trisomy 3 1 0.6
cornea and/or microphthalmos were the main ocular associations Marfan’s syndrome 3 0.6†
in the hereditary group. Turner’s syndrome 1 0.6
Table 3 lists the number (n ⫽ 60) and incidence of cataract
cases associated with syndromes/chromosomal anomalies. Consti- COFS ⫽ cerebro-oculofacial–skeletal; HARD ⫾ E ⫽ hydrocephalus,
tuting 3% of all 1027 cases, trisomy 21 was by far the most agyria, and retinal dysplasia, with or without encephalocele; WAGR ⫽
frequent syndrome, being responsible for almost 50% of the con- Wilm’s tumor, aniridia, genital anomalies, and mental retardation.
genital/infantile cataract cases associated with syndromes. *Based on the number of patients born in Denmark from 1977 to 2001
Overall, 17 cataract patients had aniridia, 6 (35%) having a divided by the total number of children born in Denmark in the same
parent affected with aniridia (3 cases in the genetic, hereditary period (approximately 1 500 000 children).
†
Some of the listed cases were from patients born outside Denmark and/or
cataract group and 3 cases in the genetic, hereditary other ocular born before 1977 and were therefore excluded from the estimation.
dysmorphology group; Table 2); 5 of the remaining 11 sporadic

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 Ophthalmology Volume 111, Number 12, December 2004

Table 4. Clinical Classification of Congenital/Infantile Cataract Discussion

Caused by Intrauterine Infection Registered in Denmark from
1977 to 2001* among Children (0 –17 Years)
In this study, the 2 major etiological groups of congenital/
Clinical Classification and Agent No. of Cases infantile cataract were idiopathic and then genetic, and the
majority of cases were bilateral. Most of the bilateral pa-
Isolated cataract
Rubella 2 tients were male, and most of the unilateral, female. The
Cytomegalovirus 1 idiopathic cases differentiated themselves clinically from
Additional ocular dysmorphology, nonsystemic the cases of known etiology primarily by an equal distribu-
Rubella 1 tion of laterality (the majority of cases of known etiology
Systemic anomalies
Rubella 26
being bilateral) and by a higher proportion of cases with
Toxoplasmosis 2 additional ocular dysmorphology.
Enterovirus 1 The cases included in this study were identified from a
Herpes simplex virus 1 hospital discharge register based on mandatory nationwide
Total 34 registration. From 1977 to 2001 all inpatients were in-
cluded, and since 1995 outpatients also were registered. The
*The measles, mumps, and rubella vaccination was introduced in 1987, review of all medical records of children with a diagnosis of
and 27 of the 29 congenital rubella cases were from patients born before congenital/infantile cataract and the additional review of
1987.
medical records of children with another nonacquired cata-
ract diagnosis have given high credibility to the validity of
the number of congenital/infantile cataract cases included in
Time Trends, 1977 to 2001 this study. The use of hospital registers may lead to an
In 1987, rubella immunization was introduced to the Danish child- underestimation of cases. Thus, patients who were seen only
hood vaccination program. In the period 1977 to 1986, the per- by a private ophthalmologist in the study period or who
centage of cases caused by intrauterine infection was high— were outpatients before 1995 could not be traced. However,
namely, 6%—whereas it was 1% in 1987 to 2001. For the 2 other children with congenital/infantile cataract most likely have
major etiological categories, unknown and genetic, there was no been evaluated at an eye department at some time during
change in distribution over time, nor was there any change in the childhood. In addition, we have previously reported the risk
distribution of laterality over time. of congenital/infantile cataract in our study as higher than
those in most earlier published studies, even when based on
Cumulative Risks of Idiopathic/Unknown and inpatients only.16 Furthermore, the inclusion of outpatients
Hereditary Congenital/Infantile Cataract Cases, does not seem to change the distribution of etiology and
1995 to 2000 laterality substantially. Thus, we found no difference in the
distribution of etiology and laterality before or after 1995.
Comprising both inpatients and outpatients, Table 6 shows the The information obtained in the medical records from
cumulative risks for idiopathic and hereditary congenital/infantile hospitals was in general very detailed. However, in a retro-
cataract cases in the most recent registration period, 1995 to 2000
(n ⫽ 273). Overall incidences of idiopathic congenital/infantile
spective chart review information needed for classification
cataract were similar in boys and girls (47/100 000 children). may be missing. Therefore, to improve the classification of
However, unilateral cataract was more common in girls, and cases we also reviewed medical records from private oph-
bilateral cataract was seen more often in boys. Males predominated thalmologists, and in addition, we linked the cases with an
significantly among the hereditary cataracts, which were almost existing register on congenital cataract (Danish Family Ar-
exclusively bilateral. chive for Hereditary Eye Disorders). After this supplemen-

Table 5. Morphology of Congenital/Infantile Cataract Cases Registered in Denmark from 1977 to 2001
among Children (0 –17 Years)

Percentage of Cases
Syndromes/
Chromosomal
Unknown/Idiopathic Hereditary Cataract Anomalies Intrauterine Infection Others Total
Morphology (n ⫽ 645) (n ⫽ 240) (n ⫽ 60) (n ⫽ 34) (n ⫽ 48)* (n ⫽ 1027)
Nuclear/zonular 26 61 25 44 13 34
Dense 17 9 22 23 8 15
Posterior cortical/subcapsular 17 6 7 9 20 14
Mixed 10 13 8 9 6 10
Posterior polar 14 2 2 15 10
Anterior polar 7 4 2 13 6
Other 7 4 29 3 15 8
Not reported 2 1 5 12 10 3

*Includes 4 hereditary other ocular dysmorphology, 1 thalidomide, and 43 classification not possible.

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 Haargaard et al 䡠 Nationwide Danish Study of Congenital/Infantile Cataracts
Table 6. Cumulative Risk per 100 000 Children (0 –17 Years) of Registered Unknown/Idiopathic and Hereditary
Congenital/Infantile Cataract Cases in Denmark from 1995 to 2000, According to Laterality and Gender
Cumulative Risk per 100 000 Children (95% CI)
Etiology and
Laterality Male
Unknown/idiopathic 45.4 (39.8–51.1)
Unilateral 19.9 (8.1–31.7)
Bilateral 25.6 (18.1–33.0)
Hereditary cataract 19.6 (11.7–27.6)
Unilateral ⬍1
Bilateral 19.2 (11.2–27.1)
CI ⫽ confidence interval.
tary information, only 4% of all cases could not be etiolog-
ically classified, because the medical/family history was
incomplete or unavailable from the medical records.
The etiological distribution in the present study is con-
sistent with the findings of 2 studies of congenital/infantile
cataract, one covering southeastern Australia in a time pe-
riod corresponding to ours (n ⫽ 421)14 and another based on
cases collected over a 12-month period in the mid-1990s in
the United Kingdom (n ⫽ 243).13 However, compared with
our results, the United Kingdom proportion of genetic cat-
aract was higher, due to a higher proportion of syndromes
(14% vs. 8% [95% CI, 6%–12%] in 1995–2001). Consistent
with our results, the United Kingdom study found similar
clinical features in the unknown cataract cases—namely, no
difference in laterality and a higher proportion of additional
ocular dysmorphology.
Boys were more likely to have bilateral cataract than
girls, which has also been reported in a study of American
children with congenital/infantile cataract.21 Interestingly,
this male predominance was found among both idiopathic
and hereditary cases of bilateral cataract. Some of the idio-
pathic bilateral cases might be genetically based, but to
explain the gender difference more cases should be X-
linked. However, the proportion of known X-linked cata-
racts in Denmark was found to be low. Still, some of the
bilateral idiopathic cases might be of genetic etiology. In
fact, it has previously been estimated that the risk of cataract
in children of parents with apparently sporadic cataract is
ⱖ10%.22
Trisomy 21 dominated the cases associated with syn-
dromes. Compared with the incidence of trisomy 21 of
approximately 1 in 600 to 800 children,23–25 the occurrence
of trisomy 21 in this study was 20 times higher than in the
population. Overall, the occurrence of cataract among the
expected number of patients with trisomy 21 was only 1%,
a lower percentage than that found in 2 previous case
studies of similar age groups.26,27
As would be expected, the proportion of congenital/
infantile cataract cases caused by maternal rubella infection
decreased during the study period. In 1987, vaccination for
rubella was fully implemented as part of the Danish child-
hood vaccination program. Before 1987, it was recom-
mended to test fertile women serologically for rubella an-
tibodies,28 but only a limited number of fertile women were
vaccinated.29 In the present study, the majority of the 28
Female All
49.3 (43.1–55.4) 47.3 (43.2–51.4)
32.5 (22.7–42.2) 26.0 (18.8–33.2)
16.8 (9.5–24.5) 21.3 (15.9–26.7)
8.6 (0–20.9) 14.2 (6.9–21.5)
⬍1 ⬍1
8.6 (0–20.9) 14.0 (6.7–21.3)
children with congenital rubella were born before 1987
(93%); 1 was born in 1988 and 1 in 1992, the mother of the
latter being from Brazil. Otherwise, we did not find any
change in the distribution of cases by etiology over time.
This finding, along with our previous finding of no time
trend in the overall incidence of congenital/infantile cata-
ract,16 shows that there is no time trend in the incidence of
either idiopathic or genetic congenital/infantile cataract.
Our study illustrates that major differences exist between
distributions of idiopathic and hereditary cataract cases. Of
particular interest is the idiopathic group, which, by defini-
tion, is unexplained. We found no indication of a change in
the incidence of this subgroup over time and, thus, no strong
indication that the changes in our society over the past
decades are significant in the development of idiopathic
congenital/infantile cataract. It has been suggested that in-
fections occurring in utero might be responsible for the
development of some cataract cases. In this regard we note
that, despite a constant rate of idiopathic congenital/infan-
tile cataract, the pattern of infectious diseases has changed
significantly, including the pattern of childhood infections.
The constant incidence of idiopathic congenital/infantile
cataract could argue for a particular influence of risk factors
that are stable over prolonged periods. Looking for clues to
a better understanding of the pathogenesis of idiopathic
congenital/infantile cataract, we are puzzled by the nearly
2-fold increased female predominance among unilateral
cases of the idiopathic type. Unfortunately, we have at
present no obvious explanation for this finding.
In conclusion, the prevention of congenital/infantile cat-
aract continues to be a major challenge also in industrialized
countries, because of the high proportion of idiopathic
cases. Studies addressing risk factors for these cases are
important to the future planning of primarily preventive
strategies against congenital/infantile cataract.
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