Strabismus, 20(2), 74–77, 2012

© 2012 Informa Healthcare USA, Inc.

ISSN: 0927-3972 print/1744-5132 online
DOI: 10.3109/09273972.2012.680234

ORIGINAL ARTICLE

Ocular Abnormalities and Systemic Disease in

Down Syndrome
Retrospective clinical study, University Eye Hospital, Ljubljana, Slovenia
Branka Stirn Kranjc, MD, PhD
Retrospective clinical study, University Eye Hospital, Ljubljana, Slovenia

Abstract
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Introduction: Ocular problems as refractive errors, strabismus, accommodation, and cataract are well known
in children with Down syndrome (DS). However, there is little information on the possible correlation of eye
problems with systemic diseases such as heart defect (with or without surgery), hypotony, hypothyroidism,
hearing loss, and others.
Methods: Ophthalmic problems versus certain systemic diseases were studied in 65 children with DS, aged 2
months to 13 years, referred to the University Eye Hospital Ljubljana, Slovenia from 2008 to 2010. Standard
ophthalmic examination methods were used, and physical data were taken from pediatric records.
Results: Ocular findings included nystagmus (29.2%), esotropia (26.1%), epiphora (21.5%), Brushfield spots
(16.9%), lens opacities (12.3%), abnormalities of the retinal vessels, foveal hypoplasia, or retinal pigment epi-
For personal use only.

thelium hyperplasia (32.2%), and optic disc pallor (7.6%). Hyperopia (36.9%) was the most frequent refractive
error in the group, followed by astigmatism (29.2%) and myopia (24.6%). No diagnosed systemic abnormalities
were found in 18.3% of the children, while 30.7% had congenital heart defect. Hypothyroidism, hypotony,
hearing loss, gastrointestinal tract malformations, and leukemia were less common. Nystagmus was related
to myopia and esotropia, and to heart disease and heart operations.
Conclusions: Comorbidities are common in DS and complicate diagnosis, development, and therapy.

KEYWORDS:  Down syndrome, ocular findings, systemic findings

Introduction Congenital heart disease is present in 30%–40% of

Down syndrome (DS) is the most frequent chromo-
somal aberration associated with mild to moderate
mental disability, a characteristic facial appearance,
and poor muscle tone in infancy. It occurs in about 1
in 600–800 newborns, with small male predominance.
The risk of having a child with DS increases with
maternal age.
DS, also known as trisomy 21, was one of the first
chromosomal disorders to be identified (Lejeune et al.,
1959). Three free copies of chromosome 21 are present
in 95% of individuals with trisomy 21. In the other 5%
of patients, 1 copy is translocated to another acrocen-
tric chromosome, most often chromosome 14 or 21.
Recognizable mosaicism for a trisomic and a normal
cell line is present in 2%–4% of individuals with free
trisomy 21 (Hook et al., 1983).
individuals with DS, ventricular septal defect being
the most common (Ahmed et al., 2005). Leukemia
and leukemoid reactions show increased incidence
in DS (Robinson, 1992), and hypothyroidism is com-
mon. The neuropathologic hallmarks of Alzheimer’s
disease develop at a much earlier age than in indi-
viduals without trisomy 21. DS patients have sig-
nificant hearing loss, usually of the conductive type
(Mazzoni et al., 1994).
The most commonly described ocular findings
in DS are the following: upward slanting of the
palpebral fissure, epicanthus, epiblepharon, astig-
matism, hyperopia, myopia, esotropia, exotropia,
nystagmus, nasolacrimal duct obstruction, blepha-
roconjunctivitis, retinal abnormalities, cataract,
glaucoma, iris Brushfield spots, and keratoconus
(Kim et al., 2002).

Received 22 September 2011; revised 05 March 2012; accepted 13 March 2012

Address for Correspondence: Branka Stirn Kranjc, MD, PhD, University Medical Centre, University Eye Hospital Ljubljana, Grabloviceva 46,
1000 Ljubljana, Slovenia. E-mail: branka.stirn@guest.arnes.si

74
 Down Syndrome, Ocular, Systemic Abnormalities   75

Since there are few data on ocular findings in DS
and systemic disease (Bromham et al., 2002) (e.g., heart
defect with or without operation, hypothyroidism,
hypotony, hearing loss), a retrospective study was
carried out to estimate these features in our referred
population.
METHODS
The study consisted of 65 consecutive (40 male, 25
female) children with DS born between 1995 and 2009,
and examined from 2008 to 2010. These children were
consecutively referred by personal pediatricians, devel-
opmental pediatricians, and or local ophthalmologists
to the tertiary ophthalmic center in Ljubljana, Slovenia.
The health care system stipulates that all at-risk chil-
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29.19 years, and 15% of the mothers were older than 35
years at the time of the birth.
The most common systemic finding in our study group
of 65 children, born between 1995 and 2009, were heart
defects, mostly ventricular and atrial septal defect and
patent ductus arteriosus. Of the 65 children with DS, 20
(30.7%) had heart defects, and 4 (or 18% of the 20) required
surgery. Gastrointestinal tract malformations (duodenal,
intestinal atresia, Hirschprung disease) were present in 4
(6.1%) children, 9 (13.8%) had hypothyroidism, 7 (10.7%)
had moderate to severe hypotony, 5 (7.6%) had mild to
moderate conductive type of hearing loss, 2 had cerebral
paroxisms, 1 had equinovarus and 1 child was treated for
acute myeloic leukemia at 2 years of age. Only 12 (18.3%)
children did not exhibit systemic abnormalities.
All of the 65 children had at least one expected
craniofacial abnormality, mostly mongoloid slant,

dren in the state have access to the center. Mean age of
the studied group at the last examination was 7.4 years
(age range from 2 months to 13 years). The children
were examined between 1 and 6 times. The results of
the last examination are analyzed retrospectively. The
genetic data of the children were not complete, but the
majority had trisomy 21. The clinical characteristics
of their ocular pathology, including nystagmus, were
investigated by performing a complete ophthalmo-
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ear abnormalities and epicanthic folds. Ocular find-
ings are presented in Table 1. Eight children (12.3%)
children were emetropes, 24 (36.9%) had hyperopia,
16 (24.6%) were myopes (half of them >-3.0 D), 19
(29.2%) had astigmatism, and 7 (10.7%) anisometropia.
TABLE 1  Ocular findings in 65 children with Down syndrome
Ocular manifestation n = 65
Nystagmus 19 (29.2%)

logical examination, expanded according to the child’s Strabismus 17 (26.1%)

needs (i.e., probing, electrophysiology, ultrasound,  Esotropia 9 (13.8%)
neuroimaging). Visual acuity was assessed monocu-   Intermittent esotropia 8 (12.3%)
larly in cooperative children; otherwise it was assessed  Exotropia –
binocularly using Teller Acuity Cards, Cambridge Epiphora 14 (21.5%)
Crowding Cards, Lea symbols, various preverbal opto- Brushfield spots 11 (16.9%)
types, or the Lang stereo test. Cycloplegic refraction Lens opacities 8 (12.3%)
was performed at all examinations by retinoscopy and Retinal vessel abnormalities 11 (16.9%)
automatic refraction done with Nikon Retinomax Plus Hypoplastic fovea 6 ( 9.2%)
K2. Accommodation was determined using dynamic Retinal pigment epithelium hyperplasia 4 ( 6.1%)
retinoscopy (Woodhouse et al., 1993). Strabismus was Optic disc pallor 5 ( 7.6%)
evaluated with the Hirschberg test, the cover test, Glaucoma –
prisms, or other orthoptic methods, if possible. Eye Keratoconus –
motility was evaluated by observing eye movements
when fixating a moving target or video recordings. The
main systemic abnormalities were recorded and ana-
lyzed from the pediatric documentation.
The chi-square test was used to determine the
bivariate correlation between nystagmus and ocular
findings as well as between nystagmus and systemic
abnormalities.

RESULTS

To set the study in a national context, data from demo-

graphic surveys showed that there were 92,261 infants
born in Slovenia between 2003 and 2007. During this
period, 67 babies were diagnosed with DS (0.073% or
FIGURE 1   Evaluated strabismus, refractive errors vs nystagmus
one in 1377 infants). Of these children, 37 had trisomy in 65 children with Down syndrome; nystagmus was mostly
21, translocation was present in 26, and the remaining related to esotropia and myopia ≥ –3.0 D and not to hyperopia,
4 had mosaicism. The avarage age of the mother was anisometropia, and astigmatism.

© 2012 Informa Healthcare USA, Inc.

 76    B. Stirn Kranjc
Refractive errors of the last examination vs nystagmus
are shown in Figure 1. No significant difference in
systemic or ocular findings between sexes was found.
Electrophysiological evaluation showed normal electro-
retinograms and normal latencies, but lower amplitude
of responses to flash and/or pattern visual evoked
potentials in all tested cases. None of the children had
exotropia or vertical deviation. No strabismus was
noticed, in 48 (73.4%) children, and the rest had eso-
tropia or intermittent esotropia. Accommodation deficit
(≥1.5 D) was still evident in 8 (12.3%) children despite
refraction correction and addition for near and all of
them had hypermetropia ≥+3.0 D. Children with DS
and higher myopia had bulbar axial length >24.3 mm.
None of the children had severe visual deficit. For the
majority, best corrected visual acuity ranged from 0.5-
0.3 LogMAR while 20 children (30%) showed normal
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visual acuity for age. Where testing was possible, no
deterioration of color or near vison was found. Stereo
vision was present in 7 (10.7 %) of the children. All of
the children except infants were successfully integrated
into kindergardens or adjusted school programs.
Nystagmus was noticed in 19 (29.2%) children,
and was latent/manifest or latent in 2 cases, with the
onset in infancy (2–6 months after birth) in all children.
Esodeviation of 10 to 30 prism diopters was present in
For personal use only.
14 children with nystagmus. There was no clinically
recognizable ocular pathology to account for the
nystagmus. Head tilt was evident in 5 children with
developed null zone. Comparing of ocular and systemic
findings in DS children with and without nystagmus
showed a statistically significant relationship between
heart defect and nystagmus (P = 0.001) as well as
heart surgery and nystagmus (P = 0.002), while
hypothyroidism, hypotony and hearing loss were not
significantly correlated with nystagmus (P > 0.49).
DISCUSSION
Our data for the 5-year period between 2003 and 2007
show that the occurrence rate of Down syndrome
in Slovenia is lower than that cited in the literature:
1/1377 vs 1/600–800 babies (Ahmed et al., 2005; Hook
et al., 1993; Kim et al., 2002). This difference might be
explained by the fact that our methodology took into
account already known general data on DS, or that there
are different prenatal screening strategies in the country.
We also found fewer cases of trisomy 21 (55.2% vs 95%)
and many more translocations (38.8% vs 5%), while the
percentage of mosaicism did not differ (Hook et al., 1993).
Our ophthalmological findings are similar to that of
Wagner et al. (1990), with 29.2% vs. 29.8% of children
found to have nystagmus. This may be a reflection
of the pattern to referral to a pediatric ophthalmolo-
gist, as the reported incidence of nystagmus in other
studies ranged mostly from 3.2%–17% and also 33.3.%
(Catalano, 1990; Kava et al., 2004; Shapiro & France,
1985). Studies showing lower incidence of nystagmus in
DS also used different methodologies, such as studying
younger children (neonates and babies after 1 month of
age) with DS. Our study also found esotropia, myopia,
and nystagmus to be associated with heart defects in
children with DS. These findings are similar to those
previously described in Bromham et al. (2002), in a
cohort of DS with full trisomy 21. The type of nystag-
mus as horizontal, fine, rapid, or latent/manifest latent
is described clinically as typical of DS, however eye
movement recordings would specify the characteristics
of the waveforms (Averbuch-Heller et al., 1999). The
nystagmus found in DS does not generally seem to be
associated with neurological or ocular defects (Haugen
& Høvding, 2001; Wagner et al., 1990).
Significant refractive errors were found in our study
(Figure 1); however, we found lower incidence of strabis-
mus (26.6% vs. 38%, 47%), compared with other studies
(Da Cunha & Moreira, 1996; Stephen et al., 2007). This
may be a reflection of the high prevalence of accommo-
dative esotropia and hypermetropia, or possibly of the
earlier prescription of glasses in our children (in the first
to third year of age). The link between under-accommo-
dation and hypermetropia was found to be present in
early infancy in children with DS (Stewart et al., 2007).
Asian studies on ocular status in children with DS
describe similar ocular abnormalities, with a higher
prevalence of exotropia (10.5%) than previously
reported. Ethnicity might be a reason for this finding
since it is also well known from previous reports that
esotropia is more common in DS than other forms of
strabismus (Haugen & Høvding, 2001; Stewart et al.,
2007). These studies found more bilateral congenital
cataracts (13.3%), keratoconus, glaucoma, and retino-
blastoma, but no Brushfield spots, which seem to be
pathognomonic for DS in light-colored irises in the
Caucasian population. Spoke wheel retinal vessels
crossing the optic nerve head margin are well known in
DS (reported to be present in 13%–42%) and are possibly
associated with the role of chromosome 21 (Da Cunha &
Moreira, 1996; Kim et al., 2002; Kim and Hwang, 2009;
Liza-Sharmini et al., 2006).
The high prevalence of ocular disorders in children
with DS underscores the urgent need for their evalua-
tion and treatment. As shown in this study, the clinicians
should be aware that comorbidity is quite common in
DS, especially heart defects, which are highly associated
with esotropia, myopia, and nystagmus.
ACKNOWLEDGMENTS
Presented at the 13th biannual CVRS (Child Vision
Research Society) Meeting, Huizen, The Netherlands,
June 15–18, 2011.
Declaration of interest: The author declares no conflicts
of interest.
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 Down Syndrome, Ocular, Systemic Abnormalities   77
References
Ahmed I, Ghafoor, T, Samore NA, Chattha MN. Down syndrome:
clinical and cytogenetic analysis. J Coll Physicians Surg Pak.
2005; 15:426–429.
Averbuch-Heller L, Dell’Osso LF, Jacobs JB, Remler BF. Latent and
congenital nystagmus in Down syndrome. J Neuroophthalmol.
1999; 19:162–172.
Bromham NR, Woodhouse JM, Cregg M, Webb E, Fraser WI.
Heart defects and ocular anomalies in children with Down’s
syndrome. Br J Ophthalmol. 2002; 86: 1367–1368.
Catalano RA. Down syndrome. Surv Ophthalmol. 1990; 34:
385–398.
Da Cunha RP, Moreira JB. Ocular findings in Down’s syndrome.
Am J Ophthalmol. 1996; 122:236–244.
Haugen OH, Høvding G. Strabismus and binocular function with
Down syndrome. A population-based, longitudinal study.
Acta Ophthalmol Scand. 2001; 79:133–139.
Hook EB, Cross PK, Schreinenmachers DM. Chromosomal abnor-
mality rates at amniocentesis and in live-born infants. JAMA.
Strabismus Downloaded from informahealthcare.com by Monash University on 06/10/13
1983; 249:2034–2038.
Kava MP, Tullu MS, Muranjan MN, Girisha KM. Down syn-
drome: Clinical profile from India. Arch Med Res. 2004;
35:31–35.
Kim JH, Hwang JM, Kim HJ, Yu YS. Characteristic ocular find-
ings in Asian children with Down syndrome. Eye. 2002;
16:710–714.
For personal use only.
© 2012 Informa Healthcare USA, Inc.
Kim U, Hwang JM. Refractive errors and strabismus in Asian
patients with Down syndrome. Eye. 2009; 23:1560–1564.
Liza-Sharmini AT, Azlan ZN , Zilfalil BA. Ocular findings in
Malaysian children with Down syndrome. Singapore Med J.
2006; 47:14–19.
Lejeune J, Gautier M, Turpin R. Etude des chromosomes soma-
tiques de neuf enfants mongoliens. CR Acad Sci. 1959;
248:1721–1722.
Mazzoni DS, Ackley, RS, Nash DJ. Abnormal pinna type and hear-
ing loss correlations in Down’s syndrome. J Intellect Disabil.
1994; 38:549–560.
Robinson LL. Down syndrome and leukemia. Leukemia. 1992;
6:5–7.
Shapiro MB, France TD. The ocular features of Down’s syndrome.
Am J Ophthalmol. 1985; 99:659–663.
Stephen E, Dickson J, Kindley AD, Scott CC, Charleton, PM.
Surveillance of vision and disorders in children with Down
syndrome. Dev Med Child Neurol. 2007; 49:513–515.
Stewart RE, Woodhouse JM, Cregg M, Pakeman VH. Association
between accommodative accuracy, hypermetropia, and stra-
bismus in children with Down’s syndrome. Optom Vis Sci.
2007; 84:149–155.
Wagner RS, Caputo AR, Raynolds RD. Nystagmus in Down’s
syndrome. Ophthalmology. 1990; 97:1439–1444.
Woodhouse JM, Meades JS, Leat SJ, Saunders KJ. Reduced
accommodation in children with Down syndrome. Invest
Ophthalmol Vis Sci. 1993;34: 2382–8237.