Amblyopia Risk Factors in Newborns With

Congenital Nasolacrimal Duct Obstruction

Aldo Vagge, MD, PhD; Claudia Tulumello, MD; Marco Pellegrini, MD; Marco Di Maita, MD;
Michele Iester, MD, PhD; Carlo Enrico Traverso, MD

ABSTRACT isometropia might develop later on, all patients with

Purpose: To investigate the presence of amblyopia risk CNLDO should be monitored for amblyopia.
factors in newborns with congenital nasolacrimal duct
obstruction (CNLDO) and age-matched healthy control [J Pediatr Ophthalmol Strabismus. 2020;57(1):39-43.]
subjects.

Methods: This retrospective case-control study involved INTRODUCTION

newborns aged 30 to 60 days with CNLDO and age-
matched healthy control subjects. Amblyopia risk factors
were identified in accordance with the American Asso-
ciation for Pediatric Ophthalmology and Strabismus Vision
Screening Committee recommendations. The prevalence
of amblyopia risk factors was compared in newborns with
CNLDO and age-matched healthy control subjects, new-
borns with unilateral and bilateral CNLDO, and the affect-
ed eye and fellow eye of newborns with unilateral CNLDO.
Results: Amblyopia risk factors were found in 18 pa-
tients (11.9%) with CNLDO and 19 control subjects
(8.7%) (P = .314). Eyes with CNLDO showed a signifi-
cantly lower spherical equivalent compared to control
eyes (2.01 ± 1.21 vs 2.79 ± 1.14 diopters, P < .001). No
difference in amblyopia risk factors was found in eyes
with unilateral and bilateral CNLDO (11.5% vs 12.1%; P
= .908) or in eyes with unilateral CNLDO and fellow eyes
(9.8% vs 12.3%; P = .540).
Conclusions: CNLDO does not seem to be associated
with amblyopia risk factors in newborns. Because an-
Congenital nasolacrimal duct obstruction
(CNLDO) is one of the ophthalmic conditions most
commonly encountered by pediatric ophthalmolo-
gists,1,2 occurring in 5% to 15% of full-term new-
borns.3,4 CNLDO is characterized by unilateral or
bilateral epiphora and/or intermittent mucopurulent
discharge that in approximately 90% of patients re-
solves spontaneously in the first 12 to 18 months
of life.5 Although CNLDO is considered a benign
condition, several authors have reported a possible as-
sociation between CNLDO and amblyopia risk fac-
tors.6-15 In particular, hyperopia and anisometropia
have been observed to be associated with same-sided
unilateral CNLDO. This condition may predispose
affected children to develop clinical amblyopia.8
However, as far as we know, no previous study has
extensively investigated these aspects in newborns.
The aim of this study was to compare amblyopia risk
factors in (1) newborns with CNLDO and age-matched
healthy control subjects, (2) newborns with unilateral
and bilateral CNLDO, and (3) the affected eye and fel-
low eye of newborns with unilateral CNLDO.

From University Eye Clinic of Genoa, Policlinico San Martino (AV, MD, MI, CET) and the School of Medicine and Pharmacy (CT), Department of
Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy; IRCCS Ospedale Policlinico San
Martino, Genova, Italy (AV, MI, CET); and the Ophthalmology Unit, S. Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy (MP).
Submitted: July 11, 2019; Accepted: November 5, 2019
The authors have no financial or proprietary interest in the materials presented herein.
Correspondence: Aldo Vagge, MD, PhD, University Eye Clinic of Genoa, Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal
and Child Health, University of Genoa, IRCCS Ospedale Policlinico San Martino, Viale Benedetto XV, 5, 16132 Genova, Italy. E-mail: aldo.vagge@unige.it
doi:10.3928/01913913-20191111-01

Journal of Pediatric Ophthalmology & Strabismus • Vol. 57, No. 1, 2020 39

 TABLE 1
Characteristics of Patients With CNLDO and Control Subjects
Characteristic CNLDO Group (n = 151)
Female gender, n (%) 88 (58)
Age (days) 44.4 ± 9.0
Birth weight (g) 3,185.1 ± 515.6
Gestational age (wks) 38.5 ± 2.1
CNLDO = congenital nasolacrimal duct obstruction
PATIENTS AND METHODS
A chart review of consecutive patients aged 30
to 60 days examined at the University Eye Clinic of
Genova, Policlinico San Martino, Department of
Neuroscience, Rehabilitation, Ophthalmology, Ge-
netics, Maternal and Child Health, Genova, Italy, for
CNLDO was conducted. The study itself was per-
formed in accordance with the tenets of the Declara-
tion of Helsinki. Institutional review board approval
was obtained. As is standard practice in our clinic, all
records reviewed for this study documented a detailed
anterior segment evaluation, a complete cycloplegic
refraction, red reflex test, and fundus examination
performed 30 minutes following the instillation of
one to two drops of a pediatric “combo drop” of trop-
icamide 1% and phenylephrine 2.5%. The diagnosis
of CNLDO was made clinically, based on the pres-
ence of epiphora, discharge, and presence of reflux
with digital pressure over the nasolacrimal sac. At the
examiner’s discretion, CNLDO was confirmed with
the dye disappearance test. Only first-encounter re-
cords were used. Exclusion criteria for this study were
eyes with any findings that could cause excess tearing,
such as trichiasis.
Data were collected regarding patient demo-
graphics, including age, gender, birth weight, ges-
tational age, laterality of CNLDO, and other oph-
thalmologic diagnoses. CNLDO was classified into
unilateral and bilateral. Amblyopia risk factors were
identified in accordance with the American Associa-
tion for Pediatric Ophthalmology and Strabismus
(AAPOS) Vision Screening Committee recommen-
dations.15 In particular, guidelines for detection of
amblyopia risk factors in toddlers were followed.
The recommended target refractive magnitude for
detection was astigmatism of greater than 2.00 di-
opters (D), hyperopia of greater than 4.50 D, myo-
pia of greater than 3.50 D, and anisometropia of
greater than 2.50 D. Any media opacity greater than
40
Control Group (n = 218) P
131 (60) .727
45.8 ± 9.6 .310
3,145.1 ± 484.9 .448
38.7 ± 1.8 .196
1 mm in size was considered a nonrefractive ambly-
opia risk factor.
Statistical Analysis
The SPSS statistical software (SPSS, Inc., Chi-
cago, IL) was used for data analysis. The chi-square
or Fisher’s exact test was used to compare categori-
cal variables between patients with CNLDO and
control subjects, eyes with unilateral and bilateral
CNLDO, and affected and fellow eyes of patients
with bilateral CNLDO. Continuous variables were
expressed as means ± standard deviation. An inde-
pendent samples t test was used to compare con-
tinuous variables between patients with CNLDO
and control subjects and eyes with unilateral and
bilateral CNLDO. A paired-samples t test was used
to compare continuous variables between affected
and fellow eyes of patients with bilateral CNLDO.
A P value of less than .05 was considered significant.
RESULTS
Medical records of 151 consecutive patients with
a diagnosis of CNLDO (mean age: 44.4 ± 9.0 days)
were compared with those of 218 healthy control
subjects (mean age: 45.8 ± 9.6 days). Demographic
and clinical characteristics of the study population are
reported in Table 1. No significant differences were
found in age, gender, birth weight, and gestational
age between the two groups (all P > .05). CNLDO
was unilateral in 122 patients (80.8%) and bilateral
in the remaining 29 patients (19.2%).
The amblyopia risk factors observed in patients
with CNLDO and control subjects are reported
in Table 2. Overall, 18 patients with CNLDO
(11.9%) and 19 control subjects (8.7%) had ambly-
opia risk factors, and the difference was not statisti-
cally significant (P = .314). In particular, no signifi-
cant differences were found between the two groups
in astigmatism of greater than 2.00 D (P = .403),
Copyright © SLACK Incorporated
 TABLE 2
Amblyopia Risk Factors in Patients With CNLDO and Control Subjects
Amblyopia Risk Factor CNLDO Group (n = 151) Control Group (n = 218) P
Astigmatism > 2.00 D, n (%) 3 (2.0) 2 (0.9) .403
Hyperopia > 4.50 D, n (%) 10 (6.6) 15 (6.8) .923
Myopia > 3.50 D, n (%) 1 (0.7) 1 (0.5) 1.000
Anisometropia > 2.50 D, n (%) 3 (2.0) 1 (0.5) .309
Media opacity > 1 mm, n (%) 2 (1.3) 1 (0.5) .570
CNLDO = congenital nasolacrimal duct obstruction; D = diopters

TABLE 3
Amblyopia Risk Factors in Eyes With Unilateral and Bilateral CNLDO
Amblyopia Risk Factor Unilateral CNLDO (n = 122) Bilateral CNLDO (n = 58) P
Astigmatism > 2.00 D, n (%) 3 (2.5) 0 (7.4) .552
Hyperopia > 4.50 D, n (%) 8 (6.6) 4 (6.6) .932
Myopia > 3.50 D, n (%) 1 (0.8) 0 (0.8) 1.000
Anisometropia > 2.50 D, n (%) 2 (2.0) 2 (0.5) .595
Media opacity > 1 mm, n (%) 1 (0.8) 1 (0.8) .542
CNLDO = congenital nasolacrimal duct obstruction; D = diopters

TABLE 4
Amblyopia Risk Factors in Eyes With Unilateral CNLDO and Fellow Eyes
Amblyopia Risk Factor Unilateral CNLDO (n = 122) Fellow Eyes (n = 122) P
Astigmatism > 2.00 D, n (%) 3 (2.5) 9 (7.4) .136
Hyperopia > 4.50 D, n (%) 8 (6.6) 8 (6.6) 1.000
Myopia > 3.50 D, n (%) 1 (0.8) 1 (0.8) 1.000
Media opacity > 1 mm, n (%) 1 (0.8) 1 (0.8) 1.000
CNLDO = congenital nasolacrimal duct obstruction; D = diopters

hyperopia of greater than 4.50 D (P = .923), myo-
pia of greater than 3.50 D (P = 1.000), anisometro-
pia of greater than 2.50 D (P = .309), and media
opacity of greater than 1 mm (P = .570). Eyes with
CNLDO showed a significantly lower spherical
equivalent compared to control eyes (2.01 ± 1.21 vs
2.79 ± 1.14 D, P < .001). Conversely, no significant
difference in astigmatism between the two groups
was found (0.23 ± 0.50 vs 0.23 ± 0.47 D, P = .919).
The amblyopia risk factors observed in eyes with
unilateral and bilateral CNLDO are reported in Table
3. Overall, 14 eyes (11.5%) of patients with unilateral
CNLDO and 7 eyes (12.1%) of patients with bilateral
CNLDO had amblyopia risk factors (P = .908). In
particular, no significant differences were found be-
tween the two groups in astigmatism of greater than
2.00 D (P = .552), hyperopia of greater than 4.50 D
(P = .932), myopia of greater than 3.50 D (P = 1.000),
anisometropia of greater than 2.50 D (P = .595), and
media opacity of greater than 1 mm (P = .542). No
significant difference between the two groups was
found for spherical equivalent (2.04 ± 1.24 vs 1.96 ±
1.06, P = .674) and astigmatism (0.25 ± 0.53 vs 0.18
± 0.37, P = .403).
The amblyopia risk factors observed in eyes
with unilateral CNLDO and fellow eyes are re-
ported in Table 4. In the 122 patients with bilateral
CNLDO, 12 of the affected eyes (9.8%) had ambly-
opia risk factors compared to 15 of the unaffected
eyes (12.3%) (P = .540). No significant differences
were found between the two eyes in astigmatism of
greater than 2.00 D (P = .136), hyperopia of greater

Journal of Pediatric Ophthalmology & Strabismus • Vol. 57, No. 1, 2020 41

than 4.50 (P = 1.00), myopia of greater than 3.50 D
(P = 1.00), and media opacity of greater than 1 mm
(P = 1.00). No significant difference was found be-
tween the two groups for spherical equivalent (2.03
± 1.24 vs 2.00 ± 1.23, P = .213) and astigmatism
(0.25 ± 0.53 vs 0.25 ± 0.53, P = .319).
DISCUSSION
The possible relationship between CNLDO
and amblyopia has been increasingly studied. Sev-
eral studies evaluated the presence of amblyopia risk
factors in patients with CNLDO, reporting a preva-
lence ranging from 9.5% to 35%.6,9-14 In addition, a
significantly higher incidence of anisometropia with
higher hyperopia was observed in eyes with unilater-
al CNLDO compared to fellow eyes.7,11,14 Similarly,
a higher rate of anisometropia was reported in eyes
with unilateral compared to bilateral CNLDO.8,13
However, other studies did not identify any signifi-
cant difference in the incidence of amblyopia be-
tween eyes with CNLDO and control eyes,16 and
between eyes with unilateral CNLDO and fellow
eyes.17 This heterogeneity may depend on differenc-
es in inclusion criteria, sample sizes, and definitions
of anisometropia or amblyopia.
In the current study, we evaluated the pres-
ence of amblyopia risk factors in newborns with
CNLDO. Patients with CNLDO and healthy con-
trol subjects showed no significant difference in
amblyopia risk factors. In addition, no significant
differences in amblyopia risk factors were observed
in eyes with unilateral and bilateral CNLDO or in
eyes with unilateral CNLDO and fellow eyes. These
results are in agreement with those of Ellis et al.,16
who found no relationship between CNLDO and
amblyopia in a large cohort of 4,792 children. How-
ever, in contrast to Ellis et al., our study included
only newborns aged 30 to 60 days. To the best of
our knowledge, this is the first study evaluating the
association between CNLDO and amblyopia in this
age group. This may explain the discrepancies with
other studies, which documented an increased risk
of amblyopia in older children with CNLDO.6-15
The mechanism by which patients with
CNLDO might develop anisometropia and am-
blyopia is still unknown. One hypothesis is that
a congenital abnormality of the orbit may lead to
both an impaired canalization of the nasolacrimal
duct and a reduced axial length of the globe.12 The
results of this study are in contrast with this hypoth-
42
esis, because no relationship between CNLDO and
anisometropia or hyperopia was found in newborns.
Furthermore, eyes with CNLDO were slightly less
hyperopic compared to control eyes. Interpreting
such an observation is not certain and requires fur-
ther investigation to be confirmed.
Another possibility is that watering and mu-
copurulent discharge in eyes with CNLDO might
cause the development of anisometropia and am-
blyopia.8,12 The rapid phase of emmetropization
takes place between 3 and 9 months of age, mainly
because of an increase in axial length.18 This age is
also associated with peak symptoms of CNLDO.
Therefore, blurring of vision caused by CNLDO
may interfere with the visual feedback guiding em-
metropization, resulting in increased incidence of
anisometropia. This may explain why newborns
with CNLDO showed a similar incidence of am-
blyopia risk factors as healthy control subjects in
this study, whereas other studies including older
children reported a higher risk of amblyopia risk
factors associated with CNLDO. The hypothesis is
further supported by the results of Bagheri et al.,7
who documented that increasing age in patients
with CNLDO is associated with a higher prevalence
and severity of anisometropia.
This study has some limitations that should
be taken into account. First, amblyopia risk fac-
tors were identified using AAPOS recommenda-
tions, which are designed for children older than 12
months. However, no recognized criteria for infants
exist. In addition, due to the cross-sectional design
of the study, we could not determine the develop-
ment of anisometropia and/or amblyopia at an older
age and the possible effect of CNLDO treatment on
visual development. Finally, newborns are known
to display a wide range of refractive errors, and this
may have reduced the power of the study to detect
significant differences. Further larger studies are re-
quired to confirm our results.
CNLDO does not seem to be associated with
amblyopia risk factors in newborns. However, an-
isometropia might develop later. Careful follow-up
and monitoring for amblyopia are recommended
for all patients with CNLDO.
REFERENCES
1. Guerry D III, Kendig EL Jr. Congenital impatency of the nasolac-
rimal duct. Arch Ophthalmol. 1948;39(2):193-204. doi:10.1001/
archopht.1948.00900020198006
2. Kamal S, Ali MJ, Gauba V. Congenital nasolacrimal duct obstruc-
Copyright © SLACK Incorporated
 tion. In: Ali MJ, ed. Principles and Practice of Lacrimal Surgery, 2nd
ed. Singapore: Springer; 2018:117-132. doi:10.1007/978-981-10-
5442-6_14
3. Sevel D. Development and congenital abnormalities of the nasolacri-
mal apparatus. J Pediatr Ophthalmol Strabismus. 1981;18(5):13-19.
4. MacEwen CJ, Young JD. Epiphora during the first year of life. Eye
(Lond). 1991;5(Pt 5):596-600. doi:10.1038/eye.1991.103
5. Vagge A, Ferro Desideri L, Nucci P, et al. Congenital nasolacrimal
duct obstruction (CNLDO): a review. Diseases. 2018;6(4):E96.
doi:10.3390/diseases6040096
6. Matta NS, Silbert DI. High prevalence of amblyopia risk factors in
preverbal children with nasolacrimal duct obstruction. J AAPOS.
2011;15(4):350-352. doi:10.1016/j.jaapos.2011.05.007
7. Bagheri A, Safapoor S, Yazdani S, Yaseri M. Refractive state in chil-
dren with unilateral congenital nasolacrimal duct obstruction. J Oph-
thalmic Vis Res. 2012;7(4):310-315.
8. Kipp MA, Kipp MA Jr, Struthers W. Anisometropia and amblyopia
in nasolacrimal duct obstruction. J AAPOS. 2013;17(3):235-238.
doi:10.1016/j.jaapos.2012.11.022
9. Ozgur OR, Sayman IB, Oral Y, Akmaz B. Prevalence of amblyopia
in children undergoing nasolacrimal duct irrigation and probing.
Indian J Ophthalmol. 2013;61(12):698-700. doi:10.4103/0301-
4738.124737
10. Kim JW, Lee H, Chang M, Park M, Lee TS, Baek S. Amblyopia
risk factors in infants with congenital nasolacrimal duct obstruc-
tion. J Craniofac Surg. 2013;24(4):1123-1125. doi:10.1097/
SCS.0b013e3182902b3d
11. Eshraghi B, Akbari MR, Fard MA, Shahsanaei A, Assari R, Mirmo-
hammadsadeghi A. The prevalence of amblyogenic factors in chil-
Journal of Pediatric Ophthalmology & Strabismus • Vol. 57, No. 1, 2020
dren with persistent congenital nasolacrimal duct obstruction. Graefes
Arch Clin Exp Ophthalmol. 2014;252(11):1847-1852. doi:10.1007/
s00417-014-2643-1
12. Ramkumar VA, Agarkar S, Mukherjee B. Nasolacrimal duct obstruc-
tion: does it really increase the risk of amblyopia in children? Indian J
Ophthalmol. 2016;64(7):496-499. doi:10.4103/0301-4738.190101
13. Siddiqui SN, Mansoor H, Asif M, Wakeel U, Saleem AA. Compari-
son of anisometropia and refractive status in children with unilateral
and bilateral congenital nasolacrimal duct obstruction. J Pediatr Oph-
thalmol Strabismus. 2016;53(3):168-172. doi:10.3928/01913913-
20160405-06
14. Badakere A, Veeravalli TN, Iram S, Naik MN, Ali MJ. Unilateral
congenital nasolacrimal duct obstruction and amblyopia risk fac-
tors. Clin Ophthalmol. 2018;12:1255-1257. doi:10.2147/OPTH.
S171029
15. Donahue SP, Arnold RW, Ruben JB; AAPOS Vision Screening
Committee. Preschool vision screening: what should we be detecting
and how should we report it? Uniform guidelines for reporting results
of preschool vision screening studies. J AAPOS. 2003;7(5):314-316.
doi:10.1016/S1091-8531(03)00182-4
16. Ellis JD, MacEwen CJ, Young JD. Can congenital nasolacrimal duct
obstruction interfere with visual development? A cohort case control
study. J Pediatr Ophthalmol Strabismus. 1998;35(2):81-85.
17. AlHammad F, Al Tamimi E, Yassin S, et al. Unilateral congenital na-
solacrimal duct obstruction, is it an amblyogenic factor? Middle East
Afr J Ophthalmol. 2018;25(3-4):156-160.
18. Flitcroft DI. Emmetropisation and the aetiology of refractive errors.
Eye (Lond). 2014;28(2):169-179. doi:10.1038/eye.2013.276
43