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Comparative Effect of Feeding Human Milk as Opposed to Formula on Visual

Function and Ocular Anatomy

Article  in  Breastfeeding Medicine · August 2019

DOI: 10.1089/bfm.2018.0263

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 BREASTFEEDING MEDICINE
Volume XX, Number XX, 2019
ª Mary Ann Liebert, Inc.
DOI: 10.1089/bfm.2018.0263

Comparative Effect of Feeding Human Milk as Opposed

to Formula on Visual Function and Ocular Anatomy

Erdinç Bozkurt,1 Hayrunnisa Bekis Bozkurt,2 and Mehmet Barısx Üçer3

Abstract

Background/Objective: Performance of ocular examinations on children who were breastfed, fed with formula,
and combination of the two for the first 6 months of age. Subsequently, refractive errors, allergic conjunctivitis,
Downloaded by 37.154.95.251 from www.liebertpub.com at 08/05/19. For personal use only.

and retinal nerve fiber layer (RNFL) thickness were evaluated.

Materials and Methods: The present study included a total of 242 eyes of 121 children (aged 60–84 months, 65
males, 56 females) admitted to the outpatient clinic of our institution. The patients were divided into three
groups according to their feeding pattern during their first 6 months postdelivery: breastfed children (Group 1,
n = 40), children fed with a combination of breast and formula milk (Group 2, n = 41), and children exclusively
fed with formula-milk (Group 3, n = 40). All patients underwent detailed ophthalmologic examinations, and
measurements of the RNFLs were recorded.
Results: No significant difference was observed between the groups in terms of refractive error. In Group 3, we
found that allergic conjunctivitis was significantly higher than in the other groups. In addition, in Group 3, the
thickness of the RNFL was found to be significantly higher in the superior quadrants of both the eyes of children
than in Groups 1 and 2 ( p < 0.05).
Conclusions: We found that the type of feeding experienced by infants in their first 6 months has no effect on
refractive error but has significant effects on both allergic conjunctivitis and RNFL. To determine the cause of
this difference in the RNFL and to further validate the present study, future studies with larger patient groups
and animal experiments are needed.

Keywords: breastfeeding, refractive disorder, allergic conjunctivitis, retinal nerve fiber layer thickness

Introduction positive emotional support to the baby separated from the

uterus in the postnatal period and has many other benefits.3,4

A lthough breast milk is considered to be more im-

portant for developing countries, it is very important for
all babies regardless of their socioeconomic status. While the
rate of breastfeeding in the first 6 months of life is 37% in
developing countries, this rate is quite low in developed
countries.1 Especially in developed countries, formula foods
are widely used instead of breast milk. However, the World
Health Organization strongly recommends only breastfeed-
ing during the first 6 months of life.2
It is thought that breastfeeding is not only a simple source
of nutrients but also that it supports the immunity of infants
and that it contributes to brain maturation through the poly-
unsatured fatty acids, which it includes. Breast milk is con-
sidered to be an almost ‘‘miraculous’’ substance that provides
In this context, the relationship between the intake of
breast milk and many diseases has been examined. In par-
ticular, the role of breastfeeding in protection against obesity
and malnutrition has been studied. Likewise, the positive
relationship between breast milk and brain development,
cognitive functions, and educational success is known.5,6 The
relationship between ocular morbidity and breastfeeding is
similarly of interest.
Although differing results have been obtained, studies on
allergic conjunctivitis, refractive errors, visual acuity, and
amblyopia have been performed.7–9
To our knowledge, this is the first study to examine the
relationship between retinal nerve fiber layer (RNFL) mea-
surement and breastfeeding and formula use. The aim of this

Departments of 1Ophthalmology and 2Pediatrics, Faculty of Medicine, Kafkas University, Kars, Turkey.
3
Department of Ophthalmology, Faculty of Medicine, Hitit University, Cxorum, Turkey.

1
 2 BOZKURT ET AL.
study was to evaluate the relationship of breastfeeding and
formula intake to ocular morbidity and RNFL measurements.
Materials and Methods
The study was planned as a prospective and cross-sectional
study. Two hundred forty-two eyes of 121 children who were
admitted to the Ophthalmology outpatient clinic of our hos-
pital aged between 60 and 84 months were included in the
study. The age, gender, sociodemographic features, and nu-
tritional status of the patients were recorded.
The best corrected visual acuity was evaluated with
(LogMAR) in all cases. Refraction conditions were measured
with an auto kerato-refractometer (Topcon KR-1, Japan) and
intraocular pressures were measured with a noncontact to-
nometer (Tomey FT-1000, Japan). Anterior segment exam-
ination was conducted with slit lamp biomicroscopy and
detailed fundus examinations were performed with 90 D
lens. Optical coherence tomography (Optovue OCT V 5.1,
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RTVue 100-2; Optovue, Fremont, CA, ABD) was performed
to measure RNFL in both eyes of the patients. For the optic
nerve, measurements of the four quadrants (upper, inferior,
nasal, and temporal) were recorded. The patients were di-
vided into three groups according to their feeding pattern
during the first 6 months after delivery.
Patients fed only breast milk during the first 6 months were
classified as Group 1 patients, fed both breast milk and for-
mula Group 2, and Group 3 comprised patients fed only
formula, without any breastfeeding. The parents of all pa-
tients included in the study were informed about the study
and their written informed consent was obtained.
During the study, the ethical standards set out in the De-
claration of Helsinki were complied with and approved by the
local Ethics Committee. Approval was obtained from the
local Ethics Committee of 2018/05 dated March 28, 2018.
Visual assessment: patients were measured with an auto
refractometer without using cycloplegics. The best corrected
visual acuity at a distance of 3 meters was assessed by the
LogMAR scale (Keeler Ltd., Windsor, United Kingdom).
Spherical and cylindrical values for both eyes, -1.00, and
more negative values were recorded as myopia, +1.00, and
higher values were recorded as hypermetropia.
Inclusion criteria
Sixty to 84 months, birth at full term with normal birth
weight (2,500–4,000 g), height and weight within normal
limits, no condition such as congenital glaucoma that could
cause damage to the optic nerve, no corneal scarring that
could prevent imaging, no nephelion, or lens disease.
Exclusion criteria
Height and body weight less than third percentile, obesity,
prior ocular surgery, history of ocular trauma, systemic
chronic disease, optic disc head abnormalities such as mye-
linated nerve fiber, and papillary edema.
In addition, mothers who used drugs for any reason were
excluded from the study.
For statistical analysis, descriptive, chi-square test and
ANOVA-bonferroni tests were applied using the SPSS 21
program.
Results
Of the 121 children included in the study, 53.7% (n = 65)
were male and 46.3% (n = 56) were female. Group 1
FIG. 1. Right eyes spherical
equivalent refraction.
 BREASTFEEDING, VISUAL FUNCTION, AND OCULAR ANATOMY
Table 1. Gender, Age, Allergic Conjunctivitis, and Refractive Disorder
Group 1
Male/Female 20/20
Age, months 71.68 – 9.1
Allergic conjunctivitis 3 (7.5%)
Refractive disorder 11 (27.5%)
Chi-square, one-way ANOVA.
*p < 0.05.
consisted of 40 patients fed only breast milk in the first 6
months postpartum, Group 2 consisted of 41 patients fed
breast milk with formula, and Group 3 consisted of 40 pa-
tients fed only formula. The spheric and astigmatic values of
the patients according to autorefractometer measurements
are considered to have a significant refractive error when they
are bigger or smaller than –1. A significant refractive error
was found in 27.5% of Group 1, 36.5% of Group 2, and
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32.5% of Group 3. A hyperopic shift was observed in Groups
1 and 2, whereas myopic values were more prominent in
Group 3, but this difference was not statistically significant
(Fig. 1 and Table 1).
In the biomicroscopic examination, patients with symp-
toms of conjunctival hyperemia and the presence of papillae
under the eyelids were defined as having allergic conjuncti-
vitis. The proportion of allergic conjunctivitis was 7.5% in
Group 1, 9.7% in Group 2, and 32.5% in Group 3. The fre-
quency of allergic conjunctivitis in patients using only for-
mula was significantly higher than in the other two groups
(Table 1).
RNFL thickness was analyzed in four quadrants, including
superior, inferior, nasal, and temporal by analyzing the head
of the optic nerve in both eyes of all patients. The parameters
of the RNFL section ring, which is 3.45 mm away from the
disc center, were automatically evaluated with the OCT de-
vice. In Group 3, we found that the superior, inferior, and
nasal parts of the retina nerve fiber layer in the right eye and
the superior and temporal parts in the left eye were statisti-
cally significantly higher than in Groups 1 and 2 (Fig. 2 and
Table 2).
FIG. 2. Retinal nerve fiber layer superior segment for right and left eyes by the groups.
3
Group 2 Group 3 P
22/19 23/17 0.797
69.54 – 8.2 73.05 – 9.5 0.213
4 (9.7%) 13 (32.5%) 0.001*
15 (36.5%) 13 (32.5%) 0.681
The sociodemographic characteristics of the groups
namely residence, education, economic income, and nutrition
were evaluated. No statistically significant difference was
found between the sociodemographic features of the mothers
in relationship to the groups (Table 3).
Discussion
The effect of breast milk intake on diseases has been ex-
amined for many years. In particular, the polyunsatured fatty
acids and antioxidants contained in breast milk have been
directly related to the development of the retina and neural
development.10,11 Since formula feeding is frequently used in
developed countries, formulas which are close to breast milk
have been developed. For example, docosahexaneoic acid
(DHA), which was present in lower amounts in the formulas
than in breast milk, has been added to formula foods in recent
years. Although the fatty acids in the content of the mother’s
milk depend on the mother’s diet, it is known to contain *8–
30% linoleic acid, 0.5–2% a-linoleic acid, 0.5–0.8% arachi-
donic acid (ARA), and 0.1–0.4% DHA.12
DHA is known as a long-chain polyunsatured fatty acid
and is important for neuroretinal development. In fact, before
scientists found that the retina was a continuation of the brain
in a developmental and anatomical way, philosophers dis-
cussed this issue with the idea that the ‘‘eye is a window to the
soul.’’ Over time, studies have shown that the optic nerve fibers
formed by the ganglion cell axons of the retina are actually
central nervous system axons.13 Therefore, we expect to see
similar effects of breast milk on the brain and on the retina.
 4 BOZKURT ET AL.

Table 2. Retinal Nerve Fiber Layer Thickness by Groups

Segments Group 1 Group 2 Group 3 p
Right eye
Superior 141.60 – 168 141.12 – 16.96 156.1 – 23.46 0.001*
Inferior 122.65 – 137.3 124.46 – 20.10 132.65 – 18.22 0.028*
Temporal 81.40 – 14.76 78.78 – 8.03 81.90 – 9.37 0.398
Nazal 66.43 – 10.3 67.41 – 8.64 73.63 – 10.94 0.030*
Left eye
Superior 143.73 – 16.23 149.29 – 21.51 162.45 – 23.92 0.000*
Inferior 124.8 – 14.04 127.22 – 16.43 130.70 – 17.25 0.257
Temporal 75.60 – 12.05 73.24 – 7.16 78.95 – 9.06 0.038*
Nazal 69.40 – 11.38 69.93 – 9.63 72.55 – 10.20 0.353
One-way ANOVA.
*p < 0.05.

In a study of children between 10 months and 4 years of age, Using electroencephalography (EEG) and magnetic re-
Deoni et al. found that there was a positive relationship between sonance imaging (MRI) in patients up to 1-year-old, Jing
the duration of breastfeeding and white matter development, et al. reported that myelinization peaked at an early age in
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and that the increase in white matter volume in late-mature
areas, especially in the frontal and temporal regions was note-
worthy.14 In another study, the same group of researchers found
that breastfeeding in children between 16 months and 2 years
positively correlated with the increase in myelinization along
with the development of white matter. They reported that the
duration of breastfeeding affected the time of myelinization, that
formula feeding reduced the growth of white matter, and that the
volume of white matter was lower than in children fed with
breastmilk. The volume of white matter in children fed with
formula which contained DHA and ARA was close to that in
children fed with breast milk; although it was lower than that in
breastfed children.
In the light of these findings, Deoni et al. stated that helped
the development of white matter in infants that were fed with
formula.15 In an experimental animal study on rhesesus mon-
keys, Liu et al. found that there was no difference in the size of
the brain or the volume of gray and white matters in the groups
that received breast milk and formula.16 However, this finding
has been contradicted in numerous studies on people.17,18
infants fed with formula (at 6 months) and at the ninth month
in infants fed with breast milk. This study emphasized that
differential trajectories and cognitive development in the
brain may trigger different pathways in neurodevelopment.19
In another study examining breast milk and brain develop-
ment between 12 and 18 years of age, the parietal cortex
was found to be thicker in the breast milk group, and it was
found that it did not have any effect on vision and refractive
disorder.20
While there are many studies on the physiological effect of
breast milk and the development of the brain, there has been
no previous study in which the thickness of the RNFL in the
orbit known as an extension of the brain has been evaluated.
In this study, we investigated whether there was a relation-
ship between the intake of breast milk and RNFL thickness.
We found that the superior, inferior, and nasal parts of the
right eye and the superior and temporal parts of the left eye of
children fed only formula were significantly thicker in the
right and left eyes compared with the other two groups. Al-
though the retina appears to be the continuation of the

Table 3. Sociodemographic Feature of Patients

Group 1 Group 2 Group 3 p
Region
Rural 27 30 32 0.330
Urban 13 10 7
Mother’s education level
Secondary school and lower 10 17 9 0.115
High school and above 30 23 30
Father’s education level
Secondary school and lower 6 10 6 0.428
High school and above 34 30 33
Economic income
Middle-High 32 29 28 0.646
Low 8 11 11
Mother’s diet
Vegan 0 0 0
Based on protein 8 10 5 0.387
Healthy diet 32 30 34
Chi-square.
 BREASTFEEDING, VISUAL FUNCTION, AND OCULAR ANATOMY
embryogenetic and anatomical brain, this finding shows that
nutrition may have different effects on the retina and brain.
Neurotrophic substances are known to be present in breast
milk. In recent years, formula foods that are close to breast
milk in content have been developed.21 Synthetic supple-
ments such as DHA and ARA, which are now present at a
high level in formulas and which are important in the de-
velopment of white matter, can also increase RNFL. There-
fore, a marked thinning of RNFL is not expected in children
with a formula-fed diet. In our study, we found that the RNFL
was thicker in the formula-fed infants, although we were
expecting it to be thicker in the breastfed children.
Despite this result, thickness of the RNFL does not always
mean neurotrophy. RNFL thickness may be increased by
certain pathological events. For example, amiodarone in-
duced lipidosis by inhibiting the axoplasmic flow in retinal
toxicity causes an increase in RNFL thickness.22 Thiamin
deficiency also increases RNFL thickness in the acute peri-
od.23 Moreover, it is not known whether this increase in
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thickness is a healthy increase or an adaptive change in the
RNFL. How children whose RNFL is thicker will respond at
a later age to neurodegenerative diseases with increased in-
traocular pressure, such as glaucoma, and the degree of re-
sistance to atrophy remain to be determined. In the light of
this, it is not clear whether the RNFL increase in children fed
with formula is a healthy neurotrophy or an abnormal hy-
pertrophy. More extensive studies with more patients are
needed to clarify this situation.
Our next study, using electroretinography (ERG) will be
to investigate ganglion cell functions and histopathological
changes such as hypertrophy and hyperplasia in the optic
nerves of rats fed with formula and breast milk. We believe
that this work will provide an important impetus for new
research.
The relationship between refraction defects and breast-
feeding intake has been investigated in several studies and
differing results have been obtained. In 2018, Liu et al. re-
ported that spherical equivalent refraction (SER) is more
hyperopic in breastfed children, that there is a correlation
between reduced myopic risk and breastfeeding, but that
there is no correlation between axial length and breast milk.24
In another study Sham et al. emphasized that breastfeeding is
associated with hyperopic SER.25 Shirzadeh et al. did not find
any relationship between feeding pattern during the first 6
months of life and refractive errors or the level of vision.26 In
this study, we observed that diet did not make a significant
difference in SER, but the tendency to myopia was observed
in the formula-fed children as in Shirzadeh et al.’s study.
A number of studies have been conducted in recent years
on whether there is a link between allergic diseases and the
duration of breastfeeding. Among these studies, there are
studies which suggest that breast milk is not associated with
allergic diseases as well as studies which suggest that it
prvides a defense against allergic diseases. Huang et al. found
that children who had been breastfed for 3–6 months had
a lower risk of asthma and wheezing, and that the risk of
fever, rhinitis, pneumonia, and eczema was significantly
lower in children who had breastfed for more than 6
months.27 On the contrary, Bion et al. argued that the dura-
tion and intensity of breastfeeding was not associated in the
long term with allergic diseases such as asthma, eczema,
rhinitis, and atopy.28
5
In our study, we found that the frequency of allergic con-
junctivitis in children fed only formula was significantly
higher than the other two groups. Although the frequency of
allergic conjunctivitis in children feeding both of breast milk
and formula was found to be more than feeding only breast
milk, there was no significiant difference.
Conclusions
As a result of this study, we found that breast milk protects
against allergic conjunctivitis.
Even though there was a hyperopic shift in the group fed
with breast milk, there was no significant effect on SER in our
study. In addition, the significantly higher level of RNFL
thickness in the superior quadrants, especially in the formula-
fed children should be further investigated in studies to be
performed with large patient groups and animal experiments
are needed to explain the pathophysiology.
Acknowledgments
This research did not receive any specific grant from
funding agencies in the public, commercial, or not-for-profit
sectors.
Disclosure Statement
Conflicts of interest: None.
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Address correspondence to:
Erdinç Bozkurt, MD
Department of Ophthalmology
Faculty of Medicine
Kafkas University
Kars 36100
Turkey
E-mail: drerdincbozkurt@hotmail.com