Low-Concentration Atropine Monotherapy vs. Combined with MiSight 1 Day Contact Lenses for Myopia Management

Abstract

Objectives:
To assess the decrease in myopia progression and rebound effect using topical low-dose atropine compared to a combined treatment with contact lenses for myopic control.

Methods:
This retrospective review study included 85 children aged 10.34 ± 2.27 (range 6 to 15.5) who were followed over three years. All had a minimum myopia increase of 1.00 D the year prior to treatment. The children were divided into two treatment groups and a control group. One treatment group included 29 children with an average prescription of 4.81 ± 2.12 D (sphere equivalent (SE) range of 1.25-10.87 D), treated with 0.01% atropine for two years (A0.01%). The second group included 26 children with an average prescription of 4.14 ± 1.35 D (SE range of 1.625-6.00 D), treated with MiSight 1 day dual focus contact lenses (DFCL) and 0.01% atropine (A0.01% + DFCL) for two years. The control group included 30 children wearing single-vision spectacles (SV), averaging -5.06 ± 1.77 D (SE) range 2.37-8.87 D).

Results:
There was an increase in the SE myopia progression in the SV group of 1.19 ± 0.43 D, 1.25 ± 0.52 D, and 1.13 ± 0.36 D in the first, second, and third years, respectively. Myopia progression in the A0.01% group was 0.44 ± 0.21 D (p < 0.01) and 0.51 ± 0.39 D (p < 0.01) in the first and second years, respectively. In the A0.01% + DFCL group, myopia progression was 0.35 ± 0.26 D and 0.44 ± 0.40 D in the first and second years, respectively (p < 0.01). Half a year after the cessation of the atropine treatment, myopia progression (rebound effect) was measured at -0.241 ± 0.35 D and -0.178 ± 0.34 D in the A0.01% and A0.01% + DFCL groups, respectively.

Conclusions:
Monotherapy low-dose atropine, combined with peripheral blur contact lenses, was clinically effective in decreasing myopia progression. A low rebound effect was found after the therapy cessation. In this retrospective study, combination therapy did not present an advantage over monotherapy.

Full text

Vision 2022, 6, 73. https://doi.org/10.3390/vision6040073 www.mdpi.com/journal/vision
Article
Low-Concentration Atropine Monotherapy vs. Combined with
MiSight 1 Day Contact Lenses for Myopia Management
Nir Erdinest 1,2, Naomi London 3,*, Itay Lavy 1, David Landau 1, Dror Ben Ephraim Noyman 4, Nadav Levinger 1,5
and Yair Morad 2,6
1 Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Faculty of Medicine,
Hebrew University of Jerusalem, Jerusalem 9574409, Israel
2 The Myopia Center, Rishon LeZion 4951732, Israel
3 Naomi Vision Boutique, 5 Even Israel St., Jerusalem 9422805, Israel
4 Department of Ophthalmology, Rambam Health Care Campus, Haifa 3525408, Israel
5 Department of Ophthalmology, Enaim Refractive Surgery Center, Jerusalem 9438307, Israel
6 Department of Ophthalmology, Assaf Harofeh Medical Center, Zerifin7033001, Israel
* Correspondence: imnl4u@gmail.com; Tel.: +972-545406646; Fax: +972-25004333
Abstract: Objectives: To assess the decrease in myopia progression and rebound effect using topical
low-dose atropine compared to a combined treatment with contact lenses for myopic control.
Methods: This retrospective review study included 85 children aged 10.34 ± 2.27 (range 6 to 15.5)
who were followed over three years. All had a minimum myopia increase of 1.00 D the year prior
to treatment. The children were divided into two treatment groups and a control group. One
treatment group included 29 children with an average prescription of 4.81 ± 2.12 D (sphere equiv-
alent (SE) range of 1.25–10.87 D), treated with 0.01% atropine for two years (A0.01%). The second
group included 26 children with an average prescription of 4.14 ± 1.35 D (SE range of 1.625–6.00 D),
treated with MiSight 1 day dual focus contact lenses (DFCL) and 0.01% atropine (A0.01% + DFCL)
for two years. The control group included 30 children wearing single-vision spectacles (SV), aver-
aging −5.06 ± 1.77 D (SE) range 2.37–8.87 D). Results: There was an increase in the SE myopia pro-
gression in the SV group of 1.19 ± 0.43 D, 1.25 ± 0.52 D, and 1.13 ± 0.36 D in the first, second, and
third years, respectively. Myopia progression in the A0.01% group was 0.44 ± 0.21 D (p < 0.01) and
0.51 ± 0.39 D (p < 0.01) in the first and second years, respectively. In the A0.01% + DFCL group,
myopia progression was 0.35 ± 0.26 D and 0.44 ± 0.40 D in the first and second years, respectively (p
< 0.01). Half a year after the cessation of the atropine treatment, myopia progression (rebound
effect) was measured at −0.241 ± 0.35 D and −0.178 ± 0.34 D in the A0.01% and A0.01% + DFCL
groups, respectively. Conclusions: Monotherapy low-dose atropine, combined with peripheral
blur contact lenses, was clinically effective in decreasing myopia progression. A low rebound effect
was found after the therapy cessation. In this retrospective study, combination therapy did not
present an advantage over monotherapy.
Keywords: myopia; myopia progression; myopia control; atropine; contact lenses
1. Introduction
Myopia is the most common refractive error in the world and a leading cause of vi-
sion loss [1,2]. A recent study estimated that the prevalence of myopia between the ages
of 8–16 in the United States is currently approximately 16.5% [3]. The prevalence of
myopia is expected to increase, and it is estimated that, by the year 2050, myopia will
affect approximately half the population in the Middle East as well as the world’s pop-
ulation, and high myopia (5.00 diopters (D) and above) will affect about 10% of the
world’s population [4].
In those with myopia, the cornea’s refractive power or the eye’s length is too pow-
Citation: Erdinest, N.; London, N.;
Lavy, I.; Landau, D.;
Ben Ephraim Noyman, D.;
Levinger, N.; Morad, Y.
Low-Concentration Atropine
Monotherapy vs. Combined with
MiSight 1 Day Contact Lenses for
Myopia Management. Vision 2022, 6,
73. https://doi.org/10.3390/
vision6040073
Received: 1 November 2022
Accepted: 6 December 2022
Published: 12 December 2022
Publisher’s Note: MDPI stays neu-
tral with regard to jurisdictional
claims in published maps and insti-
tutional affiliations.
Copyright: © 2022 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license
(https://creativecommons.org/license
s/by/4.0/).

Vision 2022, 6, 73 2 of 11
erful, causing the light rays to focus in front of the retina. When this deficiency begins to
develop from the age of six to ten, it tends to progress at a more rapid rate. Adults with
lower refractive errors tend to stabilize, though not absolutely, around the age of 15–18
[5–7].
Myopia is a disease with severe implications in terms of treatment costs and possible
eye complications, including glaucoma, retinal holes, tears, and detachments, and even
the appearance of strabismus and double vision [8–10]. Myopia is considered one of the
leading causes of blindness in the western world and Israel as well [11]. Myopia is Israel’s
third most common cause of blindness after age-related macular degeneration and
glaucoma [8–10,12].
Many theories have been linked to the causes of myopia progression. Beyond the
genetic component, a lack of exposure to natural daylight (many children spend very lit-
tle time outside) and an abundance of short-range work (reading or using digital screens)
contribute to the progression [3,13,14].
Among the tools currently available to try and manage myopia, orthokeratology
contact lenses, dual-focus contact lenses, and multifocal contact lenses with a far-center
design have exhibited moderate to considerable success [15].
The most effective treatment to date, as shown in research studies, is atropine drops,
though it seems to be influenced by individual characteristics (for example, age, genetic
makeup, and degree of myopia) and is dose-dependent. Although atropine at high con-
centrations (1% and 0.5%) achieved a higher efficacy at slowing myopia progression, a
low concentration of atropine, such as 0.01% and particularly 0.05%, was found to be
similarly effective, with the advantage of a minimal effect on accommodation and pupil
dilation, and less of a rebound effect (high increase in myopia after stopping treatment)
[1,11,16].
Topically administered atropine is believed to operate on several fronts to control
myopia. First, as a muscarinic antagonist, it slows down the rate of eye elongation and
affects the processes of the growth of the sclera. In addition, atropine affects the release of
cellular dopamine and, therefore, influences the retinal signals that control the growth
rate of the eye [8,9,17].
Topical atropine treatment is commonly prescribed in low concentrations, such as
0.01% and 0.05% atropine, the latter of which is currently discussed in the published lit-
erature as the preferred concentration [1,11,16–18]. Atropine at such a low concentration
has many advantages, including a minimal effect on pupil size (less than 0.8 mm), min-
imal loss of accommodation (1.5 diopters on average), and less loss of near vision com-
pared to higher concentrations [1,11,16–18]. The results were also supported by another
study in which it was found that atropine at a concentration of 0.01% significantly re-
duces the rate of myopia progression over a year with minimal side effects [1,11,16–18]. It
should be noted that, for myopia with a rapid progressive nature, higher concentrations
of atropine treatment are required [1,11,16–18]. Multicenter studies have also shown the
effectiveness of atropine treatment. After three years, the axial length increased signifi-
cantly less than the control group, causing glare and requiring near-work spectacles [1].
A multiparticipant study treated with atropine concentrations of 0.5%, 0.1%, and 0.01%
showed a significant slowing in myopia progression compared to children treated with
saline [19]. Children treated with the low concentrations of atropine did not complain of
blurred near vision or glare, unlike those treated with atropine at the high concentration
[19]. However, three years after the end of the study and the cessation of treatment, the
children treated with high concentrations suffered from an increased rebound phenom-
enon compared with the children treated with low concentrations [19]. The professional
literature has shown that the combination treatments in some challenging cases can often
be more effective than atropine alone, such as atropine and orthokeratology (ortho-k)
contact lenses treatment, or atropine and bifocal spectacles maintain a decreasing axial
growth [1,20–22].

Vision 2022, 6, 73 3 of 11
At the same time, studies have found that retinal peripheral hyperopic blurring is a
leading factor in axial length increase, hence the importance of controlling peripheral re-
fraction [1,17,23]. Peripheral refraction control contact lenses are contact lenses with a
double-focus point similar to prescription contact lenses for vision correction, where the
peripheral addition reduces the relative hyperopia caused by a monofocal distance lens.
Unlike spectacles, where the correction for near vision is only in the inferior area of the
lens, in a contact lens, the addition for near vision is in the entire circumference of the lens
[1,17,23]. The center of the lens corrects the distance vision, while at the periphery, the
power of the lens decreases gradually toward the periphery (in a concentric design), by
approximately 2.00–3.00 D. These lenses were found to slow myopia progression by ap-
proximately 50% compared to spectacles [1,17,23]. Recently, a published study found
these lenses to be effective for three years and have a high safety profile [1,17,23].
2. Materials and Methods
The study included 85 Caucasian children with a myopic refractive error. The clinic
that conducted this study primarily treats patients specifically interested in myopia con-
trol. The treatments are determined using multiple considerations including the severity
of myopia, the rate of progression prior to consultation, and the willingness of the child
and their caregivers to wear contact lenses. In general, the children who present with a
history of rapid myopia progression, particularly the younger aged children, and the
children and parents who consent to wearing contact lenses will be encouraged to receive
combined treatments, yet it was not always accepted. The average age was 10.3 ± 2.2
(range 6 to 15.5), and the spherical equivalent (SE) value was 4.69 ± 1.8 D (Range −1.25 to
−10.87 D) at the beginning of the treatments.
The children were divided into two treatment groups and a control group, which
included 30 children who wore single-vision spectacles (SV), averaging −5.06 ± 1.77 D,
ranging in a sphere equivalent (SE) from −2.37–8.87 D. The first study group included 29
children with an average SE prescription of −4.81 ± 2.12 D (range −1.25–10.875 D), who
were treated with 0.01% atropine for two years (A0.01%) and followed up to one year
after that. The second group included 26 children with an average SE prescription of 4.14
± 1.35 D (SE range of 1.625–6.00 D) and who were treated with MiSight® 1 day (Cooper
Vision, Pleasanton, CA, USA) contact lenses with dual focus (DFCL) and 0.01% atropine
(A0.01% + DFCL) for two years and followed for one year after that. The children all had
a minimal increase in myopia of 1.00 D during the year prior to treatment. The children’s
demographics are summarized in Table 1.
Table 1. Children demographics. SV: single-vision spectacle lenses (control group). A0.01: 0.01%
atropine for two years of treatment. A0.01% + DFCL: contact lenses with dual focus and topical
0.01% atropine for two years. VA = visual acuity; SD = standard deviation; SE = spherical equiva-
lent.
A0.01% + DFCL
A0.01
%
SV Groups
26 29 30 n
62% female 51% female 53% male Gender
11.12 ± 1.99 10.93 ± 1.94 9.08 ± 2.31
Avg and
SD Age
9–15.5 8–15 9–15.5 Range
p
<
0.01 SV vs. A0.01%
p
<
0.01 SV vs. A0.01% + DFCL
p
>
0.05 A0.01% vs. A0.01% + DFCL
0.171 ± 0.259 0.097 ± 0.07
0.055 ±
0.065
(LogMar)
VA and SD
4.14 4.81 5.06 AVG
SE (D) 1.35 2.12 1.77 SD
1.625 1.25 2.375 Min

Vision 2022, 6, 73 4 of 11
6.00 10.875 8.875 Max
p
>
0.05
SV vs. A0.01%
p < 0.0
5
SV vs. A0.01% + DFCL
p
>
0.05 A0.01% vs. A0.01% + DFCL
After two years of treatments, the first and second groups stopped myopia man-
agement, and an SE comparison was made to the SV group at the end of the third year.
2.1. Ethical Principles
This study followed the tenets of the Helsinki Declaration. The Medical Center In-
stitutional Review Board (IRB) approval was obtained for this study (HMO-0354-21), and
all procedures were carried out per their guidelines. The parents were aware that their
children were participating in this study.
2.2. Inclusion and Exclusion Criteria
Inclusion criteria included both a cycloplegic spherical equivalent refraction (SER)
equal to or above −1.00 D in each eye and a best-corrected visual acuity of 6/9 or superior.
The children had a myopic progression documented in their file of at least −1.00 D during
the year prior to beginning treatment.
Children with systemic or ocular diseases, such as connective tissue disorders, stra-
bismus, or any previous atropine therapy (for myopia progression or amblyopia), were
excluded. Children with astigmatism greater than 2.00 D, and anyone that had experi-
ence with rigid gas permeable contact lenses, including orthokeratology lenses, were ex-
cluded. Anyone that habitually wore spherical or astigmatic soft contact lenses ceased
lens wear for two or four weeks, respectively, before commencing treatment.
2.3. Treatment Components
The preparation of atropine sulfate 0.01% was provided by a chain pharmacy (Su-
per-Pharm Professional, Petach-Tikva, Israel). The drops were packaged in opaque bot-
tles to prevent photodegrading. The sterile bottle size was 10.0 mL, consisted of 5 mL of
preparation preserved with Benzalkonium chloride 0.01%. The bottles were stored at 4 °C
for no longer than 21 days. The parents of the appropriate groups were instructed to in-
still one drop daily before bedtime.
The soft contact lenses prescribed were MiSight® 1 day (Cooper Vision, Pleasanton,
CA, USA) containing 60% water and 40% Omafilcon A, hydrogel contact lens material
(non-ionic) for daily wear single use. The lens has a total diameter of 14.2 mm, compris-
ing an 11.66 mm optic zone with four alternating distance and near prescription zones
(maximum treatment zones with an addition of +2.00 diopters). The central distance optic
zone is 3.66 mm in diameter. Children were instructed to wear the lenses daily for eight
hours a day.
2.4. Follow-Up Visits
The children were examined bi-annually throughout the three years of the study
(including a one-year washout). Refraction was measured at each visit with two instilla-
tions of 1% tropicamide, one drop instilled in each eye at 5-min intervals. Subjective re-
fraction was performed post-cycloplegia approximately half an hour after instillation of
the second drop by a single practitioner in the same examination room. The children
wore the correction modality prescribed at the beginning of the study (bifocals, progres-
sive added lenses, contact lenses). Distance visual acuity (VA) was measured monocu-
larly at each visit with the same Snellen chart and identical ambient lighting. The optical
devices were changed as required after each visit to the newly measured refraction.

Vision 2022, 6, 73 5 of 11
2.5. Cessation of Atropine Therapy
Atropine therapy cessation was conducted gradually under detailed guidelines to
reduce possible subsequent rebound [24]. This study implemented the discontinuance
protocol at the end of two years.
The number of atropine instillation days per week was reduced monthly (one day
per week per month) over the course of six months. During the first month
post-treatment, the patient would instill atropine six days per week, five days per week
during the second month. During the third month, four days per week (every other day),
and during the fourth month, days one, three, and five. During the fifth month, on days
one and four and during month six, once a week.
A cycloplegic refraction and retinal exam were performed at the end of months
seven, and six months later.
2.6. Statistical Analysis
Analysis of the myopia progression for each group, between the groups including
age and refractive error, was performed using the Statistical Package for Social Sciences
software 25.0 (SPSS Inc., Chicago, IL, USA) with One-way Analysis of Variance (ANO-
VA) and Tukey-Kramer Multiple Comparisons Tests.
3. Results
There was an increase in the SE myopia progression in the SV group of 1.19 ± 0.43 D,
1.25 ± 0.52 D, and 1.13 ± 0.36 D in the first, second, and third years, respectively. The
myopia progression in the A0.01% group was 0.44 ± 0.21 D (p < 0.01) and 0.51 ± 0.39 D (p <
0.01) in the first and second years, respectively. In the A0.01% + DFCL group, the myopia
progression increased by 0.35 ± 0.26 D and 0.44 ± 0.40 D in the first and second years,
respectively (p < 0.01). The total progression over the three years in the SV group was 3.57
D (average 1.19 ± 0.43 D annually), in the A0.01% group 1.196 D (average 0.34 ± 0.34 D
annually), and in the A0.01% + DFCL group 0.96 D (average 0.324 ± 0.33 D annually)
(Figure 1).
Figure 1. Increase in myopia over three years in the group wearing single-vision spectacle lenses
(SV), two years of treatment with 0.01% atropine (A0.01%), and two years wearing dual-focus
contact lenses (DFCL) with A0.01% (A0.01% + DFCL). One asterisk (*) represents a significant p
value (p < 0.01). SV: single-vision spectacle lenses. A0.01: 0.01% atropine for two years of treatment.
A0.01% + DFCL: contact lenses with dual focus and topical 0.01% atropine for two years.
Half a year after the cessation of the atropine treatment, the myopia progression
(rebound effect) was −0.24 ± 0.35 D and −0.18 ± 0.34 D in the A0.01% and A0.01% + DFCL
groups, respectively (Table 2, Figure 2).

Vision 2022, 6, 73 6 of 11
Figure 2. The rebound effect was tested one year after the cessation of treatment in the SV group,
atropine at a concentration of 0.01% (A0.01) and after contact lenses with dual focus (DFCL) to-
gether with 0.01% atropine (A0.01% + DFCL). One asterisk (*) represents a significant p value (p <
0.01).
Table 2. Myopia progression during three years of the study SE: spherical equivalent, SV: sin-
gle-vision spectacle lenses. A0.01: 0.01% atropine for two years of treatment. A0.01% + DFCL: con-
tact
Myopia Progression SE (D)
Groups Year 1 Year 2 Year 3
SV 1.19 ± 0.43 1.25 ± 0.52 1.13 ± 0.36
A0.01% 0.44 ± 0.21 0.51 ± 0.39 0.24 ± 0.35
A0.01% + DFCL 0.35 ± 0.26 0.44 ± 0.40 0.18 ± 0.34
SV vs. A0.01%
p
<
0.001
p
<
0.001
p
<
0.001
SV vs. A0.01% + DFCL
p
<
0.001
p
<
0.001
p
<
0.001
A0.01% vs. A0.01% + DFCL
p
>
0.05
p
>
0.05
p
>
0.05
4. Discussion
This study shows the effectivity of atropine therapy as a stand-alone treatment and
combined with peripheral defocus lenses, and the low rebound effect when atropine is
tapered following the treatment.
4.1. Method Strengths and Weaknesses and Rebound
Refractive error measurements were performed under cycloplegia. Cycloplegia was
achieved with tropicamide, not cyclopentolate, which may raise some questions. Alt-
hough cyclopentolate is the more prevalent and, in some cases (particularly hyperopes),
preferred as it has been shown to produce more effective cycloplegia, trials have shown
equal effectiveness between the two, and this was the preferred method of these care-
givers [6].
Though many studies prefer the high-resolution availability of the autorefractor to
monitor the myopia progression, a subjective cycloplegic refraction is the preferred
method of many clinicians. It is considered the “gold standard” for accurate refraction
and spectacle prescription rather than automated or retinoscopic objective refractions
[25]. Though some autorefractors are more accurate than others, some tend to stray even
further from the subjective with cycloplegia, and further from the subjective than reti-
noscopy [26,27], which is generally very close to the subjective when performed by a
skilled clinician [26,27].
There is a concentration-dependent response for low-concentration atropine, as
shown in the Low-concentration Atropine for Myopia Progression (LAMP) [28]. Fur-
thermore, the child’s age plays a vital role on two levels. First, a young age is associated

Vision 2022, 6, 73 7 of 11
with the need for a higher concentration to achieve high efficacy [29], and, second,
younger children tend to have a faster myopic progression [29].
Even at the same concentration and within the same age group, there are still varia-
tions in treatment responses [29]. The current study showed a relatively large age diver-
sity, which may be considered a limitation, with the control group (SV) containing the
lowest age and the A0.01% + DFCL group containing the highest age. However, there
was a similar range between the groups and, between the treatment groups, there was no
statistical difference in the myopia progression (or lack thereof). Both were significantly
effective at decreasing previous myopia progression.
Younger children treated with lower concentrations showed a rebound effect similar
to older children treated with higher concentrations [30]. The LAMP study further sug-
gested that low-concentration atropine treatment in children should be ended at older
ages when both the natural myopic progression rate and the rebound effect become
smaller [30]. The World Health Organization has begun suggesting that treatment cessa-
tion for one year should be considered if good treatment responses are observed after
two years of continuous therapy, and those who show progression after the one-year
cessation can be offered further treatment [1]. While no study, as yet, can precisely
quantify the number of years of treatment that would be appropriate, the literature is
starting to examine the tolerance, safety, and effectivity of treatment lasting three years or
longer [23,30,31].
While younger children may require 0.05% atropine to achieve adequate control
over progression, this concentration often induces significantly more mydriasis and loss
of accommodation amplitude than 0.01% atropine in Caucasian children who may be less
tolerant of the side effects. In addition, it is important to note that a greater rebound effect
was associated with a 0.05% atropine concentration (compared to 0.01%) in the younger
age group at the treatment cessation [28], and, in this cohort, the lower concentration
proved effective.
At the time these children were treated, the predominant and preferred concentra-
tion in the published literature was 0.01%. The advantage of the 0.05% concentration,
particularly in younger children who may be less affected by the 0.01% concentration,
was published later. When the 0.01% concentration proves insufficient, one option is to
combine the treatment with another that will assist from a different approach, for exam-
ple, peripheral defocus, to reduce the hyperopic shift in the retina’s periphery. The com-
bined therapy in the group here uses a contact lens with two treatment zones which have
been shown to be effective as a monotherapy and add effectivity in a case series [32].
4.2. Peripheral Defocus Design
The trial conducted by Anstice and Philips showed that eyes wearing MiSight
(Cooper Vision, Pleasanton, CA, USA) contact lenses had significantly less axial elonga-
tion than eyes wearing single-vision lenses [33]. Following the above study, Chamber-
lain et al. conducted a multicenter study in several countries over three years. The re-
fractive error progression in the first year was 0.40 D less compared to the control group.
In the second year, the progression was 0.54 D less and, in the third year, 0.73 D less
than the control group. The axial elongation change was as follows: at 12 months, the
axial length change in the control group was 0.24 mm compared to 0.09 mm in the
MiSight group. At 24 and 36 months, the axial length change was 0.24 and 0.32 mm, re-
spectively, less than the control group. Regarding refraction, the myopia control effect
after three years was 59%, and, in the axial length control, the effect was a 52% decrease
[34].
The Bifocal Lenses In Nearsighted Kids (BLINK) study, which began in 2017, com-
pared identical design single-vision and center distance soft multifocal contact lenses
with a +1.50 D addition to a +2.50 D addition [35,36]. The results so far suggest that there
may be either a dioptric threshold or a minimal area of visual field blur necessary to
achieve the inhibitory effect [1]. This information supports using a lens such as the

Vision 2022, 6, 73 8 of 11
MiSight, which incorporates two concentric circles of peripheral blur, thereby providing
a larger retinal area of peripheral defocus and assuring blur in both photopic and sco-
topic environments.
The precise mechanism underlying the positive influence of optical peripheral my-
opic defocus is not understood. Hypotheses include reducing the accommodative lag [37]
and possibly suspending Bruch’s membrane’s excessive expansion [38]. Still undeter-
mined is the exact location on the retina, the surface area required, or the depth of myopic
defocus required for maximum efficacy.
Orthokeratology (Ortho-K) lenses are rigid contact lenses with a design profile of
reverse geometry [15,39]. This method puts a contact lens on the eye while sleeping at
night [15,39], effectively decreasing the myopia progression by using a similar mecha-
nism of peripheral defocus [1,15,39]. It is also sometimes used in combination with
low-dose atropine. Studies that compared the effects of Ortho-K and atropine in myopia
control showed that Ortho-K treatments might sometimes be superior to a very low at-
ropine concentration (0.125% and 0.02%) in inhibiting the axial length in children with
high myopia [40,41]. A combined treatment of 0.01% atropine and Ortho-k can provide
better efficacy than monotherapy, as shown in studies over one and two years of treat-
ment [16]. A recent study further analyzed and discovered an advantage of the Ortho-K
effectivity in the younger cohort [16], which, when considering the need for a slightly
higher atropine concentration in young children, as discussed earlier, may encourage the
use of combination treatments of peripheral defocus and a slightly higher concentration
of atropine (0.02% or 0.05%) in a young cohort with multiple parameters possibly con-
tributing to a substantial rapid progression for maximum control.
Gradual tapering of the atropine therapy induced a low rebound effect in this co-
hort, and the combination therapy did not influence it.
4.3. Limitations
This study’s limitations are partially inherent within its retrospective nature, in or-
der to assure similar demographics between the groups. While contact lenses may have
been recommended to other patients with similar baseline characteristics, they do not
always accept the clinician’s proposal. Additionally, a larger cohort would have been
preferable. The three groups in this study were comparable in age and refractive error
range; however, the wide range of ages within each group may affect the significance of
the results as the effectiveness of the treatment is also impacted by the age of the myopia
onset [1,9,11].Furthermore, binocular vision measures were not recorded; binocular vi-
sion disorders, including esophoria, accommodation lag, and high accommodation ver-
sus convergence ratio may influence myopia progression [1,11]. The most effective addi-
tion in the periphery of a contact lens and the desired area of the pupil area required to
reduce peripheral hyperopia is still being researched. As these data emerge and are im-
plemented, the treatment effects may differ. The authors acknowledge the importance of
documenting eye length in the progression of myopia, which is the primary reason
treatment is initiated. While changes in the corneal and deceleration of lens power loss of
the crystalline lens can contribute, to date, the axial length is still noted to be the defining
contributor to myopia progression [42,43]. A limitation to this study is the lack of axial
length measurements, which were unavailable, but, as axial length measurements are far
more sensitive than refraction, the low myopia progression in this cohort can be reas-
suring.
In addition, it has been known for a long time that environmental factors contribute
to myopia development. In recent years, evidence has accumulated that activity outside
the home in daylight effectively delays myopia onset [44]. This information is relevant to
the group of children in the study who wore contact lenses and were also treated with
atropine, as they may be more active and spend more time outside than those who wore
spectacles [45]. If this hypothesis is correct, the study may have been biased because of
sunlight’s positive effect on myopia progression [46].

Vision 2022, 6, 73 9 of 11
5. Conclusions
Monotherapy low-dose atropine, combined with peripheral blur contact lenses, was
clinically effective in decreasing myopia progression. A low rebound effect was found
after therapy cessation. Combination therapy did not present an advantage over mono-
therapy in this retrospectively selected cohort.
Author Contributions: Conceptualization, N.E., Y.M. and N.L. (Naomi London); methodology,
N.E., I.L. and D.L.; data curation, D.B.E.N., N.E., Y.M., D.L., I.L. and N.L. (Naomi London); writ-
ing—original draft preparation, N.E.; writing—review and editing, Y.M., I.L., D.L., N.E., N.L.
(Nadav Levinge) and N.L. (Naomi London). All authors have read and agreed to the published
version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: This study followed the tenets of the Helsinki Declaration.
The Medical Center In-stitutional Review Board (IRB) approval was obtained for this study
(HMO-0354-21), and all procedures were carried out per their guidelines.
Informed Consent Statement: The parents were aware that their children were participating in this
study.
Data Availability Statement: The data is available upon request from the corresponding author.
Acknowledgments: Nir Erdinest is grateful to the Azrieli Foundation for the award of a Post-doc
Azrieli Fellowship and Hadassah-Hebrew University Medical Center for the award of a
post-doctoral fellows.
Conflicts of Interest: The authors declare no conflict of interest.
References
1. Brennan, N.A.; Toubouti, Y.M.; Cheng, X.; Bullimore, M.A. Efficacy in myopia control. Prog. Retin. Eye Res. 2021, 83, 100923.
2. Chamberlain, P.; Bradley, A.; Arumugam, B.; Hammond, D.; McNally, J.; Logan, N.S.; Jones, D.; Ngo, C.; Peixoto-de-Matos,
S.C.; Hunt, C. Long-term effect of dual-focus contact lenses on myopia progression in children: A 6-year multicenter clinical
trial. Optom. Vis. Sci. 2022, 99, 204–212.
3. Rey-Rodriguez, D.V.; Moreno-Montoya, J.; Álvarez-Peregrina, C. Prevalence of Myopia in America: A Systematic Review and
Meta-Analysis. Cienc. Tecnol. Salud Vis. Ocul. 2021, 19, 72–86.
4. Holden, B.A.; Fricke, T.R.; Wilson, D.A.; Jong, M.; Naidoo, K.S.; Sankaridurg, P.; Wong, T.Y.; Naduvilath, T.J.; Resnikoff, S.
Global prevalence of myopia and high myopia and temporal trends from 2000 through 2050. Ophthalmology 2016, 123, 1036–
1042.
5. Group, C. Myopia stabilization and associated factors among participants in the Correction of Myopia Evaluation Trial
(COMET). Investig. Ophthalmol. Vis. Sci. 2013, 54, 7871.
6. Iribarren, R.; Galán, M.M.; Szeps, A.; Irigaray, L.F.; Kotlik, C.; Rodríguez, G.; Aguirre, R. Consensus on progressive myopia
management. Oftalmol. Clín. Exp. 2022, 15, e137–e156.
7. Hou, W.; Norton, T.T.; Hyman, L.; Gwiazda, J.; Group, C. Axial elongation in myopic children and its association with myopia
progression in the Correction of Myopia Evaluation Trial (COMET). Eye Contact Lens Sci. Clin. Pract. 2018, 44, 248.
8. Morgan, I.G.; Jan, C.L. China Turns to School Reform to Control the Myopia Epidemic: A Narrative Review. Asia-Pac. J. Oph-
thalmol. 2022, 11, 27–35.
9. Hou, X.-W.; Wang, Y.; Ke, C.; Pan, C.-W. Metabolomics facilitates the discovery of metabolic profiles and pathways for myopia:
A systematic review. Eye 2022, 1, 1–8. https://doi.org/10.1038/s41433-022-02019-0.
10. Han, X.; Liu, C.; Chen, Y.; He, M. Myopia prediction: A systematic review. Eye 2022, 36, 921–929.
11. Rhee, M.K. Update on Myopia Control: The US Perspective. Eye Contact Lens Sci. Clin. Pract. 2022, 48, 105–109.
12. Erdinest, N.; London, N.; Levinger, N.; Lavy, I.; Pras, E.; Morad, Y. Treatment of Rapid Progression of Myopia: Case Series and
Literature Review. Case Rep. Ophthalmol. 2021, 12, 875–881.
13. Tsai, T.-H.; Liu, Y.-L.; Ma, I.-H.; Su, C.-C.; Lin, C.-W.; Lin, L.L.-K.; Hsiao, C.K.; Wang, I.-J. Evolution of the prevalence of myopia
among Taiwanese schoolchildren: A review of survey data from 1983 through 2017. Ophthalmology 2021, 128, 290–301.
14. Zhao, C.; Cai, C.; Ding, Q.; Dai, H. Efficacy and safety of atropine to control myopia progression: A systematic review and
meta-analysis. BMC Ophthalmol. 2020, 20, 478.
15. Hiraoka, T. Myopia Control with Orthokeratology: A Review. Eye Contact Lens Sci. Clin. Pract. 2022, 48, 100–104.
16. Xu, S.; Li, Z.; Zhao, W.; Zheng, B.; Jiang, J.; Ye, G.; Feng, Z.; Long, W.; He, L.; He, M.; et al. Effect of atropine, orthokeratology
and combined treatments for myopia control: A 2-year stratified randomised clinical trial. Br. J. Ophthalmol. 2022.
https://doi.org/10.1136/bjo-2022-321272.

Vision 2022, 6, 73 10 of 11
17. Khorrami-Nejad, M.; Naghdi, T.; Gheibi, A. Latest Updates on Pharmacological Management of Myopia Control; A review
article. J. Mod. Rehabil. 2022, 16, 214–221.
18. Hieda, O.; Hiraoka, T.; Fujikado, T.; Ishiko, S.; Hasebe, S.; Torii, H.; Takahashi, H.; Nakamura, Y.; Sotozono, C.; Oshika, T.; et al.
Efficacy and safety of 0.01% atropine for prevention of childhood myopia in a 2-year randomized placebo-controlled study. Jpn.
J. Ophthalmol. 2021, 65, 315–325.
19. Chia, A.; Lu, Q.-S.; Tan, D. Five-year clinical trial on atropine for the treatment of myopia 2: Myopia control with atropine 0.01%
eyedrops. Ophthalmology 2016, 123, 391–399.
20. Pancham, K.; Kalika, B. Role of Short Term Open Eye Orthok Lens Wear in Inducing Myopia Control Changes in Eyes with
Moderate Myopia. Indian J. Forensic Med. Toxicol. 2021, 15, 851–857.
21. Tan, Q.; Ng, A.L.; Cheng, G.P.; Woo, V.C.; Cho, P. Combined atropine with orthokeratology for myopia control: Study design
and preliminary results. Curr. Eye Res. 2019, 44, 671–678.
22. Sánchez-González, J.-M.; De-Hita-Cantalejo, C.; Baustita-Llamas, M.-J.; Sánchez-González, M.C.; Capote-Puente, R. The Com-
bined Effect of Low-dose Atropine with Orthokeratology in Pediatric Myopia Control: Review of the Current Treatment Status
for Myopia. J. Clin. Med. 2020, 9, 2371.
23. Azuara-Blanco, A.; Logan, N.; Strang, N.; Saunders, K.; Allen, P.M.; Weir, R.; Doherty, P.; Adams, C.; Gardner, E.; Hogg, R.; et
al. Low-dose (0.01%) atropine eye-drops to reduce progression of myopia in children: A multicentre placebo-controlled ran-
domised trial in the UK (CHAMP-UK)—Study protocol. Br. J. Ophthalmol. 2020, 104, 950–955.
24. Upadhyay, A.; Beuerman, R.W. Biological Mechanisms of Atropine Control of Myopia. Eye Contact Lens Sci. Clin. Pract. 2020, 46, 129.
25. Bamdad, S.; Momeni-Moghaddam, H.; Abdolahian, M.; Piñero, D.P. Agreement of wavefront-based refraction, dry and cy-
cloplegic autorefraction with subjective refraction. J. Optom. 2020, 15, 100–106.
26. Guo, R.; Shi, L.; Xu, K.; Hong, D. Clinical evaluation of autorefraction and subjective refraction with and without cycloplegia in
Chinese school-aged children: A cross-sectional study. Transl. Pediatr. 2022, 11, 933.
27. Mukash, S.N.; Kayembe, D.L.; Mwanza, J.-C. Agreement between retinoscopy, autorefractometry and subjective refraction for
determining refractive errors in Congolese children. Clin. Optom. 2021, 13, 129–136.
28. Yam, J.C.; Jiang, Y.; Tang, S.M.; Law, A.K.; Chan, J.J.; Wong, E.; Ko, S.T.; Young, A.L.; Tham, C.C.; Chen, L.J. Low-concentration
atropine for myopia progression (LAMP) study: A randomized, double-blinded, placebo-controlled trial of 0.05%, 0.025%, and
0.01% atropine eye drops in myopia control. Ophthalmology 2019, 126, 113–124.
29. Li, F.F.; Zhang, Y.; Zhang, X.; Yip, B.H.K.; Tang, S.M.; Kam, K.W.; Young, A.L.; Chen, L.J.; Tham, C.C.; Pang, C.P. Age Effect on
Treatment Responses to 0.05%, 0.025%, and 0.01% Atropine: Low-Concentration Atropine for Myopia Progression Study.
Ophthalmology 2021, 128, 1180–1187.
30. Yam, J.C.; Zhang, X.J.; Zhang, Y.; Wang, Y.M.; Tang, S.M.; Li, F.F.; Kam, K.W.; Ko, S.T.; Yip, B.H.; Young, A.L. Three-Year
clinical trial of low-concentration atropine for myopia progression (lamp) study: Continued versus washout: Phase 3 report.
Ophthalmology 2022, 129, 308–321.
31. Huang, J.; Mutti, D.O.; Jones-Jordan, L.A.; Walline, J.J. Bifocal & Atropine in Myopia (BAM) Study: Baseline Data and Methods.
Optom. Vis. Sci. 2019, 96, 335.
32. Erdinest, N.; London, N.; Levinger, N.; Morad, Y. Myopia control with combination low-dose atropine and peripheral Defocus
soft contact lenses: A case series. Case Rep. Ophthalmol. 2021, 12, 548–554.
33. Anstice, N.S.; Phillips, J.R. Effect of dual-focus soft contact lens wear on axial myopia progression in children. Ophthalmology
2011, 118, 1152–1161.
34. Chamberlain, P.; Peixoto-de-Matos, S.C.; Logan, N.S.; Ngo, C.; Jones, D.; Young, G. A 3-year randomized clinical trial of MiSight
lenses for myopia control. Optom. Vis. Sci. 2019, 96, 556–567.
35. Walline, J.J.; Giannoni, A.G.; Sinnott, L.T.; Chandler, M.A.; Huang, J.; Mutti, D.O.; Jones-Jordan, L.A.; Berntsen, D.A.; BLINK
Study Group. A randomized trial of soft multifocal contact lenses for myopia control: Baseline data and methods. Optom. Vis.
Sci. 2017, 94, 856.
36. Mutti, D.O.; Sinnott, L.T.; Reuter, K.S.; Walker, M.K.; Berntsen, D.A.; Jones-Jordan, L.A.; Walline, J.J.; Bifocal Lenses In Near-
sighted Kids (BLINK) Study Group. Peripheral Refraction and Eye Lengths in Myopic Children in the Bifocal Lenses In Near-
sighted Kids (BLINK) Study. Transl. Vis. Sci. Technol. 2019, 8, 17. https://doi.org/10.1167/tvst.8.2.17.
37. Sankaridurg, P. Contact lenses to slow progression of myopia. Clin. Exp. Optom. 2017, 100, 432–437.
38. Wu, P.-C.; Chuang, M.-N.; Choi, J.; Chen, H.; Wu, G.; Ohno-Matsui, K.; Jonas, J.B.; Cheung, C.M.G. Update in myopia and
treatment strategy of atropine use in myopia control. Eye 2019, 33, 3–13.
39. Cheung, S.W.; Cho, P.; Fan, D. Asymmetrical increase in axial length in the two eyes of a monocular orthokeratology patient.
Optom. Vis. Sci. 2004, 81, 653–656. https://doi.org/10.1097/01.opx.0000144742.57847.b1.
40. Lyu, Y.; Ji, N.; Fu, A.-C.; Wang, W.-Q.; Wei, L.; Qin, J.; Zhao, B.-X. Comparison of administration of 0.02% atropine and or-
thokeratology for myopia control. Eye Contact Lens Sci. Clin. Pract. 2021, 47, 81–85.
41. Lin, H.-J.; Wan, L.; Tsai, F.-J.; Tsai, Y.-Y.; Chen, L.-A.; Tsai, A.L.; Huang, Y.-C. Overnight orthokeratology is comparable with
atropine in controlling myopia. BMC Ophthalmol. 2014, 14, 1–8. https://doi.org/10.1186/1471-2415-14-40.
42. Han, X.; Xiong, R.; Jin, L.; Chen, Q.; Wang, D.; Chen, S.; Chen, X.; Ha, J.; Li, Y.; Qu, Y.; et al. Longitudinal changes in lens
thickness and lens power among persistent non-myopic and myopic children. Investig. Ophthalmol. Vis. Sci. 2022, 63, 10.
43. Rozema, J.; Dankert, S.; Iribarren, R.; Lanca, C.; Saw, S.-M. Axial growth and lens power loss at myopia onset in Singaporean
children. Investig. Ophthalmol. Vis. Sci. 2019, 60, 3091–3099.

Vision 2022, 6, 73 11 of 11
44. Huang, J.; Wen, D.; Wang, Q.; McAlinden, C.; Flitcroft, I.; Chen, H.; Saw, S.M.; Chen, H.; Bao, F.; Zhao, Y. Efficacy comparison of
16 interventions for myopia control in children: A network meta-analysis. Ophthalmology 2016, 123, 697–708.
45. Zeri, F.; Di Vizio, A.; Ruffinato, T.; Naroo, S. Contact lens use in sport: Practice and perception in Italy. Contact Lens Anterior Eye
2018, 41, S32–S33.
46. Lanca, C.; Yam, J.C.; Jiang, W.J.; Tham, Y.C.; Hassan Emamian, M.; Tan, C.S.; Guo, Y.; Liu, H.; Zhong, H.; Zhu, D.; et al. Near
work, screen time, outdoor time and myopia in schoolchildren in the Sunflower Myopia AEEC Consortium. Acta Ophthalmol.
2022, 100, 302–311.