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ORIGINAL RESEARCH

Amblyopia Treatment Efficacy in Anisometropia

This article was published in the following Dove Press journal:
Clinical Ophthalmology

Hessa M Al Ammari Purpose: To compare the treatment efficacy of optical correction and occlusion therapy and/
Fatemah T Al Shamlan or penalization for different anisometropic refractive errors (hyperopic, myopic, and mixed).
Methods: Medical records of 51 patients with anisometropic amblyopia managed by both
Pediatric Ophthalmology and Strabismus
Department, Dhahran Eye Specialist optical correction and occlusion therapy and/or penalization were evaluated retrospectively.
Hospital, Dhahran, Saudi Arabia Patients were categorized into hyperopic, myopic or mixed anisometropia groups.
Cycloplegic refraction, spherical anisometropia, baseline visual acuity, baseline interocular
difference, final visual acuity and final interocular difference were analyzed to
assess association between type of anisometropia with both resolution of anisometropic
amblyopia and the time required to achieve it.
Results: Baseline visual acuity of the amblyopic was 0.94±0.47 in the hyperopic group; 1.12
±0.56, in the myopic group; and 1.08 ±0.39 in the mixed group. Final visual acuity in the amblyopic
eye was 0.34±0.30 in the hyperopic group, 0.78±0.59 in the myopic group, and 0.78±0.56 in the
mixed group. The difference in final visual acuity in the amblyopic eye between the groups was
significant (P=0.014). The amblyopia was improved in 50% of patients in the hyperopic group,
23.8% in the myopic group, and 14.3% in the mixed group (P=0.081). The type of anisometropia
was significantly associated with the improvement of visual acuity in the amblyopic eyes (P=0.044).
The mean time for amblyopia improvement was 16.50±10.52 months in the hyperopic groups,
15.60±12.44 months in the myopic group, and 21.00±21.21 months in the mixed group (P=0.947).
Conclusion: Lower amounts of hyperopic anisometropia are as amblyogenic as higher
amounts of myopic or mixed anisometropia. Mean improvement in visual acuity of an
amblyopic eye with both optical correction, occlusion therapy and/or penalization is higher
in patients with hyperopic anisometropia in comparison with myopic or mixed anisometro-
pia. No significant difference was found in the time required to achieve improvement
between the study groups.
Keywords: amblyopia, anisometropia, hyperopia, myopia, occlusion therapy, penalization

Introduction
Amblyopia is the most common cause of preventable monocular visual loss in
children,1–3 affecting approximately 1.6–3.6% of the population.4 It is defined as
a decrease in best-corrected visual acuity due to refractive error, strabismus or depriva-
tion at the critical period of visual development.5 Anisometropia is a refractive imbal-
ance between the patient’s eyes.6 The eye that results in anisometropic amblyopia is the
one that receives blurred image to retina and transmits it to the brain. It is the only
amblyogenic factor detected in 37% of cases.6 Anisometropic amblyopia is still being
treated by glasses or contact lenses, or with adding patching or other modalities that
Correspondence: Fatemah T Al Shamlan
Dhahran Eye Specialist Hospital, 7630 H.E cause the two eyes to be stimulated differentially.
Ali Naimi Street, Aljamiah District,
Anisometropia has been evaluated in numerous studies.7–9 However, the compar-
Dhahran 34257, Saudi Arabia
Email Fatemah.alshamlan@gmail.com ison of efficacy of amblyopia treatment with both optical correction and occlusion

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therapy and/or penalization between different types of ani- Patients were classified into three groups – myopic,
sometropia (hyperopic, myopic, astigmatic and mixed) has hyperopic or cylindrical anisometropia. If a cylindrical
not, we believe, been evaluated or conducted in our region or component was present with either myopia or hyperopia
elsewhere. the classification of anisometropia was based on the com-
The purpose of our study is to compare the treatment ponent with the highest degree. In cases where one eye was
efficacy of optical correction and patching and/or penali- myopic and the other hyperopic, patients were classified as
zation and discover which type of anisometropic refractive a mixed group. The amount of the amblyopia corrected was
error is more responsive to treatment so that we can defined as (VAas-VAae/VAas-Vase) ×100 (%), where VAas
deliver optimal care and management for our patients’ is the visual acuity of the amblyopic eye at the beginning;
condition. VAae is the visual acuity of the amblyopic eye at the end;
Vase is the visual acuity of the sound eye at the end.12
Method Amblyopia was considered resolved when the difference
A retrospective cohort study was conducted at Dhahran between the eyes was ≤1 line.
Eye Specialist Hospital, Dhahran, Saudi Arabia. The Visual acuity was in a logarithm of minimum angle of
approval to conduct the study was obtained from the improvement (Log MAR) for statistical analysis. The ana-
ethical board and research committee in Dhahran Eye lysis was performed with IBM SPSS v.22 for Windows
Specialist Hospital and in compliance with the (IBM, Armonk, New York, USA). The normality of data
Declaration of Helsinki. All patients upon having was measured using the Shapiro–Wilk test. Normally dis-
a medical record in the hospital sign an acknowledgment tributed data were tested by analysis of variance
and agreement that their medical records can be reviewed (ANOVA), non-normally distributed data were tested by
and used for research purposes. The medical records of Kruskal–Wallis. A P-Value < 0.05 was considered stati-
patients who had anisometropic amblyopia diagnosed cally significant.
between January 2008 and January 2018 were included. The required sample size was determined to be 66
The selection criteria of patients were; patients with G* Power software (v3.1.9.2, University
Kiel, Germany) using large size effect of 0.4, 3 groups,
● Anisometropia ≥1 diopters (spherical and/or cylindrical). and a study power of 80%. However, with a sample size of
● Difference of ≥2 lines in best-corrected visual acuity. 51 patients the power achieved was 70%.
● Age at first presentation between 3 and 12 years.
● Minimum follow-up of 12 months. Results
● No ocular or neurological disorder. The study included 51 patients (29 male and 22 female)
● Absence of strabismus or other forms of amblyopia. with a mean age at presentation of 7.04±2.63 years. All
● No previous ocular surgery. had a minimum follow-up of 12 months, and out of the 51
patients, 21 were followed for up to 36 months (41.1%)
Fifty-one patients were included in the study. All patients (Table 1). The mean follow-up of patients was 25.65±9.30
went through a complete ophthalmological examination months. Final visual acuity was defined as final follow-up
including cycloplegic retinoscopy, slit-lamp examination, after 12 months. The hyperopic group consisted of 16
and fundoscopy and motility tests. Best-corrected visual patients, followed by 21 in the myopic group, 0 in the
acuity was measured using Allen pictures, Sheridan– cylindrical group and 14 in the mixed group. Since the
Gardiner test, Snellen chart which was obtained on the cylindrical anisometropia group had no patients, that group
next visit after prescribing glasses or contact lens based on was omitted. Hence, the number of groups was reduced to
cycloplegic refraction result. The appropriate refractive three (hyperopic, myopic, and mixed anisometropia). The
correction was prescribed together with occlusion in the mean age at presentation was 6.60±3.00 years in the
form of adhesive patches placed on the sound eye as per hyperopic group, 8.10±2.61 years in the myopic group,
the recommendation of the Pediatric Eye Disease and 5.85±1.46 years in the mixed group (P=0.042). The
Investigator Group10 or penalization using atropine oint- mean follow-up time was 24.38±8.89 months in the
ment 1% once daily on the sound eye11 (both therapeutic hyperopic group, 24.86±9.54 months in myopic group,
components were prescribed together). Contact lenses and 28.29±9.54 months in the mixed group (18–36
were given wherever required to decrease the aniseikonia. months) [P=0.509].

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Table 1 Demographic Features of Patients in the Study Baseline visual acuity of the amblyopic and sound eye
Parameter Group Value was 0.94±0.47, 0.13±0.17, respectively, in the hyperopic
group (Table 2, Figure 1); 1.12±0.56, 0.20±0.20 in the
Number of patients (n) Hyperopic 16 (31.4%)
Myopic 21 (41.2%)
myopic group (Table 2, Figure 2); and 1.08 ±0.39, 0.17
Mixed 14 (27.5%) ±0.18 in the mixed group (Table 2, Figure 3). Baseline
All 51 (100%) interocular difference was 0.81 ±0.42, 0.92 ±0.64, 0.90
Gender (males/females) Hyperopic 7/8 ±0.37 in the hyperopic, myopic and mixed groups, respec-
Myopic 12/9 tively (Table 3, Figure 4). There was no significant differ-
Mixed 9/4 ence in the baseline visual acuity of the amblyopic eye,
All 29/22
sound eye and in interocular difference in the three groups
Age at presentation (year) Hyperopic 6.60±3.00 (P=0.595, 0.416, 0.831, respectively) (Table 3).
Myopic 8.10±2.61 Final visual acuity in the amblyopic and sound eye was
Mixed 5.85±1.46
0.34±0.30, 0.03±0.07, respectively, in the hyperopic group
All 7.04±2.63
(Table 3, Figure 1); 0.78±0.59, 0.11±0.17 in the myopic
Follow-up time (month) Hyperopic 24.38±8.89 group (Table 3, Figure 2); and 0.78±0.56, 0.07±0.09 in the
Myopic 24.86±9.54
mixed group (Table 3, Figure 3). Final interocular difference
Mixed 28.29±9.54
All 25.65±9.30
was 0.30±0.31, 0.67±0.61, 0.71±0.57 in the hyperopic, myo-
pic and mixed groups, respectively (P=0.065) (Table 3,
Figure 4). The mean increase in visual acuity of the amblyopic
The mean spherical anisometropia was 2.29±1.02 diop- eyes from the first presentation to the final evaluation was 0.61
ters in the hyperopic group, 7.57±3.93 diopters in the myopic ± 0.37 in the hyperopic group, 0.34 ± 0.37 in the myopic
group, and 10.21±3.61 diopters in the mixed group. This was group, and 0.29 ± 0.55 in the mixed group (P=0.086)
statistically significant (P < 0.001). The mean cylindrical (Figure 5). The improvement in visual acuity of the sound
anisometropia was 0.45±0.70 diopters in the hyperopic eye from baseline to the final evaluation was 0.10 ± 0.17 in
group, 0.82±0.89 diopters in the myopic group, and 1.09 hyperopic group, 0.09 ± 0.20 in myopic group, and 0.10 ±0.16
±1.48 diopters in the mixed group (P=0.371). in the mixed group (P=0.993).

Table 2 Evaluation of Visual Acuity in Log MAR During Follow-Up

Evaluation Eye Group

Hyperopic Myopic Mixed

Baseline (n=51) Amblyopic 0.94±0.47 1.12±0.56 1.08±0.39

Sound 0.13±0.17 0.20±0.20 0.17±0.18

3 months (n=27) Amblyopic 0.74±0.35 1.12±0.36 0.83±0.29

Sound 0.05±0.11 0.19±0.21 0.22±0.26

6 months (n=35) Amblyopic 0.50±0.26 0.84±0.11 0.93±0.55

Sound 0.07±0.13 0.12±0.15 0.15±0.09

12 months (n=41) Amblyopic 0.38±0.31 0.92±0.52 0.84±0.35

Sound 0.05±0.09 0.12±0.19 0.08±0.11

18 months (n=37) Amblyopic 0.37±0.28 0.74±0.52 0.71±0.36

Sound 0.04±0.07 0.12±0.20 0.05±0.06

24 months (n=27) Amblyopic 0.38±0.30 0.80±0.58 0.75±0.59

Sound 0.01±0.02 0.23±0.28 0.07±0.07

36 months (n=21) Amblyopic 0.50±0.27 0.48±0.29 0.68±0.70

Sound 0±0 0.17±0.25 0.06±0.17

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Figure 1 Visual acuity in hyperopic anisometropia group during follow-up.

Figure 2 Visual acuity in myopic anisometropia group during follow-up.

The mean time for amblyopia resolution was 16.50 The age at presentation was not a predictive factor for
±10.52 months in the hyperopic groups, 15.60±12.44 final visual acuity (P=0.898).
months in the myopic group, and 21.00±21.21 months in
the mixed group (P=0.947). Discussion
Final visual acuity of 20/20 was achieved in the In our study the average age at presentation was 7.04±2.63
amblyopic eye in 25% (n=4) of patients in the hyperopic years. This is possible because anisometropic amblyopia is
group, 4.8% (n=1) in the myopic group, and 0% in the not detected until children go to school. Presentation of
mixed anisometropia group. children with strabismus is with a mean age of 3.5 years,

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Figure 3 Visual acuity in mixed anisometropia group during follow-up.

yet those with anisometropic amblyopia and no detected anisometropia compared to myopic anisometropia with the
strabismus are on average 3 years older.13–15 Furthermore, same degree of anisometropia.16 Tanlamai and Goss stated
anisomyopes presented at an older age (8.10±2.61 years) that regardless of the way anisometropia was measured,
when compared with anisohyperopia (6.60±3.00 years). occurrence of amblyopia in anisohyperopia equals aniso-
This could be because myopia increases later in life, as myopes with two diopters more of anisometropia.17
the eye enlarges during age progresses. This can be attributed to that defocus happens more in
The average spherical anisometropia was found to be the eye with higher hyperopia in anisohyperopic cases. Yet
significantly different between the three groups (p<0.001). in the case of anisomyopes the eye with higher degree of
Despite this statistically significant difference, the initial myopia can see near objects and the one with lesser degree
visual acuity of the amblyopic eyes and the initial intero- of myopia will see the distant objects, thus the defocus of
cular difference in the three groups were not significantly one eye will be less. Furthermore, amblyopia may be
different (p=0.595, 0.831, respectively). This may indicate much worse in anisohyperopia because anisohyperopia
that lower amounts of hyperopic anisometropia are as presents in an early age.
amblyogenic as higher amounts of myopic or mixed ani- In our study, resolution of amblyopia with both optical
sometropia. Results similar to ours were found in a study correction, occlusion therapy and/or penalization was found
by Levi et al where amblyopia was doubled in hyperopic to be higher in patients with hyperopic anisometropia (50%)

Table 3 Spherical Anisometropia, Visual Acuity, and Interocular Difference Among Study Group
Parameter Anisometropia P-Value

Hyperopic Myopic Mixed

Spherical anisometropia (D) 2.29±1.02 7.57±3.93 10.21±10.31 <0.001

Baseline VA (log MAR) of amblyopic eye 0.94±0.47 1.12±0.56 1.08±0.39 0.595
Final VA (Log MAR) of amblyopic eye 0.34±0.30 0.78±0.59 0.78±0.56 0.014
Baseline interocular difference (Log MAR) 0.81±0.42 0.92±0.64 0.90±0.37 0.831
Final interocular difference (Log MAR) 0.30±0.31 0.67±0.61 0.71±0.57 0.065

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Figure 4 Intraocular difference in visual acuity among anisometric groups.

Figure 5 Improvement in visual acuity in amblyopic eye from baseline to final evaluation.

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in comparison with patients with myopic or mixed anisome- A study conducted by Chen et al5 illustrated that there
tropia (23.8%, 14.3%, respectively) [P=0.081]. Although the was no difference in the percentage of patients who
difference in resolution of amblyopia among anisometropic reached resolution and the time to achieve this between
groups was not statistically significant, it was clinically different anisometropic refractive error groups. The dis-
important.18 The mean resolution in visual acuity in amblyo- parity between this study and ours might be because of
pic eye from baseline to final evaluation was also higher in various definitions of anisometropia types. Chen et al clas-
the hyperopic anisometropia group (P=0.044) although all sified patients with spherical and cylindrical anisometropia
three groups were subjected to the same modalities of treat- into a mixed group, while we classified patients into myo-
ment (spectacle correction with either patching or penaliza- pic, hyperopic or cylindrical groups based on the compo-
tion). These results indicate that hyperopic anisometropia is nent with the highest degree of anisometropia. And if
more responsive to treatment than myopic and mixed ani- myopic and hyperopic errors were present patients were
sometropia taking into consideration that the amount of classified as a mixed group.
anisometropia in hyperopic group was as amblyogenic as We found that age at presentation was not a predictive
the amount of anisometropia found in myopic and mixed factor for final visual acuity in the amblyopic eye. This
group which indicates that the amblyopia was associated
could be explained by the age of our patients, since none
with the type of anisometropia rather than the amount.
of them was over 12 years on presentation. Other
Steele et al analyzed the efficacy of treating different
studies21,22 indicated that for patients treated with patch-
anisometropic refractive errors with only glasses
ing, the age at presentation was not a significant factor in
correction.19 The results of this study showed a statistically
affecting duration to cure or final visual acuity.
significant increase in visual acuity of the amblyopic eye in
Like other studies, ours has some limitations. First, this
the hyperopic and astigmatic anisometropia groups with only
study is retrospective in nature with the follow-up visits
glasses correction. In our study, 25% (n=4) of anisohyperopia
spaced variably, unlike those of a prospective-design
achieved 20/20 vision or better, compared with 39% (n=7) in
study. Second, the follow-up period was not the same for
the Steele et al study. This difference can be explained by the
all patients. Third, no patients with cylindrical anisome-
number of patients in their study group (28 patients) that is
tropia were included in the study. Fourth, long-term stabi-
less than what we collected and the better baseline visual
acuity of amblyopic eyes (20/60) in comparison with the lity of visual acuity after discontinuing of patching and/or
baseline visual acuity in our study (20/174). In addition, penalization was not evaluated. And finally, we did not
they only included patients who were responsive to spectacle evaluate the changes in anisometropia along the course of
correction and excluded those who failed this modality of follow-up treatment, which could, by itself, be a cause of
treatment and required occlusion therapy, while our study improvement or decline in the status of the amblyopic eye.
included patients treated with optical correction with occlu-
sion therapy and/or penalization. Conclusion
The time required to achieve resolution in the three Although there was no significant difference in time
groups of our study was longer than that of Steele et al required to achieve resolution between the three groups,
(6–36 months, compared with 3–22 weeks). This may be it was found that the type of anisometropia rather than the
attributed to two factors. First, the better initial visual amount of anisometropia is a significant factor on the
acuity at Steele et al. Second, our study was retrospective.
degree of amblyopia and the response to treatment (ani-
Follow-up visits were variable according to the preference
sometropic hyperopia was having similar results of
of the treating ophthalmologist. Therefore, it is difficult to
amblyopia compared to anisometropic myopia and mixed
know exactly when improvement and resolution happened.
although the amount of anisometropia is less in the former.
In a prospective pilot study conducted by Pang et al,
Furthermore, it responded better to treatment than the
the outcomes of treating amblyopia associated with myo-
latter groups). Further, larger prospective studies are
pic anisometropia with both optical correction and occlu-
needed to address these findings.
sion therapy were evaluated. The mean increase in visual
acuity in the amblyopic eye was 2.59 lines.20 This is
consistent with mean increase in visual acuity of aniso- Disclosure
myopes found in our study (0.34 ± 0.37). The authors report no conflicts on interest in this work.

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