Original Article

Comparison of cycloplegia with atropine 1% versus cyclopentolate 1%

Ram P Singh, Abadan K Amitava, Nikita Sharma, Yogesh Gupta, Syed A Raza,
Aparna Bose, Ganga S Meena
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Purpose: Cycloplegic refraction is mandatory for children to know the eye’s refractive status. In this study, Access this article online
we compared cycloplegia induced by cyclopentolate 1% to that induced by atropine 1% by means of Website:
retinoscopy. Methods: In this parallel‑designed interventional study, we included 67 children aged between https://journals.lww.com/ijo
YQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8KKGKV0Ymy+78= on 12/01/2023

4 and 17 years. After the initial retinoscopy under cyclopentolate 1% (used twice in each eye), we repeated DOI:
it a week later under atropine ointment 1% (used twice a day for 3 days); both were done by the same 10.4103/IJO.IJO_1159_23
trained optometrist masked to the drug. Each eye’s refraction was converted to spherical equivalents (SEs), PMID:
*****
and the values averaged between the two eyes of each child under each drug. We compared SE with paired
t‑test (JASP 16.4). In addition, we performed correlational analysis, and looked for agreement using the Quick Response Code:
Bland–Altman plot. Significance was set at P < 0.05. Wherever possible, 95% confidence intervals (CIs)
are quoted. Results: The mean SE with atropine was +1.93 ± 2.0 D, compared to +1.75 ± 1.95 D under
cyclopentolate. On average, atropine induced greater cycloplegia by a mere 0.18 D (95% CI: 0.07 to 0.29 D,
P value 0.002). The two cycloplegic refractions correlated significantly (Pearson’s r: 0.975, P < 0.001). The
Bland–Altman plot revealed the limits of agreement as 1.06 and −0.71 D. Conclusion: Our study suggests
that cyclopentolate works for the most part as well as atropine to attain cycloplegia. Atropine may be
considered for children less than 15 years of age with greater than 5.0 D of hyperopia. Cycloplentolate, with
its advantages of quick action and short duration, should form the first go-to topical cycloplegic in busy
outpatient clinics.

Key words: Atropine, children, cyclopentolate, cycloplegia

Refractive errors are a global health issue affecting a large
proportion of the population. To ascertain the refractive
status of the eye, cycloplegic refraction is still often resorted
to, especially among small children and uncooperative
adolescents.[1] Atropine is considered as being more effective
in children, especially those with dark irides.[2]
In order of decreasing potency, the cycloplegic agents are
atropine, cyclopentolate, homatropine, and tropicamide.[2,3]
Despite its supremacy, atropine must be administered at home
two to three times a day for 3 days before the examination
to achieve optimal cycloplegia, but may have unwanted
effects, which may include flush (40.8%), fever (30%), flush
with fever (15.5%), and rash.[4,5] Prolonged atropine‑induced
cycloplegia may also have amblyogenic potential in
children.[6] Adverse effects associated with cyclopentolate
are drowsiness (37%), red eye (14.8%), fever (11.1%), and
flush (11.1%).[5]
Proper cycloplegia is very much important for obtaining
correct refractive error and to prevent overestimation of myopia
or underestimation of hypermetropia in children.
Use of cycloplegia is recommended in detailed fundus
examination, refraction, accommodative esotropia, corneal
traumas, uveitis to prevent iris adhesion, and in ocular
inflammatory disease to reduce ocular pain and photophobia.
For achieving the greatest amount of cycloplegia, atropine is
the gold standard.[8]
Methods
After obtaining ethical clearance from the Institutional Review
Board, we recruited phakic children with clear media, between
4 and 17 years of age, from the out‑patient department of
ophthalmology. After obtaining parental consent and the
child’s assent where possible, we initially enrolled 83 children.
Since 11 failed to return for atropine refraction and five had
incomplete epidemiological data, we analyzed data of 67
children in this parallel‑designed study.
All included children underwent the following:
a. At the first contact, they underwent instillation of two drops
of cyclopentolate 1% in each eye, spaced 10 min apart, after
pinching the lower lid and either ensuring gentle closure of

Spherical equivalent = sphere power + ½ of cylinder[7]

Institute of Ophthalmology, Jawaharlal Nehru Medical College, Aligarh
Muslim University, Aligarh, Uttar Pradesh, India
Correspondence to: Dr. Abadan K Amitava, Institute of
Ophthalmology, Jawaharlal Nehru Medical College, Aligarh
Muslim University, Aligarh ‑ 202 002, Uttar Pradesh, India.
E‑mail: akamitava@gmail.com
Received: 04‑May‑2023 Revision: 05‑Aug‑2023
Accepted: 10‑Aug‑2023 Published: 20-Nov-2023
This is an open access journal, and articles are distributed under the terms of
the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License,
which allows others to remix, tweak, and build upon the work non‑commercially,
as long as appropriate credit is given and the new creations are licensed under
the identical terms.
For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
Cite this article as: Singh RP, Amitava AK, Sharma N, Gupta Y, Raza SA,
Bose A, et al. Comparison of cycloplegia with atropine 1% versus cyclopentolate
1%. Indian J Ophthalmol 2023;71:3633-6.

© 2023 Indian Journal of Ophthalmology | Published by Wolters Kluwer - Medknow

 3634 Indian Journal of Ophthalmology
the lids for 5 min or punctal pressure for 2 min.[2] Cycloplegia
was confirmed by unchanging retinoscopy reflexes when
viewing targets at different distances.
b. The possibility of atropine toxicity and adverse reaction and
the action to be taken in case of such an event were explained
and printed material on the same was provided. The child
was followed up after a week, ensuring that atropine 1%
ointment, half a grain of rice sized, had been instilled twice
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a day for the 3 days preceding the day of the appointment
and retinoscopy was repeated.[3]
All retinoscopy procedures were carried out in a dimly lit
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room by an experienced optometrist who was masked to the
drug instilled, at a standard distance of 2/3 m. Snellen’s letter
E or Landolt C chart was used as targets. After subtracting the
diopteric distance, the cycloplegic refraction was converted to
spherical equivalent (SEs) in diopters for data analysis.
Outcomes
SEs in the two eyes, for each drug separately, were then
averaged to obtain cycloplegic refractive data for each child
under the two drugs.
Statistical tests
We performed statistical analyses using JASP 16.4 version[9] and
MedCalc.[10] Wherever possible, 95% confidence intervals (Cls)
are quoted. Significance was set at P < 0.05. In addition, we
performed correlational analysis and looked for agreement
using the Bland–Altman plot.
Results
Of the 67 children analyzed, there was marginally higher
number of females (55.2%) compared to males (37 to 30) and
the mean age was 10.85 ± 3.2 years. The mean cycloplegia was
significantly greater with atropine (1.93 ± 2.03 D) compared
to cyclopentolate (1.76 ± 1.95 D) by 0.18 D (95% CI: 0.07 to
0.29; P = 0.002, on paired t‑test) [Fig. 1]. Unsurprisingly, the
correlation was excellent and significant (Pearson’s r = 0.975,
P < 0.001) [Fig. 2].
We then looked for agreement between the cycloplegic
SE obtained with atropine and cyclopentolate [Fig. 3a]. It is
Figure 1: Raincloud plots of cycloplegic spherical equivalents under
atropine (orange) and cyclopentolate (green), reflecting largely similar
and overlapping measurements. The marginally larger median value
under atropine compared to cyclopentolate is evident in the box plots
Volume 71 Issue 12
clear that on average, the cycloplegia obtained by atropine is
more by a mere 0.18 D, with 95% CI for difference of 0.07–0.29
D, with the limits of agreement being +1.06 D and −0.71 D.
Importantly, the regression line, with 95% CI, slopes upward
and to the right and crosses the line of no difference obliquely,
suggesting that with increasing myopia, the cycloplegia
obtained under atropine is less than that with cyclopentolate
and with increasing hypermetropia, this is reversed. This is
especially more likely when the refractions exceed 5D, whether
in terms of hypermetropia or myopia. We, therefore, explored
the agreement including only those in the sample whose
refraction on average was within ±5.0 D [Fig. 3b]. Within this
range, we observed minimal slope of the regression line, which
instead seemed to overlap the line of mean difference.
Subgroup analysis of children aged less than 8 years with
hypermetropia
The mean cycloplegia with atropine was insignificantly
greater with atropine (2.28 ± 1.45 D) compared to
cyclopentolate (2.04 ± 1.26 D) by 0.24 D (P = 0.074, on paired
t‑test). P value was not significant. We had data of only nine
patients aged less than 8 years with hypermetropia [Fig. 4].
Discussion
Our study on 67 children, aged 4–17 years, from an
ophthalmology OPD, with a mean ± standard deviation (SD)
refraction of 1.9 ± 2.0 D, revealed that when compared to
topical cyclopentolate 1%, the ocular instillation of atropine
1% ointment led to statistically significantly (P = 0.002),
though clinically unimportant, greater cycloplegia (on
average of 0.18 D). Understandably, this does not amount to
a difference of much clinical import. A more careful study
of the Bland–Altman agreement plot [Fig. 3a] suggests that
as the children became more hyperopic, atropine seemed to
become a more effective cycloplegic than cyclopentolate: this is
evident in the regression line on the Bland–Altman plot sloping
Figure 2: Correlation between mean cycloplegic spherical equivalents
under atropine and cyclopentolate (Pearson’s r = 0.975, P < 0.001)
 Singh, et al.: Atropine versus cyclopentolate – Cycloplegia
December 2023 3635
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a b
Figure 3: (a) Bland–Altman plot to compare agreement between cycloplegia obtained with atropine and cyclopentolate in the entire sample of
67 children. (b) Bland–Altman plot for agreement between cycloplegia obtained under atropine and cyclopentolate for the 63 children who had
refractive measurement within ±5.0 D
Figure 4: Raincloud plots of cycloplegic spherical equivalents under
atropine (orange) and cyclopentolate (green) of children less than
8 years with hypermetropia, reflecting largely similar and overlapping
measurements. The marginally larger median value under atropine
compared to cyclopentolate is evident in the box plots
upward and to the right. Also, there is much disparity and
variability between the two methods for those with ≥5.0 D of
hyperopia. Since there were just four such subjects, we explored
the agreement between the two cycloplegic drugs for those
with <5.0 D of hyperopia: removing the four with refraction
from 5.0 to 9.4 D [Fig. 3b]. Not surprisingly, the regression line
lost much of its slope, which suggests that from −4.0 to <5.0 D,
the increased cycloplegia achieved by atropine when compared
to cyclopentolate seems to be marginally less changing. It seems
from our study that for most cases, barring those with >5.0
D of hyperopia, cyclopentolate should provide cycloplegia
comparable to atropine. Indeed, in our cohort, a mere 5.9% of
the children had SE exceeding 5 D.
With an intent to compare the change in biometry in 207
myopes, aged 6–12 years, Ye L et al. compared biometric data
before and after administration of cyclopentolate 1% and
then randomly allocated them to receive either 1% or 0.01%
atropine daily for a week.[11] While cyclopentolate reduced the
lens power by −0.14 ± 0.37 D and resulted in a corresponding
significant hyperopic shift of 0.14 ± 0.22 D, the atropine
1%‑induced lens power reduction (in half the sample) was
0.50 ± 0.37 D, with an SE change of 0.52 ± 0.23 D (all values with
P < 0.001). Using their data and plugging them into GraphPad
QuickCalcs,[12] it is clear that these different hyperopic shifts
are significantly different, despite their tiny values (P < 0.001,
for t‑test). It is understandable that in myopes, the differential
cycloplegic effects are likely to be small.
Khurana et al. compared the cycloplegic effects of
cyclopentolate, homatropine, and atropine in 20 children
(40 eyes) with hypermetropia, aged 4–15 years. When we look at
data comparable to our study, we find that the mean difference
between the retinoscopic finding of atropine and cyclopentolate
was 0.26 ± 0.14 D, compared to our difference of 0.18 ± 0.11 D.[3]
In a pertinent study on 32 children aged 5–10 years
with refractive accommodative esotropia and a deviation
<10 prism diopter (PD), Çelebi and Aykan compared the
retinoscopy done with cyclopentolate 1% (right eye [RE]:
5.10 ± 1.21 D and left eye [LE]: 5.2 ± 1.4D) and with 1%
atropine (RE: 5.2 ± 1.2 D, LE: 5.3 ± 1.2 D). They found no
significant difference (P > 0.05). The authors concluded
that cyclopentolate is as effective as atropine in achieving
cycloplegia. Incidentally, they had comparable findings with
autorefractometry and on biometry. This is revealing, since
in our sample, with increasing hyperopia, we had marginally
more cycloplegia being obtained with 1% atropine than with
cyclopentolate. Moreover, we found marginally and statistically
significantly more cycloplegia with atropine (1.93 ± 2.02 D)
compared to cyclopentolate (1.76 ± 1.95 D), with a mean
difference of 0.18 D, 95% CI: 0.06–0.28 D. Interestingly, we can
estimate a difference of 0.10 D in Çelebi and Aykan’s study.
These results can be considered similar to ours, although we
did not include refractive accommodative children.[13]
In an interestingly designed randomized controlled
trial (RCT) in 67 children between 3 and 6 years of age, van
Minderhout et al. compared three different cycloplegics.
Initially, in a paired design, one eye of each subject was
randomized to two drops of cyclopentolate 1% (C–C) while the
 3636 Indian Journal of Ophthalmology
other received a combination of one drop each of cyclopentolate
and tropicamide 1% (C–T), and cycloplegic SE obtained. Two
weeks later, both eyes received atropine 0.5% and were labeled
as atropine‑CC if the eye had previously received C–C and
atropine‑CT if the previous instillation was of C–T. Between
the eyes, SE showed no significant differences: −0.03 ± 0.65 D,
95% CI: −0.16 to + 0.11 D. Compared to C–C, the atropine‑CC
cycloplegia was significantly more by +0.40 ± 0.43 D
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(95% CI: +0.31 to + 0.52 D), while the atropine‑CC cycloplegia
significantly exceeded the C–T values by +0.33 ± 0.39 D (95% CI:
+0.24 to +0.34 D). Like us, they too achieved significantly
more cycloplegia with the stronger atropine compared to
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cyclopentolate or cyclopentolate–tropicamide combination,
although unlike us, they used 0.5% atropine while we instilled
1%. Interestingly, despite the stronger strength of atropine,
our excess cycloplegia was much less at +0.18 D (95% CI for
difference: 0.06 to 0.28 D).[2]
Conclusion
In our study, on average, atropine 1% induced statistically
significantly greater cycloplegia than 1% cyclopentolate,
although it is not likely to be clinically meaningful. For use as
a routine cycloplegic in most children, for the most part, our
study suggests that cyclopentolate works as well as atropine
to attain cycloplegia. Atropine may be considered for children
less than 15 years with greater than 5.0 D of hyperopia.
Cycloplentolate, with its advantages of quick action and short
duration, should form the first go-to topical cycloplegic in busy
outpatient clinics.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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