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An overlooked effect of systemic anticholinergics: alteration on accommodation amplitude
Mehmet Ali Sekeroglu1, Emre Hekimoglu2, Mustafa
Alpaslan Anayol1, Yasemin
Tasci3, Ismail Dolen3
1Department of Ophthalmology, Ulucanlar Eye Training and Research Hospital, Ankara 06230, Turkey
2Department of Ophthalmology, Etlik Zubeyde Hanim Maternity and Research Hospital, Ankara 06230, Turkey
3Department of Urogynecology, Etlik Zubeyde Hanim Maternity and Research Hospital, Ankara 06230, Turkey
Correspondence to: Mehmet Ali Sekeroglu. Department of Ophthalmology, Ulucanlar Eye Training and Research Hospital, Ankara 06230, Turkey. msekeroglu@yahoo.com
Received: 2014-06-21
Accepted: 2015-09-06
Abstract
AIM: To investigate the
effect of oral solifenacin succinate, tolterodine-L-tartarate and oxybutinin
hydrochloride (HCl) on accommodation amplitude.
METHODS: Female overactive bladder
syndrome (OAB) patients who were planned to use oral anticholinergics, patients that uses solifenacin
succinate 5 mg (Group I,
n=25), tolterodine-L-tartarate 4 mg (Group II, n=25), and oxybutinin HCl 5 mg b.i.d (Group
III, n=25) and age matched healthy female subjects (Group IV, n=25)
were recruited and complete ophthalmological examination and accommodation
amplitude assessment were done at baseline and 4wk after
initiation of treatment.
RESULTS: The mean age of 100 consecutive female subjects was 51.6±5.7 (40-60)y and there were no statistically significant
difference with regard to the mean age (P=0.107) and baseline
accommodation amplitude (P=0.148) between study groups. All
treatment groups showed a significant decrease in accommodation amplitude
following a 4-week course of anticholinergic treatment (P=0.008 in Group I, P=0.002 in Group II, P=0.001 in Group III), but
there was no statistically significant difference in Group IV (P=0.065).
CONCLUSION: A 4-week course of oral
anticholinergic treatment have statistically significant effect on
accommodation amplitude. Clinicians should avoid both overestimating this
result, as this would unnecessarily restrict therapeutic possibilities, and
also underestimating it which may lead to drug intolerance.
KEYWORDS: accommodation; anticholinergics; overactive bladder
DOI:10.18240/ijo.2016.05.19
Citation: Sekeroglu MA, Hekimoglu E, Anayol MA, Tasci Y,
Dolen I. An overlooked effect of systemic anticholinergics:
alteration on accommodation amplitude.
Int J Ophthalmol 2016;9(5):743-745
INTRODUCTION
Overactive bladder syndrome (OAB) which has a significant
negative impact on health related quality of life can be defined as urgency
with or without urge incontinence, generally accompanied by more than eight
micturitions in a 24h period and more than one micturition per night[1-4]. As parasympathetic
cholinergically mediated innervation is the predominant stimulus for bladder
contraction, anticholinergics are the most effective agents currently available
to control OAB symptoms[5-8].
However, significant peripheral adverse effects, such as dry mouth,
tachycardia, drowsiness, decreased cognitive function, constipation and blurred
vision may limit drug tolerability. Blurred vision especially for near objects
is thought to occur secondary to blockage of cholinergic stimulation to the
ciliary muscle of the crystalline lens[9-12].
Accommodation is an increase in the dioptric power of the
crystalline lens that enables the image of near objects to be focused on retina
which occurs due to cholinergically mediated contraction of the ciliary muscles[13]. Age related loss of
accommodation leads to presbyopia. As patients develop presbyopia, they present
clinically with difficulty in near-vision tasks. These problems manifest at
about 45y of age when the accommodative reserve starts to become insufficient
to focus on near objects[14].
Solifenacin succinate, tolterodine-L-tartarate and oxybutinin
hydrochloride (HCl) are different type of anticholinergics that are commonly
used to treat OAB. The clinical efficacy of these agents is limited by adverse
systemic effects attributed to blockage of muscarinic reseptors throughout the
body. In this study, we investigated the effect of these agents on
accommodation amplitude (AA) and compared these results with those of healthy
control subjects.
SUBJECTS AND METHODS
The study was designed as a prospective study undertaken at a
single hospital and was carried out with approval from the Institutional Review
Board. Only patients who fulfilled the selection criteria and gave written
informed consent in line with the Decleration of Helsinki were included in the
study.
Patients were recruited between May 2012 and February 2013
for the study. Female OAB patients who were diagnosed at Department
of Urogynecology
following detailed gynecologic examination and planned to use solifenacin
succinate 5 mg was included in Group I, tolterodine-L-tartarate 4 mg was included in Group II, and oxybutinin HCl 5 mg b.i.d in Group III. The Group IV was composed of
consecutive age matched urogynecologically healthy female subjects.
After obtaining detailed medical history, all patients
underwent complete ophthalmological examination at first admission and 4wk after initiation of oral treatment, including best corrected
Snellen visual acuity testing, slit-lamp examination, Goldmann applanation
tonometry, gonioscopic evaluation and dilated fundus examination using a
90-diopter lens in order to exclude the subjects who were contraindiceted to
use anticholinergics. The patients at Group IV were also examined at day 0 and
day 28. All aforementioned assessments were done by one of the authors
(Sekeroglu MA) who was blinded to the group of patients. After detecting best
corrected visual acuity of patients at Snellen chart, additional minus spheres
were added until the eye was unable to overcome the minus power by
accommodation, and was unable to read letters smaller than 20/25 on the chart.
This was recorded as AA[15].
All examinations were done by one of the authors (Sekeroglu
MA) and were carried out at the same time interval of the day (between 9-10
o’clock a.m.) in order to prevent diurnal variations and also other
confounding factors such as fatigue and reading during the day. All assessments
were also done in the same room with a standard illumination in order to
prevent the effect of environmental factors on AA. In order to eliminate
confounding factors that could affect visual acuity and/or accommodation, the
patients with ocular diseases such as glaucoma, cataract, ocular surface
disorders, retinal diseases, amblyopia,
strabismus, a history of ocular surgery or trauma, refraction error ≥4 D, and
those with a history of central nervous system disorders were excluded.
Statistical Analysis SPSS 11.5.0 software for Windows
(SPSS, Chicago, IL, USA) was used
for statistical analyses. The normality of each variable was
tested by using the Shapiro-Wilk test. Kruskal-Wallis one-way ANOVA test was used to determine differences
among the four groups for quantitative variables
with a normal distribution. Spearman’s rho was used to determine the
correlation between two quantitative variables. Wilcoxon signed-rank test was
used for comparison of two dependent variables for non-normal variables. Descriptive
statistics were expressed as frequency and percentage for categorical variables
whereas quantitative data were expressed as mean±standard deviation for
normally distributed variables and median (minimum-maximum) for non-normally
distributed data. P<0.05 was considered statistically significant.
RESULTS
One-hundred consecutive female subjects [(75 OAB patients that uses
solifenacin succinate 5 mg (Group I, n=25), tolterodine-L-tartarate 4 mg (Group II, n=25), and oxybutinin HCl 5 mg b.i.d. (Group III, n=25) and age-matched healthy
control subjects (Group IV, n=25)] with a mean age of 51.6±5.7
(40-60)y who had completed 4wk of
follow-up were recruited for this study.
There were no statistically significant difference with
regard to the mean age (52.6±5.3y in Group I, 52.8±4.5y in Group II, 51.9±5.5y
in Group III and 49.8±6.7y in Group IV; P=0.107) and baseline AA (P=0.148) between study groups (Table 1).
Table 1 The
initial and final accommodation amplitude of Group
I, II, III and IV patients 
(min-max)
|
Groups |
Baseline
AA (D) |
AA at
4wk (D) |
P |
|
Group I (n=25) |
2.69±1.40
(0.75-6.50) |
2.62±1.38
(0.75-6.25) |
0.008 |
|
Group II (n=25) |
2.64±1.28
(1.00-5.50) |
2.49±1.29
(0.75-5.50) |
0.002 |
|
Group III (n=25) |
2.92±1.53
(0.50-6.50) |
2.73±1.55
(0.50-6.50) |
0.001 |
|
Group IV (n=25) |
3.21±1.75
(0.75-6.50) |
3.18±1.77
(0.75-6.50) |
0.065 |
AA: Accommodation amplitude.
All treatment groups showed a significant decrease in AA following
a 4-week course of anticholinergic treatment.
There was also a decrease in AA of Group IV from baseline to day 28, but this
change was not clinically significant (Table 1). AA was found to be decreased
in 7 patients in Group I, 11 patients in Group II, 14 patients in Group III and
in 5 patients in Group IV at the end of 4wk.
DISCUSSION
Anticholinergic drugs have been the
main pharmacotherapy option of OAB for many years[16]. As cholinergically mediated innervation is the
predominant stimulus for bladder contraction, anticholinergics can improve
frequency, urgency and urge incontinence by blocking receptors of the detrusor
muscle. Significant peripheral adverse effects, attributed to blockade of
muscarinic receptors throughout the body, may limit drug tolerability. In a
study of Garely et al[10],
of the 2225 OAB patients who were treated with solifenacin, 21.4% reported dry
mouth, 13.3% constipation, 3.4% headache, 2.6% blurred vision, 1.8% nausea,
2.5% dyspepsia, and 1.3% dry eye. Dry eye may also cause blurred vision but blurred vision in the
aforementioned study was thought to be mostly related to the relaxation of the ciliary
muscle and temporary impairment of visual accommodation. This study was
conducted to ascertain the change in AA following a 4-week course of oral solifenacin, tolterodine and oxybutinin
treatment, and found a clinically significant effect in short term.
Choppin et al[17] stated that muscarinic receptors
mediating contraction of the rabbit iris sphincter muscle and urinary bladder
smooth muscle are similar and equate most closely with the
pharmacologically-defined muscarinic M3 receptor. There are many
studies regarding the ocular side effects of systemic anticholinergics. But
little data present evaluating the effects on accommodation amplitude which is
the possible cause of blurred vision during treatment.
Altan-Yaycioglu et al[15] stated that oxybutinin
and tolterodine affect the parasympathetic control of the eye and thus reduce
accommodation in adults over 22 years old. Chapple and Nilvebrant[18] found that the normal
dosage of tolterodine (2 mg twice daily) may have less effect on visual
accommodation than the equivalent dosage of oxybutinin (5 mg three times daily)
in patients with OAB. Abrams et al
[19] reported abnormal accommodation
in 3% of tolterodine and 7% of oxybutinin treated patients. Wong et al[20] reported a 5 years old girl who developed
esotropia following oxybutinin treatment for pediatric enuresis. They stated
that it was due to a reduction in AA in combination with her uncorrected
moderate hyperopia which may have driven the need to generate accommodation
using other mechanisms such as convergence accommodation. As far as we know,
our study is the first study in the literature investigating the effect of a novel
oral anticholinergic, solifenacin succinate on AA.
Elderly patients are both more likely to have OAB and to be
very susceptible to the side effects of anticholinergics. Therefore, if an elderly patient is prescribed an anticholinergic drug
for OAB, the patient must be followed carefully and must be seen soon after
initiation of therapy, to ensure that she does not sustain side effects that
are inadvertently attributed to the ageing process. The patients with OAB have
usually presbyopia, and the AA change induced by anticholinergics can be easily
compensated by changing their presbyopic glasses. Thus, the potential benefit
of oral anticholinergics in the treatment of OAB should not be undermined as
the AA deficit is fully correctable. But we should be carefull for younger
patients who do not use presbyopic glasses.
The present study should be viewed in context of some
limitations. First of all, small number of patients and short follow-up
duration may influence the power of statistical analysis. Also the effect of
these agents on AA can not be generalized to all systemic anticholinergics. Thirdly, the other medications which are used for
systemic diseases can be a confounding factor which may also affect AA. Finally, there may be
cumulative effect of the drug after prolonged treatment period or these changes
in AA may be temporary which can only be detected after a drug free period.
In conclusion, a 4-week course of oral
anticholinergic treatment have statistically significant effect on AA.
Clinicians should avoid both overestimating this result, as this would
unnecessarily restrict therapeutic possibilities, and also underestimating it
which may lead to drug intolerance. However further larger and prolonged
studies are needed to determine the effect of anticholinergic medication on AA.
ACKNOWLEDGEMENTS
Conflicts of Interest: Sekeroglu MA, None; Hekimoglu E,
None; Anayol MA, None; Tasci Y, None; Dolen I, None.
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