The Effect of a1 Adrenergic Receptor Antagonist Tamsulosin Flomax on Iris Smooth Dilator Muscle Anat

1

The Effect of a1 Adrenergic Receptor Antagonist
Tamsulosin (Flomax) on Iris Smooth Dilator Muscle
Anatomy
Terry Kim1, MD, John J. DeStafeno1, MD, Sara E.
Miller 2, PhD, Sandra S. Stinnett3, DrPH, Alan D.
Proia2, MD Dept. of Ophthalmology1, Dept. of
Pathology2, Dept. of Biostatistics3, Duke
University Medical Center, Durham, NC
Discussion
Purpose
Results
The intraoperative phenomenom known as floppy
iris syndrome increases the risk of complications
during phacoemulsification secondary to a
flaccid, billowing iris, progressive miosis, and
a tendency for iris prolapse despite properly
constructed wounds. Chang and Campbell1 linked
this syndrome to use of the a1A-adrenergic
receptor antagonist tamsulosin. Tamsulosin is
the most frequently prescribed medication to
treat benign prostatic hypertrophy. The exact
mechanism of floppy iris syndrome and the effect
of tamsulosin on iris mechanics and behavior are
unknown. It has been hypothesized that a disuse
atrophy of the iris dilator muscle may occur
secondary to chronic adrenergic receptor
blockade. We examined the iris dilator muscle
both histologically and by transmission electron
microscopy to determine if any structural
changes were evident. In our study, there was
no significant difference in either the maximal
or minimal dilator muscle thickness between the
control group and the tamsulosin treated group
when measurements were performed via light
microscopy. There was also no difference found
between patients on tamsulosin of differing
duration. We did expect that an observed
difference may not be detected on such a
macroscopic level, therefore, we performed
electron microscopy. Review of the electron
microscopic findings revealed altered muscle
architecture. Although certain elements, such as
nuclei of muscle cells, appeared normal, no
identifiable myofibrils were found in the three
specimens.3 Limitations of electron microscopy
included the use of small iridectomy specimens
and possible artifactual changes due to fixing
and processing of specimens. We must emphasize
that this studied primarily examined possible
muscular changes related to tamsulosin. Other
factors, such as innervation to the muscle, was
not studied. It is reasonable to suggest that
future focus should be directed at the
a-adrenergic receptor. Chronic receptor
blockade by tamsulosin (and other receptor
antagaonists) may alter the mechanism of the iris
dilator muscle, possibly permanently. Some
recent clinical observations support this idea as
the floppy iris syndrome has occurred in patients
despite discontinuation of tamsulosin2. Future
studies investigating additional medications and
contributing factors need to be conducted to
reduce the incidence and surgical complications
related to floppy iris syndrome.    
To determine the effect of the a1-adrenergic
receptor antagonist, tamsulosin (Flomax), on
human iris dilator smooth muscle.
There was no significant difference in either the
mean maximal or minimal dilator muscle thickness
between the control group and the tamsulosin
patients (p0.89, 0.25) (Table 1, Figure 1). A
history of angiotensin antagonist or nitrates use
did not result in thickness differences between
the groups. Iris dilator thickness was not
significantly different among patients above or
below 80 years in either control or treatment
group (p gt 0.05). There was no direct
relationship between duration of tamsulosin use
and dilator muscle thickness (Table 2). No
variables were significant when used together in
a model to predict either maximal or minimal
thickness. Normal muscle architecture in treated
patients was qualitatively difficult to
appreciate by TEM (Figure 2).
Methods
A retrospective study was conducted comprising a
total of 16 eyes obtained at autopsy from 8
patients with a prior history of tamsulosin use
and 6 control patients. Specimens were sectioned
through the pupillary axis in the horizontal
meridian and were reviewed by light microscopy
(HE). Patient age, medical, surgical, and
ocular history, medications, gender, and
duration/dosage of tamsulosin use were recorded.
A morphometric analysis using Optimas 6.5
photometric analyzing software was used to
measure the maximum and minimum thickness (um) of
the iris dilator muscle in each patient. A
minimum of 6 measurements were obtained from each
eye. A separate prospective study of iridectomy
specimens obtained during surgery of 3 eyes from
tamsulosin treated patients was used to evaluate
dilator muscle using transmission electron
microscopy (TEM). All microscopic evaluations and
measures were performed by a masked observer.
SAS release 8.02 (Cary, NC) was used for
statistical analysis.
Control Patient
Tamsulosin (Flomax) Patient
Table 1 Morphometric Results of Iris Dilator
Specimens
Figure 1 Human iris dilator smooth muscle (
) in control and patient treated with
a1-adrenergic receptor antagonist, Tamsulosin
(Flomax). (HE, 600x)
Conclusions
Table 2 Iris Dilator Muscle Thickness in
Patients Using Tamsulosin for Different Durations

• The use of tamsulosin did not reveal any
  discernable difference in iris dilator muscle
  thickness when examined or measured by
  histological methods.
• Lack of identifiable myofibrils was observed on
  transmission electron microscopy (TEM).
• Future studies examining the effect of
  tamsulosin and other a1 adrenergic receptor
  antagonists need to be conducted.

A
B
References
Figure 2 TEM of human iris dilator smooth muscle
in patient treated with tamsulosin (Flomax). A
pronounced lack of identifiable myofibrils is
evident in Figure B (8800x).
1. Chang DF, Campbell JR. Intraoperative floppy
iris syndrome associated with tamsulosin. J
Cataract Refract Surg 2005 31664-673. 2.
Afshari NA, Schwinn DA. a1-Adrenergic
Antagonists and Floppy Iris Syndrome Tip of the
Iceberg. Ophthalmology 2005 1122059-2060. 3.
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