Intraoperative Floppy Iris Syndrome IFIS: Comparison of alphaantagonist medications using an objecti

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Intraoperative Floppy Iris Syndrome (IFIS)
Comparison of alpha-antagonist medications using
an objective video scoring system

• Marc F. Jones, MD
• Pranjal Thakuria, MD
• Ryan Taban, MD
• Lawrence E. Lohman, MD, FACS
• Northeast Ohio Eye Surgeons
• Northeastern Ohio Universities College of
  Medicine
• Summa Health System / Akron City Hospital

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Introduction

• Intraoperative Floppy Iris Syndrome (IFIS), as
  first described by Chang and Campbell, is
  characterized by a billowing flaccid iris, a
  propensity for the iris to prolapse toward
  surgical wounds, and progressive intraoperative
  pupil constriction.1 These patients tend to
  dilate poorly and respond poorly to mechanical
  pupil stretching during surgery. IFIS has been
  commonly seen during cataract surgery in patients
  taking tamsulosin (Flomax). There are also
  reports of an association between other alpha
  antagonists and IFIS, although it is thought that
  this association is not as strong.2 There are few
  objective reports comparing the severity of IFIS
  between different alpha-antagonist medications.
  Similarly, there is little objective data about
  how length of alpha-antagonist use and drug
  discontinuation affect IFIS. Most published
  reports use subjective methods to evaluate the
  presence and severity of IFIS based on the
  surgeons intra-operative experience.
• We have developed an objective scoring system for
  rating the severity of IFIS. Using this system,
  IFIS scores were determined by reviewing surgical
  videos of patients undergoing cataract surgery on
  alpha-antagonist medications. The medication
  type, length of drug use, and discontinuation of
  drug prior to surgery were examined for their
  effect on the severity of IFIS. Multivariate
  statistical analysis was performed to evaluate
  relationships between IFIS score and other
  variables such as age, iris color, and
  preoperative pupil size.

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Methods

• One surgeon performed cataract surgery on 97
  consecutive eyes over 12 months in patients
  treated with the alpha-antagonists tamsulosin
  (Flomax), doxazosin (Cardura), and terazosin
  (Hytrin). A standardized surgical technique of
  vertical chop phacoemulsification was employed.
  The technique was modified for poorly dilated
  pupils with the use of highly cohesive
  viscoelastic (Healon V) and decreased flow and
  vacuum settings. Surgical dilation was obtained
  with Cyclogyl (1) and Neosynephrine (2.5).
• Surgical video recordings were reviewed in a
  blinded manner by a separate cataract surgeon.
  The severity of IFIS was evaluated with a scoring
  system based on the following characteristics
• Average pupil size
• Intraoperative change in pupil size (miosis)
• Iris wound entrapment
• Iris capture by phaco or I/A tip
• Iris trampolining
• Need for mechanical iris retraction.
• An IFIS score was calculated by objectively
  rating all six characteristics. Each
  characteristic was normalized such that the most
  severe case received a maximum score of five and
  the mildest a score of zero. The six individual
  scores were added to achieve an overall IFIS
  score ranging from zero to 30. In the one case
  which required iris hooks, a maximum score of 30
  was assigned due to the inability to calculate an
  accurate IFIS score. Several variables were
  analyzed to determine their effect on IFIS score.
  Statistical analysis was performed using the
  students t-test, Pearsons correlations and
  multiple regression.

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Components of IFIS Score

• IFIS Score

Examples of each component in accompanying video


Intraoperative Miosis
Trampolining
Average Pupil Size



Need for Mechanical Iris Manipulation
Iris to Phaco or I/A tip
Iris to Wound
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Results
Figure 1 Sex of patients.

• From the 97 consecutive eyes undergoing surgery,
  62 videos (59 patients) were available for
  review. 35 videos were unavailable due to
  technical difficulties with the video equipment.
• Average age was 78 years (62-95). 88.7 were male
  (Figure 1). 37 eyes (59.7) were on tamsulosin,
  15 eyes (24.2) on doxazosin, and 10 eyes (16.1)
  on terazosin (Figure 2). Average duration of
  alpha-antagonist treatment was 46 months (1 day
  to 10 years). 27 (43.5) patients discontinued
  use of the medication prior to surgery. 39
  (62.9) eyes had light colored irises.
• Vision improved from an average of 20/68
  pre-operatively to 20/30 postoperatively. No
  patient experienced a loss in best corrected
  vision. There were no intraoperative
  complications aside from one patient with
  pre-existing zonular instability requiring
  removal of the capsular bag and placement of an
  ACIOL.

Figure 2 Percentage of patients on each
alpha-antagonist drug.
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Figure 3 IFIS Scores of alpha-antagonist
medications.
IFIS scores averaged 10.9 (0.5 to 30). The
average IFIS score for patients on tamsulosin was
14.1, terazosin 7.8, and doxazosin 5.2 (Figure
3). There was a statistical difference in IFIS
scores between the tamsulosin and doxazosin
groups (plt.001), and tamsulosin and terazosin
groups (plt.001). There was no statistical
difference between the terazosin and doxazosin
groups (p0.35). There were two terazosin
patients and one doxazosin patient with clear
signs of IFIS and IFIS scores above 15 (Video 1).
Video 1 Terazosin (Hytrin) patient demonstrating
signs of IFIS with an IFIS score of 20.9.
Figure 4 Pupil size at four surgical steps for
each medication.
See accompanying video
Tamsulosin patients had smaller pupils and
demonstrated greater intraoperative miosis. The
flaccidity of the iris in these patients caused a
more pronounced mydriasis with viscoelastic
instillation at the time of the capsulorhexis.
In contrast, once the viscoelastic was removed
after I/A the pupils became markedly miotic
(Figure 4).
Start of Case
Capsulorhexis
End of I/A
End of Case
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Figure 6 Effect of length of drug use on IFIS
score. All three drugs combined.
Small pre-operative pupil size was a significant
predictor of higher IFIS scores (plt0.0001) .
Each millimeter of decrease in pupil size was
associated with an increase in IFIS Score of 5.0
units (Figure 5).
Figure 7 Effect of length of drug use on IFIS
score. Each drug individually.
There was no correlation between IFIS score and
duration of drug use (p0.293) (Figure 6).
Tamsulosin (Flomax) users showed a trend towards
higher IFIS scores with longer drug use but this
did not reach statistical significance (Figure 7).
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There was no correlation between IFIS score and
discontinuation of the drug prior to surgery
(p0.641). The 27 patients that discontinued
their medication approximately two weeks prior to
surgery had an average IFIS score of 11.6. The
average IFIS score for patients continuing their
medication was 10.4. There was also no
correlation between IFIS score and
discontinuation of tamsulosin when tamsulosin
patients were evaluated in isolation. Two
patients has significant IFIS despite
discontinuing two months and three months prior
to surgery with IFIS scores of 25.2 and 17.7,
respectively (Video 2).
There was a significant association between
increasing age and increasing IFIS scores
(r20.33 p0.008) (Figure 8). Patients greater
than 80 years of age were twice as likely to have
severe IFIS (IFIS score gt 20) when compared to
younger patients.
Figure 8 Effect of patient age on IFIS score.
R² 0.33
Video 2 Tamsulosin (Flomax) patient 56 days
after discontinuing the medication.
See accompanying video
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The mean IFIS score was significantly higher in
light colored irises than dark colored irises
(p0.04). The mean IFIS score for light irises
was 12.5 and in dark irises 8.35. Light irises
had consistently smaller pupils throughout all
stages of surgery (Figure 9).
Figure 9 Average pupil size for light and dark
irises throughout surgery.
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Discussion
Method of grading the degree of IFIS We present a
novel method of grading intraoperative floppy
iris syndrome that is objective and rates the
signs of IFIS on a continuous scale rather than
simply by its presence or absence. In addition,
this study is unique in that the degree of IFIS
was determined by a separate blinded surgeon
reviewing videos of the surgical cases. The
resultant IFIS score potentially allows for more
powerful statistical analysis. Differences
between alpha-antagonist medications Intraoperativ
e floppy iris syndrome, as determined by the IFIS
score, was observed in patients taking each of
the three alpha-antagonist medications. Previous
reports have implicated tamsulosin as the most
frequent medication associated with IFIS and our
study confirms this.1,6,7 There are few reports
of other alpha-antagonists causing IFIS.2,5 Our
results support that both doxazosin and terazosin
can cause IFIS, but it is much less frequent and
less severe with these drugs. It is yet to be
determined if doxazosin and terazosin groups
differ from patients not taking alpha-antagonist
medications. This analysis is currently in
progress. Discontinuing alpha-antagonists prior
to surgery When IFIS was first recognized many
surgeons discontinued these medications prior to
surgery However, the benefit of stopping these
medications was questionable.1 Our study found
no effect of stopping the medications two weeks
prior to surgery. In fact, some patients
exhibited significant IFIS even after
discontinuing their alpha-antagonist for several
months. This may support the contention that IFIS
is caused by smooth muscle atrophy1. In
contrast, there was one patient who had severe
IFIS after taking tamsulosin for only one day.
There was no correlation between length of
alpha-antagonist treatment and severity of IFIS.
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Discussion
Effect of pupil size on IFIS Small preoperative
pupil size was a significant predictor of IFIS.
As suggested in other reports, this may be the
most useful clinical indicator to identify which
patients will develop IFIS.8 In those patients
with more severe IFIS, the pupil was small at the
beginning of surgery and enlarged significantly
with instillation of viscoelastic. This may also
be an early intraoperative indication of IFIS
caused by the relative flaccidity of the
iris. Effect of patient age and iris color For
reasons that are unclear, both advancing age and
light colored irises were associated with more
severe IFIS.
Conclusion IFIS was observed in all groups of
alpha-antagonist treated patients and was most
severe in patients treated with tamsulosin. IFIS
could occur at all durations of drug treatment
and was unaffected by discontinuing the drug.
Smaller preoperative pupil size, advancing
patient age, and light colored irises were
associated with more severe IFIS.
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References

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• Acknowledgement for statistical analysis is
  given to Elizabeth E. Piatt, Ph.D., assistant
  professor at Northeastern Ohio Universities
  College of Medicine.