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Prevention and Management of Intraoperative Floppy Iris Syndrome

Allan Storr-Paulsen

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11 
Management of Intraocular Floppy  
Iris Syndrome (IFIS) in Cataract Surgery 
Allan Storr-Paulsen 
Department of Ophthalmology, Cataract Outpatient Surgery Unit,  
Frederiksberg University Hospital, Frederiksberg,  
Denmark 
1. Introduction 
Intraoperative floppy iris syndrome (IFIS) was first described in 2005 (Chang & Campbell 2005; 
Parssinen 2005). The fullblown syndrome comprises a triad of: 1) billowing of the iris stroma 
in response to normal irrigation currents, 2) the floppy iris tends to prolapse through the phaco 
and the side port incisions, and 3) a progressive pupillary constriction during the surgical 
procedure. Although IFIS may be multifactorial in etiology, systemic treatment with α-1a 
adrenergic receptor (AR) antagonists, and tamsulosin in particular, seems to play a pivotal 
role. The clinical presentation varies widely, from a mild form with a fluttering iris only, to the 
more severe case with the complete triad (Chang et al. 2007). The condition potentially increases 
the risk of intraoperative complications, such as iris trauma, zonular dehiscence, posterior 
capsule rupture, vitreous loss, as well as postoperative complications, including increased 
intraocular pressure and cystoid macular oedema. The prevalence of IFIS in cataract surgery 
varies among different countries, from 0.5 % to 2.0 % (Chang & Campbell 2005; Cheung et al. 
2006; Chadha et al. 2008). The incidence of IFIS during cataract surgery in patients on 
tamsulosin medication varies from 43 – 100%. In contrast, the incidence of IFIS in patients 
taking one of the other α-1a AR antagonists, e.g. alfuzosin, is 10-15% (Blouin et al. 2007). 
2. Etiology 
Adrenergic α-1 receptors are frequently found in smooth muscles of the human prostate / 
bladder neck, and in the iris dilator muscle of the eye, predominantly the subtypes α-1a and 
the α-1d. Stimulation of the iris dilator muscle and the smooth muscles in the prostate and 
the bladder neck is mediated by the adrenergic α-1a and α-1d receptors.  
Lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) is a 
common condition among elderly male patients and the prevalence of BPH and cataract is 
similar, increasing with age. Benign prostatic hyperplasia implies both a static and a 
dynamic component. The static component is characterized by an increased prostatic mass, 
and the dynamic component by an increased α-1 AR mediated tone in the smooth muscles 
of the bladder neck and in the prostate. Inhibition of the α-1a ARs relaxes the muscular tone, 
which decreases the pressure within the lower urinary tract improving urinary outflow, and 
at the same time produces relaxation of the iris dilator muscle causing a floppy iris and 
miosis. Thus, systemic treatment with α-1 AR inhibitors (alfuzosin, doxazosin, tamsulosin 
  
Cataract Surgery 
 
144 
and terazosin) has been a successful therapy of LUTS including benign prostatic 
hyperplasia, but the same treatment may cause some degree of IFIS during cataract surgery. 
Due to a better cardio-vascular profile tamsulosin and alfuzosin seems to be better tolerated 
than doxazosin and terazosin (Djavan et al. 2004). However, tamsulosin also has a very high 
affinity for the α-1a and α-1d ARs in the smooth muscular tissue of the iris. On the other 
hand, alfuzosin acts clinically in a more uro-selective manner, which may explain, why 
alfuzosin causes IFIS less frequent than tamsulosin, decreasing the odd ratio for IFIS to 1:32 
compared to patients exposed to tamsulosin (Blouin et al. 2007).  
3. Management of IFIS 
3.1 Preoperative precautions 
3.1.1 Medical history 
The risk of unexpectedly encountering IFIS during surgery in cataract patients should be 
minimized through a thorough questioning of the previous and the current medical history. 
Of particular interest is a history of symptoms from the lower urinary tract and the prostate. 
This also applies to women, as α-1a AR inhibitors may be prescribed for LUTS and arterial 
hypertension in females. IFIS may develop in patients treated with tamsulosin for only a few 
months. It might seems rational to stop the treatment with α-1 AR antagonists 
preoperatively, but there is little or no clinical effects on the severity of IFIS by stopping the 
treatment with tamsulosin, although the preoperative pupil diameter may be larger (Chang 
et al. 2007; Nguyen et al. 2007). The authors´ institution does not recommend the patients 
stop treatment with α-1 AR inhibitors prior to surgery.  
3.1.2 Preoperative dilatation 
A preoperative maximum pupillary dilatation is mandatory. The author recommends an 
anticholinergic agent to relax the sphincter of the pupil (cyclopentolate 1%) combined with 
an α-1 AR agonist (phenylephrine 2.5 – 10%) to enhance the dilatation and increase the tone 
of the iris dilator stroma administrated twice at 15-20 minutes interval before surgery. The 
author adds a non-steroid anti-inflammatory drug (diclofenac 0.1% / ketorolac 0.5%) to 
provide a more stable dilatation throughout the surgery. A poorly dilated pupil 
preoperatively may predict eyes likely to manifest IFIS during operation. At the authors´ 
institution, a preoperative pupil diameter ≤ 6 mm in IFIS patients indicates the need for iris 
retractors, pupil expansion rings or intracameral phenylephrine.  
Atropine 1% applied topically prior to cataract surgery in patients on tamsulosin has been 
recommended to obtain a maximum preoperative dilatation (Bendel & Phillips 2006; Masket 
& Belani 2007). In the case series by Bendel & Philips, atropine 1% was prescribed twice 
daily for 10 days. Thirteen out of 16 patients (81%) on tamsulosin did not require other 
modification of their cataract surgery. Masket & Belani used a presurgical administration of 
topical atropine 1% three times daily for two days in addition to routine preoperative 
mydriatics. During the operative procedure, 0.3 to 0.5 mL intracameral epinephrine diluted 
1:2500 with BSS was placed under the iris. They reported 19 eyes out of 20 to have an 
excellent pupil dilatation without signs of IFIS.  
Atropine, a potent anti-cholinergic agent, relaxes the sphincter of the pupil, but care should be 
taken due to the risk of intensified LUTS and acute urinary retention, especially if tamsulosin 
is stopped preoperatively. Treatment with atropine 1% also represent a risk in the elderly 
group of cataract patients because of atropine’s well-know cardiac and cerebral side-effects.  
 
Management of Intraocular Floppy Iris Syndrome (IFIS) in Cataract Surgery 
 
145 
3.2 Operative strategies 
3.2.1 Epinephrine in irrigation solution 
Epinephrine, a combined α- and β- AR agonist, should be added to the irrigation solution. 
The author recommends 1 mL epinephrine 1 mg/mL (preservative- and sulphite free) in 
1000 mL balanced salt solution (1: 1 000 000) with a pH within the range of 6.5 – 8.5. 
Irrigation and aspiration flow rates should be reduced to prevent iris fluttering. 
3.2.2 Intracameral injection of epinephrine 
Myers & Shugar reported good effect of an intracameral mydriatic and anesthetic mixture, 
the “epi-Shugar” solution, comprised of epinephrine 0.025% and lidocaine 0.75% in BSS 
Plus. The technique showed excellent results in a paired prospective single masked study 
(Myers & Shugar 2009). The epi-Shugar solution consists of a 1 : 4000 epinephrine mixture 
with a pH of 6.9. There was no report of corneal endothelial cell damage (Shugar 2006). 
Masket & Belani injected 0.3 – 0.5 mL epinephrine diluted with BSS (1 : 2500) intracameral 
and placed under the iris with excellent results (Masket & Belani 2007). Takmaz & Can 
suggested a mixture of 0.1 mL non-preserved epinephrine (0.5 mg /mL) diluted with 2 mL 
BSS (1 : 4000 solution) (Takmaz & Can 2007). They reported no change in the incidence of 
IFIS, but the mixture seemed effective in order to prevent miosis.  
However, intracameral injection in these concentrations may cause local damage, since 
severe changes has been described in corneal endothelial cell morphology after 
intracameral use of 0.5 mL epinephrine in a 1:10.000 solution (Edelhauser et al. 1982; Pong 
et al. 2008).  
3.2.3 Intracameral injection of phenylephrine 
Intracameral injection of phenylephrine, an α-1 AR agonist, has been recommended to 
reverse intraoperative iris fluttering and pupil constriction (Manvikar & Allen 2006; 
Gurbaxani & Packard 2007). In both studies diluted phenylephrine 2.5% was used 
(Minims®, buffered with bisulphite and edetate). Manvikar & Allen used a solution with 
0.25 mL unpreserved phenylephrine 2.5% (Minims) diluted with 2 mL BSS. This 
corresponds to a 1:360 dilution with a pH of 6.4. The authors argued in a study comprising 
32 eyes that the solution had a good effect in order to prevent IFIS. Gurbaxani & Packard 
reported on the use of intracameral phenylephrine 2.5% mixed with 1 mL BSS in a study 
with seven patients on tamsulosin. All patients had significant reduction in the signs of IFIS, 
and a sustained pupillary dilation in all cases. No clinical signs of corneal edema were 
reported, but unfortunately the density of endothelial cell was not evaluated. 
In an early report by Edelhauser et al., a cytotoxic effect on the endothelium of 
phenylephrine at a concentration of 2.5% was described in cases where the epithelium was 
removed (Edelhauser et al. 1979). In a recent report on corneal endothelial cell changes in 
cataract patients on tamsulosin we found no association between the intracameral use of 
0.25 mL phenylephrine 2.5% (Minims®) in 2 mL BBS and postoperative endothelial cell loss 
(Storr-Paulsen et al. 2013).  
3.2.4 Capsular staining 
Capsular staining with trypan blue 0.06% (Vision Blue, DORC, The Netherlands) is an 
excellent technique to visualize an obscured leading edge of the capsulorrhexis at the 
beginning of the operation due to a small pupil or a mature cataract. Trypan blue is also 
  
Cataract Surgery 
 
146 
very effective to visualize the border of the rhexis, if iris retractors are required later in the 
procedure due to progressive miosis. Trypan blue is safe and effective as an adjunct for 
capsule visualization (de Waard et al. 2002; Jacobs et al. 2006) 
3.2.5 Use of ophthalmic viscosurgical devices (OVDs) 
Injection of Healon5 was one of four different surgical strategies used to manage IFIS in a 
multicenter study. A total of 98 of 103 cases were completed with Healon5 alone and the 
remaining five cases required additional use of iris retractors / iris expansion rings (Chang 
et al. 2007). In a survey of surgeons’ experiences with IFIS in the UK, 27% of the responding 
surgeons answered that they used Healon5, and 85% found it effective (Nguyen et al. 2007).  
In 1999, Arshinoff described a technique, where a lower viscosity dispersive OVD was used 
together with a higher viscosity cohesive OVD (Arshinoff 1999). This “soft-shell” technique 
is performed with the dispersive injected into the anterior chamber until the chamber is 75-
80% full. The cohesive is then injected on the surface of the anterior capsule, pushing the 
dispersive OVD upward and outward until the pupil stops dilating. The technique was later 
modified to improve surgery, especially in IFIS patients (Arshinoff 2006).  
3.2.6 Use of iris retractors 
The use of flexible iris retractors to enlarge the pupil was originally described in the early 
1990s (de Juan E Jr & Hickingbotham 1991; Nichamin 1993) and later modified to create a 
diamond shape, which is very suitable in IFIS surgery (Oetting & Omphroy 2002). In the UK 
survey of surgeons´ preferences in cases of IFIS, 61% of the responders chose iris retractors, 
and 72% of that group found them effective (Nguyen et al. 2007). In the American 
multicenter study, iris retractors were only used in 31% of the cases. The difference may be 
explained by the fact that the British survey questioned all UK eye surgeons about their 
experiences; whereas the American study only asked 15 selected and highly experienced 
surgeons (Chang et al. 2007). Pupil stretching and sphincterotomies are usually of no effect 
because of the elasticity of the pupil margin, and may on the contrary worsen the 
constriction of the pupil (Chang & Campbell 2005). 
3.2.7 Use of pupil expansion rings 
Pupil expansion rings have been used to enlarge the pupil and to maintain the size 
throughout the surgery. Expansion rings were only used by 3% of the surgeons in the UK 
survey (Nguyen et al. 2007), and expansion rings were the least used of four alternatives (4% 
of cases) in the American multicenter study (Chang et al. 2007). The expansion rings were 
found to cause less trauma to the iris, but was the most time- and cost consuming method, 
when compared to the use of iris retractors (Akman et al. 2004).  
4. Conclusion 
To reduce possible complications in cataract patients taking α-1 AR antagonists (especially 
tamsulosin), the surgeon should: 
1. highlight the patient´s medical history, particularly for symptoms of LUTS and benign 
prostate hyperplasia. A thorough questioning regarding current and previous therapy 
is strongly recommended. Remember that α-1 AR antagonists are also prescribed for 
LUTS and arterial hypertension in women. 
 
Management of Intraocular Floppy Iris Syndrome (IFIS) in Cataract Surgery 
 
147 
2. use a preoperative dilation including cyclopentolate, phenylephrine, and a NSAID. 
Atropine may be used, but cautions should be taken in elderly patients because of the 
risk of cardiac side effects and acute urinary retention.  
3. use capsular staining in order to facilitate visualization of the rhexis edge. 
4. use a viscoadaptive or the soft-shell technique in all cases of IFIS. 
5. keep phenylephrine ready for intracameral injection in case of a progressive pupil 
constriction during surgery. 
6. consider the use of iris retractors or iris expansion rings if preoperative dilation is ≤ 6 
mm.  
5. References 
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methods for phacoemulsification in eyes with a small pupil secondary to 
pseudoexfoliation. Ophthalmology 111: 1693-1698.  
Arshinoff SA. (1999): Dispersive-cohesive viscoelastic soft shell technique. J Cataract Refract 
Surg 25: 167-173.  
Arshinoff SA. (2006): Modified SST-USST for tamsulosin-associated intraoperative 
[corrected] floppy-iris syndrome. J Cataract Refract Surg 32: 559-561.  
Bendel RE, Phillips MB. (2006): Preoperative use of atropine to prevent intraoperative 
floppy-iris syndrome in patients taking tamsulosin. J Cataract Refract Surg 32: 
1603-1605.  
Blouin MC, Blouin J, Perreault S, Lapointe A, Dragomir A. (2007): Intraoperative floppy-iris 
syndrome associated with alpha1-adrenoreceptors: comparison of tamsulosin and 
alfuzosin. J Cataract Refract Surg 33: 1227-1234.  
Chadha V, Borooah S, Tey A, Styles C, Singh J (2007): Floppy iris behaviour during  cataract 
surgery: associations and variations. Br J Ophthalmol 91: 40-42 
Chang DF, Campbell JR. (2005): Intraoperative floppy iris syndrome associated with 
tamsulosin. J Cataract Refract Surg 31: 664-673.  
Chang DF, Osher RH, Wang L, Koch DD. (2007): Prospective multicenter evaluation of 
cataract surgery in patients taking tamsulosin (Flomax). Ophthalmology 114: 957-
964.  
Cheung CM, Awan MA, Sandramouli S. (2006): Prevalence and clinical findings of 
tamsulosin-associated intraoperative floppy-iris syndrome. J Cataract Retract Surg 
32: 1336-1339  
de Juan E Jr, Hickingbotham D. (1991): Flexible iris retractor. Am J Ophthalmol 111: 776-777.  
de Waard PW, Budo CJ, Melles GR. (2002): Trypan blue capsular staining to "find" the 
leading edge of a "lost" capsulorhexis. Am J Ophthalmol 134: 271-272.  
Djavan B, Chapple C, Milani S, Marberger M. (2004): State of the art on the efficacy and 
tolerability of alpha1-adrenoceptor antagonists in patients with lower urinary tract 
symptoms suggestive of benign prostatic hyperplasia. Urology 64: 1081-1088.  
Edelhauser HF, Hine JE, Pederson H, Van Horn DL, Schultz RO. (1979): The effect of 
phenylephrine on the cornea. Arch Ophthalmol 97: 937-947.  
Edelhauser HF, Hyndiuk RA, Zeeb A, Schultz RO. (1982): Corneal edema and the 
intraocular use of epinephrine. Am J Ophthalmol 93: 327-333.  
Gurbaxani A, Packard R. (2007): Intracameral phenylephrine to prevent floppy iris 
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Cataract Surgery 
 
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Jacobs DS, Cox TA, Wagoner MD, Ariyasu RG, Karp CL. (2006): Capsule staining as an 
adjunct to cataract surgery: a report from the American Academy of 
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Manvikar S, Allen D. (2006): Cataract surgery management in patients taking tamsulosin 
staged approach. J Cataract Refract Surg 32: 1611-1614.  
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intracameral nonpreserved epinephrine hydrochloride 1:4000 [corrected] for 
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580-582.  
Myers WG, Shugar JK. (2009): Optimizing the intracameral dilation regimen for cataract 
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35: 273-276.  
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floppy iris syndrome in the United Kingdom. Eye 21: 443-444.  
Nichamin LD. (1993): Enlarging the pupil for cataract extraction using flexible nylon iris 
retractors. J Cataract Refract Surg 19: 793-796.  
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corneal cataract surgery. J Cataract Refract Surg 28: 596-598.  
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Ophthalmol Scand 83: 624-626.  
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intraocular lens repositioning with intracameral epinephrine. J Cataract Refract 
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Site-Directed and Random Insertional Mutagenesis in Medically Important Fungi

Inherited Connective Tissue Disorders of Collagens: Lessons from Targeted Mutagenesis

Prevention and Management of Intraoperative Floppy Iris Syndrome

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