Intraoperative Floppy Iris Syndrome (IFIS)

Key Points at a Glance

Key Points of This Disease

• Intraoperative floppy iris syndrome (IFIS) presents with the triad of “iris billowing,” “progressive miosis,” and “iris prolapse” during cataract surgery.
• The representative causative drug is tamsulosin, and a history of taking α1-adrenergic receptor blockers is the greatest risk factor.
• Occurs in approximately 1-2% of all cataract surgeries, with reported prevalence ranging from 2% to 12.6%.
• Atrophy of the iris dilator muscle caused by α1-blockers is irreversible and cannot be prevented by preoperative discontinuation of the drug.
• The most important preventive measure is obtaining a preoperative medication history, allowing anticipation of IFIS and implementation of countermeasures.
• Management options include viscoelastic substances, intracameral phenylephrine, iris retractors, and pupil expansion rings.
• With appropriate measures, surgery can be performed safely, but if unrecognized or unanticipated, the complication rate increases.

1. What is Intraoperative Floppy Iris Syndrome (IFIS)?

Intraoperative floppy iris syndrome (IFIS) is a complication during cataract surgery first reported by Chang and Campbell in 2005 ⁵⁾. In patients taking α1-adrenergic receptor blockers, which are used to treat benign prostatic hyperplasia, the following triad occurs:

• Billowing of the iris with irrigation fluid: The relaxed iris stroma billows in response to normal intraocular irrigation.
• Progressive miosis: The pupil gradually becomes smaller during surgical manipulation.
• Iris prolapse or incarceration: The iris protrudes toward the incision or side port.

IFIS occurs in approximately 1.1% of all cataract surgeries ⁶⁾. The prevalence in patients undergoing phacoemulsification ranges from 2% to 12.6%. The reported prevalence of IFIS or iris prolapse is 0.5-2.0% ³⁾. This variability is due to subjective clinical definitions, the continuous nature of severity, and changes in prescribing rates of related medications.

When IFIS is unrecognized or unanticipated, the rate of surgical complications is higher ²⁾³⁾. It is important to check for a history of α1-blocker use preoperatively and anticipate the occurrence of IFIS.

Q Does IFIS occur in surgeries other than cataract surgery?

A

IFIS is most problematic in cataract surgery (phacoemulsification). Iris relaxation may affect other intraocular surgeries involving iris manipulation, but the phenomenon is clinically defined and reported during cataract surgery.

2. Main Symptoms and Clinical Findings

Subjective Symptoms

IFIS itself is an intraoperative phenomenon, and patients’ preoperative subjective symptoms are limited.

• Poor dilation: Poor response to preoperative dilating drops.
• Postoperative photophobia: If iris damage occurs, patients may complain of photophobia after surgery.

If extensive iris defects result from severe IFIS-related iris damage, visual disturbances such as blurred vision, photophobia, and glare may persist postoperatively⁴⁾.

Clinical Findings

The severity of IFIS is classified as follows.

Mild

Iris billowing only: The iris stroma billows in response to irrigation fluid, but no significant miosis or prolapse is observed.

Moderate

Iris billowing + miosis: In addition to billowing, progressive intraoperative miosis is observed. Visualization becomes somewhat difficult.

Severe

All three signs present: Iris billowing, marked miosis, and strong iris prolapse tendency are observed. The risk of complications is highest.

In IFIS, the iris is elastic and dilation cannot be maintained even with mechanical stretching, which distinguishes it from other causes of small pupils. Pupil stretching and sphincterotomy are ineffective²⁾¹⁰⁾.

Intraoperative risks of IFIS include the following.

• Difficulty in capsulotomy: The small pupil restricts the capsulotomy diameter, increasing the risk of capsular edge damage.
• Reduced visibility: The red reflex is diminished, making it difficult to visualize the lens and capsule.
• Iris damage: The iris may be damaged by accidental aspiration or iris prolapse into the wound during surgery. A small pupil is the most important intraoperative risk factor for iris damage³⁾.

3. Causes and Risk Factors

The most common cause of IFIS is alpha-1 adrenergic receptor antagonists (α1-ARAs) used to treat benign prostatic hyperplasia (BPH). There are three subtypes of α1 receptors: A, B, and D. The α1-A subtype is the main regulator of the iris dilator muscle.

Causative Medications

Drug Class	Representative Drugs	IFIS Risk
Selective α1-ARAs	Tamsulosin, Silodosin	High
Non-selective α1-ARAs	Doxazosin, Terazosin	Moderately low
Others	Finasteride, saw palmetto	Low

• Tamsulosin: The most frequent drug causing IFIS. It has high selectivity for the α1-A subtype and selectively blocks the iris dilator muscle ⁷⁾. Its half-life is 48–72 hours, but sustained blockade causes disuse atrophy of the dilator muscle. This degeneration is irreversible and cannot be prevented by discontinuation. Patients taking tamsulosin have a significantly higher incidence of IFIS compared to those taking doxazosin ⁸⁾. It shows sustained pharmacological action on the iris dilator muscle, and IFIS findings may persist even after discontinuation ⁹⁾.
• Silodosin, naftopidil: Newer drugs with α1-A selectivity similar to tamsulosin. IFIS risk has been reported.
• Non-selective α1-ARAs (doxazosin, terazosin, prazosin): Low affinity for α1-A, weaker association with IFIS compared to tamsulosin.
• Others: Finasteride, saw palmetto (Serenoa repens), antipsychotics, etc. have also been reported to be associated ²⁾. Large cohort studies have confirmed that use of selective α1-blockers including tamsulosin is associated with risk of serious ocular complications such as posterior capsule rupture and vitreous loss after cataract surgery ¹⁵⁾.

Other risk factors

• Aging: Risk increases with age due to iris vascular dysfunction and changes in norepinephrine efficacy.
• Diabetes: Autonomic neuropathy partially denervates the pupillary dilator muscle.
• Reduced preoperative pupil dilation: Regardless of α1-ARA use, decreased pupil diameter is associated with IFIS risk. In tamsulosin users, a dilated pupil diameter of 6.5 mm or less is a predictor of IFIS.
• Other causes of small pupil: Pseudoexfoliation syndrome, uveitis, glaucoma, trauma, history of miotic eye drops, previous intraocular surgery, etc. can also cause small pupils and may require similar intraoperative management as IFIS ³⁾.

Prevention and daily care

• If you are planning to undergo cataract surgery, be sure to inform your ophthalmologist of any history of taking medications for benign prostatic hyperplasia (such as tamsulosin, silodosin, etc.).
• Even if you have taken them in the past, you must report it. Discontinuation does not reverse the effects on the iris.
• Inform your urologist about the planned cataract surgery and discuss the choice of medications.

Q Can IFIS be prevented by discontinuing tamsulosin?

A

Atrophy of the iris dilator muscle caused by α1-blockers is irreversible, and discontinuing the drug before surgery does not reduce the risk of IFIS. Preoperative medication history review and appropriate intraoperative measures are important.

4. Diagnosis and Examination Methods

IFIS is not a disease that can be definitively diagnosed before surgery; it is determined by preoperative risk assessment and intraoperative clinical findings.

Preoperative Risk Assessment

• Medication history: Check current and past use of α1-adrenergic receptor blockers. Since a risk assessment and classification system for IFIS has not yet been established, evaluate the medication history together with other risk factors comprehensively ³⁾.
• Pupil dilation test: Check the preoperative pupil dilation diameter. Poor dilation is a predictor of IFIS.
• Observation of iris characteristics: Use a slit lamp microscope to observe thinning of the iris stroma and loss of tone.

Intraoperative Judgment

IFIS is diagnosed when any of the following three signs are observed, and countermeasures should be initiated.

• Billowing of the iris stroma in response to irrigation fluid
• Progressive intraoperative miosis
• Tendency for iris prolapse through the incision or side port

Q Can IFIS occur in women?

A

The reason it is more common in men is that α1-blockers are used to treat BPH. However, α1-blockers may also be prescribed to women for urinary retention or hypertension, and they can develop IFIS. Preoperative medication history taking is important regardless of gender.

5. Standard Treatment

Management of IFIS consists of two stages: preoperative preventive measures and intraoperative management.

Preoperative Preventive Measures

• Medication history review and information sharing: Always check for a history of α1-blocker use. Although there is no clear benefit from discontinuing the medication, some reports recommend switching to a non-selective α1-ARA (e.g., alfuzosin).
• Enhanced preoperative mydriasis: Use topical mydriatics such as high-concentration cyclopentolate (2%) or phenylephrine (10%). For patients taking tamsulosin, preoperative 1% atropine eye drops (4 times daily) for one week may be useful.
• Preoperative NSAID eye drops: Preoperative use of flurbiprofen or ketorolac is also supported to block prostaglandins that promote intraoperative miosis.

Intraoperative Management

The most effective intraoperative management for IFIS is to frequently use a well-retained ophthalmic viscosurgical device to stabilize the iris, while completing phacoemulsification and cortical aspiration as quickly as possible with the lowest possible irrigation pressure.

Pharmacological Measures

• Intracameral phenylephrine: Intracameral administration of phenylephrine, an α1-receptor agonist, is effective for promoting mydriasis and managing IFIS¹⁾. Low concentration (0.31%, combined with anticholinergic and lidocaine) is used for maintaining mydriasis, while high concentration (1–1.25%) is used for IFIS management¹⁾.

In a systematic review by Chua et al. (2024), intracameral phenylephrine doses of 0.62–9 mg were not associated with systemic adverse events in randomized controlled trials¹⁾. Compared to topical administration, intracameral administration results in less systemic absorption; the detection rate of phenylephrine in blood was 100% in the topical 10% group versus 14.3% in the intracameral 0.31% group¹⁾.

• Intracameral epinephrine irrigation: Intracameral injection of 1:10,000 preservative-free epinephrine solution promotes mydriasis. Epinephrine-supplemented irrigation fluid is effective for maintaining mydriasis in IFIS cases¹³⁾.
• Sub-Tenon injection of 2% lidocaine: There are reports that it reduces the occurrence of IFIS signs in patients taking α-blockers.

Use of Ophthalmic Viscosurgical Devices (OVD)

• Cohesive viscoelastic (e.g., Healon V®) for viscomydriasis: Effectively dilates the small pupil and provides a physical barrier to prevent iris prolapse and inversion. However, low aspiration flow rate and low vacuum settings are required.
• Dispersive viscoelastic (e.g., Viscoat®): For iris incarceration in the side port, locally placed between the wound and the iris to relieve and prevent incarceration.
• Modified soft-shell technique: Injecting dispersive viscoelastic peripherally and cohesive viscoelastic centrally enhances intraoperative mydriasis stability when high vacuum is needed for a hard nucleus.

Surgical Technique Modifications

• Optimizing wound construction: Ensure a sufficient corneal internal valve to prevent iris incarceration. Side ports should also be made slightly more corneal. Incomplete wound construction can cause iris prolapse independent of IFIS, so ensure adequate tunnel length, incision width matching the tip, and avoid a posterior incision start.
• Careful hydrodissection: In IFIS, the adhesion between the capsule and cortex tends to be strong. Perform gently step by step to prevent iris prolapse.
• Fluid control: Lower irrigation and aspiration flow rates to minimize the impact of fluid on the iris. Specifically, set the bottle height low, aim for aspiration pressure <200 mmHg, and aspiration flow rate <26–30 mL/min. Remove nuclear fragments at or anterior to the iris plane, directing irrigation fluid anterior to the iris. In severe cases, turn off the irrigation bottle before removing the ultrasound tip from the eye to lower intraocular pressure.
• Caution during IOL insertion: Operate the injector cartridge bevel-up to prevent iris entrapment.

Pupil Expansion Devices

The first choice of auxiliary device for IFIS is an iris retractor or a pupil expansion ring. Either can provide a wide field of view with a pupil diameter of 6.0 mm or more.

Pupil Expansion Ring

Malyugin Ring®: Available in two sizes: 6.25 mm and 7.0 mm. Can be inserted through a small incision using an injector. Minimally invasive as it does not overstretch the iris.

I-Ring®: One size of 7 mm. A square ring made of polypropylene that evenly expands the pupil margin.

Iris Retractor

Iris retractor: Nylon or polypropylene hooks. Four hooks are placed in a diamond configuration to dilate the pupil.

Advantages: The degree of dilation can be freely adjusted. There is a recommended placement method by the ASCRS committee ²⁾.

Management method	Certainty	Ease of use	Risk of iris damage
Viscoelastic substance	Low	Easy	None
Hook	Somewhat low	Difficult	Low
Iris retractor	High	Somewhat difficult	Low

Supplement on Device Selection in IFIS

Iris hook types require many corneal ports and carry a risk of multiple incarcerations in IFIS. Pupil expansion ring types are considered a safer option for IFIS. However, in eyes with shallow anterior chamber, placement of a pupil expansion ring (e.g., I-Ring®) may be difficult, and selection according to the case is necessary.

Management of Iris Prolapse

If iris prolapse occurs, manage with the following steps:

1. Lower intraocular pressure by draining aqueous humor from a side port.
2. Push the iris back from outside the wound using a spatula or hook. Attempting to pull it from inside the anterior chamber with viscoelastic material may worsen the prolapse.
3. Inject a high-retention viscoelastic material below the iris to return the iris into the eye. Avoid touching the iris with instruments as much as possible.
4. If the wound width is larger than the tip, place a temporary 8-0 silk suture to prevent leakage of irrigation fluid.
5. If prolapse persists, perform a peripheral iridectomy to create an escape route for irrigation fluid from the posterior chamber to the anterior chamber.
6. If the iris does not return at the end of surgery, inject air into the anterior chamber. Be cautious because excessive air can cause reverse pupillary block after a few hours.

For iris prolapse reduction in IFIS, the tassel method has been attempted ¹²⁾.

Cautions in Treatment

• Pupillary margin incision or mechanical pupil stretching is of low efficacy in IFIS and may worsen iris damage or miosis; therefore, avoid these maneuvers ¹¹⁾.
• In severe IFIS, the risk of iris prolapse and damage is high; if unexpected, posterior capsule rupture or nuclear drop may occur.
• Extensive iris damage may lead to persistent photophobia postoperatively. Management of iatrogenic iris defects requires specialized intervention ¹⁴⁾. In severe cases, artificial iris implantation may be considered ⁴⁾.
• Excessive administration of intracameral phenylephrine carries a risk of systemic cardiovascular adverse events (e.g., hypertension, arrhythmia). It is recommended to administer repeated doses of 0.25 mL or less and to minimize spillage ¹⁾.
• When repositioning iris prolapse, injecting viscoelastic material from the anterior chamber to pull it back tends to worsen the prolapse. The principle is to push it back from outside the wound.
• Injecting a large amount of air into the anterior chamber may cause reverse pupillary block several hours later.

Q Can cataract surgery be safely performed while taking an alpha-1 blocker?

A

With appropriate preoperative evaluation and intraoperative measures, surgery can be performed safely. It is important to inform the ophthalmologist about the history of alpha-1 blocker use before surgery. Discontinuing the medication does not prevent IFIS, so surgery should proceed with countermeasures in place.

6. Pathophysiology and Detailed Mechanism

The core mechanism of IFIS is pharmacological blockade of alpha-1 adrenergic receptors (especially the alpha-1A subtype) in the iris dilator muscle.

Alpha-1 Receptor Blockade and Iris Dilator Muscle Degeneration

Tamsulosin has high selectivity for the alpha-1A subtype. This subtype is abundantly expressed not only in the smooth muscle of the prostatic urethra but also in the iris dilator muscle. Sustained receptor blockade leads to the following changes:

• Disuse atrophy of the dilator muscle: Normal smooth muscle tone is lost, and the iris becomes flaccid.
• Irreversible structural changes: Long-term use causes permanent anatomical changes in the iris dilator muscle. Even after discontinuing the medication, it does not fully recover.
• Interaction with melanin: Some reports suggest that the interaction between the drug and melanin contributes to atrophy of the iris dilator muscle.

Intraoperative Effects

Relaxation of the iris dilator muscle results in insufficient pharmacological mydriasis before surgery. During surgery, the triad manifests through the following mechanisms:

• Iris billowing: The flaccid iris stroma is easily flipped by the flow of irrigation fluid.
• Progressive miosis: Because the dilator muscle lacks tone, it cannot counteract the constriction of the pupillary sphincter caused by surgical manipulation.
• Iris prolapse: The flaccid iris is pushed out through the wound along with the irrigation fluid.

Adhesion between the capsule and the cortex also tends to be strong, and forceful injection of irrigation fluid during hydrodissection can easily induce iris prolapse.

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7. Latest Research and Future Perspectives (Investigational Reports)

For patients: Please read this

The following content is currently under investigation or in clinical trials and is not standard treatment available at general hospitals. It is reference information for professionals regarding future medical developments.

Optimal Concentration of Intracameral Phenylephrine

The safe and effective optimal concentration of intracameral (IC) phenylephrine has not yet been fully studied.

A systematic review by Chua et al. (2024) showed that low concentrations (0.31%, combined with anticholinergic agents and lidocaine) are often sufficient for initial mydriasis, but higher concentrations (1–1.25%) may be necessary for IFIS management ¹⁾. In a prospective randomized contralateral eye comparison study by Lorente et al. (2012), the IC phenylephrine 1.5% group had 0% IFIS signs, whereas the placebo group had 88.09% IFIS signs ¹⁶⁾.

In the future, accumulation of randomized controlled trials comparing different concentrations of IC phenylephrine is needed.

Iris Reconstruction with Iris Prosthesis

For cases with extensive iris defects due to severe iris damage associated with IFIS, implantation of a foldable artificial iris is being considered.

Watanabe et al. (2023) reported a case of an 81-year-old man who developed extensive iris defects due to severe IFIS during cataract surgery and underwent fixation of a foldable artificial iris (Iris Prosthesis Model C0, Ophtec) in the ciliary sulcus ⁴⁾. Corrected visual acuity of 20/25 was achieved at 3 months postoperatively, with improvement in glare and photophobia. However, corneal endothelial damage was observed postoperatively, and further improvement in insertion technique was concluded to be necessary.

Long-term complications of artificial iris include residual iris retraction syndrome (RITS), glaucoma, chronic inflammation, etc., and long-term follow-up is required ⁴⁾.

FLACS (Femtosecond Laser-Assisted Cataract Surgery) and IFIS

Femtosecond laser-assisted cataract surgery (FLACS) has been reported to have a higher incidence of intraoperative miosis compared to conventional phacoemulsification. The indications and management strategies for FLACS in IFIS cases remain topics for future investigation.

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8. References

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2. American Academy of Ophthalmology. Cataract/Anterior Segment Preferred Practice Pattern. Ophthalmology. 2021.
3. European Society of Cataract and Refractive Surgeons (ESCRS). ESCRS Cataract Surgery Guideline. 2024. URL: https://www.escrs.org/escrs-guideline-for-cataract-surgery/
4. Watanabe N, Kobayakawa S. A case of foldable artificial iris implantation for treatment of postcataract surgery aniridia. Case Rep Ophthalmol. 2023;14:7-12.
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10. Chang DF. Intraoperative floppy iris syndrome. Curr Opin Ophthalmol. 2008;19:37-44.
11. Chang DF, Braga-Mele R, Mamalis N, et al. ASCRS White Paper: clinical review of intraoperative floppy-iris syndrome. J Cataract Refract Surg. 2008;34:2153-2162. doi:10.1016/j.jcrs.2008.08.031.
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13. Shugar JK. Use of epinephrine for IFIS prophylaxis. J Cataract Refract Surg. 2006;32:1074-1075.
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16. Lorente R, de Rojas V, Vazquez de Parga P, et al. Intracameral phenylephrine 1.5% for prophylaxis against intraoperative floppy iris syndrome: prospective, randomized fellow eye study. Ophthalmology. 2012;119:2053-2058. PMID: 22709418. doi:10.1016/j.ophtha.2012.04.028.