Irrigation Misdirection Syndrome

Key Points at a Glance

Key Points of This Complication

• Infusion misdirection syndrome (IMS) is a serious intraoperative complication during cataract surgery in which infusion fluid (BSS) accumulates through the zonular gaps into the posterior chamber and vitreous cavity, causing sudden anterior chamber collapse and elevated intraocular pressure ^1,2).
• Synonyms include infusion misdirection syndrome, aqueous misdirection, and acute fluid misdirection syndrome (FMS); the chronic form is continuous with malignant glaucoma ^2,3).
• The incidence is approximately 1–1.5% of cataract surgeries, typically occurring in elderly women, hyperopic eyes, and eyes with short axial length ⁴⁾.
• The mechanism involves movement of infusion fluid into Berger’s space and vitreous cavity through discontinuities in the Wieger ligament attachment, followed by secondary ciliary block ^2,5).
• Initial management includes immediate cessation of infusion, removal of viscoelastic material from the wound, and fundus examination to rule out suprachoroidal hemorrhage and choroidal detachment ³⁾.
• Cases that do not improve with conservative treatment require 23-gauge needle aspiration via pars plana, anterior vitrectomy, Nd:YAG laser anterior hyaloidotomy, and ultimately zonulo-hyaloido-vitrectomy ^5,7).
• As preventive measures for high-risk eyes, infusion hydrodissection, low infusion pressure setting, prophylactic anterior vitrectomy, and monitoring of the fellow eye are recommended ⁸⁾.

1. What is infusion misdirection syndrome?

Definition

Infusion misdirection syndrome (IMS) is an intraoperative complication during cataract surgery in which the infusion fluid (balanced salt solution; BSS) deviates from the normal outflow pathway from the anterior chamber into the posterior vitreous cavity, causing sudden shallowing of the anterior chamber and elevation of intraocular pressure ^1,2).

This condition was first reported by Mackool in 1993 ¹⁾. Multiple synonyms exist, and different terms are used in the literature.

Term	Proponent/Source	Characteristics
Infusion misdirection syndrome	Mackool 19931)	Emphasizes acute intraoperative condition
Irrigation misdirection syndrome (IMS)	Widely used in Japanese literature	Emphasizes deviation of irrigation fluid pathway
Aqueous misdirection syndrome	Classical term	Posterior misdirection of aqueous humor or irrigation fluid
Acute fluid misdirection syndrome (FMS)	Grzybowski 20182)	Unified pathophysiological term
Acute intraoperative rock-hard eye syndrome	Lau 20144)	Emphasizes hardening of the eyeball
Malignant glaucoma	von Graefe 1869	Chronic type, postoperative onset type

History

The concept of malignant glaucoma was first described by von Graefe in 1869 ⁹⁾. The acute type occurring during cataract surgery was first named “infusion misdirection syndrome” by Mackool in 1993, defined as abnormal migration of irrigation fluid during phacoemulsification ¹⁾.

Subsequently, Grzybowski et al. in 2018 proposed a unified concept based on pathophysiology as acute and chronic fluid misdirection syndrome ²⁾. In 2020, intraoperative OCT (iOCT) directly observed the movement of irrigation fluid into the Berger space, confirming the pathomechanism ⁵⁾.

Epidemiology

• The incidence was reported by Lau 2014 as 6 eyes out of 413 eyes (1.45%) ⁴⁾.
• In the case series by Varma 2014, all 18 cases (20 eyes) were female, mean age 44–86 years, mean axial length 21.30±1.40 mm, preoperative ACD unknown ¹⁰⁾.
• Commonly occurs in elderly women, hyperopic eyes, and eyes with narrow angles^4,10).
• A chronic form may develop weeks to years after surgery, with myopic shift (myopic surprise) sometimes being the only initial finding¹¹⁾.

Q Are fluid misdirection syndrome and malignant glaucoma the same disease?

A

Both are understood as a continuous disease spectrum. Fluid misdirection syndrome is an acute condition during cataract surgery, where the irrigating fluid acts as the direct trigger. Malignant glaucoma is a chronic condition occurring weeks to years postoperatively, with aqueous humor itself misdirected posteriorly. Mechanistically, both involve ciliary block via the anterior hyaloid membrane. Grzybowski et al. have proposed a unified concept treating both as acute and chronic fluid misdirection syndrome²⁾.

2. Main Symptoms and Intraoperative Findings

Typical Intraoperative Findings

IMS occurs suddenly during surgery. The most characteristic finding is a sudden shallowing of the anterior chamber and hardening of the eyeball ^2,4).

Anterior chamber shallowing

Finding: The posterior capsule suddenly moves forward, making cortical aspiration or nuclear fragment removal difficult.

Characteristic: The anterior chamber does not deepen even after injecting ophthalmic viscosurgical device (OVD). The injected OVD is pushed back into the posterior chamber ³⁾.

Rock-hard eye

Finding: When palpated, the eyeball feels as hard as a brick.

Intraocular pressure: Markedly elevated. Lau et al. emphasize acute intraocular pressure elevation during surgery as a diagnostic finding ⁴⁾.

Anterior iris movement and prolapse

Finding: The iris bulges forward, with repeated prolapse through the wound.

Differential diagnosis: Similar findings can occur with simple posterior chamber pressure elevation (retrobulbar hemorrhage, lid speculum compression), so the cause must be investigated ²⁾.

Poor surgical field

Finding: Visibility is reduced due to corneal distortion/edema and repeated anterior chamber collapse and reperfusion.

Course: Continuing the operation increases the risk of posterior capsule rupture, nucleus drop, and choroidal hemorrhage³⁾.

Findings in the postoperative-onset type

The chronic and postoperative-onset types present the following findings^10,11).

• Shallow anterior chamber (ACD < 2.5mm)
• Moderate to severe intraocular pressure elevation (often 20–40 mmHg)
• Myopic surprise: refractive change due to anterior displacement of the lens/IOL
• Angle closure (without pupillary block)
• No signs of suprachoroidal hemorrhage or choroidal detachment

In one case report, IMS was diagnosed several years later based solely on myopic shift even with a relatively deep anterior chamber¹¹⁾.

Q What intraoperative findings should raise suspicion for IMS?

A

During nuclear processing or cortical aspiration, if the previously stable anterior chamber suddenly becomes shallow and does not reform with OVD injection, IMS should be strongly suspected. Characteristic features include elevated intraocular pressure, a hard eye to palpation, and forward movement of the iris. However, similar findings can occur with suprachoroidal hemorrhage or acute choroidal effusion, so immediate fundus examination is necessary for differentiation³⁾.

3. Causes and Risk Factors

Anatomical Risk Factors

IMS tends to occur in eyes with specific axial and anatomical features ^2,4,10).

Risk Factor	Mechanism/Association
Short axial length (<22mm, especially <21mm)	Smaller volume for irrigating fluid; even slight misdirection can cause pressure elevation
Hyperopia (+6D or more)	Correlated with short axial length
Nanophthalmos	Triple risk: scleral thickening + choroidal congestion + short axial length8)
Shallow anterior chamber (ACD < 2.5mm)	Limited anterior chamber space
Angle-closure glaucoma / PACG	Has anterior chamber structural abnormalities
Plateau iris	Ciliary body/lens position abnormality
Elderly female	Statistical predominance4,10)

Acquired risk factors

• Pseudoexfoliation syndrome (PXF): Associated with zonular weakness and predisposes to IMS. In a few reported cases, multiple patients had PXF as a background ¹²⁾.
• Intraoperative floppy iris syndrome (IFIS): Occurs in patients taking α1-blockers. Combined with iris prolapse and miosis, it makes surgery difficult.
• Zonular weakness: Caused by trauma, exfoliation, high myopia, or previous vitrectomy.
• History of IMS in the fellow eye: High risk of recurrence ⁸⁾.
• Topiramate use: Reported to induce aqueous misdirection in nanophthalmic eyes ¹³⁾.

Factors related to intraoperative manipulation

• High perfusion pressure setting
• Repeated BSS leakage from the wound and anterior chamber collapse
• Excessive residual ophthalmic viscosurgical device
• Hydrodissection via side port (OVD does not escape externally, causing increased intracapsular pressure)
• IMS is more likely to occur in cases with anterior vitreous detachment

Occurrence in high myopia

Conventionally, IMS was considered a complication of short axial length eyes, but in 2025, the first case of onset during ICL implantation in high myopia (long axial length) was reported ¹⁴⁾. It has been shown that it can also occur in long axial lengths, and mechanistically, inappropriate movement of irrigation fluid was confirmed as a common factor.

Q In which patients should the risk of irrigation fluid misdirection syndrome be assessed preoperatively?

A

In cases with axial length less than 22 mm (especially less than 21 mm), preoperative ACD less than 2.5 mm, hyperopia +6 D or more, primary angle closure glaucoma, nanophthalmos, or a history of the condition in the fellow eye, preoperative risk assessment should be performed and intraoperative preparations made. Exfoliation syndrome increases the risk of onset in conjunction with intraoperative zonular weakness, so it should be evaluated separately ^2,4,8).

4. Diagnosis and differential diagnosis

Intraoperative diagnostic algorithm

IMS must be diagnosed immediately based on intraoperative findings and exclusion diagnosis ^2,3).

1. First step: Recognize sudden anterior chamber collapse and intraocular pressure elevation during nucleus aspiration or cortical aspiration.
2. Second step: Immediately stop irrigation and suspend all maneuvers.
3. Third step: Attempt to remove viscoelastic material from the wound or inject into the anterior chamber, and observe the response. If the anterior chamber deepens with OVD, it is transient mechanical shallow anterior chamber, and IMS is unlikely.
4. Fourth step: Perform fundus examination to rule out suprachoroidal hemorrhage, acute choroidal effusion, and choroidal detachment.
5. Fifth step: If these are excluded, diagnose intraoperative IMS.

Major Differential Diagnoses

Suprachoroidal Hemorrhage

Findings: Sudden shallowing of the anterior chamber, severe eye pain (during awake surgery), dome-shaped elevation of the fundus, dark red reflex

Urgency: Most severe. Surgery must be stopped and immediate hemostasis is required

Differentiation: Can be confirmed by fundus examination³⁾

Acute Choroidal Effusion

Findings: Posterior capsule bulge, difficulty in cortical aspiration, choroidal detachment

Mechanism: Suprachoroidal fluid accumulation due to increased choroidal vascular permeability

Course: Serous, not hemorrhagic. Discontinue surgery and wait until choroidal detachment resolves³⁾

Retrobulbar hemorrhage / retrobulbar anesthesia complication

Findings: Proptosis, elevated posterior chamber pressure, findings resembling lid speculum compression

Differentiation: Differs from IMS in that it improves with loosening the lid speculum or removing pressure

Simple mechanical shallow anterior chamber

Findings: Imbalance between infusion and aspiration, wound leakage

Differentiation: Improves with setting changes or temporary wound suturing. Differs from IMS in that the anterior chamber deepens with OVD

Diagnosis of chronic and postoperative types

Diagnosis of postoperative IMS or malignant glaucoma requires the following ^10,11).

• Coexistence of shallow anterior chamber and elevated intraocular pressure
• No findings of pupillary block despite peripheral iridotomy (LPI) having been performed
• Exclusion of suprachoroidal hemorrhage, tumor, and uveitis
• Confirmation of anterior rotation of the ciliary body and anterior displacement of the lens or IOL by UBM¹⁵⁾
• Quantification of myopic shift by refraction testing

Since the report by Tello et al., UBM has been established as the first-line imaging test for diagnosing pseudophakic malignant glaucoma¹⁵⁾.

Q What is the method for immediate differentiation between IMS and suprachoroidal hemorrhage during surgery?

A

Both conditions present with anterior chamber loss and elevated intraocular pressure, but suprachoroidal hemorrhage is characterized by severe eye pain (under local anesthesia), dark red fundus reflex, and dome-shaped choroidal elevation. The fundus is observed using an indirect ophthalmoscope or surgical microscope at maximum magnification, and differentiation is made based on the presence or absence of choroidal findings. If B-mode ultrasonography can be performed immediately, a definitive diagnosis is possible ^2,3).

5. Standard Management

Stepwise Approach for Intraoperative Management

Once IMS is diagnosed, the following stepwise management is performed ^2,3,4).

Step 1: Conservative Management

1. Immediate cessation of infusion
2. Temporary suturing of the wound and side port (to minimize leakage)
3. Removal of OVD from the wound (if remaining)
4. Intravenous hyperosmotic agent: 20% mannitol 1.0–1.5 g/kg infused over 30–60 minutes
5. Carbonic anhydrase inhibitor: acetazolamide 250–500 mg orally or intravenously
6. Instillation of mydriatic/cycloplegic eye drops (atropine 1%)
7. Waiting for about 1 hour

Conservative management is said to resolve many cases. In a Korean 2021 study, all three cases were able to complete IOL insertion on the same day with mannitol infusion and acetazolamide ¹²⁾.

Step 2: Mechanical decompression

If the anterior chamber does not recover with conservative management, consider the following ⁴⁾.

• Vitreous aspiration via pars plana: Insert a 23G needle into the vitreous cavity through the pars plana 3.5 mm posterior to the limbus, and aspirate 0.2–0.5 mL of fluid with a 3 cc syringe. This immediately reduces vitreous pressure and deepens the anterior chamber ⁴⁾.

Step 3: Anterior vitrectomy

If there is no improvement or recurrence after mechanical decompression ^5,6).

• Anterior vitrectomy via the anterior chamber: Resect the anterior vitreous from the anterior chamber side using a 25G or 27G trocar.
• Pars plana anterior vitrectomy: Approach via the pars plana using a trocar.
• Simultaneous resection of the anterior vitreous membrane, zonules, and peripheral iris (zonulo-hyaloido-vitrectomy; ZHV).

Bitrian and Caprioli recommend a combination of PPV + ZHV + iridectomy. This is radical in that it permanently secures communication between the anterior and posterior chambers ⁶⁾.

Postoperative Management

In cases where IMS occurs intraoperatively, the following management is required postoperatively.

• Evaluate slit-lamp findings, intraocular pressure, anterior chamber depth, and fundus findings on postoperative days 1 and 2.
• Continue atropine 1% eye drops (for 1–2 weeks).
• Continue aqueous suppressants.
• Watch for chronicity (re-elevation after days to weeks).

Wiedenmann et al. reported that malignant glaucoma after cataract surgery can become chronic in some cases, emphasizing the need for long-term follow-up ¹⁶⁾.

Treatment of Pseudophakic Malignant Glaucoma

For malignant glaucoma occurring weeks to years after surgery, stepwise treatment is standard ¹⁰⁾.

Treatment Step	Details
1. Medical therapy	Mydriatic/cycloplegic agents (atropine), aqueous suppressants, hyperosmotic agents. Miotics are contraindicated.
2. Laser therapy	Nd:YAG iridozonulohyaloidotomy. Penetrates the posterior capsule and anterior hyaloid face to create communication between the anterior and posterior chambers.
3. AC reformation / IOL pushback	Reform the anterior chamber with OVD and push the IOL posteriorly
4. Vitrectomy	PPV + ZHV + iridectomy. Last resort but highly curative 6)
5. Cyclophotocoagulation	Diode cyclophotocoagulation. Modifies the ciliary-hyaloid interface 17)

In a study of 18 cases (20 eyes) by Varma et al., 2 eyes were managed with medication alone, 7 with laser, 6 with anterior chamber reformation and IOL pushback, and 5 required vitrectomy ¹⁰⁾. Dave et al. also reported that medication alone is often insufficient in many cases ¹⁸⁾.

Q If IMS occurs during surgery, should the surgery be stopped or continued?

A

The decision depends on the stepwise response. If the anterior chamber deepens with conservative management using mannitol infusion and acetazolamide, surgery can be carefully continued to complete IOL insertion. In Korean 2021, all 3 cases were completed on the same day ¹²⁾. Conversely, if there is no improvement with conservative management, surgery should be stopped, and a second surgery or combined procedure with PPV and ZHV should be planned on another day ²⁾. If choroidal detachment or suprachoroidal hemorrhage is observed in the fundus, surgery should be immediately stopped ³⁾.

6. Pathophysiology

Abnormal pathway of irrigation fluid

In normal cataract surgery, irrigation fluid flows from the anterior chamber out of the eye through the wound and side ports. In IMS, part of the irrigation fluid enters the posterior segment through the following pathways ^2,5).

1. Entry route: gaps between zonular fibers
2. Intermediate reservoir: Berger’s space, bounded by the posterior lens surface and Wieger’s ligament (hyaloideocapsular ligament)
3. Final destination: across the anterior hyaloid membrane via discontinuities in Wieger’s ligament attachment, accumulating in the vitreous cavity or around the vitreous gel

In an intraoperative OCT (iOCT) study by Grzybowski 2020, accumulation of fluid and fine particles (lens fragments, triamcinolone) in Berger’s space was confirmed in multiple cases at the end of cataract surgery, providing imaging evidence for the pathogenic mechanism of IMS⁵⁾.

Formation of ciliary block

Fluid accumulation in the vitreous cavity establishes the following vicious cycle²⁾.

1. Increased intravitreal pressure → anterior hyaloid membrane moves forward
2. Anterior displacement of lens, IOL, and iris → anterior chamber loss
3. Angle closure → obstruction of aqueous outflow
4. Irrigation fluid cannot return to anterior chamber, flows posteriorly again through zonular spaces → vicious cycle

This is the pathological entity called ciliary block / cilio-lenticular block. The anterior hyaloid membrane acts as a physical barrier, obstructing normal aqueous humor movement from the posterior chamber to the anterior chamber²⁾.

Anatomical vulnerability in short axial length eyes

Grzybowski and Kanclerz explained the reduced efficiency of perfusate movement in short axial length eyes as follows ²⁾.

• In normal eyes, diffusion of aqueous humor and perfusate within the vitreous gel occurs in a donut-shaped region (diffusional zone) between the ciliary body margin and the central lens-vitreous adhesion surface.
• In short axial length eyes, this region is only about half that of normal eyes.
• The return pathway for perfusate after it moves into the vitreous is narrow, making it prone to accumulation.
• As a result, pressure elevation and anterior chamber shallowing progress rapidly.

Compression mechanism of the vitreous gel

When fluid enters the vitreous cavity, the vitreous gel itself becomes compressed ²⁾.

• The vitreous is a semi-solid gel structure, and its volume decreases with fluid infiltration.
• Compressed vitreous has reduced fluid conductivity, further decreasing the return pathway.
• A vicious cycle of compression and fluid accumulation progresses.

This gel compression phenomenon is the essence of the rapid course of IMS.

7. Latest Research and Future Perspectives

For patients: Please read this

The following content pertains to findings that are currently under research or to special surgical techniques. It may differ from standard cataract surgery procedures, and the appropriate approach depends on the judgment of the operating ophthalmologist and the individual condition of the eye. Although this condition is a serious complication, its incidence in modern cataract surgery is limited to about 1–2%, and with appropriate management, good visual outcomes can be achieved in most cases. Please discuss risks and questions with your doctor before surgery.

Prophylactic anterior vitrectomy

Thompson et al. investigated the efficacy of prophylactic core anterior vitrectomy (CAV) performed simultaneously with cataract surgery in high-risk eyes, such as those with chronic angle-closure glaucoma, short axial length, nanophthalmos, plateau iris, or a history of IMS in the fellow eye ⁸⁾. In their case series, combining posterior capsulotomy with anterior vitrectomy via the anterior chamber resulted in zero cases of postoperative IMS ⁸⁾.

Phaco sleeve irrigation assisted hydrodissection

Recently, phaco sleeve irrigation assisted hydrodissection, which uses irrigation pressure from the sleeve irrigation port of the ultrasound tip, has been reported. This technique maintains a constant anterior chamber volume under closed-eye conditions, reducing the risk of anterior chamber collapse, intraocular pressure spikes, and IMS. It is applicable to difficult cases such as those with zonular weakness, shallow anterior chamber, IFIS, microphthalmos, and posterior pole fragility.

Application of Intraoperative OCT (iOCT)

A study by Grzybowski 2020 showed that iOCT can directly observe fluid accumulation in the Berger space ⁵⁾. In the future, the widespread use of iOCT-integrated surgical microscopes may enable early detection and intraoperative monitoring of IMS.

Fluid Misdirection Syndrome as a Unified Concept

In 2018, Grzybowski et al. proposed acute fluid misdirection syndrome (during or immediately after surgery) and chronic fluid misdirection syndrome (weeks to years after surgery) as a unified concept based on pathophysiology ²⁾. The two differ only in time course and share a common mechanism of posterior misdirection of aqueous humor or irrigation fluid due to ciliary block. This concept provides a framework for understanding IMS and malignant glaucoma as a continuum.

Reports of Onset in Highly Myopic Eyes

Conventionally, IMS has been considered a complication of short axial length eyes. However, in 2025, the first case of onset during ICL implantation in a long axial length (high myopia) eye was reported in BMC Ophthalmology ¹⁴⁾. This suggests that the condition depends not on axial length itself but on the general conditions leading to inappropriate fluid movement. Future research is needed to identify risk factors in long axial length eyes.

Latest Treatment Trends

A study examining the outcomes of various treatments for chronic aqueous misdirection in pseudophakic eyes reported that PPV + ZHV + iridectomy showed the highest recurrence suppression effect ¹⁹⁾.

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8. References

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19. Lincke JB, Häner N, Schawkat M, et al. Treatment of pseudophakic aqueous misdirection syndrome. Sci Rep. 2025;15:1415. DOI: 10.1038/s41598-024-83659-y.