UGH Syndrome (Uveitis-Glaucoma-Hyphema Syndrome)

Key Points at a Glance

Key Points of This Disease

• UGH syndrome (uveitis-glaucoma-hyphema syndrome) is a complication caused by mechanical chafing of the iris due to malposition of an intraocular lens (IOL), presenting with the triad of uveitis, glaucoma, and hyphema.
• It is rare now that in-the-bag fixation of posterior chamber IOLs is standard, but it is more likely to occur when a single-piece acrylic IOL is placed in the ciliary sulcus (out of the bag).
• The related condition “iris chafing syndrome” is characterized mainly by iris atrophy and recurrent hyphema, and may not fully meet the UGH triad.
• Evaluation of IOL-iris contact using ultrasound biomicroscopy (UBM) or anterior segment OCT is useful for diagnosis.
• Medical treatment is only symptomatic; definitive treatment is repositioning or exchange of the IOL.
• If the haptic protrudes into the anterior chamber and contacts the corneal endothelium, urgent repositioning is required.
• In iris chafing syndrome, after IOL removal, exchange with a shorter overall length IOL or scleral fixation is effective for preventing recurrence.

1. What is UGH Syndrome?

UGH syndrome (uveitis-glaucoma-hyphema syndrome) is a condition caused by mechanical chafing of the iris when an intraocular lens (IOL) is fixated out of the bag or asymmetrically, causing the haptic to directly contact the iris and surrounding tissues. When the iris is chafed, released iris pigment clogs the trabecular meshwork, leading to pigmentary glaucoma. Severe iris damage may be accompanied by iridocyclitis (uveitis) and hyphema, and this triad is called UGH syndrome.

The term was coined by Ellingson (1978). UGH stands for Uveitis, Glaucoma, and Hyphema.

Epidemiology and incidence:

• Previously more common with anterior chamber IOLs, but now rare since posterior chamber IOL in-the-bag fixation has become standard.
• Currently more likely when a single-piece acrylic IOL is placed out of the bag (in the ciliary sulcus).
• Ciliary sulcus fixation of single-piece acrylic IOLs is contraindicated due to the risk of associated complications (IOL decentration, iris chafing, pigment dispersion, elevated intraocular pressure, recurrent hyphema, inflammation) from contact of the thick square-edged haptics and square-edged optic with the posterior iris surface ²⁾.
• A review of 71 cases by Armonaite & Behndig (2021) showed that pseudophacodonesis is a significant risk factor for UGH syndrome ¹⁾.

Iris chafing syndrome:

First reported in the 1980s, this related condition occurs when the support or optic edge of a posterior chamber IOL persistently rubs against the iris or angle vessels, causing iris depigmentation and recurrent hyphema. It is characterized mainly by iris atrophy and recurrent hyphema, and may not fully meet the UGH triad. Now very rare since in-the-bag fixation has become common.

Q How rare is UGH syndrome?

A

With standard in-the-bag fixation of posterior chamber IOLs, occurrence is rare. However, risk increases when a single-piece acrylic IOL is placed in the ciliary sulcus (out of the bag), when there is IOL decentration, or when the patient is on anticoagulants. It is important to consider UGH syndrome in the differential diagnosis when recurrent hyphema or uncontrolled intraocular pressure elevation occurs after cataract surgery.

2. Main symptoms and clinical findings

Subjective symptoms

• Decreased visual acuity: due to pigment dispersion, hyphema, and inflammation.
• Eye pain: associated with elevated intraocular pressure and iridocyclitis.
• Photophobia: light sensitivity.
• Hyperemia: Conjunctival injection including ciliary injection

Clinical findings of the UGH triad

Uveitis (iridocyclitis)

Anterior chamber inflammation: Increased anterior chamber flare and cells.

Keratatic precipitates (KP): Observed on the corneal endothelium.

Recurrent inflammation: Inflammation recurs as long as IOL chafing continues.

Glaucoma (pigmentary/secondary)

Accumulation of iris pigment in the trabecular meshwork: Causes obstruction of aqueous outflow.

Secondary intraocular pressure elevation: Progressive elevation due to pigmentary glaucoma mechanism.

Pigment deposition in the angle: Confirmed by gonioscopy.

Hyphema

Recurrent nature: Repeated bleeding due to chafing injury to iris vessels.

Exacerbation in anticoagulant users: Bleeding tendency is more likely.

Blood accumulation in the anterior chamber: Direct cause of vision loss.

Findings of iris chafing syndrome:

• Iris atrophy (depigmentation): Thinning of the iris and transillumination defects due to continuous chafing
• Recurrent hyphema: Caused by repeated mechanical damage to iris blood vessels
• Secondary ocular hypertension: Obstruction of the trabecular meshwork due to dispersion of iris pigment

Additional findings:

• When thick square-edged haptics and a square-edged optic are placed in the ciliary sulcus, they can cause pigment dispersion, iris transillumination defects, elevated intraocular pressure, and recurrent inflammation/hemorrhage²⁾
• Pseudophacodonesis (IOL movement) has been identified as a risk factor for UGH syndrome¹⁾

Q Should UGH syndrome be suspected in cases of recurrent hyphema?

A

If recurrent hyphema occurs after cataract surgery, UGH syndrome or iris chafing syndrome should be actively considered in the differential diagnosis. Examination of IOL fixation status with a slit lamp and evaluation of IOL-iris contact using UBM or anterior segment OCT are key to diagnosis.

3. Causes and Risk Factors

Major IOL-related factors:

• Single-piece acrylic IOL placed in the ciliary sulcus: Thick square-edged haptics and a square-edged optic mechanically chafe the posterior iris surface. When sulcus placement is chosen as an alternative fixation method in cases of posterior capsule rupture, a three-piece IOL is recommended²⁾
• Extracapsular or asymmetric IOL fixation: The supporting elements come into direct contact with the iris
• Anterior chamber IOL: Inappropriate size (too short or too long), iris tuck after insertion, or rotation of the haptic through a peripheral iridectomy^{1, 3)}
• IOL decentration or pseudophacodonesis: Significant risk factors for UGH syndrome¹⁾
• Angulated loops or IOLs with long overall length: Higher risk of contact with the iris

Patient-related factors:

• Use of anticoagulants/antiplatelet agents: Increases bleeding risk, making hyphema more likely.

Q Is surgery for UGH syndrome possible while taking anticoagulants?

A

Surgery itself is possible, but taking anticoagulants/antiplatelet agents increases the risk of hyphema. Before surgery, coordinate with the primary care physician to consider discontinuation, change, or bridging therapy of anticoagulants. It is important to individually assess the balance with thromboembolism risk.

4. Diagnosis and Examination Methods

Key points for clinical diagnosis:

• Confirmation of the UGH triad (uveitis + glaucoma + hyphema) is fundamental.
• Incomplete forms without all three features (e.g., iris chafing syndrome) also exist.

Examination methods used for diagnosis:

Examination method	Evaluation content
Slit-lamp microscopy	IOL fixation status (out-of-bag, decentration, tilt), anterior chamber inflammation (flare, cells, KP), presence of hyphema, iris atrophy/depigmentation.
Gonioscopy	Pigment deposition on the trabecular meshwork, evaluation of secondary glaucoma.
Ultrasound biomicroscopy (UBM)	Detailed evaluation of the positional relationship between IOL and iris/ciliary body, useful for identifying lens-iris contact2)
Anterior segment OCT (AS-OCT)	Non-invasive imaging of the contact site between IOL and iris, useful for identifying lens-iris contact2)
Intraocular pressure measurement	Assessment of the degree and course of secondary intraocular pressure elevation

Differential diagnosis:

Disease	Onset timing	Main findings	IOL-related findings
UGH syndrome	Weeks to months after surgery	Triad of uveitis, elevated intraocular pressure, and hyphema	Extracapsular fixation or dislocation present
Infectious endophthalmitis	Within a few days after surgery	Severe eye pain, hypopyon, vitreous opacity	Usually none
TASS (Toxic Anterior Segment Syndrome)	12 to 48 hours after surgery	Diffuse corneal edema, anterior chamber inflammation	Usually none
Persistent pseudophakic uveitis (PUPPI)	Weeks to months after surgery	Chronic anterior chamber inflammation	IOL in normal position
Retained lens cortex	Days to weeks after surgery	Anterior chamber inflammation, elevated intraocular pressure	Cortical remnants
Pigmentary glaucoma (primary)	Gradual progression	Elevated intraocular pressure, pigment dispersion	No IOL chafing

Q How to differentiate whether chronic inflammation after cataract surgery is due to UGH syndrome?

A

The key to differentiation is the presence or absence of IOL-iris contact. UBM or anterior segment OCT is used to evaluate the positional relationship between the IOL and the iris/ciliary body. If mechanical contact is confirmed, UGH/Iris chafing is suspected. If the IOL position is normal and only inflammation persists, consider PUPPI (persistent pseudophakic iridocyclitis) or retained lens cortex.

5. Standard Treatment

Treatment strategy overview: Since the cause is mechanical chafing by the IOL, the definitive treatment is repositioning or exchange of the IOL. Drug therapy is only temporary symptomatic treatment.

Conservative Treatment

• Mydriasis + supine position: If the iris and IOL are not adherent, spontaneous repositioning can be expected.
• Steroid eye drops: Symptomatic anti-inflammatory therapy with 0.1% betamethasone sodium phosphate eye drops (e.g., 4 times daily). 1% atropine sulfate eye drops may also be added, but long-term efficacy is low.
• Intraocular pressure management: Aqueous humor suppressants such as 0.5% timolol maleate eye drops (twice daily) or 1% dorzolamide hydrochloride eye drops (three times daily) are used.
• Consideration of anticoagulant discontinuation: In coordination with internal medicine, determine appropriate discontinuation or change.

Surgical Treatment (UGH Syndrome)

1. Invasive IOL repositioning: Performed when mydriasis does not resolve. The procedure is easy if the iris and capsule are not severely adherent.
2. IOL exchange: Selected when there is firm adhesion to the iris or capsule, or dislocation of the IOL into the anterior chamber. Because it is highly invasive, it is performed only when visual function is significantly impaired.
3. Emergency repositioning: If the haptic is protruding into the anterior chamber and contacting the corneal endothelium, reposition as soon as possible.

Surgical treatment (Iris chafing syndrome)

• IOL removal is first choice: Once a definitive diagnosis is made, remove the IOL that is irritating the iris. Drug therapy (steroids, atropine, discontinuation of anticoagulants) has low fundamental improvement effect, and mechanical removal is the most reliable.
• Options after IOL removal:
  • Insert a 3-piece IOL with a slightly shorter overall length into the ciliary sulcus.
  • Transscleral suture fixation of the IOL.
  • Intrascleral fixation of the IOL (Yamane technique, etc.).
• If the IOL is well-centered, recurrence is rare.

Treatment flow

1. Mild (inflammation only) → Steroid eye drops, intraocular pressure management, observation.
2. No improvement with conservative treatment / recurrent → Consider IOL repositioning.
3. Irreducible / severe (recurrent hyphema, persistent high intraocular pressure) → IOL exchange.
4. Contact with corneal endothelium → Emergency repositioning or exchange.

Q If diagnosed with UGH syndrome, is surgery always necessary?

A

Surgery is not always necessary. In mild cases, first try conservative repositioning with mydriasis and supine positioning. If this does not improve the condition or if symptoms recur or persist, consider surgical repositioning or IOL exchange. However, if contact with the corneal endothelium is confirmed, urgent surgical intervention is required.

6. Pathophysiology and Detailed Mechanism

The mechanism of UGH syndrome is explained by the following chain of events.

1. IOL dislocation/extracapsular fixation: Due to posterior capsule rupture, zonular weakness, inappropriate IOL selection (e.g., single-piece acrylic IOL placed in the ciliary sulcus), the IOL deviates from its normal fixation position.
2. Mechanical chafing of the iris: The IOL haptic or optic edge continuously contacts the posterior iris surface, causing repeated mechanical friction.
3. Pigment dispersion and trabecular meshwork obstruction: Melanin granules are released from the iris pigment epithelium due to chafing and accumulate in the trabecular meshwork. This impairs aqueous outflow, leading to pigmentary glaucoma (elevated intraocular pressure).
4. Iridocyclitis: Mechanical irritation and tissue damage trigger an inflammatory response in the iris and ciliary body, resulting in anterior chamber flare and cells.
5. Hyphema: Direct chafing injury to iris vessels causes bleeding. The risk of bleeding is increased in patients using anticoagulants.

Risk characteristics of single-piece acrylic IOLs:

Single-piece acrylic IOLs with thick square-edged haptics and a square-edged optic, when placed in the ciliary sulcus, have a larger contact area with the posterior iris surface, leading to stronger chafing effects²⁾. Therefore, when fixation in the ciliary sulcus is necessary as an alternative in cases of posterior capsule rupture, the use of a three-piece IOL is recommended²⁾.

Special mechanism of UGH in anterior chamber IOLs:

In anterior chamber IOLs, UGH occurs due to size mismatch (too short or too long), iris tuck after insertion, or rotation of the haptic through a peripheral iridectomy^{1, 3)}.

7. Latest Research and Future Perspectives

For patients: Please read this

The following content includes information that is currently under research or under discussion. It may include techniques and knowledge that are not standard treatments available at general hospitals. This is reference information for experts regarding future medical developments.

• Large-scale case review: In a 71-case analysis by Armonaite & Behndig (2021), the clinical features of UGH syndrome were systematically analyzed, and pseudophacodonesis was identified as a risk factor. It was shown that UGH can occur with various IOL types, including anterior chamber IOLs, posterior chamber IOLs, and sulcus-fixated IOLs¹⁾
• Improvements in IOL design: The avoidance of using single-piece acrylic IOLs in the ciliary sulcus and the use of three-piece IOLs when the posterior capsule is damaged have become widely accepted²⁾
• Advances in imaging diagnostics: Higher resolution of UBM and AS-OCT technologies now allow real-time, non-invasive assessment of IOL-iris contact, enabling early diagnosis and early intervention²⁾
• Widespread adoption of intrascleral fixation (Yamane technique): The secondary IOL implantation method using flanged polyvinylidene fluoride (PVDF) haptics fixed within the sclera has expanded stable fixation options after IOL exchange
• Natural history and long-term prognosis of UGH: Prospective studies on long-term visual function after repositioning or exchange remain a future challenge, and establishment of follow-up systems including regular intraocular pressure management and visual field testing is needed

8. References

1. Armonaite L, Behndig A. Seventy-one cases of uveitis-glaucoma-hyphaema syndrome. Acta Ophthalmol. 2021;99:69-74.
2. Chang DF, Masket S, Miller KM, et al. Complications of sulcus placement of single-piece acrylic intraocular lenses: recommendations for backup IOL implantation following posterior capsule rupture. J Cataract Refract Surg. 2009;35:1445-1458.
3. Zemba M, Camburu G. Uveitis-Glaucoma-Hyphaema Syndrome. General review. Rom J Ophthalmol. 2017;61:11-17.