Urrets-Zavalia syndrome (UZS) is a rare postoperative complication in which the pupil becomes dilated and fixed after ophthalmic surgery and does not respond to light stimulation or miotics. In 1963, Argentine ophthalmologist Alberto Urrets-Zavalia first reported six cases of fixed dilated pupil, posterior synechiae, and iris atrophy after penetrating keratoplasty (PKP).
Initially recognized as a complication after PKP, it is now known to occur after many ophthalmic surgeries 1, 2, 3, 4). The incidence after PKP is reported to be 0–17.7%, and it usually occurs unilaterally. The overall incidence after cataract surgery is reported to be 8.2% 4). Approximately 100 case reports have been published to date 2, 4).
| Related Surgery | Features |
|---|---|
| Penetrating keratoplasty (PKP) | Most common, incidence 0–17.7% |
| Deep anterior lamellar keratoplasty (DALK) | Second most common, incidence 7.5% |
| Descemet’s stripping automated endothelial keratoplasty (DSAEK) | Occurs after air injection or reinjection |
| Cataract surgery | Often associated with TASS4) |
| Phakic intraocular lens (ICL) | Associated with pupillary block3) |
| Endoscopic cyclophotocoagulation (ECP) | First reported case2) |
| Scleral-fixated intraocular lens | First reported case1) |
UZS was initially reported as a complication after PKP, but has now been reported after numerous ophthalmic surgeries including DALK, DSAEK, cataract surgery, trabeculectomy, phakic intraocular lens (ICL) insertion, endoscopic cyclophotocoagulation (ECP), and scleral-fixated intraocular lens insertion 1, 2, 3, 4). Furthermore, it has also been reported after argon laser peripheral iridoplasty and transscleral cyclophotocoagulation. Common factors are situations that can cause iris ischemia and postoperative intraocular pressure elevation.
Pupillary Findings
Fixed mydriasis: Does not respond to light stimulation or accommodation. Pupil diameter reaches 7.5–9 mm 1, 2, 3, 4).
No response to miotics: Does not respond to pilocarpine 2–4% or carbachol 1, 2, 3).
Onset timing: 80.9% are detected by postoperative day 2, but some cases are delayed up to 5 months postoperatively.
Iris and Anterior Chamber Findings
Iris atrophy: Diffuse atrophy of the anterior and posterior layers is observed 4). Transillumination defects are present.
Peripheral anterior synechiae (PAS): Cause angle closure 4).
Posterior synechiae: May be accompanied by pigment deposition on the anterior lens capsule 4).
In keratoconus eyes, the incidence of UZS after PKP is about 10 times higher than in non-keratoconus eyes (7.8% vs 0.8%). The following mechanisms are considered. First, the low scleral rigidity in keratoconus eyes makes it easier for the iris root vessels within the sclera to become occluded during surgery. Second, there may be inherent iris abnormalities in keratoconus eyes. However, there are reports of no UZS in 201 PKP cases, so the extent of keratoconus involvement remains debated.
UZS is diagnosed clinically based on characteristic clinical findings and surgical history. Postoperative fixed mydriasis that does not respond to miotics is diagnostic.
| Differential Diagnosis | Key Points for Differentiation |
|---|---|
| Traumatic mydriasis | History of ocular trauma, irregular pupil dilation |
| Adie pupil (tonic pupil) | Hypersensitive to low-concentration pilocarpine |
| Oculomotor nerve palsy | Ptosis and eye movement disorder |
| TASS | Early postoperative anterior chamber inflammation |
| Pharmacologic mydriasis | Resolves when the effect of mydriatic drugs wears off |
| After acute glaucoma attack | History of high intraocular pressure attack |
Toxic anterior segment syndrome (TASS) is one of the important risk factors for UZS. In TASS, anterior chamber inflammation occurs early after surgery, leading to necrosis of the pupillary sphincter and resulting in fixed mydriasis 5). Typically, fixed mydriasis appears simultaneously with TASS inflammation, but delayed cases have also been reported where inflammation appeared 2 weeks after surgery and UZS developed 1 week later 4). Rather than differentiating TASS from UZS, there is a causal relationship in which TASS causes UZS.
Since UZS is often irreversible once it occurs, prevention is most important.
Preoperative preventive measures:
Intraoperative preventive measures:
Postoperative preventive measures:
Management of elevated intraocular pressure
Anterior chamber washout: Perform immediately if residual blood or viscoelastic material is the cause.
Angle recession: If caused by iris-corneal contact due to shallow anterior chamber, reform the anterior chamber to relieve contact.
Pharmacologic intraocular pressure reduction: Combination of brinzolamide, brimonidine, timolol, etc. 1).
Pharmacotherapy
Dapiprazole: A sympatholytic agent. Used to address overactivity of the iris sympathetic nervous system and induce miosis.
Guanethidine and pilocarpine combination: Reported for treating iris sympathetic spasm, but many reports indicate limited efficacy.
Since the exact cause of UZS is unknown, complete prevention is difficult, but several effective preventive measures have been reported. Preoperative intravenous mannitol reduces the incidence from 4% to 1.5%. Preoperative YAG laser iridotomy is also considered effective. Intraoperatively, it is important to maintain a deep anterior chamber, perform peripheral iridectomy, and ensure complete removal of viscoelastic material. Postoperatively, strict intraocular pressure management for 24 hours and avoidance of mydriatic agents are recommended. For patients with plateau iris configuration, some suggest using mechanical dilation (iris hooks) instead of pharmacologic dilation 1).
The most widely accepted pathophysiology of UZS is iris ischemia and necrosis of the pupillary sphincter muscle1, 2).
Iris fluorescein angiography in UZS patients shows delayed filling, segmental filling, tortuosity of iris vessels, and late leakage. These findings are consistent with severe iris ischemia.
A leading theory is that acute postoperative elevation of intraocular pressure occludes iris vessels, causing iris ischemia. Elevated IOP within 24 hours after PKP is a significant risk factor for UZS. In cataract surgery, if endophthalmitis, TASS, or excessive IOP elevation occurs in the perioperative period, pupillary sphincter necrosis can lead to chronic mydriasis5).
On the other hand, UZS cases without elevated IOP have also been reported, and all cases in Urrets-Zavalia’s original paper had normal IOP.
A 72-year-old man underwent bilateral ECP/cataract surgery; both eyes had postoperative IOP elevation to 36 mmHg, but UZS developed only in the right eye with lower baseline IOP (17 mmHg), not in the left eye with higher baseline IOP (21 mmHg)2). This suggests that eyes with lower baseline IOP may be more susceptible to iris ischemia even with similar IOP elevation.
In eyes with plateau iris configuration, the peripheral iris is close to the cornea, so peripheral iris vessels are easily compressed during mydriasis1). A report described plateau iris configuration in the fellow eye of a patient who developed UZS after scleral-fixated IOL implantation, suggesting that iris anatomical features may predispose to UZS1).
Epinephrine in the vitrectomy infusion fluid has a vasoconstrictive effect on small vessels and may cause intraoperative iris ischemia1). Combined with prolonged mydriasis, it may lead to irreversible ischemic damage to the pupillary sphincter.
The pathophysiology of UZS cannot be explained by a single mechanism and is considered multifactorial2). Cases without iris ischemia on iris fluorescein angiography have also been reported, so not all UZS can be explained by iris ischemia. Direct surgical trauma to the iris, toxicity of mydriatic agents, and inflammatory reactions may also be involved.
In recent years, cases of UZS following surgeries not previously reported have been reported one after another. In 2024, the first case after scleral-fixated intraocular lens implantation was reported 1), and the first case after combined endoscopic cyclophotocoagulation (ECP) and cataract surgery was also reported 2). In 2025, a case of UZS secondary to pupillary block after phakic intraocular lens (ICL) implantation was reported 3).
“Surgeons should consider screening for plateau iris configuration in patients scheduled for prolonged intraocular surgery, and in such patients, mechanical dilation (e.g., iris hooks) should be used instead of pharmacological dilation” 1)
The exact pathophysiology of UZS has not yet been fully elucidated, and effective treatments have not been established. Establishing preoperative risk assessment methods, developing early detection methods for iris ischemia, and the possibility of recovery of pupillary sphincter function after onset are future research topics.
