Urrets-Zavalia Syndrome

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Definition and Historical Background

In 1963, Alberto Urrets-Zavalia described six patients with wide and rigid pupils, multiple posterior synechiae, and iris atrophy after undergoing PKP.

Historically, Urets-Zavalia Syndrome (UZS) has been defined as a fixed and dilated pupil following penetrating keratoplasty (PKP) for keratoconus in patients who receive mydriatics.

Incidence and epidemiology

The reported incidence of UZS after PKP varies widely, ranging from 0 % to 17.7%.

UZS usually occurs unilaterally despite bilateral surgery.

Risk Factors

Possible risk factors for UZS are increase intraocular pres-sure (IOP) during or after surgery, the use of atropine or other mydriatic agents, the presence of keratoconus,viscoelastic material left in the eye,and anterior chamber inflammatory reaction in the postoperative period.

Pathogenesis

The mechanism of UZS has not been fully determined and is probably multifactorial. The most widely accepted theories are ischemia of the iris and acute rise in IOP. Iris abnormalities, which may be more common in keratoconus, the instillation of strong mydriatics, and bringing the iris into contact with the peripheral cornea to produce peripheral anterior synechiae may also be triggers.

Iris Ischemia and Atrophy

The leading explanation for the development of UZS is ischemic atrophy of the sphincter muscle secondary to iris strangulation with resultant pupil dilatation. The cause for iris ischemia could be an acute post-operative increase in IOP, compression of iris vessels against the incision edge of the host cornea as the lens-iris diaphragm moves forwards during surgery, and visco-elastic material left in the anterior chamber angle.

Patients who had a fixed dilated pupil after PKP reveals delayed and segmental filling of the iris vessels. The vessels are also tortuous, and at a late stage the iris vessels leak. These angiographic findings are compatible with severe iris ischemia. Surgical trauma to the iris caused by the trephine or scissors can also result in a fixed dilated pupil.

Increased IOP

Tuft et al reported three patients with UZS following PKP who had transient elevated IOP postoperatively. They speculate that raised IOP occluded the iris vessels. The low rigidity of a keratoconus eye may allow the occlusion of vessels at the root of the iris within the sclera. [1] Figueiredo et al found that elevation of the IOP within 24 hours after PKP was a significant risk factor in the development of UZS. [2] Walton et al stated that UZS is unequivocally the result of acute elevation of the IOP to a level sufficient to cause iris ischemia and secondary pupillary sphincter atrophy,resulting in permanent mydriasis.

There are other reports of UZS patients with normal IOP and none of the cases in Urrets-Zavalia’s original article had an elevated IOP. Alberth and Schnitzler reported a 10% incidence of irreversible mydriasis following PKP, but IOP was normal in all patients. [3]

Another hypothesis is a toxic reaction of the iris to topical agents. Nizamani et al reported fixed and dilated pupils as a sequela of Toxic Anterior Segment Syndrome. [4]

Associations with Ophthalmic Surgeries

Following PKP

The majority of the reports of fixed and dilated pupils are in the setting of PKP. The reason why this occurs much more often after PKP than after other surgeries is not fully understood, and several explanations,especially regarding the surgical technique have been offered.

In PKP, the iris vessels are more vulnerable to compression against the incision edge of the host cornea,which may lead to iris ischemia.

The trephine or the scissors used to cut the cornea may cause trauma to the sphincter.

During PKP, pressure from the vitreous can cause the lens to prolapse upward resulting in damage to the iris.

To prevent the forward vitreous pressure, Price developed a technique of suturing the donor on top of the recipient cornea and had no further cases of fixed and dilated pupils. [5]

Following deep anterior lamellar keratoplasty ( DALK )

DALK : second most common after PKP that is associated with UZS. Some of those incidents occurred after air had been left in the anterior chamber ,because of Descemet membrane microperforation although others followed uneventful DALK. A retrospective case series found a 7.5% incidence rate of fixed and dilated pupil after DALK, with all affected eyes experiencing an IOP rise after the surgery. To prevent postoperative IOP rise,the authors subsequently administered 20%mannitol to every patient with DALK during which air had been injected into the anterior chamber.

Maurino et al described 3 cases of fixed and dilated pupils which were associated with Descemet membrane microperforation and injection of gas or air into the anterior chamber either intraoperatively or postoperatively. [6]

Following Descemet Stripping Endothelial Keratoplasty ( DSAEK )

One suggestion is that the air bubble left in the anterior chamber at the end of surgery may have moved backwards, pushing the iris forward into contact with the cornea, and causing irreversible mydriasis. Anwar et al reported seven eyes with features similar to UZS after undergoing DSAEK. In all, IOP was elevated on postoperative day 1 or after re-bubbling for graft dislocation, and the high IOP may have led to iris ischemia. [7]Excess surgical manipulation may increase the risk of damaging the iris vasculature and cause pupillary abnormalities.

Glaucoma surgeries such as trabeculectomy, goniotomy and iridoplasty may also cause fixed and dilated pupils.

Cataract surgery may result in fixed and dilated pupils.The viscoelastic material was suspected to be toxic to the sphincter or vasculature of the iris resulting in fixed dilated pupil.

UZS have also been reported after phakic IOL and intracameral gas injection.

Relation to Keratoconus

Davies and Ruben compared non keratoconic eyes with keratoconus eyes undergoing PKP and found a UZS incidence of 0.8% in the former group compared with 7.8% in the latter group. [8]

One possibility is that the low rigidity of keratoconic eyes allows occlusion of vessels at the root of the iris within the sclera during surgery. Another theory is that an intrinsic iris abnormality is present in keratoconic eyes.

In opposition to these suggested associations, others reported no cases of UZS in their studied keratoconus patients. Kirkness et al reported no evidence of UZS in 201 cases of PKPs performed in keratoconus eyes. [9]

The Role of Mydriatics

Mydriatic agents were originally thought to play a critical role inUZS.The explanation for that is not clear, but it is related to the action of the mydriasis itself and not to the parasympatholytic effect of atropine, because UZS has been described with other mydriatics, such as phenylephrine.

Mydriatics were also found to cause permanent mydriasis in two populations, individuals with Down syndrome and those with pigment dispersion syndrome. Mocan reported two subjects with pigment dispersion syndrome who developed UZS following pharmacologic pupil dilation.

On the one hand, reports have shown that UZS may occur even when no mydriatics are instilled. And On the other hand,there was no case of UZS in a prospective study on 83 keratoconus eyes undergoing PKP with all patients receiving atropine at the end of surgery, leading the authors to conclude that this syndrome, if it exists, is not related to the use of mydriatics. Bertelsen and Seim found that postoperative dilatation was detected equally in keratoconus patients whether or not they had received mydriatic drops. They concluded that the use of mydriatics postoperatively does not play any role in the pathogenesis of UZS.

Clinical Findings

A fixed, dilated pupil will not react to light or accommodation and will usually be noticed during the immediate postoperative period . Jastaneiah et al reported that a dilated pupil will be detected by the first two postoperative days in 80.9% of patients.[10]

Others, however, stated that although UZS will typically occur 1 or 2 weeks after PKP, it does not occur within the first postoperative days. UZS is also reported to occur up to 5 months postoperatively.

There is a diffuse atrophy of the anterior layers of the iris and pigmentary granules on the corneal endothelium and the anterior capsule of the lens in the incomplete and sometimes transient form of UZS, and reduction in pupil size is possible over time in such cases. Between one-third to two-thirds of patients with UZS will recover some form of pupil reactivity within 1 to 18 weeks, with some patients regaining normal pupil size.

Jastaneiah et al reported that only 4.8% will regain normal pupil size. [10] Patients with the complete form have marked atrophy of both the anterior and posterior layers of the iris, which makes the mydriasis irreversible. Posterior synechiae and opacities on the anterior capsule (glaukomflecken) are then common. The permanent mydriasis brings the iris close to the trabecular meshwork and causes adhesions and occlusion of the angle, which results in secondary angle-closure glaucoma.

Another classification of UZS was suggested by Jastaneiah et al, who described two different manifestations of the syndrome. One presentation is of quiet eye with or without a documented rise in IOP. The second presentation is of an eye with congested conjunctiva and an inflammatory reaction in the anterior chamber. They stated that the occurrence of a fixed and dilated pupil without signs or symptoms of raised IOP or inflammation cannot be explained.

A fixed, dilated pupil does not cause a decrease in visual acuity but can cause halos, glare, and photophobia ,as well as cosmetic abnormality.

Thus, it is not the mydriasis,but rather the secondary glaucoma, that constitutes the chief clinical problem.

Prevention

Preventing Urrets-Zavalia syndrome is difficult because the precise cause of the syndrome is uncertain.

Preoperative

Intravenous mannitol given preoperatively was found to decrease the rate of fixed, dilated pupil from 4%to 1.5%. The mannitol reduces vitreous volume and could prevent iris strangulation. YAG laser iridotomy performed one day prior to PKP was shown to prevent UZS.

Intraoperative

Some steps are needed to be taken during surgery to prevent the occurrence of UZS.

  • First, the anterior chamber should be kept deep throughout.
  • Second, special care must be taken to avoid surgical trauma to the iris.
  • Third, the surgeon should consider performing peripheral iridotomy that can reduce the risk of iris strangulation and pupillary block.


Nguyen et al reported not having encountered any case of UZS since they have starting peripheral iridectomies for PKP.

As for other ocular surgeries, it is recommended to have meticulous clearance of any viscoelastic material and to leave only a small amount of air at the anterior chamber when air is needed (i.e., in DSAEK or DALK with Descemet membrane perforation). In these cases, the surgeon should also consider the use of mannitol.

Postoperative

  • Close IOP control is needed during the first 24 postoperatively in all patients undergoing PKP, particularly for keratoconus.
  • Avoid mydriatics.

Management

General treatment

Spontaneous partial recovery is possible in UZS.


Medical therapy

Some reports in the literature were suggesting the use of dapiprazole and guanethidine drops, which are sympatholytic agents, there were suggested as a measure to cope with the hypertony of the sympathetic system of the iris and to induce miosis after UZS has occurred.

One report demonstrated that guanethidine in combination with pilocarpine treated iris sympathetic spasm and induced miosis but many other reports were showing no benefit of either of them.


Surgery

When the cause for a fixed dilated pupil is a shallow anterior chamber and as a result an iris-host cornea touch,that contact should be broken by a cyclodialysis spatula while simultaneously reforming the anterior chamber to avoid recurrence of the iris-cornea touch. The pupil will start to contract as soon as this contact is broken.

If UZS has developed secondary to elevated IOP because of blood or viscoelastic residue left in the anterior chamber, immediate anterior chamber washout is recommended.

Several reconstructive surgical treatments are available for symptomatic permanent mydriasis. These include corneal tattooing, a black diaphragm intraocular lens, and iris sutures. A femtosecond-assisted keratopigmentation technique was described in order to improve visual complaints and cosmetic appearance.

References

  1. Tuft SJ, Buckley RJ. Iris ischaemia following penetrating keratoplasty for keratoconus (Urrets-Zavalia syndrome). Cornea. 1997;6:120
  2. Figueiredo GS, Kolli SS, Ahmad S, et al. Urrets-Zavalia syndrome following penetrating keratoplasty for keratoconus. Graefes Arch Clin Exp Ophthalmol. 2013;251:809e15
  3. Alberth B, Schnitzler A. Irreversible mydriasis following keratoplasty for keratoconus. Klin Monbl Augenheilkd. 1971;159:330e5
  4. Nizamani NB, Bhutto IA, Talpur KI. Cluster of Urrets-Zavalia syndrome: a sequel of toxic anterior segment syndrome. Br JOphthalmol. 2013;97:976e9
  5. Price FW Jr. Fixed dilated pupil (Urrets-Zavalia syndrome) in corneal dystrophies. Cornea. 2005;24:363
  6. Maurino V, Allan BD, Stevens JD, et al. Fixed dilated pupil (Urrets-Zavalia syndrome) after air/gas injection after deep lamellar keratoplasty for keratoconus. Am J Ophthalmol. 2002;133:266e8
  7. Anwar DS, Chu CY, Prasher P, et al. Features of Urrets-Zavalia syndrome after Descemet stripping automated endothelial keratoplasty. Cornea. 2012;31:1330e4
  8. Davies PD, Ruben M. The paretic pupil: its incidence and aetiology after keratoplasty for keratoconus. Br J Ophthalmol. 1975;59:223e8
  9. Kirkness CM, Ficker LA, Steele AD, et al. The success of penetrating keratoplasty for keratoconus. Eye (Lond). 1990;4(Pt 5):673e88
  10. 10.0 10.1 Jastaneiah S, Al Towerki A E, Al Assiri A. Fixed dilated pupil after penetrating keratoplasty for macular corneal dystrophy and keratoconus. Am J Ophthalmol 2005. 140. 484–489.
  1. Spierer, Oriel et al. Urrets-Zavalia syndrome (fixed and dilated pupil following penetrating keratoplasty for keratoconus) and its variants. Survey of Ophthalmology, 2014., Volume 59, Issue 3, 304 - 310