|Year : 2023 | Volume
| Issue : 1 | Page : 39-44
Toxic anterior segment syndrome and Urrets-Zavalia syndrome: Spectrum of the same entity?
Niruban Ganesan1, Renuka Srinivasan2, Subashini Kaliaperumal1
1 Department of Ophthalmology, JIPMER, Karaikal, Tamil Nadu, India
2 Department of Ophthalmology, Pondicherry institute of Medical Sciences, Puducherry, Tamil Nadu, India
|Date of Submission||28-Nov-2021|
|Date of Decision||13-Jun-2022|
|Date of Acceptance||26-Aug-2022|
|Date of Web Publication||26-Dec-2022|
Department of Ophthalmology, JIPMER, Karaikal, Puducherry, Tamil Nadu
Source of Support: None, Conflict of Interest: None
| Abstract|| |
PURPOSE: The purpose of the study was to analyze the outcomes of patients with toxic anterior segment syndrome (TASS) and Urrets-Zavalia (UZ) syndrome.
MATERIALS AND METHODS: The records of all patients with TASS and UZ syndrome were studied. Corrected distance visual acuity (CDVA), intraocular pressure (IOP), and the details of surgeries performed were recorded at 1 and 3 months. We studied the changes in CDVA and IOP using repeated-measure ANOVA and paired t -test, respectively.
RESULTS: Four patients (44.4%) developed refractory UZ syndrome, and five (55.6%) patients had TASS. At the end of 3 months of follow-up, all nine patients had concentric rings of iris atrophy and corneal edema. None of the cases had hypopyon or vitritis. Peripheral anterior synechiae (PAS) with secondary glaucoma was present only in cases of UZ syndrome. Among the four cases of UZ syndrome, goniosynechialysis was performed for 2 cases and trabeculectomy for one case. Despite these interventions, IOP could not be controlled. Patients in the TASS group did not exhibit PAS formation, and IOP was normal, but corneal edema and concentric rings of iris atrophy persisted. Descemet's stripping endothelial keratoplasty was performed for all the TASS cases. There was a statistically significant drop in CDVA ( P = 0.028) and an increase in IOP ( P = 0.029) at 3-month postcataract surgery.
CONCLUSION: TASS and UZ syndrome could result in sight-threatening complications. They may be considered diseases of the same entity as both the conditions were found in the same cluster. TASS could be considered as an abortive attack of UZ syndrome.
Keywords: Refractory, toxic anterior segment syndrome, Urrets-Zavalia syndrome
|How to cite this article:|
Ganesan N, Srinivasan R, Kaliaperumal S. Toxic anterior segment syndrome and Urrets-Zavalia syndrome: Spectrum of the same entity?. Oman J Ophthalmol 2023;16:39-44
|How to cite this URL:|
Ganesan N, Srinivasan R, Kaliaperumal S. Toxic anterior segment syndrome and Urrets-Zavalia syndrome: Spectrum of the same entity?. Oman J Ophthalmol [serial online] 2023 [cited 2023 Mar 31];16:39-44. Available from: https://www.ojoonline.org/text.asp?2023/16/1/39/365464
| Introduction|| |
Toxic anterior segment syndrome (TASS) is a sterile inflammatory reaction that classically presents with limbus-to-limbus corneal edema, severe iridocyclitis, and hypopyon within 24 h of intraocular surgery. Vitritis is typically absent. It can also present with glaucoma and fixed dilated pupil, similar to Urrets-Zavalia (UZ) syndrome. It can be due to the impurities in the intraocular lens, powdered gloves, viscoelastic,, and trypan blue.
UZ syndrome was first described by Castroviejo in a series of six patients who underwent penetrating keratoplasty (PKP) for keratoconus. This syndrome manifests with fixed dilated pupil, peripheral anterior synechiae (PAS), increased intraocular pressure (IOP), pigment dispersion, posterior subcapsular cataract, glaucomflecken, and iris ectropion. Although classically described after keratoplasty, it is also described in patients after deep anterior lamellar keratoplasty,,,, Descemet's stripping automated endothelial keratoplasty,, argon laser iridoplasty, trabeculectomy, goniotomy, cataract surgery,, implantable collamer lens placement, and intravitreal cidofovir injection.
Fortunately, most of the TASS cases resolve completely, and many reports in the literature portray the good visual outcome following TASS. However, a few cases end up in sight-threatening long-term complications. We describe a single cluster of nine patients with UZ syndrome and TASS with long-term complications.
| Materials and Methods|| |
This retrospective analysis was conducted in a tertiary care multispecialty hospital in South India. Ethics committee approval was obtained, and the study conforms to the Declaration of Helsinki. It was on a cluster of nine patients with UZ syndrome and TASS who underwent uneventful cataract surgery in 7 days. All patients were comprehensively examined for corrected distance visual acuity (CDVA), slit lamp examination, Goldman applanation tonometry, and fundus with + 90 diopter lens. B-scan was also performed to rule out vitritis.
Preoperatively, patients were dilated using tropicamide 1% with phenylephrine 10% (tropicacyl plus eye drops, Sunways [P] Ltd., Ahmedabad, India) and flurbiprofen (Proflur eye drops, Pushkar Pharma, Madhya Pradesh, India). None of the patients had glaucoma. The peribulbar block was given for cases 2, 3, 4, 7, 8, and 9 using 5 ml of xylocaine 2% (Loxicard, Neon laboratories Ltd., Mumbai, India) and 3 ml bupivacaine hydrochloride (Kwality Pharmaceuticals Ltd., Amritsar, India). The rest of the patients were operated on under topical anesthesia using proparacaine eye drops (Aurocaine, Aurolab, Madurai, India). The eye to be operated was cleaned with 10% povidone-iodine solution, and 5% povidone-iodine drops (Cipladine, Cipla, Mumbai, India) was instilled in the conjunctival cul-de-sac. Routine aseptic precautions were followed during surgery. Povidone iodine drops was not instilled before patching the eye. Phacoemulsification, small incision cataract surgery, and conventional extracapsular cataract extraction were performed for 6, 2, and 1 cases, respectively. Hydroxypropyl methylcellulose viscoelastic and Ringer lactate (RL) (Claris Otsuka [P] Ltd., Ahmedabad, India) with 0.5 ml of 1 in 1000 adrenaline (Bioaderna, Biocare, Mumbai, India) was used for all the patients. Hydrophilic acrylic foldable lens and rigid polymethyl methacrylate lens (Acryfold, Heera, Appasamy Ocular Devices [P] Ltd, Puducherry, India) was implanted. For cases that were operated by peribulbar block, gentamycin sulfate (Modern Laboratories, Indore, India) and dexamethasone (Peridex, Pushkar Pharma, Madhya Pradesh, India) were injected subconjunctivally, and the eye was patched with chloramphenicol hydrocortisone eye ointment (Chlorocol-H, Jawa Pharmaceuticals [P] Ltd., Jaipur, India) at the end of surgery. No intracameral drugs were used for any of the patients. An investigation was performed to find the inciting agent, as shown in [Figure 1].
|Figure 1: Investigation protocol to find the inciting agent of TASS, TASS: Toxic anterior segment syndrome|
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We diagnosed TASS when (1) postoperative inflammation was severe with or without fibrin occurring within the 1st postoperative day; (2) absence of vitritis on clinical examination and B-scan; and (3) complete resolution of inflammation with topical steroids.
UZ syndrome was diagnosed when (1) dilated nonreacting pupil with PAS was present, (2) iris atrophic changes, and (3) secondary glaucoma. We did not perform anterior chamber and vitreous tap for any of the patients as none of them had hypopyon.
The records of all patients were screened for age, gender, CDVA, IOP at 1 month and 3 months, cataract status, comorbidities present in the patient, type of surgery, and additional surgeries performed. In addition, IOP following goniosynechialysis (case 1 and 2) and trabeculectomy (case 4) was also noted. Anterior chamber reaction (based on the standardization of uveitis nomenclature working group grading scheme), corneal edema, pupil size and reaction, and iris atrophy were documented at 1 and 3 months. Corneal edema and iris atrophy were noted as present or absent. Pupil size of <4 mm was documented as “constricted.”
Preoperative versus postoperative differences in CDVA were studied using repeated measures ANOVA and difference in IOP was studied using paired t -test. P < 0.05 was considered statistically significant. Data analysis was performed using IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY, US: IBM Corp.
| Results|| |
In our case series, four patients (cases 1–4) developed UZ syndrome, and five patients (cases 5–9) had TASS. Preoperative and postoperative parameters of all patients are tabulated in [Table 1]. With all the other drugs and IOL of the same brand and batch, using a new brand of viscoelastic could have resulted in all these complications. On changing the viscoelastic to the older brand, retaining the same batch of all the other previously used products, there were no such complications. Hence, we suspected that the viscoelastic could be the offending agent and had caused the adverse reactions. We analyzed the viscoelastic and found that the pH, osmolarity, viscosity, and other physiochemical properties of the viscoelastic were ideal and unaltered. Methylcellulose, being a plant extract, can have varying chemical structures based on the terrain, which in turn can cause these adverse reactions. However, tests to study the chemical structure of methylcellulose and find Pseudomonas endotoxins were not done as we did not have enough samples to perform the test. The samples sent from RL and the instruments in operation theater for microbiological analysis were reported sterile.
Before surgery, the average IOP was 17 ± 1.3 mmHg. All patients had corneal edema and eye pain on the 1st postoperative day with inflammation ranging from +1 to +3. IOP of cases 1–4 had increased to 28, 26, 25, and 28 mmHg, respectively, at 1 week and were started on antiglaucoma medications. All patients were treated with hourly ciprofloxacin–dexamethasone eye drops (Cipla, Mumbai, India) and one course of tapering oral prednisolone 1 mg/kg/day in addition to nepafenac 0.1% and homatropine 2%. The topical steroids were tapered on a case-to-case basis. Pilocarpine was advised for patients with a dilated nonreacting pupil at 1 week postsurgery (Pilo eye drops, Aurolab, Madurai, India), but there was no response to it. Guanethidine was not used.
At 1 month, cases 1–4 had corneal edema with microcysts, PAS, fixed dilated pupil, and an increased IOP of 30, 34, 28, and 40 mmHg, respectively [Figure 2]a and [Figure 2]c. The rest of the five cases had only corneal edema. The average IOP was 24.6 ± 8.7 mmHg. There was a statistically significant drop in CDVA ( P = 0.028) and a significant increase in IOP ( P = 0.029). Goniosynechialysis was performed for cases 1 and 2 with a cyclodialysis spatula. There was an immediate clearing of the corneal edema, constriction of pupil, and reduction in IOP to 20 and 22 mmHg [Figure 2]b and [Figure 2]d. Cases 3 and 4 did not opt for goniosynechialysis. Trabeculectomy was performed for case 4 at 6 weeks when the inflammation had subsided, following which IOP reduced to 20 mmHg. Although there was a reduction in IOP following these surgical interventions, it was short-lived in all the cases, following which they were referred for further treatment by 3 months.
|Figure 2: Anterior segment pictures of case 1 and case 2. (a) 4 weeks postoperative picture of case 1 showing corneal edema, fixed dilated pupil, and peripheral anterior synechiae with intraocular pressure of 30 mmHg, (b) intraoperative picture after goniosynechialysis of case 1 showing clear cornea with Descemet membrane folds. Intraocular pressure after goniosynechialysis was 20 mmHg, (c) 4 weeks postoperative picture of case 2 showing corneal edema, fixed dilated pupil, and peripheral anterior synechiae with intraocular pressure of 34 mm Hg, (d) Intraoperative picture of case 2 showing clear cornea and 5 mm pupil after goniosynechialysis. Intraocular pressure was 22 mmHg|
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Postoperative inflammation had subsided in all patients by 1 month. There was no vitritis or hypopyon in any of the patients during the entire postoperative period. Patients in the TASS group did not have PAS and secondary glaucoma at 3 months postsurgery, but corneal edema persisted [Figure 3]a, [Figure 3]b, [Figure 3]c. CDVA at 3 months was the same as that of their respective 1-month CDVA. Descemet's stripping endothelial keratoplasty was performed for these cases, and visual acuity improved.
|Figure 3: Patients with TASS, (a-c) showing corneal edema, constricted pupil, and concentric rings of iris atrophy (arrow) 3 months after cataract surgery among TASS patients. TASS: Toxic anterior segment syndrome|
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| Discussion|| |
A multitude of TASS outbreaks has continued to occur in the last few decades. The unabated occurrence of TASS takes an emotional toll on the patient, the surgeon, and the hospital staff over the looming visual prognosis. TASS can occur following exposure to contaminants during intraocular surgery.,,,, Similarly, UZ syndrome, though first reported following PKP, has been reported following numerous other intraocular surgeries.,,,,,,,,,,,,, A literature review has reported 8.2% of its incidence following cataract surgery.
Infectious endophthalmitis, a close mimic of TASS with similar clinical features, needs to be ruled out before labeling a case as TASS. The time of presentation, associated intense fibrinous reaction, and ultrasound B-scan help distinguish both entities. TASS can be rightly called “a diagnosis of exclusion” as the confirmation on the diagnosis is obtained only after prompt resolution of inflammation with topical steroids and without intravitreal antibiotics. The severity and duration of the inflammation and type of contaminant play a role in the evolution of long-term complications. Our case series is one such which describes the deleterious consequences of these disease entities. The incidental discovery of a cluster of postoperative corneal edema cases with severe inflammation made us retrospectively analyze the cause of this syndrome. We speculate that it could probably be due to the new brand of viscoelastic used, although it could not be proved.
The etiology of this syndrome can be due to direct compression of the iris against the crystalline lens when air or perfluoropropane is injected into the anterior chamber or neuronal injury as in injury to the peripheral parasympathetic fibers during a laser iridotomy. Nevertheless, in our case series, we postulate that retained viscoelastic or contaminants in viscoelastic could have elicited an immune response, resulting in concentric rings of iris atrophy, PAS formation, and secondary glaucoma. Although all nine cases had concentric rings of iris atrophy, only the anterior layers of the iris would have been affected in five cases resulting in TASS. The rest four cases might have had atrophy involving all the layers of the iris, leading to UZ syndrome. The iris stromal ischemic insult is irreversible and is demonstrated by the fact that its consequences were not amenable to both medical (pilocarpine) and surgical treatment (goniosynechialysis). Secondary glaucoma was refractory to conventional treatment and necessitated tube shunt in all patients with UZ syndrome. Nonresolving corneal edema was also present in all nine cases. It could be related to the preoperative corneal endothelial count and the duration and severity of inflammation. However, Parikh and Edelhauser postulated that corneal edema could be due to direct corneal endothelial toxicity. Avisar and Weinberger proved that the endothelial cell count in TASS eyes was reduced compared to the fellow pseudophakic eye.
Several studies reported corneal decompensation following TASS. Choi and Shyn reported that five eyes required PKP out of the 15 cases of TASS, wherein the etiology was unknown. Unal et al . outlined six cases of TASS caused by glutaraldehyde residue with five requiring PKP. Werner et al . described eight cases of TASS attributable to antibiotic–steroid ointment seeping into the anterior chamber with three requiring PKP. However, in their case series, Tan and Humphry demonstrated fixed dilated pupils in patients in whom hypromellose was used. Yet, another cluster of TASS reported by Nizamani et al.  cited RL as the offending agent. None of the patients in both studies developed long-term complications. Instead, they demonstrated improvement in visual acuity in their patients, unlike ours.
Secondary glaucoma is a long-term complication of TASS. Four cases in our series developed fixed dilated pupil and PAS, resulting in secondary intractable angle-closure glaucoma, mimicking UZ syndrome. Glaucoma filtering surgery was needed in all four cases of UZ syndrome in our series. Our results are comparable to one of the 15 cases in Choi and Shyn's case series, two of the six cases in Unal et al .'s series, and 1 of the 8 in Werner et al. 's series. Despite reports about excellent visual outcomes following TASS, we join a handful of studies reporting the worse outcomes of this condition. In view of this and the findings from other studies, we postulate that TASS may represent abortive versions of UZ syndrome. We hypothesize that TASS and UZ syndrome may represent the spectrum of the same entity.
Corneal endothelial count and effective phacoemulsification time values could have added more value to this study to exclude other potential causes of corneal edema. The retrospective design of this study, limited follow-up time, and lack of identifiable etiology may add to the shortfall of our study. Limitations aside, we highlight the potential, dreaded, sight-threatening complications of TASS and UZ syndrome. In a single case series of nine patients, only five cases developing TASS and the rest four developing UZ syndrome prompt the authors to speculate that both the disorders belong to the same entity. These entities may not always turn out uneventful, and the long-term complications listed in our study may not be considered over-representing the severity. All eye care facilities should exercise strict quality checks of instruments and sterilization protocols to avoid such untoward incidence.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]