gL

yo

s

minor surgical trauma. Anterior segment inflammation this condition toxic anterior segment syndrome (TASS). It

J CATARACT REFRACT SURG - VOL 32, FEBRUARY 2006following cataract surgery may be due to surgical trauma,

retained lens material, bacteria, sterile toxic substances,

or other uncommon factors such as previous uveitis. Since1980, there have been several reports of a severe form of an-

terior segment inflammation after cataract surgery that

resulted in hypopyon formation and varying degrees

of anterior segment damage from toxic substances.112

This was initially referred to as sterile postoperative

is noteworthy that some cases of TASSdthose with local-ized corneal endothelial damagedhave been termed toxicendothelial cell destruction syndrome (TECDS).1317

CLINICAL FINDINGS OF TASS

Toxic anterior segment syndrome most commonly oc-

curs acutely following anterior segment surgery of any

kind, but it can have a delayed onset. The postoperative in-

flammation is sterile (Gram stain and culture negative) and

is due to a noninfectious substance that accidentally enters

the anterior segment, eliciting toxic cellular and extracellu-lar damage to intraocular tissues. Toxic anterior segment

syndrome has a constellation of signs and symptoms simi-

lar to those of infectious bacterial endophthalmitis. Among

the common complaints are blurry vision, ocular pain, and

eye redness following cataract surgery.

The typical hallmark of TASS is an inflammatory

process that starts within 24 hours of cataract surgery, is

limited to the anterior segment of the eye, is always Gramstain and culture negative, and improves with steroid treat-

ment. The anterior segment inflammation is typically

quite severe, usually resulting in hypopyon formation

Accepted for publication December 29, 2005.

From John A. Moran Eye Center, Department of Ophthalmology,University of Utah School of Medicine, Salt Lake City, Utah (Mama-lis, Chew, LeBoyer, Werner), Emory Eye Center, Emory UniversitySchool of Medicine, Atlanta, Georgia (Edelhauser, Dawson), USA.

Presented in part at the annual meeting of the American Acad-emy of Ophthalmology, New Orleans, Lousiana, USA, October2004.

Supported in part by NIH grants EY-00933 and T32-EY07092 andan unrestricted departmental grant from Research to PreventBlindness.

Reprint requests to Nick Mamalis, MD, John A. Moran Eye Center,University of Utah, 50 North Medical Drive, Salt Lake City, Utah,84132, USA. E-mail: nick.mamalis@hsc.utah.edu.

Q 2006 ASCRS and ESCRS 0886-3350/06/$-see front matterREVIEW/

Toxic anterior se

Nick Mamalis, MD, Henry F. Edelhauser, PhDRussell M. LeBoyer, MD,

Toxic anterior segment syndrome (TASS) is a sterby a noninfectious substance that enters the aintraocular tissues. The process typically starts 12gery, is limited to the anterior segment of the eyeusually improves with steroid treatment. The primthalmitis. Review of the literature indicates that ptions with inappropriate chemical composition,denatured ophthalmic viscosurgical devices; enzmetal deposits and residues; and factors related ting or sterilizing compounds. An outbreak of TAthat requires complete analysis of all medicationplete review of operating room and sterilization

J Cataract Refract Surg 2006; 32:324333 Q 2006

Cataract surgery with intraocular lens (IOL) implantation

has evolved into a highly successful surgery. It typically re-

sults in slight transient postoperative inflammation due toPublished by Elsevier Inc.

324UPDATE

ment syndrome

, Daniel G. Dawson, MD, Jesse Chew, MD,iliana Werner, MD, PhD

ile postoperative inflammatory reaction causednterior segment, resulting in toxic damage toto 48 hours after cataract/anterior segment sur-, is always Gram stain and culture negative, andary differential diagnosis is infectious endoph-ossible causes of TASS include intraocular solu-concentration, pH, or osmolality; preservatives;matic detergents; bacterial endotoxin; oxidizedintraocular lenses such as residues from polish-SS is an environmental and toxic control issueand fluids used during surgery, as well as com-protocols.

ASCRS and ESCRS

endophthalmitis, which is a misnomer since the inflamma-

tion primarily involves only the anterior segment of the

eye (Figure 1). In 1992, Monson et al.6 accurately termeddoi:10.1016/j.jcrs.2006.01.065

REVIEW/UPDATE: TASS(Figure 2, A). Another common sign of TASS is diffuse, lim-

bus-to-limbus corneal edema (Figure 2, B). This latter find-

ing is apparently due to widespread endothelial cell

damage. In severe cases of TASS, fibrin formation may

also be noted in the anterior chamber and/or on the surface

of the iris and IOL. The syndrome can result in permanentiris damage, which may cause a dilated, irregular pupil that

constricts and dilates poorly (Figure 2, C), and/or trabecu-

lar meshwork damage. Although TASS patients frequently

have decreased intraocular pressure (IOP) during the early

postoperative course, permanent trabecular meshwork

damage may eventually lead to ocular hypertension or sec-

ondary glaucoma (G.K. Kopecky, MD, J.E. Hill, MD, TASS

Symposium: What You Dont Know Could Be Toxic, pre-sented at the annual meeting of the American Academy of

Ophthalmology, New Orleans, Louisiana, USA, October

2004).

It is difficult to differentiate TASS from infectious bac-

terial endophthalmitis. Although there are several helpful

differentiating symptoms or signs of TASSdit typicallyoccurs within 24 hours compared with 4 to 7 days for

infectious bacterial endophthalmitis; it is almost alwayslimited to the anterior segment; it improves with topical

Figure 1. Diagram illustrating how cases of TASS usually affect only the

anterior segment of the eye (yellow). Cases of toxic endophthalmitis

may occur, which would affect both the anterior segment (yellow) and vit-

reous cavity (light blue), but this is rare relative to the total number of TASS

cases. In contrast, bacterial endophthalmitis usually manifests in the en-

tire ocular cavity and is often most severe in the vitreous cavity.J CATARACT REFRACT SURG -Figure 2. Slitlamp photographs showing some characteristic clinical find-

ings of TASS. A: Hypopyon formation. B: Diffuse limbus-to-limbus corneal

edema. C: Dilated and slightly irregular pupil.VOL 32, FEBRUARY 2006 325

REVIEW/UPDATE: TASSand/or oral steroids and commonly presents with diffuse

corneal edemadnone is specific enough to definitively di-agnose TASS or completely rule out an infectious etiology.

Vitreous involvement is usually prominent in cases of en-

dophthalmitis. Pain is noted in 75% of endophthalmitis pa-

tients, and other signs of infection such as lid swelling andconjunctival chemosis and discharge as well as diffuse ocu-

lar injection are often present (Figure 3). Severe anterior

segment inflammation with hypopyon or fibrin formation

is commonly observed in TASS and endophthalmitis and

initially does not help differentiate the 2 conditions. Added

to this problem is that a certain percentage of patients with

infectious bacterial endophthalmitis have biopsy samples

(ie, vitreous or anterior chamber taps) that are Gram stainand culture negative.9,10

ETIOLOGY OF TASS

Although rare, TASS is a growing problem for intraoc-

ular surgeons, especially because it often represents an en-

demic outbreak of cases at a specific surgical center. Since

the causes of TASS are numerous and varied (Figure 4), itcan be difficult for the surgeon and faculty at a surgical cen-

ter to isolate a cause directly. Any medication injected

around the eye, such as subconjunctival or sub-Tenons in-

jections, or placed topically in the eye at the conclusion of

surgery or in the immediate postoperative period may be

implicated in causing or worsening this condition.

The histopathologic hallmark of TASS is toxic anterior

segment damagedcellular necrosis and/or apoptosis andextracellular damage resulting in a severe acute inflamma-

tory immune response. Since the corneal endothelium is

the most sensitive anterior segment tissue to toxic agents,

the cornea is usually the structure most severely affected

Figure 3. Slitlamp photograph of a case of bacterial endophthalmitis.

Prominent hypopyon formation and diffuse ocular injection can be ob-

served. This case had significant vitreous involvement.J CATARACT REFRACT SURG326by TASS. It can result from simple overlooked problems

such as intraocular irrigating solutions in which the chem-

ical composition, pH, or osmolality is incompatible with

tissue preservation.1822 Additionally, toxic contaminating

residues composed of denatured ophthalmic viscosurgical

devices (OVDs),5 detergents,4,23,24 bacterial endotoxin,25

or other impurities may be injected into the eye, resulting

in corneal endothelial cell damage. These latter causes are

a particular problem with reusable intraocular instruments

(eg, cannulas). Toxicity to the corneal endothelium has

been directly linked to many different ocular medications

and can be due to the chemical composition, the concentra-

tion, the pH, or the osmolality of the medication or vehicle

or whether preservatives or additives are mixed in themedication.22,26,27

Edelhauser et al.1315,1922,24 have performed much of

the pioneering work on the effect of intraocular irrigating

solutions, instrument-related contaminants, and intraocu-

lar medications on the corneal endothelium. The common

finding in all the studies is that the mechanism of corneal

edema is related initially to acute breakdown of endothelial

junctions and acute loss of the barrier function. Over thelong-term, if the remaining viable corneal endothelial cells

cannot adequately cover the damaged area(s) by migration,

thinning, and spreading to cover a larger surface area, per-

manent edema results.

Preservatives

The corneal endothelium is exquisitely sensitive topreservatives commonly used in topical ocular medica-

tions. It is important that any medication injected into

the eye be preservative free. There are several reports of

medications with preservatives inadvertently injected into

Irrigating solutions or ophthalmic viscosurgical devicesIncomplete chemical composition Incorrect pH (8.5) Incorrect osmolality (400 mOsm) Preservatives or additives (eg, antibiotics, dilating medications)

Ophthalmic instrument contaminants Detergent residues (ultrasonic, soaps, enzymatic cleaners) Bacterial lipopolysaccharides or other endotoxin residuesMetal ion residues (copper and iron)Denatured OVDs

Ocular medicationsIncorrect drug concentration Incorrect pH (8.5) Incorrect osmolality (400 mOsm) Vehicle with wrong pH or osmolality Preservatives in medication solution

Intraocular lenses Polishing compoundsCleaning and sterilizing compounds

Figure 4. Known causes of TASS.- VOL 32, FEBRUARY 2006

REVIEW/UPDATE: TASSthe eye during anterior segment surgery. Liu et al.16 de-

scribe several cases of TASS from inadvertent intraocular

use of Eye Stream (Alcon Laboratories), an eye rinse for

external use only that is preserved with benzalkonium

chloride (BAK) 0.01%. All patients who were evaluated

postoperatively showed generalized corneal edema withnormal IOP. Only 1 of the 19 patients reported transient

pain. Most eyes ended up with a final visual acuity of count-

ing fingers secondary to persistent corneal edema. Other

than corneal transplantation, no treatment was beneficial

in these latter patients.

Eleftheriadis et al.17 report a series of similar cases in

post-cataract-surgery patients. They found significant cor-

neal edema and endothelial damage resulting from anOVD containing BAK. If used chronically and on a frequent

basis, normal concentrations of BAK in topical ocular med-

ications (0.005% to 0.01%) have been found to damage and

irritate the conjunctiva and cornea mildly; topical applica-

tion of BAK 2% (200- to 400-fold higher than the normal

topical concentration) has been shown to cause necrosis

of the conjunctiva and cornea.17 Endothelial damage

from topical ocular medications containing 0.005% to0.01% BAK is exceedingly uncommon when these medica-

tions are used and applied correctly. The threshold for the

start of physiologic and ultrastructural alterations to the

corneal endothelium with BAK is 0.0001%, and the highest

tolerable intraocular concentration of BAK is 0.001%.26,27

However, these latter figures are extrapolated from rabbit

studies.

Intraocular Anesthetics

Intracameral use of commercially available prepara-

tions of preservative-free bupivicaine hydrochloride 0.5%

and preservative-free lidocaine hydrochloride 2.0% have

caused significant corneal thickening and opacification

postoperatively.28 Although they are preservative free, in-

tracameral use of these commercially available anesthetic

agents can potentially cause corneal endothelial cell dam-

age.2830 By comparison, intracameral use of preservative-free lidocaine hydrochloride 1% appears to be safe for

routine cataract surgery, provided it is immediately fol-

lowed by cataract surgery (ie, phacoemulsification) in

which most of the lidocaine 1% is washed out of the cornea

and iris.3133

Sterilization/Detergents

Any substance used in cleaning and sterilizing ophthal-

mic instruments may cause TASS (Figure 5). Various enzy-

matic and nonenzymatic detergents are used in cleaningreusable ocular instruments between cases (eg, ultrasonic

bath and cleaning detergents). The detergents may accu-

mulate as deposits and, eventually, residues on the innerJ CATARACT REFRACT SURGand outer surfaces of reusable instruments; most com-

monly, reusable instruments that contain residual OVD

material. The enzymes or other active ingredients in the de-

tergents are deactivated only when exposed to tempera-

tures higher than 140C. Since most autoclaves reach120C to 130C, there is a possibility of accidentally in-jecting the active detergents into the eye during anterior

segment surgery, especially with reusable cannulas and

irrigation/aspiration (I/A) tips. The only effective way to re-

move detergent deposits from reusable instruments im-

mediately after cleaning is by flushing instruments with

adequate amounts of sterile deionized water. For example,

each port of the I/A tips should be flushed with 120 cc of

sterile deionized water.Parikh et al.22,24 report in vitro data showing a dose-

related increase in corneal thickness from corneal endo-

thelial damage in rabbits and humans due to enzymatic

detergents. They also report increased corneal endothelial

permeability and an inflammatory response in rabbits

when the enzymatic detergent is injected into the anterior

chamber. Some of the earliest reported cases of TASS

described as sterile hypopyon endophthalmitis weredue to toxic detergent residues on reusable ocular instru-

ments from ultrasonic cleaning solutions, heat-stable

cleaning detergents, or cleaning or finishing compounds

on IOLs.3,34,35

Detergent residues on ophthalmic surgical instruments

have been reported to cause more localized anterior seg-

ment toxicity; this syndrome has been referred to as

TECDS. Breebaart et al.13 describe severe toxic endothelialcell destruction of the cornea following extracapsular cata-

ract surgery from detergent residues found on reusable can-

nulas. The patients had profound corneal edema within

24 hours of surgery that was traced to the toxic effects of

an ultrasonic detergent on the corneal endothelium.

In addition to detergent residues, outbreaks of TASS

are thought to be related to endotoxin contamination of

instruments during sterilization. Water baths, ultrasoundbaths, and even autoclave reservoirs may harbor gram-

negative bacteria, particularly water baths and reservoirs

that have not been changed regularly. Although gram-

negative bacteria are destroyed during the heat-sterilization

process of autoclaving, heat-stable lipopolysaccharide

(LPS) endotoxins from the gram-negative bacterial cell

wall remain enzymatically active and may remain attached

to the instruments as deposits. When dried, the endotoxindeposits become residues that can be removed from the

instrument only by rinsing and wiping with alcohol or ac-

etone. Injection of a heat-stable LPS endotoxin into the eye

during surgery has caused significant anterior segment

inflammation.25 Klebsiella pneumoniae bacteria was cul-

tured from the cleaning water bath and equipment in that

outbreak. Recent outbreaks of diffuse lamellar keratitis- VOL 32, FEBRUARY 2006 327

REVIEW/UPDATE: TASS(DLK) in patients who had laser in situ keratomileusis have

been traced to LPS endotoxin contamination of micro-

keratome blades.36 Whitby and Hitchins37 first suggested

that heat-stable bacterial endotoxin from contaminated

autoclave water reservoirs can deposit on intraocularinstruments even during the steam autoclave sterilization

process.

Another potential cause of TASS secondary to a sterili-

zation procedure involves oxidized metal deposits and res-

idues, which may form on reusable surgical tubing or metal

hubs of cannulas when plasma gas sterilization is used.15,38

In patients with acute postoperative inflammation follow-

ing cataract surgery, a toxic residue composed of traceamounts of copper and zinc ions was found on sterilized

surgical instruments. The chrome covering the cannulas

may have worn away or the solder joint decomposed, re-

sulting in leaching and oxidization of the underlying

exposed brass metal, which allowed toxic concentrations

of copper and zinc deposits to accumulate. After steriliza-

tion, toxic copper and zinc residues formed and remained

in the lumen of the cannula until they were flushed into

the eye during surgery.

Denatured Ophthalmic Viscosurgical Devices

Another potential TASS source related to reusable in-

traocular instruments is the introduction of retained dena-

tured OVD residues into the anterior segment of the eye. If

reusable cannulas and I/A tips are not properly flushed

following surgery, residual OVD material may be broken

down or altered during sterilization, which could causetoxic inflammation when flushed into the eye. Kim5 has re-

ported the adverse effects in patients who had intraocular

inflammation secondary to denatured OVD substances

Figure 5. Effects of enzymatic detergents on the corneal endothelium. A: Scanning electron microscopy (SEM) of human corneal endothelium after being

perfused with BSS Plus for 3 hours in an artificial anterior chamber (ie, normal control). The SEM shows an undisrupted monolayer of corneal endothelial cells

with intact intercellular junctions (original magnification540). B: Transmission electronmicroscopy (TEM) of the cornea in (A) shows the healthy endothelialcells in cross-section (original magnification 4350). C: Scanning electron microscopy of corneal endothelium after being perfused with 1.56% enzymaticdetergent in BSS Plus solution for 3 hours in an artificial anterior chamber (ie, toxic case). The SEM shows severe loss of the corneal endothelial cell monolayer

and intercellular junctions (original magnification 540). D: Transmission electron microscopy of the cornea in (C) shows that the corneal endothelial cellswere necrotic, apoptotic, or in a severe degenerative state. Notice the bare areas of exposed Descemets membrane (original magnification 4350).J CATARACT REFRACT SURG -328 VOL 32, FEBRUARY 2006

REVIEW/UPDATE: TASSbeing injected into the eye. These cases probably also had

detergents trapped in the retained OVDmaterial, so it is un-

clear whether the OVD residue by itself caused the toxicity.

Antibiotic Agents

Toxicity from antibiotic agents most commonly occurs

when they are used in irrigating solutions or injectedinto the anterior segment at the conclusion of surgery to

prevent endophthalmitis. The use of gentamicin sulfate

and vancomycin in irrigating solutions or direct intracam-

eral injection was initially devised for the prevention of en-

dophthalmitis.39 Concern about the possibility of toxicity

from intraocular gentamicin use (gentamicin has been re-

ported to cause macular toxicity, even in a few cases given

subconjunctivally40,41) as well as about possible resistanceto vancomycin has been expressed. The concerns led to

the investigation of other intraocular antibiotic agents

for the prophylaxis of endophthalmitis, particularly the

cephalosporins (eg, cefazolin, ceftazidime, cefotaxime, or

cefuroxime).

Two agents, cefotaxime and cefuroxime, have recently

been promoted for use intracamerally at the conclusion

of cataract surgery. Kramann et al.42 studied the effects ofprophylactic intracameral cefotaxime on human corneal

endothelium. They found no significant endothelial dam-

age or toxicity 3 months after surgery. A dose of cefotaxime

0.25% solution instilled in the anterior chamber was not

toxic. The use of intracameral cefuroxime has gained

widespread acceptance for endophthalmitis prophylaxis

after cataract surgery in some countries, such as Sweden.

Montan et al.43 have published 2 reports showing that a1.0 mL dose of intracameral cefuroxime apparently had

no signs of local toxicity. They also report that cefuroxime

had no significant effect on endothelial cell density or ante-

rior segment inflammation measured by laser flare interfer-

ometry. The authors of the latter conclude that prophylactic

intracameral cefuroxime has a major role in decreasing the

rate of postoperative endophthalmitis in Sweden. However,

these results are from an uncontrolled retrospective obser-vational study and therefore must be confirmed by further

prospective studies.

Overall, despite some promising data, prophylactic in-

tracameral antibiotic agents are currently not routinely rec-

ommended for endophthalmitis prophylaxis after cataract

surgery in most countries, including the U.S., since the

risk for toxicity and/or infectious complications is high

and they have not been shown to reduce endophthalmitisrates.

Water

In 2002, an outbreak of TASS after cataract surgery in-

volved 3 surgeons at 2 affiliated facilities.11 After an initialJ CATARACT REFRACT SURG -investigation, attention turned to the quality of the water

and steam provided for sterilization by the autoclave steam

generator. Samples of the feed water and autoclave steam

condensates were collected and analyzed by spectroscopy,

ion chromatography, pH, and conductivity studies. Results

showed a carry-over of sulfate, silica, copper, zinc, andnickel in the condensates. Increased sulfate levels on the

surface of cataract surgery equipment that were retired dur-

ing the outbreak were documented by analysis of ultrasonic

rinsates. Sulfate was the impurity found in the autoclave

steam and was thought to have caused the TASS outbreak.

This would explain the relatively benign course of these

cases in comparison with the course in other cases, such

as those attributed to copper and zinc residues.15,38

In the analysis of the 2002 TASS outbreak caused by

sulfate water impurities,11 a review of maintenance records

showed that the autoclave steam generator had been sup-

plied with softened city water, which was flushed and

drained weekly during its first 5 years of use. In 2000, the

frequency of flushing and draining was decreased to once

every 4 to 8 weeks; this might have promoted the accumu-

lation and carry-over of impurities in feed water. No TASScases were observed after the steam generator was replaced

and a system to supply the new generator with deionized,

ultrafiltered water was installed.

DELAYED-ONSET POSTOPERATIVE STERILEENDOPHTHALMITIS

While most reported TASS cases are acute, there have

been several instances of delayed-onset TASS following cat-

aract surgery.

Intraocular Lens-Induced Inflammation

Jehan et al.8 report 10 cases of a delayed-onset acute

IOL inflammation following cataract surgery. In all pa-

tients, a hydrophilic acrylic IOL (MemoryLens) was

implanted. The onset of the inflammation occurred 1 to

21 days postoperatively. All the anterior chamber taps

were Gram stain and culture negative. The patients im-

proved with intense topical antiinflammatory medication.

It was theorized that a residual polishing compound onthe MemoryLens was responsible for the postoperative

inflammation.

One of the first terms used to describe patients with

TASS was sterile hypopyon or sterile endophthalmitis. This

was initially described by Meltzer1 in 1980. It is theoreti-

cally possible that the IOL was the source of inflammation

andmaterial or substance in the packaging or solution coat-

ing the lens was retained and led to a toxic inflammation.The IOL finish and design as well as chemicals used in pol-

ishing, cleaning, and sterilizing the lens have been impli-

cated as causes of this type of inflammation.VOL 32, FEBRUARY 2006 329

REVIEW/UPDATE: TASSOphthalmic Ointments

Another potential source of delayed-onset TASS isthe ingress of ophthalmic ointment used postoperatively in

the anterior segment of the eye. An outbreak of delayed-

onset TASS was recently described by Werner et al.12 In

that study, an oily material coating the anterior surface

of the IOL or forming small globules within the anterior

chamber was found in a group of delayed-onset TASS

patients from Canada (Figure 6, A). Several patients had

significant corneal edema, and 2 had penetrating kerato-plasty. Evaluation of the corneas revealed severe destruc-

tion of corneal endothelial cells (Figure 6, B). Analysis

of some explanted IOLs showed a significant residue of

hydrocarbons on the IOL surfaces (Figure 6, C). The com-

position of these hydrocarbons exactly matched the vehi-

cle within the postoperative ointment that was placed in

the eye. It is hypothesized that the use of a clear corneal

wound and postoperative topical ointment containing pe-troleum as well as tight patching allowed ingress of this

material into the anterior segment of the eye, causing de-

layed-onset TASS.

TREATMENT OF TASS

The main treatment for TASS centers on prevention

because once the toxic agent enters the eye and causesdamage, the clinician can do little other than suppress

the secondary inflammatory immune response. Thus,

once an infectious etiology has been ruled out, themainstay

of treatment for TASS is intense topical corticosteroid

drops. The patient should be started on a regimen of pred-

nisolone acetate 1% drops every 1 to 2 hours and carefully

followed, especially during the first days of topical cortico-

steroid use, to ensure that the inflammatory condition isnot worsening and is stabilizing. Careful slitlamp examina-

tion allows the surgeon to document resolution of anterior

segment inflammation and corneal edema.

The IOP should also be closely followed after a toxic

sterile insult to the anterior segment of the eye.1,35 As max-

imum damage to the anterior segment has presumably

already occurred, anterior chamber washout is currently

not routinely recommended for treatment of TASS. Whilethe IOP may initially be low, recovery of the production

of aqueous humor by the ciliary processes can cause a pre-

cipitous rise in IOP several days after the initial insult. This

IOP change occurs because the toxic agent(s) can injure

the trabecular meshwork, causing acute trabeculitis and

subsequent chronic long-term damage to the trabecular

meshwork.

As soon as the cornea clears sufficiently to allow ade-quate visualization of the anterior chamber angle, the pa-

tient should have a gonioscopic evaluation to look for

peripheral anterior synechias, which may indicate thatJ CATARACT REFRACT SURG330Figure 6. Toxic anterior segment syndrome secondary to intraocular pene-

trationofophthalmicointment.A: Clinical picture takenduringthe firstpost-

operativeweek showsadistinct bubble inside the anterior chamber.B: Light

photomicrograph of a histologic section obtained from a corneal button

shows variable areas of epithelium thinning, thickening of the stroma,

with condensation of posterior lamellae, intact Descemets membrane,

and complete absence of the corneal endothelium (hematoxylin and eosin

stain; original magnification 100). C: Explanted silicone lens with an oilymaterial coating large areas of the anterior and posterior optic surfaces.- VOL 32, FEBRUARY 2006

REVIEW/UPDATE: TASSchronic long-term trabecular meshwork damage has oc-

curred.1,35 Specular or confocal microscopy of the corneal

endothelium is also helpful at this point to assess the degree

of endothelial cell damage.

CLINICAL COURSE

The clinical outcome of individual patients with TASS

depends on many factors such as the type and amount of

substance introduced into the eye, the duration of exposure

to the substance, and when treatment occurred in the

course of the injury. Patients with relatively mild casesshow rapid clearing of the inflammation, with slightly

less rapid clearing of the cornea (days to weeks). Patients

who have moderate TASS have a more prolonged clearing

(weeks to months), with possibly slight residual corneal

edema and/or increased IOP. Patients who have severe

TASS generally have permanent damage to the eye such

as persistent, nonclearing corneal edema that requires

corneal transplantation, significant trabecular meshworkdamage that leads to uncontrolled IOP, chronic anterior

segment inflammation that may cause transient or perma-

nent cystoid macular edema, or significant iris damage

that may lead to a permanently fixed, dilated pupil. Patients

with severe trabecular meshwork damage sometimes de-

velop glaucoma that is relatively resistant to medical treat-

ment alone. These cases usually require surgical treatment

such as trabeculectomy or placement of a tube shuntdevice.1,35

ANALYSIS: TOXIC ANTERIOR SEGMENT SYNDROME

As the mainstay of treatment for TASS centers on pre-

vention, it is critically important that the entire surgicalteam (surgical nurses, operating room technicians, resi-

dents, physicians, and pharmacists) knows what is appro-

priate for use in the eye. This is especially true for anyone

involved in cleaning and sterilizing ophthalmic instru-

ments. Those involved in ordering ocular medications to

be used in anterior segment surgery or preparing these

medications should also be involved. A basic step is to en-

sure that everyone involved in cleaning and sterilizing reus-able intraocular instruments is thoroughly instructed in

the protocols to properly clean and sterilize the instru-

ments (ie, preventing the possibility of toxic residues from

accumulating on the reusable instruments). Furthermore,

reusable instrument use should be kept to a minimum, par-

ticularly those that are high risk for contamination (eg, can-

nulas or damaged instruments). The reusable instruments

that cannot be switched or are chosen not to be switchedto disposable types, eg, I/A tips and phacoemulsification

handpieces, should be thoroughly rinsed at the conclusion

of each cleaning step with sterile, deionized water. It isJ CATARACT REFRACT SURGespecially important to rinse the phacoemulsification

handpiece and I/A tips through both inflow and aspiration

ports.

Ultrasound water baths should be replaced daily since

the dirty bath water often grows gram-negative bacteria

such as Klebsiella or Pseudomonas species, which couldlead to a buildup of heat-stable LPS endotoxins. The use

of a steam autoclave sterilizer requires that the water re-

servoir be changed at least weekly to prevent the buildup

of gram-negative bacteria and potentially toxic LPS

endotoxins.

The surgical center staff should remain vigilant when

ordering any agentdirrigating solutions, OVDs, or othermedicationsdthat will be used in the eye during anteriorsegment surgery. This includes the ordering of complete in-

traocular irrigating solutions such as balanced salt solution

(BSS) or BSS Plus, as well as intraocular medications of any

kind. The surgical staff should also be up to date on the

newest, most complete irrigants that would have a limited

shelf life if it were not that they come as a 2-component so-

lution, which means the 2 components must be reconsti-

tuted before intraocular use. For example, AMO EndosolExtra is the newest complete ocular irrigant to come on

the market and should be bioequivalent to BSS Plus. A ma-

jor issue with Endosol Extra is that the large part-1 compo-

nent, 500 mL, has a pH of 3.5. If the part-2 component is

not added with part 1, severe damage to the intraocular tis-

sue will occur. Care should also be taken to check that the

intraocular medications used during anterior segment sur-

gery are preservative-free and at the proper intraoculardrug concentration. This is especially important for epi-

nephrine, which is added to irrigating solutions, or for in-

tracameral anesthetics or antibiotics, which are injected

directly into the eye. In addition, the surgical staff should

be attuned to the proper concentrations of medications

and the proper pH and osmolality of vehicles needed

during intraocular surgery. For example, intracameral

lidocaine used to help anesthetize the eye should be meth-ylparaben-free; intracameral lidocaine, indocyanine green,

trypan blue, acetylcholine chloride (Miochol), and carba-

chol (Miostat) should be mixed with BSS and not sterile

water (L.J. Ronge, Toxic Anterior Segment Syndrome:

Why Sterile Isnt Clean Enough, Eyenet 2002, Novem-

ber/December, pages 1718).4446

An outbreak of TASS in a surgical center is an environ-

mental and toxin control issue that requires complete anal-ysis of all medications and fluids used during the surgery. It

is the surgeons responsibility to let the surgical team and

center know that a case occurred since they are usually

the first to recognize a case. Appointing a staff member to

coordinate the clinical review and establishing flow charts

to track changes or factors potentially responsible for the

case or outbreak is typically helpful. It is critically- VOL 32, FEBRUARY 2006 331

REVIEW/UPDATE: TASSimportant to prove that the medications used during sur-

gery were the intended medications ordered for use by

the surgeon. A complete review of operating room proto-

cols should be undertaken by the surgeon as well as repre-

sentatives from the surgical center and all involved nursing

staff and personnel. Protocols used in the sterilization andpreparation of instruments from surgery should be care-

fully evaluated to rule out the potential sources of TASS.

The American Society of Cataract and Refractive Sur-

gery has established a center at the University of Utah to

evaluate unexplained cases of postoperative inflammation

or endophthalmitis. This center has developed protocols

to be used in the evaluation of patients with TASS. Ophthal-

mic research fellows are available to provide analyses ofoutbreaks of TASS, with subsequent recommendations on

ways to prevent future occurrences. Contact information:

Nick Mamalis, MD, Director, Intermountain Ocular Re-

search Center, John A. Moran Eye Center, University of

Utah School of Medicine, 50 North Medical Drive, Salt

Lake City, Utah 84132, USA; phone (801) 581-6586;

e-mail: nick.mamalis@hsc.utah.edu. Edelhauser has also

formed a response team at Emory University Eye Center,which has the Centers for Disease Control and Prevention

adjacent to its medical campus for assistance in evaluating

and preventing further cases or outbreaks or for the inves-

tigation and analysis of TASS. Contact information: Henry

F. Edelhauser, PhD, Emory Eye Center, Emory University,

1365B Clifton Road NE, Atlanta, Georgia 30322, USA;

phone (404) 778-5853; e-mail: ophthfe@emory.edu. Both

centers are available as a resource to physicians and surgicalcenters to aid in the investigation of outbreaks of TASS to

help find the etiology of these cases and eliminate potential

sources of postoperative inflammation.

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REVIEW/UPDATE: TASSJ CATARACT REFRACT SURG - VOL 32, FEBRUARY 2006 333

Toxic anterior segment syndromeClinical Findings of TASSEtiology of TASSPreservativesIntraocular AnestheticsSterilization/DetergentsDenatured Ophthalmic Viscosurgical DevicesAntibiotic AgentsWater

Delayed-Onset Postoperative Sterile EndophthalmitisIntraocular Lens-Induced InflammationOphthalmic Ointments

Treatment of TASSClinical CourseAnalysis: Toxic Anterior Segment SyndromeREFERENCES