J CATARACT REFRACT SURG - VOL 32, FEBRUARY 2006

REVIEW/UPDATE

Toxic anterior segment syndrome

Nick Mamalis, MD, Henry F. Edelhauser, PhD, Daniel G. Dawson, MD, Jesse Chew, MD,
Russell M. LeBoyer, MD, Liliana Werner, MD, PhD

Toxic anterior segment syndrome (TASS) is a sterile postoperative inflammatory reaction caused
by a noninfectious substance that enters the anterior segment, resulting in toxic damage to
intraocular tissues. The process typically starts 12 to 48 hours after cataract/anterior segment surgery, is limited to the anterior segment of the eye, is always Gram stain and culture negative, and
usually improves with steroid treatment. The primary differential diagnosis is infectious endophthalmitis. Review of the literature indicates that possible causes of TASS include intraocular solutions with inappropriate chemical composition, concentration, pH, or osmolality; preservatives;
denatured ophthalmic viscosurgical devices; enzymatic detergents; bacterial endotoxin; oxidized
metal deposits and residues; and factors related to intraocular lenses such as residues from polishing or sterilizing compounds. An outbreak of TASS is an environmental and toxic control issue
that requires complete analysis of all medications and fluids used during surgery, as well as complete review of operating room and sterilization protocols.
J Cataract Refract Surg 2006; 32:324333 Q 2006 ASCRS and ESCRS

Cataract surgery with intraocular lens (IOL) implantation

has evolved into a highly successful surgery. It typically results in slight transient postoperative inflammation due to
minor surgical trauma. Anterior segment inflammation
following cataract surgery may be due to surgical trauma,
retained lens material, bacteria, sterile toxic substances,
or other uncommon factors such as previous uveitis. Since
1980, there have been several reports of a severe form of anterior 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

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 (Mamalis, Chew, LeBoyer, Werner), Emory Eye Center, Emory University
School of Medicine, Atlanta, Georgia (Edelhauser, Dawson), USA.
Presented in part at the annual meeting of the American Academy of Ophthalmology, New Orleans, Lousiana, USA, October
2004.
Supported in part by NIH grants EY-00933 and T32-EY07092 and
an unrestricted departmental grant from Research to Prevent
Blindness.
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
Published by Elsevier Inc.

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endophthalmitis, which is a misnomer since the inflammation primarily involves only the anterior segment of the
eye (Figure 1). In 1992, Monson et al.6 accurately termed
this condition toxic anterior segment syndrome (TASS). It
is noteworthy that some cases of TASSdthose with localized corneal endothelial damagedhave been termed toxic
endothelial cell destruction syndrome (TECDS).1317

CLINICAL FINDINGS OF TASS

Toxic anterior segment syndrome most commonly occurs acutely following anterior segment surgery of any
kind, but it can have a delayed onset. The postoperative inflammation is sterile (Gram stain and culture negative) and
is due to a noninfectious substance that accidentally enters
the anterior segment, eliciting toxic cellular and extracellular damage to intraocular tissues. Toxic anterior segment
syndrome has a constellation of signs and symptoms similar 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 Gram
stain and culture negative, and improves with steroid treatment. The anterior segment inflammation is typically
quite severe, usually resulting in hypopyon formation
0886-3350/06/$-see front matter
doi:10.1016/j.jcrs.2006.01.065

REVIEW/UPDATE: TASS

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 vitreous cavity (light blue), but this is rare relative to the total number of TASS
cases. In contrast, bacterial endophthalmitis usually manifests in the entire ocular cavity and is often most severe in the vitreous cavity.

(Figure 2, A). Another common sign of TASS is diffuse, limbus-to-limbus corneal edema (Figure 2, B). This latter finding 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 permanent
iris damage, which may cause a dilated, irregular pupil that
constricts and dilates poorly (Figure 2, C), and/or trabecular 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 secondary glaucoma (G.K. Kopecky, MD, J.E. Hill, MD, TASS
Symposium: What You Dont Know Could Be Toxic, presented at the annual meeting of the American Academy of
Ophthalmology, New Orleans, Louisiana, USA, October
2004).
It is difficult to differentiate TASS from infectious bacterial endophthalmitis. Although there are several helpful
differentiating symptoms or signs of TASSdit typically
occurs within 24 hours compared with 4 to 7 days for
infectious bacterial endophthalmitis; it is almost always
limited to the anterior segment; it improves with topical

Figure 2. Slitlamp photographs showing some characteristic clinical findings of TASS. A: Hypopyon formation. B: Diffuse limbus-to-limbus corneal
edema. C: Dilated and slightly irregular pupil.

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REVIEW/UPDATE: TASS

and/or oral steroids and commonly presents with diffuse

corneal edemadnone is specific enough to definitively diagnose TASS or completely rule out an infectious etiology.
Vitreous involvement is usually prominent in cases of endophthalmitis. Pain is noted in 75% of endophthalmitis patients, and other signs of infection such as lid swelling and
conjunctival chemosis and discharge as well as diffuse ocular 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 stain
and culture negative.9,10
ETIOLOGY OF TASS

Although rare, TASS is a growing problem for intraocular surgeons, especially because it often represents an endemic outbreak of cases at a specific surgical center. Since
the causes of TASS are numerous and varied (Figure 4), it
can be difficult for the surgeon and faculty at a surgical center to isolate a cause directly. Any medication injected
around the eye, such as subconjunctival or sub-Tenons injections, 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 and
extracellular damage resulting in a severe acute inflammatory 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

by TASS. It can result from simple overlooked problems

such as intraocular irrigating solutions in which the chemical 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 concentration, the pH, or the osmolality of the medication or vehicle
or whether preservatives or additives are mixed in the
medication.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 intraocular 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 the
long-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, permanent edema results.
Preservatives

The corneal endothelium is exquisitely sensitive to

preservatives commonly used in topical ocular medications. 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 devices

Incomplete chemical composition
Incorrect pH (<6.5 or >8.5)
Incorrect osmolality (<200 mOsm or >400 mOsm)
Preservatives or additives (eg, antibiotics, dilating medications)
Ophthalmic instrument contaminants
Detergent residues (ultrasonic, soaps, enzymatic cleaners)
Bacterial lipopolysaccharides or other endotoxin residues
Metal ion residues (copper and iron)
Denatured OVDs
Ocular medications
Incorrect drug concentration
Incorrect pH (<6.5 or >8.5)
Incorrect osmolality (<200 mOsm or >400 mOsm)
Vehicle with wrong pH or osmolality
Preservatives in medication solution
Intraocular lenses
Polishing compounds
Cleaning and sterilizing compounds

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

Prominent hypopyon formation and diffuse ocular injection can be observed. This case had significant vitreous involvement.

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Figure 4. Known causes of TASS.

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the eye during anterior segment surgery. Liu et al.16 describe 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 with
normal IOP. Only 1 of the 19 patients reported transient
pain. Most eyes ended up with a final visual acuity of counting 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 corneal edema and endothelial damage resulting from an
OVD containing BAK. If used chronically and on a frequent
basis, normal concentrations of BAK in topical ocular medications (0.005% to 0.01%) have been found to damage and
irritate the conjunctiva and cornea mildly; topical application 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% to
0.01% BAK is exceedingly uncommon when these medications 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 preparations 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, intracameral use of these commercially available anesthetic
agents can potentially cause corneal endothelial cell damage.2830 By comparison, intracameral use of preservativefree lidocaine hydrochloride 1% appears to be safe for
routine cataract surgery, provided it is immediately followed 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 ophthalmic instruments may cause TASS (Figure 5). Various enzymatic and nonenzymatic detergents are used in cleaning
reusable ocular instruments between cases (eg, ultrasonic
bath and cleaning detergents). The detergents may accumulate as deposits and, eventually, residues on the inner

and outer surfaces of reusable instruments; most commonly, reusable instruments that contain residual OVD
material. The enzymes or other active ingredients in the detergents are deactivated only when exposed to temperatures higher than 140 C. Since most autoclaves reach
120 C to 130 C, there is a possibility of accidentally injecting 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 remove detergent deposits from reusable instruments immediately 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 doserelated increase in corneal thickness from corneal endothelial 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 were
due to toxic detergent residues on reusable ocular instruments 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 segment toxicity; this syndrome has been referred to as
TECDS. Breebaart et al.13 describe severe toxic endothelial
cell destruction of the cornea following extracapsular cataract surgery from detergent residues found on reusable cannulas. 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, ultrasound
baths, and even autoclave reservoirs may harbor gramnegative bacteria, particularly water baths and reservoirs
that have not been changed regularly. Although gramnegative 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 endotoxin
deposits become residues that can be removed from the
instrument only by rinsing and wiping with alcohol or acetone. Injection of a heat-stable LPS endotoxin into the eye
during surgery has caused significant anterior segment
inflammation.25 Klebsiella pneumoniae bacteria was cultured from the cleaning water bath and equipment in that
outbreak. Recent outbreaks of diffuse lamellar keratitis

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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 magnification 540). B: Transmission electron microscopy (TEM) of the cornea in (A) shows the healthy endothelial
cells in cross-section (original magnification 4350). C: Scanning electron microscopy of corneal endothelium after being perfused with 1.56% enzymatic
detergent 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 cells
were necrotic, apoptotic, or in a severe degenerative state. Notice the bare areas of exposed Descemets membrane (original magnification 4350).

(DLK) in patients who had laser in situ keratomileusis have

been traced to LPS endotoxin contamination of microkeratome blades.36 Whitby and Hitchins37 first suggested
that heat-stable bacterial endotoxin from contaminated
autoclave water reservoirs can deposit on intraocular
instruments even during the steam autoclave sterilization
process.
Another potential cause of TASS secondary to a sterilization procedure involves oxidized metal deposits and residues, 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 following cataract surgery, a toxic residue composed of trace
amounts 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, resulting in leaching and oxidization of the underlying

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exposed brass metal, which allowed toxic concentrations

of copper and zinc deposits to accumulate. After sterilization, 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 intraocular instruments is the introduction of retained denatured 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 cause
toxic inflammation when flushed into the eye. Kim5 has reported the adverse effects in patients who had intraocular
inflammation secondary to denatured OVD substances

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being injected into the eye. These cases probably also had
detergents trapped in the retained OVD material, so it is unclear 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 injected
into the anterior segment at the conclusion of surgery to
prevent endophthalmitis. The use of gentamicin sulfate
and vancomycin in irrigating solutions or direct intracameral injection was initially devised for the prevention of endophthalmitis.39 Concern about the possibility of toxicity
from intraocular gentamicin use (gentamicin has been reported to cause macular toxicity, even in a few cases given
subconjunctivally40,41) as well as about possible resistance
to 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 of
prophylactic intracameral cefotaxime on human corneal
endothelium. They found no significant endothelial damage 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 a
1.0 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 anterior segment inflammation measured by laser flare interferometry. 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 observational study and therefore must be confirmed by further
prospective studies.
Overall, despite some promising data, prophylactic intracameral antibiotic agents are currently not routinely recommended 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 endophthalmitis
rates.
Water

In 2002, an outbreak of TASS after cataract surgery involved 3 surgeons at 2 affiliated facilities.11 After an initial

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, and
nickel in the condensates. Increased sulfate levels on the
surface of cataract surgery equipment that were retired during 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 supplied 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 accumulation and carry-over of impurities in feed water. No TASS
cases 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 STERILE
ENDOPHTHALMITIS

While most reported TASS cases are acute, there have

been several instances of delayed-onset TASS following cataract surgery.
Intraocular Lens-Induced Inflammation

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

IOL inflammation following cataract surgery. In all patients, 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 improved with intense topical antiinflammatory medication.
It was theorized that a residual polishing compound on
the 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 theoretically possible that the IOL was the source of inflammation
and material or substance in the packaging or solution coating the lens was retained and led to a toxic inflammation.
The IOL finish and design as well as chemicals used in polishing, cleaning, and sterilizing the lens have been implicated as causes of this type of inflammation.

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Ophthalmic Ointments

Another potential source of delayed-onset TASS is

the ingress of ophthalmic ointment used postoperatively in
the anterior segment of the eye. An outbreak of delayedonset 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 keratoplasty. Evaluation of the corneas revealed severe destruction 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 composition of these hydrocarbons exactly matched the vehicle 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 petroleum as well as tight patching allowed ingress of this
material into the anterior segment of the eye, causing delayed-onset TASS.
TREATMENT OF TASS

The main treatment for TASS centers on prevention

because once the toxic agent enters the eye and causes
damage, the clinician can do little other than suppress
the secondary inflammatory immune response. Thus,
once an infectious etiology has been ruled out, the mainstay
of treatment for TASS is intense topical corticosteroid
drops. The patient should be started on a regimen of prednisolone acetate 1% drops every 1 to 2 hours and carefully
followed, especially during the first days of topical corticosteroid use, to ensure that the inflammatory condition is
not worsening and is stabilizing. Careful slitlamp examination 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 maximum damage to the anterior segment has presumably
already occurred, anterior chamber washout is currently
not routinely recommended for treatment of TASS. While
the IOP may initially be low, recovery of the production
of aqueous humor by the ciliary processes can cause a precipitous 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 adequate visualization of the anterior chamber angle, the patient should have a gonioscopic evaluation to look for
peripheral anterior synechias, which may indicate that

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Figure 6. Toxic anterior segment syndrome secondary to intraocular penetration of ophthalmic ointment. A: Clinical picture taken during the first postoperative week shows a distinct 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 oily
material coating large areas of the anterior and posterior optic surfaces.

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chronic long-term trabecular meshwork damage has occurred.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 cases
show 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 meshwork
damage that leads to uncontrolled IOP, chronic anterior
segment inflammation that may cause transient or permanent cystoid macular edema, or significant iris damage
that may lead to a permanently fixed, dilated pupil. Patients
with severe trabecular meshwork damage sometimes develop glaucoma that is relatively resistant to medical treatment alone. These cases usually require surgical treatment
such as trabeculectomy or placement of a tube shunt
device.1,35
ANALYSIS: TOXIC ANTERIOR SEGMENT SYNDROME

As the mainstay of treatment for TASS centers on prevention, it is critically important that the entire surgical
team (surgical nurses, operating room technicians, residents, physicians, and pharmacists) knows what is appropriate for use in the eye. This is especially true for anyone
involved in cleaning and sterilizing ophthalmic instruments. 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 ensure that everyone involved in cleaning and sterilizing reusable intraocular instruments is thoroughly instructed in
the protocols to properly clean and sterilize the instruments (ie, preventing the possibility of toxic residues from
accumulating on the reusable instruments). Furthermore,
reusable instrument use should be kept to a minimum, particularly those that are high risk for contamination (eg, cannulas or damaged instruments). The reusable instruments
that cannot be switched or are chosen not to be switched
to 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 is

especially 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 could
lead to a buildup of heat-stable LPS endotoxins. The use
of a steam autoclave sterilizer requires that the water reservoir 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 other
medicationsdthat will be used in the eye during anterior
segment surgery. This includes the ordering of complete intraocular 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 solution, which means the 2 components must be reconstituted before intraocular use. For example, AMO Endosol
Extra is the newest complete ocular irrigant to come on
the market and should be bioequivalent to BSS Plus. A major issue with Endosol Extra is that the large part-1 component, 500 mL, has a pH of 3.5. If the part-2 component is
not added with part 1, severe damage to the intraocular tissue will occur. Care should also be taken to check that the
intraocular medications used during anterior segment surgery are preservative-free and at the proper intraocular
drug concentration. This is especially important for epinephrine, which is added to irrigating solutions, or for intracameral 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 methylparaben-free; intracameral lidocaine, indocyanine green,
trypan blue, acetylcholine chloride (Miochol), and carbachol (Miostat) should be mixed with BSS and not sterile
water (L.J. Ronge, Toxic Anterior Segment Syndrome:
Why Sterile Isnt Clean Enough, Eyenet 2002, November/December, pages 1718).4446
An outbreak of TASS in a surgical center is an environmental and toxin control issue that requires complete analysis 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

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important to prove that the medications used during surgery were the intended medications ordered for use by
the surgeon. A complete review of operating room protocols should be undertaken by the surgeon as well as representatives from the surgical center and all involved nursing
staff and personnel. Protocols used in the sterilization and
preparation of instruments from surgery should be carefully evaluated to rule out the potential sources of TASS.
The American Society of Cataract and Refractive Surgery 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. Ophthalmic research fellows are available to provide analyses of
outbreaks of TASS, with subsequent recommendations on
ways to prevent future occurrences. Contact information:
Nick Mamalis, MD, Director, Intermountain Ocular Research 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 investigation 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 surgical
centers 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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