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REVIEW/UPDATE
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
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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
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
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
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REVIEW/UPDATE: TASS
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
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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REVIEW/UPDATE: TASS
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).
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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
REVIEW/UPDATE: TASS
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
In 2002, an outbreak of TASS after cataract surgery involved 3 surgeons at 2 affiliated facilities.11 After an initial
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REVIEW/UPDATE: TASS
Ophthalmic Ointments
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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.
REVIEW/UPDATE: TASS
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
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
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REVIEW/UPDATE: TASS
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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