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PURPOSE: To identify the most common risk factors associated with toxic anterior segment
syndrome (TASS).
SETTING: Ophthalmic surgical centers in the United States, Argentina, Brazil, Italy, Mexico, Spain,
and Romania.
METHODS: A TASS questionnaire on instrument cleaning and reprocessing and extraocular and in-
traocular products used during cataract surgery was placed on the American Society of Cataract and
Refractive Surgery web site. A retrospective analysis of questionnaires submitted by surgical cen-
ters reporting cases of TASS was performed between June 1, 2007, and May 31, 2009, to identify
commonly held practices that could cause TASS. Members of the TASS Task Force made site visits
between October 1, 2005, and May 31, 2009, and the findings were evaluated.
RESULTS: Data from 77 questionnaires and 54 site visits were analyzed. The reporting centers
performed 50 114 cataract surgeries and reported 909 cases of TASS. From January 1, 2006, to
date, the 54 centers reported 367 cases in 143 919 procedures; 61% occurred in early 2006. Com-
mon practices associated with TASS included inadequate flushing of phaco and irrigation/aspiration
handpieces, use of enzymatic cleansers, detergents at the wrong concentration, ultrasonic bath,
antibiotic agents in balanced salt solution, preserved epinephrine, inappropriate agents for skin
prep, and powdered gloves. Reuse of single-use products and poor instrument maintenance and
processing were other risk factors.
CONCLUSIONS: The survey identified commonly held practices associated with TASS. Understand-
ing these findings and the safe alternatives will allow surgical center personnel to change their
practices as needed to prevent TASS.
Financial Disclosure: No author has a financial or proprietary interest in any material or method
mentioned.
J Cataract Refract Surg 2010; 36:10731080 Q 2010 ASCRS and ESCRS
Toxic anterior segment syndrome (TASS) is a sterile in- however, in severe cases there may be lasting sequelae,
flammatory reaction of unknown incidence that can oc- such as permanent corneal edema, glaucoma, and
cur after anterior segment surgery. It typically presents other effects of chronic inflammation. Various entities
within 12 to 48 hours of surgery. The most common have been shown to cause TASS. These include, but
finding is diffuse limbus-to-limbus corneal edema are not limited to, endotoxin; denatured ophthalmic
(Figure 1) secondary to damage from a toxic insult to viscosurgical devices (OVDs); preservatives such as
the endothelial cell layer. Widespread breakdown of benzalkonium chloride, bisulfites, and metabisulfites;
the bloodaqueous barrier is another hallmark of this heavy-metal residue, fine-matter particulates, and
condition, with fibrin in the anterior chamber and hypo- substances introduced into the anterior chamber that
pyon present in 75% of cases (Figure 2). Damage to the are at a pH or concentration that is toxic to the sensitive
iris may cause the pupil to dilate or become slightly endothelial cells. In addition, residue of materials used
irregular, and glaucoma secondary to trabecular mesh- in the cleaning and sterilization of ophthalmic instru-
work damage may also occur. ments are an increasingly important source of TASS.
Treatment with intense topical steroidal agents will Members of industry and the American Society of
eventually lead to resolution of the inflammation; Cataract and Refractive Surgery (ASCRS) have joined
been established and may actually be prohibited in the completely removed from instruments before they
manufacturers directions for use for specific products. are immersed in bath water. Then, after each use,
Furthermore, the use of detergents mixed at the wrong and if in accordance with the manufacturers direc-
concentration has been linked to TASS outbreaks.10 tions for use, the bath water should be emptied and
Seven percent of centers visited were using the wrong the tub cleaned with an Environmental Protection
concentration of detergents, putting their patients at Agencyregistered facility-approved disinfectant.
risk for TASS as a result of residual detergents and in- This should be followed with a rinse using volumes
complete rinsing. of sterile or tap water adequate to remove the cleaning
Enzymatic detergents often have the exotoxin sub- agent completely. Then, 70% to 90% ethyl or isopropyl
tilisin or a-amylase enzymes as their active ingredi- alcohol should be used to clean the tub if this is in
ents. These are only deactivated at temperatures accordance with the manufacturers directions for
higher than 140 C, and most autoclaves do not reach use and not associated with a risk of fire. Endotoxin
temperatures higher than 120 C to 130 C. Thus, it is can be removed from the walls of the bath by wiping
likely that residue from enzymatic detergents will the walls with ethyl or isopropyl alcohol.1,14 The tub
build up on reused instruments.11 Human and rabbit should then be dried completely with a lint-free cloth
studies evaluating the effect of enzymatic detergents and refilled immediately before use.
on the anterior chamber showed dose-related corneal This process of cleaning must be followed after each
swelling; ultrastructural damage to the endothelial use to prevent endotoxin buildup. However, only 19%
layer, leading to increased corneal permeability; and of centers responding to the questionnaire cleaned the
an increased inflammatory response in the iris.12 ultrasonic bath after each use as recommended and 4%
The purpose behind the use of enzymatic detergents of centers visited had no protocol for routine cleaning
is to rid ophthalmic instruments of debris. If instru- of the ultrasonic bath.
ments are kept moist immediately after use before Of centers reporting via questionnaire, 25% added
flushing and if proper flushing with an adequate antibiotic agents to the balanced salt solution irrigant
volume is performed, there should be no adherent and 21% used intracameral antibiotic agents. The use
debris and thus no need for enzymatic detergents. If of antibiotic agents may be associated with toxicity
detergents are used, it is imperative that strict when they are included in anterior chamber irrigant
attention is paid to the dilution and expiration date. and when injected intracamerally at the end of
Furthermore, instruments processed with detergents a case.7 If antibiotic agents are improperly mixed, the
must be rinsed with copious amounts of fluid accord- concentration may be too high or the pH incorrect,
ing to the manufacturers directions for use. Recom- both of which can prove toxic to the anterior chamber
mended volumes should be considered a minimum tissues.
volume, and the final rinse should be performed The use of vancomycin and gentamicin sulfate in
with sterile distilled or sterile deionized water.1 anterior segment surgery has been described for
Sixty-three percent of reporting facilities used an prophylaxis against endophthalmitis.15 However, the
ultrasonic bath as part of the processing of their use of these products is associated with concerns
ophthalmologic instruments. This has been associated over vancomycin-resistant organisms as well as
with the accumulation of heat-stable endotoxins aminoglycoside-related macular toxicity, respectively.
produced by bacteria in the bath water.13 Endotoxin Furthermore, the concentration used in irrigating
remaining on instruments after cleaning and steriliza- solution and the time of contact with a possible
tion can induce the inflammatory reaction of TASS. contaminant is inadequate for their bacteriostatic or
As with enzymatic detergents, the purpose of the bacteriocidal properties to function.
ultrasonic bath is to dislodge dried debris from instru- Studies to evaluate intraocular cefotaxime for endo-
ments, particularly OVDs. Again, if instruments are thelial toxicity have been performed. A prospective
kept moist after use and then properly flushed with randomized masked study of 66 patients by
an adequate volume of water, there should be no Kramann16 found no toxicity with 0.4 mL of 0.25%
adherent debris and thus no need for an ultrasonic cefotaxime in the anterior chamber. Other studies
bath. evaluating the use of cefuroxime17,18 found no toxicity
If an ultrasonic bath is used, the manufacturers and a role for the agent in endophthalmitis prevention.
directions for use for instruments should be verified These findings were strengthened with the results in
because some instruments should not be processed a prospective randomized partially masked study in
in this manner. In addition, the ultrasonic bath should which 1.0 mg cefuroxime in 0.1 mL normal saline
be designated for medical use only and the manufac- injected into the anterior chamber after surgery de-
turers directions for maintenance should be strictly creased the risk for endophthalmitis (0.05% incidence
followed. Furthermore, all gross material should be rate when counting all endophthalmitis cases)
compared with a placebo or perioperative treatment sleeves, not be reused. Fifty-two percent of centers vis-
with a third-generation fluoroquinolone drop.19 How- ited were reusing these items. The reprocessing of
ever, an endophthalmitis incidence of 0.056% was these items is regulated and enforced by the U.S.
found with the perioperative use of a fourth- Food and Drug Administration.B
generation fluoroquinolone drop.20 Poor autoclave maintenance, including autoclave
At this time, because there are effective alternatives residue, instrument milk, rust, particulates, and lint
and because there is a risk for TASS from toxicity due within the autoclave, was documented at 28% of cen-
to the wrong concentration or pH of an improperly ters visited. Any such contaminants would be suspect
mixed antibiotic agent, use of intracameral antibiotic for causing TASS. One documented example of poor
agents must be viewed with caution.7 maintenance leading to heavy-metal contamination
Of surgical centers visited, 52% were using preserved of instruments showed carryover of sulfate, silica,
epinephrine in balanced salt solution and 37% were copper, zinc, and nickel from feedwater into steam
using other preserved medications intracamerally. In condensates associated with TASS outbreaks.26 This
addition, at least 36% of questionnaire respondents was found to be the result of changing from flushing
were adding preserved epinephrine to balanced salt so- and draining the steam generator once a week to
lution. Although bisulfites are not technically a preser- once every 4 to 8 weeks when maintenance was
vative but rather an antioxidant, they can also cause outsourced.
ocular toxicity. Benzalkonium chloride (BAC), a com- Surgical centers should make sure that preventive
monly used preservative, is highly toxic to ocular tis- maintenance, cleaning, and inspection of autoclaves
sues,21 and rabbit studies22 show a dose-response are performed as directed by the manufacturers direc-
pattern of conjunctivitis, flare, iritis, and corneal tions for use and also be documented. In addition, it
changes. In the rabbit study, a safety factor of 10 was should be verified that the sterilizer is functioning
used to set the safest intraocular concentration at properly on a daily basis where possible, or at least
0.001%, a level at which the preservative efficacy is weekly. Steam sterilization should be performed in
questionable. accordance with published guidelines, and instru-
An outbreak of TASS was associated with the use of ments should be sterilized according to directions for
Eye Stream rinse solution (Alcon Laboratories) pre- use provided by their manufacturer as well as the
served with 0.01% BAC, in which a concentration of sterilizers manufacturer. A terminal sterilization
0.013% was inadvertently irrigated into the anterior should be performed at the end of each surgical
chamber.23 Toxic anterior segment syndrome has day.3,5 Glutaraldehyde should not be used in the
also been reported after use of OVD preserved with sterilization process because it is highly toxic to the
BAC,24 and the use of lidocaine gel preserved with tissues of the anterior chamber and will cause TASS
BAC was recently implicated in a TASS outbreak if inadequately rinsed.27 Plasma gas sterilization has
(unpublished data). We recommend that no products also been shown to lead to degradation of brass to
with preservatives or additives (stabilizers), such as copper and zinc on cannulated surgical instruments
bisulfites and metabisulfites, be used in the anterior and should not be used because this has led to heavy
chamber.7,11 metalinduced TASS.28
Twenty percent of sites visited were using intraocular The use of powdered gloves can also be a source of
ointment after clear corneal cases. This practice was TASS because the powder can be toxic to the anterior
associated with a TASS outbreak in 8 cases. Of the chamber structures. Of sites visited, 28 were using
patients affected, 4 required penetrating keratoplasty powdered gloves during anterior chamber cases.
and glaucoma with no light perception developed in Powder-free gloves can also pose a risk for develop-
1 patient. Examination of each of these patients showed ing TASS. These gloves are made with a releasing com-
that petroleum-based ophthalmic ointments had pound that allows the glove to be easily removed from
gained access to the anterior chamber through a clear the mold after production. The releasing compound
corneal wound that was patched postoperatively.25 stays on the surface of the gloves and can cause ante-
Site visits showed that 69% of centers were using rior chamber toxicity if it comes in contact with IOLs
reusable cannulas. Cleaning cannulas is difficult to or any instrument entering the anterior chamber.C
perform and validate, and there are no manufacturers This can occur if the IOL or other instruments entering
directions for use. Furthermore, if the cannulas are the anterior chamber are touched during cataract
processed with enzymatic detergents, residue will surgery, a practice observed at 18 surgical centers
likely build up and then be irrigated into the anterior visited (33%).
chamber. Therefore, when possible, disposable cannu- Of questionnaire respondents, at least 13% indicated
las should be used.7,11 In addition, it is important that that ophthalmic instruments were processed for clean-
single-use devices, such as cannulas, blades, tips, and ing alongside dirty surgical trays from other,
nonophthalmic surgeries. However, ASCRS experts 11. Parikh CH, Edelhauser HF. Ocular surgical pharmacology:
recommend that all ophthalmic instruments be kept corneal endothelial safety and toxicity. Curr Opin Ophthalmol
2003; 14:178185
separate from other types of surgical instruments 12. Parikh CH, Sippy BD, Martin DF, Edelhauser JF. Effects of
during all steps of processing to avoid contamination enzymatic sterilization detergents on the corneal endothelium.
with bioburden or cleaning chemicals.1 Arch Ophthalmol 2002; 120:165172
In conclusion, analysis of data reported in question- 13. Kreisler KR, Martin SS, Young CW, Anderson CW, Mamalis N.
naires as well as in site visits from centers reporting Postoperative inflammation following cataract extraction caused
by bacterial contamination of the cleaning bath detergent.
TASS were analyzed carefully. The most common fac- J Cataract Refract Surg 1992; 18:106110
tors associated with TASS were inadequate cleaning 14. Franken KLMC, Hiemstra HS, van Meijgaarden KE, Subronto Y,
and flushing of ophthalmic instruments and handpie- den Hartigh J, Ottenhoff THM, Drijfhout JW. Purification of his-
ces. This included the use of detergents and ultra- tagged proteins by immobilized chelate affinity chromatography:
sound water baths. In addition, the use of intraocular the benefits from the use of organic solvent. Protein Expr Purif
2000; 18:9599
medications with preservatives or additives was 15. Gills JP. Filters and antibiotics in irrigating solution for cataract
associated with TASS in a significant number of cases. surgery [letter]. J Cataract Refract Surg 1991; 17:385
The proper cleaning and sterilization of ophthalmic in- 16. Kramann C, Pitz S, Schwenn O, Haber M, Hommel G, Pfeiffer N.
struments, as well as proper attention regarding the Effects of intraocular cefotaxime on the human corneal endothe-
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17. Montan P, Wejde G, Setterquist H, Rylander M, Zetterstrom C.
can help prevent the occurrence TASS. These findings Prophylactic intracameral cefuroxime; evaluation of safety and
continue to validate the need to follow the recom- kinetics in cataract surgery. J Cataract Refract Surg 2002;
mendations detailed in the recommended practices 28:982987
document created by the TASS Task Force.1 18. Montan P, Wejde G, Koranyi G, Rylander M. Prophylactic in-
tracameral cefuroxime; efficacy in preventing endophthalmitis
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