Toxic Anterior Segment Syndrome (TASS)

Toxic anterior segment syndrome (TASS) is an acute postoperative inflammatory reaction in which a noninfectious substance enters the anterior segment and induces toxic damage to the intraocular tissues.[1]  Almost all cases occur after uneventful cataract surgery, and it has been reported after phakic intraocular lens implantation.[1, 2] Previously, this syndrome was defined by many names, such as sterile endophthalmitis or postoperative uveitis of unknown cause. Furthermore, a condition termed toxic endothelial cell destruction (TECD) syndrome has been described and is now believed to be a variant of TASS. 

Diffuse limbus-to-limbus corneal edema and anterior segment inflammation noted in a patient with toxic anterior segment syndrome (TASS).

TASS results from the inadvertent entry of toxic substances into the anterior chamber.[1, 2] This causes a marked inflammatory reaction that varies in intensity depending on the type and duration of the toxin.

The histopathologic hallmark of TASS is toxic anterior segment damage. Cellular necrosis and/or apoptosis and extracellular damage occur, resulting in the severe acute inflammatory response. The corneal endothelium is often the most damaged structure because of its inability to regenerate and replace dead cells.

Toxic agents specifically induce the acute breakdown of endothelial junctions with loss of the barrier function. This results in the remaining viable endothelial cells to migrate and spread over the damaged areas in an effort to maintain the endothelial pumping system. If significant damage occurs, however, the remaining viable cells will not be able to sufficiently compensate the loss, with ensuing permanent corneal edema being the consequence.

Trabecular meshwork damage can also develop, resulting in decreased drainage, scarring, and peripheral anterior synechiae formation with a subsequent rise in intraocular pressure.

Etiology

Possible etiologies of TASS include the following[1, 2] :

• Intraocular solutions such as balanced salt solution (BSS)
• Improper sterilization or cleaning of instruments
• Intracameral antibiotics
• Topical ophthalmic drops
• Intracameral anesthetics such as lidocaine
• Ophthalmic viscosurgical devices (viscoelastics), especially if left in eye at end of case
• Intravitreal injections such as bevacizumab

Frequency

United States

Data on the incidence of TASS are lacking. Clusters ranging from a few cases to up to 20 cases occur several times each year.

Furthermore, in 2005, audience response during the American Academy of Ophthalmology Annual Meeting revealed that 52% of attendees had seen one case of TASS, and 7% of attendees reported seeing more than five cases.

Mortality/Morbidity

TASS can induce permanent corneal endothelial damage, in addition to trabecular meshwork damage,[3] thus debilitating vision. Depending on the type and duration of the toxic insult, the visual outcome can range from 20/20 to no light perception. Patients may require further intraocular procedures, such as penetrating keratoplasty and/or glaucoma filtering procedure surgery, to regain visual function.

Race

No racial predilection has been found with TASS.

Sex

No known difference exists in the incidence of TASS between men and women.

Age

No known association of TASS exists with increasing age.

In the setting of postoperative inflammation, distinguishing toxic anterior segment syndrome (TASS) from infectious endophthalmitis is very important. However, this can be difficult, because both conditions can present in a similar fashion.[1, 2]

The hallmark of TASS is its rapid onset, usually within 12 to 24 hours. Rarely, TASS can present as delayed onset postoperative inflammation, which can confuse it with infectious endophthalmitis.[3] Patients with TASS are usually pain free; however, if pain is present, it is mild.

Depending on the severity of the insult, the presentation can vary. Features that are unique to TASS include the following:

• Limbus-to-limbus corneal edema is considered to be the classic finding of TASS; however, not all cases have this finding. Most frequently, the occurrence appears as a milder form with increased anterior chamber cells in excess of that seen after surgery.[1]

  Diffuse limbus-to-limbus corneal edema and anterior segment inflammation noted in a patient with toxic anterior segment syndrome (TASS).

• Anterior chamber reaction can be moderate to severe with the presence of hypopyon and fibrin. Unlike infectious endophthalmitis, vitreous inflammation is rare, and, if it occurs, it is considered to be the result of a posterior diffusion from the anterior chamber.[3]

• An unreactive dilated pupil may be noted.

• The intraocular pressure can be elevated secondary to trabecular meshwork damage.

• Cystoid macular edema has been reported in a few cases.

Unlike infectious endophthalmitis, TASS often rapidly improves after topical steroids are instituted, which serves as a distinguishing feature from infectious endophthalmitis.

The following table summarizes the classic presentation of TASS and infectious endophthalmitis to help differentiate the two entities.[1, 2]

Table 1. Differentiating Toxic Anterior Segment Syndrome and Infectious Endophthalmitis (Open Table in a new window)

Multiple causes and associations have been implicated with TASS. They can be divided into the following categories:

Extraocular substances that inadvertently enter the anterior chamber during or after surgery include the following[1, 2] :

• Topical antiseptic agents

• Talc from surgical gloves

• Ophthalmic ointment

Products that are introduced into the anterior chamber as part of the procedure include the following[1, 2] :

• Anesthetic agents (eg, lidocaine 2% vs 1%)

• Preservatives (eg, benzalkonium chloride)

• Inappropriately reconstituted intraocular preparations

• Mitomycin-C

• Intraocular lenses, including phakic intraocular lenses

• Contaminated irrigating solutions (eg, balanced salt solution contaminated with bacterial endotoxin)

One study shows that corneal toxicity from intracameral agents may be associated with the concentration of free radicals present in the agents.[4]

Contaminants on the surfaces of intraocular surgical instruments that have accumulated as a consequence of inadequate or inappropriate instrument cleaning include the following[1, 2] :

• Denatured viscosurgical devices

• Enzymatic detergents

• Bacterial endotoxin contamination of ultrasound water bath cleaners

• Impurities of autoclave steam

• Oxidized metal deposits and residues

Because of the multiple causes and associations implicated, it is often difficult for the surgical center to isolate a cause directly.

Patients who present with toxic anterior segment syndrome (TASS) should be assessed carefully, and infectious endophthalmitis should be ruled out.[1, 2]

If at all unclear as to the exact etiology, the protocol for infectious endophthalmitis should be performed. This protocol includes performing an anterior chamber aspirate, a vitreous tap, and/or a vitreous biopsy for Gram stains and microbiologic cultures.

The US Food and Drug Administration's (FDA's) Center for Devices and Radiological Health staff has embarked on a number of projects to mitigate medical device–related TASS outbreaks. These include conducting animal studies to explore various etiologies of TASS, capturing the clinical information necessary to assist investigations of potential future outbreaks, and partnering with the US Centers for Disease Control and Prevention to facilitate a potential TASS investigation, including expediting the analysis of potentially contaminated medical devices.[5]

The vitreous should be examined carefully to rule out vitritis. A B-scan ultrasound may be needed if the view is obscured by corneal edema and/or anterior chamber inflammation.

Patients with suspected toxic anterior segment syndrome (TASS) should be treated as if infectious endophthalmitis is present if the clinical picture is unclear as to the exact etiology of the inflammation.

Once TASS is confirmed, patients should be started on topical steroids. The usual regimen is one drop every 30 to 60 minutes for the first 3 days with gradual tapering.

The response is typically rapid once patients are started on topical steroids. Patients should be reassessed later the same day or the next day to help confirm that the condition is indeed TASS versus infectious endophthalmitis, in which case, steroids alone would worsen the condition.[1, 2]

Careful assessment and treatment of elevated intraocular pressure is important to prevent optic nerve damage.

Nonsteroidal anti-inflammatory drops have been shown to be a helpful adjunct in several cases of TASS.[1, 2]

No clear benefit has been demonstrated for immediate anterior chamber washout. In cases of a severe and refractory fibrin reaction due to TASS, intracameral recombinant tissue plasminogen activator (r-tPA) may be beneficial.[6]

In cases where the intraocular lens is suspected to be the cause of the inflammation, an intraocular lens exchange may be needed if no response to medical treatment is demonstrated.

If corneal edema persists for more than 6 weeks despite medical treatment, the corneal decompensation is likely permanent and a corneal transplantation is required. 

Long-term sequelae of toxic anterior segment syndrome (TASS) with persistent corneal edema.

If intraocular pressure cannot be controlled medically, seton valve procedures may be required.

There are no dietary restrictions.

There are no activity restrictions.

Medical therapy for toxic anterior segment syndrome (TASS) includes corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs).[1, 2]

Class Summary

NSAIDs inhibit enzyme cyclooxygenase and also can be used in the prevention of cystoid macular edema (CME). NSAIDs are administered topically, usually for 3-4 months.

Nepafenac ophthalmic (Nevanac)

Nonsteroidal anti-inflammatory prodrug for ophthalmic use. Following administration, converted by ocular tissue hydrolases to amfenac, an NSAID. Inhibits prostaglandin H synthase (cyclooxygenase), an enzyme required for prostaglandin production. Indicated for treatment of pain and inflammation associated with cataract surgery.

Diclofenac ophthalmic (Voltaren)

Inhibits prostaglandin synthesis by decreasing activity of enzyme cyclooxygenase, which, in turn, decreases formation of prostaglandin precursors. Commonly used in the treatment of CME and postoperative inflammation in patients who have undergone cataract extraction.

Ketorolac ophthalmic (Acular)

For treatment of CME and postoperative inflammation in patients who have undergone cataract extraction. Inhibits prostaglandin synthesis by decreasing activity of the enzyme, cyclooxygenase, which results in decreased formation of prostaglandin precursors, which, in turn, results in reduced inflammation.

Class Summary

These agents decrease inflammation. Corticosteroid treatment is often initiated only after consultation with an ophthalmologist.

Prednisolone acetate 1% (Pred Forte, Omnipred Plus)

Strongest steroid of its group and best choice for uveitis. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Initially, patients with toxic anterior segment syndrome (TASS) should be examined on a daily basis to assess their response to treatment.

Once the inflammation is resolved, patients need to be assessed carefully for corneal and/or trabecular meshwork damage.[1, 2]

All preoperative, intraoperative, and postoperative steps at the surgical center should be thoroughly assessed, including the following[1, 2] :

• Surgical equipment and instruments

• Sterilization process

• Preoperative, intraoperative, and postoperative medications

• Ultrasound water

• Irrigating solutions

Depending on the type of toxin, duration of exposure, and response to treatment, the following complications may result[1, 2] :

• Corneal endothelial cell loss with resultant edema

• Trabecular meshwork damage causing glaucoma

• Iris sphincter muscle damage with resultant permanent dilated pupil

• Cystoid macular edema

Prognosis is generally divided into three groups depending on the severity of TASS.

A mild presentation of TASS will result in rapid clearing of the corneal edema with no long-term corneal or trabecular damage and normal or near normal visual acuity.

A moderate presentation of TASS will result in a persistent corneal edema that will take several weeks to clear, intraocular pressure that is difficult to control, and a moderate effect on visual acuity.

A severe presentation of TASS will result in a marked corneal edema that does not clear, iris and trabecular meshwork damage with resultant glaucoma, and possible cystoid macular edema. Visual outcome is usually poor despite medical or surgical intervention. A potential sequel manifestation of TASS is Urrets-Zavalia syndrome (UZS).[7]

Despite the above descriptions, predicting the outcome for patients remains difficult because of the multiple etiologies and associations linked to TASS.

Patients should be instructed to immediately report any pain and/or a decline in visual acuity postoperatively. The sooner that TASS can be detected and treated, the better the outcome will be for the patients.