Toxic Anterior Segment Syndrome (TASS) is a sterile acute anterior segment inflammatory reaction that occurs after anterior segment surgery such as cataract surgery. It is caused by non-infectious substances that enter the eye during surgery and cause toxic irritation. Particularly, metals or surface treatment agents adhering to the IOL are often the cause. 1)
Typically, it develops within 12 to 48 hours after surgery and presents with clinical features similar to infectious endophthalmitis, making differentiation an important issue. It may also be described as subacute to delayed onset. 1)
The incidence is reported to be approximately 0.1 to 2.1% of cataract surgeries. 8) In a retrospective study of 26,408 cases at the Aravind Eye Hospital in India, 60 cases (0.22%) were confirmed in one year. 1) Both sporadic cases and cluster outbreaks occur, and many cases have no identifiable cause. 1)
TASS has also been reported after various anterior and posterior segment surgeries besides cataract surgery, including posterior chamber phakic intraocular lens (ICL) implantation, corneal transplantation, vitrectomy, and trabeculectomy. 3)4)5)6)
Cataract surgery is the most common, but cases have also been reported after phakic intraocular lens implantation, corneal transplantation (full-thickness and deep anterior lamellar), vitrectomy, and trabeculectomy. The possibility of TASS should always be considered in any ophthalmic surgery involving the anterior segment.
Subjective symptoms of TASS are often milder than those of infectious endophthalmitis.
Key diagnostic point: Consider TASS when signs of infection such as discharge and eyelid swelling are mild or when both eyes are affected.
Characteristic Findings
Diffuse corneal edema: Extensive limbus-to-limbus corneal edema due to toxic damage to corneal endothelial cells. 1)
Severe anterior chamber inflammation: Cells, flare, and fibrin exudation are observed. 1)
Hypopyon: Frequently observed. Requires differentiation from infectious endophthalmitis.
Mydriasis failure and irregular pupil: Caused by toxic damage to the iris.
Posterior Segment
Normal posterior segment: The posterior segment is essentially not affected. This is an important distinguishing feature from infectious endophthalmitis.
Vitreous involvement (rare): In less than 25% of cases, a “spill-over” into the anterior vitreous may occur. 2)
Intraocular pressure fluctuations: Initially, inflammation may reduce aqueous humor production, leading to low intraocular pressure; later, trabecular meshwork obstruction may cause elevated intraocular pressure. 2)
Atypical cases of late-onset TASS occurring 7 days or more after surgery also exist. In such cases, the onset overlaps with infectious endophthalmitis, making differentiation even more difficult. 2)
Although rare, inflammation spreading to the anterior vitreous (anterior vitritis) has been reported in less than 25% of cases. Even when posterior segment involvement is suspected, TASS should be considered if inflammation is predominantly anterior and pain is mild. In TASS after vitrectomy, spread to the residual anterior vitreous is also observed.
The causes of TASS are diverse, and many cases cannot be identified. 1) The main causative agents are as follows.
Surgical instruments, cleaning, and sterilization-related:
Intraocular administration-related substances:
IOL-related:
Contaminated Products:
In addition to surgical procedures and instruments, patient systemic characteristics may also contribute to the development of TASS. Type 2 diabetes, hypertension, and hyperlipidemia have been reported as significant risk factors. 2)
The diagnosis of TASS is primarily based on clinical findings. There is no specific test for a definitive diagnosis.
The most important clinical challenge is differentiating it from infectious endophthalmitis.
| Item | TASS | Infectious endophthalmitis |
|---|---|---|
| Onset time | 12–48 hours postoperatively | 3–7 days postoperatively |
| Eye pain | Mild or absent | Severe (pain in 75%) |
| Eyelid swelling and discharge | Usually absent | Characteristic findings |
| Corneal edema | Diffuse (limbus to limbus) | Often localized |
| Posterior segment | Usually uninvolved | Vitritis, retinal lesions |
| Steroid response | Rapid | Poor |
進行速度による鑑別も重要である。急性・亜急性期に炎症が急速に増悪する場合は感染が疑われ、早期の硝子体手術を検討する。一方、緩徐に悪化する場合は、遅発性眼内炎、TASS、内因性ぶどう膜炎を考慮するが、いずれも緊急手術に踏み切る必要はない。確実に精査を行い、慎重に手術決定をすべきである。
TASS often progresses slowly and does not require emergency surgery. Careful observation with steroid therapy as the mainstay is recommended.
The first-line treatment for TASS is steroid therapy.
Topical therapy (first-line):
Systemic therapy (severe cases):
Other local therapies:
Rapid response to anti-inflammatory therapy is characteristic of TASS, with significant improvement in anterior chamber inflammation expected within 5–7 days after appropriate treatment initiation. 2)
In cases of accidental intraocular injection of methylene blue or exposure to severe toxic substances, irreversible damage to the corneal endothelium can lead to pseudophakic bullous keratopathy, requiring DSEK or DMEK. In TASS, complications threatening visual function such as corneal endothelial failure, refractory glaucoma, and cystoid macular edema have been reported, and early recognition and prompt treatment are important1).
TASS is caused by activation of the inflammatory cascade and cytotoxicity due to non-infectious substances that enter the eye.
When toxic substances enter the anterior segment of the eye, tissue damage progresses through the following mechanisms: 1)
Inadvertent intracameral administration of methylene blue (MB) causes particularly severe TASS. MB impairs cellular respiration through reactive oxygen species (ROS) production and inhibition of mitochondrial complex IV (cytochrome c oxidase), inducing apoptosis of corneal endothelial cells. Its high lipophilicity and penetration into intraocular tissues result in widespread toxicity. 3)Trypan blue has lower toxicity due to its larger molecular weight and lower membrane permeability, making it a safer dye recommended for anterior capsule staining. 3)
Metal cutting residues, heavy metals, polishing agents, and residues from cleaning and sterilization processes adhering to IOLs during manufacturing can enter the eye and cause TASS. Cluster outbreaks related to IOLs have been reported, highlighting the importance of quality control in manufacturing, distribution, and the operating room. 1)
TASS often occurs in clusters (outbreaks). Common causes include biofilm formation in contaminated tabletop autoclave water reservoirs, introduction of new cleaning agents, and use of specific IOL lots. 1)The occurrence of multiple cases on the same day, by the same surgeon, or in the same operating room suggests a common cause.
When there is a rapid response to appropriate steroid therapy, inflammation subsides and visual recovery can be expected. Clear improvement in anterior chamber inflammation is observed 5 to 7 days after treatment initiation. 2)
If corneal endothelial damage persists, corneal edema may become prolonged, and in severe cases, corneal transplantation may be required. 1)3) Incomplete mydriasis (atonic pupil) may be permanent. Cases with residual secondary glaucoma have also been reported.
In cluster outbreaks, multiple cases are affected, so it is important to quickly identify the cause and implement recurrence prevention measures. 1)
While improvement can be expected in many cases of TASS, long-term management is required if corneal endothelial failure or secondary glaucoma persists 1). Prognosis depends on the toxicity of the causative agent, exposure dose, and speed of treatment initiation.
A large-scale review by Verma et al. (Indian J Ophthalmol 2024) detailed the cluster outbreak patterns and diversity of causative agents in TASS. 1) In a large Indian series, the incidence rate was approximately 0.22%, with clusters ranging from 3 to 20 cases.
Reports of delayed-onset TASS (onset 7 days or more after surgery) and same-day bilateral onset (after same-day bilateral surgery) are increasing. 2) In cases of bilateral TASS following same-day bilateral refractive cataract surgery, recovery to best corrected visual acuity of 20/25 at 6 months after treatment has been reported. 2)
TASS has been shown to occur not only after cataract surgery but also after various intraocular surgeries such as vitrectomy 5), trabeculectomy 4)6), and phakic intraocular lens implantation 7). This increases the need to consider TASS in the differential diagnosis of postoperative inflammation after any intraocular surgery.
ASCRS TASS Task Force (https://tassregistry.org/）は疑い例の登録と予防に関するリソースを提供している。1)標準化された薬剤確認プロトコル・ダブルチェックシステムの導入が手術室での薬剤エラーを40%削減すると報告されている。3)
