Acute intraocular inflammation caused by endotoxin after intravitreal injection of counterfeit bevacizumab in Shanghai, China.
OBJECTIVE
To describe an outbreak of intraocular inflammation caused by endotoxin-contaminated counterfeit bevacizumab in China.


METHODS
Retrospective, observational case series.


METHODS
Patients undergoing intravitreal injection at a public hospital in September 2010.


METHODS
The medical records and microbiology results of patients who presented with intraocular inflammation after injection with intravitreal counterfeit bevacizumab were reviewed.


METHODS
The incidence of intraocular inflammation, results of pathogen cultures, and clinical features of inflammation.


RESULTS
A total of 116 patients (70 men and 46 women) were injected from 3 vials of counterfeit bevacizumab. Intraocular inflammation developed in 80 patients. The estimated median incubation period was 12 hours (range, 2-24 hours), and the median duration of symptoms was 6 days (range, 3-22 days). All patients were treated initially with topical corticosteroid and antibiotics. Vitreous tap and intravitreal injection were performed on 43 patients. Twenty-one patients with hypopyon and significant vitreous inflammation underwent vitrectomy. Microscopic evaluations and microbiologic cultures of all ocular specimens were negative for bacterial and fungal contamination. The presence of endotoxin in specimens was confirmed by laboratory testing. We refer to this new clinical syndrome as "endotoxin-induced ocular toxic syndrome" (EOTS). The inflammation regressed rapidly after treatment, and 63 patients (78.8%) recovered their pre-injection vision.


CONCLUSIONS
This study implicates endotoxin as the cause of intraocular inflammation after the intravitreal injection of counterfeit bevacizumab. The EOTS appeared clinically distinct from typical infectious endophthalmitis.
Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Fenghua
F
Wang
Suqin
S
Yu
Kun
K
Liu
Feng-E
FE
Chen
Zhengyu
Z
Song
Xi
X
Zhang
Xun
X
Xu
Xiaodong
X
Sun
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use; D000068258:Bevacizumab; D002681:China; D058110:Counterfeit Drugs / Q000009:adverse effects*; D004340:Drug Contamination; D004359:Drug Therapy, Combination; D009877:Endophthalmitis / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D004731:Endotoxins / Q000009:adverse effects*; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D012164:Retinal Diseases / Q000188:drug therapy; D012189:Retrospective Studies; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014821:Vitrectomy; D055815:Young Adult
D020533:Angiogenesis Inhibitors; D000900:Anti-Bacterial Agents; D061067:Antibodies, Monoclonal, Humanized; D058110:Counterfeit Drugs; D004731:Endotoxins; D005938:Glucocorticoids; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab