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Retinal toxicity of intravitreal tenecteplase in the rabbit

Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Western Australia, Australia

Correspondence to:
Correspondence to:
Professor Dao-Yi Yu
Centre for Ophthalmology and Visual Science, The University of Western Australia, Nedlands, WA 6009, Australia; dyyu{at}cyllene.uwa.edu.au

Aim: To investigate the retinal toxicity of intravitreal injection of a novel fibrinolytic tenecteplase in rabbit eyes.

Methods: Tenecteplase (25–350 µg in 0.1 ml BSS) was injected into the vitreous cavity of normal rabbit eyes. Control (fellow) eyes received 0.1 ml of BSS. One day, 1 week, and 2 months post-injection, the eyes were examined by slit lamp biomicroscopy, indirect ophthalmoscopy, and electroretinography, and then harvested for histopathological examination.

Results: No evidence of retinal toxicity was seen with tenecteplase doses up to and including 50 µg. At a dose of 150 µg ophthalmoscopy was normal, but histology showed mild retinal damage in the inner nuclear layer and electroretinography showed a temporary reduction in B-wave amplitude. At doses of 200 µg and above, there was evidence of retinal toxicity on electroretinography, ophthalmoscopy, and histology. Ophthalmoscopic findings included vitreal fibrosis, retinal necrosis and tractional retinal detachment and light microscopy revealed necrosis of retinal pigment epithelium and other retinal layers. Damage was centred around the injection site but was more widespread with the higher doses.

Conclusion: A dose of 50 µg tenecteplase appears safe for intravitreal injection in the rabbit. Tenecteplase could have potential applications in the treatment of submacular haemorrhage and retinal vein occlusion.

Keywords: tenecteplase; toxicity; retina; intravitreal; tissue plasminogen activator

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