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Updated: Jul 16, 2026
Intravitreal Injections in the Ovine Eye
Published on: July 5, 2022
Intravitreal toxicity of high-dose etanercept
Muhamet Kivilcim1, Gholam A Peyman, Abdul Ahad Kazi
1Department of Ophthalmology, University of Arizona, Arizona Health Sciences Center, Tucson, AZ 85711, USA.
Purpose:
The aim of this study was to evaluate the retinal toxicity of high-dose intravitreal etanercept, a U.S. Food and Drug Administration-approved anti-inflammatory drug, in the rabbit model.
Methods:
Twenty (20) New Zealand albino rabbits were divided into 5 groups (n=4); eyes in each group were intravitreally injected with one of the following doses of etanercept: 125 microg, 250 microg, 500 microg, 1 mg, or 2.5 mg. One (1) eye in each animal was used for the study dose; the fellow eye was injected with buffered sterile saline as a control. All animals were examined using indirect ophthalmoscopy and slit-lamp biomicroscopy before and after intravitreal injection and at days 1, 7, and 14. Electroretinography (ERG) was performed on all animals before intravitreal injection and 14 days after injection. The animals were euthanized on day 14. Histological preparations of the enucleated eyes were examined with light microscopy for retinal toxicity.
Results:
Clinical examination, histological evaluation, and ERG results of all 5 groups demonstrated no signs of retinal toxicity.
Conclusions:
Intravitreal doses as high as 2.5 mg of etanercept did not cause retinal toxicity. Intravitreal doses of up to 2.5 mg of etanercept may provide a more potent, prolonged effect than the lower doses previously recommended.
Insights
High-dose intravitreal etanercept (etanercept) up to 2.5 mg did not cause retinal toxicity in rabbits. This finding suggests higher doses may offer a more potent and prolonged anti-inflammatory effect.
Area of Science:
- Ophthalmology
- Pharmacology
- Toxicology
Background:
- Etanercept is an FDA-approved anti-inflammatory drug.
- Intravitreal administration is a potential route for ocular drug delivery.
- Evaluating the safety of higher drug doses is crucial for therapeutic optimization.
Purpose of the Study:
- To assess the retinal toxicity of high-dose intravitreal etanercept in a rabbit model.
- To determine the safety profile of etanercept at doses up to 2.5 mg administered intravitreally.
Main Methods:
- New Zealand albino rabbits received intravitreal injections of etanercept at doses of 125 microg, 250 microg, 500 microg, 1 mg, or 2.5 mg.
- Control eyes received sterile saline injections.
- Ocular examinations included indirect ophthalmoscopy, slit-lamp biomicroscopy, and electroretinography (ERG).
- Histological analysis of retinal tissues was performed post-mortem.
Main Results:
- No clinical signs of retinal toxicity were observed during ophthalmoscopy and biomicroscopy.
- Electroretinography (ERG) results showed no abnormalities.
- Histological examination revealed no evidence of retinal damage.
Conclusions:
- Intravitreal etanercept, even at a high dose of 2.5 mg, is not toxic to the retina in rabbits.
- Higher intravitreal doses of etanercept may be safe and could potentially offer enhanced therapeutic benefits.
- These findings support further investigation into the use of higher-dose intravitreal etanercept for ocular inflammatory conditions.