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Experimental study links toxic effects of triamcinolone with drug's vehicle
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The vehicle used in commercially available formulations of intravitreally injected triamcinolone acetonide may cause retinal toxicity and increased lens density, according to an experimental study.
Jiang Yanrong and colleagues at the People Eye Center of the People's Hospital in Beijing, China, tested four different concentrations of triamcinolone acetonide in 40 New Zealand white rabbits. Two rabbit groups received 25 mg of either vehicle-reduced or non-reduced triamcinolone, and two groups received 4 mg of triamcinolone either vehicle-reduced or non-reduced triamcinolone. A fifth group of animals received sterile saline injections and served as controls, according to the study.
All four experimental groups experienced similar increases in IOP after injection. The researchers found triamcinolone particles within the trabecular meshwork in all study eyes, possibly preventing aqueous outflow and causing the increased IOP.
At 1 week, eyes injected with non-reduced vehicle-containing triamcinolone experienced significant transient increases in lens density, with the greatest increases seen in eyes treated with 25-mg doses. The increased density was evenly distributed throughout the lens, which suggests it occurred independently of increased IOP, the authors noted. IOP-induced lens density has only been associated with posterior subcapsular cataracts, they added.
"To our knowledge, this is the first report of such a strong correlation between the increase of lens density and the vehicle of [triamcinolone]," the authors said.
Electron microscopy showed swelled or ruptured mitochondria in the photoreceptors of the vehicle-containing groups. Control eyes and eyes injected with vehicle-reduced triamcinolone appeared normal, according to the study.
The authors noted that the vehicle used for commercially available triamcinolone formulations contains additives, including isotonic sodium chloride, 0.99% benzyl alcohol, 0.75% sodium carboxymethycellulose and 0.04% polysorbate. Further studies are needed to pinpoint the exact vehicle component at fault, they said.
"According to the results of our study, we consider a dosage of [triamcinolone acetonide] (vehicle reduced) less than 25 mg safe for intravitreal injection in vivo," the authors said.
Surgeons should use centrifugation to reduce the delivery vehicle prior to injection; this method does not inadvertently reduce the triamcinolone dosage, they added.
The study is published in the September issue of Graefe's Archive for Clinical and Experimental Ophthalmology.