Abstract
Purpose: :
To study drug safety of triamcinolone and its conservative benzyl alcohol, after intra-vitreal injection into the rabbit eye.
Methods: :
48 rabbits of mixed strain (6 months of age, bodyweight ≈ 3 kg) were randomized into four groups (n=12). The rabbits were examined with ffERG and with mfERG 2 - 3 weeks before drug exposure. The rabbits were then injected intra-vitreally with triamcinolone acetonide, purified triamcinolone, benzyl alcohol and balanced saline solution. FfERG was assessed at 1 and 6 weeks post injection. MfERG was assessed at 2 and 8 weeks post injection. After 8 weeks the rabbits were sacrificed and the sectioned retina was studied. Immunohistochemistry directed against Glial FibrillaryAcidic Protein , Parvalbumin, Rhodopsin, Calbindin, Protein Kinase C and Peanut Agglutinin was performed.
Results: :
At 1 week after injection, rabbits injected with benzyl alcohol showed a highly significant reduction of the isolated rod b-wave amplitude in the ffERG compared to the controls. The total retinal response was also significantly reduced compared to the triamcinolone and to the triamcinololone+bensylalcohol injected rabbits. The isolated cone response was not affected. At 6 weeks after injection some of these effects remained, however with less significance. On the contrary, triamcinolone injected rabbits showed a significant increase in rod and cone response compared to controls at 1 but not at 6 weeks after injection. The mfERG was less affected with a slightly prolonged implicit time in all 3 groups compared to controls and a significantly increased amplitude in the lower region of the mfERG in the triamcinolon injected rabbits at 2 weeks but not at 8 weeks after injection. Immunohistochemistry results will be presented at the meeting.
Conclusions: :
Intra-vitreal injection of bensyl alcohol reduces retinal function in healthy rabbit eye . The toxic effect remains up to 8 weeks after injection. Purified triamcinolone has an opposite effect on the healthy rabbit eye, showing a positive, amplitude increasing effect on both rods and cones but only 1 week after injection. Our results indicate that triamcinolone when needed as an intravitreal injection should be used in its purifed form without bensyl alcohol. Further, when evaluating treatment effects after triamcinolone, we should consider that an improvement of retinal function may not represent a specific effect on pathogenesis, but a general enhancing cortisone effect which would be achieved also in a healthy eye.
Keywords: drug toxicity/drug effects • electroretinography: non-clinical • injection