SurModics Inc (SRDX)

[aslan2772]

Intravitreal triamcinolone toxicity study

It's not surprising that toxicity was observed at higher doses in this study. I think this study speaks to one of the advantages of I-vation type devices: not only is the drug concentration targeted to within the clinically effective range for a longer period of time, but if burst release can be avoided, the toxicity associated with higher IVT doses (which are given to reduce the frequency of injection) can be avoided. There is more to sustained release, at least in theory, than convienence!

Retinal toxicity of intravitreal triamcinolone acetonide: a morphological study.Yu SY, Damico FM, Viola F, D'Amico DJ, Young LH.
Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, 02114, USA.

PURPOSE: To evaluate the morphologic effects of intravitreal triamcinolone acetonide (TA) on rabbit retina. METHODS: Intravitreal injections of 0.5 mg, 1 mg, 4 mg, 8 mg, and 20 mg of TA (Kenalog-40; Bristol-Myers Squibb, Princeton, NJ) in 0.1 mL were given to pigmented rabbits. For control, 0.1 mL of TA vehicle and saline were injected. Animals were killed on day 14, and retinas were analyzed by light as well as electron microscopy. RESULTS: No ophthalmoscopic change was found. Eyes injected with 0.5 mg and 1 mg of TA did not have morphologic abnormality. Eyes injected with 4 mg, 8 mg, and 20 mg showed destruction of photoreceptor outer segments and migration of macrophage-like cells in the subretinal space. Eyes injected with 20 mg showed more extensive damage and increased pigment granules in the retinal pigment epithelium cells with large oil droplets in the cytoplasm. Electron microscopy also showed loss of photoreceptor/retinal pigment epithelium interdigitations. Eyes injected with vehicle or saline did not show morphologic changes. CONCLUSION: Single intravitreal injection of 0.5 mg or 1 mg of TA did not produce morphologic retinal changes in pigmented rabbits. However, injections of 4 mg, 8 mg, and 20 mg of TA produced outer retina toxic effects. These findings suggest that long-term retinal toxicity studies should be carried out, using single and repeated injections before this therapy becomes more widely used.


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...