Ocular distribution and toxicity of intravitreal injection of triamcinolone acetonide in normal equine eyes.

OBJECTIVE: To determine ocular distribution and toxicity of a single injection of intravitreal triamcinolone acetonide (TA) in normal horses. ANIMALS STUDIED: Six adult horses, donated to North Carolina State University. PROCEDURES: Six horses were injected intravitreally with either 10, 20, or 40 mg (n = 2 each) of TA. The opposite eye of each horse was injected with balanced salt solution (BSS). Ocular toxicity was assessed by biomicroscopy, tonometry, indirect ophthalmoscopy, and electroretinogram. Aqueous humor (AH), vitreous humor (VH), and plasma samples were collected. Horses were euthanized 7 or 21 days after injection and eyes enucleated for histopathology. TA concentrations in AH, VH, and plasma were measured by HPLC. RESULTS: Three control eyes and one TA eye developed inflammation after injection or collection of AH. Positive bacterial cultures (Corynebacterium spp., Staphylococcus spp., and Streptococcus spp.) were obtained from three of these eyes. Other than transient corneal edema in TA injected eyes, which resolved by 7 days after injection, no other changes were observed. TA crystals were visible within the vitreous body. No evidence of TA toxic effect was noted on histopathology. TA was detected in all AH and VH samples from treated eyes following injection. Drug was not detected in the plasma. CONCLUSIONS: There was no evidence of overt toxicity from intravitreal TA in normal horses and a single intravitreal injection resulted in TA ocular levels for 21 days. However, the risk for bacterial infections with intravitreal injection or anterior chamber aspirations in horses is high. Use of topical and systemic antibiotics after injection is recommended.

Ocular toxicity and distribution of subconjunctival and intravitreal rapamycin in horses.

In vitro photosensitivity of rapamycin (RAPA) and ocular toxicity and distribution of intravitreal and subconjunctival RAPA was evaluated in normal horses. RAPA (2.5 mg, 5 mg, and 10 mg) was placed in 10 mL of PBS and maintained in a water bath at 37 degrees C, kept in the dark or subjected to room light, and sampled for up to 3 months for RAPA levels. Six normal adult horses received either 5 mg (n = 2) or 10 mg (n = 2) of RAPA intravitreally or 10 mg (n = 2) subconjunctivally. Ophthalmic exams and electroretinography (ERG) were performed prior to injection and on days 1, 7, 14, and 21 post-injection. Eyes were enucleated and samples were collected for RAPA concentrations and histopathology. No difference in light vs. dark RAPA concentrations was observed, suggesting a lack of RAPA phototoxicity. No evidence of ocular toxicity was noted on ophthalmic examination or histopathology. RAPA was not detected intraocularly 7 days post-injection in eyes receiving subconjunctival RAPA, but was detected in the vitreous at 21 days post-injection. Drug could be detected in both the aqueous and vitreous humor after intravitreal injection. Further study is needed to determine the efficacy of intravitreal RAPA.

[Synthesis and identification of bromoacetylalprenololmenthane (BAlpM)].

A highly potent beta-adrenergic irreversible antagonist--Bromoacetylalprenololmenthane (BAlpM) was synthesized by a six step method with phenol and allychloride as the starting materials. Some improvement on purification of the product was described. The final product is identified by melting point, elemental analysis, UV and IR spectral analysis and mass spectrometry as well as beta-adrenergic receptor binding assays. [125I] +/- IODOPINDOLOL binding assay of mouse lung cell membrane preparations treated with BAlpM in vitro or in vivo showed that there was a dose-dependent decrease in the density of specific binding sites with no change in the Kd values. This result confirms that BAlpM is a beta-adrenergic irreversible antagonist.