Evaluation of clearance, intraocular pressure and histopathological change resulting from two depot steroids injected into the vitreous cavity of rabbits.

Abstract

Abstract: : Purpose: In this study we investigate the clearance, effect on intraocular pressure, and compare the histopathological changes induced by the depot steroid; triamcinolone in the acetonide and the diacetate form. Methods:Twenty–five New Zealand white rabbits were randomly assigned into five treatment groups: two groups receiving triamcinolone diacetate suspension (one at 4mg/0.1ml and the other group at 8mg/0.2ml concentration) and three groups receiving suspensions of triamcinolone acetonide at 4mg/0.1ml, 8mg/0.2ml and 16mg/ml (8mg/0.2ml over 2 days) respectively. All depot steroid doses were injected into the vitreous cavities of the right eyes, while the left eyes served as the control. Control eyes received the same volume of sterile balanced salt solution (BSS) in using similar injection techniques. At day 1, and at post injection weeks 1, 2, 3, 4 and 8 all eyes were evaluated by indirect ophthalmoscopy and for recording intraocular pressure measurements. At these same time points an animal from each of the experimental groups was sacrificed and the enucleated eyes evaluated for histopathological changes or assessed for residual corticosteroid using HPLC. The histopathologic changes were evaluated in a masked fashion using a semiquantitative grading system. Results: No clinical differences were noted between animals in both drug groups. Two eyes receiving triamcinolone diacetate developed cataracts. These changes might represent damage to the lens capsule during injection rather than an effect of the drug itself. No differences were observed in the range of intraocular pressure in either of the treatment groups or control (treatment group range 9–38mmHG, control range 13–39mmHG ). Analysis of the vitreous samples by HPLC detected residual steroid in both the diacetate and acetonide groups at 8 weeks. Histopathologic examination did not demonstrate any pathologic changes in the anterior segments in all eyes. Retinal ganglion cell loss was noted in both steroid groups while vacuolization in the nerve fiber layer was observed in experimental and control eyes. Conclusions: Based on data collected from our study it appears that that triamcinolone diacetate and triamcinolone acetonide have similar effects on clinical exam findings, intra–ocular pressure, and induction histopathological changes in the retina. Our data also demonstrates that triamcinolone in the diacetate and acetonide forms are detectable by HPLC analysis from isolated vitreous samples for at least 8 weeks post injection.

Keywords: vitreous • retina • pharmacology