Komarowska Izabela, Heilweil Gad, Rosenfeld Philip J, Perlman Ido, Loewenstein Anat
Department of Physiology and Biophysics, Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology and the Rappaport Institute, Haifa, Israel.
Retina. 2009 Jan;29(1):98-105. doi: 10.1097/IAE.0b013e31817d8c09.
To determine whether intravitreal injection of a commercially available ketorolac tromethamine preparation causes retinal toxicity in albino rabbits.
Nine albino rabbits were injected intravitreally with ketorolac tromethamine (3 mg; 0.1 mL) in one eye and saline (0.1 mL) in the fellow eye. Six of the rabbits received a single injection of ketorolac, and the other three rabbits underwent biweekly injection for a total of four injections. Electroretinography testing was performed on both eyes at different time intervals during 4 weeks of follow-up in the single injection group, and during 12 weeks of follow-up in the multiple injection group. Visual evoked potentials were recorded from each rabbit using monocular and binocular stimulation at the end of the follow-up period. Animals were then killed, and the retinas were prepared for morphologic examination at the light microscope level and for immunostaining for glial fibrillary acidic protein, as a marker of retinal damage.
The electroretinography responses from the control and experimental eyes were similar throughout the follow-up period in all rabbits of both experimental groups. There were no differences in the flash visual evoked potential responses between experimental and control eyes in the single injection group, while in the repeated injection group, statistically significant differences were found. Light microscopy did not identify significant histologic differences between the retinas from control and experimental eyes after a single dose. However, after repeated dosing, two of three eyes showed histologic evidence of local toxicity. Immunocytochemical analysis showed no glial fibrillary acidic protein staining in Muller (glial) cells throughout the retina in the single injection group. Slight glial fibrillary acidic protein staining was detected in only one of the three retinas from rabbits in the repeated injection group.
Commercially available ketorolac tromethamine was found to be toxic to the retinas of albino rabbits following multiple intravitreal injections at a dose of 3 mg while no electrophysiologic toxicity was found. Therefore, the use of commercially available ketorolac containing alcohol, for intravitreal injection is not recommended.
确定玻璃体内注射市售酮咯酸氨丁三醇制剂是否会对白化兔视网膜产生毒性。
9只白化兔，一只眼睛玻璃体内注射酮咯酸氨丁三醇（3毫克；0.1毫升），另一只眼睛注射生理盐水（0.1毫升）。6只兔子接受单次酮咯酸注射，另外3只兔子每两周注射一次，共注射4次。单次注射组在4周的随访期间，多次注射组在12周的随访期间，于不同时间间隔对双眼进行视网膜电图测试。在随访期结束时，使用单眼和双眼刺激记录每只兔子的视觉诱发电位。然后处死动物，制备视网膜用于光镜水平的形态学检查以及作为视网膜损伤标志物的胶质纤维酸性蛋白的免疫染色。
在两个实验组的所有兔子的整个随访期内，对照眼和实验眼的视网膜电图反应相似。单次注射组实验眼和对照眼的闪光视觉诱发电位反应没有差异，而在重复注射组中发现有统计学意义的差异。单剂量后，光镜检查未发现对照眼和实验眼视网膜之间有明显的组织学差异。然而，重复给药后，三只眼中有两只显示出局部毒性的组织学证据。免疫细胞化学分析显示，单次注射组整个视网膜中的穆勒（神经胶质）细胞没有胶质纤维酸性蛋白染色。重复注射组兔子的三只视网膜中只有一只检测到轻微的胶质纤维酸性蛋白染色。
发现市售酮咯酸氨丁三醇在以3毫克剂量多次玻璃体内注射后对白化兔视网膜有毒性，而未发现电生理毒性。因此，不建议使用含酒精的市售酮咯酸进行玻璃体内注射。
