Mazza Orit, Habot-Wilner Zohar, Shahar Jonathan, Mann Irit, Loewenstein Anat, Perlman Ido
Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology and the Rappaport Institute, Haifa, Israel.
Division of Ophthalmology, Tel Aviv Medical Center, Tel Aviv, Israel.
Transl Vis Sci Technol. 2018 Nov 14;7(6):2. doi: 10.1167/tvst.7.6.2. eCollection 2018 Nov.
To evaluate retinal toxicity of intravitreal trimethoprim-sulfamethoxazole (TMP-SMX) in an albino rabbit model.
Albino rabbits ( = 10) were treated in the right eye with the maximum intravitreal dose of TMP-SMX mixture (1600 μg/8000 μg /0.1 mL), while 0.1 mL saline was injected into the vitreous of the left eye. Clinical examination and electrophysiological (electroretinogram [ERG] and visual evoked potentials [VEPs]) testing were conducted before injection, 3 days, 1, 2, and 4 weeks postinjection. Retinal structure and expression of glial fibrillary acidic protein (GFAP) were assessed from histology and immunocytochemistry respectively at the end of the follow-up period.
Clinical examination was normal throughout the follow-up period. ERG responses from the experimental eyes were similar to those recorded from the control eyes, but the sum of oscillatory potentials decreased in the experimental eyes at 2 weeks postinjection. The VEP responses, elicited by stimulation of the experimental eyes, were abnormal having reduced amplitude and prolonged implicit time. Histological damage in the experimental eyes was expressed by thickness reduction of whole, outer, and inner nuclear layers. GFAP was expressed in retinal Müller cells of all experimental eyes, but none of control eyes.
A single intravitreal injection of TMP-SMX mixture (1600 μg/8000 μg, respectively) causes functional and structural damage to the inner retina and retinal output. Signs of retinal stress were also evident by GFAP expression in retinal Müller cells of all experimental eyes. Therefore, the use of TMP-SMX via intravitreal administration should be done with caution.
These findings highlight the risk of retinal toxicity after intravitreal injection of trimethoprim-sulfamethoxazole and emphasize that this treatment should be carefully considered.
在白化兔模型中评估玻璃体内注射甲氧苄啶 - 磺胺甲恶唑（TMP - SMX）的视网膜毒性。
10只白化兔右眼接受玻璃体内最大剂量的TMP - SMX混合物（1600μg/8000μg/0.1mL）治疗，左眼玻璃体内注射0.1mL生理盐水。在注射前、注射后3天、1、2和4周进行临床检查和电生理检查（视网膜电图[ERG]和视觉诱发电位[VEP]）。在随访期结束时，分别通过组织学和免疫细胞化学评估视网膜结构和胶质纤维酸性蛋白（GFAP）的表达。
在整个随访期临床检查均正常。实验眼的ERG反应与对照眼记录的反应相似，但注射后2周实验眼的振荡电位总和降低。刺激实验眼诱发的VEP反应异常，振幅降低且潜伏期延长。实验眼的组织学损伤表现为全层、外层和内层核层厚度减少。所有实验眼的视网膜Müller细胞中均表达GFAP，而对照眼中均未表达。
单次玻璃体内注射TMP - SMX混合物（分别为1600μg/8000μg）会对内视网膜和视网膜输出造成功能和结构损伤。所有实验眼的视网膜Müller细胞中GFAP表达也表明存在视网膜应激迹象。因此，玻璃体内注射TMP - SMX的使用应谨慎。
这些发现突出了玻璃体内注射甲氧苄啶 - 磺胺甲恶唑后视网膜毒性的风险，并强调应仔细考虑这种治疗方法。
