Department of Ophthalmology, University of São Paulo, São Paulo, Brazil.
J Ocul Pharmacol Ther. 2011 Aug;27(4):327-31. doi: 10.1089/jop.2010.0174. Epub 2011 Jun 13.
To evaluate the ocular toxicity of escalating doses of intravitreous adalimumab (Humira®) in the rabbit eye.
Thirty New Zealand albino rabbits received intravitreous injections of 0.5 mg (6 eyes), 1.0 mg (6 eyes), 2.5 mg (6 eyes), 5 mg (6 eyes), and 10 mg (6 eyes) adalimumab. Slit lamp biomicroscopy and fundoscopy were carried out at baseline, day 7, and day 14 after intravitreous injection, whereas electroretinography (ERG) was carried out at baseline and day 14. Animals were euthanized on day 14, and histopathological examination of the eyes was performed.
Slit lamp biomicroscopy and fundoscopy were normal in all eyes receiving doses up to 5 mg. In the 10 mg group, 3 of 6 eyes showed mild anterior chamber inflammatory reaction on day 7. Similarly, scotopic and photopic a- and b-wave ERG amplitudes at baseline and day 14 were similar in all groups up to 5 mg, but there was a significant decrease in the photopic-wave ERG response in the 10 mg group (P=0.046). Finally, histopathology demonstrated no differences among eyes receiving balanced salt solution, 0.5, 1.0, 2.5, 5.0, or 10 mg of adalimumab.
Intravitreous adalimumab exhibited no associated ocular short-term toxicity in rabbit eyes up to the 5 mg dose. In the 10 mg group mild clinical findings and ERG amplitude reduction could reflect early toxicity.
评估玻璃体内递增剂量阿达木单抗（修美乐）对兔眼的眼毒性。
30 只新西兰白兔接受玻璃体内注射 0.5mg（6 只眼）、1.0mg（6 只眼）、2.5mg（6 只眼）、5.0mg（6 只眼）和 10.0mg（6 只眼）阿达木单抗。在玻璃体内注射后第 7 天和第 14 天进行裂隙灯生物显微镜检查和眼底检查，而视网膜电图（ERG）则在基线和第 14 天进行。第 14 天处死动物，并对眼睛进行组织病理学检查。
所有接受剂量至 5mg 的眼的裂隙灯生物显微镜检查和眼底检查均正常。在 10mg 组中，有 3 只眼在第 7 天出现轻度前房炎症反应。同样，在 5mg 以下的所有组中，基线和第 14 天的暗适应和明适应 a 波和 b 波 ERG 幅度相似，但在 10mg 组中明适应波 ERG 反应显著降低（P=0.046）。最后，组织病理学检查显示接受平衡盐溶液、0.5、1.0、2.5、5.0 或 10mg 阿达木单抗的眼之间没有差异。
玻璃体内阿达木单抗在兔眼内至 5mg 剂量时未显示出相关的短期眼毒性。在 10mg 组中，轻微的临床发现和 ERG 幅度降低可能反映了早期毒性。
