Retinal toxicity study of intravitreal ganciclovir in albino rabbit

Abstract

Objective: To elevated the retinal toxicity of intravitreal ganciclovir in albino rabbit eyes. Methods: Experimental study. Twenty-four New Zealand albino rabbits (forty-eight eyes) were divided into four groups by random. Three groups were prepared for ganciclovir experiment, named A, B, C. Each group received intravitreal injection ganciclovir dose at 400 μg/0.05 ml, 2 mg/0.05 ml and 5 mg/0.05 ml respectively. The other group named D served as a control accepted intravitreal injection 0.9% normal saline 0.1 ml. Before and after 1, 2 and 4 weeks, flicker full field electroretina gram (ERG) was recorded. After 1, 2 and 4 weeks light and electron microscopic tests were recorded for further toxicity study. Results: There was significant difference in amplitude of maximal combined response a wave in one week(χ(2)=8.319, P=0.04), and pairwise comparison the 5 mg group (140.50 μV) was significantly lower than the control group (165.00 μV) (χ(2)=-2.830, P=0.028). Maximal combined response b wave in four weeks(χ(2)=-10.626, P=0.014), and pairwise comparison the 5 mg group (261.50 μV) was significantly lower than the control group (398.00 μV) (χ(2)=-2.973, P=0.018). 30 Hz flicker response in one, two and four weeks(χ(2)=17.589, 8.225, 8.997, P=0.001, 0.042, 0.02), and pairwise comparison the 5 mg group (71.3μV, 106.00μV, 63.60μV) was significantly lower than the control group (118.50μV, 129.00μV, 116.50μV) (χ(2)=-4.142, -2.826, -2.713, P=0.000, 0.028, 0.040). There was no histologic retinal toxicity evidence of group 400 μg and control group observed by light microscopy in any stage of the study. Histologic changes of group 2 mg four week later, group 5 mg two and four week later include inner nuclear layer loose arranged, nuclear of ganglia were widened and outer plexiform layer stained less in four week later. By electron microscopic observation, the ultrastructure of retina changed to different degrees and became worse in each experimental group with significant mitochondrial swelling and hydropic changes were seen in the inner segments of photoreceptors, loosely arranged and disordered in the outer segment of photoreceptors four weeks later. Conclusions: The retinal function and morphology were normal in group 400 μg. Group 2 mg and 5 mg had retinal toxicity, and 5 mg was more severe. Therefore, the clinical application of ganciclovir in the treatment of acute retinal necrosis (ARN) should select the minimum effective dose to avoid the occurrence of retinal toxicity. (Chin J Ophthalmol, 2020, 56:279-285).