The influence of aphakia and vitrectomy on experimental retinal toxicity of aminoglycoside antibiotics

To study the effect of lens and vitreous surgery on the dose threshold of aminoglycoside-induced retinal toxicity, we performed extracapsular lens extraction (Group 1) or lensectomy and vitrectomy (Group 2) on Dutch Belted rabbits. A single dose of amikacin or gentamicin ranging from 100 to 4,000 micrograms was administered intravitreally. Retinal toxicity was examined by light and transmission electron microscopy seven days after injection. Both groups showed retinal toxicity after 400 micrograms of gentamicin or 1,500 micrograms of amikacin, doses identical to those causing toxicity in intact, phakic rabbit eyes. Thus, neither surgical procedure increased the toxic threshold of injected aminoglycoside. Given the accelerated aminoglycoside clearance reported in aphakic eyes, these findings imply that the mechanism of aminoglycoside toxicity may be related to peak drug concentration rather than duration of tissue exposure.