Intravitreal application of ganciclovir in rabbits: ERG and electron-microscopic findings

The retinal toxic effect after intravitreal use of ganciclovir has been the subject of our experimental investigation on 20 New Zealand rabbits. Different doses of ganciclovir ranging from 200 to 600 micrograms/0.1 ml were injected intravitreously, and ERG changes were recorded at different time points after drug administration. Finally the animals were killed and the retinal lesions were studied by electron microscopy. According to our experiments, ganciclovir doses of 300-600 micrograms/0.1 ml have a clearly toxic effect on the retina as shown by ERG changes. One month after the injection, the electroretinogram is either extinguished or clearly affected. Noteworthy is the fact that in a dose of 200 micrograms/0.1 ml, the ERG b-wave shows a 20% reduction of its normal amplitude 4 months after ganciclovir delivery. Electron microscopy of the retina revealed in the inner segment of the receptor cells the existence of dilatation and vesiculation of the endoplasmic reticulum in the surrounding nuclear cytoplasm and swelling of the mitochondria with fragmentation of the cristae in several of them. In the outer segment of the photoreceptor cells, degeneration and destruction of the lamellae accompanied by disintegration of the adjacent protoplasm in parts of certain rods and cones appeared. Finally large vacuoles of irregular shape in the synapses and degenerative mitochondria and empty vacuoles in the optic nerve fibers were shown.