Effect of various single doses of intravitreal topotecan on the ultrastructure of the rabbit retina
DOI:
https://doi.org/10.31288/Ukr.j.ophthalmol.202654653Keywords:
intravitreal chemotherapy, topotecan, retinal ultrastructure, rabbits, experiment, retinoblastomaAbstract
Purpose. To assess ultrastructural changes in the rabbit retina after various single doses of intravitreal topotecan.
Material and Methods. Eyes of 12 Chinchilla rabbits were divided into an experimental group (20 eyes) and a control group (4 eyes). The former group was divided into five subgroups of four eyes each to receive an intravitreal injection (IVI) of 0.1 ml topotecan at a dose of 20, 30, 40, 50 or 60 µg. The control group was given an IVI of 0.1 ml saline. Animals were followed up the next day after injection and at weeks 1, 2, 3 and 4 to evaluate their general status and examine their eyes by slit lamp microscopy and direct ophthalmoscopy. At one month after injection, both eyes were enucleated and rabbits were euthanized by air embolism. Thereafter, chorioretinal complex samples were examined by electron microscopy. The evaluation of ultrastructural changes in the chorioretinal complex was qualitative and descriptive in nature.
Results. The rabbits’ general well being and general condition of the anterior segment of the eye were unaffected in all groups. Ophthalmoscopically, no pathological changes were observed after 20- to 40-µg injection. However, one week after 50- to 60-µg injection, there was evidence of mild retinal whitening which did not increase in severity at subsequent follow-up evaluations. Ultrastructural changes were dose dependent. After 20 to 30-µg injection, we observed mild reversible hydropic changes in retinal pigment epithelial cells and inner retinal layers, but the retina retained its layered structure. A 40 to 50-µg injection was followed by more apparent hydropic dystrophy of chorioretinal complex structures. After 60-µg injection, we observed initial alterations in individual neural organelles.
Conclusion. 20-30-µg intravitreal topotecan injection caused only mild reversible changes in retinal ultrastructure. A dose of 40 to 50 μg (equivalent to 80 to 100 μg in the human eye) may be considered a dosage that achieves an optimal efficacy/toxicity balance. A dose of 60 μg (equivalent to 120 μg in the human eye) caused initial alterations in the chorioretinal complex. Our findings (1) confirm that topotecan has a lower toxicity than melphalan and (2) may be used to justify the selection of a safe dose for intravitreal chemotherapy for retinoblastoma.
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