Duration 5min, Q&A 3min
Intravitreal Topotecan Inhibits Laser Induced Choroidal Neovascularization in a Rat Model
A two phase preclinical study was designed to determine the safe dose of intravitreal topotecan and its inhibitory effect on choroidal neovascular membrane (CNV) development in a rat model of laser induced CNV.
62 pigmented Lister Hooded rats
In phase I of the study, 35 animals were assigned into 5 treatment groups and received intravitreal injection of serial concentrations of topotecan(0.125 µg, 0.25 µg, 0.5 µg, 0.75 µg and 1.0 µg per 5 µl) in one eye, while the fellow eye (control) received no injection. In addition, 7 other animals were assigned into a double control group and received 5 µl of normal saline in one eye. All the eyes were subjected to ophthalmic and electroretinography ( ERG ) examinations 7 , 14 and 28 days later. After the last examination, animals were sacrificed and enucleated globes were fixed with formalin 10% and processed for light microscopy examination. Immunohistochemical staining for glial fibrillary acidic protein (GFAP) was performed in addition to the routine hematoxylin and eosin. In phase II, CNV was induced by laser in the treatment and control groups. Infrared diode-laser photocoagulation was performed on the right eyes (8 lesions per eye) of 20 rats by a slit lamp laser delivery system using a setting of 75µm, 0.05 sec and 200 mW. Immediately after undergoing the laser procedure, eyes in the treatment group (n=10) received 1 µg/5µl of topotecan and control eyes (n=10) received 5µl of normal saline intravitreally. Four weeks later, animals were euthanized after fluorescein angiography, and the enucleated eyes were fixed with formalin 10%. Serial sections of each laser induced lesion were examined under light microscopy.
Results and Conclusion
The results of ophthalmic and histopathologic examinations in the first phase of the study revealed no abnormality in topotecan-treated and control eyes; GFAP immunoreactivity was also unremarkable. No significant differences were found in ERG responses between topotecan-injected and control eyes (p>0.05). Based on these results, 1µg/5µl was chosen as the treatment dose for the second phase. Late stage fluorescein angiography leakage scores were significantly lower in the topotecan-treated eyes compared to controls (p<0.01). Eyes that received topotecan had a significantly lower incidence of fibrovascular proliferation (8.7% vs 96.2%) as evaluated by histopathology, and the average area of CNV membrane was smaller in these eyes compared to controls (p<0.01). In conclusion, results of this experimental study show that intravitreally injectied topotecan may be a safe and promising therapy for choroidal neovascularization.
[ Keyword ]
topotecan / intravitreal / choroidal neovascularization / safe dose / electroretinography
[ Conflict of Interest ]