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Sarah Molokhia, Kongnara Papangkorn, Charlotte Butler, Randon Michael Burr, John Higuchi, Balbir Brar, Balamurali Ambati, William Higuchi; . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2293.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the efficacy and pharmacodynamics of a single dose electroosmotic delivery of bevacizumab (BEV) in a choroidal neovascularization (CNV) rabbit model in comparison to the single dose of intravitreal (IVT) injection of BEV (1.25 mg, standard dose).
Nine Dutch belted rabbits received subretinal injections of adeno-associated virus (AAV) encoding human VEGF165 in both eyes. Approximately 20 ul per injection of 5x1011 VP/mL was injected to induce CNV. Three weeks after the AAV injections, the rabbits were divided to three groups (n= 3 for each group): Group 1 was a control (no treatment); Group 2 was treated bilaterally with IVT injections of BEV (1.25 mg); and Group 3 was treated unilaterally with electroosmosis of BEV. Electroosmosis was conducted using the Visulex-I system at 3 mA for 20 min with the low ionic strength 12.5 mg/ml BEV. Fluorescein angiogram (FA) was performed at weeks 1, 2, 4, 5, 7, 8 and 12 and 16. The efficacies of the BEV treatments were measured in terms of the delays in the time of appearance of the retina neovascularization in the rabbit. The subretinal lesion diameters were also measured.
All of the control eyes developed retina neovascularization at approximately week 4 ± 1 week. The IVT injection of BEV showed suppression of retina neovascularization in all 6 eyes up to week 12 after subretinal AAV injections. The electroosmosis-BEV group showed suppression of retina neovascularization in all treated eyes and had a delayed onset of retina neovascularization of up to 8 weeks after subretinal injection. Comparing electroosmosis-BEV treatment to no treatment, the electroosmosis-BEV treatment was capable of suppressing the retina neovascularization for an average of 4 weeks. Both BEV treatment groups showed a tendency of smaller lesion diameter after week 6 compared to the control group.
The model responded well to both BEV treatment modalities (i.e., IVT and electroosmosis). The present finding of the 4 week suppression of retina neovascularization in the rabbit with the electroosmosis-BEV treatment (compared to 8 weeks suppression of IVT-BEV) is highly encouraging for the further development of Visulex-I. The results demonstrate that BEV, a large anti-VEGF macromolecule, potentially can be delivered non-invasively to the back of the eye in therapeutically relevant concentrations.
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