Intracameral Injection of Bevacizumab for Eyes with Iris Neovascularization

1. Intracameral Injection of Bevacizumab for Eyes with Iris Neovascularization Yong Wook Park, MD, Hong Kyun Kim, MD, Jae Pil Shin, MD. Department of Ophthalmology, Kyungpook National University College of Medicine, Daegu, Korea

2. Purpose • To evaluate the safety and efficacy of intracameral injection of Bevacizumab in rabbit model and in patients with iris neovascularization (INV).

3. Methods 1. Corneal Toxicity of Intracameral Bevacizumab in Rabbit Model • Two albino rabbits were used. Bevacizumab (1.25mg/0.05ml) was injected intracamerally in right eye of two rabbits and balanced saline solution (0.05ml) was injected into contralateral eye as a control. • Slit lamp examination, specular microscopy, pachymetry and tonometry were performed before and 1, 7 days after intracameral bevacizumab injection. • All rabbits were euthanized at day 7 and enucleated eyes were prepared for electron microscopic examination.

4. Methods 2. Efficacy of Intracameral Injection of Bevacizumab in Patients with Neovascular Glaucoma (NVG) • Four eyes of four patients with NVG were enrolled in this study. • All eyes were received intracameral injection of bevacizumab (1.25mg/0.05ml) during Ahmed valve implantation. • All patients were followed up for more than four weeks. • Visual acuity, intraocular pressure measurement, slit-lamp examination and iris fluorescein angiography were performed before and 1 and 4 weeks after operation.

5. Results 1. Corneal Toxicity of Intracameral Bevacizumab in Rabbit Model • Corneal endothelial count and central corneal thickness showed no significant differences between the treated and control eyes and also, intraocular pressure was not increased (Table 1). • The scanning electron microscopic photographs showed normal corneal endothelial appearance in intracameral injection group (Figure 1). The hexagonal shape of corneal endothelium was preserved. No abnormal endothelial cells such as bleb formation and disintegration of cellular border were found. Smooth and distinct cell borders were detected between each endothelial cell. Intercellular border thickness was also normal in all groups.

6. Results 2. Efficacy of Intracameral Injection of Bevacizumab in Patients with Neovascular Glaucoma • Regression of INV and decreased vascular permeability (Figure 2,3) were observed in all eyes within 1 week after intracameral bevacizumab injection. • At the final examination, the visual acuity was stable or improved in all eyes. The intraocular pressure remained stable in all eyes with medical treatment (Table 2). • There was no complication or inflammation. • No relapse was seen within the follow-up of period.

8. SEM Photographs of corneal endothelium after intracameral bevacizumab injection A B Figure 1. Scanning electron microscopic photographs of corneal endothelial cells of the rabbits (X1000). (A) 1 week after intracameral injection of bevacizumab, (B) 1 week after intracameral injection of balanced salt solution.

10. A B D C Figure 2. Gonioscopy examination before (A) and 1 week after (C) intracameral bevacizumab (case 1). Note the regression of angle neovascularization. Iris fluorescein angiography before (B) and 1 week after (D) intracameral bevacizumab injection.

11. A B C D Figure 3. Clinical appearance of the iris before (A) and 1 week after (C) intracameral bevacizumab injection (case 3). Note the regression of iris neovascularization. Iris fluorescein angiography before (B) and 1 week after (D) intracameral bevacizumab injection.

12. Discussion • INV and subsequent development of NVG are serious consequences for patients with ischemic retinopathies. • Previous studies have shown that INV is correlated highly with retinal ischemia, which stimulates the production of vascular endothelial growth factor (VEGF), a key molecule in ocular neovascularization. • Therefore, direct targeting of VEGF might be another possible therapeutic strategy to treat neovascularization.

13. Discussion • Bevacizumab (Avastin®) is a full-length humanized anti-VEGF monoclonal antibody. • Recently, several case series have been published regarding the off-label use of intravitreal bevacizumab for the treatment of cystoid macular edema and age-related macular degeneration. • In our study, we evaluated the safety intracameral injection of bevacizumab in a rabbit model, and efficacy of intracameral injection of bevacizumab in patients with INV.

14. Discussion • There was no corneal toxicity of intracameral bevacizumab in rabbits. In our cases, all patients had regression of INV after intracameral bevacizumab and Ahmed valve implantation. • Although there is no published long-term safety data for intracameral bevacizumab, it seems to be well tolerated in short-term studies. • Even if its effect is transient, bevacizumab may have at least an adjunctive role because of its rapid, dramatic biologic effect.

15. Conclusion • Intracameral injection of bevacizumab was safe and effective in eyes with INV. • Although the small samples limits our observations, the intracameral bevacizumab may provide an additional strategy for the treatment of INV.