Intravitreal and intracameral bevacizumab to treat neovascular complications of retinopathy of prematurity

Abstract

Editor, A 26-year-old White woman was referred for management of neovascular glaucoma complicating retinopathy-of-prematurity-related retinal detachment. She had previously undergone cryotherapy and scleral buckling for mixed tractional and exudative retinal detachment in the right eye (RE) and had lost her left eye because of phtisis bulbi. Visual acuity (VA) was hand movements (HM); intraocular pressure (IOP) was 31 mmHg. There was iris neovascularization in all quadrants, the drainage angle was open with isolated areas of peripheral anterior synechiae (PAS) and there was a long-standing partial retinal detachment. Treatment was started with topical hypotensive therapy but within 2 months the pain became worse with corneal oedema, florid iris neovascularization, ectropion uveae (Fig. 1A), angle neovascularization and 330° PAS. VA remained HM but IOP was 68 mmHg and unresponsive to oral acetazolamide. Photocoagulation was not feasible because of the retinal detachment. We treated the RE with an intravitreal injection of bevacizumab (1.25 mg in 0.05 ml) (Avastin®; Genentech Inc., San Francisco, California, USA). Two weeks after the injection, iris neovascularization had substantially regressed and we implanted a vicryl-ligated Baerveldt 350 mm2 aqueous shunt (AMO Groningen B.V. Groingen, the Netherlands) (Fig. 1B). One month later, IOP was 9 mmHg without ocular hypotensive medication, although iris new vessels had become more prominent in appearance (Fig. 1C). (A) Florid iris neovascularization and ectropion uveae at presentation. (B) Partial regression of iris new vessels following intravitreal bevacizumab injection and Baerveldt tube implant (10 days postoperatively). (C) More prominent iris new vessels at 6 weeks postoperatively. (D) Obstruction of the Baerveldt tube intracameral lumen by proliferating neovascular tissue (3 months postoperatively). (E) Partial resolution of the obstruction and regression of the iris new vessels 3 days after application of Nd-YAG laser and intracameral injection of bevacizumab. (F) Appearance of the anterior segment at the last follow-up, 5 weeks after intracameral injection of bevacizumab: note the large surgical iridectomy to prevent recurrent tube occlusion and the substantial regression of iris new vessels. Three months after the operation, the eye became painful again. IOP was 48 mmHg and the intracameral lumen of the Baerveldt tube was obstructed by proliferating neovascular tissue (Fig. 1D). We applied Nd-YAG-laser to tube opening, re-establishing aqueous outflow: IOP fell to 18 mmHg. An hour later, we gave an intracameral injection of bevacizumab (0.625 mg in 0.025 ml). Three days later, iris neovascularization had regressed (Fig. 1E) and at surgery we created a large surgical iridectomy adjacent to the tube lumen to remove the scaffold for recurrent fibrovascular proliferation (Fig. 1F). Five weeks later, VA was still HM and the eye was comfortable with an IOP of 18 mmHg. Bevacizumab is a recombinant, full length, anti-vascular endothelial growth factor (VEGF) monoclonal antibody able to bind all isoforms of VEGF-A. Previous case reports (Davidorf et al. 2006; Iliev et al. 2006; Silva Paula et al. 2006) have shown that bevacizumab can induce regression of anterior-segment neovascularization. We used anti-VEGF as a preoperative intravitreal injection before surgical treatment for neovascular glaucoma to reduce the risk of perioperative bleeding and gave a second injection 3 months later intracamerally to induce regression of a recurrent neovascular membrane occluding a glaucoma drainage device. A recent report (Beer et al. 2007) has shown that in humans, a single dose of intravitreal bevacizumab is likely to provide complete intravitreal VEGF blockade for a minimum of 4 weeks. Our patient developed recurrent neovascularization 6 weeks after injection. When this occluded the drainage tube, we chose to give bevacizumab via intracameral rather than intravitreal injection because the need was to treat an anterior chamber neovascular membrane; furthermore, intracameral injection is simpler and more comfortable for the patient. There is one previous report to our knowledge (Grisanti et al. 2006) of intracameral use of bevacizumab for treatment of neovascular glaucoma. Three patients were given 0.04 ml intracameral bevacizumab with a dramatic reduction of leakage demonstrated by iris fluoroscein angiography, which was still evident 30 days after injection. In our case, a significantly lower intracameral dose of bevacizumab resulted in rapid iris neovascularization regression. Intraocular bevacizumab, by either intravitreal or intracameral injection, can prove useful as an adjunct to glaucoma drainage surgery. The authors would like to thank the technicians Kanom Bibi, the photographer Matthew Richardson and the research officer Laura Gangadeen. This article has been supported by the National Health Service, Research and Development, UK.