CASE REPORT
Vascular Changes After Intra-bleb Injection of Bevacizumab Michael A. Coote, MBBS, FRANZCO,*w Jonathan B. Ruddle, MBBS, FRANZCO,*w Queena Qin, BMedSci,* and Jonathan G. Crowston, MD, PhD*w
Purpose: To illustrate changes in bleb vascularity after subconjunctival bevacizumab injection. Methods: Longitudinal changes in bleb vascularity were followed over 6 months pre and postbevacizumab injection. Results: Bleb vascularity associated with increased scarring activity was observed 10 days postcataract surgery in an eye that had undergone trabeculectomy 3 months previously. A single subconjunctival avastin injection led to a dramatic reduction in bleb vascularity for 6 weeks. With continued steroids, a diffuse, healthy, well functioning bleb with minimal scar tissue was present at 6 months.
He underwent left trabeculectomy with a limbal-based conjunctival flap and mitomycin C (0.3 mg for 3 min). Postoperatively, his IOP was reduced to 5 mm Hg. Over the ensuing months, his IOP increased gradually to 12 mm Hg in the presence of mild bleb hyperemia (Fig. 1A) and his cataract worsened. Three months after trabeculectomy, the patient underwent uncomplicated clear corneal phacoemulsification cataract surgery with intraocular lens implantation. In the early postoperative period he developed mild anterior chamber inflammation and was treated with 2-hourly topical dexamethasone (1 mg/mL). At 10-day postoperation his bleb had increased bleb vascularity (Fig. 1B). A single injection of subconjunctival bevacizumab (1 mg) was given into the bleb. His other
Conclusions: Subconjunctival injection of bevacizumab reduced bleb vascularity and may provide an adjunct to current antifibrosis therapy. Further studies to establish the effect of bevacizumab on postoperative scaring are warranted. Key Words: trabeculectomy bleb, antifibrosis, bevacizumab (J Glaucoma 2008;17:517–518)
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ub-conjunctival fibrosis, a major cause of inadequate intraocular pressure (IOP) lowering after trabeculectomy, is heralded by increased bleb vascularity. Reduction in bleb vascularity may limit the amount of scar formation. This report illustrates long-term reduction in bleb vascularity following a single subconjunctival injection of bevacizumab.
CASE REPORT A 60-year-old man with type-2 diabetes, proliferative diabetic retinopathy, and macular edema developed elevated IOP in the left eye, which persisted around 40 mm Hg despite maximum tolerated medical therapy (timolol, brimonidine, latanoprost, and oral acetazolamide). Gonioscopy revealed an open irido-corneal drainage angle and there was no evidence of rubeosis. Received for publication August 3, 2007; accepted September 20, 2007. From the *Centre for Eye Research Australia, University of Melbourne; and wGlaucoma Investigation and Research Unit, Royal Victoria Eye and Ear Hospital, East Melbourne, Australia. Reprints: Dr Jonathan G. Crowston, MD, PhD, Centre for Eye Research Australia, University of Melbourne, Locked Bag 8, East Melbourne, Vic 8002, Australia (e-mail:
[email protected]). Copyright r 2008 by Lippincott Williams & Wilkins
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FIGURE 1. A, Bleb before cataract surgery 3 months posttrabeculectomy. B, Bleb 10 days postcataract surgery, before bevacizumab injection. C, Bleb 4 weeks postcataract surgery, 2 weeks after bevacizumab. D, Bleb 8 weeks after cataract surgery, 6 weeks after bevacizumab. E, Bleb 3 months after cataract surgery, 10 weeks after bevacizumab. F, Bleb 7 months after cataract surgery, 24 weeks after bevacizumab.
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postoperative medication was not changed. Two weeks postinjection, the bleb was significantly less vascular (Fig. 1C). By 8-week postoperation, he had a visual acuity of 20/40 and an IOP of 9 mm Hg. His bleb had become more vascular again (Fig. 1D), and the frequency of topical dexamethasone was increased. At 3 and 6 months of postoperation, his IOP was well controlled at 10 mm Hg with a diffuse quiet functioning bleb. A small avascular area over the sclerostomy was noted (Figs. 1E, F).
DISCUSSION Vascular endothelial growth factor (VEGF) is a potent angiogenic growth factor expressed in hypoxic and ischemic retina. Up-regulation of VEGF expression occurs in the context of retinal vein occlusion and diabetic retinopathy.1 Experimental animal models of retinal ischemia have demonstrated a strong quantitative and temporal correlation between VEGF expression and neovascularization of the retina and iris.2,3 VEGF is a small peptide that readily diffuses through the vitreous to the iris, where it acts as a potent mediator of angiogenesis.2,3 Intravitreal injection of human VEGF induced iris neovascularization in nonhuman primates,2 and the use of an experimental anti-VEGF therapeutic (antisense) prevented ischemia-induced iris neovascularization.3 Furthermore, VEGF levels are elevated in patients with rubeosis iridis. In a study of 16 patients with ischemic central retinal vein occlusion, a strong correlation was found between aqueous VEGF levels and the course of iris neovascularization and increased vascular permeability.4 Bevacizumab and 5-fluorouracil are used concomitantly for the treatment of colorectal cancer. An increased incidence of wound dehiscence has also been reported, suggesting that this combination of agents inhibits wound
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healing.5 The antifibrotic activities of bevacizumab have not been formally studied. The use of subconjunctival bevacizumab for the management of postoperative fibrosis after trabeculectomy has been reported previously.6 This case provides a longitudinal demonstration of the reduction in conjunctival vascularity after a single intrableb injection of bevacizumab in an eye with presumed elevated VEGF and at high risk of excess postoperative scar formation. Further research is warranted to establish an antifibrosis effect of bevacizumab after trabeculectomy. Subconjunctival bevacizumab may provide a new therapeutic approach to inhibiting fibrosis in eyes with elevated intraocular levels of VEGF that are at risk of postoperative scarring. REFERENCES 1. Aiello LP, Avery RL, Arrigg PG, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994;331:1480–1487. 2. Tolentino MJ, Miller JW, Gragoudas ES, et al. VEGF is sufficient to produce iris neovascularization and neovascular glaucoma in a nonhuman primates. Arch Ophthalmol. 1996;114:964–970. 3. Bhistikul RB, Robinson GS, Moulton RS, et al. An antisense oligodeoxynucleotide against vascular endothelial growth factor in a nonhuman primate model of iris neovascularization. Arch Ophthalmol. 2005;123:214–219. 4. Boyd SR, Zachary I, Chakravarthy U, et al. Correlation of increased vascular endothelial growth factor with neovascularization and permeability in ischemic central vein occlusion. Arch Ophthalmol. 2002;120:1644–1650. 5. Scappaticci FA, Fehrenbacher L, Cartwright T, et al. Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol. 2005;91:173–180. 6. Kahook MY, Schuman JS, Noecker RJ. Needle bleb revision of encapsulated filtering bleb with bevacizumab. Ophthalmic Surg Lasers Imaging. 2006;37:148–150.
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