¡¡¡¡Case 4  A 65ª²yearª²old man got neovascular glaucoma resulted from Branch retinal vein occlusion for 2 months He refused the photocoagulation after Branch retinal vein occlusion was diagnosed one year ago. Rubeosis and hyphema was observed under slitª²lamp exam and IOP was 48 mmHg. His vision was counting finger. Despite of extensive treatment, the IOP did not decrease and iris neovascular persisted. Therefore intracameral injection of Bevaciazumab (avastin) 0.03cc, 0.75mg was performed. 48 hours later, the IOP decreased to 24mmHg. Hyphema absorbed quickly and neovascular surprisingly disappeared. IOP decreased to 14mmHg 1 week later without any assistant medicine. The IOP waved in the range of 14ª²17 mmHg after 3 months followª²up visits.

¡¡¡¡Case 5  This is a complex and interesting case. A 27ª²yearª²old  young woman, who lost her vision of right eye half a year ago, came to my outpatient department because of headache. Slitª²lamp exam showed corneal edema, rubeosis, and serious hemorrhage in vitreous cavity. VA was no light perception and IOP was 58 mmHg, the fundus photography revealed extensive nonª²perfusion area, serious active neovascular on disc and else where, and severe macular edema in left eye, although the vision acuity of left eye was 0.2. We first diagnosed this case as retinal periphlevitis (Eale¬ðs disease). Although she had not any symptom of diabetes mellitus, the serology examination reported that her blood glucose reached 23mmol Lª²1 . Obviously, the diagnosis was diabetic retinopathy. Indeed, active iris neovascularization and hypertension were unresponsive to traditional treatment. So we injected Bevaciazumab (avastin) 0.03cc into the anterior chamber of right eye as we do before, meanwhile the left eye was injected bevaciazumab 0.05cc/1.25mg intravitreally. Panretinal photoª²coagulation in the left eye after injection. The headache caused by hypertension attenuated after 72 hours, but the intraocular pressure still remained 28mmHg with the help of carbonic anhydrease inhibitors (brinzolaminde). Gonioscopy showed closed angle with anterior synechia. She refused to accept further treatment due to financial reason.

¡¡¡¡The mean age of all the 5 patients is 47 years. Followª²up visits range from 3 to 5 months. The injection appeared to be well tolerated in all patients, no patient developed uveitis, endophthalmitis, ocular toxicity, corneal endothelia toxicity, or other obvious systemic adverse events.

¡¡¡¡DISCUSSION

¡¡¡¡Angiogenesis is involved in many ocular diseases including proliferative diabetic retinopathy and ischemic central or branch retinal vein occlusion, retinal periphlevitis (Eale¬ðs disease). Panretinal photocoagulation has been the important treatment for neovascularization. It has proved to be remarkably effective and saved vision of countless patients over the past decades. However, it is a destructive therapy with adverse side effects such as loss of peripheral visual field and night vision as well as exacerbation of macular edema and subsequent reduction of central vision[2.3]. In patients with a media opacity such as vitreous hemorrhage, it is not always possible to administer complete panretinal photocoagulation.

¡¡¡¡Furthermore, patients with iris neovascular and neovascular glaucoma often present hyphema and corneal edema, which prevent full laser treatment. In some cases, after vitrectomy and tamponading silicon oil, progressive retinal anterior hyaloidal proliferation and iris neovascualrization developed despite of extensive panretinal photocoagulation[4].Traditional treatment was dioder laser cyclophotocoagulation and cyclocryosurgery, however, it is not effective for neovascularization.

¡¡¡¡The discovery and cloning of vascular endothelial growth factor was reported in 1989 and the subsequent development of antibodies to it allowed for the identification of VEGF's key role in the development of retinal neovascularization[5]. Inhibition of VEGF can prevent iris neovascularization in primates[6].

¡¡¡¡Bevaciaumab is a recombinant, fullª²length, antiª²VEGF monoclonal antibody that bids to all forms of VEGFª²A. Its offª²label use has shown promise for treatment of neovascular ageª²related macular degeneration and macular edema secondary to central retinal vein occlusion when given by intravitreal injection[7].This encouraging reports prompted us to use it for iris neovascularization and subsequent severe PDR. However, there are just one case report about adverse effects of injection of bevacizumab[8] .Most data presents to date shows that bevacizumab was injected into vitreous cavity to treat PDR or iris neovascularization. Meanwhile the adverse events of intravitreal injection were less than or equal to 0.21%[9]. There are only one case about intracameral bevacizumab for rubeosis[10].

¡¡¡¡In this study, Case 1 and 2 are silicon oil tamponaded eye. The space of liquor in vitreous cavity is limited to 0.05mL, and we don¬ðt know how the bevacizumab works in silicon oil tamponaded vitreous cavity. The resolution for these cases we selected intracameral injection of bevacizumab, which proved to be safe in anterior chamber.
Case 3, 4 and 5, the measure of intracameral injection was selected for rubeosis out of to avoid the risk of pupillary blocking under the condition of hypertension if the intravitreal injection was made.

¡¡¡¡Although this is a shortª²term study of intracameral injection of bevacizumab (avastin), the safety and rapid, dramatic biologic effect was proved even if its effect is transient. Intracameral injection of Bevacizumab, however, creates an opportunity for further treatment in the cases of neovascular glaucoma.

    ¡¾²Î¿¼ÎÄÏס¿

    1 Ferrara N. Vascular endothelial growth factor: basic science in clinical progress. Endocr Rev 2004;25(4):581ª²611

¡¡¡¡2 Early Treatment Diabetic Retinopathy Study Research Group. Early photocoagulation for diabetic retinopathy.ETDRS report number 9. Ophthalmology1991;98(suppl):766ª²785

¡¡¡¡3 Shimura M, Yasuda K, Nakazawa T,et al Quantifying alterations of macular thickness before and after panretinal photocoagulation in patients with severe diabetic retinopathy and good vision. Ophthalmology 2003;110(12):2386ª²2394

¡¡¡¡4 Avery RL, Pearlman J, Pieramici DJ, Rabena MD, Castellarin AA. Nasir MA, Kano T, Ohta S, Tamai M . Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy. Ophthalmology2006;113(10)1695.elª²15

¡¡¡¡5 Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE,. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med1994;331(22):1480ª²1487

¡¡¡¡6 Adamis AP, Shima DT, Tolentino MJ, Gragoudas ES, Ferrara N, Folkman J, D'Amore PA, Miller JW. Inhibition of vascular endothelial growth factor prevents retinal ischemiaassociated iris neovascularizatino in a nonhuman primate. Arch Ophthalmol1996;114(1):66ª²71

¡¡¡¡7 Rosenfeld PJ. Moshfeghi AA, Puliafito CA. Optical coherence tomography findings after an intravitreal injection of bevaciaumab(avastin)for neovascular ageª²related macular degeneration. Ophthalmic
Surg Lasers Imaging2005;36(4):331ª²335

¡¡¡¡8 Pieramici DJ,Avery RL,Castellarin AA,Nasir MA.Rabena M. Case of anterior uveitis after intravitreal injection of bevaciaumab. Retina2006;26(7):841ª²842

¡¡¡¡9 Lynch SS, Cheng CM. Bevacizumab for neovascular ocular diseases. Ann Pharmacother2007;41(4):614ª²625

¡¡¡¡10 Grisanti S, Biester S,Peters S, Tatar O, Ziemssen F, Gartaª²Schhmidt KU: Tuebinqen Bevacizumab Study Group. Intracameral bevacizumab for iris rubeosis. Am J Ophthalmol2006;142(1):158ª²160

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