当前位置：药品说明书与价格首页 >> 眼科 >> 研究进展 >> 前房注射Bevacizumab治疗虹膜红变的疗效观察

前房注射Bevacizumab治疗虹膜红变的疗效观察

2010-06-28 11:14:17 作者：新特药房来源：互联网浏览次数：118 文字大小：【大】【中】【小】

简介： 【摘要】　　目的:观察眼前房注射Bevacizumab(avastin)对虹膜红变的疗效及安全性。方法:5例（5眼）虹膜红变者分别继发于糖尿病视网膜病变，静脉周围炎，静脉阻塞。其中2例为玻璃体切割术后硅油填充眼 ...

关键字：前房;虹膜红变;曲安奈德Bevacizumab（Avastin)

【摘要】　　
目的:观察眼前房注射Bevacizumab(avastin)对虹膜红变的疗效及安全性。方法:5例（5眼）虹膜红变者分别继发于糖尿病视网膜病变，静脉周围炎，静脉阻塞。其中2例为玻璃体切割术后硅油填充眼，给予前房注射0.03ml(0.75mg)Bevacizumb(avastin)。其中1例联合小梁切除手术，1例联合睫状体冷凝术。结果:所有手术眼虹膜新生血管迅速消退，眼内压在联合使用抗青光眼手术或药物后降低，随访2~5mo没有虹膜红变复发，眼内压控制良好。结论:前房注射Bevacizumab(avastin)有效地减轻了虹膜红变，特别是在一些不适合玻璃体腔注射的病例，短期的研究随访证实前房注射迅速消退虹膜新生血管且无明显副作用。

【关键词】前房;虹膜红变;曲安奈德Bevacizumab（Avastin)

Intracameral bevacizumab for treatment of iris rubeosis

Tao Liu

Department of Ophthalmology,No.3201 Hospital,Hanzhong 723000,Shannxi Province,China

Correspondence to: Tao Liu. Department of Ophthalmology,No.3201 Hospital,Hanzhong 723000,Shannxi Province,China. taoliustone@163.com

AbstractAIM: To report the curative effect and safty of intracameral bevacizumab (avastin) in patients with rubeosis iridis. METHODS: 5 cases (5 eyes) with iris rubeosis secondary to diabetic retinopathy, retinal periphlebitis (Eales disease) and branch/central retinal vein occlusion, among which 2 cases were silicon oil eyes and were performed intracameral bevacizumab(avastin) 0.03 cc (0.75mg) , one case is combined with trabeculectomy, and another with cyclocryosurgery. RESULTS: The rubeosis of all cases disappeared quickly, meanwhile the intraocular pressure decreased to normal range with the help of antiglaucoma operation and medicine.There are not any sign of rubeosis again in the 25 months followup visits and intraocular pressure were wellcontrolled. CONCLUSION: Intracameral bevacizumab (avastin) was an effective treatment for rubeosis, esp, for some cases that can not be injected to vitreous cavity. Short term study of intracameral bevacizumab demonstrated rapid regression of rubeosis and welltolerated injection with no obvious side effects.

KEYWORDS: intracameral; iris rubeosis; Bevacizumab (Avastin)

INTRODUCTION

Vascular endothelial growth factor (VEGF) plays an important role in the formation of neovascula in proliferative diabetic retinopathy, central retinal vein occlusion and other abnormal vessel diseases[1]. Until the appearance of inhibitor of VEGF, there isnt a satisfied way for the rubeosis derived from abnormal retinal blood vessels to be treated.

Recently, intravitreal injection of Bevacizumab has been reported to show effect in regression of iris rubeosis. This report demonstrates rapid improvement of rubeosis iridis by intracameral injection of Bevacizumab (avastin).

CASE REPORT

Case 1 A 57yearold man who had underwent Pars Plana Vitrectomy (PPV) with incompleted membrane peeling, panretinal photocoagulation and silicon oil tamponaded for proliferative diabetic retinopathy half a year ago presented vision loss in left eye. Unfortunately, even after surgery, anterior and posterior segment neovascularization developed in an active way. The ophthalmic examination showed that the intraocular pressure (IOP) was 67 mmHg and neovascular glaucoma was diagnosed. No medicine worked effectively in the management of his left eye and there were no reports about the intravitreal injection of Avastin in silicon oil tamponade eye. Surely, after extensive discussions about the potential systemic and ocular side effects, we got the agreement of patient himself to inject the 0.75mg 0.03mL avastin into anterior chamber of left eye. A dramatic reduction of iris neovascular was observed and the IOP was 42 mmHg on the first day after surgery. All the rubeosis iridis disappeared on the second day, but the IOP was around 30~40mmHg. So the cyclocryosurgery was performed. IOP decreased to 16 mmHg 1 week later. 5 months followup visits had been carried out until number. The IOP was 17mmHg, and there is no sign of rubeosis.

Case 2 A 21yearold man presented retinal periphlebitis (Eales disease) of both eyes. He had lost his left eye vision acuity 2 months ago and felt blurred in the right eye. The visual acuity of his right and left eyes were 0.1 and light perception respectively. Severe vitreous hemorrhage without any sign of rubeosis iridis was observed in the left eye and B ultrasound exam showed that there was tractional retina detachment. Mild vitreous hemorrhage, retinal hemorrhage and neovascular were observed in the right eye. The neovascular membrane failed to be removed completely for the bleeding during PPV in the left eye. 3 weeks postoperatively, he felt no light perception in the left eye. The rubeosis was observed under slitlamp exam and the IOP increased to 56 mmHg. With intracameral injection of avastin 0.03cc, 0。75mg, rubeosis was no longer visible by slitlamp examination and IOP decreased to 32mmHg 24 hours later, and the IOP was 18mmHg 7 days later. To our astonishment, the patient told us he got visual acuity again 3 months later. The visual acuity of the left eye recovered unbelievably to 0.02.

Case 3 A 66yearold lady with central retinal vein occlusion in right eye for 2 years presented rubeosis and neovascular glaucoma for 2 months. The VA was 0.1 and IOP increased to 45mmHg. The Gonioscopy of right eye showed closed angle with neovascularization. She signed a comprehensive consent after discussion of the potential risks and benefits of Bevaciazumab (avastin). Rubeosis was no longer visible under slitlamp examination 24 hours after intracameral injection of avastin 0.03 cc, 0.75mg. The injection was tolerated without obvious side effects. Due to the closed anterior chamber angle, the IOP decreased little. Then she underwent trabeculectomy, during which there were no obvious bleeding and the filter bulb was well established, IOP declined to 12mmHg. There are not any sign of rubeosis 4 months later.

Case 4 A 65yearold 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 slitlamp 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 1417 mmHg after 3 months followup visits.

Case 5 This is a complex and interesting case. A 27yearold young woman, who lost her vision of right eye half a year ago, came to my outpatient department because of headache. Slitlamp 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 nonperfusion 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s disease). Although she had not any symptom of diabetes mellitus, the serology examination reported that her blood glucose reached 23mmol L1 . 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 photocoagulation 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. Followup 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s 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, fulllength, antiVEGF monoclonal antibody that bids to all forms of VEGFA. Its offlabel use has shown promise for treatment of neovascular agerelated 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t 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 shortterm 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.

【参考文献】
1 Ferrara N. Vascular endothelial growth factor: basic science in clinical progress. Endocr Rev 2004;25(4):581611

2 Early Treatment Diabetic Retinopathy Study Research Group. Early photocoagulation for diabetic retinopathy.ETDRS report number 9. Ophthalmology1991;98(suppl):766785

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):23862394

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.el15

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):14801487

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):6671

7 Rosenfeld PJ. Moshfeghi AA, Puliafito CA. Optical coherence tomography findings after an intravitreal injection of bevaciaumab(avastin)for neovascular agerelated macular degeneration. Ophthalmic
Surg Lasers Imaging2005;36(4):331335

8 Pieramici DJ,Avery RL,Castellarin AA,Nasir MA.Rabena M. Case of anterior uveitis after intravitreal injection of bevaciaumab. Retina2006;26(7):841842

9 Lynch SS, Cheng CM. Bevacizumab for neovascular ocular diseases. Ann Pharmacother2007;41(4):614625

10 Grisanti S, Biester S,Peters S, Tatar O, Ziemssen F, GartaSchhmidt KU: Tuebinqen Bevacizumab Study Group. Intracameral bevacizumab for iris rubeosis. Am J Ophthalmol2006;142(1):158160