4  前景与展望

    综上所述，短期临床资料表明，VEGF抑制剂在治疗糖尿病性视网膜病变中（如糖尿病性黄斑水肿、增殖性糖尿病性视网膜病变等）有显著的效果，治疗眼视力稳定或有所提高，可减轻增殖性病变的牵引，抑制毛细血管渗漏，减少术中出血，并具有抗炎作用，尤其是Avastin，其效果明显，价格优廉，具有广阔的研究和应用前景。但需要强调的是，VEGF抑制剂能改善糖尿病性视网膜病变的严重程度，但它本质上是一个治标不治本的药物，其长期的安全性和有效性尚有待进一步研究。目前VEGF抑制剂在我国仍未被批准用于临床，本综述将为其基础性研究和进一步的临床应用提供参考。

   【参考文献】

[1] Senger DR， Van de Water L， Brown LF， et al. Vascular permeability factor （VPF， VEGF） in tumor biology[J]. Cancer Metastasis Rev，1993，12(3-4)：303-324.

[2] Funatsu H， Yamashita H， Nakamura S， et al. Vitreous levels of pigment. epithelium?鄄derived factor and vascular endothelial growth factor are related to diabetic macular edema[J]. Ophthalmology，2006；113(2)：294-301.

[3] Isbida S， Usui T， Yamashiro K， et al. VEGF164 is proinflammatory in the diabetic retina[J]. Invest Ophthalmol Vis Sci， 2003，44(5)：2155-2162.

[4] 李媛，卢艳． 糖尿病视网膜病变早期发病机制研究进展[J]． 国际眼科杂志，2005；5(4)：750-754.

[5] 张小玲，邱曙东，陈艳炯，等． 糖尿病视网膜病变发病机制研究进展[J]． 国际眼科杂志，2005，5(6)：1239-1241.

[6] Cohen AF， Van Bronswijk H. New medications：bevacizumab[J].Ned Tijdschr Geneeskd，2006，150(40)：2194-2195.

[7] 高峨媚，徐建明. VEGF靶向药Avastin治疗实体瘤的研究进展[J]. 中国肿瘤临床与康复，2006，13(5)：473-475.

[8] Muller YA， Chen Y， Christinger HW， et al. VEGF and the Fab fragment of a humanized neutralizing antibody：crystal structure of the complex at 2.4 A resolution and mutational analysis of the inteface[J]. Structure，1998，6(9)：1153-1167.

[9] Fernando NH， Hurwitz HI. Inhibition of vascular endothelial grow factor in the treatment of colorectal cancer[J]. Semin Oncol，2003，30(3 Suppl 6)：39-50.

[10] Moshfeghi AA， Rosenfeld PJ， Puliafito CA， et al. Systemic bevacizumab (Avastin) therapy for neovascular age-related macular degeneration； 24-week results of an uncontrolled， open label clinical study[J]. Ophthalmology，2006，113(11)：2002.e1-12.

[11] Sledge G， Miller K， Novotny W， et al. A phase Ⅱ trial of singleangent rhuMAb VEGF(recombinant humanized monoclonal antibody to vascular endothelial cell growth)in patients with relapsed metastatic breast cancer[C]. 36th Annual Meeting of the American Society of Clinical Oncology，2000，20(19)：3-20.

[12] Rosenfeld PJ， Moshfeghi AA， Puliafito CA. Optical coherence tomography findings after an intravitreal injection of bevacizumab(Avastin) for neovascular age-related macular degeneration[J]. Ophthalmic Surg Lasers Imaging，2005，36(4)：331-335.

[13] Fung AE， Rosenfeld PJ， Reichel E. The international intravitreal bevacizumab safety survey：using the intemet to assess drug safety world wide[J]. Br J Ophthahmol，2006，90(11)：1344-1349.

[14] Lazic R， Gabric N. Intravitreally administered bevacizumab(Avastin) in minimaly classic and occult choroidal neovascularization secondary to age-related macular degeneration[J]. Graefes Arch Clin Exp Ophthalmol，2007，245(1)：68-73.

[15] Macugen(pegatanib sodium)[package insert]. New York：Eyetech Pharmac- euticals，Inc，and Pfizer Inc，2004：1-9.

[16] Antonetti DA， Barber AJ， Hollinger LA， et al. Vascular endothelial growth factor induces rapid phosphorylation of tight junction proteins occludin and zonula occluden 1. A potential mechanism for vascular permeability in diabetic retinopathy and tumors[J]. J Biol Chem，1999，274(33)：23463-23467.

[17] Hofmar P， Blaauwgeers HG， Tolentino MJ， et al. VEGF-A induced hyperpermeability of blood-retinal barrier endothelium in vivo is predominantly associated with pinocytotic vesicular transport and not with formation of fenestrations. Vascular endothelial growth factor-A[J]. Curr Eye Res，2000，21(2)：637-645.

[18] Feng Y， Venema VJ， Venema RC， et al. VEGF-induced permeability increase is mediated by caveolae[J]. Invest Ophthalmol Vis Sci，1999，40(1)：157-167.

[19] Aiello LP， Bursell SE， Clermont A， et al． Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective beta-isoform-selective inhibitor[J]. Diabetes，1997，46(9)：1473-1480.

[20] Funastu H， Yamashita H， Ikeda T， et al. Angiotension Ⅱ and vascular endothelial growth factor in the vitreous fluid of patients with diabetic macular edema and other retinal disorders[J]． Am J Ophthalmol，2002，133(4)：537-543.

[21] Mason JO 3rd， Albert MA Jr， Vail R. Intravitreal bevacizumab (Avastin) for refractory pseudophakic cystoid macular edema[J]. Retina，2006，26(3)：356-357.

[22] 王启常，唐罗生. 外源性VEGF诱导的大鼠视网膜血管病变[J]. 国际眼科杂志，2006，6(2)：369-372.

[23] Jorge R， Costa RA. Calucci D， et al. Intravitreal bevacizumab (Avastin) for persistent new vessels in diabetic retinopathy(IBEPE study)[J]. Retina，2006，26(9)：1006-1013.

[24] Davidorf FH， Mouser JG， Derick RJ. Rapid improvement of rubeosis iridis from a single bevacizumab(Avastin) injection[J].Retina，2006，26(3)：354-356.

[25] Bevacizumab pretreatment and long-acting gas infusion on vitreous clear-up after diabetic vitrectomy[J]. Am J Ophthalmol，2008，146(2)：211-217.

[26] Gandhi JS， Tan LT， Pearce I， et al. Bevacizumab (Avastin) as a surgical adjunct in diabetic vitrectomy for fibrovascular disease[J]. Eye，2009，23（3）：742-743.

[27] Ishikawa K， Honda S， Tsukahara Y， et al. Preferable use of intravitreal bevacizumab as a pretreatment of vitrectomy for severe proliferative diabetic retinopathy[J]. Eye，2009，23(1)：108-111.

[28] Avery RL， Pearlman J， Pieramici DJ， et al. Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy[J]. Ophthalmology，2006，113(10)：1695-1715.

[29] Paques M， Massin P， Gaudric A. Growth factors and diabetic retinopathy[J]. Diabetes Metab，1997，23(2)：125-130.

[30] Ferris F. Early photocoagulation in patients with either type I or type Ⅱ diabetes[J]. Trans Am Ophthalmol Soc，1996，94：505-537.

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