贝伐单抗抑制角膜新生血管的实验研究

目的评价贝伐单抗（avastin）局部应用对小鼠角膜新生血管（CNV）的抑制作用。方法通过碱烧伤建立CNV模型,将30只Balb／c小鼠随机分成5组,A组贝伐单抗1mg／mL每日点眼2次;B组贝伐单抗3mg／mL每日点眼2次;C组贝伐单抗5mg／mL每日点眼2次;D组0．1％地塞米松每日点眼2次;E组生理盐水每日点眼2次。分别于术后3、7、14d观察CNV情况并拍照。术后第14天,处死全部小鼠,行CNV内皮细胞荧光标记,计算CNV所占全角膜面积的比例。结果各组CNV面积为A组（37．11±3．17）％、B组（29．75±3．56）％、C组（18．76±2．55）％、D组（20．91±2．75）％,E组（41．65±2．11）％。各组小鼠CNV面积依次为c组〈D组〈B组〈A组〈E组,C组同A、B、E组比较差异均有统计学意义（P〈0．01）,c组与D组比较差异无统计学意义（P=0．694）。结论局部应用贝伐单抗对小鼠角膜化学烧伤后的CNV有抑制作用。     

Subconjunctival bevacizumab for corneal neovascularization

Acta Ophthalmol. 2010: 88: 868–871

Abstract.

Purpose: This work aimed to study and evaluate the effect of subconjunctival bevacizumab injection in patients with corneal neovascularization (CNV) resulting from different ocular surface disorders. Methods: Ten eyes with CNV caused by different ocular surface disorders were studied. All eyes had both major and minor vessel CNV caused by factors such as healed corneal ulcers, long‐standing chronic inflammatory diseases and corneal ischaemia (caused by contact lenses). All eyes received a single subconjunctival injection of 2.5 mg (0.1 ml) bevacizumab. Morphological changes in the major and minor vessels were evaluated using slit‐lamp biomicroscopy and corneal photography. Results: Conspicuous recession of the minor vessels of CNV was observed in all eyes at 2 weeks post‐injection. The extent of CNV of the major vessels was significantly decreased at 2 weeks post‐injection. The level of CNV continued to decrease noticeably for 3 months and then stabilized for the remainder of the 6‐month follow‐up period. Parameters used for evaluation included the total area of CNV, which amounted to 14.0 ± 5.4% of the corneal surface pre‐injection, compared with 9.4 ± 3.9% post‐injection (p < 0.01), reflecting a mean decrease in CNV of 33 ± 8%, and the extent of neovascularization, which decreased from 4.3 ± 1.5 clock hours pre‐injection to 2.4 ± 1.1 clock hours post‐injection (p < 0.01). During the 6‐month follow‐up, none of the 10 eyes showed any complication that could be related to subconjunctival bevacizumab injection. Conclusions: Bevacizumab can be used safely and effectively for CNV resulting from different ocular surface disorders. It represents an effective treatment for minor vessel neovascularization caused by long‐standing chronic inflammation (e.g. trachoma) or long‐standing corneal ischaemia (e.g. contact lenses), as well as for major vessel neovascularization resulting from different causes. Bevacizumab was well tolerated over the 6‐month follow‐up period.     

人参皂甙Rg3在大鼠角膜新生血管中的作用研究

目的研究人参皂甙Rg3对大鼠角膜新生血管(CNV)的作用。方法建立角膜碱烧伤后CNV模型,SD大鼠随机分为对照组和0.1、0.2、0.5mg/L人参皂甙Rg3治疗组。显微镜下观察各组CNV生长情况并计算CNV面积;免疫组织化学和半定量逆转录聚合酶链式反应(RT-PCR)检测各组角膜内血管内皮生长因子(VEGF)在不同时间点的表达变化。结果人参皂甙Rg3不同质量浓度组均能显著抑制CNV生长,0.5mg/L人参皂甙Rg3组抑制作用最显著(P<0.05)。结论人参皂甙Rg3对大鼠角膜碱烧伤后CNV的生长有明显抑制作用,其作用机制与抑制VEGF表达有关。     

黄芩黄素抑制兔角膜新生血管的形成

目的探讨12-LOX选择性抑制剂黄芩黄素(baicalein)对兔角膜新生血管形成的影响。方法角膜微袋法制作兔角膜新生血管动物模型,动物右眼均滴30μmol/L黄芩黄素滴眼液,左眼为阴性对照,4次/d,1滴/次,共10d。墨汁灌注后照相,照片扫描后进行软件分析得新生血管面积。结果10d后角膜新生血管面积对照组为(12102·40±284·97)像素,实验组为(1614·67±182·31)像素。角膜新生血管被抑制了86·66%。病理组织学检查,对照组角膜基质浅层新生血管较多且粗大,呈各种形态的空泡状断面,空泡内可见黑色墨汁,未见大量炎细胞浸润。实验组新生血管明显减少,只见少许黑色墨汁小点,亦未见大量炎细胞浸润。结论黄芩黄素可有效抑制兔角膜新生血管的形成;将为临床治疗角膜新生血管提供一条新的更有效的途径。     

microRNAs与角膜新生血管

正常角膜的无血管化状态能够维持角膜的免疫赦免和透明性,角膜处于富含血管的环境中却能保持无血管化,归因于内源性血管抑制因子。microRNAs(miRs)是一类内源性小分子非编码RNA,在角膜新生血管形成过程中,多种miRs发挥重要的调控作用,是重要的内源性血管抑制因子。本文就miRs在角膜新生血管中的相关研究进行综述,以期为角膜新生血管的治疗和进一步研究提供借鉴。     

Bevacizumab inhibits corneal neovascularization in an alkali burn induced model of corneal angiogenesis

BACKGROUND: New and uncontrolled blood vessel development in the cornea is a pivotal process in the pathogenesis of several corneal diseases. These corneal diseases may finally cause blindness and managing them therapeutically is problematic. The data supporting a causal role for vascular endothelial growth factor in corneal neovascularization are extensive. This study aimed to evaluate the effect of subconjunctival bevacizumab (Avastin) on experimental corneal neovascularization in rabbits. METHODS: Chemical cauterization of the cornea was performed by touching central cornea with a 5-mm-diameter NaOH-soaked cotton applicator for 10 s in 20 eyes of 20 White New Zealand rabbits. The rabbits were then divided randomly into two equal groups. Bevacizumab (2.5 mg) was administered to 10 eyes (group 1) by a subconjunctival injection immediately after chemical cauterization of corneal surface. As a control, 10 eyes (group 2) received an injection of distilled water. Rabbits were examined daily for detection of the first signs of neovascularization. Three weeks later, the extent of corneal neovascularization was evaluated by direct examination and photograph analyses. Total corneal neovascularization area, degree of circumference involved and longest neovascular pedicle length were assessed. RESULTS: Bevacizumab significantly decreased the total neovascularization area (P < 0.009), the circumference involved (P < 0.011) and the longest neovascular pedicle length (P < 0.023). CONCLUSION: Local injection of bevacizumab has a significant effect on inhibition of alkali burn-induced corneal neovascularization. This shows the potential value of bevacizumab in the treatment of corneal neovascularization.     

姜黄素对大鼠碱烧伤角膜新生血管的抑制作用

目的:探讨姜黄素(curcumin)对大鼠角膜新生血管(corne-al neovascularization,CNV)形成的影响及CNV形成过程中血管内皮生长因子(vascular endothelial growth factor,VEGF)和诱导型一氧化氮合酶(inducible nitric oxide syn-thesis,iNOS)的表达情况。方法:以碱烧伤建立角膜新生血管模型,采用裂隙灯照相、免疫组化和RT-PCR等方法分别检测使用姜黄素前后各时期角膜组织中VEGF和iNOS的表达情况,并进行统计学分析。结果:姜黄素结膜下注射组角膜新生血管面积明显减少(t值分别为4.453,4.440,3.887,4.718,3.585,P<0.05);免疫组化染色,VEGF和iNOS在正常角膜上皮基底细胞有弱表达,新生血管对照组表达明显增强,其表达主要分布在新生血管形成区域和上皮全层;结膜下注射组表达明显减少;VEGF mRNA和蛋白表达一致。结论:姜黄素可以有效抑制角膜新生血管的发生,其机制与降低角膜新生血管VEGF和iNOS有关。     

Comparison of the inhibitory effect of different doses of subconjunctival bevacizumab application in an experimental model of corneal neovascularization

AIM: To evaluate the inhibitory effect of subconjunctival bevacizumab as single- and multiple-dose application, and compare their effects on corneal neovascularization in a rat model. METHODS: Thirty adult Sprague-Dawley rats were used in this experimental study. The central cornea of the rats was cauterized chemically. The rats were randomly enrolled into three groups. All groups received subconjunctival injections. In Group 1 (control group, n=10), 0.05 mL 0.9% NaCl solution was injected on the first day. In Group 2 (single-dose group, n=10), 0.05 mL bevacizumab (1.25 mg) was injected on the first day. In Group 3 (multiple-dose group, n=10), four doses of 0.05 mL bevacizumab (1.25 mg) were injected on the first, third, fifth and seventh day. Slit-lamp examination of all rats was performed at the third and ninth day. Digital images of the corneas were taken and analyzed using image analysis software to calculate corneal neovascularization area. All rats were sacrificed on the tenth day. In corneal sections, the number of blood vessels, state of inflammation and collagen formation was evaluated histopathologically. RESULTS: In Group 3, corneal edema grades were significantly lower than Group 1 and Group 2 (P=0.02, and P=0.035, respectively). The mean percentage of neovascularized corneal area in Group 3 was significantly lower than Group 2 (P=0.005). On histopathological examination, Group 2 and Group 3 showed significantly less number of blood vessels than Group 1 (P=0.005, and P=0.001, respectively). Additionally, Group 3 showed significantly less number of blood vessels compared to Group 2 (P=0.019). Inflammation and edema grades were significantly lower in Group 3 compared to Group 1 (P=0.001). CONCLUSION: Subconjunctival bevacizumab injection is effective in inhibition of newly formed corneal neovascularization. The multiple-dose bevacizumab treatment seems to be more effective compared to single-dose treatment.     

促红细胞生成素小干扰RNA对兔角膜新生血管的抑制作用

目的：评估促红细胞生成素(erythropoietin,EPO)在兔角膜新生血管发病机制中的作用,并观察促红细胞生成素小干扰RNA(siRNA)对角膜新生血管的抑制作用。

方法：健康新西兰白兔22只,随机分为实验组及正常对照组,实验组兔双眼行碱烧伤法建立角膜新生血管模型,造模后每日裂隙灯检查角膜形态学改变并计算新生血管面积,同时自造模当日起右眼每日结膜下注射siRNA 1U组成siRNA治疗组,左眼以control siRNA为实验对照组,分别于术后3、7、14、21d取角膜组织行免疫组化染色,观察EPO的表达情况。

结果：实验组最早于碱烧伤后3d可见CNV长入,7～14d生长最为旺盛,免疫组织化学染色见随碱烧伤时间延长,角膜EPO的表达逐渐增加; siRNA治疗后CNV延迟长入,面积较实验对照组明显减小,炎性细胞浸润减轻,且角膜中EPO的表达较前者明显降低,差异有统计学意义(P<0.05)。

结论：EPO可能在CNV的发生发展中发挥重要作用,碱烧伤后siRNA的早期干预可能通过影响EPO的表达而抑制CNV的生长。     

雷帕霉素滴眼液对碱烧伤角膜新生血管的影响

目的探讨雷帕霉素（Rapamycin）滴眼液对兔碱烧伤后角膜新生血管的抑制作用。方法48只新西兰白兔右眼碱烧伤制成新生血管模型,随机分成A组（0．1％雷帕霉素滴眼液组）,B组（0．5％雷帕霉素滴眼液组）,C组（1％雷帕霉素滴眼液组）,D组（赋形剂对照组）。烧伤后每天滴眼4次。观测角膜浑浊、融解情况和新生血管生长并测量长度。角膜组织HE染色观察病理改变,炎性细胞计数,免疫组化检测角膜内皮生长因子（VEGF）的表达。结果碱烧伤后各组角膜均出现不同程度的角膜浑浊、融解,随时间延长,对照组角膜浑浊、融解明显,角膜基质内大量炎性细胞浸润和粗大新生血管形成。治疗组的角膜浑浊、融解减轻,伤后7d、14dB、C组炎症细胞计数、角膜新生血管面积及VEGF表达均小于对照组（P〈0．05）。各组角膜新生血管面积与角膜炎性细胞数及VEGF表达呈正相关。结论0．5％及1％雷帕霉素滴眼液可有效抑制碱烧伤引起的角膜免疫炎症反应,抑制角膜新生血管的生长,为眼碱烧伤后角膜新生血管的治疗提供了新的选择。     

结膜下注射Avastin抑制角膜新生血管的实验研究

目的:观察结膜下注射Avastin对实验性兔眼角膜新生血管(neovascularization,NV)的抑制作用,初步探讨作用机制。方法:应用5mm直径的加样器(末端附有棉片)吸入1mol/LNaOH接触新西兰兔右眼(20眼)中央角膜区烧灼30s,制作碱烧伤兔眼角膜NV模型。将实验兔随机分成2组,10眼(A组)碱烧伤后立即结膜下注射Avastin 2.5mg;其余10眼为对照组(B组),结膜下注射等量生理盐水。烧灼后次日每天裂隙灯观察角膜NV、角膜水肿情况,分别于3,7,14,21,28d裂隙灯照相并计算NV面积及NV抑制率。伤后7,28d各组随即处死5只实验兔,取角膜组织做石蜡切片行组织病理学检查及VEGF免疫组织化学检测。结果:两组兔眼伤后第1d角膜缘血管网明显扩张充血,3d时血管开始侵入角膜,7～14d时NV达到高峰,14～21d后NV稳定并逐渐回退。两组角膜NV长度、NV面积及角膜水肿程度存在差异(P<0.05);A组各时间点角膜NV抑制率为44.2%～55%。A组角膜上皮及实质层水肿较轻,NV较少,后弹力层基本完整,VEGF表达明显弱于B组。结论:结膜下注射Avastin对碱烧伤诱导的兔眼角膜NV形成及生长具有明显的抑制作用,可能通过下调VEGF表达发挥作用。     

Avastin不同给药途径对兔角膜新生血管及超微结构的影响

目的研究阿瓦斯汀不同给药途径对兔角膜新生血管及超微结构的影响。方法健康新西兰大白兔50只,随机选取48只兔左眼制作碱烧伤角膜新生血管动物模型,造模成功后随机分为局部滴眼组(A组)、结膜下注射组(B组)、角膜基质注射组(C组)和模型对照组(D组),每组12只,未造模2只兔双眼为空白对照,于碱烧伤后第1天、第4天、第11天、第18天、第32天观察兔眼结膜充血、角膜混浊、新生血管生长情况,并进行眼前节照相,同时计算各实验兔眼角膜新生血管面积;第11天、第18天、第32天每组各处死4只兔,即刻抽取左眼房水检测血管内皮生长因子(vascular endothelial growth factor,VEGF)含量,取新生血管生长最旺盛的角膜组织分别固定,待做电镜、免疫组织化学等检测。结果角膜新生血管在碱烧伤后11d内生长迅速,第18天时有所消退,第32天时趋于相对稳定,A组、B组、C组角膜新生血管面积与D组在各个时间点之间比较,差异均有统计学意义(均为P<0.05)。碱烧伤后各时间点房水中VEGF浓度均高于正常水平,碱烧伤后11d内房水中VEGF浓度逐渐升高,至第18天时达到高峰,第32天时有所下降并趋于较稳定的水平。CD31在正常兔眼角膜组织中未见表达,A组、B组、C组阳性细胞数明显少于D组,差异均有统计学意义(均为P<0.05)。A组、B组、D组角膜超微结构在第11天、第18天、第32天时除碱烧伤损伤外无明显其他改变,在第18天、第32天时C组角膜超微结构损伤重于A组、B组、D组。结论局部滴眼、结膜下注射、角膜基质注射三种给药途径均对角膜新生血管有较好的抑制作用。局部滴眼与结膜下注射给药途径简单安全、效果稳定,未见对角膜超微结构产生明显影响;角膜基质注射虽短期效果显著,但对角膜超微结构产生了较明显的影响。     

维替泊芬介导的光动力疗法治疗兔眼角膜新生血管

目的:旨在探讨和评估光敏剂维替泊芬(vertporfin)介导的光动力疗法(PDT)对角膜新生血管(CoNV)治疗的效果。方法:新西兰白兔随机分为2组:两组采用角膜基质层缝线的方法诱导CoNV形成。Ⅰ组行vertporfin-PDT治疗CoNV,verteporfin以1.5mg/kg静注。Ⅱ组不治疗,为阳性对照。治疗后裂隙灯显微镜观察CoNV变化并记录面积,取处理组及对照组的角膜、虹膜睫状体组织,行组织病理学检查,免疫组织化学(SABC法)检测血管内皮生长因子(VEGF)在角膜组织中的表达。结果:治疗后3d;1,2wk,Ⅰ组CoNV面积均明显小于Ⅱ组(P<0.01)。组织病理学检查显示,Ⅰ组CoNV管壁破坏,形成血栓。VEGF的表达Ⅰ组明显低于Ⅱ组(P<0.01)。结论:Vertporfin-PDT对兔模型眼CoNV有明显的抑制作用,不损伤邻近的正常血管及组织。     

环氧合酶-2及其抑制剂对角膜新生血管作用的研究

目的:观察大鼠角膜新生血管(cornealneovasculariza-tion,CNV)形成过程中环氧合酶-2(COX-2)的表达情况及与CNV的关系,探讨COX-2抑制剂Celecoxib对CNV的抑制作用。方法:利用免疫组织化学方法、RT-PCR法检测碱烧伤后各个时期COX-2和VEGF蛋白、mRNA在角膜各层中的分布,并对其进行半定量。比较实验组和对照组各个时期COX-2和VEGF蛋白和mRNA表达量的差别,并对其进行统计学分析,了解COX-2与VEGF的相关性。结果:①活化的COX-2和VEGF蛋白、mRNA的表达在角膜新生血管的形成中均有一动态变化。②VEGF的表达区域和COX-2表达的部位高度一致。③实验II组和实验Ⅲ组COX-2和VEGF蛋白、mRNA表达量与对照组的差别有显著性(P<0.05),实验I组与对照组的差别无显著性(P>0.05)。实验组和对照组COX-2与VEGF的表达呈正相关。结论:①COX-2在炎症性角膜新生血管形成过程中表达上调,其调控VEGF的表达,在角膜新生血管的形成过程中起着重要作用。②Celecoxib能抑制COX-2的表达,有效的抑制角膜新生血管的形成。     

COX-2 and its inhibitor Celecoxib in corneal neovascularization

To observe the expression of COX-2 in rat corneal neovascularization (CNV) and its relationship to CNV, and to explore the inhibition of Celecoxib, a COX-2 inhibitor, to CNV. · METHODS: The distribution and quantification of COX-2 and VEGF was detected by immunohistochemistry. Expression of COX-2 and VEGF mRNA was quantified by RT-PCR. The difference in protein and mRNA expressions of COX-2 and VEGF was analyzed to find the correlation between them. · RESULTS: Expression of activated COX-2 and VEGF protein and mRNA in CNV had a dynamic change. VEGF and COX-2 co-localized. Compared with the control group, expression of both protein, mRNA of COX-2 and VEGF in experimental group II and III had significant difference(P <0.05),indicating the correlation between COX-2 and VEGF, while that in experimental group I had no statistical difference (P >0.05). · CONCLUSION: COX-2 expression was up-regulated in inflammatory CNV. COX-2 modulates the expression of VEGF, playing a very important role in CNV. Celecoxib inhibit COX-2 expression so as to hold back the CNV.     

姜黄素对兔角膜新生血管模型中多形核白细胞计数和VEGF表达的影响

目的研究姜黄素对兔角膜新生血管(corneal neovascularization,CNV)模型中血管内皮生长因子(vascular endothelial growth factor,VEGF)表达和多形核白细胞(polymorphonuclear leukocyte,PMN)计数的影响。方法40只健康新西兰大白兔,其中5只不做任何处理作为正常对照组(A组);其余35只建立碱烧伤角膜新生血管模型,右眼不应用姜黄素滴眼液为实验对照组(B组),左眼应用姜黄素滴眼液作为实验干预组(C组)。裂隙灯观察角膜新生血管生长情况,免疫组织化学方法检测应用姜黄素后不同时间点VEGF在兔CNV中的表达,显微镜下PMN计数,并作统计分析。结果A组未见PMN,而VEGF没有表达或仅在上皮基底膜有微弱表达。B组PMN增多和VEGF表达明显增强,其表达部位主要分布在新生血管形成区域和上皮全层。与B组相比,C组角膜新生血管密度明显减低,PMN明显减少,VEGF在相应角膜基质层新生血管形成区域表达减少。结论姜黄素可以有效地抑制兔角膜碱烧伤诱发的CNV生长,可能是通过显著降低角膜新生血管PMN增生和VEGF的表达来实现的。     

恒温下兔角膜热烧伤后继发新生血管建模初步研究

目的：初步研究恒温条件下兔角膜热烧伤后继发的角膜新生血管（ CNV）快速制模的合适条件。 方法：新西兰大白兔45只,随机分为（ A,B,C,D,E）五组恒温烧灼器诱导实验性CNV模型,除E组为5只,其他组均为10只。 A组：100℃, B组：200℃, C组：300℃, D组：400℃,E组：空白对照。以左眼为实验眼,比较建模后第4,7,14,30 d在裂隙灯显微镜下观察各组角膜新生血管的生长情况并计算角膜新生血管生长面积。采用SPSS 19.0统计软件包对数据进行分析,计算资料用x-±s表示,各时间点各自新生血管面积的比较采用重复测量数据的方差分析;显著性标准为α=0.05。 结果：制模后第4,7,14,30d,A组角膜热烧伤后无明显新生血管生长,仅少量留有角膜云翳（n=2）。 B组新生血管面积分别为：9.16±1.45,37.73±5.49,62.44±7.54,40.28±7.39mm2;C组新生血管面积分别为：11.45±1.04,44.51±4.64,66.13±4.13,43.04±2.33mm2;D组新生血管面积分别为：13.23±0.86,47.26±4.59,67.57±4.56,45.59±4.44mm2;D组部分角膜局部出现焦化（n=4）,3d内出现穿孔（ n=6）。 E组未见新生血管生长。各时间点的CNV面积比较,差异有显著性（P〈0.05）,B,C,D分组之间有统计学差异（P〈0.05）。 结论：角膜热烧伤4~7d时,制模温度越高,新生血管生长越快,面积越大;14~30 d 新生血管面积无明显差别,但400℃角膜制模失败率高,200℃~300℃制作的兔角膜新生血管模型均一性及重复性高。     

人羊膜匀浆提取液抑制大鼠角膜碱烧伤后新生血管生成

目的:研究人羊膜匀浆提取液对角膜碱烧伤后新生血管形成过程中色素上皮衍生因子(pigment epithelium-derived fac-tor,PEDF)和血管内皮生长因子(vascular-endothelial growthfactor,VEGF)的表达影响及对角膜新生血管的抑制作用。方法:SD大鼠54只建立双眼角膜碱烧伤模型,随机分为3组:A组为3g/L氧氟沙星滴眼液组,B组为10g/L泼尼松龙滴眼液组,C组为新鲜人羊膜匀浆提取液组,并分别于治疗后不同时间点进行角膜新生血管增生情况观察,HE染色病理学观察,免疫组化行VEGF和PEDF的表达检测。结果:B,C组比A组新生血管增生少,多形核白细胞(poly-morphonuclear leukocyte,PMN)浸润程度轻,VEDF表达水平显著降低,但B,C两组之间VEDF表达无显著性差异(P>0.05)。C组PEDF表达水平显著高于A,B组(P<0.01),但A,B之间PEDF表达无显著性差异(P>0.05)。结论:新鲜人羊膜匀浆提取液能减少碱烧伤后角膜组织中PMN浸润,增强角膜组织PEDF的表达水平。     

Therapeutic effect of subconjunctival injection of bevacizumab in the treatment of corneal neovascularization

Purpose: To investigate the efficacy of subconjunctival injection of bevacizumab in the treatment of patients with corneal neovascularization. Methods: Twenty‐nine eyes of 29 patients with corneal neovascularization were treated with subconjunctival injection [1.25 mg/0.05 ml (seven eyes), 2.5 mg/0.1 ml (15 eyes) and 5.0 mg/0.2 ml (seven eyes)] of bevacizumab. Best‐corrected visual acuity, intraocular pressure and area of corneal neovascularization were measured before injection and at 1 week, 1 month and 3 months after treatment. Results: At 1 week, the mean neovascularized corneal area decreased significantly to 85.5 ± 18.0% (p = 0.01) in the eyes treated with 2.5 mg bevacizumab and to 73.1 ± 23.4% (p = 0.02) in the eyes treated with 5.0 mg bevacizumab. At 3 months, the mean neovascularized corneal area was 93.6 ± 10.6% (p = 0.10 compared to baseline; p < 0.01 compared to 1 week) in the eyes treated with 2.5 mg bevacizumab and 83.3 ± 25.8% (p = 0.03 compared to baseline; p = 0.02 compared to 1 week) in the eyes treated with 5.0 mg bevacizumab. However, there were no significant changes in the areas of the eyes injected with 1.25 mg bevacizumab. Conclusion: Subconjunctival injection of bevacizumab can partially reduce corneal neovascularization in the short term, and the efficacy of this treatment correlates with the injection dose.