Effect of subconjunctival bevacizumab (Avastin) on experimental corneal neovascularization in guinea pigs

PURPOSE: To evaluate the effect of subconjunctival bevacizumab (Avastin) on experimental corneal neovascularization in guinea pigs. METHODS: Forty eyes of 40 guinea pigs were chemically cauterized with 75% silver nitrate and 25% potassium nitrate sticks. Fifteen eyes (group 1) received 2 subconjunctival injections of bevacizumab (0.1 mL, 1.25 mg) simultaneously with cauterization and 3 days later. Fifteen eyes (group 2) received 2 subconjunctival injections of bevacizumab (0.1 mL, 1.25 mg) 3 and 5 days after cauterization. Ten eyes (group 3, control group) received 2 subconjunctival injections of 0.1 mL of balanced salt solution 3 and 5 days after cauterization. After we determined the burn and neovascularization scores for all groups, the animals were killed on the 10th day. The percentages of neovascularization on the surface of the cornea were measured in terms of pixels on digital photographs. The average number of vessels at maximally vascularized areas was determined for each specimen. RESULTS: Neovascularization score was 1.1 +/- 0.3 in group 1, 2.46 +/- 1.3 in group 2, and 3.5 +/- 0.5 in the control group. The difference was statistically significant (P < 0.001). The area of neovascularization at the cornea surface was 15.6% +/- 10.1% in group 1, 19.74% +/- 11.2% in group 2, and 23.5% +/- 7.4% in the control group (P = 0.194). The average number of neovascular vessels at group 1 was significantly reduced in comparison with group 2 and the control group (P < 0.001). CONCLUSIONS: Subconjunctival injection of bevacizumab decreases the extent of chemically induced corneal neovascularization in guinea pigs. The antineovascular effect of bevacizumab is higher if the injection is performed simultaneously with the chemical cauterization.     

Subconjunctival bevacizumab injection for corneal neovascularization

PURPOSE: To report on the clinical use of subconjunctival bevacizumab in patients with corneal neovascularization. METHODS: The charts of 10 consecutive patients with corneal neovascularization who received subconjunctival injections of bevacizumab (2.5 mg/0.1 mL) were reviewed. Digital photographs of the cornea were graded by 2 masked observers for density, extent, and centricity of corneal vascularization. Image analysis was used to determine the area of cornea covered by neovascularization as a percentage of the total corneal area. RESULTS: No significant ocular or systemic adverse events were observed during 3.5 +/- 1.1 months of follow-up. Seven patients showed partial regression of vessels. The extent decreased from 6.0 +/- 1.2 (SD) clock hours before the injection to 4.6 +/- 1.0 clock hours after bevacizumab injection (P = 0.008). Density decreased from 2.7 +/- 0.2 to 1.9 +/- 0.3, respectively. (P = 0.007). No change was noticed in the centricity of corneal vessels. Corneal neovascularization covered, on average, 14.8% +/- 2.5% (SD) of the corneal surface before the injections, compared with 10.5% +/- 2.8% (P = 0.36, t test) after bevacizumab injection. Therefore, bevacizumab decreased corneal neovascularization by 29%. CONCLUSIONS: Short-term results suggest that subconjunctival bevacizumab is well tolerated and associated with a partial regression of corneal neovascularization.     

Inhibition of corneal neovascularization after alkali burn: comparison of different doses of bevacizumab in monotherapy or associated with dexamethasone

Background: To compare the effects of different doses of bevacizumab with both saline and dexamethasone on inflammatory angiogenesis in the rat cornea induced by small chemical lesions. Methods: Corneal chemical cauterization was performed on 24 rats. Animals were divided randomly into six groups and received a daily subconjunctival injection for 7 days of: balanced salt solution 0.1 mL or dexamethasone phosphate 4 mg/day or bevacizumab 2.5 mg/day, 3.75 mg/day, 5.0 mg/day or bevacizumab 5.0 mg/day + dexamethasone phosphate 4 mg/day. Clinical examination under slit lamp was performed daily for 7 days to evaluate corneal opacity and vessel size evolution. Computer‐assisted quantitative image analysis was used to measure the total corneal area covered by neovascularization. Results: At final examination, the dexamethasone, bevacizumab 5.0 mg/day and dexamethasone + bevacizumab groups showed a significant lowering in corneal opacity score as compared with control (P = 0.024, P = 0.006 and P = 0.013, respectively). Also, a significant reduction on new vessels size score was observed. Surface of corneal neovascularization was significantly reduced in dexamethasone, bevacizumab 5.0 mg/day and dexamethasone + bevacizumab groups compared with control (P = 0.045, P = 0.047 and P = 0.044, respectively). Conclusion: Our study demonstrates the ability of a 5.0 mg/day bevacizumab subconjunctival injection, in monotherapy or associated with dexamethasone, to cause a short‐term involution of corneal neovascularization after corneal alkali burn. Combination of both of these treatments may have advantages to monotherapy approaches.     

The Effect of Bevacizumab on Corneal Neovascularization in Rabbits

Purpose

To determine the efficacy of topical application and subconjunctival injection of bevacizumab in the treatment of corneal neovascularization.

Methods

Corneal neovascularization was induced with a silk suture of the corneal stroma in 12 rabbits (24 eyes). One week after suturing, four rabbits were treated with topical bevacizumab at 5 mg/mL (group A) and another four rabbits were treated with topical bevacizumab 10 mg/mL (group B) in the right eyes twice a day for two weeks. A subconjunctival injection of bevacizumab 1.25 mg/mL was done in the right eyes of four rabbits (group C). All of the left eyes (12 eyes) were used as controls. The area of corneal neovascularization was measured after one and two weeks, and the concentration of vascular endothelial growth factor (VEGF) in corneal tissue was measured after two weeks.

Results

The neovascularized area was smaller in all treated groups than in the control group (p<0.001). Upon analysis of the neovascularized area, there was no significant difference between groups A and B. However, the mean neovascularized area of group B was significantly smaller than that of group C after two weeks of treatment (p=0.043). The histologic examination revealed fewer new corneal vessels in all treated groups than the control group. The concentration of VEGF was significantly lower in all treated groups compared to the control group (p<0.01), but no difference was shown between treated groups.

Conclusions

Topical and subconjunctival bevacizumab application may be useful in the treatment of corneal neovascularization and further study is necessary.     

Comparison of subconjunctivally injected bevacizumab, ranibizumab, and pegaptanib for inhibition of corneal neovascularization in a rat model

AIM:To compare the efficacies of subconjunctival bevacizumab, ranibizumab, and pegaptanib sodium injections for the inhibition of corneal neovascularization in an experimental rat model. METHODS:Sixteen corneas of 16 rats were chemically cauterized and randomized into four groups:bevacizumab group that treated with 0.05mL/1.25mg bevacizumab, ranibizumab group that treated with 0.05mL/0.5mg ranibizumab, pegaptanib group that treated with 0.05mL/0.15mg pegaptanib sodium, and control group that treated with 0.05mL saline solution. Digital photographs of the corneas were taken and analyzed using an image analysis software program. All corneas were excised and examined histologically on the 15^th day. RESULTS: Each treatment group had significantly less neovascularized corneal areas and fewer blood vessels than the control group (all P<0.05). In addition, bevacizumab group had significantly less neovascularized corneal areas and fewer blood vessels than ranibizumab and pegaptanib groups (both P<0.05). However, there was no significant difference between the ranibizumab and pegaptanib groups regarding percentage of neovascularized corneal areas and number of blood vessels (both P>0.05). CONCLUSION:Subconjunctival bevacizumab, ranibizumab, and pegaptanib sodium were effective with no corneal epitheliopathy for inhibiting corneal neovascularization after corneal burn in rats. Bevacizumab was more effective than ranibizumab and pegaptanib sodium.     

Topical and subconjunctival bevacizumab for corneal neovascularization in an experimental rat model

Aims: To evaluate and compare the inhibitory effects of topical and subconjunctival bevacizumab on corneal neovascularization in a rat model. Methods: Twenty corneas of 20 rats were chemically cauterized with silver nitrate sticks. Animals were randomized into four groups: a control group that received only topical artificial tear drops twice daily, a subconjunctival injection group that received 1.25 mg (0.05 ml) of bevacizumab on the 1st, 4th, and 7th day, and two topical bevacizumab groups that received instillation of 4 or 12.5 mg/ml bevacizumab twice daily. Digital photographs of the cornea were taken and analyzed using an image analysis software program. On the 10th day, corneas were excised and examined histologically. Results: The mean percentage of the vascularized corneal area (%) in the control group was 63.32 ± 13.10 (mean ± SD), compared with 30.22 ± 15.73 in the subconjunctival injection group, 26.76 ± 10.23 in the 4-mg/ml topical group, and 25.52 ± 12.45 in the 12.5-mg/ml group. The differences between the control and each treatment group were significant (all p < 0.01). Further, histological examination revealed that each treatment group had fewer vessels than the control group (all p < 0.01). Conclusions: Both subconjunctival injection and topical use of bevacizumab are effective and safe in controlling corneal neovascularization.     

Measurement of central corneal thickness and pre-corneal tear film thickness of rabbits using the Scheimpflug system

AIM:To measure central corneal thickness (CCT) and pre-corneal tear film thickness using the Galilei dual-Scheimpflug analyzer (GSA) in New Zealand white rabbits.METHODS:Ten normal New Zealand white rabbits (20 eyes) were included in this study. With the assistance of 0.1% fluorescein, the pre-corneal tear film can be well visualized. Both eyes of each rabbit were scanned once with the GSA pre- and post-instillation of 1μL 0.1% fluorescein. The difference between the two measurements of CCT (4-mm diameter) was recorded as the pachymetric values of the central tear film.RESULTS:The CCT of pre- and post-instillation was 388.8±9.5μm and 407.0±10.5μm, respectively. After a paired t-test analysis, the central pre-corneal tear film thickness of 4mm diameter was 18.2±5.31μm with a 95% confidence interval of (15.7, 20.6)μm (P<0.001).CONCLUSION:GSA can be used to measure CCT and analyze central tear film thickness of rabbits with the help of fluorescein.     

Inhibition of corneal neovascularization by subconjunctival bevacizumab in an animal model

PURPOSE: To evaluate the effect of subconjunctival injection of bevacizumab on experimentally induced corneal neovascularization. DESIGN: Experimental animal study. METHODS: Twelve New Zealand white rabbits were involved, divided equally into four groups. Only one eye per rabbit was used. Topical instillation of 10 microl 5% NaOH solution was used, under general anesthesia, to induce corneal neovascularization secondary to corneal alkali burn in groups 2, 3, and 4. A single dose of 3.75 mg (25 mg/ml) bevacizumab was injected subconjunctivally. Group 1 (control group 1) was neither cauterized nor treated. Group 2 (control group 2) received a sham injection of balanced salt solution on day 14. Group 3 was treated on day 14 (after corneal neovascularization had been established). Group 4 was treated on day 1. Digital photographs were obtained and analyzed during the entire 28-day procedure. The area of neovascularization and scarring were measured in terms of the percentage of corneal surface affected. RESULTS: On day 28, the difference of neovascularization between groups 2, 3, and 4 was found to be statistically significant at the .05 level (one-way analysis of variance [ANOVA]): group 4 (4.7%+/-3.1%).1, one-way ANOVA). No side effects were noted. CONCLUSIONS: Subconjunctival administration of bevacizumab inhibits corneal neovascularization effectively in the rabbit experimental model, especially if administered early.     

The effect of different doses of subconjunctival bevacizumab injection on corneal neovascularization

To evaluate the effects of various doses of subconjunctival bevacizumab injections in the treatment of patients with corneal neovascularization. During the 6-month-follow-up, no significant ocular or systemic adverse events were observed related to the subconjunctival bevacizumab injection. In Group 1, the total area of corneal neovascularization before injection was 14.8 ± 3.2 % of the corneal surface and 10.2 ± 2.8 % 6 months after injection (p < 0.01). The mean decrease in Group 1 was 32.0 ± 3.0 %. In Group 2, the total area of corneal neovascularization before and 6 months after the injection was 14.2 ± 2.5 and 9.8 ± 2.3 %, respectively (p < 0.01). The mean decrease in Group 2 was 31.0 ± 2.3 %. The difference between the two groups was not statistically significant (p > 0.05). Twenty-four eyes of 24 patients with corneal neovascularization who were treated with a subconjunctival injection of bevacizumab were included in this retrospective study. Fourteen eyes were treated with 2.5 mg/0.1 ml (Group 1), and 10 eyes were treated with 5.0 mg/0.2 ml (Group 2) of subconjunctival bevacizumab. Digital photographs of the cornea were used to determine the area of corneal neovascularization before injection and at 1 month, 3 months, and 6 months after treatment. Subconjunctival injection of bevacizumab is well tolerated and associated with a partial regression of corneal neovascularization. The efficacy of this treatment is not correlated to the injection dose.     

Comparison of the effects of bevacizumab and ranibizumab injection on corneal angiogenesis in an alkali burn induced model

AIM: To investigate the effects of bevacizumab and ranibizumab on corneal neovascularization in an alkali burn-induced model of corneal angiogenesis. METHODS: Fifteen Wistar albino rats were divided randomly into 3 groups after chemical cauterization of the cornea. The first group received a single dose of 0.1mL saline solution as a control group whereas second and third groups received a single dose of 2.5mg bevacizumab or 1mg ranibizumab by subconjunctival injection, respectively. After three weeks, the rat corneas were evaluated by biomicroscopy and corneal photographs were taken. The percentage of neovascularization area, length of the longest new vessel, corneal edema and corneal opacity scores were assessed. RESULTS: The analysis of digital photographs showed that the percentage of neovascularization area to the total corneal area, the length of the longest new vessel, corneal edema and opacity scores were significantly lower in both study groups compared to the control group (P<0.05). Additionally, the percentage of corneal neovascularization area, the length of the longest new vessel and corneal opacity score were less with bevacizumab than ranibizumab. CONCLUSION: Subconjunctival bevacizumab and ranibizumab treatments may be effective methods in reducing corneal neovascularization. Furthermore, bevacizumab is more effective than ranibizumab in the inhibition of corneal neovascularization.     

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。     

Inhibition of experimental corneal neovascularization by using subconjunctival injection of bevacizumab (Avastin)

PURPOSE: To evaluate the effect of subconjunctival bevacizumab (Avastin) administration on corneal neovascularization (NV) in rabbits. METHODS: NV was induced by placing a suture at the corneal periphery of the right eye of 20 rabbits. Immediately after suturing and again 1 week later, rabbits were divided into 2 groups and administered a subconjunctival injection of normal saline (control) or bevacizumab (Avastin; 5 mg/0.2 mL), respectively. On day 14, digital photographs of the cornea were taken and analyzed to determine the area of the cornea covered by NV. In addition, immunohistochemical analysis was used to determine CD31 and vascular endothelial growth factor (VEGF) expression in corneal tissue. RESULTS: Analysis of digital photographs showed that there was less corneal NV in bevacizumab-treated eyes than in controls (P < 0.001, Mann-Whitney U test). In addition, there was less staining for VEGF and CD31 in corneas from bevacizumab-treated eyes than in control eyes. Subconjunctival bevacizumab injections were not associated with any complications during observation. CONCLUSIONS: Subconjunctival bevacizumab administration decreased suture-induced corneal neovascularization in rabbits.     

结膜下注射贝伐单抗对兔角膜新生血管的抑制作用

目的 观察碱烧伤后不同时间结膜下注射贝伐单抗（Bevacizumab）角膜新生血管（CNV）的形成与转归.方法 新西兰白兔54只,制成单眼碱烧伤模型,随机分为3组,每组18只眼,A组碱烧伤后结膜下立即注射贝伐单抗2.5 mg（0.1 ml）,B组碱烧伤后3d结膜下注射贝伐单抗2.5 mg（0.1 ml）,C组结膜下注射生理盐水0.1ml,为对照组.共观察28 d.裂隙灯显微镜下观察角膜新生血管生长情况,行眼前段照相并计算其面积,伤后7、14、28 d各组随机取6例角膜行共焦显微镜检查,观察角膜组织炎性细胞浸润情况及角膜新生血管形态学变化.结果 A、B及C组角膜新生血管开始出现的时间分别为（5.9＋0.8）d、（3.5＋0.6）d及（3.4＋1.1）d,其中A组明显较C组延长（P＜0.05）,B组与C组差异无统计学意义（P =0.068）.伤后各时间点A、B组角膜新生血管的生长面积均明显较C组减少（P＜0.05）,A组与B组角膜新生血管面积比较,差异有统计学意义（P＜0.05）.共焦显微镜检查可见C组烧伤区大量炎性细胞浸润及新生血管形成,而A组角膜炎性细胞较少,烧伤区无新生血管形成,B组见少量新生血管侵入烧伤区.3组基质层均可见纤维及瘢痕组织增生,其中治疗组纤维增生程度与瘢痕组织均较对照组轻.结论 结膜下注射贝伐单抗可抑制角膜炎性细胞形成,改善损伤角膜基质,促进角膜愈合,从而减少碱烧伤引起的角膜新生血管的生长,在早期注射能取得更好的疗效.     

贝伐单抗联合曲安奈德治疗穿透性角膜移植术后新生血管

目的：观察球结膜下注射贝伐单抗和曲安奈德治疗穿透性角膜移植术后新生血管的临床疗效。
　　方法：对19例20眼因眼外伤行穿透性角膜移植术后3mo,新生血管增生达到Ⅲ度以上患眼随机分为四组。 A组：对照组;B组：贝伐单抗2.5mg(0.1mL);C组：贝伐单抗及曲安奈德各0.1mL;D 组：曲安奈德0.1mL;每月1次,共两次球结膜下注射药物。
　　结果：平均随访3a,B组和C组视力保持稳定或稍有增进,新生血管和免疫反应明显减退(P<0.01),患者眼痛、畏光流泪症状减轻。
　　结论：贝伐单抗联合曲安奈德在治疗穿透性角膜移植术后新生血管的过程中能够有效减退新生血管,并减轻排斥反应,对保持植片的透明性有积极的治疗作用。     

Corneal endothelial safety following subconjunctival and intrastromal injection of bevacizumab for corneal neovascularization

The purpose of this study is to determine the effect on endothelial cell density and morphology of combined subconjunctival and intracorneal injection of bevacizumab for the treatment of corneal neovascularization (NV). The charts and specular microscopy images of ten consecutive patients with corneal NV, who received combined subconjunctival+intracorneal injections of bevacizumab were reviewed. Patients received three injections of bevacizumab 25 mg/mL (1.25 mg/0.05 mL subconjunctival and 1.25 mg/0.05 mL intrastromal) 4–6 weeks apart. Endothelial cell counts (ECCs) and morphological changes were assessed by non-contact specular microscopy performed at baseline, 1 month after each injection and at 3 and 6 months after the last injection. There were no significant changes in ECCs (p = 0.663), coefficient of variation (p = 0.076), percentage of hexagonal cells (p = 0.931) or mean corneal thickness (p = 0.462) from pre-injection values to the 6-month follow-up values. There were no intraoperative or postoperative complications. In our series, the use of combined subconjunctival and intracorneal bevacizumab did not cause any decrease in ECCs or morphological alterations up to 6 months after the last of three injections. Further studies are required to confirm long-term safety in a larger sample population with longer follow-up, as well as the ideal dose, route of administration and frequency of bevacizumab administration.     

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.     

Downregulation of IRS-1 expression causes inhibition of corneal angiogenesis

PURPOSE: The antiangiogenic effect of an antisense oligodeoxynucleotide (ODN) targeting insulin receptor substrate (IRS)-1 was evaluated on rat corneal neovascularization. METHODS: Eyes with neovessels were treated with subconjunctival injections of IRS-1 antisense oligonucleotide (ASODN), IRS-1 sense ODN (SODN), or PBS. At 8 and 24 hours after the first subconjunctival injection, the expression of IRS-1, VEGF, and IL-1beta mRNA was evaluated. IRS-1 protein levels were also measured at 8 hours by Western blot analysis (n = 4/group). On day 10, corneal neovascularization was quantified in flatmount corneas of rats treated daily from days 4 to 9. RESULTS: On day 10, new vessels covered 95.5% +/- 4% of the corneal area in PBS-treated eyes, 92% +/- 7% in SODN-treated eyes and 59% +/- 20% in ASODN-treated eyes (P < 0.001). In the ASODN-treated group, the expression and synthesis of IRS-1 were significantly downregulated when compared with the control groups. ASODN did not significantly affect the expression of VEGF but significantly decreased the expression of IL-1beta at 24 hours (P = 0.04). CONCLUSIONS: Subconjunctival injections of IRS-1 antisense ODN significantly inhibit rat corneal neovascularization. This effect may be mediated by a downregulation of IL-1beta. IRS-1 proteins may be interesting targets for the regulation of angiogenesis mediated by insulin, hypoxia, or inflammation.     

Regression of Iris Neovascularization after Subconjunctival Injection of Bevacizumab

To describe three cases of neovascular glaucoma (NVG) where iris or angle neovascularization regressed remarkably after subconjunctival bevacizumab injections used as the initial treatment before pan retinal photocoagulation (PRP) and/or filtering surgery. Three consecutive NVG patients whose intraocular pressure (IOP) was not controlled with maximal medication were offered an off-label subconjunctival injection of bevacizumab (2.5-3.75 mg/0.1-0.15 mL, Avastin). Bevacizumab was injected into the subconjunctival space close to the corneal limbus in two or three quadrants using a 26-gauge needle. Serial anterior segment photographs were taken before and after the injection. Following subconjunctival injection of bevacizumab, iris or angle neovascularization regressed rapidly within several days. Such regression was accompanied by lowering of IOP in all three cases. The patients underwent subsequent PRP and/or filtering surgery, and the IOP was further stabilized. Our cases demonstrate that subconjunctival bevacizumab injection can be potentially useful as an initial treatment in NVG patients before laser or surgical treatment.     

A case of ocular benign lymphoid hyperplasia treated with bevacizumab injection

We report the first case of ocular benign lymphoid hyperplasia (BLH) treated with subconjunctival injection of bevacizumab (Avastin). A 27-year-old man presented to our clinic with conjunctival masses and limbal neovascularization. An incisional biopsy yielded the diagnosis of BLH. The patient was subsequently given a subconjunctival injection of bevacizumab (1.25 mg / 0.1 mL). The patient did not experience recurrence or malignant metaplasia during the one-year follow-up period. In patients with conjunctival BLH, subconjunctival injection of bevacizumab can be a useful treatment option in patients unable to undergo a surgical procedure due to limbal neovascularization.     

Effect of bevacizumab on corneal neovascularization in experimental rabbit model

Purpose:  To investigate the effect of bevacizumab in an experimental rabbit model of corneal neovascularization.
Methods:  The right eyes of 24 white New Zealand rabbits were included in a corneal neovascularization model using alkaline burn. They were divided into four groups. Topical bevacizumab was installed three times daily in group 1, 5 mg bevacizumab subconjunctivally every 2 days in group 2, 10 mg bevacizumab subconjunctivally every 2 days in group 3 and 0.2 cc of normal saline in the same way in group 4 (control group). All eyes were treated for 7 days. Then the animals were killed and corneal specimens sent for histopathological analysis. Tear film and aqueous humour samples were obtained to assess vascular endothelial growth factor (VEGF) levels.
Results:  Seven days after topical bevacizumab treatment the neovascular index in group 1 was lower than that in the control group ( P  = 0.028). In groups 2 and 3 the neovascular index was lower 2 days after subconjunctival bevacizumab treatment than that in control group ( P  = 0.009 and P  = 0.009, respectively). In the control group the VEGF level in aqueous humour increased by 66% from day 7 to 14. In groups 1–3 it decreased by 49.80%, 70.20% and 76.44%, respectively ( P  = 0.043). The VEGF level in tear film of the control group increased by 35.23% from day 7 to 14, which was not significant ( P  = 0.893), while in groups 1–3 it decreased by 57.26%, 34.59% and 67.97%, respectively, which was only significant in groups 1 and 3 ( P  = 0.043).
Conclusions:  Subconjunctival 5 mg/mL bevacizumab is effective in reducing corneal neovascularization in animal models and in reducing VEGF levels. Further research is needed to assess the potential side effects and minimal effective dose.