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.     

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.     

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.     

Subconjunctival bevacizumab in the impending recurrent pterygia

The aim of this study is to evaluate the efficacy and safety of subconjunctival bevacizumab injection(s) in the treatment of impending recurrent pterygia. Twenty-three eyes of 23 patients who developed impending recurrence after pterygium surgery with conjunctival autografting and were treated with subconjunctival bevacizumab injection(s) (2.5 mg/0.1 mL) were included in the study. Anterior segment photographs were taken prior to and at 1 week, 1, 3 and 6 months after the injection, and at the end of the follow-up period. Image analysis was performed using an image processing and analysis software program. Recurrence rate and complications were recorded. The mean age and follow-up time of the patients were 51.2 ± 6.2 (31–60 years) and 16.8 ± 3.1 (12–22 months), respectively. The average number of injections was 2 ± 0.78 (1–3). Sixteen eyes required re-injection (two injections in nine eyes, three injections in seven eyes), due to progression of vascularization. There were significant differences between size percentage of lesions before injection and at 1 week, 1, 3 and 6 months after the injection (p < 0.05 for all). Corneal recurrence developed in only one patient and no ocular or systemic side-effects of bevacizumab were observed. Repeated injections of bevacizumab may help to prevent the high recurrence rate of residual impending pterygium, due to its adjuvant role in decreasing lesion size, especially in the first year after surgery.     

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.     

Inhibitory effects of topical cyclosporine A 0.05 % on immune-mediated corneal neovascularization in rabbits

Background

We aimed to study the inhibitory effects of topical cyclosporine A (CsA) 0.05 % on immune-mediated corneal neovascularization, and to compare its efficacy with those of dexamethasone 0.1 % and bevacizumab 0.5 %.

Methods

Immune-mediated corneal neovascularization was created in 36 right eyes of 36 rabbits. The rabbits were then randomized into four groups. Group I received CsA 0.05 %, Group II received dexamethasone 0.1 %, Group III received bevacizumab 0.5 %, and Group IV received isotonic saline twice a day for 14 days. The corneal surface covered with neovascular vessels was measured on the photographs. The rabbits were then sacrificed and the corneas excised. Paraffin-embedded sections were stained with hematoxylin-eosin and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay.

Results

The means of percent area of corneal neovascularization in Group I, II, III, and IV were 24.4 %, 5.9 %, 37.1 %, and 44.1 %, respectively. The inhibitory effect of CsA 0.05 % was found to be better than the effect found in the bevacizumab 0.5 % and control groups (p?=?0.03 and p?=?0.02, respectively). CsA 0.05 % was found to have significantly lesser inhibitory effects on corneal neovascularization than dexamethasone 0.1 % (p?<?0.001). Apoptotic cell density was higher in Group III and Group IV than in Group I and Group II. There was no difference between Group I and Group II in terms of apoptotic cell density (p?=?0.7).

Conclusions

Topical CsA 0.05 % was shown to have an inhibitory effect on immune-mediated corneal neovascularization in rabbits.     

Bevacizumab球结膜下注射联合滴眼液治疗角膜新生血管

目的：观察bevacizumab结膜下注射联合眼液滴眼治疗角膜新生血管( corneal neovascularization,CNV)的临床效果及安全性。方法：采用自身前后对照比较,观察 CNV 患者25例32眼,其中碱烧伤6例8眼,慢性角膜炎14例19眼,单纯角膜穿通伤5例5眼。采取患眼下方结膜下注射bevacizumab 2.5mg,治疗后应用自配的5mg/mL bevacizumab眼液滴眼4次/d,连续滴眼15d。1mo后重复上述治疗,共3次。于治疗前、再次治疗前和3次治疗停止后1、3、6 mo观察视力、眼压、前房反应、CNV面积、角膜血管翳及血压、心率的变化情况,探讨 bevacizumab 治疗CNV的效果、治疗次数和安全性。结果：所有患者治疗后血压、心率、眼压及前房反应与治疗前无明显变化,角膜血管翳有不同程度的减轻,平均CNV面积与治疗前比较,差异有统计学意义( F=5.574、6.221、6.221,P<0.05)。治疗停止后1mo,18眼(56%)视力提高两行以上;20眼(63%) CNV 面积减小;有效率为56%。3mo后23眼(72%)视力提高两行以上;25眼(78%) CNV面积减小;有效率为72%。6 mo后情况与3 mo基本相同。
　　bevacizumab对不同病因引起的CNV均表现出治疗效果效果,碱烧伤、慢性角膜炎及单纯角膜穿通伤的改善率分别为62%、79%和60%。在32眼中,观察视力或CNV改善情况,第1次治疗后44%得到改善,第2次治疗后56%改善,第3次治疗后63%改善,3次治疗后两组组间比较改善率,治疗2次和3次与治疗1次比较,差异均有统计学意义(χ2=46.274、48.532,P<0.05)。结论：Bevacizumab结膜下注射联合眼液滴眼治疗CNV方法简便,短期观察效果明确,未见明显不良反应。     

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 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.     

Inhibitory effects of bevacizumab on angiogenesis and corneal neovascularization

Background

To evaluate the inhibitory effects of bevacizumab (Avastin®) on angiogenesis using cultured human umbilical vein endothelial cells (HUVECs) in vitro and on corneal neovascularization by subconjunctival injection of bevacizumab in vivo.

Methods

After the HUVECs were exposed to different concentrations of bevacizumab stimulated with VEGF (10 ng/ml) for 2, 6, and 24 hours, cellular-activity-like proliferation, migration and tube formation were assessed. Subconjunctival injection of bevacizumab (2.5 mg/0.1 ml) was performed after corneal chemical burn injury. Then the cornea was evaluated by biomicroscopy, fluorescein angiography, and light microscopy.

Results

The inhibitory effects of bevacizumab on VEGF-induced HUVECs proliferation showed a dose-dependent response for 2 and 6 hours, but all groups were effectively inhibited regardless of the concentration of bevacizumab for 24 hours. The inhibitory effects of bevacizumab on the migration of VEGF-induced HUVECs showed a time- and dose-dependent response. The inhibitory effects of bevacizumab on VEGF-induced HUVECs tube formation showed a dose-dependent response only for 24 hours. On days 3 and 8 after the subconjunctival injection, bevacizumab-treated eyes showed less neovascular growth than BSS-treated eyes in biomicroscopic, fluorescein angiographic, and light microscopic findings in vivo.

Conclusions

Bevacizumab effectively inhibits angiogenesis and corneal neovascularization, and could be used as a inhibitor of corneal neovascularization in the future.

     

Avastin use in high risk corneal transplantation

Background

Corneal neovascularization is a major risk factor for graft failure after corneal transplantation. The purpose of this study was to investigate the effect of subconjunctival, perilimbal, and/or intrastromal bevacizumab (Avastin®) on corneal neovascularization in patients with penetrating keratoplasty (PKP).

Methods

Fourteen eyes of 14 patients with high risk corneal transplantation and corneal neovascularization after PKP (nine men and five women with a mean age of 63 years) were included in this non-comparative interventional case series. Indications for PKP were: vascularized leucomas after herpetic keratitis and chemical burn, advanced pseudophakic bullous keratopathy with superficial and deep corneal vascularization, keratoconus, severe infection in hereditary corneal dystrophy, and failed corneal grafts. Subconjunctival, perilimbal, and/or intrastromal bevacizumab of dose of 2.5 mg/ 0.1 ml/ per affected quadrant was injected at the site of neovascularization in each patient at the end of surgery and/or at follow up visits. One or two injections were applied. At each visit a full eye examination with photo documentation was performed. Follow-up period was 2 to 8 months (mean 7.1 months).

Results

Decrease of corneal neovascularization was observed in eleven patients (78.6%). Regression of neovascularization with fading of small vessels was demonstrated. Despite high- risk patient pool, twelve grafts (85.7%) remained transparent for the period of observation, and patients maintained good visual acuity. In two patients with initial graft rejection and vascularization, subconjunctival and perilimbal application of bevacizumab was beneficial in overcoming the corneal inflammation and initial rejection. No adverse reactions have been detected to date in patients with subconjunctival, perilimbal, and/or intrastromal injection of bevacizumab.

Conclusions

Bevacizumab is an efficient and safe additional treatment option for improvement of prognosis in high-risk corneal transplantation with pre- and postoperative corneal neovascularization.

     

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.     

Subconjunctival bevacizumab as an adjuvant in first-time filtration surgery for patients with primary glaucomas

To investigate subconjunctival bevacizumab as an adjuvant in first-time glaucoma filtration surgery, we conducted a non-comparative, interventional case series, enrolling consecutive patients with uncontrolled primary glaucomas. All patients underwent trabeculectomy with mitomycin C and received a 1.25 mg subconjunctival bevacizumab injection at completion of the surgery. Main outcome measurements were success rates, bleb morphology [standardized classification based on vascularity (0–1), extension (0–1) and height (0–1); ranging from 0 to 3 (0 = poor; 1 = regular; 2 = good; 3 = excellent)] and post-operative complications. Twenty-five eyes from 25 patients (mean age 64.3 ± 12.8 years) were included. After a mean follow-up of 16.7 ± 6.1 months, mean intraocular pressure (IOP) was significantly reduced from 22.7 ± 10.8 to 12.9 ± 4.3 mmHg at the last follow-up (p < 0.01). Complete success rates at 12 months ranged between 71 and 88 %, while qualified success rates ranged between 84 and 96 %, depending on the criterion adopted (the strictest success criterion was defined as IOP between 6 and 12 mmHg). Blebs were graded as good or excellent in 80 % of the cases. No serious post-operative complication or avascular blebs were observed. These mid-term results suggest subconjunctival bevacizumab as a safe and effective adjuvant in first-time filtration surgery for primary glaucoma patients.     

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.     

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.     

Concentration of Vascular Endothelial Growth Factor After Intracameral Bevacizumab Injection in Eyes With Neovascular Glaucoma

Purpose

To study the concentration of vascular endothelial growth factor (VEGF) in the aqueous humor before and after intracameral injection of bevacizumab in eyes with neovascular glaucoma, and to detect the duration of an anti-VEGF effect of bevacizumab in the anterior chamber.

Methods

In this prospective interventional case series, 1.25 mg of bevacizumab was injected into the anterior chamber of five eyes in five neovascular glaucoma patients. Aqueous humor samples were obtained just before intracameral injection of bevacizumab and two weeks after injection. The concentrations of VEGF in the aqueous humor were measured using ELISA. To investigate corneal endothelial damage after intrecameral bevacizumab injection, specular microscopy was performed before injection and two weeks after injection. Slit lamp photo and iris fluorescent angiography was performed to determine the regression of iris neovascularization.

Results

After injection, substantial regression of neovascularization or fluorescein leakage was seen in all treated eyes. The VEGF concentrations in the aqueous humor in eyes with NVG were 1181.8±1248.3 pg/mL before intracameral injection of bevacizumab. Two weeks after injection, the VEGF concentrations decreased to 33.2±12.2 pg/mL (p=0.04, Wilcoxon signed rank test). There were no significant changes in IOP or corneal endothelial cells.

Conclusions

Intracameral bevacizumab injection can remarkably reduce iris neovascularization in neovascular glaucoma patients. VEGF levels were significantly decreased two weeks after injection and corneal toxicity was not observed during short term follow-up.     

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.     

Subconjunctival bevacizumab injection for corneal neovascularization in recurrent pterygium

PURPOSE: We report on the use of subconjunctival bevacizumab on corneal vessel density in recurrent pterygia. METHODS: The charts of 5 patients with recurrent pterygium, who received subconjunctival injections of bevacizumab (2.5 mg/0.1 ml) were retrospectively reviewed. Ophthalmic evaluation included Snellen visual acuity (VA), tonometry and complete examination before the injection and at 1 week and 1 and 3 months thereafter. Digital photographs of the eyes were analyzed by image analysis software to determine the area of cornea covered by new vessels as a percentage of the total corneal area. RESULTS: No ocular or systemic adverse events were observed. No change in visual acuity was noted in any patient following the injection. The mean change in corneal vascularization after one bevacizumab injection was 0.03%+/-0.45, while after two injections the change was 0.025%+/-0.19 (both not statistically different than zero, t-test). CONCLUSIONS: Short-term results suggest that subconjunctival bevacizumab is well tolerated but does not cause regression of corneal vessels in recurrent pterygium.     

Subconjunctival bevacizumab for corneal neovascularization

Objective To report the efficacy of subconjunctival bevacizumab injection in patients with corneal neovascularization (NV). Methods This retrospective interventional case study included two eyes of two patients with corneal NV due to aqueous-deficient dry eye with filamentary keratitis in the first case, and corneal graft failure in the second case. Patients received a subconjunctival injection of 2.5 mg (0.1 ml) bevacizumab. Morphologic changes were investigated by slit-lamp biomicroscopy and corneal photography. Results Corneal NV was dramatically regressed a week after injection in the first case. In the second case, minor vessels were regressed while the major one did not. No infection or inflammation was observed. No relapse was seen within the follow-up of two to three months. Conclusion Subconjunctival injection of bevacizumab may offer an additional strategy for the treatment of corneal NV.     

The Effect of Bevacizumab versus Ranibizumab in the Treatment of Corneal Neovascularization: A Preliminary Study

Purpose

To compare the short term effects of bevacizumab and ranibizumab injections on the regression of corneal neovascularization (NV).

Methods

Sixteen eyes of 16 patients with corneal NV were randomly assigned for an injection with 2.5 mg of bevacizumab (group 1, n = 8) or 1 mg of ranibizumab (group 2, n = 8) through subconjunctival and intrastromal routes. The patients were prospectively followed-up for one month after the injections. Corneal NV areas, as shown on corneal slit-lamp photographs stored in JPEG format, were calculated using Image J software before the injection, one week after the injection, and one month after the injection. The corneal NV areas were compared before and after the injections.

Results

Seven women and nine men, with an average age of 51 years, presented with corneal NV secondary to herpetic keratitis (7 cases), graft rejection (6), chemical burn (1), pemphigoid (1), and recurrent ulcer (1). In group I, the preoperative corneal NV area (8.75 ± 4.33%) was significantly decreased to 5.62 ± 3.86% one week after the injection and to 6.35 ± 3.02% one month after the injection (p = 0.012, 0.012, respectively). The corneal NV area in group 2 also exhibited a significant change, from 7.37 ± 4.33% to 6.72 ± 4.16% one week after the injection (p = 0.012). However, no significant change was observed one month after the injection. The mean decrease in corneal NV area one month after injection in group 1 (28.4 ± 9.01%) was significantly higher than in group 2 (4.51 ± 11.64%, p = 0.001).

Conclusions

Bevacizumab injection resulted in a more effective and stable regression of corneal NV compared to the ranibizumab injection. The potency and dose of these two drugs for the regression of corneal NV require further investigation.