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.     

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.     

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.     

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.     

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.     

Attenuation of corneal neovascularization by topical low-molecular-weight heparin-taurocholate 7 without bleeding complication

AIM: To investigate the antiangiogenic effects and safety of topically administered low-molecular-weight heparin-taurocholate 7 (LHT7) on corneal neovascularization (CoNV). METHODS: Twenty-four Sprague-Dawley rats were randomly distributed into four groups of six rats each. The central corneas were cauterized using a silver/potassium nitrate solution. From 2d after cauterization, 12.5 mg/mL (low LHT7 group) or 25 mg/mL (high LHT7 group) LHT7 was topically administered three times daily; 12.5 mg/mL bevacizumab was topically administered as positive control (bevacizumab) group, with normal saline (NS) administered as negative control (NS group). The corneas were digitally photographed to calculate the CoNV percentage from the neovascularized corneal area at 1 and 2wk. RESULTS: The 4 study groups did not have different CoNV percentages at 1wk after injury (P>0.05). However, the low LHT, high LHT, and bevacizumab groups had significantly lower CoNV percentages than the NS group at 2wk (all P<0.05). No significant differences in CoNV percentage were found among the low LHT, high LHT, and bevacizumab groups (all P>0.05). All groups except the NS group had lower CoNV percentages at 2wk post-injury than the levels observed at 1wk (all P<0.05). CONCLUSION: Topically-administered LHT7 inhibited CoNV without complication after chemical cauterization in the rat.     

Local and Systemic Complications after Intravitreal Administration of Anti-Vascular Endothelial Growth Factor Agents in the Treatment of Different Ocular Diseases: A Five-Year Retrospective Study

Abstract

Purpose: To observe the frequency of complications in patients undergoing intravitreal anti-VEGF injections for different ocular diseases in a five-year period. Materials and Methods: Charts of patients receiving intravitreal anti-VEGF were retrospectively reviewed. Out of 1173 eyes, 762 were treated with bevacizumab, 382 with ranibizumab, and 29 with pegaptanib. Data recorded included demographic information, clinical findings, total injections received, and info about the onset of adverse effects. Results: 12.86% of the eyes treated with bevacizumab presented side-effects, while ratings in the ranibizumab and pegaptanib groups were 15.97% and 20.69%, respectively. Odds ratios calculated comparing incidences after each anti-VEGF are 0.78 (bevacizumab versus ranibizumab, p?=?0.152), 0.57 (bevacizumab versus pegaptanib, p?=?0.227), and 0.73 (ranibizumab versus pegaptanib, p?=?0.508). A total of 185 complications were detected (62.16% after bevacizumab). Ocular side-effects registered were 40 cases of sustained intraocular pression (IOP) elevation, one infectious uveitis, one retinal detachment, and one sub-retinal hemorrhage. Other cases were related to transient IOP elevation immediately after injection. Systemic complications registered were one case of nausea, one episode of chest pain with acute vision loss, and one case of acute blood hypertension. Conclusions: The majority of significant complications occurred in patients receiving multiple bevacizumab administrations. However, results may be affected by the difference in the utilization amount for each drug. AMD patients were the most represented, probably due to greater indication to treatment.     

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.     

Evaluating the safety of intracameral bevacizumab application using oxidative stress and apoptotic parameters in corneal tissue

AIM:To investigate the possible effects of intracameral bevacizumab on oxidative stress parameters and apoptosis in corneal tissue.METHODS:In total, 30 rats were assigned randomly into the following three groups of 10 rats each:a sham group (Group 1; n=10), a control group [Group 2; balanced salt solution (BSS) was administered at 0.01 mL; n=10], and a treatment group (Group 3; bevacizumab was administered at 0.25 mg/0.01 mL; n=10). The total antioxidant status (TAS) and the total oxidant status (TOS) in the corneal tissue and blood samples were measured, and the oxidative stress index (OSI) was calculated. Additionally, corneal tissue histopathology was evaluated for caspase-3 and -8 staining and apoptotic activity.RESULTS:In the blood samples, the TAS, TOS, and OSI levels were not significantly different (all P>0.05). Compared with the sham and control groups, the TOS and OSI levels in the corneal tissues were significantly different in the bevacizumab group (all P<0.05). No statistically significant differences were observed between the sham and control groups (all P>0.05). However, compared with the sham and control groups, greater immunohistochemical staining for caspases-3 and -8 and an elevated level of apoptotic activity were observed in the bevacizumab group.CONCLUSION:This study revealed that intracameral bevacizumab injections seemed to be systemically safe but may have elicited local toxic effects in the corneal tissue, as indicated by the oxidative stress parameters and histopathological evaluations.     

Combined scraping,coagulation, and subconjunctival bevacizumab in corneal transplantation for bullous keratopathy with corneal neovascularization

PurposeThis study investigated clinical outcomes of the combined method of scraping, coagulation, and subconjunctival bevacizumab for the treatment of corneal neovascularization (NV) in penetrating keratoplasty (PKP).MethodsThis study included patients undergoing PKP who were diagnosed with bullous keratopathy with dense subepithelial scarring that was not suitable for Descemet’s stripping automated endothelial keratoplasty. Corneal NV was treated by scraping the corneal epithelium and lightly coagulating the superficial corneal stromal NV combined with subconjunctival bevacizumab injection at the end of surgery. Patients without corneal NV were used as the control group.ResultsThere were six patients with vascularized corneas in the study group and three patients without vascularized corneas in the control group. The original corneal NV in the study group disappeared in all patients after surgery. Three of the six (50%) study patients experienced recurrent corneal NV. One of the three (33%) control patients developed corneal NV. These patients had no corneal NV recurrences over the next 6 months after repeat treatment. In both groups, no graft failure or chronic epithelial defects occurred.ConclusionThe combination of scraping the corneal epithelium, coagulating the superficial corneal stromal NV and the feeding vessels in the sclera after peritomy, and subconjunctival bevacizumab injection is an effective method to treat corneal NV in corneal transplantation for bullous keratopathy.     

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。     

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.     

The inhibitory effect of different concentrations of topical bevacizumab on corneal neovascularization

Acta Ophthalmol. 2010: 88: 862–867

Abstract.

Purpose: This study aimed to evaluate the effects of different concentrations of topically administered bevacizumab (Avastin) on experimental corneal neovascularization (NV) in rats. Methods: Corneal NV was induced by chemical cauterization with silver nitrate sticks applied to the centre of the corneas of 37 Wistar rats. The rats were then randomized to four topical treatment groups: group 1 (n = 10) received 4 mg/ml bevacizumab; group 2 (n = 9) received 2 mg/ml bevacizumab; group 3 (n = 10) received 1 mg/ml bevacizumab, and group 4 (n = 8) represented a control group and received saline. All drops were initiated immediately after cauterization and applied twice per day for 7 days. Corneal NV was assessed 8 days after cauterization in a masked fashion, both qualitatively by clinical evaluation and quantitatively by blood vessel count in photographs of histological sections. Results: On clinical evaluation, groups 1 and 2 showed significantly less NV compared with the saline‐treated control group (p = 0.006 and p = 0.024, respectively). Histopathological evaluation showed that only group 1 differed significantly from controls (5% significance level) and normal corneal epithelium was seen in all groups. Conclusions: Topically administered bevacizumab at a concentration of 4 mg/ml significantly reduces corneal NV according to both clinical and histopathological evaluations; lower concentrations were less effective on both parameters. No corneal epitheliopathy was found using these concentrations.     

促红细胞生成素(Epo)及其受体(EpoR)在正常及碱烧伤诱导的鼠新生血管化角膜上的表达(英文)

目的:促红细胞生成素(Epo)是促红细胞生成的因子,由胎儿肝脏和成人肾脏产生,是贫血及缺氧时的一种应答反应。视网膜异常血管形成,如早产儿视网膜病变(ROP),增殖性糖尿病性视网膜病变(PDR)时Epo水平增高,提示Epo在病理性眼部血管生成中的作用。Epo参与视网膜血管生成,但其与角膜新生血管是否有关尚未见报道。本研究旨在探讨Epo/EpoR是否在正常和新生血管化角膜表达及角膜内注射Epo是否可诱发角膜新生血管的产生,从而了解其与角膜新生血管的联系。方法:(1)制备碱烧伤诱导鼠角膜新生血管模型,免疫组织化学的方法检测Epo及EpoR是否在正常角膜及新生血管化角膜表达;(2) Epo的克隆、表达及纯化;(3)角膜基质内分别注射Epo(6μL,1μg)及Epo对照(载体对照)及盐水,第14d观察角膜是否有新生血管产生。结果:Epo及EpoR在正常角膜及碱诱发的新生血管化角膜的角膜上皮细胞,角膜内皮细胞,基质细胞均有表达,并在新生血管化角膜表达加强,同时也在基质内炎症细胞及新生血管均有表达。角膜基质内注射Epo后第14d,6眼中5眼产生新生血管,对照组6眼均未见新生血管。结论:本文首次报道了Epo及其受体表达于正常角膜和新生血管化角膜。角膜内注射注射Epo可诱发角膜新生血管。Epo及其受体系统与角膜新生血管化的形成有关。     

Treatment of neovascular age-related macular degeneration with pegaptanib and boosting with bevacizumab or ranibizumab as needed

BACKGROUND AND OBJECTIVE: Neovascular age-related macular degeneration presents a therapeutic challenge. The efficacy of pegaptanib sodium, a selective inhibitor of vascular endothelial growth factor 165, was examined as a therapeutic mainstay combined with "as needed" boosts of nonselective vascular endothelial growth factor blockade with bevacizumab or ranibizumab. PATIENTS AND METHODS: A retrospective chart review of outcomes of patients treated with pegaptanib and later boosted with bevacizumab or ranibizumab was conducted. Visual acuity, optical coherence tomography, and fluorescein angiography findings were recorded and assessed. RESULTS: During a mean follow-up of 12.1 months, an average of 7.8 injections of pegaptanib 0.3 mg, 1.4 injections of bevacizumab 1.25 mg, and 0.9 injections of ranibizumab 0.5 mg were administered to 17 eyes. In all, 47% of eyes gained 3 or more lines of visual acuity and 76% gained 0 or more lines. CONCLUSION: Pegaptanib as a mainstay of neovascular age-related macular degeneration therapy with an occasional boost of bevacizumab or ranibizumab appears to be an effective treatment option.     

Submacular haemorrhage after intravitreal bevacizumab compared with intravitreal ranibizumab in large occult choroidal neovascularization

Background: Submacular haemorrhage may occur following intravitreal bevacizumab injection for large occult choroidal neovascularization (CNV) in age‐related macular degeneration (AMD). We report the occurrence of submacular haemorrhage following intravitreal ranibizumab compared with intravitreal bevacizumab for large occult CNV in AMD. Methods: Retrospective, comparative evaluation of two interventional case series. Evaluation of consecutive patients with occult CNV ≥ 15 mm² treated with intravitreal bevacizumab (n = 14) and intravitreal ranibizumab (n = 22) over a 2‐year period within a single institution. Postoperative submacular haemorrhage, Early Treatment Diabetic Retinopathy Study‐derived visual acuity, preoperative blood pressure and anticoagulant use were noted. The two groups were compared using Fisher's exact test. Results: The mean surface area of occult CNV at presentation was 20.9 ± 5.4 mm² in the bevacizumab group and 24.0 ± 11.0 mm² in the ranibizumab group. Fresh submacular haemorrhage was seen in 4 out of 14 patients following bevacizumab compared with 0 out of 22 patients following ranibizumab (P = 0.017, odds ratio = 19.29). Mean preoperative blood pressures were very similar between the groups. 28.6% of patients in the bevacizumab group were on oral anticoagulants compared with 31.8% in the ranibizumab group. None of the patients who developed postoperative haemorrhage were on anticoagulants. Conclusions: Acute submacular haemorrhages appear to be a significant adverse event following intravitreal bevacizumab in occult CNV ≥ 15 mm². Intravitreal ranibizumab appears to have a significantly lower incidence of postoperative submacular haemorrhage in occult CNV ≥ 15 mm². Larger studies are required to identify the most appropriate agent for the treatment of large occult CNV.     

Bevacizumab and ranibizumab for neovascular age-related macular degeneration: a treatment approach based on individual patient needs

ObjectiveTo compare the efficacy of intravitreal bevacizumab and ranibizumab for the treatment of neovascular age-related macular degeneration using an as-needed treatment regimen.DesignRetrospective chart review.ParticipantsOne hundred and ninety two eyes of 184 patients.MethodsPatients received an initial treatment of 3 monthly intravitreal injections of ranibizumab or bevacizumab and retreatment is individually considered for each patient on the basis of optical coherence tomography, angiography, and clinical examination.ResultsFifty eyes treated with ranibizumab and 142 eyes treated with bevacizumab were included. The average age of the patients at baseline was 76.9 ± 8 years and 76.4 ± 8 years in the ranibizumab and bevacizumab group respectively. Mean visual acuity improved from 0.69 to 0.55 logMAR at 12 months in the ranibizumab group and from 0.70 to 0.67 logMAR in the bevacizumab group. At 12 months, 92% of eyes treated with ranibizumab had lost fewer than 0.3 logMAR, as compared with 83% in the bevacizumab group. The ranibizumab group received a mean of 4.92 injections, compared to 4.75 injections in the bevacizumab group over 12 months. After the first 3 injections, 20% of patients in the ranibizumab group and 26% in the bevacizumab group never needed another injection.ConclusionsAn approach based on clinical onset and choroidal neovascularization progression at angiography may provide benefit by reducing the number of intravitreal injections required.     

Management of pediatric choroidal neovascular membranes with intravitreal anti-VEGF agents: a retrospective consecutive case series

Objective: To report the results of pediatric choroidal neovascular membranes (CNVMs) secondary to a variety of etiologies treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents.Design: Retrospective case series.Participants: Four pediatric patients at the Hosptial for Sick Children with CNVMs secondary to a variety of etiologies.Methods: Each patient received multiple treatments with one of the following anti-VEGF agents: pegaptanib sodium, bevacizumab, or ranibizumab. Progress was monitored by clinical exam, optical coherence tomography (OCT), and fluorescein angiography.Results: The mean age of our patients was 11.5 years (range, 8–15 years). Patients were followed for a mean of 10 months (range, 4–14 months). One patient was treated with pegaptanib sodium, 2 with bevacizumab, and 1 with ranibizumab. Following treatment, 1 patient showed an improvement and 3 showed stabilization of vision with reduction of fluid on clinical exam and OCT, and cessation of leakage on the fluorescein angiogram. Patients required 2–5 injections of the anti-VEGF agent. No ocular or systemic adverse events were observed in any of our treated patients.Conclusions: Anti-VEGF agents were effective in the treatment of pediatric CNVMs in this case series. However, we do not know how these results would have differed from other treatment modalities, including observation. We did not observe any adverse side effects; however, larger studies are required to document the safety of these medications in the pediatric population where normal angiogenesis is occurring.     

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.     

Are intravitreal bevacizumab and ranibizumab effective in a rat model of choroidal neovascularization?

Background  Vascular endothelial growth factor (VEGF) is an important stimulator of choroidal neovascularization (CNV). Bevacizumab (Avastin), ranibizumab (Lucentis) and pegaptanib sodium (Macugen) are anti-VEGF medications that have been used in the treatment of CNV. The purpose of our study is to evaluate the efficacy and safety of intravitreal injections of bevacizumab, ranibizumab and pegaptanib sodium in the treatment of CNV in a rat model. Methods  Multiple CNV lesions were induced by laser photocoagulation of the retina in Brown-Norway rats. After 3 weeks, 17 rats were divided into three groups and received intravitreal injections of bevacizumab, ranibizumab or pegaptanib sodium in different dosages. The lesions were evaluated by fluorescein angiography 1, 7, 14, and 28 days later to assess the efficacy of these medications. Results  Different doses of bevacizumab did not show any effect on stopping the leakage on fluorescein angiography on days 1, 7, 14, and 28. Ranibizumab and pegaptanib sodium did not stop the leakage of CNV either. No angiographic or histopathologic toxicity was observed. Conclusions  These three anti-VEGF agents did not show any therapeutic effect on stopping CNV leakage in rats. Previous experiments with ranibizumab in monkeys resulted in a significant decrease in leakage of CNV. The difference may be due to the fact that both ranibizumab and bevacizumab are humanized and species-specific. There are several studies evaluating the effect of bevacizumab in non-primates. Since bevacizumab is humanized, the results of studies on non-primates may not be similar to humans and non-human primates. Grant Support: Leir Foundation The authors have full control of the primary data and will provide it to Graefe’s Archive for Clinical and Experimental Ophthalmology at their request. Neither author has any conflict of interest, financial or otherwise, to report.