Laboratory research advancement in bevacizumab / 中华实验眼科杂志

Vascular endothelial growth factor (VEGF) is a key factor for neovascular diseases of ophthalmology.Bevacizumab is a full-length,humanized monoclonal IgG antibody,which prevents VEGF-A to combine with its receptors on the endothelial surface,and inhibits the endothelial cell proliferation and new blood vessel formation.Nowadays,anti-VEGF drugs are widely used to treat neovascularization diseases in ophthalmology.Bevacizumab has been more extensively applied because of its high security and low cost.The article reviewed the advancement of laboratory researches on the permeability,safety,pharmacokinetics of bevacizumab and research in vitro.

Efficacy of subconjunctival bevacizumab injection in corneal neovascularisation.

Aim: To evaluate the therapeutic effect of subconjunctival Bevacizumabon corneal neovascularisation Design: A prospective randomized noncomparative study. Method: The charts of 10 consecutive patients with corneal neovascularisation who received single S.C. inj. of Bevacizumab (2.5mg/0.1ml) were reviewed. Digital photographs of the cornea were taken pre & post injection & then at 1 wk,3wk & 2months duration. Digital photographs of the cornea were analyzed to determine the length, density, extent, centricity of corneal neovascularisation and the area of cornea covered by neovascularisation as a percentage of the total corneal area. Results: Subconjunctival injection of Bevacizumab (Avastin) caused significant regression of corneal neovascularisation in 1 pt, partial regression in 6 pts and no effect in 3 pts as measured by length and surface area of neovascularisation. No significant ocular or systemic complications were found. Conclusion: Subconjunctival inj. of Bevacizumab is effective in regressing corneal neovascularisation.

Intravitreal Bevacizumab Injection as Preoperative Adjuvant of Vitrectomy for Proliferative Diabetic Retinopathy

PURPOSE:The effect of preoperative intravitreal bevacizumab (Avastin(R)) injection was investigated in primary vitrectomy for severe proliferative diabetic retinopathy. METHODS: Eyes that underwent vitectomy for proliferative diabetic retinopathy were followed up at least 6 months and were reviewed retrospectively. The authors reviewed functional outcomes, complications, and operation time between preoperative bevacizumab injection (group I) and non-injection groups(group II). RESULTS: Among 93 eyes of 87 patients, the injection group consisted of 44 eyes of 41 patients and the non-injection gauge group consisted of 49 eyes of 46 patients. The mean interval between injection and vitrectomy was 5.8 days. Final visual acuity significantly improved as compared to preoperative visual acuity, and group I showed better visual acuity than group II (p=0.008). Visual acuity improved logMAR 0.2 or more in 36 eyes in group I and 43 eyes in group II (p=0.167). The average duration of postoperative vitreous hemorrhage was 1.02 days in group I, and 4.02 days in group II (p=0.2.08). Recurrence of vitreous hemorrhage was not observed in group I or in 2 eyes of group II (p=0.274). Epiretinal membrane occurred in 2 eyes of group I, and in 9 eyes of group II (p=0.031). Only a single eye in group I had neovascular glaucoma after vitrectomy (p=0.527). The operation time of group I was 64.8 minutes, which was significantly shorter than 78.1 minutes of group II (p=0.018). CONCLUSIONS: Intravitreal bevacizumab injection before vitrectomy in proliferative diabetic retinopathy facilitated removal of the fibrovascular membrane, and leads to less postoperative complications and better functional outcomes. Intravitreal bevacizumab injection before vitrectomy can be considered as an effective preoperative adjuvant.

Effectiveness of Preoperative Intravitreal Bevacizumab Injections in Pars Plana Vitrectomy for Proliferative Diabetic Retinopathy

PURPOSE: To evaluate the efficacy of preoperative intravitreal bevacizumab (Avastin(R); Genetech, San Francisco, CA, USA) injections of pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR). METHODS: Thirty patients (30 eyes) who underwent PPV for treatment of PDR and received a preoperative intravitreal bevacizumab injection of 1.25 mg were retrospectively analyzed. The study group (group 1, 30 patients, 30 eyes) was compared with a control group (group 2, 29 patients, 30 eyes and matched with the study group for preoperative parameters) who underwent PPV without preoperative intravitreal bevacizumab injection. RESULTS: In both groups, visual acuity improved but there was no statistical significance. Intraoperative vitreous hemorrhage occurred in 14 eyes (46.7%) from group 1 and 11 eyes (36.7%) from group 2. There was no statistical significance of intraoperative bleeding occurrence (p=0.3). Postoperative vitreous hemorrhage occurred in 4 eyes from group 1 and 14 eyes from group 2. The group 1 had a lower incidence of postoperative hemorrhage than group 2 (p=0.005). CONCLUSIONS: Preoperative intravitreal bevacizumab injection appears effective in decreasing early postoperative vitreous hemorrhage and maybe technically helpful in PPV for PDR.

Effectiveness of Preoperative Intravitreal Bevacizumab Injections in Pars Plana Vitrectomy for Proliferative Diabetic Retinopathy

PURPOSE: To evaluate the efficacy of preoperative intravitreal bevacizumab (Avastin(R); Genetech, San Francisco, CA, USA) injections of pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR). METHODS: Thirty patients (30 eyes) who underwent PPV for treatment of PDR and received a preoperative intravitreal bevacizumab injection of 1.25 mg were retrospectively analyzed. The study group (group 1, 30 patients, 30 eyes) was compared with a control group (group 2, 29 patients, 30 eyes and matched with the study group for preoperative parameters) who underwent PPV without preoperative intravitreal bevacizumab injection. RESULTS: In both groups, visual acuity improved but there was no statistical significance. Intraoperative vitreous hemorrhage occurred in 14 eyes (46.7%) from group 1 and 11 eyes (36.7%) from group 2. There was no statistical significance of intraoperative bleeding occurrence (p=0.3). Postoperative vitreous hemorrhage occurred in 4 eyes from group 1 and 14 eyes from group 2. The group 1 had a lower incidence of postoperative hemorrhage than group 2 (p=0.005). CONCLUSIONS: Preoperative intravitreal bevacizumab injection appears effective in decreasing early postoperative vitreous hemorrhage and maybe technically helpful in PPV for PDR.

Intravitreal bevacizumab (Avastin) treatment of macular edema in branch retinal vein occlusion / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To report the safty and efficiency of intravitreal injection of bevacizumab (Avastin) in patients with macular edema (ME) due to branch retinal vein occlusion (BRVO).METHODS: A consecutive series of patients with ME due to BRVO who were treated with intravitreal bevacizumab injection (2.5g/0.1L) were retrospectively studied. Patients underwent complete ophthalmoscopic examination, including Snellen visual acuity testing, optical coherence tomography (OCT) imaging, and/or flurescence angiographic testing at baseline and follow-up visits.RESULTS: There were 32 eyes of 32 consecutive patients who received at least one intravitreal bevacizumab injections (range from 1 to 3). The mean length of follow-up was 4.7 (range from 3 to 8) months. The mean visual acuity improved from 20/200- at baseline to 20/100- at 1 month and 20/100+ at 3 months and last follow-up (P＜0.01). The mean central 1mm macular thickness was 483μm at baseline and decreased to 275, 314,and 301μm at 1 month,3 months, and last follow-up (P＜0.01)respectively.No adverse side effects were observed following injections in any eyes.CONCLUSION: Intravitreal bevacizumab (Avastin) showed a marked decrease in ME secondary to BRVO, improvement in visual acuity and lack of adverse side effects.

Anti-Tumor Effects of Vascular Endothelial Growth Factor Inhibitor on Oral Squamous Cell Carcinoma Cell Lines

Tumor angiogenesis is a process leading to formation of blood vessels within tumors and is crucial for maintaining a supply of oxygen and nutrients to support tumor growth and metastasis. Vascular endothelial growth factor(VEGF) plays a key role in tumor angiogenesis including induction of endothelial cell proliferation, migration, survival and capillary tube formation. VEGF binds to two distinct receptors on endothelial cells. VEGFR-2 is considered to be the dominant signaling receptor for endothelial cell permeability, proliferation, and differentiation. Bevacizumab(Avastin, Genetech, USA) is a monoclonal antibody against vascular endothelial growth factor. It is used in the treatment of cancer, where it inhibits tumor growth by blocking the formation of new blood vessels. The goal of this study is to identify the anti-tumor effect of Bevacizumab(Avastin) for oral squamous cell carcinoma cell lines. Human squamous cell carcinoma cell line(HN4) was used in this study. We examined the sensitivity of HN4 cell line to Bevacizumab(Avastin) by using in vitro proliferation assays. The results were as follows. 1. In the result of MTT assay according to concentration of Bevacizumab(Avastin), antiproliferative effect for oral squamous cell carcinoma cell lines was observed. 2. The growth curve of cell line showed the gradual growth inhibition of oral squamous cell carcinoma cell lines after exposure of Bevacizumab(Avastin). 3. In the apoptotic index, groups inoculated Bevacizumab(Avastin) were higher than control groups. 4. In condition of serum starvation, VEGFR-2 did not show any detectable autophosphorylation, whereas the addition of VEGF activated the receptor. Suppression of phosphorylated VEGFR-2 and phosphorylated MAPK was observed following treatment with Bevacizumab(Avastin) in a dose-dependent manner. 5. In TEM view, dispersed nuclear membrane, scattered many cytoplasmic vacuoles and localized chromosomal margination after Bevacizumab(Avastin) treatment were observed. These findings suggest that Bevacizumab(Avastin) has the potential to inhibit MAPK pathway in proliferation of oral squamous cell carcinoma cell lines via inhibition of VEGF-dependent tumor growth.

Results of Intravitreal Bevacizumab for Macular Edema with Retinal Vein Occlusion and Diabetic Macular Edema

PURPOSE: To evaluate the short-term effect and safety of intravitreally injected bevacizumab in patients with macular edema (ME) caused by retinal vein occlusion (RVO) and diabetic macular edema (DME). METHODS: We retrospectively evaluated 59 eyes of 51 patients, 29 with ME caused by RVO and 30 with DME, who received intravitreal injection of bevacizumab. Fifty-one consecutive patients (59 eyes) with ME associated with RVO and DME were treated with intravitreal injections of 1.25-2.5 mg (0.05-0.1 ml) of bevacizumab. Ophthalmic evaluation was performed at baseline and at 1, 3, 6 months after each injection. Clinical evidence of toxicity and complications, changes of visual acuity with an ETDRS chart (LogMAR), and central macular thickness (CMT) using optical coherence tomography (OCT), were evaluated. RESULTS: The follow-up period was 7.3 months (7.3+/-0.31) and the mean number of injections was 1.2. The baseline mean LogMAR was 1.06+/-0.53 and mean CMT was 479.6+/-160.4 micrometer. At 1, 3 and 6 months, the mean LogMAR was 0.90+/-0.52, 0.80+/-0.39 and 0.78+/-0.39, respectively, and the mean CMT was 316.9+/-86.7 micrometer, 281.1+/-67.4 micrometer and 278.4+/-64.6 micrometer, respectively. No adverse incidents were observed, including cataract, retinal detachment, vitreous hemorrhage, and endophthalmitis, although transient increased intraocular pressure was observed. CONCLUSIONS: Intravitreal bevacizumab injections are safe and effective in ME caused by RVO and DME.

Two Cases of Subconjunctival Bevacizumab Injection to Prevent Bleb Failure After Trabeculectomy

PURPOSE: Angiogenesis is an integral part of wound healing, which is an unwanted process in the postoperative period after trabeculectomy. It was the aim of this study to report on the subconjunctival use of bevacizumab (Avastin(R)) as an antiproliferative agent to augment trabeculectomy. CASE SUMMARY: This clinical interventional case study included 2 patients with secondary glaucoma associated with uveitis who underwent antiglaucomatous filtering surgery combined with a subconjunctival injection of bevacizumab. Limbal-based trabeculectomy was performed, and subconjunctival injections (1.25 mg/0.05 ml) were given at the end of the surgery adjacent to the bleb, which was raised using a single-use 26 gauge needle. At 1 and 2 weeks and 1, 3, and 6 months after surgery, intraocular pressure was reduced in both patients to 11 mmHg with functioning filtering blebs. No complications were observed. CONCLUSIONS: The results suggest that subconjunctival bevacizumab injection may be helpful in reducing the risk of postoperative scarring of the filtering bleb.

Intracameral bevacizumab for treatment of iris rubeosis / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:.To report the curative effect and safty of intracameral bevacizumab(avastin)in patients with rubeosis iridis.METHODS:5 cases(5 eyes)with iris rubeosis secondary to diabetic retinopathy,retinal periphlebitis(Eales disease)and branch/central retinal vein occlusion,among which 2 cases were silicon oil eyes and were performed intracameral bevacizumab(avastin)0.03 cc(0.75mg),one case is combined with trabeculectomy.and another with cyclocryosurgery.RESULTS:The rubeosis of all cases disappeared quickly,meanwhile the intraocular pressure decreased to normal range with the help of anti-glaucoma operation and medicine.There are not any sign of rubeosis again in the 2-5 months follow-up visits and intraocular pressure were well-controlled.CONCLUSION:Intracameral bevacizumab(avastin)was an effective treatment for rubeosis,esp,for some cases that can not be injected to vitreous cavity.Short term study of intracameral bevacizumab demonstrated rapid regression of rubeosis and well-tolerated injection with no obvious side effects.