Injection of intravitreal bevacizumab (Avastin) as a preoperative adjunct before vitrectomy surgery in the treatment of severe proliferative diabetic retinopathy (PDR). Intravitreal bevacizumab for prevention of early postvitrectomy hemorrhage in diabetic patients: a randomized clinical trial. Intravitreal injection of bevacizumab before vitrectomy for proliferative diabetic retinopathy. Adjuvant 5-fluorouracil and heparin prevents proliferative vitreoretinopathy : Results from a randomized, double-blind, controlled clinical trial. Intravitreal bevacizumab for surgical treatment of severe proliferative diabetic retinopathy. Randomized trial of intravitreal bevacizumab alone or combined with triamcinolone versus macular photocoagulation in diabetic macular edema. Bevacizumab compared with macular laser grid photocoagulation for cystoid macular edema in branch retinal vein occlusion. Effects of major liver resection, with or without recombinant bactericidal/permeability-increasing protein (rBPI21), on the angiogenic profile of patients with metastatic colorectal carcinoma. Randomized phase II study of erlotinib combined with bevacizumab compared with bevacizumab alone in metastatic renal cell cancer.
To evaluate the use of preoperative intravitreal bevacizumab (IVB) in patients undergoing pars plana vitrectomy (PPV) for complications of proliferative diabetic retinopathy (PDR).
                We studied 22 patients with severe PDR. A preoperative complexity score (CS) was recorded. Eleven eyes were treated with IVB, 1.25 mg, 5-7 days before PPV (group 1), and 11 eyes underwent direct PPV (group 2). Surgical time and intra-operative manoeuvres were recorded. Main outcome measure was feasibility of surgery, secondary goal was the visual and anatomic outcome at 6 months.
                The average CS was 5.5, and was similar in the two groups. Mean surgical time was 57 minutes in group 1 vs 83 minutes in group 2; mean tool exchanges was 27 vs 53, intraoperative bleeding 5 vs 15, endodiathermy 2 vs 9. No complications were recorded after IVB. Mean pre-operative BCVA was 1.87 logMAR in group 1 and logMAR 2.04 in group 2. Mean pre-operative BCVA was 1.87 logMAR in the bevacizumab group and 2.04 logMAR in group 2, not significantly different (p = 0.7). Mean post-operative BCVA at 6 months was 0.88 logMAR in group 1 and logMAR 2.01 in control group 2, significantly different (p = 0.01). Post-operative BVCA improved in bevacizumab group from pre-operative value (p = 0.15), while in control group there was non-significant increase (p = 0.96). Anatomical attachment was achieved in 11 patients in group 1 vs nine patients in group 2.
                IVB administered prior to vitrectomy was well tolerated and reduced active neovascularization, thus facilitating PPV. To evaluate the effect of preoperative intravitreal bevacizumab (IVB) injection on the rate of early (< or =4 weeks) postvitrectomy hemorrhage in patients with proliferative diabetic retinopathy (PDR).
                Prospective, randomized, double-masked clinical trial.
                Sixty-eight eyes of 68 patients undergoing pars plana vitrectomy for management of PDR complications.
                Eligible eyes were assigned randomly to 1 of 2 groups: the IVB group received 1.25 mg intravitreal bevacizumab 1 week before surgery, and the control group underwent a sham procedure.
                The primary outcome measure was the incidence of early postvitrectomy hemorrhage. Secondary outcome measures included changes in best-corrected visual acuity (BCVA) and IVB-related adverse events.
                Of 68 eyes, 35 and 33 eyes were in the IVB and control groups, respectively. In the intention-to-treat analysis, the incidence of postvitrectomy hemorrhage 1 week and 1 month after surgery was significantly lower in the IVB group compared with the control group (P = 0.023 and P = 0.001, respectively). Mean BCVA improved from 1.88 logarithm of minimum angle of resolution (logMAR) units in both study groups before surgery to 0.91 logMAR units and 1.46 logMAR units 1 month after vitrectomy in the IVB and control groups, respectively (P = 0.001). Resolution of vitreous hemorrhage was observed in 9 eyes (25.7%) after IVB injection, obviating the need for vitrectomy; the corresponding figure was 2 eyes (6.1%) in the control group (P = 0.028). The per-protocol analysis included 16 eyes in the IVB group and 18 eyes in the control group; postvitrectomy hemorrhage occurred less frequently 1 week and 1 month after surgery in the IVB group compared with the control group (P = 0.033 and P = 0.003, respectively). Mean improvement in BCVA 1 month after vitrectomy was -1.05 logMAR units in the IVB group and -0.42 logMAR units in the control group (P = 0.004). No IVB-related complication was observed in the treatment group.
                Intravitreal injection of bevacizumab 1 week before vitrectomy seems to reduce the incidence of early postvitrectomy hemorrhage in diabetic patients. The need for vitrectomy also may be decreased significantly in these cases. To evaluate the use of preoperative intravitreal bevacizumab (IVB) injection in patients undergoing pars plana vitrectomy for complications of proliferative diabetic retinopathy (PDR).
                In this prospective surgeon-masked randomized clinical trial, 40 eyes of 40 diabetic patients who were candidates for vitrectomy were randomly assigned to receive 2.5 mg IVB 3-5 days before operation (injected group) or no injection before operation (noninjected group). A preoperative complexity score (CS) was recorded. Best-corrected visual acuity, number of endodiathermy applications, backflush needle applications, duration of surgery, and postoperative vitreous hemorrhage were recorded.
                Twenty-two patients with a CS of 6+/-0.95 in the injected group and 18 patients with a CS of 5.7+/-1.1 in the noninjected group (p=0.3) were studied. Postoperative visual acuities were significantly better than preoperative visual acuities. Preoperative and 3-month postoperative visual acuities were the same for both groups; however, in the last follow-up examinations (mean 7+/- 3.6 months) the injected group had better visual acuities than the noninjected group (1.1+/-0.4 and 1.4+/-0.3 logMAR, respectively, p=0.006). Mean surgical time was 62+/-57.3 minutes in the injected group vs 95.5+/-36 minutes in the noninjected group (p=0.03): endodiathermy applications 6.0+/-4.3 vs 11.0+/-5.8 (p=0.004), backflush cannula applications 11.0+/-7.2 vs 18.1+/-7.8 (p=0.004). In non-silicone-filled eyes, no patient in the injected group developed significant postoperative vitreous hemorrhage obscuring the fundus details, while 7 eyes of noninjected eyes had this complication (p=0.01).
                IVB injection before vitrectomy for PDR facilitates the surgery, and may decrease the rate of postoperative vitreous hemorrhage and improve the visual acuity results of the operation. To assess the safety and efficacy of adjuvant combination therapy using 5-fluorouracil (5-FU) and low molecular weight heparin (LMWH) for prevention of proliferative vitreoretinopathy (PVR) after vitrectomy and retinal reattachment surgery.
                Prospective randomized, double-masked, placebo controlled trial.
                One hundred seventy-four high-risk patients were randomized to receive either 5-FU and LMWH therapy or placebo. Patients were selected from all patients undergoing primary vitrectomy for rhegmatogenous retinal detachment.
                Results of standard surgery with 5-FU and LMWH therapy or placebo were compared at the 6-month follow-up.
                Development of postoperative PVR, retinal reattachment at 6 months after surgery, single operation reattachment rate, number of reoperations, and best-corrected visual acuity.
                There were 87 patients in the 5-FU and LMWH therapy group and 87 in the placebo group. The incidence of postoperative PVR was significantly lower (P = 0.02) in the 5-FU and LMWH therapy compared with the placebo group. In 26.4% (23/87) of the placebo group and in 12.6% (11/87) of the 5-FU and LMWH group, postoperative PVR developed. In the 5-FU and LMWH group, the number of patients undergoing more than one operation was 19.5% (17/87) and the number of reoperations resulting from PVR was 52.9% (9/17). In the placebo group, the number of patients undergoing more than one operation was 25.3% (22/87) and the number of reoperations resulting from PVR was 72.7% (16/22). The difference in visual acuity was not statistically different in the two treatment groups, although those patients in whom postoperative PVR developed tended to have poorer vision (P < 0.0001). There were no differences in complication rates between the two groups.
                There is a significant reduction in the incidence of postoperative PVR in patients receiving the 5-FU and LMWH therapy and in the reoperation rate resulting from PVR. This trial shows that incidence of PVR can be reduced with inexpensive and simple pharmacologic treatment with 5-FU and LMWH and should be used routinely in the treatment of patients at risk of developing PVR. The purpose of this study is to evaluate the role, the safety and the effectiveness of intravitreal bevacizumab (IVB) injections as an adjunct to vitrectomy in the management of severe proliferative diabetic retinopathy (PDR).
                Case-Control Study
                Randomized controlled trial performed on 72 eyes of 68 patients affected by vitreous haemorrhage (VH) and tractional retinal detachment (TRD), which occurred as a consequence of active proliferative diabetic retinopathy (PDR). We randomly assigned eligible patients in a 1: 1: 1 ratio to receive a sham injection or an intravitreal injection of 1.25 mg of bevacizumab, either 7 or 20 days before the vitrectomy. In order to obtain three homogeneous groups of surgical complexity, we assigned to the following preoperative parameters a score from 0 to 3: a) vitreous haemorrhage, b) prior retinal laser-photocoagulation, c) morphological types of retinal detachment such as focal, hammock, central diffuse, table-top. Complete ophthalmic examinations and color fundus photography were performed at baseline and 1, 6, 12, and 24 weeks after the surgery.
                Intraoperative management, safety, efficacy of IVB at different time injection as an adjunct to vitrectomy in the management of severe PDR RESULTS: Group A (sham injection): intraoperative bleeding occurred in 19 cases (79.1%), the use of endodiathermy was necessary in 13 patients (54.1%), relaxing retinotomy was performed on one patient (4.1%), and in four cases (16.6%) iatrogenic retinal breaks occurred. The surgical mean time was 84 minutes (SD 12 minutes). Group B (bevacizumab administered 7 days before vitrectomy): intraoperative bleeding occurred in two cases (8.3%) and the use of endodiathermy was necessary in two patients (8.3%). No iatrogenic breaks occurred during the surgery. The surgical mean time was 65 minutes (SD 18 minutes). Group C (bevacizumab administered 20 days before vitrectomy): intraoperative bleeding occurred in three cases (12.5%), the use of endodiathermy was necessary in three patients (1.5%), and an iatrogenic break occurred in one patient (4.1%) while the delamination of fibrovascular tissue was being performed. The surgical mean time was 69 minutes (SD 21 minutes). The average difference in the surgical time was statistically significant between group A and group B (p = 0.025), and between group A and group C (p = 0.031). At the end of the surgery, the retina was completely attached in all eyes. At the 6-month follow-up, we observed the development of tractional retinal detachment (TRD) in one out of 24 patients from group C (4%).
                A preoperative intravitreal injection of bevacizumab may represent a new strategy for the surgical treatment of severe PDR by reducing retinal and iris neovascularization: this would make surgery much easier and safer, thus improving the anatomical and functional prognosis. According to our study, the best surgical results are achieved performing the IVB 7 days preoperatively. To compare the results of intravitreal bevacizumab (IVB) injection alone or in combination with intravitreal triamcinolone acetonide (IVT) versus macular laser photocoagulation (MPC) as a primary treatment of diabetic macular edema (DME).
                Randomized 3-arm clinical trial.
                A total of 150 eyes of 129 patients with clinically significant DME and no previous treatment.
                The eyes were randomly assigned to 1 of the 3 study arms: the IVB group, patients who received 1.25 mg IVB (50 eyes); the IVB/IVT group, patients who received 1.25 mg of IVB and 2 mg of IVT (50 eyes); and the MPC group, patients who underwent focal or modified grid laser (50 eyes). Retreatment was performed at 12-week intervals whenever indicated.
                Change in best-corrected visual acuity (VA) at week 24.
                VA changes among the groups were statistically significant at 6 (P<0.001) and 24 (P = 0.012) weeks. The significant treatment effect was demonstrated in the IVB group at all follow-up visits and in the IVB/IVT group at 6 and 12 weeks. VA changes +/- standard deviation at 36 weeks were -0.28+/-0.25, -0.04+/-0.33, and +0.01+/-0.27 logarithm of minimum angle of resolution in the IVB, IVB/IVT, and MPC groups, respectively (P = 0.053). Significant central macular thickness (CMT) reduction was observed in all groups only up to 6 weeks; however, CMT changes were not significant among the groups in all visits. Overall, retreatment was required for 27 eyes up to 36 weeks (14 in the IVB group, 10 in the IVB/IVT group, and 3 in the MPC group). In the IVB group, in which a greater VA improvement was observed, only 1 injection was required in 72% of the cases. VA improvement >2 Snellen lines at 36 weeks was detected in 37%, 25%, and 14.8% of patients in the IVB, IVB/IVT, and MPC groups, respectively.
                Intravitreal bevacizumab injection in patients with DME yielded a better visual outcome at 24 weeks compared with macular photocoagulation. A change in CMT beyond the 6-week time point that corresponded to the vision change was not detected. No adjunctive effect of IVT was demonstrated.
                The author(s) have no proprietary or commercial interest in any materials discussed in this article. To evaluate the outcome of cystoid macular edema treated with intravitreal injections of bevacizumab and macular grid laser photocoagulation (GLP), in patients with perfused branch retinal vein occlusion.
                Thirty eyes of 30 consecutive patients with cystoid macular edema secondary to nonischemic branch retinal vein occlusion were assigned to either GLP group or to intravitreal bevacizumab (IB) group. Complete ophthalmologic examinations were performed just before GLP and IB injection at 1, 3, 6, and 12 months after treatment. Changes in logarithm of minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA), central macular thickness (CMT) shown by optical coherence tomography-3 were evaluated.
                Baseline BCVA (logMAR) and CMT were, respectively, 0.89 +/- 0.13 and 650 +/- 140 microm for the GLP group, 0.87 +/- 0.16 and 690 +/- 120 microm for the IB group. After the treatment, at 1, 3, 6, and 12 months in the GLP group, BCVA had improved by 0.19, 0.22, 0.21, and 0.20 logMAR, CMT had decreased by 40%, 41.3%, 40.5%, and 42%. In the IB group, BCVA had improved by 0.31, 0.32, 0.30, and 0.31 logMAR and CMT had decreased by 59.5%, 59%, 60%, and 60.3%. The group receiving bevacizumab had better BCVA and lower CMT values at all time points (P < 0.05).
                Intravitreal bevacizumab injection improves BCVA and reduces CMT more than GLP. Intravitreal bevacizumab injection was well tolerated and could be used as primary treatment in patients with cystoid macular edema secondary to perfused branch retinal vein occlusion. Surgery induces a process of wound healing, which has immunological and angiogenic aspects. Bactericidal/permeability-increasing protein (BPI) is found in azurophilic granules of human neutrophils, which is bactericidal and neutralizes lipo-polysaccharide (LPS). This may reduce postoperative infectious complications. In addition, BPI has been shown to be an inhibitor of angiogenesis.
                A total of 18 patients with metastasized colorectal carcinoma to the liver were double blind randomized. The levels of the pro-angiogenic factors interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) and the angiogenesis inhibitor endostatin were investigated after liver surgery with perioperative administration of either rBPI(21) or placebo.
                The highest IL-6 levels were found during the first 24 hr and reached peak levels already at 2 hr postoperatively in both groups. In both groups VEGF levels decreased sharply in the postoperative hours, returning to baseline levels in the days afterwards. In both groups, an immediate decrease in endostatin levels was observed which remained significantly low. RBPI(21) transiently influenced IL-6 and VEGF.
                RBPI(21) only marginally affected IL-6 and VEGF levels. Surgery per se induced an immediate immune response (IL-6) and an immediate angiogenic response, reflected in an initial VEGF decrease and a longer lasting decrease of endostatin. These findings demonstrate the dynamics of tissue responses in the first phase of wound healing.
                Copyright 2003 Wiley-Liss, Inc. Bevacizumab (Bev) has clinical activity in advanced renal cell carcinoma (RCC), and, when combined with erlotinib (Erl), has shown encouraging objective response rate (ORR) and progression-free survival (PFS). We performed a phase II, randomized, double-blind, multicenter, placebo-controlled trial to assess whether Erl provides additional clinical benefit with regard to PFS and ORR when combined with Bev in first-line treatment of metastatic RCC.
                One hundred four patients received intravenous Bev (10 mg/kg) every 2 weeks in combination with oral Erl (150 mg) or placebo daily. Patients were treated until progression or toxicity.
                A landmark analysis was performed 9 months after enrollment was completed (median follow-up, 9.8 months). Sixty-five patients had discontinued therapy; time to study discontinuation did not differ between the two treatment groups. The median PFS was 9.9 months (Bev + Erl [B+E]) versus 8.5 months (Bev; hazard ratio = 0.86; 95% CI, 0.5 to 1.49; P = .58). ORR (complete plus partial) was 14% (B+E) versus 13% (Bev). One complete response occurred in the B+E group. Median survival was 20 months for B+E but not reached for Bev. The most common grade 3/4 adverse events (> 5% of patients) were hypertension, rash, proteinuria, diarrhea, and hemorrhage. One treatment-related death occurred on study (GI perforation, B+E group).
                The addition of Erl to Bev was well tolerated, but did not provide additional clinical benefit compared with Bev alone. Bev has encouraging clinical activity for previously untreated metastatic RCC patients.
Results from one of the included studies support the use of preoperative intravitreal bevacizumab to reduce the incidence of early POVCH. There are currently no other high quality RCTs that support the use of anti-VEGF agents perioperatively to reduce the incidence of early or late POVCH. The remaining studies identified by the search suggest that the preoperative use of bevacizumab may reduce the incidence of early POVCH, but it should be recognised that there are a number of significant methodological issues in these studies that lead us to be cautious when interpreting their findings and make any definitive conclusions unwarranted.