Topical Bevacizumab Research Articles

Clinical Outcomes of Topical Bevacizumab for the Treatment of Corneal Neovascularization.

Background and objective In corneal neovascularization, the peri-corneal vascular structure grows into a normally avascular cornea. This is due to an imbalance between the angiogenic and anti-angiogenic factors that sustain corneal transparency. There are various etiologies of this condition, and they can be divided into infective or non-infective causes, such as inflammation, trauma, or surgical causes. Corneal neovascularization has been shown to improve with the current treatments using steroids and anti-vascular endothelial growth factors. This study aimed to evaluate the effectiveness of topical bevacizumab as an anti-angiogenic agent in patients with corneal neovascularization. Methods This retrospective study included patients who suffered corneal neovascularization of various etiologies and completed six months of topical bevacizumabtherapy between 2020 and 2022 at the Universiti Kebangsaan Malaysia Medical Centre. Results A total of 16 patients received treatment with topical bevacizumab over the three-yearstudy period. Based on specified inclusion and exclusion criteria, 12 patients were eligible for inclusion in this study. Eight patients (66%) showed improvement in terms of either 'clock hours' of improvement, morphology, or regression of corneal neovascularization. All infective causes of corneal neovascularization showed improvement on completion of bevacizumab compared to other causes. Conclusion Topical bevacizumab can be one of the treatment choices for corneal neovascularization. As the outcome varies depending on the severity and chronicity of the condition, the attending ophthalmologist should treat each case differently. Although topical bevacizumab is more effective in mild and moderate cases, the indications for its use in chronic cases remain debatable as the results are unfavorable in such cases.

Suppression of Neovascularization by Topical and Subconjunctival Bevacizumab After High-Risk Corneal Transplantation

To assess the effectiveness of topical and subconjunctival bevacizumab in suppressing vascularization in graft and host bed after high-risk corneal transplantation. Secondary analysis of prospective, randomized, double-blind, placebo-controlled multicentric clinical trial. The study includes patients aged > 18 years who underwent high-risk penetrating keratoplasty, which was defined as corneal vascularization in ≥ 1 quadrants of the corneal graft and host bed, excluding the limbus. Patients were randomized to treatment and control groups. The patients in the treatment group received subconjunctival injection of bevacizumab (2.5 mg/0.1 ml) on the day of the procedure, followed by topical bevacizumab (10 mg/ml) 4 times per day for 4 weeks. The patients in control group received injection of vehicle (0.9% sodium chloride) on the day of procedure, followed by topical vehicle (carboxymethylcellulose sodium 1%) 4 times a day for 4 weeks. Vessel and invasion area of vessels in the corneal graft and host beds. This study included 56 eyes of 56 patients who underwent high-risk corneal transplantation, with equal numbers in the bevacizumab and vehicle (control) treatment groups. The mean age of patients who received bevacizumab was 61.2 ± 15.9 years, and the mean age of those treated with vehicle was 60.0 ± 16.1 years. The vessel area at baseline was comparable in the bevacizumab (16.72% ± 3.19%) and control groups (15.48% ± 3.12%; P= 0.72). Similarly, the invasion areas were also similar in the treatment (35.60% ± 2.47%) and control (34.23% ± 2.64%; P= 0.9) groups at baseline. The reduction in vessel area was significantly higher in the bevacizumab-treated group (83.7%) over a period of 52 weeks compared with the control group (61.5%; P < 0.0001). In the bevacizumab-treated group, invasion area was reduced by 75.8% as compared with 46.5% in the control group. The vessel area was similar at 52 weeks postprocedure in cases of first (3.54% ± 1.21%) and repeat (3.80% ± 0.40%) corneal transplantation in patients who received bevacizumab treatment. In the vehicle-treated patients, the vessel area was significantly higher in repeat (9.76% ± 0.32%) compared with first (8.06% ± 1.02%; P < 0.0001) penetrating keratoplasty. In the bevacizumab treatment group, invasion areas at week 52 were comparable in first (11.70% ± 3.38%) and repeat (11.64% ± 1.74%) procedures, whereas invasion area was significantly higher in repeat (27.87% ± 2.57%) as compared with first (24.11% ± 2.17%) penetrating keratoplasty in vehicle-treated patients. In patients undergoing vascularized high-risk corneal transplantation, bevacizumab is efficacious in reducing vascularization of corneal graft and host bed, thereby reducing the risk of corneal graft rejection in vascularized host beds. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Intermittent Topical Bevacizumab for Treatment of Pediatric Corneal Neovascularization after Keratitis

Introduction : Corneal neovascularization imposes pediatric patients to risk of amblyopia. Current treatment of corneal neovascularization consists of topical steroids, nonsteroidal anti-inflammatory medications, immunomodulatory agents, anti-Vascular Endothelial Growth Factor (anti-VEGF) and few surgical procedures. Anti-VEGF shows promising results in treating corneal neovascularization but is difficultto obtain in developing countries such as Indonesia. We report intermittent topical use of Bevacizumab as antiVEGF in a child experiencing corneal neovascularization in the settings of limited antiVEGF availability.&#x0D; Case Illustration : A 5-year-old girl presented with corneal neovascularization after keratitis. Topical fluorometholone 4 times a day for 3 weeks was given with no clinical improvement. An intermittent topical Bevacizumab was started, each episode of treatment lasted 4 days. Corneal neovascularization regressed after 1 episode of treatment and thus continued until a total of 2 treatment episodes. She improved clinically on treatment, with some residual corneal scarring. Visual acuity improved from logMar 0.5 to logMar 0.2 following treatment.&#x0D; Discussion : Bevacizumab regresses corneal neovascularization by inhibiting proangiogenic factor VEGF which is upregulated in neovascularization. Topical Bevacizumab ability to penetrate cornea was contributed by defective corneal epithelial overlying neovascularization. Long-term use of antiVEGF may hinder VEGF beneficial role on wound recovery and trigger unwanted side effects.&#x0D; Conclusion : Intermittent short-term use of topical bevacizumab may be effective to treat corneal neovascularization during acute period in pediatric patient and is safely tolera

Long-term effects of intraoperative topical bevacizumab in sutureless scleral tunnel trabeculectomy: a prospective clinical trial.

To investigate the long-term efficacy and safety of the novel method sutureless trabeculectomy with topical administration of bevacizumab. Primary open-angle glaucoma patients with intraocular pressure (IOP) > 21mmHg despite maximum tolerated medication were included in a single-blind prospective interventional clinical trial. Group 1 underwent sutureless scleral tunnel trabeculectomy with intraoperative topical administration of bevacizumab (1.25mg) applied on the scleral incision for 1min. Group 2 underwent sutureless trabeculectomy alone and group 3 (control group) underwent conventional trabeculectomy with mitomycin C (MMC). Outcome measures were surgical success, IOP, number of needed anti-glaucoma medications, and complications. Patients were followed for two years. Finally, 50 eyes from group 1, 46 from group 2, and 47 from group 3 were analyzed. At the end of 24months, 52% (n = 26) of group 1, 34.8% (n = 16) of group 2, and 57.4% (n = 27) of group 3 had complete success (IOP < 18mmHg without medication). The difference was only significant between groups 2 and 3 (p = 0.003). 94% (n = 47) of group 1, 89.1% (n = 41) of group 2, and 91.5% (n = 43) of group 3 had qualified success (IOP < 18mmHg with ≤ 2 anti-glaucoma medications) (p = 0.69). There was a significant difference in the overall IOP mean between the three groups (p < 0.0001). There was no significant difference between the three groups in complication rates and the number of needed anti-glaucoma medications for IOP control. Sutureless trabeculectomy with topical application of bevacizumab showed comparable surgical success rates with conventional trabeculectomy and MMC in long-term follow-up. Additionally, adjuvant use of topical bevacizumab had a significant positive impact on long-term IOP control.

Effect of topical motesanib in experimental corneal neovascularization model.

This study aimed to compare the efficacy of topical bevacizumab and motesanib in an experimental corneal neovascularization model, and find the most effective motesanib dose. In experiments, 42 Wistar Albino rats were randomly divided into six groups (n = 7). Corneal cauterization was applied to all groups except the group 1. Group 1did not receive any treatment. Topical dimethylsulfoxide was applied toshamgroupthree times a day(tid). Topical bevacizumab drops (5mg/ml) were applied to Group 3 tid. Topical motesanib drops with a dose of 2.5, 5, and 7.5mg/ml were respectively applied in Groups 4, 5, and 6 tid. On the 8th day, corneal photographs of all rats were taken under general anesthesia, and the percentage of corneal neovascular area was calculated. VEGF-A mRNA, VEGFR-2 mRNA, miRNA-21, miRNA-27a, miRNA-31, miRNA-126, miRNA-184, and miRNA-204 were evaluated by the qRT-PCR method in corneas taken after decapitation. The percentage of corneal neovascularization areas and VEGF-A mRNA expression levels were decreased in all treatment groups compared to group 2 (p < 0.05). VEGFR-2 mRNA levels were found to be statistically significantly decreased in groups 4 and 6 compared to group 2 (p < 0.05).Statistically significant changes were detected in the expression levels of only miRNA-126 among all miRNAs. Motesanib with a dose of 7.5mg/ml statistically significantly suppressed the VEGFR-2 mRNA level compared with other treatment doses and may be more effective than bevacizumab. Further, miRNA-126 can be used as a proangiogenic marker.

Evaluation of effect of nilotinib in an experimental corneal neovascularization model

Aim: This study aims to investigate the neovascularization-inhibiting effect of topical nilotinib and to determine the effective dose of nilotinib.&#x0D; Material and Method: In this study, 42 healthy Wistar albino rats were randomly divided into six groups. The left corneas of all rats except group 1 were cauterized with silver nitrate. Group 1 was the healthy control, with no corneal vascularization, which did not receive any treatment; Group 2 (sham) did not receive treatment, only topical DMSO; Groups 3, 4, and 5 received topical nilotinib at doses of 10, 20, and 40 μM three times a day, respectively; Group 6 received 5 mg/dL topical bevacizumab three times for a day for seven days. On the 8th day, photographs of the corneas were taken, and the percentage of corneal neovascularization area was calculated. Following all rats being killed via anesthesia, the corneas were removed to determine the levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) ELISA and corneal immune staining. &#x0D; Results: Other than Group 3, the percentage of neovascular corneal area was lower in the treatment groups compared to Group 2 (p

Bevacizumab in High-Risk Corneal Transplantation: A Pilot Multicenter Prospective Randomized Control Trial

To determine the efficacy of local (subconjunctival and topical) bevacizumab (Avastin) treatment in patients undergoing vascularized high-risk corneal transplantation. Pilot, prospective, randomized, double-blind, placebo-controlled clinical trial conducted at 5 clinical centers in the United States, India, and Brazil. Patients aged > 18 years undergoing high-risk penetrating keratoplasty, defined as corneal neovascularization (NV) in 1 or more quadrants ≥2 mm from the limbus or extension of corneal NV to the graft-host junction in a previously failed graft. Patients were randomized to receive subconjunctival bevacizumab (2.5 mg/0.1 ml) or placebo at the time of surgery, followed by topical bevacizumab (10 mg/ml) or topical placebo, administered 4 times per day for 4 weeks. The 52-week endothelial immune rejection rate. Ninety-two patients were randomized to receive bevacizumab (n= 48) or control (n= 44). The 52-week endothelial rejection rate was 10% in the bevacizumab group and 19% in the control group (P= 0.20). Post hoc, extended follow-up at the lead study site showed an endothelial rejection rate of 3% in the bevacizumab group and 38% in the control group (P= 0.003). Treatment with bevacizumab was found to have a hazard ratio of 0.15 (95% confidence interval, 0.03-0.65, P= 0.01) in a post hoc Cox regression analysis. In patients undergoing vascularized high-risk corneal transplantation, there was no statistically significant difference in the rate of endothelial rejection at 1 year in the bevacizumab treatment group compared with the control group. This study may have been underpowered to detect a difference between treatment groups, and taken together, our data suggest that, in the current trial design, bevacizumab has a positive but not (yet) significant effect on endothelial rejection.

Recurrent Pterygium: A Review.

Purpose:To summarize the recent evidence regarding different aspects of pterygium recurrence.Methods:Human-based studies from PubMed, Scopus, and Google Scholar were identified using the following keywords: conjunctival disease, pterygium, recurrent pterygium, pterygium recurrence, pterygium management/surgery, conjunctival autograft (CAU), amniotic membrane graft/transplant, and adjuvant therapy (January 2009 to February 2021). We reviewed risk factors associated with the recurrence of pterygium, timing of recurrence, medical treatments to prevent from recurrence, and nonsurgical and surgical alternatives for management of recurrence.Results:Dry eye disease, black race, and young age are considered definite risk factors for recurrence. However, fleshy appearance of the pterygium and preoperative size remain controversial. Surgical techniques such as excessive suturing, insufficient conjunctival graft size, thick conjunctival graft with remained Tenon tissue, and postoperative graft retraction are considered possible risk factors for recurrence. Using fibrin glue instead of sutures can further reduce recurrence rates. Although recurrence could occur even after many years, most recurrences happen in the first 3–6 months after surgery. Multiple kinds of adjuvant medications are used before, during, or after the operation including mitomycin C (MMC), 5-fluorouracil (5-FU), corticosteroids, and anti-vascular endothelial growth factors (anti-VEGFs). Multiple weekly subconjunctival 5-FU injections are shown to be safe and effective in halting the progression of recurrent pterygium. Although topical bevacizumab is found to inhibit the growth of impending recurrent pterygium, the effect is mostly temporary. CAU is superior to amniotic membrane transplantation in the treatment for recurrent pterygia.Conclusions:There is yet to be a panacea in treating recurrent pterygium. Currently, there is not a globally accepted recommendation for treating recurrent pterygium with anti-VEGFs or 5-FU as a nonsurgical treatment. We strongly recommend using MMC as an adjunct to surgery in recurrent cases, with consideration of its specific complications. CAU is the most effective surgical treatment for recurrent pterygium, and other new surgical therapies need further investigation.

Effect of Bevacizumab on the Viability and Metabolism of Human Corneal Epithelial and Endothelial Cells: An In Vitro Study.

PurposeTo examine the cytotoxic effects of bevacizumab on the viability and metabolism of human corneal epithelial cells (HCEpCs) and human corneal endothelial cells (HCEnCs), as well as human retinal pigment epithelial (ARPE-19) cells for comparison.MethodsImmortalized cell lines of HCEpCs, HCEnCs, and ARPE-19 cells were exposed to clinically relevant concentrations of bevacizumab (0.313–5.00 mg/mL). The ApoTox-Glo Triplex Assay was used to assess cell viability, cytotoxicity, and apoptosis, and the Mitochondrial ToxGlo Assay was used to assess cell membrane integrity and adenosine triphosphate (ATP) levels after a 24-hour treatment period.ResultsAcross all three cell types, we observed similar results of a decrease in cell viability at 5.00 mg/mL (P < 0.05) and an increase in cytotoxicity at 5.00 mg/mL (P < 0.05), whereas apoptotic activity remained unchanged (P > 0.05), which is a profile consistent with cells undergoing primary necrosis at high concentrations. Additionally, cell membrane integrity was compromised at 5.00 mg/mL (P < 0.05), whereas no decrease in ATP levels were observed (P > 0.05). Thus, no interference with mitochondrial oxidative phosphorylation in ATP production was seen, and the cells were able to maintain normal metabolic levels at high concentrations of bevacizumab.ConclusionsHCEpCs, HCEnCs, and ARPE-19 cells experience a decrease in viability and undergo primary necrosis when exposed to bevacizumab at a concentration of 5.00 mg/mL; however, they are able to maintain normal metabolism and mitochondrial function at the high concentrations used for the treatment of corneal neovascularization.Translational RelevanceThis study provides safety data on the concentrations of bevacizumab injected intravitreally and complements clinical data showing toxicity of topical bevacizumab on corneal epithelial and endothelial cells.

Corneal Recovery Following Rabbit Peripheral Blood Mononuclear Cell–Amniotic Membrane Transplantation with Antivascular Endothelial Growth Factor in Limbal Stem Cell Deficiency Rabbits

Background: Limbal stem cell deficiency (LSCD) is a refractory ocular surface disorder characterized by progressive corneal epithelial degeneration, conjunctivalization, and neovascularization, potentially leading to blindness. There are currently no effective therapeutic options for patients experiencing routine symptomatic treatment failure. Transplantation of amniotic membrane (AM) with adherent stem cells (but not bare AM transplantation alone) has shown promise in preclinical studies for ocular surface restoration. A major limitation, however, is finding a reliable stem cell source. Stem cells can be isolated from the peripheral blood mononuclear cell (PBMC) population, and these PBMC-derived stem cells have numerous advantages over allogeneic and other autologous stem cell types for therapeutic application, including relative ease of acquisition, nonimmunogenicity, and the absence of ethical issues associated with embryonic stem cells. Experiment: We examined the efficacy of autologous PBMC-AM sheet cultures combined with postoperative antiangiogenesis treatment for corneal restoration in LSCD model rabbits. Rabbit PBMCs (rPBMCs) were isolated, labeled with EdU for in vivo tracing, and then cultured on AMs in conditioned medium before transplantation. Rabbits were transplanted with bare AMs (group 1), rPBMC-AM sheets (group 2), or rPBMC-AM sheets plus postoperative treatment with the vascular endothelial growth factor antagonist bevacizumab (group 3). Corneal opacity and neovascularization were monitored by slit-lamp imaging for 8 weeks and corneas were examined histologically at 1 and 2 months. Results: Corneal opacity decreased in all three groups over 8 weeks, but was significantly lower in group 2 and even lower in group 3. Corneal neovascularization was significantly higher in group 1 throughout the observation period, and significantly lower in group 3 than group 1 and 2 by 8 weeks post-transplant. At 4 weeks, the corneal surface completed epithelialization (although thinner than normal) in group 3 but still patchy in groups 1 and 2. By 8 weeks, the epithelium in group 3 was complete and smooth, resembling a normal epithelium. Integrin β1 as a progenitor marker was also generally higher in groups 2 and 3. Conclusions: Autologous rPBMC-AM sheets with post-transplant topical bevacizumab can effectively facilitate corneal epithelium recovery in a LSCD model, suggesting clinical utility for LSCD-related ocular surface diseases. Impact statement Limbal stem cell deficiency (LSCD) increases corneal opacity and vascularization, resulting in severe visual impairment or even blindness. Traditional surgical limbal transplant is currently the main treatment option for LSCD, but carries the risks of rejection and immunosuppressant side effects. Autologous stem cell-based therapy is a promising alternative approach, but a reliable stem cell source is a major limitation. We report that transplantation of autologous rabbit peripheral blood mononuclear cell-amniotic membrane sheets plus antivascular endothelial growth factor restored avascular transparent cornea in a rabbit LSCD model. These results demonstrate a potentially effective approach for ocular surface reconstruction in bilateral LSCD.

Long-term topical bevacizumab for prevention of corneal graft rejections.

To evaluate the safety and efficacy of 1% topical bevacizumab (10 mg/mL) on newly formed corneal neovascularization (NV) after penetrating keratoplasty (PK). This is a retrospective case series reporting three eyes (three patients) of with newly formed corneal NV after corneal transplantation. All eyes had pre-existing corneal NVs and were high risk corneal graft rejection cases. One percent topical bevacizumab was started immediately after corneal NV formation post-PK. Topical bevacizumab was kept at twice weekly throughout the follow-up period. Regression of corneal NV without donor graft invasion was noted in all three patients (100%). Duration of topical bevacizumab use was 13 to 36 months. All three corneal grafts (100%) remained clear and no signs of graft rejection were noted for the period of observation. There were no associated systemic or ocular adverse effects. Long-term use of topical 1% bevacizumab may be a safe and efficient treatment for corneal NVs and prevention of graft rejections after corneal transplantation.

Efficacy of topical bevacizumab 0.05% eye drops in dry eye disease: A double-masked, randomized trial.

The objective of this double-masked, placebo-controlled, randomized trial was to assess the efficacy and safety of bevacizumab 0.05% eye drops in dry eye patients. This study included Dry Eye Workshop Study (DEWS) Grade 3–4 dry eye participants (n = 31) whose tear break-up time (TBUT) was ≤5 seconds(s). Participants were randomized to undergo treatment with either bevacizumab 0.05% eye drops (n = 19) or placebo (n = 12). The primary outcome was TBUT, and the proportion of responders (increase of ≥3s in TBUT at week 12), ocular surface disease index (OSDI) score, Schirmer test, and Oxford scheme grade were secondary outcomes. All outcomes were measured at 1-, 4- and 12 weeks. TBUT in bevacizumab group differed significantly from TBUT in placebo group within 12 weeks (P = 0.001). Moreover, the improvement of TBUT in bevacizumab group versus placebo group at 4- and 12 weeks differed significantly from that difference at baseline (P = 0.002 and P = 0.003, respectively). The proportion of participants achieving increase of 3 seconds or more of TBUT at week 12 in the bevacizumab group was significantly greater than that in the placebo group (P = 0.02). Oxford scheme grade at 1-, 4- and 12 weeks differed significantly from the values at baseline in bevacizumab group (P = 0.001, P = 0.01, and P = 0.03, respectively). OSDI scores at 1-, 4- and 12-week follow-ups were significantly lower than that at baseline in bevacizumab group (P<0.001 at each follow-up). Schirmer test were not significantly different within or between groups (the lowest P = 0.92). No adverse events occurred in this study. Patients treated with bevacizumab 0.05% eye drops showed significant improvement in tear film stability, corneal staining and symptoms.

Comparison of Topical Pigment Epithelium-Derived Factor (PEDF) with Topical Bevacizumab for Accelerating the Regression of Corneal Neovascularization in an Experimental Model of Rabbit Corneal Angiogenesis

ABSTRACT Purpose: To evaluate the anti-angiogenic effect of topical administration of Pigment epithelium-derived factor (PEDF) on the reduction of corneal neovascularization (NV) in comparison to topical Bevacizumab. Methods: 18 eyes of 18 New Zealand rabbits were enrolled. Corneal NV was induced by a 7–0 silk suture. After suture removal, rabbits were randomly divided into three groups. In every group, one eye randomly treated with topical bevacizumab or topical PEDF or saline for 14 days. The area and length of neovascularization were measured by Image J. Histological studies were done in three groups. Results: After 14 days, the mean decrease of corneal NV length was 1.84 ± 0.17 mm (P < .001) in PEDF group and 1.6 ± 0.07 mm (P < .001) in bevacizumab group which was significantly more than the saline group (P = .001 and P < .001, respectively). There was no significant difference between PEDF and bevacizumab group in the reduction of corneal NV length (P = .85). The mean decrease of corneal NV area was 4.94 ± 0.55 mm2 (P < .001) in PEDF group and 4.23 ± 0.29 mm2 in the bevacizumab group (P < .001). PEDF and bevacizumab significantly decreased corneal NV area in comparison to the saline group (p = .017, p = .001, respectively). The mean decrease of corneal NV area did not show a significant difference between PEDF and bevacizumab groups (P = .72). Conclusion: Topical PEDF might be an effective and safe treatment option as bevacizumab in a short-term use, indicating that it is as good as the standard. However, long-term effect is required to be investigated.

Comparison of the effect of topical bevacizumab and sorafenib in experimental corneal neovascularization

Purpose The purpose of this study was to compare the neovascularization inhibiting the effect of topical bevacizumab and sorafenib and to determine the effective dose of sorafenib. Material and Methods Forty-two healthy Wistar albino rats were randomly divided into six groups. The right corneas of all rats except group 1 were cauterised with silver nitrate. Group 2 received DMSO, group 3 received topical bevacizumab (5 mg/dL, 3 times a day) and group 4, 5 and 6 received topical sorafenib (2.5 mg/dl, 5 mg/dL, 7.5 mg/dL, 2 times a day respectively), between days 1 and 7. Corneal photographs were taken on day 8 and the corneal neovascular area percentage was calculated. Following decapitation, the corneas were removed to determine the levels of VEGF ELİSA and corneal immune staining. The Mann–Whitney U-test was used for statistical analysis Results The neovascular corneal area percentage was statistically significantly lower in the treatment groups than group 2 (p < 0.05). The intensity of VEGF immune staining was also lower in groups 3, 5 and 6 from the group 2. Group 3, 5 and 6 were no significant differences compared to group 1. The VEGF ELİSA levels were statistically significantly lower in group 3, 5 and 6 compared to group 2 (p < 0.05). There was no statistically difference between VEGF ELİSA levels of group 2 and 4 (p > 0.05) Conclusions Sorafenib was as effective as bevacizumab in the regression of corneal neovascularization. The effect of sorafenib seems to be dose-dependent. The low doses and twice a day administration are important advantages of sorafenib.

Bevacizumab as an Adjunct to Trabeculectomy in Primary Open-Angle Glaucoma: A Randomized Trial.

Purpose To compare the outcomes of trabeculectomy using two different routes of bevacizumab administration as an adjunct in patients with primary open angle glaucoma. Methods Prospective, randomized, masked trial that included 180 eyes of 180 patients of documented primary open angle glaucoma were eligible for surgery. Patients were randomized to receive either a single intraoperative dose of subconjunctival bevacizumab (1.25 mg, Group I) or topical bevacizumab (5 mg/ml) for 30 days (Group II). One eye was randomly selected, if both were eligible for surgery. All patients underwent a complete ocular and systemic examination. Bleb morphology was examined and scored as per Moorfields system (MBGS) at 1, 3, 6, 12, 18, and 24 months postoperatively. Visual field, fundus photography, and disc analysis were performed. Outcome measures (at one year) included (1) comparison of bleb morphology in both groups, (2) proportion of patients achieving surgical success, and (3) side effects of treatment. Results The groups did not differ with respect to age, sex, and crystalline lens status. Group II patients had significantly lower vascularity scores for central (P=0.042) and peripheral bleb areas (P=0.042) and peripheral bleb areas (P=0.042) and peripheral bleb areas (n = 88) patients achieved average vascular scores of less than 2.5 (P=0.042) and peripheral bleb areas (n = 88) patients achieved average vascular scores of less than 2.5 (vs. 94%; P=0.042) and peripheral bleb areas (Conclusion Topical bevacizumab gives a better vascularity profile at one year, but the studied routes appear equally safe and do not seem to affect the outcome in any other way.

Comparison of the Therapeutic Efficacies of Topical Rivoceranib and Topical Bevacizumab in a Murine Model of Corneal Neovascularization

Background and Objectives: Corneal neovasculariziation (CNV) is a serious vision-threatening complication; however, all therapeutics have their clinical limitations. The aim of this study is to investigate the efficacy of topical rivoceranib compared with topical bevacizumab in a murine model of corneal neovascularization (CNV). Materials and Methods: Murine CNV was induced by means of total de-epithelization and alkali burn. Mice were divided into five groups according to topical treatment: untreated control, phosphate-buffered saline (PBS), 0.1% and 0.5% rivoceranib, and 0.5% bevacizumab. CNV area and index were measured 7 and 14 days after treatment. After corneal tissues were excised at day 14, the blood and lymphatic vessels were quantified by cluster of differentiation 31 (CD31) and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) immunofluorescence, respectively. Results: After 14 days, treatment groups with 0.1% and 0.5% rivoceranib and 0.5% bevacizumab showed a decrease in CNV area and index compared with the untreated and PBS groups (all p < 0.01). Blood and lymphatic vascularization significantly decreased in the 0.5% rivoceranib and 0.5% bevacizumab groups, as measured by CD31 and LYVE1 immunofluorescence. There was no significant difference of vascularization between the 0.5% rivoceranib and bevacizumab groups. Conclusions: Topical application of rivoceranib could effectively decrease CNV equivalent to topical bevacizumab in a murine model.

Comparison of the Effects of Dovitinib and Bevacizumab on Reducing Neovascularization in an Experimental Rat Corneal Neovascularization Model

To compare the inhibitory effects of dovitinib and bevacizumab for treatment of corneal neovascularization (CNV). Thirty-nine adult female Sprague Dawley rats weighing 180 to 250 g were used. CNV was induced by silver nitrate in the right eye of each rat. After the chemical burn, the animals were randomized into 5 groups. Group 1 did not receive any chemical substance. Group 2 received dimethyl sulfoxide, group 3 received bevacizumab 5 mg/mL, group 4 received dovitinib 5 mg/mL, and group 5 received bevacizumab 5 mg/mL + dovitinib 5 mg/mL topically administered twice daily for 14 days. On the 14th day, slit-lamp examination was performed, and anterior segment photographs were taken. The corneal neovascular area was measured on photographs as the percentage of the cornea's total area using computer imaging analysis. The corneal sections were stained with hematoxylin and eosin for histopathological examination. A statistically significant decrease in the percentage of CNV was found in all treatment groups (group 3, group 4, and group 5) compared with the control group (group 1) (P < 0.01). A statistically significant difference in the percentage of CNV was found among group 3, group 4, and group 5 (P = 0.003). The percentage of CNV in group 4 was significantly higher than that in group 3 and group 5 (P1 = 0.004; P2 = 0.006). There was no statistically significant difference in the percentage of CNV between group 3 and group 5 (P = 0.228). Dovitinib is a newly developed multitargeted tyrosine kinase inhibitor. Topical administration of dovitinib effectively inhibited CNV, but this effect of dovitinib was found less than topical bevacizumab.

Comment on “Topical Delivery of Avastin to the Posterior Segment of the Eye In Vivo Using Annexin A5‐Associated Liposomes”: Topical Liposomal Bevacizumab Results in Negligible Retinal Concentrations

The previously published report suggests that liposomes, functionalized with annexin-5, can deliver bevacizumab to the retina after topical administration as eyedrops. Topical delivery of bevacizumab would be an attractive alternative to the current treatment that involves monthly intravitreal injections to the eye. In this Comment, the retinal concentrations of topically applied liposomal bevacizumab are compared to the levels reached after intravitreal injections. The comparison reveals that the topical liposomal delivery results in retinal bevacizumab concentrations that are about 3-5 orders of magnitude below the lowest bevacizumab concentrations during clinical treatment with intravitreal injections. Major improvement is needed before topical bevacizumab delivery can be considered clinically feasible.

Is Sesamol Effective in Corneal Neovascularization?

To evaluate the effects of topically and subconjunctivally administered sesamol on experimentally induced corneal neovascularization in rats. Fifty-six right eyes of 56 Wistar Albino rats were chemically cauterized to induce corneal neovascularization in this experimental and comparative study. The subjects were divided into eight groups: topical sesamol (group 1), subconjunctival sesamol (group 2), topical bevacizumab (group 3), subconjunctival bevacizumab (group 4), topical bevacizumab+ sesamol (group 5), subconjunctival bevacizumab+ sesamol (group 6), topical Tween 80 (group 7), and control (group 8). The amount of subconjunctivally injected sesamol and bevacizumab was 1.25 mg each. Topical groups were administered 10 mg/mL drops twice daily. The control group was left untreated. To evaluate the degree of corneal neovascularization, digital photographs and corneal sections stained with hematoxylin-eosin and CD31 were used. When photographs of neovascularization areas were examined, all treatment groups showed statistically significant differences when compared with the control group (P<0.001). Topical sesamol was found to be more effective when compared with subconjunctival sesamol (P=0.003). Topical sesamol+ bevacizumab was found to be more effective when compared with topical bevacizumab (P=0.018). The numbers of new corneal vessels were as follows: 12.28±6.29 in group 1, 36.85±12.8 in group 2, 18.85±7.71 in group 3, 16.85±8.70 in group 4, 19.57±8.56 in group 5, 22.57±7.43 in group 6, 45.00±11.29 in group 7, and 51.16±5.91 in group 8 (P<0.001). The outcomes of this study suggest antiangiogenic effects of sesamol. The use of topical sesamol monotherapy or sesamol combined with bevacizumab may be options for the prevention of corneal neovascularization.

Bevacizumab for Epistaxis in Hereditary Hemorrhagic Telangiectasia: An Evidence-based Review.

Objective Epistaxis is a primary complaint in 90% to 96% of patients with hereditary hemorrhagic telangiectasia (HHT). Numerous surgical and medical treatments aim to decrease the frequency and severity of epistaxis in this patient population. Bevacizumab is a recombinant, humanized monoclonal antibody to vascular endothelial growth factor, an angiogenic factor elevated in HHT. It has been used in several forms to treat epistaxis in HHT but thus far, evidence-based recommendations are limited. Study Design Systematic review with evidence-based recommendations. Methods A systematic review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed using Embase, MEDLINE, MEDLINE In-Process/Epub, and Cochrane databases. English language abstracts were reviewed for relevance. Results Eleven manuscripts met inclusion criteria and were analyzed. Submucosal injection, submucosal injection plus laser coagulation, intravenous (IV), and topical formulations of bevacizumab were evaluated for their therapeutic impact on epistaxis in patients with HHT. Three randomized controlled trials failed to show topical bevacizumab to be more effective in controlling epistaxis than saline or other moisturizers. Conclusions The use of submucosal and IV bevacizumab shows promise, but further study is necessary to determine the true efficacy in the treatment of epistaxis as only grade C level exists currently. Based on the available literature, the use of topical bevacizumab is not recommended (grade B).