Anti-vascular Endothelial Growth Factor Drugs Research Articles

Progresses in the treatment of exudative age-related macular degeneration with anti-vascular endothelial growth factor drugs

Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs, including monoclonal antibodies (such as bevacizumab and ranibizumab) and fusion protein agents (such as aflibercept and conbercept) have been proven to be effective in the treatment of wet age-related macular degeneration (wAMD). However, there are still some patients with poor efficacy, such as no response to initial treatment or poor response, and even relapse during the course of treatment. In view of the different targets and molecular characteristics of anti-VEGF drugs, the switch of anti-VEGF drugs and the adjustment of delivery pattern, dosages and intervals have been the strategies to cope with the poor efficacy in clinic. However, there are some differences in the results of current studies. Overall, the recovery of retinal anatomical outcome achieves more benefits, and it is relatively difficult to improve visual acuity. To determine which regimen would get the biggest benefits, a large number of randomized controlled clinical trials and long study period will be needed. Key words: Wet macular degeneration/drug therapy; Angiogenesis inhibitors/therapeutic use; Antibodies, monoclonal, humanized/therapeutic use; Review

Treatment for radiation retinopathy of uveal melanoma undergone radiotherapy: the current situation

Radiotherapy is the prior treatment for uveal melanoma, but a major problem confronted most of the patients is radiation retinopathy, which accompanied with severe visual loss and secondary enucleation potential. There is no optium choice and normative strategy so far, the intraocular melanoma society has focused on application of anti-vascular endothelial growth factor drugs injection and glucocorticoids. This article reviews a series of potential managements for radiation retinopathy and its further stage . Key words: Uveal neoplasms/radiotherapy; Radiotherapy/adverse effects; Retinal diseases/therapy; Review

Intravitreal injection of a Rho-kinase inhibitor (fasudil) combined with bevacizumab versus bevacizumab monotherapy for diabetic macular oedema: a pilot randomised clinical trial

Click here to listen to the PodcastBackground/aimsTo compare the efficacy of combined intravitreal injection of bevacizumab and a Rho-kinase inhibitor, fasudil (intravitreal bevacizumab (IVB)/intravitreal fasudil (IVF)), with IVB alone for...

Different effects of various anti-angiogenic treatments in an experimental mouse model of retinopathy of prematurity.

Anti-vascular endothelial growth factor (VEGF) drugs are an option for the treatment of retinopathy of prematurity (ROP). Blocking of other angiogenic factors is also of interest. We therefore investigated in which effects would result blocking of placental growth factor (PlGF). C57BL/6 mice were exposed to 75% oxygen from P7 to P12. Intravitreal injections were performed at P12. Mice of control groups remained untouched after oxygen treatment, or phosphate buffered saline or neutral IgG molecules were injected. In the treatment groups, antibodies against VEGF or PlGF, a mixture of anti-VEGF and anti-PlGF, aflibercept or sunitinib were injected. On P17, electroretinographic (ERG) measurements were performed. Avascular zones and neovascularization were evaluated in retinal flat-mounts. Results are expressed as percent of total retinal area (median with median absolute deviation, MAD). Eyes of control groups showed similar neovascularization (1.4-3.3%, MAD 0.4-0.9%). Neovascularization was significantly less (0.5-0.7%, MAD 0.1-0.3%) in all treatment groups. Avascular zones in the retinas of control groups showed similar values (18.3-25.7%, MAD 4.8-8.8%). Avascular zones were significantly reduced down to 3.6 ± 1.3% after anti-VEGF injection, but they were not reduced significantly in the other treatment groups (13.3-22%, MAD 3.6-6.1%). ERG measurements did not reveal significant differences between the controls and the treatment groups. Blocking of PlGF or injection of sunitinib results in a similar inhibition of neovascularization as by anti-VEGF treatment in the mouse model of ROP. However, physiological angiogenesis that occurs after anti-VEGF treatment is blocked by anti-PlGF or sunitinib treatment, indicating that pathological neovascularization may follow different pathways than physiological angiogenesis.

Conbercept for Treatment of Neovascular Age-related Macular Degeneration: Results of the Randomized Phase 3 PHOENIX Study

Age-related macular degeneration (AMD) can cause irreversible vision loss leading to blindness. We aim to evaluate the efficacy and safety of intravitreal injections of 0.5mg conbercept, a new anti-vascular endothelial growth factor (anti-VEGF) drug, for treatment of AMD on a schedule more manageable for patients. A prospective, double-masked, multicenter, sham-controlled, phase III randomized trial. Patients: Patients with choroidal neovascularization (CNV) secondary to AMD were enrolled and randomized to the conbercept group or the sham control group. The conbercept group received intravitreal injections of conbercept (0.5mg) once monthly for the first 3months, then once quarterly until month 12 (3+ Q3M). The sham group received first 3monthly sham injections and then 3monthly injections of conbercept (0.5mg) followed by quarterly administrations until month 12. The primary endpoint was mean change from baseline in best-corrected visual acuity (BCVA) at month 3. A total of 114 patients (91.9%) from 9 sites in China completed the 12-month study. At the 3-month primary endpoint, the mean changes in BCVA from baseline were+9.20 letters in the conbercept group and+2.02 letters in the sham group, respectively (P< .001). At 12months, the mean changes from baseline in BCVA letter score were+9.98 letters in the conbercept group and+8.81 letters in the sham group(P= .64). The most common ocular adverse events were associated with intravitreal injections, such as conjunctival hemorrhage, and increased intraocular pressure. A conbercept dosing regimen of 3 initial monthly administrations followed by quarterly treatments is effective for treatment of AMD. In previous reports, other anti-VEGF agents were unable to maintain similar clinical benefits with the same regimen.

The Effects of Anti-Vascular Endothelial Growth Factor Drugs on Retinal Pigment Epithelial Cell Culture

Objectives:To assess the effects of anti-vascular endothelial growth factor (VEGF) drugs on retinal pigment epithelium cell culture.Materials and Methods:Aflibercept (0.5 mg/mL), bevacizumab (0.3125 mg/mL), and ranibizumab (0.125 mg/mL) were applied to retinal pigment epithelium cell cultures isolated from the enucleated eyes of New Zealand white rabbits. Viability, apoptosis, proliferation, and senescence of the cells were evaluated in control and drug-treated cultures at the end of 72 hours.Results:Cells treated with aflibercept showed increased viability and decreased apoptosis compared to the control culture and both the bevacizumab- and ranibizumab-treated groups (p<0.05). Statistically increased apoptosis and decreased viability were found in the bevacizumab and ranibizumab-treated groups compared with the control group (p<0.05). There were no statistically significant differences in cell proliferation and senescence between the groups (p>0.05).Conclusion:Anti-VEGF drugs did not affect senescence or proliferation of retinal pigment epithelium cells. Aflibercept was found to decrease apoptosis and increase cell viability, while ranibizumab and bevacizumab increased apoptosis and reduced cell viability in retinal pigment epithelium culture.

Effects of bevacizumab, ranibizumab, and aflibercept on phagocytic properties in human RPE cybrids with AMD versus normal mitochondria

PurposeA critical biological function of retina pigment epithelium (RPE) cells is phagocytosis of photoreceptor outer segment (POS) disc membranes. Mitochondrial damage and dysfunction are associated with RPE cells of age-related macular degeneration (AMD) retinas. In this study, we use a transmitochondrial cybrid model to compare the phagocytic properties of RPE cells that contain AMD mitochondria versus age-matched normal mitochondria and their response to treatment with anti-vascular endothelial growth factor (VEGF) drugs: bevacizumab, ranibizumab, and aflibercept. MethodsCybrids, which are cell lines with identical nuclei but mitochondria (mt) from different subjects, are created by fusing mtDNA depleted ARPE-19 cells with platelets from AMD or age-matched normal patients. AMD (n = 5) and normal (n = 5) cybrids were treated with 1 μm fluorescent latex beads (1.52 × 107 beads/mL) and either 2.09 μM of bevacizumab, 2.59 μM of ranibizumab, or 5.16 μM of aflibercept. These doses of anti-VEGF drugs are equivalent to intravitreal injections given to AMD patients with choroidal neovascularization. Flow cytometry was performed using the ImageStreamX Mark II to assess phagocytic bead-uptake. The average fold values for bead-uptake and SEM were calculated using GraphPad Prism software. ResultsNormal cybrids showed decreased bead-uptake with a fold value of 0.65 ± 0.103 (p = 0.01) after treatment with bevacizumab, 0.80 ± 0.034 (p = 0.0003) with ranibizumab, and 0.81 ± 0.053 (p = 0.007) with aflibercept compared to the untreated normal cybrids (baseline fold of 1). The bevacizumab-treated, ranibizumab-treated, and aflibercept-treated AMD cybrids had decreased bead-uptake with a fold value of 0.71 ± 0.061 (p = 0.001), 0.70 ± 0.101 (p = 0.02), and 0.74 ± 0.125 (p = 0.07), respectively, compared to the untreated AMD cybrids (baseline fold of 1). ConclusionsOur initial findings showed that when treated with bevacizumab and ranibizumab, both AMD cybrids and age-matched normal cybrids had a significant decrease in bead-uptake. A similar decrease in bead-uptake was found in normal cybrids treated with aflibercept and while the AMD values trended lower, they were not significant. This data suggests that anti-VEGF drugs can cause loss of phagocytic function.

Oral Anti-Vascular Endothelial Growth Factor Drugs and Ocular Adverse Events.

To evaluate possible associations between oral anti-vascular endothelial growth factor (VEGF) drugs and ocular side effects. Spontaneous reports were collected and evaluated by the National Registry of Drug-Induced Ocular Side Effects on the three oral anti-VEGF drugs (pazopanib, sorafenib, and sunitinib) for possible ocular side effects. Reported side effects include blurred or decreased vision (389 cases); periocular or eyelid edema (273 cases); superficial anterior segment toxicity (270 cases); conjunctival, retinal, or vitreous bleeding (77 cases); retinal detachments (RDs) or retinal tears (RTs) (75 cases); extraocular muscle disorders, including ptosis (51 cases); discoloration of eyelashes (36 cases); retinal arterial or venous occlusions (26 cases); optic nerve disorders, including papilledema and ischemic optic neuropathy (21 cases); uveitis (10 cases); and macular edema (7 cases). Spontaneous reports of possible RD or RT have been associated with pazopanib (31 RDs and 12 RTs), sunitinib (24 RDs and 0 RT), and sorafenib (7 RDs and 2 RTs). Oral anti-VEGF drugs can cause superficial anterior segment side effects. Pazopanib has been reported to be possibly linked to RDs and RTs. This study suggests that sorafenib and sunitinib are suspected as well. RDs were seldom differentiated into rhegmatogenous retinal detachments (RRDs) or non-RRDs. The association of oral anti-VEGF drugs with RRD and RT are unclassified although this suggests a "signal" requiring further study. The association of oral anti-VEGF drugs with serous retinal detachments, while rare, is plausible. Patients on this class of drugs should be instructed to seek immediate ophthalmic consultation if retinal symptoms occur.

TOPICAL DORZOLAMIDE-TIMOLOL WITH INTRAVITREOUS ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR FOR RETINAL VEIN OCCLUSION: A PILOT STUDY.

To evaluate topical dorzolamide hydrochloride-timolol maleate as an adjunct therapy to intravitreous anti-vascular endothelial growth factor injections in eyes with retinal vein occlusion resistant to treatment. Retinal vein occlusion patients with a history of persistent macular edema, despite fixed-interval intravitreous anti-vascular endothelial growth factor injections, were enrolled between April 4, 2016, and June 4, 2017. On enrollment, patients were instructed to administer one drop of topical dorzolamide-timolol twice daily for the duration of the study. They were maintained on the same anti-vascular endothelial growth factor drug and same interval between injections as preenrollment for the subsequent two visits. Primary outcome measures were change in central foveal thickness, central subfield thickness, and thickest macular cut at the final study visit. Eight patients (8 eyes) were eligible for enrollment and completed the study. There was a significant decrease in central foveal thickness (P = 0.02), central subfield thickness (P = 0.03), and thickest macular cut (P = 0.01) between the enrollment visit and the final visit. There was a decrease in mean (±SD) logarithm of the minimal angle of resolution from 0.52 (±0.35) (20/66, Snellen equivalent) at the enrollment visit to 0.41 (±0.35) (20/51, Snellen equivalent) at the final visit (P = 0.08). Topical dorzolamide-timolol may have a beneficial anatomical and functional effect in eyes with macular edema secondary to retinal vein occlusion resistant to treatment.

Association of Genetic Variants With Response to Anti–Vascular Endothelial Growth Factor Therapy in Age-Related Macular Degeneration

Visual acuity (VA) outcomes differ considerably among patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) drugs. Identification of pharmacogenetic associations may help clinicians understand the mechanisms underlying this variability as well as pave the way for personalized treatment in nAMD. To identify genetic factors associated with variability in the response to anti-VEGF therapy for patients with nAMD. In this multicenter genome-wide association study, 678 patients with nAMD with genome-wide genotyping data were included in the discovery phase; 1380 additional patients with nAMD were genotyped for selected common variants in the replication phase. All participants received 3 monthly injections of bevacizumab or ranibizumab. Clinical data were evaluated for inclusion/exclusion criteria from October 2014 to October 2015, followed by data analysis from October 2015 to February 2016. For replication cohort genotyping, clinical data collection and analysis (including meta-analysis) was performed from March 2016 to April 2017. Change in VA after the loading dose of 3 monthly anti-VEGF injections compared with baseline. Of the 2058 included patients, 1210 (58.8%) were women, and the mean (SD) age across all cohorts was 78 (7.4) years. Patients included in the discovery cohort and most of the patients in the replication cohorts were of European descent. The mean (SD) baseline VA was 51.3 (20.3) Early Treatment Diabetic Retinopathy Study (ETDRS) score letters, and the mean (SD) change in VA after the loading dose of 3 monthly injections was a gain of 5.1 (13.9) ETDRS score letters (ie, 1-line gain). Genome-wide single-variant analyses of common variants revealed 5 independent loci that reached a P value less than 10 × 10-5. After replication and meta-analysis of the lead variants, rs12138564 located in the CCT3 gene remained nominally associated with a better treatment outcome (ETDRS letter gain, 1.7; β, 0.034; SE, 0.008; P = 1.38 × 10-5). Genome-wide gene-based optimal unified sequence kernel association test of rare variants showed genome-wide significant associations for the C10orf88 (P = 4.22 × 10-7) and UNC93B1 (P = 6.09 × 10-7) genes, in both cases leading to a worse treatment outcome. Patients carrying rare variants in the C10orf88 and UNC93B1 genes lost a mean (SD) VA of 30.6 (17.4) ETDRS score letters (ie, loss of 6.09 lines) and 26.5 (13.8) ETDRS score letters (ie, loss of 5.29 lines), respectively, after 3 months of anti-VEGF treatment. We propose that there is a limited contribution of common genetic variants to variability in nAMD treatment response. Our results suggest that rare protein-altering variants in the C10orf88 and UNC93B1 genes are associated with a worse response to anti-VEGF therapy in patients with nAMD, but these results require further validation in other cohorts.

Morphologic Criteria of Lesion Activity in Neovascular Age-Related Macular Degeneration: A Consensus Article.

Intravitreal antivascular endothelial growth factor drugs represent the current standard of care for neovascular age-related macular degeneration (nAMD). Individualized treatment regimens aim at obtaining the same visual benefits of monthly injections with a reduced number of injections and follow-up visits, and, consequently, of treatment burden. The target of these strategies is to timely recognize lesion recurrence, even before visual deterioration. Early detection of lesion activity is critical to ensure that clinical outcomes are not compromised by inappropriate delays in treatment, but questions remain on how to effectively monitor the choroidal neovascularization (CNV) activity. To assess the persistence/recurrence of lesion activity in patients undergoing treatment for nAMD, an expert panel developed a decision algorithm based on the morphological features of CNV. After evaluating all current retinal imaging techniques, the panel identified optical coherent tomography as the most reliable tool to ascertain lesion activity when funduscopy is not obvious.

How do anti-vascular endothelial growth factor (VEGF) drugs compare with conventional laser therapy for treatment of infants with retinopathy of prematurity?

How do anti-vascular endothelial growth factor (VEGF) drugs compare with conventional laser therapy for treatment of infants with retinopathy of prematurity?

Optimizing Anti-VEGF Treatment Outcomes for Patients with Neovascular Age-Related Macular Degeneration.

The introduction of anti-vascular endothelial growth factor (anti-VEGF) drugs to ophthalmology has revolutionized the treatment of neovascular age-related macular degeneration (nAMD). Despite this significant progress, gaps and challenges persist in the diagnosis of nAMD, initiation of treatment, and management of frequent intravitreal injections. Thus, nAMD remains a leading cause of blindness in the United States. To present current knowledge, evidence, and expert perspectives on anti-VEGF therapies in nAMD to support managed care professionals and providers in decision making and collaborative strategies to overcome barriers to optimize anti-VEGF treatment outcomes among nAMD patients. Three anti-VEGF therapies currently form the mainstay of treatment for nAMD, including 2 therapies approved by the FDA for treatment of nAMD (aflibercept and ranibizumab) and 1 therapy approved by the FDA for oncology indications and used off-label for treatment of nAMD (bevacizumab). In clinical trials, each of the 3 agents maintained visual acuity (VA) in approximately 90% or more of nAMD patients over 2 years. However, in long-term and real-world settings, significant gaps and challenges in diagnosis, treatment, and management pose barriers to achieving optimal outcomes for patients with nAMD. Many considerations, including individual patient characteristics, on-label versus off-label treatment, repackaging, and financial considerations, add to the complexity of nAMD decision making and management. Many factors may contribute to additional challenges leading to suboptimal long-term outcomes among nAMD patients, such as delays in diagnosis and/or treatment approval and initiation, individual patient response to different anti-VEGF therapies, lapses in physician regimentation of anti-VEGF injection and monitoring, and inadequate patient adherence to treatment and monitoring. These latter factors highlight the considerable logistical, emotional, and financial burdens of long-term, frequent intravitreal injections and the vital importance of personalized approaches to anti-VEGF treatment decision making and management for patients with nAMD. To address these challenges and reduce the number of yearly injections, studies have examined alternative dosing regimens, including extended fixed intervals, as needed, and treat-and-extend strategies in specific nAMD patient populations. New clinical evidence and insights into expert clinical practice discussed in this article can support managed care professionals in the key role they play in addressing challenges in nAMD treatment and management and optimizing patient outcomes through appropriate management of anti-VEGF treatment. PRIME Education is an independent medical education company and has been an accredited provider of continuing education for 23 years. There is no fee for this activity as it is sponsored by PRIME through an educational grant from Regeneron. All authors contributed to the writing and reviewing of the article. Wykoff reports consultancies/research grants from Alcon Laboratories, Genentech/Roche, Clearside, and Iconic Therapeutics; consultancies/honoraria, research grants, and speaker fees from Allergan and Regeneron; research grants from Allegro, Apellis, Aura, NEI, NIH, Novartis, OHR Pharmaceuticals, Ophthotech, pSivida, Roche, Santen, SciFluor, Tyrogenex; and consultancies for Alimera Sciences, Alnylam Pharmaceuticals, Bayer, DORC, ONL Therapeutics, Thrombogenics, and Valeant. Clark reports advisory board work, consultancies, research grants, and speaker fees from Genentech/Roche and Regeneron and consultancy for Bayer. Brill reports consultancies for Aries Pharma, Avella, BaroNova, Braeburn Pharmaceuticals, Cardinal Health, Endogastric Solutions, GeneNews, Halt Medical, Lumendi, Medtronic, Monteris Medical, Natera, Phosphorus, Rebiotix, Seno Medical, UCB, Vermillion, Echosens, and HAP Innovations. Brill is a shareholder in EndoChoice, GeneNews, SonarMD, and SynerZ and reports advisory board work with Nestle Health Sciences, Indivior Pharmaceuticals, Eli Lilly, Blue Earth Diagnostics, Bayer, and AstraZeneca. Nielson reports advisory board work/consultancy and research grants for Genentech/Roche; advisory board work and research grants from Regeneron; and research grants from Alcon and Ophthotech.

The Real-World Effect of Intravitreous Anti–Vascular Endothelial Growth Factor Drugs on Intraocular Pressure: An Analysis Using the IRIS Registry

To identify sustained differences in intraocular pressure (IOP) after intravitreous injections of anti-vascular endothelial growth factor (VEGF) drugs. Database study. Patients seeing an ophthalmic provider who contributes to the database. We identified a total of 23 776 unique patients who received only a single type of anti-VEGF medication (bevacizumab, aflibercept, or ranibizumab) by injection in the right eye in the American Academy of Ophthalmology Intelligent Research in Sight Registry. Subgroups included patients with age-related macular degeneration only and patients who had not received an anti-VEGF injection for at least 1 year before the study. We examined those with at least 12, 18, and 25 injections for each of these 3 medications. For all groups, we used fellow, untreated eyes for comparison. The mean change in IOP from baseline at a minimum of 1 year of follow-up and the proportion of eyes with a clinically significant IOP increase (defined as sustained rise of at least 6 mmHg to an IOP of more than 21 mmHg). All patients in all groups receiving all drugs showed a decrease in IOP from baseline, with a mean of 0.9 mmHg in treated eyes compared with an average decrease of 0.2 mmHg in fellow untreated eyes, a statistically significant difference. A generalized linear model accounting for confounders associated bevacizumab with slightly less lowering of IOP than aflibercept and ranibizumab in most subgroups. A clinically significant IOP increase was seen in 2.6% of eyes receiving injections compared with 1.5% in the associated untreated fellow eyes. Clinically significant IOP increases occurred at a rate of 1.9%, 2.8%, and 2.8% for aflibercept, ranibizumab, and bevacizumab, respectively, which was significantly higher than untreated fellow eyes for bevacizumab and ranibizumab, but not for aflibercept. These analyses from real-world data indicate that anti-VEGF intravitreous injections are associated with a small but statistically significant decrease in IOP over time. A proportion of patients, on average 2.6%, experienced a sustained clinically significant IOP rise with these drugs overall compared with 1.5% in the fellow untreated eyes. However, such an increase was not seen with aflibercept.

Advances in the treatment of macular edema secondary to retinal vein occlusion

Retinal vein occlusion (RVO) is a common blinding retinal vascular disease, and the most important complication of vision loss is macular edema (ME). The main treatment for ME secondary to RVO was laser photocoagulation therapy previously, but some researches showed that the laser therapy did not see an obvious curative effection, and might cause certain danger in some patients.In recent years, with the further understanding and research of the pathogenesis of RVO, intravitreal injection or posterior subtenon injection of triamcinolone acetonide and anti-vascular endothelial growth factor drugs like ranibizumab, bevacizumab, aflibercept, conbercept intravitreal injections, as well as vitreous retinal surgery gradually became the main research directions of ME secondary to RVO.The following to be a review for the advances in the treatment of macular edema secondary to RVO. Key words: Retinal vein occlusion; Macular edema; Treatment; Review

Anti-vascular endothelial growth factor (VEGF) drugs for treatment of retinopathy of prematurity.

Anti-vascular endothelial growth factor (VEGF) drugs for treatment of retinopathy of prematurity.

Pathophysiology of Diabetic Retinopathy: The Old and the New.

Vision loss in diabetic retinopathy (DR) is ascribed primarily to retinal vascular abnormalities—including hyperpermeability, hypoperfusion, and neoangiogenesis—that eventually lead to anatomical and functional alterations in retinal neurons and glial cells. Recent advances in retinal imaging systems using optical coherence tomography technologies and pharmacological treatments using anti-vascular endothelial growth factor drugs and corticosteroids have revolutionized the clinical management of DR. However, the cellular and molecular mechanisms underlying the pathophysiology of DR are not fully determined, largely because hyperglycemic animal models only reproduce limited aspects of subclinical and early DR. Conversely, non-diabetic mouse models that represent the hallmark vascular disorders in DR, such as pericyte deficiency and retinal ischemia, have provided clues toward an understanding of the sequential events that are responsible for vision-impairing conditions. In this review, we summarize the clinical manifestations and treatment modalities of DR, discuss current and emerging concepts with regard to the pathophysiology of DR, and introduce perspectives on the development of new drugs, emphasizing the breakdown of the blood-retina barrier and retinal neovascularization.

Multivesicular liposomes for sustained release of bevacizumab in treating laser-induced choroidal neovascularization

Bevacizumab is an anti-vascular endothelial growth factor drug that can be used to treat choroidal neovascularization (CNV). Bevacizumab-loaded multivesicular liposomes (Bev-MVLs) have been designed and developed to increase the intravitreal retention time of bevacizumab and reduce the number of injection times. In this study, Bev-MVLs with high encapsulation efficiency were prepared by double emulsification technique, and antibody activity was determined. The results revealed that 10% of human serum albumin (HSA) could preserve the activity of bevacizumab. In vitro release of Bev-MVLs appeared to be in a more sustained manner, the underlying mechanisms of Bev-MVLs indicated that bevacizumab was released from MVLs through diffusion and erosion. Results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that bevacizumab could retain its structural integrity after being released from MVLs in vitro. In vivo imaging was used to evaluate the retention time of antibody in rat eyes, while pharmacokinetic analysis was performed on rabbit eyes. These results indicated that Bev-MVLs exhibited sustained release effects as compared to bevacizumab solution (Bev-S). Bev-MVLs could effectively inhibit the thickness of CNV lesion as compared to Bev-S at 28 days after treatment. Furthermore, these data suggest that Bev-MVLs are biologically feasible to increase the retention time of bevacizumab in vitreous humor. This novel Bev-MVLs may therefore serve as a promising sustained release drug delivery system for the treatment of CNV.

Updates in Retinal Diseases 2018

Choroidal neovascularisation (CNV) is a major cause of vision loss. For more than 10 years, intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs have been used in the treatment of CNV. While effective, this treatment strategy is limited by the injection burden. Most patients require multiple injections and response levels can vary. Early diagnosis and treatment of CNV can increase the success rate of treatment. There is, therefore, considerable interest in identifying biomarkers both to identify patients most likely to respond to treatment and to facilitate early detection of the condition. In an expert interview, Maurizio Battaglia Parodi of the University Vita-Salute Milan, Italy, discusses the latest advances in CNV.

Intravitreal Injection of Anti-vascular Endothelial Growth Factor Agents for Ocular Vascular Diseases: Clinical Practice Guideline.

Purpose:To provide the clinical recommendations for the administration of intravitreal anti-vascular endothelial growth factor (VEGF) drugs especially bavacizumab for ocular vascular diseases including diabetic macular edema, neovascular age-related macular degeneration, myopic choroidal neovascularization, retinal vein occlusion and central serous chorioretinopathy.Methods:Twenty clinical questions were developed by the guideline technical committee. Relevant websites and databases were searched to find out the pertinent clinical practice guidelines to answer the questions. The technical committee provided possible answers (scenarios) according to the available evidences for each question. All scenarios along with their levels of evidence and the supported articles were sent to the experts for external review. If the experts did not agree on any of the scenarios for one particular clinical question, the technical committee reviewed all scenarios and their pertinent evidences and made the necessary decision. After that, the experts were asked to score them again. All confirmed scenarios were gathered as the final recommendations.Results:All the experts agreed on at least one of the scenarios. The technical committee extracted the agreed scenario for each clinical question as the final recommendation. Finally, 56 recommendations were developed for the procedure of intravitreal anti-VEGF injection and their applications in the management of ocular vascular diseases.Conclusion:The implementation of this guideline can standardize the management of the common ocular vascular diseases by intravitreal injection of anti-VEGF agents. It can lead to better policy-making and evidence-based clinical decision by ophthalmologists and optimal evidence based eye care for patients.