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Summary study characteristics Study characteristic Total no of trials included (n=19)* (%) No of studies with cn-AMD (n=12) (%) No of studies with DMO (n=3) (%) No of studies with RVO-MO (n=2) (%) No of studies with m-CNV (n=2) (%)
Source publication
Objectives
To evaluate the comparative effectiveness and safety of intravitreal bevacizumab, ranibizumab and aflibercept for patients with choroidal neovascular age-related macular degeneration (cn-AMD), diabetic macular oedema (DMO), macular oedema due to retinal vein occlusion (RVO-MO) and myopic choroidal neovascularisation (m-CNV).
Design
Syst...
Context in source publication
Context 1
... In the second year, the median number of injections was: 6, 5 and 6 in the bevacizumab, aflibercept and ranibizumab groups, respectively. 52 Two smaller trials both started treatment with 3 monthly intravitreal injections, followed by monthly retreatment with persistence of macular oedema, thickening of central macular or worsening of visual acuity (table 3 and additional file 2: Appendix 10). 14 31 Harms After 24 months of treatment in the DRCR. ...Similar publications
Background: Compare the current indications for intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy, to make recommendations for planning of services. To review the current indications for intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy, in order to make recommendations for planning of services.Methods:...
This prospective comparative case series aims to compare best-corrected visual acuity (BCVA), retinal microvasculature, and retinal structural changes in patients treated with either ranibizumab or aflibercept for macular edema (ME) secondary to treatment-naïve branch retinal vein occlusion (BRVO) by optical coherence tomography angiography (OCTA)....
Purpose: We report a case of focal choroidal excavation (FCE) that resolved after intravitreal injection of anti-vascular endothelial growth factor (VEGF) for choroidal neovascularization (CNV) and we describe its tomographic features.
Case report: A 43-year-old female presented with blurred vision and metamorphopsia in her left eye (LE) evolving f...
PurposeWe aimed to investigate the association between subfoveal choroidal thickness (SCT) and the level of aqueous humor (AH) inflammatory cytokines in patients with macular edema (ME) associated with branch retinal vein occlusion (BRVO).Methods
Twenty-eight eyes of 28 BRVO ME patients who underwent intravitreal injection treatment (ranibizumab, b...
Background:
Several observational studies have reported acute kidney injury from intravitreal anti-vascular endothelial growth factor (anti-VEGF) drugs for retinal diseases. However, systematic reviews and meta-analyses of randomized controlled trials on this critical topic are scant.
Objective:
To evaluate acute kidney injury risk associated wi...
Citations
... In contrast, (15.0%) of patients were defined as non-compliant by Abu-Yaghi et al. [16]. A recent report from the U.S. that included 2302 patients with proliferative diabetic retinopathy DR and 9007 patients with AMD, showed that approximately (22%) and (28%), respectively, of patients were lost to follow-up [17]. Another study from Germany, which included 708 patients with AMD, DME, and RVO, reported that (32%), (44%), and (25%) of patients, respectively, were non-adherent [18]. ...
Background
The burden of retinal vascular and degenerative diseases on patients and healthcare systems can be significant if patients do not complete scheduled intravitreal injections. This study aimed to identify the factors that influence adherence with follow-up injections in patients with diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion receiving intravitreal injections of anti-vascular endothelial growth factor treatment.
Methods
This study utilized data from patients who received intravitreal anti-vascular endothelial growth factor injections between 2022 and 2023 at An-Najah National University Hospital. Patient information, such as demographic information, number of injections administered, and details of follow-up visits, was obtained from the hospital's electronic records. When electronic records lacked certain information, patients or their relatives were contacted to provide the missing data. Data entry and analysis were performed using chi-square tests and the Statistical Package for Social Sciences. A p-value ≤ 0.05 indicated statistical significance.
Results
A total of 107 patients, 43 (40.2%) were adherent, while 64 (59.8%) were non-adherent. Sex was significantly associated with adherence (P = 0.035), with females more likely to adhere. Planned number of injections correlated with adherence (P = 0.004), as those receiving fewer injections were more adherent. Cost problems negatively impacted adherence (P = 0.016), with non-adherent patients more frequently reporting financial barriers. Positive patient expectations for vision improvement were strongly associated with adherence (P = 0.003). Mobility problems influenced adherence (P = 0.049), as those without mobility issues adhered more. Physical assistance from relatives significantly improved adherence (P = 0.036). Factors not significantly influencing adherence included comorbidities, education level, and insurance status.
Conclusion
Our study revealed that 60% of patients did not adhere to intravitreal anti-vascular endothelial growth factor treatment injections. Factors influencing adherence included the planned number of injections, cost problems, indication for injections, sex, need for physical assistance, and mobility problems. It is crucial to increase awareness of these factors to prevent complications such as blindness. Raising awareness could lead to improved adherence rates, better treatment outcomes, and positive impacts on patient and community health.
... However, no head-to-head comparative RCT studies have been conducted on aflibercept and bevacizumab. Only an indirect comparison is available from a network meta-analysis, which suggests a mean difference between bevacizumab and aflibercept of 0.02 letters [14]. To date, no randomized prospective comparative trials of these three drugs have been performed. ...
Background
To compare the visual outcomes of different anti-vascular endothelial growth factor (VEGF) drugs, including aflibercept, ranibizumab, and bevacizumab, in a real-world setting in Korea.
Methods
We collected data from patients who received monotherapy using one of these three anti-VEGF drugs as naïve treatment after being diagnosed with neovascular age-related macular degeneration. The number of injections and visual acuity (VA) outcomes of each cohort were obtained and pairwise comparisons were performed using propensity score matching.
Results
A total of 254 aflibercept, 238 ranibizumab, and 282 bevacizumab treatment-naïve eyes were included. The mean VA change at 3 years for all cohorts combined was -1.8 letters, and the mean number of injections was 9.4. In the direct comparison of the three drugs, the mean change in the VA letter score was +2.0 letters for aflibercept and -11.7 letters for bevacizumab (P < 0.001). The number of aflibercept injections was significantly higher than the number of bevacizumab injections (P = 0.002). The visual outcomes for aflibercept and ranibizumab were +4.7 letters and -1.9 letters, respectively, and comparable results were obtained (P = 0.13). The VA outcomes for ranibizumab and bevacizumab were also not significantly different (P = 0.09). The numbers of injections for aflibercept, ranibizumab, and bevacizumab were 10.8, 6.7, and 8.8, respectively. Significant differences were observed between the injection frequencies comparisons of aflibercept and ranibizumab and ranibizumab and bevacizumab (P < 0.001 and P = 0.002, respectively).
Conclusions
In the Korean clinical medical environment, which included various confounding factors, especially socioeconomic ones, the aflibercept VA outcome was significantly better than that of bevacizumab, and aflibercept injections were the most numerous. These real-world data imply that the drug effect as well as the environment in which the drug can be sufficiently used affected patient final VA scores.
... Similar improvements have been observed in previous studies. According to Pham et al. [34], ranibizumab (37%) and aflibercept (39%) had similar odds of achieving visual gain over 2 years of therapy [34]. Demircan et al. [28] documented mean (standard deviation) baseline BCDVAs for aflibercept and ranibizumab groups of 0.67 (0.38) logMAR and 0.73 (0.34) logMAR, respectively. ...
... Similar improvements have been observed in previous studies. According to Pham et al. [34], ranibizumab (37%) and aflibercept (39%) had similar odds of achieving visual gain over 2 years of therapy [34]. Demircan et al. [28] documented mean (standard deviation) baseline BCDVAs for aflibercept and ranibizumab groups of 0.67 (0.38) logMAR and 0.73 (0.34) logMAR, respectively. ...
Background
Vascular endothelial growth factor (VEGF) is the primary substance involved in retinal barrier breach. VEGF overexpression may cause diabetic macular edema (DME). Laser photocoagulation of the macula is the standard treatment for DME; however, recently, intravitreal anti-VEGF injections have surpassed laser treatment. Our aim was to evaluate the efficacy of intravitreal injections of aflibercept or ranibizumab for managing treatment-naive DME.
Methods
This single-center, retrospective, interventional, comparative study included eyes with visual impairment due to treatment-naive DME that underwent intravitreal injection of either aflibercept 2 mg/0.05 mL or ranibizumab 0.5 mg/0.05 mL at Al-Azhar University Hospitals, Egypt between March 2023 and January 2024. Demographic data and full ophthalmological examination results at baseline and 1, 3, and 6 months post-injection were collected, including the best-corrected distance visual acuity (BCDVA) in logarithm of the minimum angle of resolution (logMAR) notation, slit-lamp biomicroscopy, dilated fundoscopy, and central subfield thickness (CST) measured using spectral-domain optical coherence tomography.
Results
Overall, the 96 eyes of 96 patients with a median (interquartile range [IQR]) age of 57 (10) (range: 20–74) years and a male-to-female ratio of 1:2.7 were allocated to one of two groups with comparable age, sex, diabetes mellitus duration, and presence of other comorbidities (all P >0.05). There was no statistically significant difference in baseline diabetic retinopathy status or DME type between groups (both P >0.05). In both groups, the median (IQR) BCDVA significantly improved from 0.7 (0.8) logMAR at baseline to 0.4 (0.1) logMAR at 6 months post-injection (both P = 0.001), with no statistically significant difference between groups at all follow-up visits (all P >0.05). The median (IQR) CST significantly decreased in the aflibercept group from 347 (166) µm at baseline to 180 (233) µm at 6 months post-injection, and it decreased in the ranibizumab group from 360 (180) µm at baseline to 190 (224) µm at 6 months post-injection (both P = 0.001), with no statistically significant differences between groups at all follow-up visits (all P >0.05). No serious adverse effects were documented in either group.
Conclusions
Ranibizumab and aflibercept were equally effective in achieving the desired anatomical and functional results in patients with treatment-naïve DME in short-term follow-up without significant differences in injection counts between both drugs. Larger prospective, randomized, double-blinded trials with longer follow-up periods are needed to confirm our preliminary results.
... Because AMD is a degenerative disease characterized by inflammation, 98 it is possible that the anti-VEGF injections may increase retinal inflammation, but many clinical studies have documented that their beneficial effects in the neovascular form prevail over their possible adverse effects. 16,86,98,99 In summary, our findings reveal in the rat retina, microglial activation, and astrocyte hypertrophy after IVI of different substances, even after PBS injection, and a stronger microglial and macroglial cell response after IVI of ranibizumab and aflibercept at the higher concentration that is accompanied of RGCs death but not ipRGC death. It remains to be shown whether this RGC death is a direct toxic effect of the humanized ranibizumab or aflibercept on RGCs or an indirect effect, consequence of glial cell activation in the retina triggered by an immunological response. ...
Purpose:
In a previous study, we documented that the Intravitreal injections (IVIs) of bevacizumab in rats caused a retinal inflammatory response. We now study whether the IVI of other humanized anti-VEGF: ranibizumab and aflibercept also cause an inflammatory reaction in the rat retina and if it depends on the dose administered. Finally, we study whether this reaction affects retinal ganglion cell (RGC) survival.
Methods:
Albino Sprague-Dawley rats received a single IVI of 5 µL of PBS or ranibizumab or aflibercept at the concentration used in clinical practice (10 µg/µL or 40 µg/µL) or at a lower concentration (0.38 µg/µL and 1.5 µg/µL) calculated to obtain within the rat eye the same concentration as in the human eye in clinical practice. Others received a single 5 µL IVI of a polyclonal goat anti-rat VEGF (0.015 µg/µL) or of vehicle (PBS). Animals were processed 7 days or 1 month later. Retinal whole mounts were immunolabeled for the detection of microglial, macroglial, RGCs, and intrinsically photosensitive RGCs (ipRGCs). Fluorescence and confocal microscopy were used to examine retinal changes, and RGCs and ipRGCs were quantified automatically or semiautomatically, respectively.
Results:
All the injected substances including the PBS induced detectable side effects, namely, retinal microglial cell activation and retinal astrocyte hypertrophy. However, there was a greater microglial and macroglial response when the higher concentrations of ranibizumab and aflibercept were injected than when PBS, the antibody anti-rat VEGF and the lower concentrations of ranibizumab or aflibercept were injected. The higher concentration of ranibizumab and aflibercept resulted also in significant RGC death, but did not cause appreciable ipRGC death.
Conclusions:
The IVI of all the substances had some retinal inflammatory effects. The IVI of humanized anti-VEGF to rats at high doses cause important side effects: severe inflammation and RGC death, but not ipRGC death.
... 53 Aflibercept Aflibercept, also known as VEGF Trap-eye (Eylea ® , Regeneron, Rensselaer, NY, USA), is a 115 kDa recombinant humanized protein that acts as a soluble decoy receptor binding to VEGF-A, VEGF-B, and placental growth factor, thereby stopping the binding and activation of VEGF receptors. 54 Since its approval by the FDA for use in nAMD following the landmark VIEW1 and VIEW2 studies, 55 intravitreal aflibercept has been approved for a variety of other pathologies in 2011. There was also a suggestion that injections every 2 months with this VEGF trap may be equivalent to ranibizumab, the gold standard at the time. ...
Currently, the treatment for ocular neovascular diseases, including diabetic macular edema (DME) and age-related macular degeneration (AMD), mainly involves repeated intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs. Although it can preserve vision, repeated injections are an invasive treatment modality, leading to serious complications and reducing patient adherence to treatment. To reduce the frequency of administration, prolong the time of drug action, and avoid repeated intravitreal injections, the combination of sustained-release materials with anti-VEGF drug therapy has become an emphasis in ophthalmology. In this review, we highlight the current state of anti-VEGF technology, its challenges, and the sustained-release strategies under investigation or being used in clinical practice. Both continuous release and considerable therapeutic effects can be achieved by encapsulating anti-VEGF drugs in sustained-release materials to minimize the number of intravitreal injections. At present, two sustained-release materials are being tested in clinical research, and although basic research shows the strong therapeutic application prospects of extended-release drugs, its challenges mainly involve the discrepancy between the release rates in vitro and the efficiency of the drugs in vivo. Briefly, sustained release of anti-VEGF agents is an advantageous strategy for treating retinal angiogenesis.
... Patients diagnosed with RVO may develop vision loss or even blindness when complications such as neovascular glaucoma and macular edema arise [2]. Currently, RVO complications, including non-perfused areas and neovascular abnormalities, are clinically treated with intravitreal injections of anti-vascular endothelial growth factors, anti-inflammatory glucocorticoids, and retinal laser photocoagulation [3,4]. Retinal revascularization has undergone extensive research in RVO patients since the injection of a tissue plasminogen activator into the obstructed retinal vein was first reported [5]. ...
... Deoxyribonuclease I (DNase I), an economical, convenient, and widely used NETs inhibitor, has rarely been used in the prevention and treatment of RVO. This study 4 aimed to verify the presence of NETs in RVO and assess the protective efficiency of DNase I through in vitro and in vivo experiments, thereby providing a theoretical basis for RVO prevention and treatment. ...
Retinal vein occlusion (RVO) ranks as the second most prevalent retinal vascular disease, following diabetic retinopathy. Neutrophil extracellular traps (NETs) play an important role in vascular diseases. This study aimed to elucidate the relationship between NETs and RVO, and to discern the potential role of deoxyribonuclease I (DNase I) in the prevention and treatment of RVO through the modulation of NETs. We analyzed circulating NETs biomarkers, namely cell-free DNA (cf-DNA), myeloperoxidase (MPO)-DNA, and neutrophil elastase (NE), in 30 RVO patients and 30 healthy individuals. We established an RVO mouse model using a retinal laser, and the mice were categorized into two groups: the DNase I group and the control group. Retinal images were taken at predetermined time points, and the state of the retinal vessels was assessed. Both tissue and blood samples were harvested for analysis of NETs expression through methods such as western blotting, immunofluorescence staining, and enzyme-linked immunosorbent assay (ELISA). Our finding indicate an increase in circulating NETs biomarkers in human and mouse RVO cases, while also verifying the presence of NETs in the retinal thrombus of the RVO model. Both in vitro and in vivo tests revealed that DNase I attenuated NETs formation. Moreover, DNase I injections led to diminished NETs biomarker levels and a reduced duration of the thrombus after the RVO model establishment. Consequently, DNase I, a well-established modulator of NETs formation, might exhibit protective properties in the prevention and treatment of RVO.
... The frequent injections required for efficacy present both a significant treatment burden and risks of complications. 12 Furthermore, some patients exhibit an incomplete response to these therapies, underlining the necessity for treatments with novel mechanisms of action. 13 Faricimab, a novel bispecific antibody, offers potential solutions to these challenges. ...
Degenerative eye conditions such as age-related macular degeneration (AMD), diabetic retinopathy, and retinal vein occlusion are major contributors to significant vision loss in developed nations. The primary therapeutic approach for managing complications linked to these diseases involves the intravitreal delivery of anti-vascular endothelial growth factor (VEGF) treatments. Faricimab is a novel, humanised, bispecific antibody that simultaneously binds all VEGF-A isoforms and Angiopoietin-2, which has been approved by regulatory agencies, such as the US Food and Drug Administration (FDA), the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA), for the treatment of neovascular AMD and diabetic macular oedema (DMO). Intravitreal faricimab holds the promise of reducing the treatment burden for patients with these conditions by achieving comparable or superior therapeutic outcomes with fewer clinic visits. The scope of faricimab’s application includes addressing complex macular conditions such as DMO. This review intends to elucidate the distinctive pharmacological characteristics of faricimab and provide an overview of the key clinical trials and real-world studies that assess its effectiveness and safety in treating degenerative macular diseases.
... Accordingly, it inhibits the binding to, and activation of VEGF receptors [6]. Based on its pharmacologic effect, excellent safety profile, and long-term efficacy; aflibercept was proposed as a first line in the treatment of DME [7]. ...
Aim
The aim of this paper is to investigate the need of deferring cataract surgery until treating the co-existing diabetic macular edema (DME) using intravitreal (IVI) anti-vascular endothelial growth factor (anti-VEGF).
Methods
A prospective randomized interventional study included diabetic patients with visually significant cataract and DME. Patients were divided into 2 groups. Group A received three preoperative intravitreal (IVI) aflibercept injections with a monthly interval; the third injection was given intra-operatively. Group B received a single intra-operative injection, and two post-operative injections with a monthly interval. The primary outcome measure was the change in central macular thickness (CMT) at 1st and 6th month post-operative. The secondary outcome measures were best corrected visual acuity (BCVA) at same points and any documented adverse effects.
Results
Forty patients were enrolled in the study, 20 patients in each group. Means of CMT at 1 month post-operatively were significantly higher in group B than group A but no statistical difference at 6 months. There was no statistical difference between the 2 groups regarding BCVA at 1 or 6 months post-operatively. Compared with the baseline values, BCVA and CMT improved significantly after 1 and 6 months within both groups.
Conclusion
IVI of aflibercept given before cataract surgeries does not seem to have superior effect over postoperative injections in either macular thickness or visual outcomes. Hence, preoperative controlling of DME might not be mandatory in patients undergoing cataract surgery.
Clinical trial registration
The study is registered in clinical trial. Gov (NCT05731089).
... A number of key insights into eye disease have been revealed in the past decade, which has resulted in the development of novel, effective, targeted therapies such as teprotumumab for the treatment of thyroid eye disease (also known as Graves' orbitopathy) [1] and intraocular injections of antivascular endothelial growth factor (VEGF) agents for many retinal diseases [2]. This Special Issue aims to update the current evidence regarding challenging topics on the diagnosis and management of ocular diseases. ...
A number of key insights into eye disease have been revealed in the past decade, which has resulted in the development of novel, effective, targeted therapies such as teprotumumab for the treatment of thyroid eye disease (also known as Graves’ orbitopathy) [...]
... Branch retinal vein occlusion (BRVO) is the second most common retinal circulatory disease, and causes the retinal edema, hemorrhage, and/or ischemia in the affected area [1,2]; involvement of the macular area in these pathological indications results in significant vision impairments [3][4][5]. Anti-vascular endothelial growth factor (VEGF) therapy can be used to treat most macular edemas (MEs) [6][7][8][9][10], and this has led to substantial improvements in the clinical management of decreased visual acuity (VA) [11][12][13]. ...
Purpose
The pathology of branch retinal vein occlusion (BRVO), a retinal circulatory disease, is related to monocular metamorphopsia-related vision impairment of the affected eyes, but the association of binocular metamorphopsia in such patients is unclear. This study aimed to examine the frequency of binocular metamorphopsia and its association with the clinical characteristics of patients with BRVO.
Methods
A total of 87 patients who were treated for BRVO-associated macular edema (ME) were included in this study. At baseline and 1 and 3 months after the initiation of anti-vascular endothelial growth factor (VEGF) treatment, we quantified metamorphopsia in the affected eyes and binocular metamorphopsia using the M-CHARTS® diagnostic tool.
Results
At baseline, 53 and 7 patients had metamorphopsia in the affected eyes and binocular metamorphopsia, respectively. Although the visual acuity improved significantly after the initiation of anti-VEGF treatment, the mean M-CHARTS score in the affected eyes did not change from the baseline score. At 3 months, 9 patients showed binocular metamorphopsia; it was significantly associated with metamorphopsia in the affected eyes with a 95% confidence interval of 0.021–0.122 (β = 0.306, p = 0.006).
Conclusion
Metamorphopsia in the affected eyes can cause binocular metamorphopsia in patients with BRVO-ME.
