Dataset Information

Increased mortality after intravitreal injections of anti-VEGF for neovascular AMD among patients with prior stroke or acute myocardial infarction.

ABSTRACT:

Objectives

To evaluate whether intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) in neovascular age-related macular degeneration (nAMD) patients with prior stroke or acute myocardial infarction (AMI) are associated with increased mortality.

Methods

From 2005 to 2013, nAMD patients in the Taiwan National Health Insurance Research Database who received IVI of anti-VEGF and had a diagnosis of stroke/AMI prior to their first injections were defined as the IVI group. The mortality of the IVI group during the study period was compared to that of the non-IVI group, which consisted of nAMD patients who had prior stroke/AMI but were never exposed to anti-VEGF. The IVI group and the non-IVI group were 1-4 matched according to propensity score (PS), which was derived from age, sex, date of stroke/AMI and comorbidities. PS-adjusted Cox regression analyses were used to estimate the hazard ratio (HR) for mortality associated with IVI of anti-VEGF. Subgroup analyses were also performed according to the interval between stroke/AMI and IVI (≤6 months, 6 months to 1 year, 1-2 years, >2 years).

Results

There were 3384 individuals in the IVI group and 13,536 individuals in the non-IVI group. The IVI group had a significantly higher mortality risk (adjusted HR = 2.37; 95% confidence interval (CI), 2.14-2.62) than the non-IVI group. Subgroup analyses revealed that elevated mortality was significant when anti-VEGF was injected within 1 year after stroke/AMI.

Conclusions

We found an increased mortality risk associated with IVI of anti-VEGF in nAMD patients with prior stroke/AMI compared to the mortality risk of nAMD patients with prior stroke/AMD but without exposure to anti-VEGF.

SUBMITTER: Chen YY

PROVIDER: S-EPMC8727623 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

Increased mortality after intravitreal injections of anti-VEGF for neovascular AMD among patients with prior stroke or acute myocardial infarction.

Chen Yu-Yen YY Lai Yun-Ju YJ Yen Yung-Feng YF Chou Pesus P

Eye (London, England) 20210302 1

<h4>Objectives</h4>To evaluate whether intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) in neovascular age-related macular degeneration (nAMD) patients with prior stroke or acute myocardial infarction (AMI) are associated with increased mortality.<h4>Methods</h4>From 2005 to 2013, nAMD patients in the Taiwan National Health Insurance Research Database who received IVI of anti-VEGF and had a diagnosis of stroke/AMI prior to their first injections were defined a ...[more]

PMID: 33654317

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Project description:Background The study aimed to evaluate the changes in retinal vascular density in exudative age-related macular degeneration (AMD) after long-term anti-VEGF treatment using optical coherence tomography angiography (OCT-A), and to compare these changes with the vascular density in AMD treated for one year and healthy eyes. Methods In our cross-sectional study OCT-A was performed on 60 eyes of 60 patients. Group AMD 20 × consisted of patients receiving long-term (minimum 20 injections) aflibercept therapy (n = 17), and Group AMD one year consisted of patients treated for one year with a treat & extend protocol (n = 25). The vascular density values obtained with OCT-A were compared with an age-matched control group of 18 healthy eyes. We examined the central retinal thickness (CRT), the vascular density of the fovea and parafovea in the superficial and deep retinal plexus, and evaluated the extent of the non-flow area and the foveal avascular zone (FAZ) on a 3 × 3 mm macular region. Kruskal–Wallis test was performed for statistical analysis. Results In Group AMD 20x, the vascular density of superficial retinal plexus in the fovea (p = 0.0022) and parafovea (p < 0.0001) was significantly lower compared to Group one year and control group. In the deep retinal plexus, vascular density in the fovea (p = 0.0033) was significantly lower in both AMD groups compared to the control group, with no difference in the parafoveal region (p = 0.0774). The extent of non-flow area (p = 0.0003) and FAZ (p = 0.0008) were significantly larger in both AMD groups compared to the control group. There was a significant difference in CRT between those treated for one year and control eyes (p = 0.0036). Conclusions In our study, we demonstrated that macular vessel density was lower in the foveal area in the superficial retinal plexus in AMD patients after one year and long-term anti-VEGF treatment. These vascular density changes were absent in the parafoveal and whole areas of the deep retinal plexus. Our results indicate that long-term anti-VEGF treatment reduces the vascular density of the superficial retinal plexus to a greater extent compared to the deep retinal plexus. Supplementary Information The online version contains supplementary material available at 10.1186/s12886-022-02700-8.

Project description:PurposeIntravitreal (IVT) injections of the anti-vascular endothelial growth factor (VEGF) agents aflibercept, bevacizumab, and ranibizumab are commonly prescribed to treat neovascular age-related macular degeneration (nAMD). Studies comparing inflammation rates in large populations of patients receiving these agents and the treatment of ocular inflammation post-IVT anti-VEGF injections are scarce. In this study, we compared rates of endophthalmitis claims (sterile and infectious) following IVT anti-VEGF injections to determine the risk factors associated with developing endophthalmitis, and examined the claims for subsequent treatment.Patients and methodsThis retrospective cohort study of USA claims data examined the risk of developing endophthalmitis following IVT injection of aflibercept, bevacizumab, or ranibizumab in patients with nAMD between 11/18/2011 and 5/31/2013. The primary study outcome was occurrence of endophthalmitis within 30 days of a claim for an IVT anti-VEGF injection. Endophthalmitis rates were calculated separately for aflibercept, bevacizumab, and ranibizumab, followed by pairwise comparisons of endophthalmitis frequencies among the 3 treatments.ResultsThis analysis included 818,558 injections from 156,594 patients with nAMD. The rates (% [n/N]) of endophthalmitis following aflibercept, bevacizumab, and ranibizumab IVT injections were 0.100% (136/135,973), 0.056% (268/481,572), and 0.047% (94/201,013), respectively. In a multivariate analysis, aflibercept was associated with a significantly higher risk of endophthalmitis vs ranibizumab (adjusted odds ratio, 2.19; 95% CI: 1.68-2.85; P<0.0001). The risk of endophthalmitis was similar for bevacizumab and ranibizumab. Within 14 days after endophthalmitis, 38.6% of cases received injectable antibiotics, 15.3% received injectable steroids, and 30.3% underwent vitrectomy.ConclusionThe rate of endophthalmitis was very low, but higher following IVT injection with aflibercept compared with both bevacizumab and ranibizumab in patients with nAMD.

Project description:Intravitreal anti-vascular endothelial growth factor (VEGF) drugs have revolutionized the treatment of neovascular age-related macular degeneration (NVAMD). However, many patients suffer from incomplete response to anti-VEGF therapy (IRT), which is defined as (1) persistent (plasma) fluid exudation; (2) unresolved or new hemorrhage; (3) progressive lesion fibrosis; and/or (4) suboptimal vision recovery. The first three of these collectively comprise the problem of persistent disease activity (PDA) in spite of anti-VEGF therapy. Meanwhile, the problem of suboptimal vision recovery (SVR) is defined as a failure to achieve excellent functional visual acuity of 20/40 or better in spite of sufficient anti-VEGF treatment. Thus, incomplete response to anti-VEGF therapy, and specifically PDA and SVR, represent significant clinical unmet needs. In this review, we will explore PDA and SVR in NVAMD, characterizing the clinical manifestations and exploring the pathobiology of each. We will demonstrate that PDA occurs most frequently in NVAMD patients who develop high-flow CNV lesions with arteriolarization, in contrast to patients with capillary CNV who are highly responsive to anti-VEGF therapy. We will review investigations of experimental CNV and demonstrate that both types of CNV can be modeled in mice. We will present and consider a provocative hypothesis: formation of arteriolar CNV occurs via a distinct pathobiology, termed neovascular remodeling (NVR), wherein blood-derived macrophages infiltrate the incipient CNV lesion, recruit bone marrow-derived mesenchymal precursor cells (MPCs) from the circulation, and activate MPCs to become vascular smooth muscle cells (VSMCs) and myofibroblasts, driving the development of high-flow CNV with arteriolarization and perivascular fibrosis. In considering SVR, we will discuss the concept that limited or poor vision in spite of anti-VEGF may not be caused simply by photoreceptor degeneration but instead may be associated with photoreceptor synaptic dysfunction in the neurosensory retina overlying CNV, triggered by infiltrating blood-derived macrophages and mediated by Müller cell activation Finally, for each of PDA and SVR, we will discuss current approaches to disease management and treatment and consider novel avenues for potential future therapies.

Dataset Information

Increased mortality after intravitreal injections of anti-VEGF for neovascular AMD among patients with prior stroke or acute myocardial infarction.

Objectives

Methods

Results

Conclusions

Publications

Increased mortality after intravitreal injections of anti-VEGF for neovascular AMD among patients with prior stroke or acute myocardial infarction.

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