scholarly journals Comparative Safety of Bevacizumab, Ranibizumab, and Aflibercept for Treatment of Neovascular Age-Related Macular Degeneration (AMD): A Systematic Review and Network Meta-Analysis of Direct Comparative Studies

2020 ◽  
Vol 9 (5) ◽  
pp. 1522 ◽  
Author(s):  
Anna A. Plyukhova ◽  
Maria V. Budzinskaya ◽  
Kirill M. Starostin ◽  
Robert Rejdak ◽  
Claudio Bucolo ◽  
...  

Background: Since the efficacy of ranibizumab (RBZ), bevacizumab (BVZ) and aflibercept (AFB) is comparable in neovascular age-related macular degeneration (AMD), we conducted a systematic review and meta-analysis to evaluate the long-term safety profiles of these agents, including ocular safety. Methods: Systematic review identifying randomized controlled trials (RCTs) comparing RBZ, BVZ and AFB directly published before March 2019. Serious ocular adverse events (SOAE) of special interest were endophthalmitis, pseudo-endophthalmitis, retinal pigment epithelium tear and newly identified macular atrophy. Results: Thirteen RCTs selected for meta-analysis (4952 patients, 8723 people-years follow-up): 10 compared RBZ vs. BVZ and three RBZ vs. AFB. There were no significant differences in almost all adverse events (systemic and ocular) between BVZ, RBZ and AFB in up to two years’ follow-up. Macular atrophy was reported heterogeneously and not reported as SOAE in most trials. Conclusions: Direct comparison of RBZ, BVZ and AFB safety profiles in the RCT network meta-analytical setting have not revealed a consistent benefit of these three commonly used anti-vascular endothelial growth factor (anti-VEGF) agents in AMD. Network model ranking highlighted potential benefits of RBZ in terms of a systemic safety profile; however, this appears a hypothesis rather than a conclusion. Newly identified macular atrophy is underestimated in RCTs—future real-world data should be focused on SOAE.

2020 ◽  
pp. 112067212090871
Author(s):  
Mariana A Oliveira ◽  
Cláudia Farinha ◽  
Tiago M Rodrigues ◽  
Amélia Martins ◽  
Maria da Luz Cachulo ◽  
...  

Purpose: To assess the development of macular atrophy, according to the new Classification of Atrophy Meetings criteria, in patients with treatment-naïve neovascular age-related macular degeneration during the first year of treatment with ranibizumab or aflibercept, and to determine baseline factors predictive of atrophy development. Methods: Retrospective subanalysis of three prospective clinical trials that included eyes with treatment-naïve neovascular age-related macular degeneration. Multimodal evaluation was performed with spectral-domain optical coherence tomography, fluorescein angiography, fundus autofluorescence and color fundus photography at baseline and after 12 months of treatment. The main outcome was the macular atrophy type, classified according to Classification of Atrophy Meeting criteria. Logistic regression models were built to test predictors of macular atrophy development. Results: A total of 85 eyes of 85 patients (63% female; mean age: 78.5 ± 6.3 years old) were included. After 12 months of antiangiogenic therapy, all four Classification of Atrophy Meeting types of macular atrophy developed de novo. The atrophy type with highest incidence at end of follow-up was incomplete retinal pigment epithelium and outer retinal atrophy (63.6%; 95% confidence interval: 45.9%–86.0%). A significant association was observed between development at 12 months and the presence of incomplete retinal pigment epithelium and outer retinal atrophy at baseline (odds ratio (95% confidence interval): 22.4 (1.6, 323.5)). The number of injections was predictive of complete outer retinal atrophy development at end of follow-up (odds ratio (95% confidence interval) 1.5 (1.1, 2.1), p = 0.011). Conclusion: Predictors of atrophy development have the potential to change treatment practices. Further research is warranted.


2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Cristian Metrangolo ◽  
Simone Donati ◽  
Marco Mazzola ◽  
Liviana Fontanel ◽  
Walter Messina ◽  
...  

Age-related macular degeneration (AMD) is the leading cause of legal blindness in elderly people. Neovascular AMD (nAMD) is responsible for the majority of cases of severe visual loss in eyes with AMD. Optical coherence tomography (OCT) is the most widely used technology for the diagnosis and follow-up of nAMD patients, which is widely used to study and guide the clinical approach, as well as to predict and evaluate treatment response. The aim of this review is to describe and analyze various structural OCT-based biomarkers, which have practical value during both initial assessment and treatment follow-up of nAMD patients. While central retinal thickness has been the most common and one of the first OCT identified biomarkers, today, other qualitative and quantitative biomarkers provide novel insight into disease activity and offer superior prognostic value and better guidance for tailored therapeutic management. The key importance of retinal fluid compartmentalization (intraretinal fluid, subretinal fluid, and subretinal pigment epithelium (RPE) fluid) will be discussed firstly. In the second part, the structural alterations of different retinal layers in various stages of the disease (photoreceptors layer integrity, hyperreflective dots, outer retinal tubulations, subretinal hyperreflective material, and retinal pigment epithelial tears) will be analyzed in detail. The last part of the review will focus on how alterations of the vitreoretinal interface (vitreomacular adhesion and traction) and of the choroid (sub-RPE hyperreflective columns, prechoroidal clefts, choroidal caverns, choroidal thickness and choroidal volume, and choroidal vascular index) interact with nAMD progression. OCT technology is evolving very quickly, and new retinal biomarkers are continuously described. This up-to-date review article provides a comprehensive description on how structural OCT-based biomarkers provide a valuable tool to monitor the progression of the disease and the treatment response in nAMD patients. Thus, in this perspective, clinicians will be able to allocate hospital resources in the best possible way and tailor treatment to the individual patient’s needs.


2014 ◽  
Vol 7 (2) ◽  
pp. 148-154
Author(s):  
Elitsa G. Hristova ◽  
Zornitsa I. Zlatarova

Summary The purpose of the study was to present the ability of Drusen analysis software tool to measure drusen area and volume in patients with dry age-related macular degeneration (AMD). Eleven patients with confirmed dry AMD aged 59-74 years were scanned with 3D OCT-2000 Topcon 3D Macula scanning protocol by a single operator. All subjects underwent a complete ophthalmologic examination including best corrected visual acuity, indirect biomicroscopy, tonometry, fluorescein angiography and OCT. Drusen analysis was performed on the macula with 6.0 × 6.0 mm volume cube scans and 512×128 pixels scan resolution. The results were presented along with calculated values in two clearly arranged reports. Mean follow-up period was 19 months (6-40). Count, area occupation, volume of the drusen and 3D retinal pigment epithelium (RPE) elevation map were presented in a Macula drusen analysis report. Drusen count and volume in 6 patients were increased at the end of follow-up period. There were 5 patients with regression in drusen count and area and volume of the drusen in 3 of them were higher than on previous examination. Another 2 were with regression not only in drusen count but also in their area and volume. With this software tool the status of RPE can be objectively and automatically examined in detail and can be followed up over time. OCT allows for precise quantitative evaluation and study of microstructural changes in patients with dry AMD and provides three-dimensional information of macular pathology in situ and in real time. This could be useful for determining stages and monitoring the progression of AMD.


F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 245 ◽  
Author(s):  
Francesco Bandello ◽  
Riccardo Sacconi ◽  
Lea Querques ◽  
Eleonora Corbelli ◽  
Maria Vittoria Cicinelli ◽  
...  

Age-related macular degeneration (AMD), the most important cause of vision loss in elderly people, is a degenerative disorder of the central retina with a multifactorial etiopathology. AMD is classified in dry AMD (d-AMD) or neovascular AMD depending on the presence of choroidal neovascularization. Currently, no therapy is approved for geographic atrophy, the late form of d-AMD, because no treatment can restore the damage of retinal pigment epithelium (RPE) or photoreceptors. For this reason, all treatment approaches in d-AMD are only likely to prevent and slow down the progression of existing atrophy. This review focuses on the management of d-AMD and especially on current data about potential targets for therapies evaluated in clinical trials. Numerous examinations are available in clinics to monitor morphological changes in the retina, RPE and choroid of d-AMD patients. Fundus autofluorescence and optical coherence tomography (OCT) are considered the most useful tools in the diagnosis and follow-up of d-AMD alterations, including the monitoring of atrophy area progression. Instead, OCT-angiography is a novel imaging tool that may add further information in patients affected by d-AMD. Several pathways, including oxidative stress, deposits of lipofuscin, chronic inflammation and choroidal blood flow insufficiency, seem to play an important role in the pathogenesis of d-AMD and represent possible targets for new therapies. A great number of treatments for d-AMD are under investigation with promising results in preliminary studies. However, only few of these drugs will enter the market, offering a therapeutic chance to patients affected by the dry form of AMD and help them to preserve a good visual acuity. Further studies with a long-term follow-up would be important to test the real safety and efficacy of drugs under investigation.


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