scholarly journals Systemic Side Effects and Geographic Atrophy after Anti-VEGF Treatment in Wet-Form (Neovascular) Age-Related Macular Degeneration

Neovascular (wet-form) age-related macular degeneration (nARMD) is one of the leading causes of serious loss of vision in the elderly population. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents are commonly used in the treatment of nARMD. Systemic side effects and geographic atrophy following intravitreal administration of anti-VEGF agents in nARMD are mentioned in this review.

2021 ◽  
Vol 62 (8) ◽  
pp. 1076-1083
Author(s):  
Yi Sang Yoon ◽  
Won Tae Yoon ◽  
Jong Woo Kim ◽  
Chul Gu Kim ◽  
Jae Hui Kim

Purpose: To evaluate the proportion of bevacizumab and the reason for its usage in wet age-related macular degeneration (AMD).Methods: Retrospective analysis of medical records was performed for 1,541 patients who received ranibizumab, aflibercept, or bevacizumab injection to treat wet AMD. The proportion of bevacizumab among the entire set of injections was identified. The reason for selecting bevacizumab was additionally identified.Results: During the study period, a total of 2,929 anti-vascular endothelial growth factor (anti-VEGF) injections were performed; 2,236 (76.3%) were ranibizumab or aflibercept injections and 693 (23.7%) were bevacizumab injections. The most common reason for bevacizumab usage was ‘having a 0.1 or worse best-corrected visual acuity or being unable to assure reimbursement due to the development of extensive scarring or geographic atrophy’ (297 bevacizumab injections, 42.9%). The second most common reason was ‘the inability to assure reimbursement such as extrafoveal choroidal neovascularization (CNV) or early CNV without definite fluid in the foveal region’ (201 bevacizumab injections, 29.0%).Conclusions: Bevacizumab was used in 23.7% of the anti-VEGF injections to treat wet AMD. When analyzing patients’ treatment burden and financial impact, the results of the present study may provide useful information. Further multi-center studies are required to evaluate more precisely the usage of anti-VEGF drugs.


2020 ◽  
Vol 2020 ◽  
pp. 1-19 ◽  
Author(s):  
Samuel Abokyi ◽  
Chi-Ho To ◽  
Tim T. Lam ◽  
Dennis Y. Tse

Age-related macular degeneration (AMD) is a common cause of visual impairment in the elderly. There are very limited therapeutic options for AMD with the predominant therapies targeting vascular endothelial growth factor (VEGF) in the retina of patients afflicted with wet AMD. Hence, it is important to remind readers, especially those interested in AMD, about current studies that may help to develop novel therapies for other stages of AMD. This study, therefore, provides a comprehensive review of studies on human specimens as well as rodent models of the disease, to identify and analyze the molecular mechanisms behind AMD development and progression. The evaluation of this information highlights the central role that oxidative damage in the retina plays in contributing to major pathways, including inflammation and angiogenesis, found in the AMD phenotype. Following on the debate of oxidative stress as the earliest injury in the AMD pathogenesis, we demonstrated how the targeting of oxidative stress-associated pathways, such as autophagy and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, might be the futuristic direction to explore in the search of an effective treatment for AMD, as the dysregulation of these mechanisms is crucial to oxidative injury in the retina. In addition, animal models of AMD have been discussed in great detail, with their strengths and pitfalls included, to assist inform in the selection of suitable models for investigating any of the molecular mechanisms.


2019 ◽  
Vol 5 (2) ◽  
pp. eaau6732 ◽  
Author(s):  
Jaeryung Kim ◽  
Jang Ryul Park ◽  
Jeongwoon Choi ◽  
Intae Park ◽  
Yoonha Hwang ◽  
...  

Choriocapillary loss is a major cause of neovascular age-related macular degeneration (NV-AMD). Although vascular endothelial growth factor (VEGF) blockade for NV-AMD has shown beneficial outcomes, unmet medical needs for patients refractory or tachyphylactic to anti-VEGF therapy exist. In addition, the treatment could exacerbate choriocapillary rarefaction, necessitating advanced treatment for fundamental recovery from NV-AMD. In this study, Tie2 activation by angiopoietin-2–binding and Tie2-activating antibody (ABTAA) presents a therapeutic strategy for NV-AMD. Conditional Tie2 deletion impeded choriocapillary maintenance, rendering eyes susceptible to NV-AMD development. Moreover, in a NV-AMD mouse model, ABTAA not only suppressed choroidal neovascularization (CNV) and vascular leakage but also regenerated the choriocapillaris and relieved hypoxia. Conversely, VEGF blockade degenerated the choriocapillaris and exacerbated hypoxia, although it suppressed CNV and vascular leakage. Together, we establish that angiopoietin-Tie2 signaling is critical for choriocapillary maintenance and that ABTAA represents an alternative, combinative therapeutic strategy for NV-AMD by alleviating anti-VEGF adverse effects.


2021 ◽  
Vol 14 (7) ◽  
pp. 1092-1099
Author(s):  
Bo-Hao Cui ◽  
◽  
Wen-Wen Wang ◽  
Hao Yang ◽  
Ya-Lan Dong ◽  
...  

AIM: To evaluate the efficacy and safety of intravitreal corticoid as an adjunctive therapy to anti-vascular endothelial growth factor (VEGF) treatment of neovascular age-related macular degeneration (nvAMD). METHODS: Four databases including PubMed, Embase, Cochrane Library, and the clinicaltrials.gov were comprehensively searched for studies comparing intravitreal corticoid plus anti-VEGF (IVC/IVA) vs anti-VEGF monotherapy (IVA) in patients with nvAMD. GRADE profiler was used to assess the quality of outcomes. Best-corrected visual acuity (BCVA), central macular thickness (CMT) and adverse events including the occurrence of severe elevation of intraocular pressure (IOP) and the progress of cataract were extracted from the eligible studies. Review Manager (RevMan) 5.3 was used to analyze the data. RESULTS: There was no statistic difference of mean change in BCVA at 6 and 12mo between IVC/IVA and IVA group [95% confidence interval (CI): -2.28 to 4.24, P=0.55; 95%CI: -3.01 to 8.70, P=0.34]. No statistic difference was found in the change of CMT between two groups at 6mo time point (95%CI: -17.98 to 16.42, P=0.93) while the CMT reduction in IVC/IVA group was significantly more obvious than IVA group at 12mo time point [mean difference (MD)=-44.08, 95%CI: -80.52 to -7.63, P=0.02]. The risk of occurrence of severe elevation of IOP in the IVC/IVA group was higher than that in the IVA group (95%CI: 1.92 to 9.48; P=0.0004). Cataract progression risk was calculated no statistic difference between two groups (95%CI: 0.74 to 4.66; P=0.18). CONCLUSION: No visual or anatomical benefits are observed in IVC/IVA group at 6mo. At 12mo, the CMT of the IVC/IVA group is significantly lower than that of the IVA group. Risk of severe elevation of IOP is significantly higher when treated by IVC/IVA.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Eui Chun Kang ◽  
Hyoung Jun Koh

Herein, we review the association between vitreomacular adhesion (VMA) and neovascular age-related macular degeneration (AMD). Meta-analyses have shown that eyes with neovascular AMD are twice as likely to have VMA as normal eyes. VMA in neovascular AMD may induce inflammation, macular traction, decrease in oxygenation, sequestering of vascular endothelial growth factor (VEGF), and other cytokines or may directly stimulate VEGF production. VMA may also interfere with the treatment effects of anti-VEGF therapy, which is the standard treatment for neovascular AMD, and releasing VMA can improve the treatment response to anti-VEGF treatment in neovascular AMD. We also reviewed currently available methods of relieving VMA.


2019 ◽  
Vol 15 (4) ◽  
pp. 382-387
Author(s):  
M. V. Budzinskaya ◽  
A. A. Plyukhova ◽  
I. V. Andreeva ◽  
A. V. Kuznetsov ◽  
A. V. Shelankova ◽  
...  

Age-related macular degeneration (AMD) is a disease that occurs in adults over 50 years old and the leading cause of irreversible blindness in developed countries. AMD is characterized with a lesion of retina macular area and leads to a deterioration in central vision. Therapy aimed at combating the vascular endothelial growth factor (VEGF) resulted in an increase of corrected visual acuity in patients with neovascular age-related macular degeneration. Possible significant differences in the response to anti-VEGF therapy are due to the existence of several anti-VEGF agents with different molecular configurations. Currently, there is no consensus on classification of the optimal response or its absence with this method of treatment. In particular, there is confusion about such terms as “defendant status” after treatment with n-AMD, “tachyphylaxis” and “resistant” n-AMD. Drug tolerance is a pharmacological concept applicable to a patient’s response to a particular drug, with the physiological drug concentration is reducing in case of re-introduced. It requires the increasement the dose or frequency of drug administration to achieve the desired therapeutic effect. Tachyphylaxis is a term indicating a sudden decrease in response to a drug after its administration. This process can develop both after the initial or several administration in small doses. Tachyphylaxis develops in the background or after treatment with ranibizumab with at least two injections of the drug.Switching the treatment regimen to aflibercept or conbercept can be effective in patients resistant to bevascizumab or ranibizumab.The involvement of other pathological processes in the development mechanism of the neovascular form of AMD in addition to increased expression of VEGF dictates the need for combined therapy for this group of patients.


2021 ◽  
Vol 15 (1) ◽  
pp. 130-136
Author(s):  
Settimio Rossi ◽  
Carlo Gesualdo ◽  
Antonio Tartaglione ◽  
Giovan Battista Scazzi ◽  
Anna Cristina D’Alessio ◽  
...  

Aim: To evaluate the real utilization of ranibizumab and aflibercept in the daily management of patients with neovascular age-related macular degeneration (nAMD) treated at the Eye Clinic of Campania University L.Vanvitelli. Background: Therapy with anti-vascular endothelial growth factor represents the gold standard in wet age-related macular degeneration. There are nonreal life italian studies of this therapy in the literature. Objective: To analyze in our sample the post-therapy variations of best-corrected visual acuity (BCVA) and central retinal thickness (CRT) observed at the end of a 12-month follow-up period. Methods: This real-life study analyzes 109 patients that underwent monthly checks for the first 4 months and then every 2 months until the end of the 12-month follow-up. The sample was first analyzed in its entirety, subsequently subdivided into 3 groups based on baseline BCVA, age, and the number of intravitreal injections performed, in order to identify possible predictive elements of the anti-VEGF response. Results: On average, patients underwent 4.16 ± 1.58 intravitreal anti-VEGF injections in 1 year. At the end of the 12-month follow-up, the patients’ average BCVA increased from 33.01 letters to 33.75 letters (+0.74 ± 9,4 letters), while the average CRT decreased from 346.86 µm to 265.39 µm (-81.47 ± 121 µm). Conclusion: The study shows the efficacy of anti-VEGF therapy in the stabilization of BCVA in nAMD, confirming the differences in visual outcomes compared to clinical trials, mainly for economic-organizational reasons.


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