scholarly journals Pharmacological Analysis of Resistance to Anti-VEGF Therapy

2019 ◽  
Vol 15 (4) ◽  
pp. 382-387
Author(s):  
M. V. Budzinskaya ◽  
A. A. Plyukhova ◽  
I. V. Andreeva ◽  
A. V. Kuznetsov ◽  
A. V. Shelankova ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Combined Therapy ◽  
Developed Countries ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Anti Vegf ◽  
Age Related ◽  
Sudden Decrease ◽  
Endothelial Growth Factor ◽  
Vision Therapy

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.

scholarly journals Tie2 activation promotes choriocapillary regeneration for alleviating neovascular age-related macular degeneration

2019 ◽  
Vol 5 (2) ◽  
pp. eaau6732 ◽  
Author(s):  
Jaeryung Kim ◽  
Jang Ryul Park ◽  
Jeongwoon Choi ◽  
Intae Park ◽  
Yoonha Hwang ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Therapeutic Strategy ◽  
Vascular Leakage ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Medical Needs ◽  
Anti Vegf ◽  
Age Related ◽  
Angiopoietin 2 ◽  
Endothelial Growth Factor

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.

scholarly journals Emerging Therapies for Wet-Form (Neovascular) Age-Related Macular Degeneration

2017 ◽  
pp. 235-240
Keyword(s):  
Macular Degeneration ◽  
Viral Vectors ◽  
Developed Countries ◽  
Age Related Macular Degeneration ◽  
Vegf Inhibitors ◽  
Anti Vegf ◽  
Age Related ◽  
Emerging Therapies ◽  
Endothelial Growth Factor ◽  
Wet Amd

Age-related macular degeneration (AMD) is the most common cause of permanent visual loss in persons over 65 years of age in developed countries. Currently, intravitreal vascular endothelial growth factor (VEGF) inhibitors are the mainstay of the treatment for patients with wet AMD. Despite significant improvements in visual acuity since the beginning of these therapies, challenges in the treatment of wet AMD are still present. Therefore, there are ongoing researches such as sustained-release anti-VEGF therapy, novel generation anti-VEGF agents, viral vectors to modify genetic transcription, and combination therapies. In this review, it is aimed to discuss these emerging therapies.

scholarly journals Clinical efficacy of intravitreal corticoid as an adjunctive therapy to anti-VEGF treatment of neovascular age-related macular degeneration: a Meta-analysis

2021 ◽  
Vol 14 (7) ◽  
pp. 1092-1099
Author(s):  
Bo-Hao Cui ◽  
◽  
Wen-Wen Wang ◽  
Hao Yang ◽  
Ya-Lan Dong ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Adjunctive Therapy ◽  
Meta Analysis ◽  
Age Related Macular Degeneration ◽  
Cochrane Library ◽  
Vascular Endothelial ◽  
Anti Vegf ◽  
Age Related ◽  
Endothelial Growth Factor ◽  
Time Point

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.

scholarly journals Effects of Vitreomacular Adhesion on Age-Related Macular Degeneration

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Eui Chun Kang ◽  
Hyoung Jun Koh
Keyword(s):  
Macular Degeneration ◽  
Standard Treatment ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Neovascular Amd ◽  
Vitreomacular Adhesion ◽  
Anti Vegf ◽  
Age Related ◽  
Meta Analyses ◽  
Endothelial Growth Factor

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.

scholarly journals Angiomatozna proliferacija v mrežnici in polipi v žilnici – fenotipa neovaskularizacij pri starostni degeneraciji makule

2016 ◽  
Vol 85 (10) ◽  
Author(s):  
Tomislav Šarenac ◽  
Mateja Groboljšek Žgavc ◽  
Polona Jaki Mekjavič
Keyword(s):  
Visual Acuity ◽  
Vision Loss ◽  
Developed Countries ◽  
Age Related Macular Degeneration ◽  
Repeated Treatment ◽  
Vascular Endothelial ◽  
Anti Vegf ◽  
Age Related ◽  
Type 3 ◽  
Endothelial Growth Factor

Age-related macular degeneration (AMD) is the leading cause of loss of visual acuity in developed countries. Antagonists of Vascular Endothelial Growth Factor (anti-VEGF) have been successfully used intravitreally in treating the neovascular form of this disease (nAMD) and limiting vision loss. With the latest developments in multimodal imaging we can discern multiple types of neovascularization, some of which have an unusual course, despite treatment with anti-VEGF. Indocianine green angiography (ICGA) and optical coherence tomography (OCT) have been used to distinguish two special forms of nARMD, i.e., retinal angiomatous proliferation (RAP) and polypoidal choroidal vasculopathy (PCV). RAP appears in 10–15 % of newly discovered nARMD, usually in older patients and is also known as type 3 neovascularisation, which starts intraretinally. It responds well to anti-VEGF. However, it requires closer monitoring, since in 75 % of patients it requires repeated treatment. In contrast, PCV evolves in the choroid and typically causes hemorrhagic exudative maculopathy, which is relatively unresponsive to anti-VEGF. It appears in 4–14 % of nAMD, and in somewhat younger patients. It requires a specifc approach to treatment, combining anti-VEGF with laser therapy, and close monitoring.Although PCV and RAP are less common forms of nARMD, we should use and properly interpret FA, ICGA and OCT in order to initiate recommended treatments and follow-up. Herewith we can lessen the adverse impact on the visual acuity and increase the quality of life of our patients.

scholarly journals Predictors of neovascular activity during neovascular age-related macular degeneration treatment based on optical coherence tomography angiography

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kunho Bae ◽  
Hyo Jung Kim ◽  
Yong Kyun Shin ◽  
Se Woong Kang
Keyword(s):  
Optical Coherence Tomography ◽  
Macular Degeneration ◽  
Optical Coherence Tomography Angiography ◽  
Multivariate Regression Analysis ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Optical Coherence ◽  
Anti Vegf ◽  
Age Related ◽  
Endothelial Growth Factor

AbstractThe advent of anti-vascular endothelial growth factor (VEGF) therapies has remarkably improved the functional outcomes of neovascular age-related macular degeneration (nAMD) patients. However, there are guidelines on how to start treatment, the guidelines for discontinuing treatment are not yet clear. In this respect, the treat-extend-stop (TES) protocol have showed us the possibility of discontinuing treatment. In this study, we tried to investigate optical coherence tomography angiography (OCTA) biomarkers related to recurrence of neovascular activity in eyes with nAMD undergoing treatment using TES protocol. A total of 134 eyes with nAMD were divided into two groups (stop, non-stop) depending on whether they met criteria for stopping anti-VEGF treatment. Quantitative and qualitative OCTA parameters including the morphologic pattern of choroidal neovascularization (CNV) were compared between groups. Of these, 44 eyes (32.8%) were in the stop group and 90 eyes (67.2%) were in the non-stop group. In multivariate regression analysis, closed-circuit pattern of CNV and the presence of peripheral loop were associated with the non-stop group (all p < 0.001). Our results imply that the morphologic appearance of CNV on OCTA after anti-VEGF treatment may be a useful biomarker to predict weaning from treatment.

scholarly journals Therapy of Age-related Exudative Macular Degeneration with Anti-vascular Endothelial Growth Factor Drugs: An Italian Real Life Study

2021 ◽  
Vol 15 (1) ◽  
pp. 130-136
Author(s):  
Settimio Rossi ◽  
Carlo Gesualdo ◽  
Antonio Tartaglione ◽  
Giovan Battista Scazzi ◽  
Anna Cristina D’Alessio ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Real Life ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Life Study ◽  
Anti Vegf ◽  
Age Related ◽  
Real Life Study ◽  
Endothelial Growth Factor

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.

Relationship Between Claims Data and the Preferences and Trends Survey: An Analysis of Anti-Vascular Endothelial Growth Factor Medication Choice for Age-Related Macular Degeneration

2018 ◽  
Vol 2 (2) ◽  
pp. 96-99 ◽  
Author(s):  
Ravi Parikh ◽  
Paula W. Feng ◽  
Lucian V. Del Priore ◽  
Ron A. Adelman ◽  
Nauman A. Chaudhry
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Macular Degeneration ◽  
Claims Data ◽  
Practice Patterns ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Anti Vegf ◽  
Age Related ◽  
Endothelial Growth Factor

Purpose: To compare published self-reported practice patterns among retina specialists with published claims data representing actual practice patterns for the use of anti-vascular endothelial growth factor (anti-VEGF) medications in the treatment of age-related macular degeneration (AMD) in the United States. Methods: We compared physician self-reported preference for anti-VEGF medications to treat AMD in the American Society of Retina Specialists’ Preferences and Trends (PAT) survey with a previously published study using claims data from 2006 to 2015 from OptumLabs Data Warehouse as a data source. A Pearson χ2 test compared the relative proportions of drug use between the 2 groups, with <.05 indicating statistical significance. Results: From 2006 to 2015, the PAT surveys had approximately 3548 respondents to questions on which anti-VEGF medication was used for the treatment of AMD. Over the study period, 62.3% (2211/3548) of respondents preferred bevacizumab, 30.4% (1078/3548) ranibizumab, and 7.3% (259/3548) aflibercept in the treatment of AMD. Claims data on anti-VEGF use for AMD noted 59.7% (359 267/601 917) of injections were for bevacizumab, 23.8% (143 200/601 917) were for ranibizumab, and 16.5% (99 450/601 917) were for aflibercept. The difference in the relative use of bevacizumab, ranibizumab, and aflibercept use was not significant between the data sets ( P = .1991). Conclusions: The PAT survey responses appear to reflect actual physician practices based upon claims data and demonstrate the prevalence of bevacizumab as the prevailing treatment for AMD.

scholarly journals Proportion of and Reason for Bevacizumab Usage in the Treatment of Wet Age-related Macular Degeneration

2021 ◽  
Vol 62 (8) ◽  
pp. 1076-1083
Author(s):  
Yi Sang Yoon ◽  
Won Tae Yoon ◽  
Jong Woo Kim ◽  
Chul Gu Kim ◽  
Jae Hui Kim
Keyword(s):  
Macular Degeneration ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Common Reason ◽  
Vascular Endothelial ◽  
Corrected Visual Acuity ◽  
Anti Vegf ◽  
Age Related ◽  
Endothelial Growth Factor ◽  
Wet Amd

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.

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