scholarly journals Anti-VEGF-Resistant Retinal Diseases: A Review of the Latest Treatment Options

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1049
Author(s):  
Josh O. Wallsh ◽  
Ron P. Gallemore
Keyword(s):  
Treatment Options ◽  
Vascular Diseases ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Vascular Endothelial ◽  
Future Directions ◽  
Anti Vegf ◽  
Age Related ◽  
Endothelial Growth Factor ◽  
Topical Medications

Anti-vascular endothelial growth factor (anti-VEGF) therapy currently plays a central role in the treatment of numerous retinal diseases, most notably exudative age-related macular degeneration (eAMD), diabetic retinopathy and retinal vein occlusions. While offering significant functional and anatomic benefits in most patients, there exists a subset of 15–40% of eyes that fail to respond or only partially respond. For these cases, various treatment options have been explored with a range of outcomes. These options include steroid injections, laser treatment (both thermal therapy for retinal vascular diseases and photodynamic therapy for eAMD), abbreviated anti-VEGF treatment intervals, switching anti-VEGF agents and topical medications. In this article, we review the effectiveness of these treatment options along with a discussion of the current research into future directions for anti-VEGF-resistant eyes.

scholarly journals Development of Anti-VEGF Therapies for Intraocular Use: A Guide for Clinicians

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Pearse A. Keane ◽  
Srinivas R. Sadda
Keyword(s):  
Vascular Diseases ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Vein Occlusion ◽  
Anti Vegf ◽  
Age Related ◽  
Vessel Growth ◽  
Vessel Networks ◽  
Endothelial Growth Factor ◽  
Made In

Angiogenesis is the process by which new blood vessels form from existing vessel networks. In the past three decades, significant progress has been made in our understanding of angiogenesis; progress driven in large part by the increasing realization that blood vessel growth can promote or facilitate disease. By the early 1990s, it had become clear that the recently discovered “vascular endothelial growth factor” (VEGF) was a powerful mediator of angiogenesis. As a result, several groups targeted this molecule as a potential mediator of retinal ischemia-induced neovascularization in disorders such as diabetic retinopathy and retinal vein occlusion. Around this time, it also became clear that increased intraocular VEGF production was not limited to ischemic retinal diseases but was also a feature of choroidal vascular diseases such as neovascular age-related macular degeneration (AMD). Thus, a new therapeutic era emerged, utilizing VEGF blockade for the management of chorioretinal diseases characterized by vascular hyperpermeability and/or neovascularization. In this review, we provide a guide for clinicians on the development of anti-VEGF therapies for intraocular use.

scholarly journals Association between Retinal Thickness Variability and Visual Acuity Outcome during Maintenance Therapy Using Intravitreal Anti-Vascular Endothelial Growth Factor Agents for Neovascular Age-Related Macular Degeneration

2021 ◽  
Vol 11 (10) ◽  
pp. 1024
Author(s):  
Timothy Y. Y. Lai ◽  
Ricky Y. K. Lai
Keyword(s):  
Visual Acuity ◽  
Retinal Thickness ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Anti Vegf ◽  
Age Related ◽  
Thickness Variability ◽  
The Mean ◽  
Endothelial Growth Factor

Previous studies based on clinical trial data have demonstrated that greater fluctuations in retinal thickness during the course of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD) is associated with poorer visual acuity outcomes. However, it was unclear whether similar findings would be observed in real-world clinical settings. This study aimed to evaluate the association between retinal thickness variability and visual outcomes in eyes receiving anti-VEGF therapy for nAMD using pro re nata treatment regimen. A total of 64 eyes which received intravitreal anti-VEGF therapy (bevacizumab, ranibizumab or aflibercept) for the treatment of nAMD were evaluated. Variability in spectral-domain optical coherence tomography (OCT) central subfield thickness (CST) was calculated from the standard deviation (SD) values of all follow-up visits after three loading doses from month 3 to month 24. Eyes were divided into quartiles based on the OCT CST variability values and the mean best-corrected visual acuity values at 2 years were compared. At baseline, the mean ± SD logMAR visual acuity and CST were 0.59 ± 0.39 and 364 ± 113 µm, respectively. A significant correlation was found between CST variability and visual acuity at 2 years (Spearman’s ρ = 0.54, p < 0.0001), indicating that eyes with lower CST variability had better visual acuity at 2 years. Eyes with the least CST variability were associated with the highest mean visual acuity improvement at 2 years (quartile 1: +9.7 letters, quartile 2: +1.1 letters, quartile 3: −2.5 letters, quartile 4: −9.5 letters; p = 0.018). No significant difference in the number of anti-VEGF injections was found between the four CST variability quartile groups (p = 0.21). These findings showed that eyes undergoing anti-VEGF therapy for nAMD with more stable OCT CST variability during the follow-up period were associated with better visual outcomes. Clinicians should consider adopting treatment strategies to reduce CST variability during the treatment course for nAMD.

Arteriosclerotic Changes after Intravitreal Injections of Anti-Vascular Endothelial Growth Factor Drugs in Patients with Exudative Age-Related Macular Degeneration

2016 ◽  
Vol 235 (4) ◽  
pp. 225-232 ◽  
Author(s):  
Tomoaki Shiba ◽  
Mao Takahashi ◽  
Izumi Yoshida ◽  
Hikari Taniguchi ◽  
Tadashi Matsumoto ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Protective Factor ◽  
Age Related Macular Degeneration ◽  
Intravitreal Injections ◽  
Vascular Endothelial ◽  
Cumulative Number ◽  
Anti Vegf ◽  
Age Related ◽  
Endothelial Growth Factor

Purpose: The aim of this study was to determine whether multiple intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs for age-related macular degeneration (AMD) exacerbate systemic arteriosclerosis, using the cardio-ankle vascular index (CAVI) and intima-media thickness (IMT). Methods: We analyzed the data of 45 AMD patients who received intravitreal injections of anti-VEGF drugs (ranibizumab and/or aflibercept) and underwent systemic evaluations at baseline and after treatment. Reevaluation was conducted at ≥12 months from the initial treatment. Results: The total number of intravitreal injections of overall anti-VEGF drugs was significantly correlated with Δserum cystatin C. The cumulative number of aflibercept injections was identified as an independent protective factor for ΔCAVI. An increase in the cumulative number of intravitreal injections of overall anti-VEGF drugs was identified as a protective factor for Δmean IMT. Conclusion: Repeated intravitreal injections of an anti-VEGF drug for AMD may lead to morphological and functional changes in large arteries.

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 Outcome of anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration in real-life setting

2017 ◽  
Vol 102 (7) ◽  
pp. 959-965 ◽  
Author(s):  
Maria Kataja ◽  
Pekko Hujanen ◽  
Heini Huhtala ◽  
Kai Kaarniranta ◽  
Anja Tuulonen ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Real Life ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Anti Vegf ◽  
Age Related ◽  
Real Life Setting ◽  
The Mean ◽  
Endothelial Growth Factor

AimsTo evaluate outcome of anti-vascular endothelial growth factor (VEGF) therapy for the treatment of neovascular age-related macular degeneration (nAMD) in the real-life setting and to compare incidence of ocular serious adverse events (SAE) after injections administered by nurses and physicians.MethodsRetrospective, single-centre study. Medical records of patients receiving anti-VEGF treatment for nAMD between 2008 and 2013 with three-loading-dose regimen were evaluated. Outcome measures were baseline visual acuity (VA), change in VA, number of intravitreal injections, incidence of ocular SAE and patients’ baseline characteristics affecting VA change. In addition, the number of injections per 1000 citizens living in the serving area and per individuals over 65 years old were estimated.Results1349 eyes in 1117 patients received a total of 11 562 intravitreal anti-VEGF injections. Twenty-one per cent of patients received treatment for both eyes. The mean baseline Snellen VA was 0.32. The mean change of VA from baseline was +2, +2 and ±0 Early Treatment Diabetic Retinopathy Study letters and the mean numbers of injections were 5.7, 4.7 and 4.9 at years 1, 2 and 3, respectively. There was a negative correlation between baseline VA and change of VA. Incidence of endophthalmitis was 0.086%. No difference in the incidence of ocular SAE was identified between injections given by nurses or by physicians. The number of intravitreal injections per all citizens was 9 per 1000 inhabitants and 45 per 1000 inhabitants over 65 years.ConclusionThe VA was maintained at the baseline level (±0 letters) with the mean of 15.3 anti-VEGF injections in real-world clinical practice during 3-year follow-up.

scholarly journals Therapies for Neovascular Age-Related Macular Degeneration: Current Approaches and Pharmacologic Agents in Development

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Mostafa Hanout ◽  
Daniel Ferraz ◽  
Mehreen Ansari ◽  
Natasha Maqsood ◽  
Saleema Kherani ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Vascular Diseases ◽  
Age Related Macular Degeneration ◽  
Treatment Modalities ◽  
Vascular Endothelial ◽  
New Therapies ◽  
Age Related ◽  
Early Phase Clinical Trials ◽  
Endothelial Growth Factor ◽  
Pharmacologic Agents

As one of the leading causes of blindness, age-related macular degeneration (AMD) has remained at the epicenter of clinical research in ophthalmology. During the past decade, focus of researchers has ranged from understanding the role of vascular endothelial growth factor (VEGF) in the angiogenic cascades to developing new therapies for retinal vascular diseases. Anti-VEGF agents such as ranibizumab and aflibercept are becoming increasingly well-established therapies and have replaced earlier approaches such as laser photocoagulation or photodynamic therapy. Many other new therapeutic agents, which are in the early phase clinical trials, have shown promising results. The purpose of this paper is to briefly review the available treatment modalities for neovascular AMD and then focus on promising new therapies that are currently in various stages of development.

scholarly journals Management of Neovascular Age-Related Macular Degeneration in Clinical Practice: Initiation, Maintenance, and Discontinuation of Therapy

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Pearse A. Keane ◽  
Adnan Tufail ◽  
Praveen J. Patel
Keyword(s):  
Clinical Practice ◽  
Macular Degeneration ◽  
Treatment Strategies ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Future Directions ◽  
Age Related ◽  
Endothelial Growth Factor ◽  
Current Guidelines ◽  
Review Current

Neovascular age-related macular degeneration (AMD) is a leading cause of irreversible visual loss in elderly populations. In recent years, pharmacological inhibition of vascular endothelial growth factor (VEGF), via intravitreal injection of ranibizumab (Lucentis) or bevacizumab (Avastin), has offered the first opportunity to improve visual outcomes in patients diagnosed with this disorder. In this paper, we provide recommendations on how bevacizumab and ranibizumab may be best applied in current clinical practice, with an emphasis on their underlying pharmacology and efficacy. In addition, we review current guidelines for the initiation, maintenance, and discontinuation of anti-VEGF therapies, as well as emerging treatment strategies and future directions in the field.

scholarly journals Anti-vascular Endothelial Growth Factor Outpatient Treatment Patterns in Patients with Exudative Age-related Macular Degeneration from a Japanese Hospital Claims Database

10.36469/9887 ◽  
2014 ◽  
Vol 2 (1) ◽  
pp. 41-52 ◽  
Author(s):  
Tomohiro Iida ◽  
Aya Narimatsu ◽  
Kenji Adachi ◽  
Edward CY Wang
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Outpatient Treatment ◽  
Treatment Patterns ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Claims Database ◽  
Anti Vegf ◽  
Age Related ◽  
Endothelial Growth Factor

Purpose: To identify outpatient treatment patterns of patients with exudative age-related macular degeneration (AMD) who received approved anti–vascular endothelial growth factor (VEGF) therapy, using real-world data from hospitals in Japan. Methods: A hospital claims database was retrospectively reviewed for patients diagnosed with exudative AMD who were treated with anti-VEGF therapy in the outpatient setting between January 2010 and December 2012. Within a treatment period of at least 12 months, the frequency of anti-VEGF injections and AMD-related visits, and time intervals between AMD-related visits and anti-VEGF injections were captured for patients who had neither cataracts nor glaucoma. “Loading dose regimen” was defined as the first 2 or 3 monthly doses and “PRN maintenance regimen” (where PRN=pro re nata) was defined as the entire period of time after the loading doses had been administered. Results: Claims data were collected from a total of 219 patients from 13 of 126 hospitals: 217 treated with ranibizumab (8 received pegaptanib as well), 2 with aflibercept. Of these, 68 patients were treated for at least 12 months (all with ranibizumab PRN), and 29 had neither cataracts nor glaucoma and were included in the treatment pattern analysis. These 29 patients received a mean of 3.8 injections in the first 12 months and another 2.5 injections in the second 12 months of treatment. The average number of all outpatient visits was 16.1 in the first 12 months and 13.7 in the second 12 months, and an average of 11.6 days elapsed between injections and the previous outpatient monitoring visits using a PRN schedule. Conclusion: In a real-world setting in Japan, anti-VEGF PRN injections are administered less frequently than in clinical trials, and with time between monitoring and re-injection visits. Nonetheless, patients still visit the hospital frequently, which can significantly burden patients, caregivers, and healthcare providers.

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.

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