Therapeutic effects of a novel siRNA-based anti-VEGF (siVEGF) nanoball for the treatment of choroidal neovascularization

Nanoscale ◽  
2017 ◽  
Vol 9 (40) ◽  
pp. 15461-15469 ◽  
Author(s):  
Na-Kyung Ryoo ◽  
Jihwang Lee ◽  
Hyunjoo Lee ◽  
Hye Kyoung Hong ◽  
Hyejin Kim ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Choroidal Neovascularization ◽  
Developed Countries ◽  
Age Related Macular Degeneration ◽  
Therapeutic Effects ◽  
Anti Vegf ◽  
Age Related

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries and is characterized by the development of choroidal neovascularization (CNV).

scholarly journals Choroidal neovascularization activity and structure by optical coherence tomography angiography in age related macular degeneration

2021 ◽  
Vol 6 (6-1) ◽  
pp. 12-18
Author(s):  
M. A. Kovalevskaya ◽  
O. A. Pererva
Keyword(s):  
Macular Degeneration ◽  
Choroidal Neovascularization ◽  
Vascular System ◽  
Developed Countries ◽  
Age Related Macular Degeneration ◽  
Control Group ◽  
Type I ◽  
Neovascular Amd ◽  
Anti Vegf ◽  
Age Related

Background. In economically developed countries, age-related macular degeneration (AMD) is the leading cause of visual disability among the population of the older age group. The main criterion for the anti-VEGF treatment of neovascular AMD is the activity of choroidal neovascularization (CNV), which is determined by its confi guration. The search for optimal criteria for quantifying the state of the macular region in order to decide on the appointment of anti-VEGF therapy continues.Aim: improving the effi ciency of diagnosis and treatment of AMD based on the assessment of the configuration of vascular system on the “Key to Diagnosis II” platform.Material and methods. The study included 341 patients: 64 % (218 patients, 267 eyes) with non-neovascular AMD, 36 % (123 patients, 174 eyes) – with neovascular AMD. 56 patients (58 eyes) had active type I CNV. Group 1A – active CNV before treatment (9 patients, 9 eyes), group 1B – non-active CNV after treatment with antiVEGF (9 patients, 9 eyes); control group – 10 patients (10 eyes) without AMD. Analysis of OCT-angio images of choriocapillaries included the isolation of CNV, its area, fractal dimension (Df) and the complexity of the vascular system (CVS) counting.Results. Group 1A: Df – 1.5871 ± 0.05, CVS – 2.29 ± 0.29, area – 11734 ± 4866; group 1B: Df – 1.6462 ± 0.08, CVS – 1.65 ± 0.18, area – 6797 ± 3818; control: Df – 1.9167 ± 0.06, CVS – 1, area – 0. Significant differences were found for CVS (p = 0.0003). Df correlates with the CNV area (p = 0.7) and is probably an unreliable parameter due to incomplete visualization of active CNV.Conclusions. CVS is a quantitative biomarker for determining the activity of type 1 CNV in patients with AMD and can serve as a parameter for convolutional neural networks training for automated analysis of OCT angiography images based on the “Key to Diagnosis II” platform

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 Subthreshold Exudative Choroidal Neovascularization Associated With Age-Related Macular Degeneration Identified by Optical Coherence Tomography Angiography

2020 ◽  
Vol 4 (5) ◽  
pp. 377-385
Author(s):  
Miin Roh ◽  
Joan W. Miller ◽  
Karen W. Jeng-Miller ◽  
Jay C. Wang ◽  
Inês Laíns ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Macular Degeneration ◽  
Choroidal Neovascularization ◽  
Age Related Macular Degeneration ◽  
Fundus Photography ◽  
Pigment Epithelial Detachment ◽  
Optical Coherence ◽  
Pigment Epithelial ◽  
Anti Vegf ◽  
Age Related

Purpose: This article describes the clinical and multimodal imaging characteristics of subthreshold exudative choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD). Methods: Among 3773 patients with AMD, 8 eyes (6 patients) were identified with the clinical phenotype of interest. Dilated fundus examinations, color fundus photography, fluorescein angiography (FA), indocyanine green angiography (ICGA), optical coherence tomography (OCT), and OCT angiography (OCTA) were performed. Results: OCT typically showed a moderately reflective irregular pigment epithelial detachment with overlying subretinal fluid (SRF). Traditional FA did not show leakage and ICGA showed no definitive neovascular network or hot spots. However, OCTA clearly demonstrated a CNV within the pigment epithelial detachment. The majority of our cases (7 of 8) did not receive antivascular endothelial growth factor (anti-VEGF) injections, and visual acuity remained stable over the available follow-up period of 1 to 10 years. Conclusions: CNV is often associated with SRF and vision loss in AMD, usually requiring frequent anti-VEGF injections. OCTA allowed us to better identify CNV not readily detected on FA and ICGA. Although some have suggested early clinical intervention with anti-VEGF injections in any case with fluid and confirmed CNV on OCTA, we describe a subset of AMD patients with SRF who may be better managed by observation. These cases may represent a more indolent, mature, and stable vascular network.

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 Switching of an inhibitor of vascular endothelial growth factor in the treatment of resistant to ranibizumab neovascular form of age-related macular degeneration. Case study

2016 ◽  
Vol 9 (3) ◽  
pp. 69-76
Author(s):  
Nanuli V Ivanova ◽  
Oleg G Rasin ◽  
Aleksey V Savchenko ◽  
Olga A Litvinenko
Keyword(s):  
Visual Acuity ◽  
Macular Degeneration ◽  
Choroidal Neovascularization ◽  
Retinal Thickness ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Neovascular Amd ◽  
Membrane Area ◽  
Anti Vegf ◽  
Age Related

Aim: To analyze the spontaneous reattachment of retinal pigment epithelium (RPE) after replacing the anti-VEGF drug - ranibizumab, with aflibercept in the treatment of neovascular AMD based on the example given in our clinical study. Material and methods. We carried out a retrospective analysis of the patient’s history with exudative detachment of RPE due to choroidal neovascularization in age-related macular degeneration. This patient was treated with anti-angiogenic treatment in the form of monthly IVI ranibizumab. At the time of treatment, the visual acuity of the left eye was 0.3 with sph + 1,5D = 0,5, in the fundus of the eye there was a high exudative detachment of RPE in the macular region common to the vascular arcades. The edges were determined by the detachment of the neuroepithelium and abundance of hard drusen. Using optical coherence tomography, (OCT) we saw that the center of the macula of the left eye had a high detachment of RPE, local detachment of the neuroepithelium at the edge of the RPE detachment and an abundance of hard drusen. The foveola was flattened, and beneath it, the RPE was detached in the center - thickness of 247 microns (m). After the seventh injection of ranibizumab, we used OCT to assess the condition of the retina. The retinas condition was almost the same as before. The thickness in the central zone was 251 m, detachment of neuroepithelium was not seen, the dome of the RPE detachment circuit was unchanged and visual acuity improved to 0.7 with a maximum correction. We then replaced ranibizumab with another anti-angiogenic drug - aflibercept. Results and discussion. Two weeks on from our control examination, we noticed there was a smooth bubble detachment of the RPE and a retinal prominence over the choroidal neovascular membrane area (CNM). The OCT scan indicated minimal RPE detachment, resorption of the exudate, presence of subretinal spindle - shaped formation near the temporal side (CNM? Scar?). Retinal thickness was 178 m at the fixation point. Intravitreal injections were stopped. Visual acuity increased to 0.8 and remained stable for 5 months, but there were signs of renewed activity of choroidal neovascularization. According to OCT, the thickness in the central parts of the retina increased to 230 m, there were intraretinal cysts and increased spindle - shaped formation under the RPE. After 10 months of IVI aflibercept, acute vision decreased to 0.5, the thickness at the point of fixing increased to 250 m, subretinal formation increased and oozing of fluid was observed mainly parafoveal, which explains the high visual acuity. We then administered IVI ranibizumab. Two weeks later, the retinal thickness was 169 m, visual acuity improved to 0.8, but 1 month later we found that the retinal thickness had increased once more and decreased to 0.7. After 3 months after IVI ranibizumab, retinal thickness at the fixation point reached 286 m and visual acuity dropped to 0.5. Conclusion. In our practice, we face patients with neovascular AMD, who respond badly to ranibizumab. For such patients, it is important to replace ranibizumab with a better, more therapeutically effective anti-VEGF drug with anti-vaso proliferative properties. Aflibercept is an effective substitute for ranibizumab which was shown in this clinical case.

scholarly journals Autophagy Genes for Wet Age-Related Macular Degeneration in a Finnish Case-Control Study

Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1318
Author(s):  
Jussi J. Paterno ◽  
Ali Koskela ◽  
Juha M.T. Hyttinen ◽  
Elina Vattulainen ◽  
Ewelina Synowiec ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Retinal Pigment ◽  
Developed Countries ◽  
Age Related Macular Degeneration ◽  
Cumulative Number ◽  
Sequestosome 1 ◽  
Anti Vegf ◽  
Age Related ◽  
Wet Amd

Age-related macular degeneration is an eye disease that is the main cause of legal blindness in the elderly in developed countries. Despite this, its pathogenesis is not completely known, and many genetic, epigenetic, environmental and lifestyle factors may be involved. Vision loss in age-related macular degeneration (AMD) is usually consequence of the occurrence of its wet (neovascular) form that is targeted in the clinic by anti-VEGF (vascular endothelial growth factor) treatment. The wet form of AMD is associated with the accumulation of cellular waste in the retinal pigment epithelium, which is removed by autophagy and the proteosomal degradation system. In the present work, we searched for the association between genotypes and alleles of single nucleotide polymorphisms (SNPs) of autophagy-related genes and wet AMD occurrence in a cohort of Finnish patients undergoing anti-VEGF therapy and controls. Additionally, the correlation between treatment efficacy and genotypes was investigated. Overall, 225 wet AMD patients and 161 controls were enrolled in this study. Ten SNPs (rs2295080, rs11121704, rs1057079, rs1064261, rs573775, rs11246867, rs3088051, rs10902469, rs73105013, rs10277) in the mTOR (Mechanistic Target of Rapamycin), ATG5 (Autophagy Related 5), ULK1 (Unc-51-Like Autophagy Activating Kinase 1), MAP1LC3A (Microtubule Associated Protein 1 Light Chain 3 α), SQSTM1 (Sequestosome 1) were analyzed with RT-PCR-based genotyping. The genotype/alleles rs2295080-G, rs11121704-C, rs1057079-C and rs73105013-T associated with an increased, whereas rs2295080-TT, rs2295080-T, rs11121704-TT, rs1057079-TT, rs1057079-T, rs573775-AA and rs73105013-C with a decreased occurrence of wet AMD. In addition, the rs2295080-GG, rs2295080-GT, rs1057079-TT, rs11246867-AG, rs3088051-CC and rs10277-CC genotypes were a positively correlated cumulative number of anti-VEGF injections in 2 years. Therefore, variability in autophagy genes may have an impact on the risk of wet AMD occurrence and the efficacy of anti-VEGF treatment.

Analysis of the Vascular Morphology of the Fibrotic Choroidal Neovascularization in Neovascular Age-Related Macular Degeneration Using Optical Coherence Tomography Angiography

2020 ◽  
Vol 237 (11) ◽  
pp. 1312-1319 ◽  
Author(s):  
Marius Book ◽  
Martin Ziegler ◽  
Kai Rothaus ◽  
Henrik Faatz ◽  
Marie-Louise Gunnemann ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Macular Degeneration ◽  
Choroidal Neovascularization ◽  
Optical Coherence Tomography Angiography ◽  
Age Related Macular Degeneration ◽  
Optical Coherence ◽  
Vascular Morphology ◽  
Anti Vegf ◽  
Age Related ◽  
Number Of Segments

Abstract Purpose Choroidal neovascularization (CNV) in neovascular age-related macular degeneration (nAMD) undergoing anti-VEGF therapy transforms into a fibrotic lesion. This fibrovascular transformation is associated with a great variety of functional and morphological effects. The aim of this study was to investigate the vascular morphology of fibrotic CNV, to compare it with its surrounding tissue and to identify phenotypes using optical coherence tomography angiography (OCTA). Methods In 18 eyes with fibrotic CNV in nAMD spectral domain OCT (SD-OCT) and OCTA were performed. The automated segmentation lines were manually adjusted. A slab from 60 µm beneath Bruchʼs membrane to the inner edge of the subretinal hyperreflective material was applied. Quantitative analysis of the vascular morphology was performed using skeletonized OCTA images. Results Compared to the perilesional rim, the number of segments per area was significantly lower (234.75 ± 25.68 vs. 255.30 ± 20.34 1/mm2, p = 0.0003) within the fibrovascular lesion. Two phenotypes could be identified within the lesion. The phenotypic traits of cluster 1 were few, long and thick vascular segments; Cluster 2 was characterized by many, short and thin vascular segments (number of segments per area: 219.4 ± 18.8 vs. 258.8 ± 13.2 1/mm2, p = 0.00009, segment length: 49.6 ± 2.7 vs. 45.0 ± 1.3 µm, p = 0.0002, vascular caliber: 26.6 ± 1.2 vs. 23.5 ± 1.8 µm, p = 0.003). The clusters did not differ significantly regarding visual acuity (0.52 ± 0.44 vs. 0.54 ± 0.18 logMAR, p = 0.25), differentiability of subretinal (OR = 3.43, CI = [0.30, 39.64], p = 0.6) and intraretinal fluid (OR = 5.34, CI = [0.48, 89.85], p = 0.14). Less normalized ellipsoid zone (EZ) loss could be observed in cluster 1 (131.0 ± 161.3 vs. 892.4 ± 955.6 1/m, p = 0.006). Conclusion In this study the vascular morphology of fibrotic CNV was analyzed using OCTA. Differences between the lesion and a perilesional rim could be detected. Two phenotypes within the fibrovascular lesion were identified. These morphological clusters could indicate different patterns of fibrovascular transformation of the CNV under long-term anti-VEGF therapy and be useful identifying possible predictive biomarkers in future studies.

scholarly journals Association of Anti-VEGF Injections with Progression of Geographic Atrophy

2016 ◽  
Vol 8 ◽  
pp. OED.S38863 ◽  
Author(s):  
Ryan Enslow ◽  
Sai Bhuvanagiri ◽  
Sravanthi Vegunta ◽  
Benjamin Cutler ◽  
Michael Neff ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Developed Countries ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Anti Vegf ◽  
Age Related ◽  
Wet Amd

Age-related macular degeneration (AMD) is one of the leading causes of blindness in developed countries in people over the age of 60 years. One of the forms of advanced AMD is wet AMD. Wet AMD is a result of leakage and bleeding from abnormal neovascularization. The principal treatment for wet AMD is intravitreal anti-VEGF injections. A second form of advanced AMD is geographic atrophy (GA). GA refers to large areas of retinal pigment epithelium loss. In the literature, there is some concern that anti-VEGF injections administered to treat wet AMD may be associated with progression of GA. This review discusses evidence suggesting the association of anti-VEGF injections with progression of GA.

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