scholarly journals Aqueous Flare, Functional-Morphological Parameters, and Cytokines in Age-Related Macular Degeneration after Anti-VEGF Treatment

2021 ◽  
Vol 15 (1) ◽  
pp. 209-216
Author(s):  
Ryosuke Motohashi ◽  
Hidetaka Noma ◽  
Kanako Yasuda ◽  
Yuko Kasezawa ◽  
Hiroshi Goto ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Aqueous Humor ◽  
Patient Group ◽  
Inflammatory Mediators ◽  
Age Related Macular Degeneration ◽  
Control Group ◽  
Suspension Array ◽  
Aqueous Flare ◽  
Anti Vegf ◽  
Age Related

Purpose: The role of inflammation and cytokines in AMD and anti-Vascular Endothelial Growth Factor (anti-VEGF) treatment remains unclear. Therefore, this study aimed to examine whether anti-VEGF treatment for exudative Age-related Macular Degeneration (AMD) affects aqueous flare value (an indicator of inflammation), functional-morphologic parameters, and aqueous humor levels of cytokines or inflammatory mediators. Methods: We compared aqueous humor levels of 8 cytokines, growth factors (including VEGF), and inflammatory mediators in 43 patients who received anti-VEGF treatment with aflibercept for AMD and 24 healthy controls by the suspension array method. In addition, we measured aqueous flare values with a laser flare meter and Central Macular Thickness (CMT) and Macular Volume (MV) by optical coherence tomography. Results: The patient group had a significantly higher aqueous flare value than the control group. At baseline, CMT showed significant correlations with aqueous humor levels of soluble intercellular adhesion molecule-1 (sICAM-1), monocyte chemoattractant protein 1 (MCP-1), interleukin (IL)-6, and IL-8 and MV, with aqueous humor levels of VEGF, sICAM-1, MCP-1, IL-6, and IL-8. Moreover, we found significant correlations between aqueous flare value and aqueous humor levels of MCP-1, IL-6, IL-8, and interferon-gamma–inducible protein 10. One month after anti-VEGF treatment, the patient group showed a significant correlation between the change in MV and improvement in best-corrected visual acuity (BCVA); CMT showed no such correlation. Conclusion: Inflammation appears to be involved in AMD. Change in MV may be an index of improvement in BCVA in patients receiving anti-VEGF treatment for AMD.

scholarly journals LRG1 Expression Is Elevated in the Eyes of Patients with Neovascular Age-Related Macular Degeneration

2021 ◽  
Vol 22 (16) ◽  
pp. 8879
Author(s):  
Lucia Mundo ◽  
Gian Marco Tosi ◽  
Stefano Lazzi ◽  
Grazia Pertile ◽  
Barbara Parolini ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Aqueous Humor ◽  
Smooth Muscle Actin ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Average Concentration ◽  
Age Related Macular Degeneration ◽  
Surrounding Tissue ◽  
Anti Vegf ◽  
Age Related

Leucine-rich a-2-glycoprotein 1 (LRG1) is a candidate therapeutic target for treating the neovascular form of age-related macular degeneration (nvAMD). In this study we examined the expression of LRG1 in eyes of nvAMD patients. Choroidal neovascular membranes (CNVMs) from patients who underwent submacular surgery for retinal pigment epithelium–choroid graft transplantation were collected from 5 nvAMD patients without any prior intravitreal anti-VEGF injection, and from six patients who received intravitreal anti-VEGF injections before surgery. As controls free of nvAMD, retina sections were obtained from the eyes resected from a patient with lacrimal sac tumor and from a patient with neuroblastoma. CNVMs were immunostained for CD34, LRG1, and α-smooth muscle actin (α-SMA). Aqueous humor samples were collected from 58 untreated-naïve nvAMD patients prior to the intravitreal injection of anti-VEGF and 51 age-matched cataract control patients, and LRG1 concentration was measured by ELISA. The level of LRG1 immunostaining is frequently high in both the endothelial cells of the blood vessels, and myofibroblasts in the surrounding tissue of CNVMs of treatment-naïve nvAMD patients. Furthermore, the average concentration of LRG1 was significantly higher in the aqueous humor of nvAMD patients than in controls. These observations provide a strong experimental basis and scientific rationale for the progression of a therapeutic anti-LRG1 monoclonal antibody into clinical trials with patients with nvAMD.

Ganglion Cell Layer Thickness Change in Neovascular Age-Related Macular Degeneration Treated With Anti-VEGF Injections

2021 ◽  
pp. 247412642110403
Author(s):  
Dimosthenis Mantopoulos ◽  
Hetal Ray ◽  
George Sanchez ◽  
Russell Pokroy ◽  
Daniel B. Roth
Keyword(s):  
Ganglion Cell ◽  
Macular Degeneration ◽  
Ganglion Cell Layer ◽  
Cell Layer ◽  
Treated Group ◽  
Age Related Macular Degeneration ◽  
Control Group ◽  
Fellow Eye ◽  
Anti Vegf ◽  
Age Related

Purpose: This work assesses bilateral ganglion cell layer–inner plexiform layer (GCL-IPL) thickness changes in patients with unilateral neovascular age-related macular degeneration (nAMD) treated with antivascular endothelial growth factor (anti-VEGF). Methods: In this single-center, retrospective, cohort study, the medical records of patients with unilateral nAMD treated with anti-VEGF were reviewed. The treated group included eyes with newly diagnosed nAMD that subsequently underwent treatment with intravitreal anti-VEGF injections. The control group was the fellow eye with dry AMD. Eyes receiving at least 10 intravitreal injections were included. Measurement of GCL-IPL thickness was performed at different time points using spectral domain–optical coherence tomography. Results: A total of 216 eyes of 108 patients met the inclusion criteria. The mean age ± SD was 80.1 ± 10.7 years. Eyes in the treated group underwent a mean ± SD of 20.2 ± 7.2 injections in 21.3 ± 6.8 months. At baseline, average mean ± SD of GCL-IPL thickness was 73.71 ± 8.81 µm and 73.84 ± 8.26 µm in the treated and fellow eye, respectively ( P = .795). After 10 injections the average thickness was 65.41 ± 14.08 µm and 68.77 ± 13.24 µm in the treated and fellow eye, respectively ( P = .007). The absolute decrease in thickness was significantly greater in the treated eye than the fellow eye (mean ± SD, 8.31 ± 11.19 µm vs 5.07 ± 10.83 µm, respectively; P = .002). Conclusions: GCL-IPL thickness decreased significantly in the treated group more than in the control group after 10 anti-VEGF injections. The mechanism and clinical significance of this observation warrants further study.

scholarly journals Comparison of Cytokine Levels in the Aqueous Humor of Polypoidal Choroidal Vasculopathy and Neovascular Age-Related Macular Degeneration Patients

2019 ◽  
Author(s):  
Huiying Zhou ◽  
Yinyu Zhao ◽  
Mingzhen Yuan ◽  
Youxin Chen
Keyword(s):  
Macular Degeneration ◽  
Aqueous Humor ◽  
Polypoidal Choroidal Vasculopathy ◽  
Age Related Macular Degeneration ◽  
Control Group ◽  
Age Related ◽  
Cytokine Levels ◽  
Treatment Naïve ◽  
And Control ◽  
Choroidal Vasculopathy

Abstract Background The concentrations of cytokines in the aqueous humor from neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) may vary. The study was conducted to compare various cytokine levels in the aqueous humor of eyes with PCV, nAMD and control.Methods The present case control study included 49 treatment-naïve eyes from 49 patients (PCV 24, nAMD 11, and cataract 14 eyes). Totally 34 angiogenic and inflammatory cytokines in the aqueous humor were measured by Luminex bead-based multiplex array.Results The aqueous humor levels of IL-8 and IL-12p70 in the nAMD group were significantly higher than the PCV group (p=0.031, p=0.012, respectively). The levels of IL-8, IL-18, IL-21, IL-31, LIF, SDF1-α, FGF-basic, VEGF-A, and VEGF-D in the aqueous humor were significantly higher in the nAMD group and PCV group than the control (nAMD vs control, p=0.004, 0.002, 0.005, <0.0001, <0.0001, <0.0001, 0.023, <0.0001, <0.0001, respectively, PCV vs control, p=0.031, <0.0001, <0.0001, <0.0001, <0.0001, <0.0001, 0.026, <0.0001, <0.0001, respectively). In contrast, the levels of BDNF, HGF, IP-10, MCP-1, and IL-13 in the aqueous humor were significantly lower in the nAMD group and PCV group than control (nAMD vs control, p=<0.0001, <0.0001, 0.003, <0.0001, <0.0001, respectively, PCV vs control, p=<0.0001, <0.0001, <0.0001, <0.0001, <0.0001, respectively). There were significant correlations among nAMD group, PCV group and control group in aqueous humor levels of HGF, IP-10, MCP-1, IL-13, IL-31, LIF, SDF1-α, VEGF-A, VEGF-D by multivariate logistic analysis.Conclusions Various cytokines involved in inflammation and angiogenesis including HGF, IP-10, MCP-1, IL-13, IL-31, LIF, SDF1-α, VEGF-A and VEGF-D may contribute to the pathogenesis of nAMD and PCV. Measurement of IL-8 and IL-12p70 in the aqueous humor may help to differentiate nAMD and PCV.

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 Intravitreal Dexamethasone in Patients with Wet Age-Related Macular Degeneration Resistant to Anti-VEGF: A Prospective Pilot Study

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ermete Giancipoli ◽  
Antonio Pinna ◽  
Francesco Boscia ◽  
Gianluigi Zasa ◽  
Giovanni Sotgiu ◽  
...  
Keyword(s):  
Pilot Study ◽  
Treatment Group ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Control Group ◽  
Foveal Thickness ◽  
Central Foveal Thickness ◽  
Anti Vegf ◽  
Age Related ◽  
Intravitreal Dexamethasone

Purpose. To evaluate the efficacy and safety of a single intravitreal dexamethasone implant (DXI) combined with intravitreal antivascular endothelial growth factor (anti-VEGF) therapy, in patients with neovascular age-related macular degeneration (wet-AMD) resistant to conventional treatment. Methods. In this randomized, controlled pilot study, 16 eyes of 15 patients, unresponsive to anti-VEGF therapy, were enrolled and randomly assigned to two groups: DXI + anti-VEGF (treatment group: 11 eyes) and monthly anti-VEGF alone (control group: 5 eyes). Patients were treated at baseline and followed for 6 months. Best corrected visual acuity (BCVA), optical coherence tomography (OCT) parameters, and fluorescein angiography (FA) were evaluated. Results. Eight eyes (72.7%) in the treatment group and 2 eyes in the control group (40%) showed complete retinal fluid resorption (p=0.049). BCVA showed no significant change from baseline in both the treatment group and the control group (p=0.40 and p=0.29, respectively). Both median central foveal thickness (CFT) and median macular volume showed a greater reduction from baseline in the treatment group. Conclusion. In patients showing an incomplete response to anti-VEGF therapy, DXI combined with intravitreal anti-VEGF seems to improve retinal fluid resorption without functional advantage. This trial is registered with ACTRN12618001102268.

scholarly journals ABCA1 rs1883025 and CYP4F2 rs2108622 Gene Polymorphism Association with Age-Related Macular Degeneration and Anti-VEGF Treatment

Medicina ◽  
2021 ◽  
Vol 57 (9) ◽  
pp. 974
Author(s):  
Ruta Mockute ◽  
Alvita Vilkeviciute ◽  
Vilma Jurate Balciuniene ◽  
Reda Zemaitiene ◽  
Rasa Liutkeviciene
Keyword(s):  
Gene Polymorphism ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Control Group ◽  
Rt Pcr ◽  
Corrected Visual Acuity ◽  
Anti Vegf ◽  
Age Related ◽  
Pcr Method ◽  
Genetic And Environmental Factors

Background and Objectives: The age-related macular degeneration (AMD) pathophysiology is multifactorial, as it consists of interactions between aging, genetic, and environmental factors. We aimed to determine a relationship between AMD and the genes controlling lipid metabolism, and to assess its association with treatment results. The purpose was to find the ABCA1 rs1883025 and CYP4F2 rs2108622 gene polymorphisms in patients with exudative AMD (eAMD) treated with anti-VEGF. Materials and Methods: The study enroled 104 patients with eAMD and 201 healthy persons in a control group. The genotyping of rs1883025 and rs2108622 was performed using the RT-PCR method. The best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were measured before anti-VEGF therapy, then at three and six months during the therapy, using optical coherence tomography (OCT). The patients were grouped to responders and non-responders according to the changes in BCVA and CRT. Results: The T allele at rs1883025 was more frequent in non-responder eAMD patients compared to responder eAMD patients (41.7% vs. 21.1%; p = 0.009). The analysis of rs2108622 gene polymorphism did not reveal any differences in the distribution of C/C, C/T, and T/T genotypes between the eAMD group and the control group (56.35%, 39.78%, and 3.87% in the eAMD group and 53.33%, 39.05% and 7.62% in the control group, respectively, p = 0.286). The comparison of CRT and BCVA between the rs2108622 genotypes revealed statistically significant differences: CRT was thicker for the CC carriers than for those with CT and TT genotypes (p = 0.030). Conclusion: The rs1883025 T allele was found to play a more significant role in non-responder eAMD patients compared to responder eAMD patients. The rs2108622 genotypes revealed statistically significant differences: CRT was thicker for the CC carriers than for those with CT and TT genotypes.

scholarly journals Genetic biomarkers in the VEGF pathway predicting response to anti-VEGF therapy in age-related macular degeneration

2019 ◽  
Vol 4 (1) ◽  
pp. e000273
Author(s):  
Irina Balikova ◽  
Laurence Postelmans ◽  
Brigitte Pasteels ◽  
Pascale Coquelet ◽  
Janet Catherine ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Macular Degeneration ◽  
Treatment Response ◽  
Multiple Testing ◽  
Age Related Macular Degeneration ◽  
Patient Specific ◽  
Multiple Testing Correction ◽  
Anti Vegf ◽  
Age Related ◽  
Vegf Pathway

ObjectiveAge-related macular degeneration (ARMD) is a leading cause of visual impairment. Intravitreal injections of anti-vascular endothelial growth factor (VEGF) are the standard treatment for wet ARMD. There is however, variability in patient responses, suggesting patient-specific factors influencing drug efficacy. We tested whether single nucleotide polymorphisms (SNPs) in genes encoding VEGF pathway members contribute to therapy response.Methods and analysisA retrospective cohort of 281 European wet ARMD patients treated with anti-VEGF was genotyped for 138 tagging SNPs in the VEGF pathway. Per patient, we collected best corrected visual acuity at baseline, after three loading injections and at 12 months. We also registered the injection number and changes in retinal morphology after three loading injections (central foveal thickness (CFT), intraretinal cysts and serous neuroepithelium detachment). Changes in CFT after 3 months were our primary outcome measure. Association of SNPs to response was assessed by binomial logistic regression. Replication was attempted by associating visual acuity changes to genotypes in an independent Japanese cohort.ResultsAssociation with treatment response was detected for seven SNPs, including in FLT4 (rs55667289: OR=0.746, 95% CI 0.63 to 0.88, p=0.0005) and KDR (rs7691507: OR=1.056, 95% CI 1.02 to 1.10, p=0.005; and rs2305945: OR=0.963, 95% CI 0.93 to 1.00, p=0.0472). Only association with rs55667289 in FLT4 survived multiple testing correction. This SNP was unavailable for testing in the replication cohort. Of six SNPs tested for replication, one was significant although not after multiple testing correction.ConclusionIdentifying genetic variants that define treatment response can help to develop individualised therapeutic approaches for wet ARMD patients and may point towards new targets in non-responders.

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