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

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.

2022 ◽  
Vol 7 (1) ◽  
pp. e000930
Author(s):  
Tora Sund Morken ◽  
Christina Knutsen ◽  
Margrete Sætre Hanssen ◽  
Dordi Austeng

ObjectiveStandard treatment of neovascular age-related macular degeneration (nAMD) is intravitreal injections (IVI) of antivascular endothelial growth factor (anti-VEGF) according to treat-and-extend (TnE). Observe-and-plan (OnP), a new regimen based on each individual’s relapse interval lead to fewer clinical visits and has so far shown to be safe in treatment-naïve patients. In this study, we explore patient satisfaction and safety in nAMD when switching from TnE to OnP.Methods and analysis38 participants treated acording to TnE for ≥12 months were included and switched from TnE to OnP with their last stable interval. Main outcome was patient satisfaction (Leeds Satisfaction Questionnaire). Secondary outcomes were best-corrected visual acuity (BCVA), central retinal thickness (CRT) before and 12 months after switch and number of monitoring visits and injections of anti-VEGF 12 months prior to and following switch.ResultsMean patient satisfaction was higher (3.7±0.5 SD) at 12 months after switch from TnE to OnP than before (3.6±0.5 SD, p=0.009, response rate 76%). BCVA and CRT were unchanged. Number of monitoring visits and injections were lower in the 12 months following than prior to switch (p<0.001).ConclusionA switch from TnE to OnP in a non-treatment-naïve population resulted in higher patient satisfaction, while maintaining stable BCVA. This indicates that OnP may be applicable in the large group of nAMD patients that have received IVI for several years. OnP may alleviate the treatment burden on both individual and society of frequent clinical visits while increasing patient satisfaction.


2021 ◽  
pp. 247412642110403
Author(s):  
Dimosthenis Mantopoulos ◽  
Hetal Ray ◽  
George Sanchez ◽  
Russell Pokroy ◽  
Daniel B. Roth

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.


Medicina ◽  
2012 ◽  
Vol 48 (8) ◽  
pp. 60 ◽  
Author(s):  
Rasa Liutkevičienė ◽  
Diana Žaliaduonytė-Pekšienė ◽  
Dalia Žaliūnienė ◽  
Olivija Gustienė ◽  
Vytautas Jašinskas ◽  
...  

Objective. The aim of our study was to determine if the genotype of the matrix metalloproteinase- 3 (MMP-3) gene might carry the risk of age-related macular degeneration (ARMD) in patients with myocardial infarction. Material and Methods. A total of 499 patients with an acute myocardial infarction or with a history of myocardial infarction were enrolled into the study. They were subdivided into 2 groups: 273 patients with ARMD and 226 patients without ARMD. The control group comprised 560 persons from a random sample of the Lithuanian population. DNA was analyzed using real-time polymerase chain reaction to genotype polymorphism 5A/6A at a position –1171 of the MMP-3 gene promoter. Results. Of the 499 patients with myocardial infarction, 47% had early-stage ARMD. The patients with ARMD were older than the patients in the group without ARMD (62.1±10.8 vs. 59.6±11.1, P<0.01). The analysis of MMP-3 gene polymorphism did not reveal any differences in the distribution of 5A/5A, 5A/6A, and 6A/6A genotypes between the ARMD group, non-ARMD group, and the control group (24.2%, 52.5%, and 23.3% in the ARMD group; 28.7%, 51.9%, and 19.4% in non-ARMD group; and 25.7%, 49.3% and 25.0%, in the control group, respectively). Conclusions. MMP-3 gene polymorphism had no predominant effect on the development of ARMD in patients with myocardial infarction.


2021 ◽  
Vol 15 (1) ◽  
pp. 209-216
Author(s):  
Ryosuke Motohashi ◽  
Hidetaka Noma ◽  
Kanako Yasuda ◽  
Yuko Kasezawa ◽  
Hiroshi Goto ◽  
...  

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.


2021 ◽  
Vol 6 (6-1) ◽  
pp. 12-18
Author(s):  
M. A. Kovalevskaya ◽  
O. A. Pererva

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


2017 ◽  
Vol 24 (2) ◽  
pp. 75-82 ◽  
Author(s):  
Rasa Liutkevičienė ◽  
Ramunė Sungailienė ◽  
Alvita Vilkevičiūtė ◽  
Loresa Kriaučiūnienė ◽  
Paulina Vaitkienė ◽  
...  

Background. Age-related macular degeneration (AMD) is the most common cause of irreversible visual loss in industrialized countries. Early symptoms of AMD include drusen and changes in retinal pigment epithelium. However, the etiology of AMD and drusen formation is not fully understood. Recent studies suggest that CYP2C8-related metabolic processes might play an important role in the development of AMD. The aim of our study is to investigate CYP2C8 rs10509681 and CYP2C8 rs11572080 genotype frequencies in patients with early AMD and to compare them with healthy controls. Materials and Methods. The  study enrolled 305 patients with early AMD and 300 healthy controls. The  genotyping of CYP2C8 rs10509681 and CYP2C8 rs11572080 was carried out using the  real-time PCR method. Results. The analysis of studied CYP2C8 polymorphisms did not reveal any statistically significant differences between the AMD and the control groups. For the CYP2C8 rs10509681 gene polymorphism the distribution of T/T, T/C, and C/C genotypes was 83.3%, 16.7%, and 0% vs. 83.7%, 15.7%, and 0.7%, p = 0.343. For the CYP2C8 rs11572080 gene polymorphism the distribution of C/C, T/C and T/T and genotypes was 84.9%, 15.1%, and 0% vs. 82.3%, 17.3%, and 0.3%, p = 0.447. Conclusion. The  study revealed that there were no statistically significant differences in the distribution of CYP2C8 rs10509681 and CYP2C8 rs11572080 genotypes in patients with early AMD and in healthy controls.


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.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Ruta Sakiene ◽  
Alvita Vilkeviciute ◽  
Loresa Kriauciuniene ◽  
Vilma Jurate Balciuniene ◽  
Dovile Buteikiene ◽  
...  

Background. Age-related macular degeneration is the leading cause of blindness in elderly individuals where aetiology and pathophysiology of age-related macular degeneration are not absolutely clear.Purpose. To determine the frequency of the genotype of rs2108622 in patients with early and exudative age-related macular degeneration.Methods. The study enrolled 190 patients with early age-related macular degeneration, 181 patients with exudative age-related macular degeneration (eAMD), and a random sample of 210 subjects from the general population (control group). The genotyping of rs2108622 was carried out using the real-time polymerase chain reaction method.Results. 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 early AMD group, the eAMD group, and the control group. TheCYP4F2(1347C>T)T/Tgenotype was more frequent in males with eAMD compared to females (10.2% versus 0.8%;p=0.0052); alsoT/Tgenotype was less frequently present in eAMD females compared to healthy control females (0.8% versus 6.2%;p=0.027).Conclusion. Rs2108622 gene polymorphism had no predominant effect on the development of early AMD and eAMD. TheT/Tgenotype was more frequent in males with eAMD compared to females and less frequently present in eAMD females compared to healthy females.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ermete Giancipoli ◽  
Antonio Pinna ◽  
Francesco Boscia ◽  
Gianluigi Zasa ◽  
Giovanni Sotgiu ◽  
...  

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.


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