Leukocyte telomere length and response to antiangiogenic therapy in patients with neovascular age-related macular degeneration

2022 ◽  
pp. 823-830
Author(s):  
А.Ж. Фурсова ◽  
А.С. Дербенева ◽  
М.С. Тарасов ◽  
И.Ф. Никулич ◽  
В.А. Девяткин ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Telomere Length ◽  
Antiangiogenic Therapy ◽  
Active Form ◽  
Age Related Macular Degeneration ◽  
Response To Treatment ◽  
Leukocyte Telomere Length ◽  
Anti Vegf ◽  
Age Related ◽  
Observation Period

Возрастная макулярная дегенерация (ВМД) становится основной причиной потери зрения людьми старше 60 лет. Неоваскулярная форма ВМД характеризуется хориоидальной неоваскуляризацией, основным триггером которой является фактор роста эндотелия сосудов (VEGF), ингибирование которого - современный стандарт лечения. Значительная вариабельность ответа на анти-VEGF-терапию определяет актуальность поиска биологических маркеров - прогностических критериев ответа на лечение. Проведен анализ зависимости ответа 110 пациентов с нВМД на анти-VEGF-терапию от функциональных и анатомических параметров сетчатки (по данным оптической когерентной томографии) и длины теломер лейкоцитов (ДТЛ, оценивали методом количественной ПЦР). В 100 % глаз наблюдали положительную динамику максимально корригированной остроты зрения (МКОЗ). Центральная толщина сетчатки (ЦТС) снизилась после третьей инъекции до 265 [234-306] мкм, к концу периода наблюдения - до 211 [190-262] мкм. Сохранение активности субретинальной неоваскулярной мембраны (СНМ) в конце периода наблюдения коррелировало с более низкими показателями исходной МКОЗ и высокими значениями исходной ЦТС. Выявлена ассоциация ДТЛ с ответом на лечение: у пациентов с большей ДТЛ чаще наблюдали переход активной формы СНМ в неактивную уже после трех инъекций, в то время как при меньшей ДТЛ чаще сохранялась активность СНМ, что определяло потребность в большем числе интравитреальных инъекций. Age-related macular degeneration (AMD) is becoming the leading cause of vision loss in people over 60 years of age. The neovascular form of AMD (nVMD) is characterized by choroidal neovascularization (CNV), the main trigger of which is vascular endothelial growth factor (VEGF), the inhibition of which is the current standard of treatment. Significant variability of response to anti-VEGF therapy determines the relevance of the search for biological markers - prognostic criteria of treatment response. We analyzed the response of 110 nVMD patients to anti-VEGF therapy depending on the functional and anatomical parameters of the retina (according to optical coherence tomography, OCT) and leukocyte telomere length (LTL, was assessed by quantitative PCR). Positive dynamics of best corrected visual acuity (BCVA) was observed in 100 % of eyes. The central retinal thickness (CRT) decreased after the 3rd injection to 265 [234-306] µm, by the end of the observation period - to 211 [190-262] µm. The retention of activity of the subretinal neovascular membrane (SNM) at the end of the observation period correlated with lower values of the initial BCVA and high values of the initial CRT. An association of LTL with response to treatment was revealed: in patients with higher LTL the active form of SNM was more often switched to inactive after three injections, while with lower LTL, the activity of SNM was more often preserved, which determined the need for more intravitreal injections.

Analysis of antiangiogenic therapy in Retinal Angiomatous Proliferation

2021 ◽  
pp. 355-359
Author(s):  
A.V. Shelankova ◽  
◽  
M.A. Afanasyeva ◽  
A.A. Plyukhova ◽  
◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Retinal Pigment ◽  
Antiangiogenic Therapy ◽  
Retinal Angiomatous Proliferation ◽  
Age Related Macular Degeneration ◽  
Anti Vegf ◽  
Age Related ◽  
Intraretinal Fluid ◽  
Observation Period

Retinal angiomatous proliferation (RAP) is a separate form of neovascular age-related macular degeneration (nAMD), which accounts for 12-15% of newly diagnosed patients with nAMD [14]. It is believed that the development of RAP is associated with vascular endothelial growth factor (VEGF) [12]. Purpose. The main goal of our work was to conduct a retrospective analysis of the use of anti-VEGF therapy in patients with retinal angiomatous proliferation. Material and methods. Under observation in 14 patients (14 eyes) with retinal angiomatous proliferation. The age of the patients ranged from 52 to 80 years. The observation period was 4 years. OCT data were used to assess the presence / absence of neuroepithelial detachment, the presence / absence of retinal pigment epithelium detachment and the presence / absence of intraretinal fluid, and the incidence of RP rupture was assessed. Results. The maximally corrected visual acuity increased already in the first year of follow-up compared to BCVA before treatment, under the condition of intravitreal injections (IVI) of anti-VEGF drug aflibercept, and continued to remain at the same level throughout the observation period. In most patients, subretinal fluid was resorbed as early as 1 year of follow-up against the background of antiangiogenic therapy; by 3 years of follow-up, ONE remained only in 2 patients. Before treatment, 71.4% of patients had intraretinal fluid (IRF) in the macular zone according to OCT data; by the 3rd year of follow-up, the percentage of patients with IRF was 33.3%. Conclusion. In the course of this work, we have shown a positive effect of intravitreal administration of the anti-VEGF drug aflibercept in patients with retinal angiomatous proliferation. Key words: age-related macular degeneration, retinal angiomatous proliferation, anti- VEGF, macular edema.

scholarly journals New Qualitative Methods for Assessing the “Fluid” in the Retina in Age-Related Macular Degeneration

2021 ◽  
Vol 18 (2) ◽  
pp. 222-227
Author(s):  
M. V. Budzinskaya ◽  
A. A. Plyukhova
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Retinal Thickness ◽  
Antiangiogenic Therapy ◽  
Functional Results ◽  
Age Related Macular Degeneration ◽  
Modern World ◽  
Time Interval ◽  
Anti Vegf ◽  
Age Related

Age-related macular degeneration (AMD) is a chronic disease of the central retina and one of the main causes of blindness in patients over 60 years of age in industrialized countries. Currently, anti-vascular endothelial growth factor therapy (anti-VEGF therapy) has become the standard of neovascular AMD treatment, leading to the prevention of progressive vision loss in more than 90 % of treated patients during a two-year follow-up period. In the modern world there are transition from quantitative assessment of “fluid” according to optical coherence tomography (OCT) — the thickness of the central retinal zone, to qualitative — the presence of IRF, SRF, fluid under RPE. The data obtained by Zinkernagel have shown that, despite good functional results (an increase in visual acuity), the administration of the drug once every 2 months leads not only to fluctuations in IRF and SRF, but also to serous PED [4]. The existing qualitative and quantitative analysis is not perfect. Fluctuation is a new qualitative marker of the study of disease activity, it is defined as the sum of all types of fluid (IRF + SRF + fluid under RPE) in a certain time interval (with monthly measurement of the indicator). The fluctuation index was determined from the cumulative change in the thickness of the retina in the fovea over time [6]. Thus, the fluid is considered as a key morphological criterion for the activity of nVMD and an indication for (initiation or continuation) of antiangiogenic therapy. At the same time, there is evidence that a lower level of each type of fluid (IRF, SRF, fluid under RPE) is associated with better BCVA results against the background of anti-VEGF therapy [17]. The stability of retinal thickness during anti-VEGF therapy is no less important parameter than the statement of fluid resolution at a certain time, and it appears that better control of the central retinal thickness was associated with higher overall NEI VFQ-25 scores and individual scales reflecting important daily activities of the patient [16]. 

scholarly journals Non-Response to Anti-VEGF in Patients with Wet-Form (Neovascular) Age-Related Macular Degeneration, Treatment Resistance and Switch of Anti-VEGF Agents

2017 ◽  
pp. 219-228
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Treatment Resistance ◽  
Drug Efficacy ◽  
Age Related Macular Degeneration ◽  
Response To Treatment ◽  
Similar Response ◽  
Anti Vegf ◽  
Age Related ◽  
Endothelial Growth Factor

Age-related macular degeneration (AMD) is a chronic and degenerative disease that causes vision loss. Although anti-vascular endothelial growth factor (Anti-VEGF) drugs are the mainstay of treatment in cases of age-related AMD, there is no similar response to treatment in each patient. In the case of non-response, the treatment approach for the cause must be regulated. Although there is no consensus on the concept of response to treatment, the use of alternative anti-VEGF in cases where drug efficacy is weak is quite common.

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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