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.

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.

Intraretinal, sub-retinal, and sub-retinal pigmented epithelium fluid in non-exudative age-related macular degeneration: follow-up with OCT imaging

2021 ◽  
pp. 112067212110362
Author(s):  
Anindya Samanta ◽  
Mahima Jhingan ◽  
Supriya Arora ◽  
Sumit Singh ◽  
Davide Tucci ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Subretinal Fluid ◽  
Age Related Macular Degeneration ◽  
Exudative Amd ◽  
Age Related ◽  
Intraretinal Fluid ◽  
Long Term Follow Up

Background/objectives: To evaluate the presence and evolution of fluid in non-exudative age-related macular degeneration (AMD) through serial OCT. Subjects/methods: A retrospective analysis of eyes with non-exudative AMD with a minimum of 4 year follow-up was done. Parameters including intraretinal fluid (IRF), subretinal fluid (SRF), and sub-retinal pigment epithelium (RPE) fluid (SRPEF); subfoveal choroidal thickness (SFCT) and type of drusen were evaluated using optical coherence tomography (OCT) scans at baseline and follow up visits. Results: Seventy-two eyes (in 63 patients) were followed up for an average of 5.83 ± 2.17 years. A total of 26/72 (36%) and 29/65 (52%) of the non-exudative eyes had fluid during baseline and the last visit. Seven eyes (10%) out of 72 eyes converted into exudative AMD or neo-vascular AMD (nAMD) during the study period. SRPEF at baseline was most common fluid location for non-exudative eyes that eventually converted to nAMD. Conclusion: Non-exudative fluid including IRF, SRF, and SRPEF is seen in patients with non-exudative AMD with increasing incidence during long term follow-up.

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.

Long-term outcome of neovascular age-related macular degeneration: association between treatment outcome and major risk alleles

2021 ◽  
pp. bjophthalmol-2021-319054
Author(s):  
Brice Nguedia Vofo ◽  
Gala Beykin ◽  
Jaime Levy ◽  
Itay Chowers
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Long Term Outcome ◽  
Risk Alleles ◽  
Macular Atrophy ◽  
Anti Vegf ◽  
Age Related

AimsTo evaluate the long-term functional and anatomical outcomes of neovascular age-related macular degeneration (nvAMD) treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) for up to 10 years, and to identify associated risk factors.MethodsClinical and optical coherence tomography findings were retrieved for nvAMD cases treated with intravitreal anti-VEGF compounds using a treat-and-extend protocol. In addition, the major risk alleles for AMD in the CFH (rs1061170), HTRA1 (rs1200638) and C3 (rs2230199) genes were genotyped.ResultsFrom 276 eligible eyes in 206 patients, 80 eyes (29%) in 66 patients (32.0%) had a follow-up period of ≥8 years and were included in this study. Over a 10-year period, 73.3±28.0 (mean±SD) anti-VEGF injections were administered. Best-corrected visual acuity (BCVA; LogMAR) deteriorated from 0.55±0.53 at baseline to 1.00±0.73 at 10 years (p<0.0005). Central subfield thickness (CST) decreased from 415.8±162.1 µm at baseline to 323±113.6 µm (p<0.0005) after three monthly injections and remained lower than baseline throughout the follow-up period. Visual outcome was associated with BCVA and intraretinal fluid (IRF) at baseline, macular atrophy, and macular thinning at follow-up. The decrease in CST was inversely correlated with the number of CFH and/or C3 risk alleles carried by the patient (Pearson’s r: −0.608; p=0.003).ConclusionsPatients with nvAMD who received anti-VEGF therapy for 10 years developed substantial vision loss associated with the presence of IRF at baseline and macular atrophy. Major risk alleles for AMD in two complement genes were associated with a reduced long-term reduction in macular thickness.

scholarly journals Antivascular Endothelial Growth Factor Treatment Might Be Continued Even After Vitrectomy for Endophthalmitis in Neovascular Age-Related Macular Degeneration

2019 ◽  
Vol 4 (1) ◽  
pp. 6-12
Author(s):  
Zofia Michalewska ◽  
Jerzy Nawrocki
Keyword(s):  
Growth Factor ◽  
Macular Degeneration ◽  
Visual Outcome ◽  
Age Related Macular Degeneration ◽  
Anti Vegf ◽  
Age Related ◽  
Antivascular Endothelial Growth Factor ◽  
Endothelial Growth Factor ◽  
Mean Time

Purpose: This article studies visual outcome and frequency of antivascular endothelial growth factor (anti-VEGF) injections continued in patients with neovascular age-related macular degeneration (AMD) who had an earlier vitrectomy for postinjection endophthalmitis. Methods: A retrospective interventional study was conducted reviewing our database for patients with a diagnosis of endophthalmitis in the course of anti-VEGF injections. Endophthalmitis diagnosis was made on clinical examination of pain, rapid decrease in visual acuity (VA), conjunctival hyperemia, hypopyon, and vitritis. In all eyes, core vitrectomy with intravitreal antibiotics was performed. Spectral-domain optical coherence tomography was performed monthly before and after surgery during follow-up. Anti-VEGF injections were continued after surgery in all cases. Results: Eight eyes with postinjection endophthalmitis were included. Mean VA immediately before endophthalmitis was 20/50 Snellen with a mean of 19 intravitreal anti-VEGF injections ( P = .45). At time of endophthalmitis diagnosis, mean VA was 20/1000 (range, 20/2000-20/200). Mean time from injection to when the patient noted first symptoms was 4.3 days (range, 1-8 days). Mean time from first symptoms to surgery was 12 hours (range, 2.5-26 hours). Final mean VA at the end of follow-up (range, 12-84 months) did not statistically differ from VA at the visit immediately before endophthalmitis diagnosis ( P = .69). Mean frequency of injections after vitrectomy did not significantly differ from the presurgical course of treatment ( P =.97). Conclusions: Anti-VEGF treatment might be continued after vitrectomy for endophthalmitis and results in satisfactory anatomical and visual outcome. Surgery did not influence the frequency of anti-VEGF injections for neovascular AMD.

scholarly journals Stem cell-based technologies in treatment of age-related macular degeneration patients: current state of the problem

2020 ◽  
Vol 12 (4) ◽  
pp. 35-41
Author(s):  
Kirill Yu. Gayduk ◽  
Sergey V. Churashov ◽  
Alexey N. Kulikov
Keyword(s):  
Stem Cells ◽  
Macular Degeneration ◽  
Cultured Cells ◽  
Therapeutic Potential ◽  
Retinal Pigment ◽  
Antiangiogenic Therapy ◽  
Age Related Macular Degeneration ◽  
Common Disease ◽  
Treatment Methods ◽  
Age Related

Age-related macular degeneration (AMD) is the most common disease of the macula the area responsible for central vision. With regard to the pathogenesis of AMD, the main focus of most researchers is on the pathological processes occurring in the retinal pigment epithelium (RPE), which is considered as the main target of the disease. For the treatment of the dry form of the disease, which accounts for about 90% of all AMD cases, up to now no effective treatment methods were elaborated, while in the therapy of the wet form, antiangiogenic therapy, photodynamic therapy, and surgical treatment methods have been used with concrete success. Stem cells, possessing enormous therapeutic potential, are gradually being introduced into medical technologies, including ophthalmology. A number of pre-clinical studies have proven the safety of using cultured cells of the RPE, which gave rise to the beginning of clinical trials of the use of stem cells in the treatment of AMD patients. The review analyzes the data of scientific literature on the current understanding of the pathogenesis of AMD, pathogenetically substantiated therapies, including those using cell-based technologies, prospects and problems of using stem cells in the treatment of AMD patients.

scholarly journals Low-Reflectivity Drusen With Overlying RPE Damage Revealed by Spectral-Domain OCT: Hint for the Development of Age-Related Macular Degeneration

2021 ◽  
Vol 8 ◽  
Author(s):  
Shasha Yang ◽  
Zongyin Gao ◽  
Haijiang Qiu ◽  
Chengguo Zuo ◽  
Lan Mi ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Macular Degeneration ◽  
Retinal Pigment ◽  
Morphological Characteristics ◽  
Age Related Macular Degeneration ◽  
Spectral Domain ◽  
Optical Coherence ◽  
Age Related ◽  
Sd Oct

Purpose: To observe the relationship between the characteristic changes in the drusen morphology revealed by the spectral-domain optical coherence tomography (SD-OCT) and the progression of age-related macular degeneration (AMD).Methods: A total of 380 drusen in 45 eyes in 35 patients with the intermediate drusen were longitudinally followed up every 6 months by SD-OCT for a period of 24 months. The drusen were divided into the dynamic group and stable group according to the following parameters: number, volume, concurrent retinal pigment epithelium (RPE)/ellipsoid zone (EZ) damage, and the development of advanced AMD. The morphological characteristics of the progressive or stable drusen were further analyzed. Odds ratios (ORs) and the risk for the drusen progression were calculated.Results: The level of interobserver and intraobserver agreement for each drusen tomographic morphological parameters ranged from 82.7 to 90%. At the end of an average follow-up of 15.92 ± 6.99 months, six patients developed choroidal neovascularization and no patients developed geographic atrophy. Finally, 139 drusen changed and 241 drusen remained stable. The drusen with low reflectivity (p &lt; 0.001; OR: 5.26; 95% CI: 2.24–12.36), non-homogeneity without a core (p &lt; 0.001; OR: 4.31; 95% CI: 2.08–8.92), RPE damage (p &lt; 0.001; OR: 28.12; 95% CI: 9.43–83.85), and the EZ damage (p &lt; 0.001; OR: 14.01; 95% CI: 5.28–37.18) were significantly associated with active change; the drusen with low reflectivity (p = 0.01; OR: 2.95; 95% CI: 1.29–6.75) and decreased overlying RPE reflectivity (p &lt; 0.001; OR: 21.67; 95% CI: 9.20–51.02) were the independent predictors for progression. The drusen with high reflectivity were significantly associated with stabilization (p = 0.03; OR: 0.17; 95% CI: 0.04–0.84).Conclusion: Spectral-domain optical coherence tomography is an optimized, accurate, and efficient method to follow-up the drusen. The intermediate non-exudative AMD prognosis of the patient was most strongly correlated with the drusen reflectivity and disruption of the overlying RPE layer. The drusen with low reflectivity and overlying RPE damage were more likely to progress and required frequent follow-up.

scholarly journals Association between visual acuity, lesion activity markers and retreatment decisions in neovascular age-related macular degeneration

Eye ◽  
2020 ◽  
Vol 34 (12) ◽  
pp. 2249-2256 ◽  
Author(s):  
Usha Chakravarthy ◽  
Natasha Pillai ◽  
Annie Syntosi ◽  
Lorna Barclay ◽  
Catherine Best ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Macular Degeneration ◽  
Subretinal Fluid ◽  
Age Related Macular Degeneration ◽  
The United Kingdom ◽  
Anti Vegf ◽  
Age Related ◽  
Intraretinal Fluid ◽  
Endothelial Growth Factor ◽  
Clinic Visits

Abstract Background/objectives To investigate the association between optical coherence tomography (OCT) markers of lesion activity and changes in visual acuity (VA) during anti-vascular endothelial growth factor (anti-VEGF) therapy of eyes diagnosed with neovascular age-related macular degeneration (nAMD); and how VA and OCT markers are considered in physicians’ decision to retreat with anti-VEGFs. Subjects/methods Retrospective, non-comparative, non-randomised cohort study involving electronic medical record data collected from 1190 patient eyes with nAMD diagnosis at two sites in the United Kingdom. Two sub-cohorts consisting of 321 and 301 eyes, respectively, were selected for analyses. Results In 321 eyes, absence of IRF or SRF at ≥2 clinic visits resulted in a gain of five ETDRS letters from baseline, compared with two letters gained in eyes with <2 clinic visits with absence of IRF (p = 0.006) or SRF (p = 0.042). Anti-VEGF treatment was administered at 421 clinic visits, and 308 visits were without treatment. Comparing treatment visits with non-treatment visits, the maximum difference in frequency of OCT markers of lesion activity were for intraretinal fluid (IRF; 24% versus 5%) and subretinal fluid (SRF; 32% versus 5%). Pigment epithelial detachment (PED) was reported in 58% of treatment visits compared with 36% in non-treatment visits. VA loss was not a consistent trigger for retreatment as it was present in 63% of injection visits and in 49% of non-injection visits. Conclusions Retreatment decision making is most strongly influenced by the presence of IRF and SRF and less by the presence of PED or VA loss.

Clinical and Functional Characteristics of Secondary Geographic Atrophy Against the Background of Exudative Age-Related Macular Degeneration

2021 ◽  
Vol 76 (4) ◽  
pp. 384-393
Author(s):  
Vladimir V. Neroev ◽  
Marina V. Zueva ◽  
Natalia V. Neroeva ◽  
Ludmila A. Katargina ◽  
Oksana A. Losanova ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Antiangiogenic Therapy ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Flicker Erg ◽  
Wet Amd

Background.Studies demonstrate the need for long-term follow-up of patients with wet age-related macular degeneration (AMD) treated with inhibitors of angiogenesis to monitor long-term vision outcomes and assess the safety of antiangiogenic therapy in relation to the risk of secondary geographic atrophy. Aims to determine the characteristic clinical and functional signs of secondary GA that developed against the background of wet AMD. Methods.In 22 patients (25 eyes) with wet AMD and 18 healthy subjects comparable in age and sex standard ophthalmological and instrumental studies were performed and photopic electroretinograms (ERGs) were recorded according to ISCEV standards, flicker-ERGs, multifocal ERGs and electrooculogram. Results.The appearance of the area of secondary atrophy against the background of wet AMD in eyes treated with inhibitors of angiogenesis is clinically indistinguishable from areas of geographic atrophy that developed as an outcome of dry AMD. The ERG-signs of secondary atrophy are described, which are similar to the biomarkers of primary atrophy and specifically differ from them. Secondary atrophy is characterized by the dependence of the increase in the b/a ratio on the atrophic area, reducing of the 8.3 Hz-flicker-ERG amplitude in the absence of 24 Hz-flicker ERG changes. In eyes with secondary atrophy, a significant decrease in the density of the multifocal ERG P1-peak was shown not only in the first hexagon but also in the parafoveal zone. The electrooculography results showed a sharper dark troughs decrease in with an increase in Ardens ratio in patients with secondary atrophya on the background of wet AMD, in contrast to the previously described changes in primary geographic atrophy. Conclusion.Comparison of the change in the b/a ratio with secondary atrophy area in patients with wet AMD may have clinical implications for assessing retinal dysfunction and predicting visual function. Secondary atrophy is associated with a pronounced inhibition of photoreceptor activity with better preservation of cone bipolar cells. The ERG and electrooculography data taking together indicate a more significant dysfunction of the retinal pigment epithelium in GA against the background of wet AMD and the associated deterioration of photoreceptor function than the changes characterizing primary geographic atrophy.

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