Morphological characteristics of eyes with neovascular age-related macular degeneration and good long-term visual outcomes after anti-VEGF therapy

2021 ◽  
pp. bjophthalmol-2021-319602
Author(s):  
Mengyuan Fang ◽  
Karntida Chanwimol ◽  
Jyotsna Maram ◽  
Ghazala A Datoo O'Keefe ◽  
Charles C Wykoff ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Retinal Pigment ◽  
Morphological Characteristics ◽  
Age Related Macular Degeneration ◽  
Neovascular Amd ◽  
Poor Vision ◽  
Anti Vegf ◽  
Age Related ◽  
Good Vision

PurposeTo analyse the morphological characteristics of eyes with neovascular age-related macular degeneration (AMD) with good long-term visual acuity after anti-VEGF (vascular endothelial growth factor) therapy.MethodsRetrospective, observational study of 175 patients with neovascular AMD with >5 years of follow-up after initiating anti-VEGF therapy. Spectral-domain optical coherence tomography images were assessed for thickness of pigment epithelial detachment (PED), subretinal hyper-reflective material (SHRM), subretinal fluid and subfoveal choroidal, as well as the integrity of the outer retinal bands.ResultsThe final analysis cohort included 203 eyes (175 patients) followed for a mean of 7.84±1.70 years (range: 5–11). The maximum PED thickness in the foveal central subfield (FCS) was significantly lower (p<0.001) in the poor vision group (13.11 μm) compared with the intermediate (86.25 μm) or good (97.92 μm) vision groups, respectively. In contrast, the maximum thickness of SHRM in the FCS was significantly thicker (p<0.001) in eyes with poor vision (149.46 μm) compared with eyes with intermediate vision (64.37 μm) which in turn were significantly thicker (p<0.001) than eyes with good vision (9.35 μm). The good vision group also had better continuity of all outer retinal bands (external limiting membrane, ellipsoid zone, and retinal pigment epithelium) compared with the other two groups (all p<0.001).ConclusionA thicker PED and thinner SHRM were correlated with better vision in eyes with neovascular AMD following long-term anti-VEGF therapy. If replicated in future prospective studies, these findings may have implications for design of optimal anatomic endpoints for neovascular AMD treatment.

scholarly journals Gene Therapy with Endogenous Inhibitors of Angiogenesis for Neovascular Age-Related Macular Degeneration: Beyond Anti-VEGF Therapy

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Selwyn M. Prea ◽  
Elsa C. Chan ◽  
Gregory J. Dusting ◽  
Algis J. Vingrys ◽  
Bang V. Bui ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Prolonged Treatment ◽  
Large Animal ◽  
Neovascular Amd ◽  
Anti Vegf ◽  
Age Related

Age-related macular degeneration (AMD) is the leading cause of substantial and irreversible vision loss amongst elderly populations in industrialized countries. The advanced neovascular (or “wet”) form of the disease is responsible for severe and aggressive loss of central vision. Current treatments aim to seal off leaky blood vessels via laser therapy or to suppress vessel leakage and neovascular growth through intraocular injections of antibodies that target vascular endothelial growth factor (VEGF). However, the long-term success of anti-VEGF therapy can be hampered by limitations such as low or variable efficacy, high frequency of administration (usually monthly), potentially serious side effects, and, most importantly, loss of efficacy with prolonged treatment. Gene transfer of endogenous antiangiogenic proteins is an alternative approach that has the potential to provide long-term suppression of neovascularization and/or excessive vascular leakage in the eye. Preclinical studies of gene transfer in a large animal model have provided impressive preliminary results with a number of transgenes. In addition, a clinical trial in patients suffering from advanced neovascular AMD has provided proof-of-concept for successful gene transfer. In this mini review, we summarize current theories pertaining to the application of gene therapy for neovascular AMD and the potential benefits when used in conjunction with endogenous antiangiogenic proteins.

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 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.

scholarly journals Long-term Use of Aspirin and Age-related Macular Degeneration

2013 ◽  
Vol 06 (02) ◽  
pp. 144 ◽  
Author(s):  
William G Christen ◽  
Emily Y Chew ◽  
◽  
Keyword(s):  
Macular Degeneration ◽  
Observational Studies ◽  
Randomized Trials ◽  
Epidemiologic Studies ◽  
Age Related Macular Degeneration ◽  
Neovascular Amd ◽  
Age Related ◽  
The Us ◽  
Regular Aspirin

Recent findings from observational epidemiologic studies have raised concern about a possible adverse effect of regular aspirin use in age-related macular degeneration (AMD), and in particular neovascular AMD, which is the leading cause of severe irreversible blindness in the US. In this report, we consider these findings in light of the relative strengths and limitations of observational studies and randomized trials. While the findings are important and warrant further investigation, the inherent limitations of observation studies, most notably uncontrolled confounding, preclude an interpretation of causality. Alternatively, the most reliable evidence with which to evaluate the effects of regular aspirin use in AMD will derive from well-designed randomized trials of sufficient size and duration.

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 Ten-year survival trends of neovascular age-related macular degeneration at first presentation

2020 ◽  
pp. bjophthalmol-2020-317161
Author(s):  
Cristina Arpa ◽  
Hagar Khalid ◽  
Shruti Chandra ◽  
Siegfried Wagner ◽  
Katrin Fasler ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Visual Outcomes ◽  
Anti Vegf ◽  
Kaplan Meier ◽  
Age Related ◽  
Treatment Naïve ◽  
Mean Trend ◽  
Endothelial Growth Factor ◽  
Good Vision

BackgroundTo describe 10-year trends in visual outcomes, anatomical outcomes and treatment burden of patients receiving antivascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD).MethodsRetrospective cohort study of treatment-naïve, first-affected eyes with nAMD started on ranibizumab before January 1, 2009. The primary outcome was time to best-corrected visual acuity (BCVA) falling ≤35 ETDRS letters after initiating anti-VEGF therapy. Secondary outcomes included time to BCVA reaching ≥70 letters, proportion of eyes with BCVA ≥70 and ≤35 letters in 10 years, mean trend of BCVA and central retinal thickness over 10 years, and mean number of injections.ResultsFor our cohort of 103 patients, Kaplan-Meier analyses demonstrated median time to BCVA reaching ≤35 and ≥70 letters were 37.8 (95% CI 22.2 to 65.1) and 8.3 (95% CI 4.8 to 20.9) months after commencing anti-VEGF therapy, respectively. At the final follow-up, BCVA was ≤35 letters and ≥70 letters in 41.1% and 21%, respectively, in first-affected eyes, while this was the case for 5.4% and 48.2%, respectively, in a patient’s better-seeing eye. Mean injection number was 37.0±24.2 per eye and 53.6±30.1 at patient level (63.1% of patients required injections in both eyes).ConclusionsThe chronicity of nAMD disease and its management highlights the importance of long-term visual prognosis. Our analyses suggest that one in five patients will retain good vision (BCVA ≥70 ETDRS letters) in the first-affected eye at 10 years after starting anti-VEGF treatment; yet, one in two patients will have good vision in their better-seeing eye. Moreover, our data suggest that early treatment of nAMD is associated with better visual outcomes.

scholarly journals Treatment for neovascular age-related macular degeneration: reasonable expectations of physicians and patients

2021 ◽  
Vol 21 (3) ◽  
pp. 169-174
Author(s):  
A.B. Durasov ◽  
◽  
◽  
◽  
◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Treatment Outcomes ◽  
Randomized Clinical Trials ◽  
Patient Characteristics ◽  
Age Related Macular Degeneration ◽  
Strict Adherence ◽  
Treat And Extend ◽  
Anti Vegf ◽  
Age Related

Neovascular age-related macular degeneration (nAMD) is a progressive chronic multifactorial disease requiring long-term, lifelong anti- VEGF therapy. Treatment outcomes are not always in line with the results of randomized clinical trials and do not meet the expectations for therapy whose success is assessed differently by patients and physicians. Good functional and anatomical results are expected from antivasoproliferative therapy under certain conditions, e.g., accurate evaluation of some patient characteristics (baseline visual acuity, type of choroidal neovascularization, comorbidities, status of retinal fluid and its differentiation), timely (as early as possible) treatment initiation after verifying diagnosis, and strict adherence to a proactive personalized "Treat-and-Extend" (T&E) regimen that implies a required number of injections with individual intervals. Poor adherence to treatment (non-compliance or nonpersistence of anti-VEGF therapy) significantly affects treatment outcomes in real-world clinical practice. This paper reviews criteria which predict the response to antivasoproliferative therapy and improving treatment adherence. The authors describe four fundamental principles to be met by an ideal regimen of anti-VEGF therapy for nAMD. Keywords: neovascular age-related macular degeneration, nAMD, "Treat-and-Extend", T&E, adherence, nonpersistence, anti-VEGF. For citation: Durasov A.B. Treatment for neovascular age-related macular degeneration: reasonable expectations of physicians and patients. Russian Journal of Clinical Ophthalmology. 2021;21(3):169–174 (in Russ.). DOI: 10.32364/2311-7729-2021-21-3-169-174.

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