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2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Kaushal Sharma ◽  
Priya Battu ◽  
Ramandeep Singh ◽  
Suresh Kumar Sharma ◽  
Akshay Anand

AbstractAge-related macular degeneration (AMD) is a devastating retinal disease that results in irreversible vision loss in the aged population. The complex genetic nature and degree of genetic penetrance require a redefinition of the current therapeutic strategy for AMD. We aimed to investigate the role of modifiers for current anti-VEGF therapy especially for non-responder AMD patients. We recruited 78 wet AMD cases (out of 278 AMD patients) with their socio-demographic and treatment regimen. Serum protein levels were estimated by ELISA in AMD patients. Data pertaining to the number of anti-VEGF injections given (in 1 year) along with clinical images (FFA and OCT) of AMD patients were also included. Visual acuity data (logMAR) for 46 wet AMD cases out of a total of 78 patients were also retrieved to examine the response of anti-VEGF injections in wet AMD cases. Lipid metabolizing genes (LIPC and APOE) have been identified as chief biomarkers for anti-VEGF response in AMD patients. Both genotypes ‘CC’ and ‘GC’ of LIPC have found to be associated with a number of anti-VEGF injections in AMD patients which could influence the expression of B3GALTL,HTRA1, IER3, LIPC and SLC16A8 proteins in patients bearing both genotypes as compared to reference genotype. Elevated levels of APOE were also observed in group 2 wet AMD patients as compared to group 1 suggesting the significance of APOE levels in anti-VEGF response. The genotype of B3GALTL has also been shown to have a significant association with the number of anti-VEGF injections. Moreover, visual acuity of group 1 (≤ 4 anti-VEGF injections/year) AMD patients was found significantly improved after 3 doses of anti-VEGF injections and maintained longitudinally as compared to groups 2 and 3. Lipid metabolising genes may impact the outcome of anti-VEGF AMD treatment.


2021 ◽  
pp. 112067212110593
Author(s):  
Anadi Khatri ◽  
Araniko Pandey ◽  
Kriti Joshi ◽  
Kinsuk Singh ◽  
Gunjan Prasai ◽  
...  

Purpose Anti vascular endothelial growth factor (anti VEGF) has been the mainstay of treatment in wet age-related macular degeneration (AMD). Subsequent decision to continue anti VEGF therapy depends on the treatment response quantified by functional (visual acuity) and morphological (optical coherence tomography) parameters then categorized from good to poor. Methods This study evaluates the agreement between OCT angiography (OCTA) and non-OCTA (logMAR VA plus OCT) to decide anti-VEGF treatment's continuity. After an anti VEGF treatment, on a follow up visit, a patient underwent non-OCTA evaluation (decision A) then OCTA evaluation (decision B) to judge the necessity of future anti VEGF application. Results Out of 129 eyes, on 72 eyes (49%), there were agreements on both decision arms, but on 55 eyes (42%) there was disagreement. Particularly, disagreement on 47/55 eyes was important, where OCTA advised “continue anti VEGF” and non-OCTA advised “Stop anti VEGF” therapy. Cohen's Kappa for probability of agreement to continue anti VEGF was fair (0.33) and to stop anti VEGF therapy was none (0.1). Conclusions Based on resulting disagreements between the two modalities on deciding the continuity of anti VEGF, we conclude that OCTA must be considered in the conventional decision making algorithm in patients with wet AMD under anti VEGF therapy.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jin-Ho Joo ◽  
Hyejee Kim ◽  
Jae-Ho Shin ◽  
Sang Woong Moon

Abstract Background To identify disease-specific cytokine and growth factor profile differences in the aqueous humor between wet age-related macular degeneration (AMD) patients and age-matched controls and to correlate their levels with the optical coherence tomography (OCT) findings. Methods Aqueous humors were obtained from 13 wet AMD eyes and 10 control eyes. Twenty cytokines and growth factors were measured using a RayBio antibody microarray technology in wet AMD and control eyes. Results The samples obtained from wet AMD patients exhibited a significantly increased expression of MCP-1, MIP-1α, MIP-1β, and vascular endothelial growth factor (VEGF). Subretinal fluid (SRF) patients showed significantly lower levels of proinflammatory cytokines, such as IL-1α and GM-CSF, than those without SRF. Pigment epithelial detachments (PED) patients showed lower levels of inflammatory cytokines, such as GM-CSF, IFN-γ, and TNF-α, than those without PED. Subretinal tissue (SRT) patients showed a higher level of IFN-γ than those without SRT. Compared with the controls, type 1 macular neovascularization (MNV) patients showed increased levels of MCP-1, MIP-1α, and MIP-1β, but not VEGF (p = 0.083). However, type 2 MNV patients showed increased levels of MCP-1 and VEGF (p = 0.040 and p = 0.040). Conclusion Inflammatory cytokines varied according to the type of AMD- and OCT-based parameters. Our observation of low levels of VEGF in patients with type 1 MNV implies that the inhibition of VEGF alone appears to be insufficient treatment for these patients and that cytokines such as MCP-1, MIP-1α, and MIP-1β should be modulated. And the presence of SRF in MNV may be associated with a positive prognosis because we found relatively low levels of proinflammatory cytokines.


2021 ◽  
Vol 22 (22) ◽  
pp. 12321
Author(s):  
Hanan ElShelmani ◽  
Ian Brennan ◽  
David J. Kelly ◽  
David Keegan

This study explored the expression of several miRNAs reported to be deregulated in age-related macular degeneration (AMD). Total RNA was isolated from sera from patients with dry AMD (n = 12), wet AMD (n = 14), and controls (n = 10). Forty-two previously investigated miRNAs were selected based on published data and their role in AMD pathogenesis, such as angiogenic and inflammatory effects, and were co-analysed using a miRCURY LNA miRNA SYBR® Green PCR kit via quantitative real-time polymerase chain reaction (qRT-PCR) to validate their presence. Unsupervised hierarchical clustering indicated that AMD serum specimens have a different miRNA profile to healthy controls. We successfully validated the differentially regulated miRNAs in serum from AMD patients versus controls. Eight miRNAs (hsa-let-7a-5p, hsa-let-7d-5p, hsa-miR-23a-3p, hsa-miR-301a-3p, hsa-miR-361-5p, hsa-miR-27b-3p, hsa-miR-874-3p, hsa-miR-19b-1-5p) showed higher expression in the serum of dry AMD patients than wet AMD patients and compared with healthy controls. Increased quantities of certain miRNAs in the serum of AMD patients indicate that these miRNAs could potentially serve as diagnostic AMD biomarkers and might be used as future AMD treatment targets. The discovery of significant serum miRNA biomarkers in AMD patients would provide an easy screening tool for at-risk populations.


2021 ◽  
Author(s):  
Xiaolu Wang ◽  
Pengfei Zhan ◽  
Yuqing Cui ◽  
Yujuan Cao ◽  
Xun Bao ◽  
...  

Abstract Age-related macular degeneration (AMD), a progressive chronic disease of the central retina, is a leading cause of blindness worldwide. Activated macrophages recruited to the injured eyes greatly contribute to the pathogenesis of choroidal neovascularization (CNV) in exudative AMD (wet AMD). This study describes the effects of cyclooxygenase-2 (COX2)/prostaglandin E2 (PGE2) signalling on the M2 macrophage recruitment and CNV formation of wet AMD. In a mouse model of laser-induced wet AMD, the mice received an intravitreal injection of celecoxib (a selective COX2 inhibitor). Optical coherence tomography (OCT), fundus fluorescein angiography (FFA), choroidal histology of the CNV lesions, and biochemical markers were assessed. The level of PGE2 expression was high in the laser-induced CNV lesions. M2 polarization and CNV development were significantly less after celecoxib treatment. E-prostanoid1 receptor (EP1R)/protein kinase C (PKC) signalling was involved in M2 polarization and interleukin-10 (IL-10) production of bone marrow-derived macrophages (BMDMs) in vitro. In addition, IL-10 was found to induce the proliferation and migration of human choroidal microvascular endothelial cells (HCECs). Thus, the PGE2/EP1R signalling network serves as a potential therapeutic target for CNV of the wet-type AMD.


2021 ◽  
Vol 76 (4) ◽  
pp. 384-393
Author(s):  
Vladimir V. Neroev ◽  
Marina V. Zueva ◽  
Natalia V. Neroeva ◽  
Ludmila A. Katargina ◽  
Oksana A. Losanova ◽  
...  

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.


JAMA ◽  
2021 ◽  
Vol 326 (15) ◽  
pp. 1472
Author(s):  
Rebecca Voelker
Keyword(s):  

2021 ◽  
Vol 11 (19) ◽  
pp. 9313
Author(s):  
Kawther Taibouni ◽  
Alexandra Miere ◽  
Abdourahmane Samake ◽  
Eric Souied ◽  
Eric Petit ◽  
...  

Choroidal Neovascularization (CNV) is the advanced stage of Age-related Macular Degeneration (AMD), which is the leading cause of irreversible visual loss for elder people in developed countries. Optical Coherence Tomography Angiography (OCTA) is a recent non-invasive imaging technique widely used nowadays in diagnosis and follow-up of CNV. In this study, an automatic screening of CNV based on deep learning is performed using OCTA choriocapillaris images. CNV eyes (advanced wet AMD) are diagnosed among healthy eyes (no AMD) and eyes with drusen (intermediate AMD). An OCTA dataset of 1396 images is used to train and evaluate the model. A pre-trained convolutional neural network (CNN) is fine-tuned and validated on 80% of the dataset while the remaining 20% is used independently for predictions. The model can accurately detect CNV on the test set with an accuracy of 89.74%, precision of 0.96 and 0.99 area under the curve of the receiver operating characteristic. A good overall classification accuracy of 88.46% is obtained on a balanced test set. Detailed analysis of misclassified images shows that they are also considered ambiguous images for expert clinicians. This novel CNN-based application is truly a breakthrough to assist clinicians in the challenging task of screening for neovascular complications.


Author(s):  
E.V. Kozina ◽  
◽  
S.N. Sakhnov ◽  
V.V. Myasnikova ◽  
E.V. Bykova ◽  
...  

Purpose. Analysis A-VEGF therapy for wet form age-related macular degeneration (AMD) complicated by retinal pigment epithelium tear (RPET), different in involvement of macular zone (MZ), with different time of RPET regarding A-VEGF therapy. Material and methods. The results of treatment 18 patients with wet AMD complicated by RPET during monthly A-VEGF injection were analyzed. In first group (10 eyes) – RPET occurred before treatment, the second (8 eyes) – RPET arisen during A-VEGF. Visometry, ophthalmoscopy, fundus photoregistration, MZ OCT before and in month after each injection. Age – 65–83 years. Results. RPET (1,5 DD) captured fovea in 7 first group patients, in 3 patients RPET (0,5 DD) didn't affect fovea, In macula registered subretinal fluid (SRF) and hemorrhage (SRH). After 2 A-VEGF injections, resorption of SRF and SRH was observed. VA increased from 0,2 to 0,7 in cases RPET without capture of the fovea. RPET involving fovea occurred in 8 patients of the second group after the first A-VEGF injection. SRH and SRF resorbed. VA of patients decreased from 0,7 to 0,15. In both groups relapses of the SRF in macula after the development of RPET were not observed. Conclusion. Wet AMD complicated by RPET as a result of the pathological process and on the background of A-VEGF therapy. When RPET is involved fovea, VA decreases to 0.15. In case of preservation RPE in fovea – VA is high. A-VEGF therapy for wet AMD with RPET leads to resorption of SRH and SRF, to stop SRF for a long time. Key words: wet form macular degeneration, Anti-VEGF therapy, retinal pigment epithelium tear, macular zone


2021 ◽  
Vol 8 (3) ◽  
pp. 160-165
Author(s):  
Dorota Maria Kaczmarek

Wet age-related macular degeneration (wet AMD) is a disease which requires regular diagnostic tests such as macular optical coherent tomography which is extremely important both in diagnosis and disease monitoring. With constant aging of the population, we are dealing with an increasing incidence rate of AMD, which makes it even more important to have a tool allowing for quick and precise analysis of anatomical changes in macular region, particularly in the current complicated epidemiological situation when diagnostic time should be used most efficiently to plan the follow-up treatment. Forum® software allows for the precise analysis of many tests performed in a single patient and combining it with treatment effectiveness assessment which substantially accelerates the diagnostics.


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