scholarly journals Association of Anti-VEGF Injections with Progression of Geographic Atrophy

2016 ◽  
Vol 8 ◽  
pp. OED.S38863 ◽  
Author(s):  
Ryan Enslow ◽  
Sai Bhuvanagiri ◽  
Sravanthi Vegunta ◽  
Benjamin Cutler ◽  
Michael Neff ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Developed Countries ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Anti Vegf ◽  
Age Related ◽  
Wet Amd

Age-related macular degeneration (AMD) is one of the leading causes of blindness in developed countries in people over the age of 60 years. One of the forms of advanced AMD is wet AMD. Wet AMD is a result of leakage and bleeding from abnormal neovascularization. The principal treatment for wet AMD is intravitreal anti-VEGF injections. A second form of advanced AMD is geographic atrophy (GA). GA refers to large areas of retinal pigment epithelium loss. In the literature, there is some concern that anti-VEGF injections administered to treat wet AMD may be associated with progression of GA. This review discusses evidence suggesting the association of anti-VEGF injections with progression of GA.

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.

scholarly journals Incidence of Retinal Pigment Epithelial Tears and Associated Risk Factors After Treatment of Age-Related Macular Degeneration with Intravitreal Anti-VEGF Injections§

2014 ◽  
Vol 8 (1) ◽  
pp. 101-104 ◽  
Author(s):  
Theodoros Empeslidis ◽  
Athanasios Vardarinos ◽  
Vasileios Konidaris ◽  
Soon Wai Ch'ng ◽  
Bharat Kapoor ◽  
...  
Keyword(s):  
Risk Factors ◽  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Anti Vegf ◽  
Age Related ◽  
Associated Risk Factors ◽  
Rpe Tear

Purpose : To study the incidence and risk factors for retinal pigment epithelium tears following intravitreal anti-vascular endothelial growth factor (VEGF) injections. Methods : Retrospective longitudinal study. 4027 intravitreal anti-VEGF injections in 628 patients (676 eyes) for choroidal neovascularisation associated with age related macular degeneration in a period of 18 months were studied. Results : Seventeen patients (mean age 83.95±5.84) developed retinal pigment epithelium tears. The incidence rate was 0.4%. Fibrovascular pigment epithelium detachment (PED) was previously observed in all cases. In 88 % (15/17) of AMD patients that had a RPE tear, PED height was found to be less than 400 microns at presentation. In 5 of 7 patients with RPE tear grade <4, continuing of anti-VEGF treatment resulted to improvement of visual acuity. Conclusion : Critical risk factors for RPE tears are presence of PED as well as advanced age. Visual improvement appears to depend more on the extent and location of the RPE tear and less on the PED height.

scholarly journals Autophagy Genes for Wet Age-Related Macular Degeneration in a Finnish Case-Control Study

Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1318
Author(s):  
Jussi J. Paterno ◽  
Ali Koskela ◽  
Juha M.T. Hyttinen ◽  
Elina Vattulainen ◽  
Ewelina Synowiec ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Retinal Pigment ◽  
Developed Countries ◽  
Age Related Macular Degeneration ◽  
Cumulative Number ◽  
Sequestosome 1 ◽  
Anti Vegf ◽  
Age Related ◽  
Wet Amd

Age-related macular degeneration is an eye disease that is the main cause of legal blindness in the elderly in developed countries. Despite this, its pathogenesis is not completely known, and many genetic, epigenetic, environmental and lifestyle factors may be involved. Vision loss in age-related macular degeneration (AMD) is usually consequence of the occurrence of its wet (neovascular) form that is targeted in the clinic by anti-VEGF (vascular endothelial growth factor) treatment. The wet form of AMD is associated with the accumulation of cellular waste in the retinal pigment epithelium, which is removed by autophagy and the proteosomal degradation system. In the present work, we searched for the association between genotypes and alleles of single nucleotide polymorphisms (SNPs) of autophagy-related genes and wet AMD occurrence in a cohort of Finnish patients undergoing anti-VEGF therapy and controls. Additionally, the correlation between treatment efficacy and genotypes was investigated. Overall, 225 wet AMD patients and 161 controls were enrolled in this study. Ten SNPs (rs2295080, rs11121704, rs1057079, rs1064261, rs573775, rs11246867, rs3088051, rs10902469, rs73105013, rs10277) in the mTOR (Mechanistic Target of Rapamycin), ATG5 (Autophagy Related 5), ULK1 (Unc-51-Like Autophagy Activating Kinase 1), MAP1LC3A (Microtubule Associated Protein 1 Light Chain 3 α), SQSTM1 (Sequestosome 1) were analyzed with RT-PCR-based genotyping. The genotype/alleles rs2295080-G, rs11121704-C, rs1057079-C and rs73105013-T associated with an increased, whereas rs2295080-TT, rs2295080-T, rs11121704-TT, rs1057079-TT, rs1057079-T, rs573775-AA and rs73105013-C with a decreased occurrence of wet AMD. In addition, the rs2295080-GG, rs2295080-GT, rs1057079-TT, rs11246867-AG, rs3088051-CC and rs10277-CC genotypes were a positively correlated cumulative number of anti-VEGF injections in 2 years. Therefore, variability in autophagy genes may have an impact on the risk of wet AMD occurrence and the efficacy of anti-VEGF treatment.

scholarly journals Nove mogućnosti liječenja „suhe” senilne makularne degeneracije

2019 ◽  
Vol 55 (2) ◽  
pp. 121-132
Author(s):  
Tea Čaljkušić-Mance ◽  
Ivan Brumini ◽  
Renata Gržetić-Lenac ◽  
Tamara Mišljenović-Vučerić ◽  
Zvjezdana Alpeza-Dunato
Keyword(s):  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Choroidal Neovascularization ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Age Related

Senilna makularna degeneracija (engl. age-related macular degeneration; AMD) jedan je od najvažnijih uzroka gubitka centralnog vida kod starije populacije. Dijelimo je na „vlažnu” i „suhu” formu, ovisno o prisutnosti koroidne neovaskularizacije (engl. choroidal neovascularization; CNV). Do sada nijedna terapija nije potvrđena i odobrena za liječenje geografske atrofije (engl. geographic atrophy; GA), najtežeg oblika „suhog” AMD-a, jer nije bilo moguće popraviti oštećenja retinalnog pigmentnog epitela (engl. retinal pigment epithelium; RPE) i fotoreceptora. Liječenje se svodilo na pokušaje zaustavljanja progresije oboljenja i širenja geografske atrofije. Namjera ovog članka je prikazati podatke novijih dovršenih i tekućih kliničkih ispitivanja s naglaskom na mjesto djelovanja potencijalnih lijekova. Danas su nam dostupne brojne nove dijagnostičke metode koje nam omogućavaju bolje praćenje morfoloških promjena mrežnice, RPE-a i žilnice, kao i širenja područja atrofije. Oksidativni stres, kronična upala, insuficijentni koroidalni protok krvi te depoziti lipofuscina za koje se pretpostavlja da bi imali važniju ulogu u razvoju bolesti predstavljaju potencijalne mete za djelovanje lijekova. Velik je broj tekućih studija koje istražuju moguća rješenja, kao što su protuupalni i neuroprotektivni lijekovi te matične stanice, dok će samo neki od lijekova biti dostupni na tržištu i pružiti nadu pacijentima za očuvanje centralnog vida, pa ih je potrebno dugoročno pratiti. Uključiti treba i tretman ispodpražnim i mikropulsnim laserom koji je kod nekih oboljenja mrežnice pokazao određene rezultate u revitalizaciji tkiva, a koji koristimo i na našoj Klinici, te su prvi kratkoročni rezultati skromni ali ohrabrujući i zahtijevaju daljnje tretmane i praćenje.

scholarly journals Progression of Retinal Pigment Epithelium Atrophy in Patients with Long-Term Anti-Vegf Treatment for Exudative Age-Related Macular Degeneration

2017 ◽  
Vol 17 (2) ◽  
pp. 9-13
Author(s):  
Lita Jekabsone ◽  
Anete Kursite ◽  
Oskars Gertners ◽  
Guna Laganovska
Keyword(s):  
Visual Acuity ◽  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
First Year ◽  
Anti Vegf ◽  
Age Related ◽  
Retinal Pigment Epithelium Atrophy

Abstract Introduction.Age-related macular degeneration is the leading cause of visual impairment in developed world. The reason for using intravitreal injections of anti-vascular endothelial growth factor (VEGF) is to prevent choroidal neovascularization which is the main pathogenic mechanism for exudative age-related macular degeneration. Although injections may improve visual acuity, there are evidence showing association of anti-VEGF injections with progression of retinal pigment epithelium (RPE) atrophy. Aim of the Study.The purpose of this study was to investigate the intravitreal anti-vascular endothelial growth factor impact on retinal pigment epithelium atrophy development and progression. Material and methods.A single-centre retrospective study was conducted. Total 51 eyes of 39 patients with exudative age-related macular degeneration undergoing intravitreal anti-vascular endothelial growth factor therapy for 48 months. Heidelberg Spectralis Optical Coherence Tomography and fundus autofluorescence were used for evaluation of retinal pigment epithelium atrophy area and retinal thickness. Measurements were made manually. Best-corrected visual acuity (BCVA) measurements were taken from patient medical histories. For statistical analysis, IBM Statistical Package for the Social Sciences, version 23.0 was used. Results.The average age of patients was 81.6 ± 6.7 years. After first year of intravitreal anti-VEGF therapy, retinal pigment epithelium atrophy area enlarged from baseline (from 1.91 ± 2.3 mm2 to 2.74 ± 2.3mm2, p < 0.001). The mean number of intravitreal anti- VEGF injections received in 48 months was 15.47 ± 5.14. There was a statistically significant correlation between total number of intravitreal injections and RPE atrophy (R = 0.757, p < 0.001). After first year of anti-VEGF therapy best-corrected visual acuity (decimals) was statistically improved from baseline (0.32 ± 0.26 to 0.37 ± 0.24, p = 0.04). However, despite significant improvement at first year, the further treatment contributed BCVA reduction. Conclusions.Retinal pigment epithelium atrophy is a frequent finding in eyes with exudative age-related macular degeneration before and after anti-VEGF therapy. Our data show statistically significant association between total number of intravitreal anti-VEGF injections and retinal pigment epithelium atrophy area enlargement. Also there was statistically significant best-corrected visual acuity improvement after first year of anti-VEGF therapy.

scholarly journals Transcriptomic and proteomic retinal pigment epithelium signatures of age-related macular degeneration.

2021 ◽  
Author(s):  
Anne Senabouth ◽  
Maciej Daniszewski ◽  
Grace Lidgerwood ◽  
Helena Liang ◽  
Damian Hernandez ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Disease Status ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Rpe Cells ◽  
Age Related ◽  
Mitochondrial Functions

Induced pluripotent stem cells generated from patients with geographic atrophy as well as healthy individuals were differentiated to retinal pigment epithelium (RPE) cells. By integrating transcriptional profiles of 127,659 RPE cells generated from 43 individuals with geographic atrophy and 36 controls with genotype data, we identified 439 expression Quantitative Trait (eQTL) loci in cis that were associated with disease status and specific to subpopulations of RPE cells. We identified loci linked to two genes with known associations with geographic atrophy - PILRB and PRPH2, in addition to 43 genes with significant genotype x disease interactions that are candidates for novel genetic associations for geographic atrophy. On a transcriptome-only level, we identified molecular pathways significantly upregulated in geographic atrophy-RPE including in extracellular cellular matrix reorganisation, neurodegeneration, and mitochondrial functions. We subsequently implemented a large-scale proteomics analysis, confirming modification in proteins associated with these pathways. We also identified six significant protein (p) QTL that regulate protein expression in the RPE cells and in geographic atrophy - two of which share variants with cis-eQTL. Transcriptome-wide association analysis identified genes at loci previously associated with age-related macular degeneration. Further analysis conditional on disease status, implicated statistically significant RPE-specific eQTL. This study uncovers important differences in RPE homeostasis associated with geographic atrophy.

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