scholarly journals Electrophysiological signs of retinal cone remodeling in geographic atrophy of the pigment epithelium in patients with non-exudative age-related macular degeneration

2021 ◽  
Vol 14 (3) ◽  
pp. 32-39
Author(s):  
N. V. Neroeva ◽  
M. V. Zueva ◽  
V. V. Neroev ◽  
I. V. Tsapenko ◽  
M. V. Ryabina ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Selective Reduction ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Fundus Photography ◽  
Exudative Amd ◽  
Age Related ◽  
Retinal Cone

Testing patients with primary geographic atrophy (GA) requires a multimodal approach and identification of functional biomarkers characterizing retinal structural remodeling.Purpose: to identify the changes in the functional activity of the retinal cone system, which may serve as biomarkers of primary GA in non-exudative age-related macular degeneration (AMD).Material and methods. We tested 22 patients (30 eyes) aged 45–83 (ave. 72.1 ± 10.8 years) with non-exudative AMD and 18 age matched controls (60.2 ± 7.6 years) all of which underwent standard ophthalmological examinations, optical coherence tomography, autofluorescence study, and fundus photography. Standard photopic ERGs, photopic flicker ERGs to stimuli with frequencies of 8.3, 10, 12, and 24 Hz, multifocal ERG (mfERG), and electrooculogram (EOG) were recorded.Results. Electroretinographic signs for GA of retinal pigment epithelium and choriocapillary layer atrophy were described. The results confirm early impairment of the activity of cones in GA and weakening of the functional interaction of M ller cells with the cone bipolar cells. The delayed P1 peak latency of mfERG indicates a decrease in the entire central retina function in non-exudative AMD. A selective reduction in the fovea's mfERG magnitude can serve as a biomarker of primary GA. The spread of the P1 anomaly to adjacent rings may indicate a possible risk of disease progression. A decrease in the dark trough on the EOG and an increase in the Arden ratio can serve as a biomarker of primary GA.Conclusion. We determined electrophysiological signs which can serve as markers of early retinal dysfunction in eyes with primary GA and non-exudative AMD.

scholarly journals Progressive dysmorphia of retinal pigment epithelium in age related macular degeneration revealed by fluorescence lifetime imaging

2021 ◽  
Author(s):  
Martin Hammer ◽  
Juliane Jakob-Girbig ◽  
Linda Schwanengel ◽  
Christine A. Curcio ◽  
Somar Hasan ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Fluorescence Lifetime ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Fundus Photography ◽  
Fluorescence Lifetime Imaging ◽  
Lifetime Imaging ◽  
Age Related

AbstractPurposeTo observe changes of the retinal pigment epithelium (RPE) on the transition from dysmorphia to atrophy in age related macular degeneration (AMD) by fluorescence lifetime imaging ophthalmoscopy (FLIO).MethodsMultimodal imaging including color fundus photography (CFP), optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, and FLIO was performed in 40 eyes of 37 patients with intermediate AMD and no evidence for geographic atrophy or macular neovascularization) (mean age: 74.2±7.0 years). Twenty-three eyes were followed for 28.3±18.3 months. Seven eyes had a second follow up after 46.6±9.0 months. Thickened RPE on OCT, hyperpigmentation on CFP, and migrated RPE, seen as hyperreflective foci (HRF) on OCT, were identified. Fluorescence lifetimes in two spectral channels (SSC: 500-560 nm, LSC: 560-720 nm) as well as emission spectrum intensity ratio (ESIR) of the lesions were measured by FLIO.ResultsAs hyperpigmented areas form and RPE migrates into the retina, FAF lifetimes lengthen and ESRI of RPE cells increase. Thickened RPE showed lifetimes of 256±49 ps (SSC) and 336±35 ps (LSC) and an ESIR of 0.552±0.079. For hyperpigmentation, these values were 317±68 ps (p<0.001), 377±56 ps (p<0.001), and 0.609±0.081 (p=0.001), respectively, and for HRF 337±79 ps (p<0.001), 414±50 ps (p<0.001), and 0.654±0.075 (p<0.001).ConclusionsIn the process of RPE degeneration, comprising different steps of dysmorphia, hyperpigmentation, and migration, lengthening of FAF lifetimes and a hypsochromic shift of emission spectra can be observed by FLIO. Thus, FLIO might provide early biomarkers for AMD progression and contribute to our understanding of RPE pathology.

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 Choriocapillaris Loss in Advanced Age-Related Macular Degeneration

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Carlos A. Moreira-Neto ◽  
Eric M. Moult ◽  
James G. Fujimoto ◽  
Nadia K. Waheed ◽  
Daniela Ferrara
Keyword(s):  
Macular Degeneration ◽  
Current Knowledge ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Advanced Age ◽  
Tissue Loss ◽  
Age Related

The purpose of this review is to summarize the current knowledge on choriocapillaris loss in advanced age macular degeneration (AMD). Several histopathological studies in animal models and human eyes had showed that the choriocapillaris density decreases with age. However, the role of choriocapillaris loss is still unclear in AMD and its advanced forms, either choroidal neovascularization (CNV) or geographic atrophy (GA). Some authors have hypothesized that choriocapillaris loss might precede overt retinal pigment epithelium atrophy. Others have hypothesized that deposition of complement complexes on and around the choriocapillaris could be related to the tissue loss observed in early AMD. The development of imaging modalities, such as optical coherence tomography angiography (OCTA), have led to a better understanding of underlying physiopathological mechanisms in AMD. OCTA showed atrophy of choriocapillaris underneath and beyond the region of photoreceptors and RPE loss, in agreement with previous histopathologic studies. The evolution of OCTA technology suggests that CNV seems to originate from regions of severe choriocapillaris alteration. Significant progress has been made in the understanding of development and progression of GA and CNV. In vivo investigation of the choriocapillaris using OCTA may lead to new insights related to underlying disease mechanisms in AMD.

scholarly journals Complement System and Potential Therapeutics in Age-Related Macular Degeneration

2021 ◽  
Vol 22 (13) ◽  
pp. 6851
Author(s):  
Young-Gun Park ◽  
Yong-Soo Park ◽  
In-Beom Kim
Keyword(s):  
Macular Degeneration ◽  
Complement System ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelium Cell ◽  
Immune Surveillance ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
The Complement System

Age-related macular degeneration (AMD) is a complex multifactorial disease characterized in its late form by neovascularization (wet type) or geographic atrophy of the retinal pigment epithelium cell layer (dry type). The complement system is an intrinsic component of innate immunity. There has been growing evidence that the complement system plays an integral role in maintaining immune surveillance and homeostasis in AMD. Based on the association between the genotypes of complement variants and AMD occurrence and the presence of complement in drusen from AMD patients, the complement system has become a therapeutic target for AMD. However, the mechanism of complement disease propagation in AMD has not been fully understood. This concise review focuses on an overall understanding of the role of the complement system in AMD and its ongoing clinical trials. It provides further insights into a strategy for the treatment of AMD targeting the complement system.

scholarly journals NLRP3 Inflammasome: Activation and Regulation in Age-Related Macular Degeneration

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Jiangyuan Gao ◽  
Ruozhou Tom Liu ◽  
Sijia Cao ◽  
Jing Z. Cui ◽  
Aikun Wang ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Elderly ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Inflammasome Activation ◽  
Related Factors ◽  
Rpe Cells ◽  
Age Related

Age-related macular degeneration (AMD) is the leading cause of legal blindness in the elderly in industrialized countries. AMD is a multifactorial disease influenced by both genetic and environmental risk factors. Progression of AMD is characterized by an increase in the number and size of drusen, extracellular deposits, which accumulate between the retinal pigment epithelium (RPE) and Bruch’s membrane (BM) in outer retina. The major pathways associated with its pathogenesis include oxidative stress and inflammation in the early stages of AMD. Little is known about the interactions among these mechanisms that drive the transition from early to late stages of AMD, such as geographic atrophy (GA) or choroidal neovascularization (CNV). As part of the innate immune system, inflammasome activation has been identified in RPE cells and proposed to be a causal factor for RPE dysfunction and degeneration. Here, we will first review the classic model of inflammasome activation, then discuss the potentials of AMD-related factors to activate the inflammasome in both nonocular immune cells and RPE cells, and finally introduce several novel mechanisms for regulating the inflammasome activity.

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 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.

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.

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