scholarly journals The Impact of Rheohaemapheresis on the Proprotein Convertase Subtilisin Kexin 9 (PCSK9) in Age-Related Macular Degeneration

2020 ◽  
Author(s):  
Vladimír Blaha ◽  
Hana Langrová ◽  
Milan Blaha ◽  
Jan Studnička ◽  
Alexander Stěpanov ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Macular Degeneration ◽  
Treated Patient ◽  
Pigment Epithelium ◽  
Significant Risk ◽  
Age Related Macular Degeneration ◽  
Long Term Effects ◽  
Age Related ◽  
The Impact

Abstract Background. Age-related macular degeneration (AMD) is a progressive chronic disease with resulting visual impairment or even blindness with limited therapeutic options. Because hyperlipidemia is a significant risk factor for AMD development we investigated long-term effects of rheohaemapheresis in the dry form of age-related macular degeneration on the lipid related parameters including PCSK9.Methods. This study evaluates 31 patients with age-related macular degeneration (AMD), treated with rheohaemapheresis. The followed-up period was 7 years. Average age was 69.1 ± 4.9 years. Each treated patient received a series of 8 sessions of rheohaemapheresis. 2 additional procedures within 1-week procedures were performed to boost the effect after the 2-year period. We measured the drusenoid pigment epithelium detachment (DPED), best-corrected visual acuity (BCVA), electroretinography (ERG), lipid, inflammatory, endothelial dysfunction and rheologically important parameters. Results. Rheohaemapheresis treatment in AMD patients was associated with a significant decrease of total cholesterol, LDL-C, HDL-C, apoprotein B, and lipoprotein (a) levels, biomarkers of inflammation, endothelial dysfunction (CD40L, MCP-1) and rheologically important parameters, and serum PCSK9 (P<0.001). The patients were further divided into 2 groups based on the ophtalmological examination. Successfully treated patients (n=10, with at least a 5-year follow-up) had significantly lower baseline LDL-C and ApoB (P<0.05) and their serum PCSK9 significantly decreased after rheohaemapheresis (P<0.001) in comparison to the patients where treatment failured (n=4). Conclusion. Over the long term, rheohaemapheresis reduced the DPED, improved the function of photoreceptors, and prevented the decline of BCVA. BCVA improvement was accompanied by lowering of LDL-C and PCSK9 and improvement of endothelial dysfunction. We suggest that rheohaemapheresis and other novel anti-PCSK9 therapies may be used synergistically to reduce severity, slow down or even induce regression of AMD.

scholarly journals Long-Term Outcomes of Rheohaemapheresis in the Treatment of Dry Form of Age-Related Macular Degeneration

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Jan Studnička ◽  
Eva Rencová ◽  
Milan Bláha ◽  
Pavel Rozsíval ◽  
Miriam Lánská ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Treated Patient ◽  
Pigment Epithelium ◽  
Age Related Macular Degeneration ◽  
Rheological Parameters ◽  
Control Group ◽  
Long Term Effects ◽  
Age Related

Purpose. Determining long-term effects of rheohaemapheresis on the dry form of age-related macular degeneration.Methods. This study evaluates 19 patients, average age of 67.6 years, treated with rheohaemapheresis and 18 patients, average age of 72.8 years, comprising the control group. Minimum follow up period was 3.5 years. Each treated patient received a series of 8 sessions of rheohaemapheresis of 1.5 plasma volumes within 10 weeks. We measured the drusenoid pigment epithelium detachment (DPED), best-corrected visual acuity (BCVA), electroretinography (ERG), and rheological parameters.Results. In the treatment group, the baseline BCVA was 0.74 (0.36–1.0) 95% CI and BCVA after 3.5 years was 0.79 (0.41–1.0) 95% CI (P=0.726). In the control group, the baseline BCVA was 0.71 (0.15–1.0) 95% CI and BCVA after 3.5 years decreased to 0.7 (0.32–0.87) 95% CI (P=0.031). Baseline DPED was 6.78 ± 3.79 mm2; after 3.5 years, it decreased to 4.13 ± 3.84 mm2(P<0.001). In the control group, the baseline DPED was 4.09 ± 3.48 mm2; after 3.5 years, it increased to 6.69 ± 4.2 mm2(P=0.001). We noted increasing levels of positive wave peaking at 50 milliseconds (P50) after treatment (P=0.022) and a stable amplitude of photopic responses of treated patients.Conclusion. Over the long term, rheohaemapheresis reduced the DPED, improved the function of photoreceptors, and prevented the decline of BCVA.

scholarly journals The Impact of Oxidative Stress on Blood-Retinal Barrier Physiology in Age-Related Macular Degeneration

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 64
Author(s):  
Annamaria Tisi ◽  
Marco Feligioni ◽  
Maurizio Passacantando ◽  
Marco Ciancaglini ◽  
Rita Maccarone
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Blood Retinal Barrier ◽  
Functional Changes ◽  
Beneficial Effects ◽  
Age Related ◽  
The Impact

The blood retinal barrier (BRB) is a fundamental eye component, whose function is to select the flow of molecules from the blood to the retina and vice-versa, and its integrity allows the maintenance of a finely regulated microenvironment. The outer BRB, composed by the choriocapillaris, the Bruch’s membrane, and the retinal pigment epithelium, undergoes structural and functional changes in age-related macular degeneration (AMD), the leading cause of blindness worldwide. BRB alterations lead to retinal dysfunction and neurodegeneration. Several risk factors have been associated with AMD onset in the past decades and oxidative stress is widely recognized as a key factor, even if the exact AMD pathophysiology has not been exactly elucidated yet. The present review describes the BRB physiology, the BRB changes occurring in AMD, the role of oxidative stress in AMD with a focus on the outer BRB structures. Moreover, we propose the use of cerium oxide nanoparticles as a new powerful anti-oxidant agent to combat AMD, based on the relevant existing data which demonstrated their beneficial effects in protecting the outer BRB in animal models of AMD.

scholarly journals Myopia and age-related macular degeneration: structural and anatomical changes of the eye

2019 ◽  
Vol 12 (3) ◽  
pp. 5-12
Author(s):  
I. B. Alekseev ◽  
Ju. A. Nam
Keyword(s):  
Visual Acuity ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Central Zone ◽  
Age Related Macular Degeneration ◽  
Visual Functions ◽  
Chorioretinal Atrophy ◽  
Age Related ◽  
High Degree ◽  
The Impact

The purpose of the study was to find out how age-related macular degeneration and medium-high degree myopia affect the structural and anatomical parameters of the eyeball, and to find whether a relationship exists between various types of myopic staphylomas and changes of visual functions.Material and methods. 120 patients (236 eyes), with medium and high degree myopia and age-related retinal changes, aged 44 to 81 years were tested for two groups of parameters: quantitative and qualitative. The former included the patients’ age, best corrected visual acuity (BCVA), computer perimetry data, the axial length, and the thickness of the retina in the central zone. The latter included retinal changes, in particular pigment epithelium (PE) defects, drusen, PE detachment, choroidal neovascular membrane (CNV), Fuchs spot and diffuse chorioretinal atrophy. The impact of various types of staphylomas on visual functions was evaluated. Results. Visual functions were found to directly depend on retinal PE integrity. If defects, detachment, or drusen are present, computer perimetry parameters and BVCA are reducing. Fuchs spot presence and diffuse chorioretinal atrophy reduces BCVA and causes an MD decrease. The lowest visual acuity and considerable light sensitivity loss was noted in patients with combined staphylomas. Conclusion. The obtained data confirm that retinal dystrophic processes directly affect visual functions: BCVA and retinal photosensitivity levels drop in all retinal changes studied. The presence of staphyloma, being a factor that aggravates myopia, undoubtedly worsens the most of the parameters studied. 

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 PEDF expression affects the oxidative and inflammatory state of choroidal endothelial cells

2018 ◽  
Vol 314 (4) ◽  
pp. C456-C472 ◽  
Author(s):  
Mitra Farnoodian ◽  
Christine M. Sorenson ◽  
Nader Sheibani
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Inflammatory Diseases ◽  
Expression Profiles ◽  
Pigment Epithelium ◽  
Age Related Macular Degeneration ◽  
Primary Role ◽  
Age Related ◽  
Inflammatory State ◽  
The Impact

Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly population, and is associated with severe macular degeneration and choroidal neovascularization (CNV). Although the pathogenesis of AMD is associated with choroidal dysfunction and CNV, the detailed underlying mechanisms remain unresolved. Altered production of pigment epithelium-derived factor (PEDF), a neuroprotective and antiangiogenic factor, contributes to CNV. Furthermore, exogenous PEDF mitigates angiogenesis in preclinical CNV models. How PEDF expression affects choroidal endothelial cell (ChEC) function is unknown. Here we isolated ChECs from PEDF+/+ and PEDF-deficient (PEDF−/−) mice and determined the impact of PEDF expression on the proangiogenic and pro-inflammatory properties of ChECs. We showed that PEDF expression significantly affects the proliferation, migration, adhesion, and oxidative and inflammatory state of ChECs. The PEDF−/− ChECs were, however, more sensitive to H2O2 challenge and exhibited increased rate of apoptosis and oxidative stress. We also observed a significant increase in production of cytokines with a primary role in inflammation and angiogenesis including vascular endothelial growth factor (VEGF) and osteopontin, and a reprograming of chemokines and cytokines expression profiles in PEDF−/− ChECs. Collectively, our results indicate that PEDF expression has a significant impact on oxidative and inflammatory properties of ChECs, whose alteration could contribute to pathogenesis of chronic inflammatory diseases including exudative AMD.

scholarly journals Long-Term Effects of Vitamins C and E, β-Carotene, and Zinc on Age-related Macular Degeneration

Ophthalmology ◽  
2013 ◽  
Vol 120 (8) ◽  
pp. 1604-1611.e4 ◽  
Author(s):  
Emily Y. Chew ◽  
Traci E. Clemons ◽  
Elvira Agrón ◽  
Robert D. Sperduto ◽  
John Paul SanGiovanni ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Long Term Effects ◽  
Age Related ◽  
Β Carotene

scholarly journals Role of FGF and Hyaluronan in Choroidal Neovascularization in Sorsby Fundus Dystrophy

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 608
Author(s):  
Alyson Wolk ◽  
Dilara Hatipoglu ◽  
Alecia Cutler ◽  
Mariya Ali ◽  
Lestella Bell ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Choroidal Neovascularization ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Rpe Cells ◽  
Age Related ◽  
Sorsby's Fundus Dystrophy

Sorsby’s fundus dystrophy (SFD) is an inherited blinding disorder caused by mutations in the tissue inhibitor of metalloproteinase-3 (TIMP3) gene. The SFD pathology of macular degeneration with subretinal deposits and choroidal neovascularization (CNV) closely resembles that of the more common age-related macular degeneration (AMD). The objective of this study was to gain further insight into the molecular mechanism(s) by which mutant TIMP3 induces CNV. In this study we demonstrate that hyaluronan (HA), a large glycosaminoglycan, is elevated in the plasma and retinal pigment epithelium (RPE)/choroid of patients with AMD. Mice carrying the S179C-TIMP3 mutation also showed increased plasma levels of HA as well as accumulation of HA around the RPE in the retina. Human RPE cells expressing the S179C-TIMP3 mutation accumulated HA apically, intracellularly and basally when cultured long-term compared with cells expressing wildtype TIMP3. We recently reported that RPE cells carrying the S179C-TIMP3 mutation have the propensity to induce angiogenesis via basic fibroblast growth factor (FGF-2). We now demonstrate that FGF-2 induces accumulation of HA in RPE cells. These results suggest that the TIMP3-MMP-FGF-2-HA axis may have an important role in the pathogenesis of CNV in SFD and possibly AMD.

Long-term effects of ranibizumab treatment delay in neovascular age-related macular degeneration

2012 ◽  
Vol 251 (2) ◽  
pp. 453-458 ◽  
Author(s):  
Philipp S. Muether ◽  
Robert Hoerster ◽  
Manuel M. Hermann ◽  
Bernd Kirchhof ◽  
Sascha Fauser
Keyword(s):  
Macular Degeneration ◽  
Treatment Delay ◽  
Age Related Macular Degeneration ◽  
Long Term Effects ◽  
Age Related ◽  
Ranibizumab Treatment
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