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Scientific Reports Nov 2023Though vascular endothelial growth factors (VEGF) and other proangiogenic factors, such as angiopoietins (Ang), may be involved in the development of neovascular...
Though vascular endothelial growth factors (VEGF) and other proangiogenic factors, such as angiopoietins (Ang), may be involved in the development of neovascular age-related macular degeneration (nvAMD), only drugs that inhibit the VEGF family are available for the treatment. The newly approved anti-VEGF drug faricimab, which also inhibits Ang-2, is expected to be effective in patients with AMD refractory to conventional anti-VEGF drugs. Therefore, we prospectively investigated the efficacy of faricimab in the treatment of aflibercept-refractory nvAMD. Patients with nvAMD who had been treated with aflibercept in the last year and required bimonthly injections were recruited. 25 eyes showed persistent exudative changes immediately before the faricimab injection (baseline). In these 25 eyes, switching to faricimab did not change visual acuity or central retinal thickness 2 months after the injection; however, 56% of eyes showed reduction or complete absorption of fluid. Notably, 25% of the eyes that showed dry macula at month 2 had no fluid recurrence for up to 4 months. These results indicate that faricimab could benefit some patients with aflibercept-refractory nvAMD.
Topics: Humans; Ranibizumab; Vascular Endothelial Growth Factor A; Treatment Outcome; Follow-Up Studies; Tomography, Optical Coherence; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Macular Degeneration; Intravitreal Injections; Angiogenesis Inhibitors; Wet Macular Degeneration
PubMed: 38036627
DOI: 10.1038/s41598-023-48190-6 -
Journal of Global Health Nov 2023Retinal disorders cause substantial visual burden globally. Accurate estimates of the vision loss due to retinal diseases are pivotal to inform optimal eye health care...
BACKGROUND
Retinal disorders cause substantial visual burden globally. Accurate estimates of the vision loss due to retinal diseases are pivotal to inform optimal eye health care planning and allocation of medical resources. The purpose of this study is to describe the proportion of visual impairment and blindness caused by major retinal diseases in China.
METHODS
A nationwide register-based study of vitreoretinal disease covering all 31 provinces (51 treating centres) of mainland China. A total of 28 320 adults diagnosed with retinal diseases were included. Participants underwent standardised ocular examinations, which included best-corrected visual acuity (BCVA), dilated-fundus assessments, and optical coherence tomography. Visual impairment and blindness are defined using BCVA according to the World Health Organization (WHO) (visual impairment: <20/63-≥20/400; blindness: <20/400) and the United States (visual impairment: <20/40-≥20/200; blindness: <20/200) definitions. The risk factors of vision loss were explored by logistic regression analyses.
RESULTS
Based on the WHO definitions, the proportions for unilateral visual impairment and blindness were 46% and 18%, respectively, whereas those for bilateral visual impairment and blindness were 31% and 3.3%, respectively. Diabetic retinopathy (DR) accounts for the largest proportion of patients with visual impairment (unilateral visual impairment: 32%, bilateral visual impairment: 60%) and blindness (unilateral blindness: 35%; bilateral blindness: 64%). Other retinal diseases that contributed significantly to vision loss included age-related macular degeneration, myopic maculopathy, retinal vein occlusion, and rhegmatogenous retinal detachment and other macular diseases. Women (bilateral vision loss: P = 0.011), aged patients (unilateral vision loss: 45-64 years: P < 0.001, ≥65 years: P < 0.001; bilateral vision loss: 45-64 years: P = 0.003, ≥65 years: P < 0.001 (reference: 18-44 years)) and those from Midwest China (unilateral and bilateral vision loss: both P < 0.001) were more likely to suffer from vision loss.
CONCLUSIONS
Retinal disorders cause substantial visual burden among patients with retinal diseases in China. DR, the predominant retinal disease, is accountable for the most prevalent visual disabilities. Better control of diabetes and scaled-up screenings are warranted to prevent DR. Specific attention should be paid to women, aged patients, and less developed regions.
Topics: Adult; Humans; Female; Aged; Visually Impaired Persons; Visual Acuity; Blindness; Vision, Low; Vision Disorders; Retinal Diseases; Macular Degeneration; Diabetic Retinopathy; Prevalence
PubMed: 37921040
DOI: 10.7189/jogh.13.04126 -
Progress in Retinal and Eye Research Sep 2023Despite comprehensive research efforts over the last decades, the pathomechanisms of age-related macular degeneration (AMD) remain far from being understood. Large-scale... (Review)
Review
Despite comprehensive research efforts over the last decades, the pathomechanisms of age-related macular degeneration (AMD) remain far from being understood. Large-scale genome wide association studies (GWAS) were able to provide a defined set of genetic aberrations which contribute to disease risk, with the strongest contributors mapping to distinct regions on chromosome 1 and 10. While the chromosome 1 locus comprises factors of the complement system with well-known functions, the role of the 10q26-locus in AMD-pathophysiology remains enigmatic. 10q26 harbors a cluster of three functional genes, namely PLEKHA1, ARMS2 and HTRA1, with most of the AMD-associated genetic variants mapping to the latter two genes. High linkage disequilibrium between ARMS2 and HTRA1 has kept association studies from reliably defining the risk-causing gene for long and only very recently the genetic risk region has been narrowed to ARMS2, suggesting that this is the true AMD gene at this locus. However, genetic associations alone do not suffice to prove causality and one or more of the 14 SNPs on this haplotype may be involved in long-range control of gene expression, leaving HTRA1 and PLEKHA1 still suspects in the pathogenic pathway. Both, ARMS2 and HTRA1 have been linked to extracellular matrix homeostasis, yet their exact molecular function as well as their role in AMD pathogenesis remains to be uncovered. The transcriptional regulation of the 10q26 locus adds an additional level of complexity, given, that gene-regulatory as well as epigenetic alterations may influence expression levels from 10q26 in diseased individuals. Here, we provide a comprehensive overview on the 10q26 locus and its three gene products on various levels of biological complexity and discuss current and future research strategies to shed light on one of the remaining enigmatic spots in the AMD landscape.
Topics: Humans; Serine Endopeptidases; Genome-Wide Association Study; Proteins; Macular Degeneration; Gene Expression Regulation; Polymorphism, Single Nucleotide; Genotype; Genetic Predisposition to Disease
PubMed: 36513584
DOI: 10.1016/j.preteyeres.2022.101154 -
Frontiers in Bioscience (Scholar... Feb 2024Age-related macular degeneration (AMD) is a multifactorial genetic disease, with at least 52 identifiable associated gene variants at 34 loci, including variants in ()... (Review)
Review
Age-related macular degeneration (AMD) is a multifactorial genetic disease, with at least 52 identifiable associated gene variants at 34 loci, including variants in () and (). Genetic factors account for up to 70% of disease variability. However, population-based genetic risk scores are generally more helpful for clinical trial design and stratification of risk groups than for individual patient counseling. There is some evidence of pharmacogenetic influences on various treatment modalities used in AMD patients, including Age-Related Eye Disease Study (AREDS) supplements, photodynamic therapy (PDT), and anti-vascular endothelial growth factor (anti-VEGF) agents. However, there is currently no convincing evidence that genetic information plays a role in routine clinical care.
Topics: Humans; Proteins; Macular Degeneration; Dietary Supplements; High-Temperature Requirement A Serine Peptidase 1; Vascular Endothelial Growth Factors; Polymorphism, Single Nucleotide; Risk Factors
PubMed: 38538345
DOI: 10.31083/j.fbs1601003 -
Survey of Ophthalmology 2023Despite the success of antiangiogenic therapy in controlling exudation in neovascular age-related macular degeneration (nAMD), the involvement of the outer retina in... (Review)
Review
Despite the success of antiangiogenic therapy in controlling exudation in neovascular age-related macular degeneration (nAMD), the involvement of the outer retina in fibrosis results in gradual vision loss over time. The development of drugs that prevent or ameliorate fibrosis in nAMD requires that it is accurately detected and quantified with reliable endpoints and identification of robust biomarkers. Achievement of such an aim is currently challenging due to the lack of a consensus definition of fibrosis in nAMD. As a first step towards the establishment of a clear definition of fibrosis, we provide an extensive overview of the imaging modalities and criteria used to characterize fibrosis in nAMD. We observed variety in the selection of individual and combinations of imaging modalities, and criteria for detection. We also observed heterogeneity in classification systems and severity scales for fibrosis. The most commonly used imaging modalities were color fundus photography, fluorescein angiography and optical coherence tomography (OCT). A multimodal approach was frequently utilized. Our review suggests that OCT offers a more detailed, objective and sensitive characterization than color fundus photography/fluorescein angiography. Thus, we recommend it as a primary modality for fibrosis evaluation. This review provides a basis for future discussions to reach a consensus definition using standardized terms based on a detailed characterization of fibrosis, its presence and evolution, and taking into consideration impact on visual function. Achieving this goal is of paramount importance for the development of antifibrotic therapies.
Topics: Humans; Visual Acuity; Retina; Tomography, Optical Coherence; Fluorescein Angiography; Fibrosis; Macular Degeneration; Wet Macular Degeneration; Angiogenesis Inhibitors
PubMed: 37023894
DOI: 10.1016/j.survophthal.2023.03.004 -
Annals of Medicine Dec 2023Neovascular age-related macular degeneration (nAMD) is a common cause for visual impairment in the ageing population. An increasing number of nAMD patients causes...
BACKGROUND/OBJECTIVES
Neovascular age-related macular degeneration (nAMD) is a common cause for visual impairment in the ageing population. An increasing number of nAMD patients causes significant health burden, although intravitreal anti-VEGF agents have revolutionized nAMD treatment during the past 15 years. We aimed to define incidence and prevalence of nAMD in different age-categories in the anti-VEGF era and to estimate the number of the individuals over 75 years of age in 2050.
PATIENTS AND METHODS
We conducted an epidemiological study of the nAMD cohort ( = 2121) in a Finnish population of 410,000 inhabitants. Demographic and clinical data were gathered from Oulu University Hospital's database during 2006-2020. The incidence and prevalence rates were calculated using population data from national registers. The three-year moving average of incidence of nAMD per 100,000 person years was estimated. Prevalence figures were calculated per 100,000 age-specific inhabitants.
RESULTS
The average age at the diagnosis of nAMD was 788 years, and 62% of the patients were women. The incidence of nAMD was 71 (95% CI 55-90) and 102 (95% CI 88-118) per 100,000 person years in 2006 and 2020, respectively. During 2006-2020, 1.2- and 2.4-fold increases in nAMD incidence were noted in 75-84 and in 85-96 age groups, respectively. In the oldest 75-84 and 85-96 age categories the nAMD prevalence was 2865/100,000 (3%, 95% CI 2665-3079) and 2620/100,000 (3%, 95% CI 2323-2956), respectively. The proportion of the inhabitants >75 years old is estimated to increase from 10% in 2020 to 17% by 2050.
CONCLUSIONS
Our results indicate constant 1.2- and 2.4-fold increases in nAMD incidence during the past 15 years in age groups of 75-84 and 85-96 years, respectively, and 3% prevalence of nAMD in 2020. An almost two-fold increase in the ageing population by the year 2050 may also predict the trends in nAMD.KEY MESSAGESThe results of the current population-based study indicate 1.2- and 2.4-fold increases in the incidence of neovascular AMD (nAMD) during the last 15 years in the Finnish population aged 75-84 and 85-96 years and 3% prevalence of nAMD in 2020.An almost two-fold increase in the number of individuals over 75 years of age by the year 2050 is estimated, which may also predict the trends in nAMD.Intravitreal anti-vascular endothelial growth factor (anti-VEGF)- agents have revolutionized the treatment and prognosis of nAMD. Timely recognition and referral of nAMD patients to ophthalmologist can ensure vision-related functionality especially among the ageing population.
Topics: Humans; Female; Aged; Male; Finland; Angiogenesis Inhibitors; Incidence; Prevalence; Vascular Endothelial Growth Factor A; Visual Acuity; Wet Macular Degeneration; Epidemiologic Studies
PubMed: 37306515
DOI: 10.1080/07853890.2023.2222545 -
Advanced Science (Weinheim,... Nov 2023Choroidal neovascularization (CNV) is the key pathological event of wet age-related macular degeneration (wAMD) leading to irreversible vision loss. Currently,...
Choroidal neovascularization (CNV) is the key pathological event of wet age-related macular degeneration (wAMD) leading to irreversible vision loss. Currently, anti-angiogenic therapy with anti-vascular endothelial growth factor (VEGF) agents has become the standard treatment for wAMD, while it is still subject to several limitations, including the safety concerns of monthly intravitreal administration and insufficient efficacy for neovascular occlusion. Combined therapy with photodynamic therapy (PDT) and anti-angiogenic agents has emerged as a novel treatment paradigm. Herein, a novel and less-invasive approach is reported to achieve anti-angiogenic and photodynamic combination therapy of wAMD by intravenous administration of a photoactivatable nanosystem (Di-DAS-VER NPs). The nanosystem is self-assembled by reactive oxygen species (ROS)-sensitive dasatinib (DAS) prodrug and photosensitizer verteporfin (VER). After red-light irradiation to the diseased eyes, intraocular release of anti-angiogenic DAS is observed, together with selective neo-vessels occlusion by VER-generated ROS. Notably, Di-DAS-VER NPs demonstrates promising therapeutic efficacy against CNV with minimized systemic toxicity. The study enables an efficient intravenous wAMD therapy by integrating a photoactivation process with combinational therapeutics into one simple nanosystem.
Topics: Humans; Reactive Oxygen Species; Porphyrins; Photochemotherapy; Verteporfin; Macular Degeneration; Choroidal Neovascularization
PubMed: 37705491
DOI: 10.1002/advs.202301985 -
Survey of Ophthalmology 2023We provide an overview of current macular imaging techniques and identify and describe biomarkers that may be of use in the routine management of macular diseases,... (Review)
Review
We provide an overview of current macular imaging techniques and identify and describe biomarkers that may be of use in the routine management of macular diseases, particularly exudative age-related macular degeneration (AMD). This perspective includes sections on macular imaging techniques including optical coherence tomography (OCT) and OCT angiography (OCTA), classification of exudative AMD, and biomarkers in structural OCT and OCTA. Fluorescein angiography remains a vital tool for assessing the activity of neovascular lesions, while indocyanine green angiography is the preferred option for choroidal vessel imaging in neovascular AMD. OCT provides a non-invasive three-dimensional visualization of retinal architecture in vivo and is useful in the diagnosis of many imaging biomarkers of AMD-related neovascular lesions, including lesion activity. OCTA is a recent advance in OCT technology that allows accurate visualization of retinal and choroidal vascular flow. OCT and OCTA have led to an updated classification of exudative AMD lesions and provide several biomarkers that help to establish a diagnosis and the disease activity status of neovascular lesions. Individualization of therapy guided by OCT and OCTA biomarkers has the potential to further improve visual outcomes in exudative AMD. Moving forwards, integration of technologically-advanced imaging equipment with AI software will help ophthalmologists to provide patients with the best possible care.
Topics: Humans; Choroidal Neovascularization; Angiogenesis Inhibitors; Visual Acuity; Vascular Endothelial Growth Factor A; Wet Macular Degeneration; Fluorescein Angiography; Tomography, Optical Coherence
PubMed: 36854371
DOI: 10.1016/j.survophthal.2023.02.004 -
Investigative Ophthalmology & Visual... Mar 2024A progression sequence for age-related macular degeneration onset may be determinable with consensus neuroanatomical nomenclature augmented by drusen biology and... (Review)
Review
A progression sequence for age-related macular degeneration onset may be determinable with consensus neuroanatomical nomenclature augmented by drusen biology and eye-tracked clinical imaging. This narrative review proposes to supplement the Early Treatment of Diabetic Retinopathy Study (sETDRS) grid with a ring to capture high rod densities. Published photoreceptor and retinal pigment epithelium (RPE) densities in flat mounted aged-normal donor eyes were recomputed for sETDRS rings including near-periphery rich in rods and cumulatively for circular fovea-centered regions. Literature was reviewed for tissue-level studies of aging outer retina, population-level epidemiology studies regionally assessing risk, vision studies regionally assessing rod-mediated dark adaptation (RMDA), and impact of atrophy on photopic visual acuity. The 3 mm-diameter xanthophyll-rich macula lutea is rod-dominant and loses rods in aging whereas cone and RPE numbers are relatively stable. Across layers, the largest aging effects are accumulation of lipids prominent in drusen, loss of choriocapillary coverage of Bruch's membrane, and loss of rods. Epidemiology shows maximal risk for drusen-related progression in the central subfield with only one third of this risk level in the inner ring. RMDA studies report greatest slowing at the perimeter of this high-risk area. Vision declines precipitously when the cone-rich central subfield is invaded by geographic atrophy. Lifelong sustenance of foveal cone vision within the macula lutea leads to vulnerability in late adulthood that especially impacts rods at its perimeter. Adherence to an sETDRS grid and outer retinal cell populations within it will help dissect mechanisms, prioritize research, and assist in selecting patients for emerging treatments.
Topics: Humans; Adult; Aged; Macular Degeneration; Retina; Macula Lutea; Geographic Atrophy; Retinal Cone Photoreceptor Cells
PubMed: 38466281
DOI: 10.1167/iovs.65.3.4 -
Scientific Reports Jan 2024We conducted a systematic review and meta-analysis to evaluate the visual, anatomical, and safety outcomes of the intravitreal faricimab, a novel vascular endothelial... (Meta-Analysis)
Meta-Analysis
We conducted a systematic review and meta-analysis to evaluate the visual, anatomical, and safety outcomes of the intravitreal faricimab, a novel vascular endothelial growth factor (VEGF)/angiopoietin-2 (Ang-2) bispecific agent, in neovascular age-related macular degeneration (nAMD) patients. The follow-up times in the included studies ranged from a minimum of 36 weeks to a maximum of 52 weeks. EMBASE, Ovid-Medline, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, the WHO ICTRP, ClinicalTrial.gov, the EU Clinical Trials Register, and Chinese Clinical Trial Registry (ChiCTR) were searched (The last literature search was performed on August 17, 2023) for randomized controlled trials (RCTs) comparing faricimab with control groups for neovascular age-related macular degeneration (nAMD). The risk of bias for eligible RCTs was independently assessed using the Cochrane Risk of Bias Tool by two authors (W.-T.Y. and C.-S.W.). The meta-analysis was conducted using Review Manager 5.4 software. The mean best corrected visual acuity (BCVA), central subfield thickness (CST), total choroidal neovascularization (CNV) area, and total lesion leakage were analyzed as continuous variables and the outcome measurements were reported as the weighted mean difference (WMD) with a 95% confidence interval (CI). The ocular adverse events and ocular serious adverse events were analyzed as dichotomous variables and the outcome measurements were analyzed as the odds ratios (ORs) with a 95% CI. Random-effects model was used in our study for all outcome synthesizing due to different clinical characteristics. Four RCTs with 1,486 patients were eligible for quantitative analysis. There was no statistically significant difference between intravitreal faricimab and anti-VEGF in BCVA [weighted mean difference (WMD) = 0.47; 95% CI: (- 0.17, 1.11)]. The intravitreal faricimab group showed numerically lower CST [WMD = - 5.96; 95% CI = (- 7.11, - 4.82)], total CNV area [WMD = - 0.49; 95% CI = (- 0.68, - 0.30)], and total lesion leakage [WMD = - 0.88; 95% CI = (- 1.08, - 0.69)] after intravitreal therapy compared with the intravitreal anti-VEGF group. There were no statistically significant differences between intravitreal faricimab and anti-VEGF in ocular adverse events (AEs) [pooled odds ratio (OR) = 1.10; 95% CI = (0.81, 1.49)] and serious adverse events (SAEs) [pooled OR = 0.84; 95% CI = (0.37, 1.90)]. The intravitreal bispecific anti-VEGF/angiopoietin 2 (Ang2) antibody faricimab with a extended injection interval was non-inferior to first-line anti-VEGF agents in BCVA. It was safe and had better anatomical recovery. Large, well-designed RCTs are needed to explore the potential benefit of extended faricimab for nAMD. This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42022327450).
Topics: Humans; Angiogenesis Inhibitors; Antibodies, Bispecific; Intravitreal Injections; Macular Degeneration
PubMed: 38291069
DOI: 10.1038/s41598-024-52942-3