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1.
Ophthalmology ; 131(6): 692-699, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38160880

RESUMO

PURPOSE: Chronic kidney disease (CKD) may elevate susceptibility to age-related macular degeneration (AMD) because of shared risk factors, pathogenic mechanisms, and genetic polymorphisms. Given the inconclusive findings in prior studies, we investigated this association using extensive datasets in the Asian Eye Epidemiology Consortium. DESIGN: Cross-sectional study. PARTICIPANTS: Fifty-one thousand two hundred fifty-three participants from 10 distinct population-based Asian studies. METHODS: Age-related macular degeneration was defined using the Wisconsin Age-Related Maculopathy Grading System, the International Age-Related Maculopathy Epidemiological Study Group Classification, or the Beckman Clinical Classification. Chronic kidney disease was defined as estimated glomerular filtration rate (eGFR) of less than 60 ml/min per 1.73 m2. A pooled analysis using individual-level participant data was performed to examine the associations between CKD and eGFR with AMD (early and late), adjusting for age, sex, hypertension, diabetes, body mass index, smoking status, total cholesterol, and study groups. MAIN OUTCOME MEASURES: Odds ratio (OR) of early and late AMD. RESULTS: Among 51 253 participants (mean age, 54.1 ± 14.5 years), 5079 had CKD (9.9%). The prevalence of early AMD was 9.0%, and that of late AMD was 0.71%. After adjusting for confounders, individuals with CKD were associated with higher odds of late AMD (OR, 1.46; 95% confidence interval [CI], 1.11-1.93; P = 0.008). Similarly, poorer kidney function (per 10-unit eGFR decrease) was associated with late AMD (OR, 1.12; 95% CI, 1.05-1.19; P = 0.001). Nevertheless, CKD and eGFR were not associated significantly with early AMD (all P ≥ 0.149). CONCLUSIONS: Pooled analysis from 10 distinct Asian population-based studies revealed that CKD and compromised kidney function are associated significantly with late AMD. This finding further underscores the importance of ocular examinations in patients with CKD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


Assuntos
Taxa de Filtração Glomerular , Degeneração Macular , Insuficiência Renal Crônica , Humanos , Masculino , Estudos Transversais , Feminino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Idoso , Degeneração Macular/fisiopatologia , Degeneração Macular/epidemiologia , Fatores de Risco , Povo Asiático/etnologia , Adulto , Razão de Chances , Prevalência , Idoso de 80 Anos ou mais
2.
Ophthalmology ; 131(10): 1175-1184, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38583493

RESUMO

PURPOSE: To describe the clinical outcome and late-stage findings of extensive macular atrophy with pseudodrusen-like appearance (EMAP). DESIGN: Retrospective cohort study. PARTICIPANTS: Seventy-eight patients (156 eyes) affected by EMAP. METHODS: We collected data on best-corrected visual acuity, kinetic perimetry, OCT, short-wavelength autofluorescence, and near-infrared autofluorescence findings. Genetic testing for the TIMP3 and C1QTNF5 genes was performed via Sanger sequencing for 58 patients, with no pathogenic variants identified. MAIN OUTCOME MEASURES: The primary outcomes were best-corrected visual acuity at the last examination, visual field at the last examination, and incidence rates and time-to-event curves for blindness with the United States Social Security Administration and World Health Organization (WHO) criteria, foveal involvement, and atrophy enlargement beyond the 30° and 55° field of view. Imaging findings at the last examination were secondary outcomes. RESULTS: At the most recent visit, mean age was 70.9 ± 5.2 years. Using United States criteria, 58.1% of the patients were blind, and 25.8% were blind according to WHO criteria. All eyes showed large central scotomas, which were associated with visual field constriction in 22.2% of eyes. We detected focal openings or large dehiscences of Bruch's membrane (BM) in 25.4% of eyes. Near-infrared autofluorescence showed increased visibility of the choroidal vessels beyond the atrophy in 87.2% of eyes. The incidence rates for blindness were 3.95 per 100 patient-years with United States criteria and 1.54 per 100 patient-years according to WHO criteria. The incidence rates were 22.8 per 100 eye-years for foveal involvement, 12.0 per 100 eye-years for atrophy enlargement beyond 30°, and 6.6 per 100 eye-years for atrophy enlargement beyond 55°. The estimates were not influenced by the age at onset. CONCLUSIONS: We identified characteristic imaging findings, including BM ruptures, in elder patients with EMAP and calculated incidence rates for different functional and anatomic outcomes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


Assuntos
Progressão da Doença , Angiofluoresceinografia , Drusas Retinianas , Tomografia de Coerência Óptica , Acuidade Visual , Campos Visuais , Humanos , Masculino , Feminino , Idoso , Acuidade Visual/fisiologia , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Drusas Retinianas/diagnóstico , Drusas Retinianas/genética , Campos Visuais/fisiologia , Angiofluoresceinografia/métodos , Pessoa de Meia-Idade , Testes de Campo Visual , Degeneração Macular/diagnóstico , Degeneração Macular/genética , Degeneração Macular/fisiopatologia , Macula Lutea/patologia , Atrofia , Inibidor Tecidual de Metaloproteinase-3/genética , Inibidor Tecidual de Metaloproteinase-3/metabolismo , Cegueira/diagnóstico , Cegueira/etiologia , Cegueira/fisiopatologia , Idoso de 80 Anos ou mais , Escotoma/diagnóstico , Escotoma/fisiopatologia
3.
J Biomed Sci ; 31(1): 48, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730462

RESUMO

Retinal degenerative diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), loom as threats to vision, causing detrimental effects on the structure and function of the retina. Central to understanding these diseases, is the compromised state of the blood-retinal barrier (BRB), an effective barrier that regulates the influx of immune and inflammatory components. Whether BRB breakdown initiates retinal distress, or is a consequence of disease progression, remains enigmatic. Nevertheless, it is an indication of retinal dysfunction and potential vision loss.The intricate intercellular dialogues among retinal cell populations remain unintelligible in the complex retinal milieu, under conditions of inflammation and oxidative stress. The retina, a specialized neural tissue, sustains a ceaseless demand for oxygen and nutrients from two vascular networks. The BRB orchestrates the exchange of molecules and fluids within this specialized region, comprising the inner BRB (iBRB) and the outer BRB (oBRB). Extracellular vesicles (EVs) are small membranous structures, and act as messengers facilitating intercellular communication in this milieu.EVs, both from retinal and peripheral immune cells, increase complexity to BRB dysfunction in DR and AMD. Laden with bioactive cargoes, these EVs can modulate the retinal microenvironment, influencing disease progression. Our review delves into the multifaceted role of EVs in retinal degenerative diseases, elucidating the molecular crosstalk they orchestrate, and their microRNA (miRNA) content. By shedding light on these nanoscale messengers, from their biogenesis, release, to interaction and uptake by target cells, we aim to deepen the comprehension of BRB dysfunction and explore their therapeutic potential, therefore increasing our understanding of DR and AMD pathophysiology.


Assuntos
Barreira Hematorretiniana , Vesículas Extracelulares , Barreira Hematorretiniana/metabolismo , Barreira Hematorretiniana/fisiopatologia , Vesículas Extracelulares/metabolismo , Humanos , Retinopatia Diabética/fisiopatologia , Retinopatia Diabética/metabolismo , Doenças Retinianas/fisiopatologia , Doenças Retinianas/metabolismo , Degeneração Macular/fisiopatologia , Degeneração Macular/metabolismo , Animais
4.
J Theor Biol ; 592: 111879, 2024 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-38909882

RESUMO

BACKGROUND: Iron-induced oxidative stress was thought to be the reason why the a-wave amplitude of the electroretinogram (ERG) dropped when iron ions were present. It is assumed that reactive oxygen species (ROS) are generated in the presence of iron ions, and this leads to a decrease in hyperpolarization of the photoreceptor. It is known that in age-related macular degeneration (AMD), sodium iodate can induce oxidative stress, apoptosis, and retinal damage, which mimic the effects of clinical AMD. Here, the reduction of the a-wave amplitude in mice with sodium iodate-induced age-related macular degeneration is explained. METHODS: The leading edge of the a-wave is divided into voltages developed by cones and rods. The same oxidative stress model is applied here since sodium iodate causes the creation of ROS in a manner similar to that caused by iron ions, with the exception that the retina is treated as a circuit of various resistances when computing the photoresponse. Moreover, sodium iodate also leads to apoptosis and, hence, may cause misalignment in cones (not in rods) during the initial stage of apoptosis in AMD. To include the effects of apoptosis and shortening in cones and rods, we have used a factor representing the fraction of total cones and rods that are alive. To include the effect of misalignment of cones on the reduction of the a-wave amplitude, we have used the Stiles-Crawford function to calculate the number of photoisomerizations occurring in a photoreceptor misaligned at an angle θ. The results are compared with experimental data. RESULTS: In sodium iodate-treated eyes, the ROS produced can attract calcium ions in the photoreceptor, which increases the calcium influx. In the case of the cones, the inclusion of the misalignment angle in the phototransduction process helps in determining the voltage and slope of the voltage vs. time graph.The smaller the fraction of active photoreceptors, the smaller the amplitude of the a-wave. The calcium influx, misaligned photoreceptors, and total photoreceptor loss all cause the amplitude of the a-wave to decrease, and at any time from the beginning of phototransduction cascade, the calcium influx causes the slope of the a-wave to increase. CONCLUSION: The reduction in the a-wave amplitude in the eyes of sodium iodate-treated mice is attributed to oxidative stress in both cones and rods and cone misalignment, which ultimately lead to apoptosis and vision loss in AMD.


Assuntos
Eletrorretinografia , Iodatos , Degeneração Macular , Estresse Oxidativo , Espécies Reativas de Oxigênio , Células Fotorreceptoras Retinianas Cones , Animais , Degeneração Macular/patologia , Degeneração Macular/fisiopatologia , Degeneração Macular/induzido quimicamente , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Células Fotorreceptoras Retinianas Cones/efeitos dos fármacos , Células Fotorreceptoras Retinianas Cones/patologia , Células Fotorreceptoras Retinianas Cones/metabolismo , Apoptose/efeitos dos fármacos , Células Fotorreceptoras Retinianas Bastonetes/efeitos dos fármacos , Células Fotorreceptoras Retinianas Bastonetes/patologia , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Modelos Animais de Doenças , Modelos Biológicos
5.
Pharmacol Res ; 208: 107380, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39216841

RESUMO

Age-related macular degeneration (AMD) is a common retinal pathology characterized by degeneration of macula's retinal pigment epithelium (RPE) and photoreceptors, visual impairment, or loss. Compared to wet AMD, dry AMD is more common, but lacks cures; therefore, identification of new potential therapeutic targets and treatments is urgent. Increased oxidative stress and declining antioxidant, detoxifying systems contribute to the pathophysiologic mechanisms underlying AMD. The present work shows that the Embryonic Lethal Abnormal Vision-Like 1/Human antigen R (ELAVL1/HuR) and the Vascular Endothelial Growth Factor (VEGF) protein levels are higher in the RPE of both dry and wet AMD patients compared to healthy subjects. Moreover, increased HuR protein levels are detected in the retina, and especially in the RPE layer, of a dry AMD model, the nuclear factor erythroid 2-related factor 2 (Nrf2) / peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) double knock-out mouse. The crosstalk among Nrf2, HuR and VEGF has been also studied in ARPE-19 cells in basal and stressful conditions related to the AMD context (i.e., oxidative stress, autophagy impairment, Nrf2 deficit), offering new evidence of the mutual influence between Nrf2 and HuR, of the dependence of VEGF expression and secretion by these two factors, and of the increased susceptibility of cells to stressful conditions in Nrf2- or HuR-impaired contexts. Overall, this study shows evidence of the interplay among Nrf2, HuR and VEGF, essential factors for RPE homeostasis, and represents an additional piece in the understanding of the complex pathophysiologic mechanisms underlying AMD.


Assuntos
Proteína Semelhante a ELAV 1 , Fator 2 Relacionado a NF-E2 , Epitélio Pigmentado da Retina , Fator A de Crescimento do Endotélio Vascular , Idoso , Idoso de 80 Anos ou mais , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Proteína Semelhante a ELAV 1/metabolismo , Proteína Semelhante a ELAV 1/genética , Atrofia Geográfica/metabolismo , Degeneração Macular/metabolismo , Degeneração Macular/fisiopatologia , Degeneração Macular/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Epitélio Pigmentado da Retina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Degeneração Macular Exsudativa/metabolismo , Degeneração Macular Exsudativa/genética
6.
Value Health ; 27(5): 642-654, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38369283

RESUMO

OBJECTIVES: This study generates VILL-UI (Vision Impairment in Low Luminance - Utility Index), a preference-weighted measure (PWM) derived from the VILL-33 measure for use in patients with age-related macular degeneration (AMD) and valued to generate United Kingdom and German preference weights. METHODS: A PWM consists of a classification system to describe health and utility values for every state described by the classification. The classification was derived using existing data collected as part of the MACUSTAR study, a low-interventional study on AMD, conducted at 20 clinical sites across Europe. Items were selected using psychometric and Rasch analyses, published criteria around PWM suitability, alongside instrument developer views and concept elicitation work that informed VILL-33 development. An online discrete choice experiment (DCE) with duration of the health state was conducted with the United Kingdom and German public. Responses were modeled to generate utility values for all possible health states. RESULTS: The classification system has 5 items across the 3 domains of VILL-33: reading and accessing information, mobility and safety, and emotional well-being. The DCE samples (United Kingdom: n = 1004, Germany: n = 1008) are broadly representative and demonstrate good understanding of the tasks. The final DCE analyses produce logically consistent and significant coefficients. CONCLUSIONS: This study enables responses to VILL-33 to be directly used to inform economic evaluation in AMD. The elicitation of preferences from both United Kingdom and Germany enables greater application of VILL-UI for economic evaluation throughout Europe. VILL-UI fills a gap in AMD in which generic preference-weighted measures typically lack sensitivity.


Assuntos
Degeneração Macular , Preferência do Paciente , Psicometria , Humanos , Degeneração Macular/psicologia , Degeneração Macular/fisiopatologia , Feminino , Masculino , Idoso , Inquéritos e Questionários , Alemanha , Reino Unido , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Qualidade de Vida
7.
Graefes Arch Clin Exp Ophthalmol ; 262(8): 2449-2459, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38483610

RESUMO

PURPOSE: To compare diagnostic power for different severities of age-related macular degeneration (AMD) of two-dimensional macular pigment optical densities (2D-MPOD) and spatially matched objective perimetry, with standard perimetry and best-corrected visual acuity (BCVA). METHODS: The ObjectiveField Analyser (OFA) provided objective perimetry, and a Heidelberg Spectralis optical coherence tomography (OCT) measured 2D-MPOD in AMD patients, both completed twice over 0.99 ± 0.16 years. From each 2D-MPOD image, we extracted 20 regions/macula, matched to the 20 OFA stimuli/macula. For each region, we calculated 7 measures from the 2D-MPOD pixel values and correlated those with OFA sensitivities and delays. We quantified 2D-MPOD changes, the ability of 2D-MPOD and OFA to discriminate AMD stages, and the discriminatory power of Matrix perimetry and BCVA using percentage area under receiver operator characteristic plots (%AUROC). RESULTS: In 58 eyes of 29 subjects (71.6 ± 6.3 years, 22 females), we found significant correlations between 2D-MPOD and OFA sensitivities for Age-Related Eye Disease Studies (AREDS)-3 and AREDS-4 severities. Delays showed significant correlations with AREDS-2. For AREDS-4, correlations extended across all eccentricities. Regression associated with the Bland-Altman plots showed significant changes in 2D-MPOD over the study period, especially variability measures. MPOD per-region medians discriminated AREDS-1 from AREDS-3 eyes at a %AUROC of 80.0 ± 6.3%, outperforming OFA, Matrix perimetry, and BCVA. CONCLUSIONS: MPOD changes correlated with central functional changes and significant correlations extended peripherally in later-stage AMD. Good diagnostic power for earlier-stage AMD and significant change over the study suggest that 2D-MPOD and OFA may provide effective biomarkers.


Assuntos
Macula Lutea , Pigmento Macular , Tomografia de Coerência Óptica , Acuidade Visual , Testes de Campo Visual , Campos Visuais , Humanos , Tomografia de Coerência Óptica/métodos , Feminino , Acuidade Visual/fisiologia , Testes de Campo Visual/métodos , Masculino , Idoso , Pigmento Macular/metabolismo , Campos Visuais/fisiologia , Macula Lutea/diagnóstico por imagem , Degeneração Macular/diagnóstico , Degeneração Macular/fisiopatologia , Degeneração Macular/metabolismo , Curva ROC , Seguimentos
8.
Graefes Arch Clin Exp Ophthalmol ; 262(6): 1737-1744, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38206414

RESUMO

BACKGROUND: Kabuki Syndrome is a rare and genetically heterogenous condition with both ophthalmic and systemic complications and typical facial features. We detail the macular phenotype in two unrelated patients with Kabuki syndrome due to de novo nonsense variants in KMT2D, one novel. A follow-up of 10 years is reported. Pathogenicity of both de novo nonsense variants is analyzed. METHODS: Four eyes of two young patients were studied by full clinical examination, kinetic perimetry, short wavelength autofluorescence, full field (ff) ERGs, and spectral-domain optical coherence tomography (SD-OCT). One patient had adaptive optic (AO) imaging. Whole exome sequencing was performed in both patients. RESULTS: Both patients had de novo nonsense variants in KMTD2. One patient had c.14843C>G; p. (Ser4948ter) novel variant and the second c.11119C>T; p. (Arg3707ter). Both had a stable Snellen visual acuity of 0.2-0.3. The retinal multimodal imaging demonstrated abnormalities at the fovea in both eyes: hyperreflectivity to blue light and a well-delimited gap-disruption of ellipsoid and interdigitation layer on OCT. The dark area on AO imaging is presumed to be absent for, or with structural change to photoreceptors. The ff ERGs and kinetic visual fields were normal. The foveal findings remained stable over several years. CONCLUSION: Kabuki syndrome-related maculopathy is a distinct loss of photoreceptors at the fovea as shown by multimodal imaging including, for the first time, AO imaging. This report adds to the literature of only one case with maculopathy with two additional macular dystrophies in patients with Kabuki syndrome. Although underestimated, these cases further raise awareness of the potential impact of retinal manifestations of Kabuki syndrome not only among ophthalmologists but also other healthcare professionals involved in the care of patients with this multisystem disorder.


Assuntos
Anormalidades Múltiplas , Eletrorretinografia , Face , Angiofluoresceinografia , Doenças Hematológicas , Imagem Multimodal , Proteínas de Neoplasias , Fenótipo , Tomografia de Coerência Óptica , Doenças Vestibulares , Acuidade Visual , Humanos , Doenças Vestibulares/genética , Doenças Vestibulares/diagnóstico , Doenças Vestibulares/fisiopatologia , Face/anormalidades , Doenças Hematológicas/genética , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/fisiopatologia , Tomografia de Coerência Óptica/métodos , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/diagnóstico , Seguimentos , Masculino , Feminino , Proteínas de Neoplasias/genética , Angiofluoresceinografia/métodos , Proteínas de Ligação a DNA/genética , Degeneração Macular/genética , Degeneração Macular/diagnóstico , Degeneração Macular/fisiopatologia , Pescoço , Fundo de Olho , DNA/genética , Sequenciamento do Exoma , Análise Mutacional de DNA , Macula Lutea/patologia , Fatores de Tempo , Adulto , Adolescente
9.
Retina ; 44(6): 997-1005, 2024 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-38261803

RESUMO

BACKGROUND: To describe the occurrence of nonexudative intraretinal fluid (IRF) in intermediate age-related macular degeneration. METHODS: A retrospective study was designed to include consecutive cases with intermediate age-related macular degeneration associated with IRF. A multimodal imaging approach was used to confirm diagnosis of IRF in intermediate age-related macular degeneration. Multimodal imaging included color fundus photograph, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, optical coherence tomography, and optical coherence tomography angiography. RESULTS: Ten eyes of 10 patients (2 male and 8 female patients, ages 68-80 years) showing IRF in intermediate age-related macular degeneration were included in the study. The mean best-corrected visual acuity was 20/40 Snellen equivalent. Multimodal imaging including fluorescein angiography/indocyanine green angiography and optical coherence tomography demonstrated the absence of macular neovascularization in all cases; optical coherence tomography-angiography did not detect any abnormal flow signal associated with IRF. Seven of 10 patients developed IRF in correspondence of pigment epithelium detachment. Three of 10 patients presented IRF in correspondence of an area of nascent geographic atrophy. CONCLUSION: Nonexudative intraretinal fluid in intermediate age-related macular degeneration is a novel, distinctive feature that is characterized by the presence of IRF with no evidence of macular neovascular lesions. The authors described different phenotypes of IRF in intermediate age-related macular degeneration. The definite diagnosis of this condition requires further studies with thorough application of multimodal imaging.


Assuntos
Angiofluoresceinografia , Imagem Multimodal , Líquido Sub-Retiniano , Tomografia de Coerência Óptica , Acuidade Visual , Humanos , Idoso , Feminino , Masculino , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Angiofluoresceinografia/métodos , Acuidade Visual/fisiologia , Degeneração Macular/diagnóstico , Degeneração Macular/fisiopatologia , Verde de Indocianina/administração & dosagem , Epitélio Pigmentado da Retina/patologia , Epitélio Pigmentado da Retina/diagnóstico por imagem
10.
Retina ; 44(8): 1351-1359, 2024 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-39047196

RESUMO

PURPOSE: In this study, differences in retinal feature visualization of high-resolution optical coherence tomography (OCT) devices were investigated with different axial resolutions in quantifications of retinal pigment epithelium and photoreceptors (PRs) in intermediate age-related macular degeneration. METHODS: Patients were imaged with standard SPECTRALIS HRA + OCT and the investigational High-Res OCT device (both by Heidelberg Engineering, Heidelberg, Germany). Drusen, retinal pigment epithelium, and PR layers were segmented using validated artificial intelligence-based algorithms followed by manual corrections. Thickness and drusen maps were computed for all patients. Loss and thickness measurements were compared between devices, drusen versus nondrusen areas, and early treatment diabetic retinopathy study subfields using mixed-effects models. RESULTS: Thirty-three eyes from 28 patients with intermediate age-related macular degeneration were included. Normalized PR integrity loss was significantly higher with 4.6% for standard OCT compared with 2.5% for High-Res OCT. The central and parafoveal PR integrity loss was larger than the perifoveal loss (P < 0.05). Photoreceptor thickness was increased on High-Res OCT and in nondrusen regions (P < 0.001). Retinal pigment epithelium appeared thicker on standard OCT and above drusen (P < 0.01). CONCLUSION: Our study shows that High-Res OCT is able to identify the condition of investigated layers in intermediate age-related macular degeneration with higher precision. This improved in vivo imaging technology might promote our understanding of the pathophysiology and progression of age-related macular degeneration.


Assuntos
Epitélio Pigmentado da Retina , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Epitélio Pigmentado da Retina/patologia , Epitélio Pigmentado da Retina/diagnóstico por imagem , Feminino , Masculino , Idoso , Idoso de 80 Anos ou mais , Células Fotorreceptoras de Vertebrados/patologia , Acuidade Visual/fisiologia , Drusas Retinianas/diagnóstico , Drusas Retinianas/diagnóstico por imagem , Degeneração Macular/diagnóstico , Degeneração Macular/fisiopatologia , Pessoa de Meia-Idade
11.
BMC Ophthalmol ; 24(1): 327, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39107704

RESUMO

BACKGROUND: Occult Macular Dystrophy (OMD), primarily caused by retinitis pigmentosa 1-like 1 (RP1L1) variants, is a complex retinal disease characterised by progressive vision loss and a normal fundus appearance. This study aims to investigate the diverse phenotypic expressions and genotypic correlations of OMD in Chinese patients, including a rare case of Vitelliform Macular Dystrophy (VMD) associated with RP1L1. METHODS: We analysed seven OMD patients and one VMD patient, all with heterozygous pathogenic RP1L1 variants. Clinical assessments included Best Corrected Visual Acuity (BCVA), visual field testing, Spectral Domain Optical Coherence Tomography (SD-OCT), multifocal Electroretinograms (mfERGs), and microperimetry. Next-generation sequencing was utilised for genetic analysis. RESULTS: The OMD patients displayed a range of phenotypic variability. Most (5 out of 7) had the RP1L1 variant c.133 C > T; p.R45W, associated with central vision loss and specific patterns in SD-OCT and mfERG. Two patients exhibited different RP1L1 variants (c.3599G > T; p.G1200V and c.2880G > C; p.W960C), presenting milder phenotypes. SD-OCT revealed photoreceptor layer changes, with most patients showing decreased mfERG responses in the central rings. Interestingly, a unique case of VMD linked to the RP1L1 variant was observed, distinct from traditional OMD presentations. CONCLUSIONS: This study highlights the phenotypic diversity within OMD and the broader spectrum of RP1L1-associated macular dystrophies, including a novel association with VMD. The findings emphasise the complexity of RP1L1 variants in determining clinical manifestations, underscoring the need for comprehensive genetic and clinical evaluations in macular dystrophies.


Assuntos
Eletrorretinografia , Proteínas do Olho , Proteínas Associadas aos Microtúbulos , Tomografia de Coerência Óptica , Acuidade Visual , Distrofia Macular Viteliforme , Humanos , Masculino , Feminino , Tomografia de Coerência Óptica/métodos , Adulto , Pessoa de Meia-Idade , Proteínas do Olho/genética , Acuidade Visual/fisiologia , Distrofia Macular Viteliforme/genética , Distrofia Macular Viteliforme/fisiopatologia , Distrofia Macular Viteliforme/diagnóstico , Proteínas Associadas aos Microtúbulos/genética , Campos Visuais/fisiologia , China/epidemiologia , Adulto Jovem , Testes de Campo Visual , Linhagem , Adolescente , Fenótipo , Mutação , Degeneração Macular/genética , Degeneração Macular/diagnóstico , Degeneração Macular/fisiopatologia , Idoso , População do Leste Asiático
12.
Optom Vis Sci ; 101(6): 435-442, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38913934

RESUMO

SIGNIFICANCE: Prior studies with large, highly visible targets report low smooth pursuit gains in individuals with macular degeneration (MD). We show that lower gains persist even when observers are pursuing a target that requires discrimination at the acuity limit. This low gain causes retinal slip, potentially leading to motion blur and target disappearance in the scotoma, which further compromise the visibility of moving object. PURPOSE: In this study, we examine whether the characteristics of smooth pursuit (pursuit gain and placement of the fixational locus relative to the target) change when the task requires dynamic visual acuity. METHODS: Using the scanning laser ophthalmoscope, we recorded smooth pursuit eye movements in 10 eyes of 6 MD participants and 7 eyes of 4 age-matched controls in response to leftward- or rightward-moving annular targets (O) that briefly (300 milliseconds) changed to a Landolt C at one of several time points during the pursuit trial. Participants were asked to pursue the target and indicate the direction of the C opening. RESULTS: Individuals with MD had lower pursuit gains and fewer saccades during the C presentation than during the O, compared with their age-matched peers. Further, pursuit gain, but not the distance of the retinal pursuit locus from the target, predicted task performance in the MD group. CONCLUSIONS: Our findings suggest that compromised pursuit gain in MD participants likely further compromises their dynamic visual acuity and thus ability to view moving targets.


Assuntos
Degeneração Macular , Acompanhamento Ocular Uniforme , Acuidade Visual , Humanos , Acuidade Visual/fisiologia , Degeneração Macular/fisiopatologia , Acompanhamento Ocular Uniforme/fisiologia , Idoso , Masculino , Feminino , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Oftalmoscopia
13.
Ophthalmic Res ; 67(1): 458-469, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39047706

RESUMO

INTRODUCTION: The objective of this study was to evaluate retinal sensitivity in subfields and its association with the novel quantitative contrast sensitivity function (qCSF) in patients with early age-related macular degeneration (eAMD), in patients with intermediate AMD (iAMD), and in healthy controls. METHODS: In this prospective longitudinal study, retinal sensitivity of a customized 24-point grid was assessed by microperimetry Macular Integrity Assessment (MAIA, CenterVue, Padova, Italy) and divided into different subfields. The Multiple Contrast Vision Meter (Adaptive Sensory Technology, San Diego, CA, USA) was used for qCSF testing. Linear models were used to test the association of functional metrics with variables of interest. RESULTS: 92 study eyes from 92 participants were analyzed (13 eAMD, 31 iAMD, and 48 controls). Microperimetry subfield comparison showed significant differences (p < 0.0001) in the control group between superior and inferior hemifield as well as between central and peripheral subfields. For eAMD, significant differences were found between central and peripheral subfields (p < 0.001) and specific subfields (p < 0.05) and finally for iAMD between specific quadrants (p < 0.05) and specific squares (p < 0.05). Significant associations of retinal sensitivity with qCSF metrics were found for the area underneath the logarithmic contrast sensitivity function, contrast acuity and for the contrast sensitivity at specific spatial frequencies. CONCLUSIONS: This study showed significant differences in the evaluated retinal sensitivity subfields, providing localized natural history data for retinal sensitivity in healthy controls and patients with eAMD and iAMD.


Assuntos
Sensibilidades de Contraste , Macula Lutea , Degeneração Macular , Retina , Tomografia de Coerência Óptica , Acuidade Visual , Testes de Campo Visual , Humanos , Sensibilidades de Contraste/fisiologia , Feminino , Masculino , Estudos Prospectivos , Idoso , Acuidade Visual/fisiologia , Tomografia de Coerência Óptica/métodos , Retina/fisiopatologia , Degeneração Macular/fisiopatologia , Degeneração Macular/diagnóstico , Pessoa de Meia-Idade , Macula Lutea/fisiopatologia , Campos Visuais/fisiologia , Seguimentos , Idoso de 80 Anos ou mais
14.
Proc Natl Acad Sci U S A ; 118(16)2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33859044

RESUMO

Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly. Canonical disease models suggest that defective interactions between complement factor H (CFH) and cell surface heparan sulfate (HS) result in increased alternative complement pathway activity, cytolytic damage, and tissue inflammation in the retina. Although these factors are thought to contribute to increased disease risk, multiple studies indicate that noncanonical mechanisms that result from defective CFH and HS interaction may contribute to the progression of AMD as well. A total of 60 ciliated sensory neurons in the nematode Caenorhabditis elegans detect chemical, olfactory, mechanical, and thermal cues in the environment. Here, we find that a C. elegans CFH homolog localizes on CEP mechanosensory neuron cilia where it has noncanonical roles in maintaining inversin/NPHP-2 within its namesake proximal compartment and preventing inversin/NPHP-2 accumulation in distal cilia compartments in aging adults. CFH localization and maintenance of inversin/NPHP-2 compartment integrity depend on the HS 3-O sulfotransferase HST-3.1 and the transmembrane proteoglycan syndecan/SDN-1. Defective inversin/NPHP-2 localization in mouse and human photoreceptors with CFH mutations indicates that these functions and interactions may be conserved in vertebrate sensory neurons, suggesting that previously unappreciated defects in cilia structure may contribute to the progressive photoreceptor dysfunction associated with CFH loss-of-function mutations in some AMD patients.


Assuntos
Fator H do Complemento/metabolismo , Heparitina Sulfato/metabolismo , Retina/metabolismo , Animais , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Cílios/metabolismo , Fator H do Complemento/fisiologia , Heparitina Sulfato/fisiologia , Degeneração Macular/metabolismo , Degeneração Macular/fisiopatologia , Neurônios/metabolismo , Fatores de Transcrição/metabolismo
15.
Medicina (Kaunas) ; 60(10)2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39459435

RESUMO

The most prevalent reason for vision impairment in aging inhabitants is age-related macular degeneration (AMD), a posterior ocular disease with a poor understanding of the anatomic, genetic, and pathophysiological progression of the disease. Recently, new insights exploring the role of atrophic changes in the retinal pigment epithelium, extracellular drusen deposits, lysosomal lipofuscin, and various genes have been investigated in the progression of AMD. Hence, this review explores the incidence and risk factors for AMD, such as oxidative stress, inflammation, the complement system, and the involvement of bioactive lipids and their role in angiogenesis. In addition to intravitreal anti-vascular endothelial growth factor (VEGF) therapy and other therapeutic interventions such as oral kinase inhibitors, photodynamic, gene, and antioxidant therapy, as well as their benefits and drawbacks as AMD treatment options, strategic drug delivery methods, including drug delivery routes with a focus on intravitreal pharmacokinetics, are investigated. Further, the recent advancements in nanoformulations such as polymeric and lipid nanocarriers, liposomes, etc., intended for ocular drug delivery with pros and cons are too summarized. Therefore, the purpose of this review is to give new researchers an understanding of AMD pathophysiology, with an emphasis on angiogenesis, inflammation, the function of bioactive lipids, and therapy options. Additionally, drug delivery options that focus on the development of drug delivery system(s) via several routes of delivery can aid in the advancement of therapeutic choices.


Assuntos
Sistemas de Liberação de Medicamentos , Degeneração Macular , Humanos , Degeneração Macular/tratamento farmacológico , Degeneração Macular/fisiopatologia , Sistemas de Liberação de Medicamentos/métodos , Estresse Oxidativo/efeitos dos fármacos , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/administração & dosagem
16.
Int Ophthalmol ; 44(1): 228, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38780873

RESUMO

AIM: It is known that a healthy and balanced diet plays an important role in the etiopathogenesis of age-related macular degeneration (AMD). The aim of this study is to show the possible relationship between the prognostic nutritional index (PNI) and AMD. METHODS: This observational longitudinal study included 50 patients who were diagnosed with AMD and 100 participants as control group in the Ophthalmology Polyclinic of Kirsehir Ahi Evran Training and Research Hospital between December 2022 and February 2023. The PNI scores of the patients were calculated with the formula (10 × albumin (g/L) + (0.005 × total lymphocyte count), using routine hemogram and biochemical assays. RESULTS: One hundred fifty participants were included in the study (average age: 73.7 ± 8.6 years, male: 53.3%). When adjusted for age, sex, and total comorbidity index score via multivariate logistic regression analysis, the association between AMD and PNI scores (OR = 0.3; CI: 0.2-0.4; p = 0.01) and Charlson Comorbidity Index (CCI) scores (OR = 6.8; CI: 2.8-16.6; p = 0.01) was statistically significant. CONCLUSION: The use of PNI scores may be practical and useful in routine clinical practice for predicting AMD.


Assuntos
Degeneração Macular , Avaliação Nutricional , Estado Nutricional , Humanos , Masculino , Degeneração Macular/diagnóstico , Degeneração Macular/fisiopatologia , Feminino , Idoso , Prognóstico , Idoso de 80 Anos ou mais , Seguimentos , Fatores de Risco
17.
Nursing ; 54(10): 50-53, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39302753

RESUMO

ABSTRACT: Age-related macular degeneration (AMD) is the leading cause of visual impairment in patients age 50 and older, with an estimated 200 million people affected worldwide and a projected 288 million by 2040. This article provides an overview of the epidemiology, risk factors, pathophysiology, clinical manifestations, diagnosis, management, and nursing considerations for AMD to equip nurses with the knowledge to play a crucial role in the early detection of this disease.


Assuntos
Degeneração Macular , Idoso , Humanos , Pessoa de Meia-Idade , Degeneração Macular/enfermagem , Degeneração Macular/diagnóstico , Degeneração Macular/epidemiologia , Degeneração Macular/fisiopatologia , Diagnóstico de Enfermagem , Fatores de Risco , Idoso de 80 Anos ou mais
18.
Vestn Oftalmol ; 140(2. Vyp. 2): 172-179, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38739148

RESUMO

Multifocal electroretinography is a valuable diagnostic method for the objective localization and quantitative assessment of functional disorders of the central retina in age-related macular degeneration. It is used to detect early changes, monitor the course of the disease and treatment outcomes. In many cases, multifocal electroretinography is a more sensitive method for detecting functional disorders at the early/intermediate stage of age-related macular degeneration compared to morphological (optical coherence tomography) and subjective (visual acuity, perimetry) testing methods.


Assuntos
Eletrorretinografia , Degeneração Macular , Retina , Humanos , Eletrorretinografia/métodos , Degeneração Macular/diagnóstico , Degeneração Macular/fisiopatologia , Retina/diagnóstico por imagem , Retina/fisiopatologia , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Diagnóstico Precoce , Progressão da Doença
19.
Vestn Oftalmol ; 140(4): 40-48, 2024.
Artigo em Russo | MEDLINE | ID: mdl-39254389

RESUMO

PURPOSE: This study analyzes the effectiveness and safety of brolucizumab in the treatment of neovascular age-related macular degeneration (nAMD) in real clinical practice. MATERIAL AND METHODS: The study included patients with nAMD who received brolucizumab treatment and evaluated the changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), macular volume, as well as the number of injections and adverse events. RESULT: The group of previously treated patients included 28 subjects (28 eyes) that were switched to brolucizumab with a loading phase. By 12 months, BCVA changed from 0.43±0.29 to 0.33±0.27 LogMAR (p=0.11), CRT decreased from 281.5±58.2 to 239.9±45.6 µm (p=0.02). The group of previously untreated patients included 29 subjects (29 eyes). By 12 months, BCVA changed from 0.47±0.32 to 0.40±0.30 LogMAR (p=0.09), CRT decreased from 333.2±77.3 to 226.2±49.6 µm (p<0.001). Patients received 6.3±0.7 injections. In this group, baseline choroidal thickness showed a statistically significant correlation with final visual acuity (r=0.54; p<0.05) and CRT (r= -0.5; p<0.05). The group of previously treated patients switched without a loading phase included 18 patients (18 eyes). By 6 months, BCVA changed from 0.42±0.2 to 0.37±0.26 LogMAR (p=0.42). CRT remained stable at 285.6±56.9 µm (p=0.97). No adverse events related to intraocular inflammation were reported during the course of 385 injections. CONCLUSION: Brolucizumab therapy helps achieve significant anatomical and functional improvements in real clinical practice both in patients switched from previous treatments and in treatment-naïve patients. Greater baseline choroidal thickness may be associated with better anatomical and functional outcomes with brolucizumab treatment.


Assuntos
Inibidores da Angiogênese , Anticorpos Monoclonais Humanizados , Injeções Intravítreas , Acuidade Visual , Humanos , Masculino , Feminino , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Resultado do Tratamento , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Tomografia de Coerência Óptica/métodos , Degeneração Macular/tratamento farmacológico , Degeneração Macular/diagnóstico , Degeneração Macular/fisiopatologia , Degeneração Macular Exsudativa/tratamento farmacológico , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/fisiopatologia
20.
Proc Natl Acad Sci U S A ; 117(5): 2579-2587, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-31964819

RESUMO

Degeneration of the retinal pigmented epithelium (RPE) and aberrant blood vessel growth in the eye are advanced-stage processes in blinding diseases such as age-related macular degeneration (AMD), which affect hundreds of millions of people worldwide. Loss of the RNase DICER1, an essential factor in micro-RNA biogenesis, is implicated in RPE atrophy. However, the functional implications of DICER1 loss in choroidal and retinal neovascularization are unknown. Here, we report that two independent hypomorphic mouse strains, as well as a separate model of postnatal RPE-specific DICER1 ablation, all presented with spontaneous RPE degeneration and choroidal and retinal neovascularization. DICER1 hypomorphic mice lacking critical inflammasome components or the innate immune adaptor MyD88 developed less severe RPE atrophy and pathological neovascularization. DICER1 abundance was also reduced in retinas of the JR5558 mouse model of spontaneous choroidal neovascularization. Finally, adenoassociated vector-mediated gene delivery of a truncated DICER1 variant (OptiDicer) reduced spontaneous choroidal neovascularization in JR5558 mice. Collectively, these findings significantly expand the repertoire of DICER1 in preserving retinal homeostasis by preventing both RPE degeneration and pathological neovascularization.


Assuntos
RNA Helicases DEAD-box/metabolismo , Degeneração Macular/metabolismo , Epitélio Pigmentado da Retina/irrigação sanguínea , Ribonuclease III/metabolismo , Animais , Neovascularização de Coroide/genética , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/patologia , Neovascularização de Coroide/fisiopatologia , RNA Helicases DEAD-box/genética , Humanos , Degeneração Macular/genética , Degeneração Macular/patologia , Degeneração Macular/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Degeneração Retiniana/genética , Degeneração Retiniana/metabolismo , Degeneração Retiniana/patologia , Degeneração Retiniana/fisiopatologia , Neovascularização Retiniana/genética , Neovascularização Retiniana/metabolismo , Neovascularização Retiniana/parasitologia , Neovascularização Retiniana/fisiopatologia , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Ribonuclease III/genética
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