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1.
PLoS One ; 15(8): e0236283, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764794

RESUMO

Geographic atrophy (GA) is an advanced form of dry age-related macular degeneration (AMD), in which local inflammation and hyperactivity of the complement pathway have been implicated in its pathophysiology. This study explores whether any surrogate biomarkers are specifically associated with GA. Plasma from subjects with GA, intermediate dry AMD and non-AMD control were evaluated in 2 cohorts. Cohort 1 was assayed in a 320-analyte Luminex library. Statistical analysis was performed using non-parametric and parametric methods (Kruskal-Wallis, principal component analysis, partial least squares and multivariate analysis of variance (MANOVA) and univariate ANCOVAs). Bioinformatic analysis was conducted and identified connections to the amyloid pathway. Statistically significant biomarkers identified in Cohort 1 were then re-evaluated in Cohort 2 using individual ELISA and multiplexing. Of 320 analytes in Cohort 1, 273 were rendered measurable, of which 56 were identified as changing. Among these markers, 40 were identified in univariate ANCOVAs. Serum amyloid precursor protein (sAPP) was analyzed by a separate ELISA and included in further analyses. The 40 biomarkers, sAPP and amyloid-ß (Aß) (1-42) (included for comparison) were evaluated in Cohort 2. This resulted in 11 statistically significant biomarkers, including sAPP and Aß(1-40), but not Aß(1-42). Other biomarkers identified included serum proteases- tissue plasminogen activator, tumor-associated trypsinogen inhibitor, matrix metalloproteinases 7 and 9, and non-proteases- insulin-like growth factor binding protein 6, AXL receptor tyrosine kinase, omentin, pentraxin-3 and osteopontin. Findings suggest that there is a preferential processing of APP to Aß(1-40) over Aß(1-42), and a potential role for the carboxylase activity of the γ-secretase protein, which preferentially splices sAPPß to Aß(1-40). Other markers are associated with the breakdown and remodeling of the extracellular matrix, and loss of homeostasis, possibly within the photoreceptor-retinal pigment epithelium-choriocapillaris complex. These data suggest novel disease pathways associated with GA pathogenesis and could provide potential novel targets for treatment of GA.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Atrofia Geográfica/sangue , Degeneração Macular/complicações , Epitélio Pigmentado da Retina/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores/metabolismo , Estudos de Coortes , Biologia Computacional , Feminino , Fundo de Olho , Atrofia Geográfica/diagnóstico , Atrofia Geográfica/etiologia , Atrofia Geográfica/patologia , Humanos , Degeneração Macular/sangue , Degeneração Macular/patologia , Masculino , Pessoa de Meia-Idade , Imagem Óptica , Transdução de Sinais , Ativador de Plasminogênio Tecidual
2.
PLoS One ; 15(8): e0238072, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822418

RESUMO

PURPOSE: Early detection and treatment are important management strategies for neovascular age-related macular degeneration (AMD). The purpose of this study was to determine the sensitivity and specificity in detecting neovascular AMD using two wide-field imaging systems: ClarusTM (CLARUS 500™, Carl Zeiss Meditec AG, Jena, Germany) and Optos®(Optos California®, Optos PLC, Dunfermline, United Kingdom), compared to conventional digital fundus photographs. METHODS: We retrospectively analyzed 109 eyes of 73 consecutive patients with neovascular AMD, who underwent standard examination and multimodal imaging, including fundus photography, and optical coherence tomography (OCT). Unmasked graders utilized slit-lamp biomicroscopy and OCT to diagnose neovascular AMD. Masked graders evaluated ClarusTM, Optos®, and digital fundus photograph methods to determine the presence of choroidal neovascularization associated with AMD. Sensitivity and specificity analyses were performed using combined fundoscopy and OCT as the reference standard. RESULTS: Ninety eyes were diagnosed with neovascular AMD and the remaining 19 eyes were normal based on the reference standard. Of these, neovascular AMD was detected using ClarusTM in 94.4% (85/90). The sensitivities of Optos® and digital fundus photographs were 81.1% (73/90) and 87.8% (79/90), respectively. The specificities using ClarusTM, Optos®, and digital fundus photographs were 89.5% (17/19), 94.7% (18/19), and 89.5% (17/19), respectively. CONCLUSION: ClarusTM, with its ability to image high-resolution wide field fundus, was considered superior for diagnosing neovascular AMD with high sensitivity and specificity. It may be a useful screening tool for early detection of neovascular AMD, facilitating prompt referral and treatment.


Assuntos
Degeneração Macular/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Feminino , Fundo de Olho , Humanos , Degeneração Macular/patologia , Masculino , Pessoa de Meia-Idade , Fotografação/métodos , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Tomografia de Coerência Óptica/métodos
3.
Proc Natl Acad Sci U S A ; 117(31): 18780-18787, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32699144

RESUMO

Macular telangiectasia type 2 (MacTel), a late-onset macular degeneration, has been linked to a loss in the retina of Müller glial cells and the amino acid serine, synthesized by the Müller cells. The disease is confined mainly to a central retinal region called the MacTel zone. We have used electron microscopic connectomics techniques, optimized for disease analysis, to study the retina from a 48-y-old woman suffering from MacTel. The major observations made were specific changes in mitochondrial structure within and outside the MacTel zone that were present in all retinal cell types. We also identified an abrupt boundary of the MacTel zone that coincides with the loss of Müller cells and macular pigment. Since Müller cells synthesize retinal serine, we propose that a deficiency of serine, required for mitochondrial maintenance, causes mitochondrial changes that underlie MacTel development.


Assuntos
Conectoma/métodos , Retina , Doenças Retinianas , Feminino , Humanos , Degeneração Macular/diagnóstico por imagem , Degeneração Macular/patologia , Microscopia Eletrônica , Pessoa de Meia-Idade , Retina/citologia , Retina/diagnóstico por imagem , Retina/patologia , Doenças Retinianas/diagnóstico por imagem , Doenças Retinianas/patologia
4.
PLoS One ; 15(7): e0236298, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32701996

RESUMO

Degeneration of the retinal pigment epithelium (RPE) plays a central role in age-related macular degeneration (AMD). Throughout life, RPE cells are challenged by a variety of cytotoxic stressors, some of which are cumulative with age and may ultimately contribute to drusen and lipofuscin accumulation. Stressors such as these continually damage RPE cells resulting in a state of chronic wounding. Current cell-based platforms that model a state of chronic RPE cell wounding are limited, and the RPE cellular response is not entirely understood. Here, we used the electric cell-substrate impedance sensing (ECIS) system to induce a state of acute or chronic wounding on differentiated human fetal RPE cells to analyze changes in the wound repair response. RPE cells surrounding the lesioned area employ both cell migration and proliferation to repair wounds but fail to reestablish their original cell morphology or density after repetitive wounding. Chronically wounded RPE cells develop phenotypic AMD characteristics such as loss of cuboidal morphology, enlarged size, and multinucleation. Transcriptomic analysis suggests a systemic misregulation of RPE cell functions in bystander cells, which are not directly adjacent to the wound. Genes associated with the major RPE cell functions (LRAT, MITF, RDH11) significantly downregulate after wounding, in addition to differential expression of genes associated with the cell cycle (CDK1, CDC6, CDC20), inflammation (IL-18, CCL2), and apoptosis (FAS). Interestingly, repetitive wounding resulted in prolonged misregulation of genes, including FAS, LRAT, and PEDF. The use of ECIS to induce wounding resulted in an over-representation of AMD-associated genes among those dysregulated genes, particularly genes associated with advanced AMD. This simple system provides a new model for further investigation of RPE cell wound response in AMD pathogenesis.


Assuntos
Degeneração Macular/patologia , Modelos Biológicos , Doença Aguda , Efeito Espectador , Ciclo Celular , Diferenciação Celular , Proliferação de Células , Doença Crônica , Feto/patologia , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Cinética , Degeneração Macular/genética , Epitélio Pigmentado da Retina/embriologia , Epitélio Pigmentado da Retina/patologia , Transcriptoma/genética , Cicatrização
5.
Proc Natl Acad Sci U S A ; 117(23): 13094-13104, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32434914

RESUMO

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. While the histopathology of the different disease stages is well characterized, the cause underlying the progression, from the early drusen stage to the advanced macular degeneration stage that leads to blindness, remains unknown. Here, we show that photoreceptors (PRs) of diseased individuals display increased expression of two key glycolytic genes, suggestive of a glucose shortage during disease. Mimicking aspects of this metabolic profile in PRs of wild-type mice by activation of the mammalian target of rapamycin complex 1 (mTORC1) caused early drusen-like pathologies, as well as advanced AMD-like pathologies. Mice with activated mTORC1 in PRs also displayed other early disease features, such as a delay in photoreceptor outer segment (POS) clearance and accumulation of lipofuscin in the retinal-pigmented epithelium (RPE) and of lipoproteins at the Bruch's membrane (BrM), as well as changes in complement accumulation. Interestingly, formation of drusen-like deposits was dependent on activation of mTORC1 in cones. Both major types of advanced AMD pathologies, including geographic atrophy (GA) and neovascular pathologies, were also seen. Finally, activated mTORC1 in PRs resulted in a threefold reduction in di-docosahexaenoic acid (DHA)-containing phospholipid species. Feeding mice a DHA-enriched diet alleviated most pathologies. The data recapitulate many aspects of the human disease, suggesting that metabolic adaptations in photoreceptors could contribute to disease progression in AMD. Identifying the changes downstream of mTORC1 that lead to advanced pathologies in mouse might present new opportunities to study the role of PRs in AMD pathogenesis.


Assuntos
Envelhecimento/patologia , Macula Lutea/patologia , Degeneração Macular/patologia , Células Fotorreceptoras Retinianas Cones/patologia , Idoso , Idoso de 80 Anos ou mais , Animais , Lâmina Basilar da Corioide/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Lipofuscina/metabolismo , Lipoproteínas/metabolismo , Macula Lutea/citologia , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Células Fotorreceptoras Retinianas Cones/metabolismo , Epitélio Pigmentado da Retina/metabolismo
6.
Cochrane Database Syst Rev ; 5: CD012208, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32374423

RESUMO

BACKGROUND: Age-related macular degeneration (AMD) is one of the leading causes of permanent blindness worldwide. The current mainstay of treatment for neovascular AMD (nAMD) is intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents: aflibercept, ranibizumab, and off-label bevacizumab. Injections can be given monthly, every two or three months ('extended-fixed'), or as needed (pro re nata (PRN)). A variant of PRN is 'treat-and-extend' whereby injections are resumed if recurrence is detected and then delivered with increasing intervals. Currently, injection frequency varies among practitioners, which underscores the need to characterize an optimized approach to nAMD management. OBJECTIVES: To investigate the effects of monthly versus non-monthly intravitreous injection of an anti-VEGF agent in people with newly diagnosed nAMD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, and three trials registers from 2004 to October 2019; checked references; handsearched conference abstracts; and contacted pharmaceutical companies to identify additional studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared different treatment regimens for anti-VEGF agents in people with newly diagnosed nAMD. We considered standard doses only (ranibizumab 0.5 mg, bevacizumab 1.25 mg, aflibercept 2.0 mg, or a combination of these). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods for trial selection, data extraction, and analysis. MAIN RESULTS: We included 15 RCTs. The total number of participants was 7732, ranging from 37 to 2457 in each trial. The trials were conducted worldwide. Of these, six trials exclusively took place in the US, and three included centers from more than one country. Eight trials were at high risk of bias for at least one domain and all trials had at least one domain at unclear risk of bias. Seven trials (3525 participants) compared a PRN regimen with a monthly injection regimen, of which five trials delivered four to eight injections using standard PRN and three delivered nine or 10 injections using a treat-and-extend regimen in the first year. The overall mean change in best-corrected visual acuity (BCVA) at one year was +8.8 letters in the monthly injection group. Compared to the monthly injection, there was moderate-certainty evidence that the mean difference (MD) in BCVA change at one year for the standard PRN subgroup was -1.7 letters (95% confidence interval (CI) -2.8 to -0.6; 4 trials, 2299 participants), favoring monthly injections. There was low-certainty evidence of a similar BCVA change with the treat-and-extend subgroup (0.5 letters, 95% CI -3.1 to 4.2; 3 trials, 1226 participants). Compared to monthly injection, there was low-certainty evidence that fewer participants gained 15 or more lines of vision with standard PRN treatment at one year (risk ratio (RR) 0.87, 95% CI 0.76 to 0.99; 4 trials, 2299 participants) and low-certainty evidence of a similar gain with treat-and-extend versus monthly regimens (RR 1.11, 95% CI 0.91 to 1.36; 3 trials, 1169 participants). The mean change in central retinal thickness was a decrease of -166 µm in the monthly injection group; the MD compared with standard PRN was 21 µm (95% CI 6 to 32; 4 trials, 2215 participants; moderate-certainty evidence) and with treat-and extend was 22 µm (95% CI 37 to -81 µm; 2 trials, 635 participants; low-certainty evidence), in favor of monthly injection. Only one trial (498 participants) measured quality of life and reported no evidence of a difference between regimens, but data could not be extracted (low-certainty evidence). Both PRN regimens (standard and 'treat-and-extend') used fewer injections than monthly regimens (standard PRN: MD -4.6 injections, 95% CI -5.4 to -3.8; 4 trials, 2336 participants; treat-and-extend: -2.4 injections, 95% CI -2.7 to -2.1 injections; moderate-certainty evidence for both comparisons). Two trials provided cost data (1105 participants, trials conducted in the US and the UK). They found that cost differences between regimens were reduced if bevacizumab rather than aflibercept or ranibizumab were used, since bevacizumab was less costly (low-certainty evidence). PRN regimens were associated with a reduced risk of endophthalmitis compared with monthly injections (Peto odds ratio (OR) 0.13, 95% CI 0.04 to 0.46; 6 RCTs, 3175 participants; moderate-certainty evidence). Using data from all trials included in this review, we estimated the risk of endophthalmitis with monthly injections to be 8 in every 1000 people per year. The corresponding risk for people receiving PRN regimens was 1 in every 1000 people per year (95% CI 0 to 4). Three trials (1439 participants) compared an extended-fixed regimen (number of injections reported in only one large trial: 7.5 in one year) with monthly injections. There was moderate-certainty evidence that BCVA at one year was similar for extended-fixed and monthly injections (MD in BCVA change compared to extended-fixed group: -1.3 letters, 95% CI -3.9 to 1.3; RR of gaining 15 letters or more: 0.94, 95% CI 0.80 to 1.10). The change in central retinal thickness was a decrease of 137 µm in the monthly group; the MD with the extended-fixed group was 8 µm (95% CI -11 to 27; low-certainty evidence). The frequency of endophthalmitis was lower in the extended-fixed regimen compared to the monthly group, but this estimate was imprecise (RR 0.19, 95% CI 0.03 to 1.11; low-certainty evidence). If we assumed a risk of 8 cases of endophthalmitis in 1000 people receiving monthly injections over one year, then the corresponding risk with extended-fixed regimen was 2 in 1000 people (95% CI 0 to 9). Other evidence comparing different extended-fixed or PRN regimens yielded inconclusive results. AUTHORS' CONCLUSIONS: We found that, at one year, monthly regimens are probably more effective than PRN regimens using seven or eight injections in the first year, but the difference is small and clinically insignificant. Endophthalmitis is probably more common with monthly injections and differences in costs between regimens are higher if aflibercept or ranibizumab are used compared to bevacizumab. This evidence only applies to settings in which regimens are implemented as described in the trials, whereas undertreatment is likely to be common in real-world settings. There are no data from RCTs on long-term effects of different treatment regimens.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Degeneração Macular/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/economia , Bevacizumab/administração & dosagem , Bevacizumab/economia , Viés , Esquema de Medicação , Endoftalmite/epidemiologia , Endoftalmite/etiologia , Humanos , Injeções Intravítreas/efeitos adversos , Degeneração Macular/patologia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Ranibizumab/administração & dosagem , Ranibizumab/economia , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/economia , Retina/efeitos dos fármacos
7.
PLoS One ; 15(4): e0231901, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32343707

RESUMO

AIM: To assess prevalence, clinical presentation and multimodal imaging characteristics of polypoidal choroidal vasculopathy (PCV) in a hospital-based setting in South India. METHODS: Electronic medical records (EMR) of new patients presenting with suspected clinical signs of wet age-related macular degeneration (AMD) in a tertiary hospital from January to December 2016 were retrospectively analyzed using keywords and filtered for patient who underwent multimodal imaging. Clinical presentations were categorized into predominantly hemorrhagic, exudative or mixed pattern. The imaging features were compared in these clinical groups. The multimodal images were graded by two masked graders and discrepancies between them were settled by a senior arbitrator. RESULTS: Of the 147 clinically suspicious cases of PCV out of 785 patients with clinical presentation of AMD as recorded in the EMR, 73 (49.7%) patients had a multimodal imaging diagnosis of PCV. There was no difference in the demography, distribution of polyps, ICGA and OCT characteristics in eyes presenting with hemorrhagic, exudative or mixed clinical features. CONCLUSION: Approximately half of South Asian patients presenting with clinical features of neovascular AMD harbor PCV irrespective of their clinical presentation and so we recommend that multimodal imaging is done in all cases of suspicious neovascular AMD in Indian population.


Assuntos
Degeneração Macular/patologia , Doenças Vasculares/diagnóstico , Adulto , Idoso , Corioide/diagnóstico por imagem , Corioide/patologia , Feminino , Angiofluoresceinografia , Humanos , Índia/epidemiologia , Degeneração Macular/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Prevalência , Estudos Retrospectivos , Fatores de Risco , Tomografia de Coerência Óptica , Doenças Vasculares/diagnóstico por imagem , Doenças Vasculares/epidemiologia
8.
J Pathol ; 251(2): 200-212, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32243583

RESUMO

Age-related macular degeneration (AMD) is a complex, multifactorial, progressive disease which represents a leading cause of irreversible visual impairment and blindness in older individuals. Human cytomegalovirus (HCMV), which infects 50-80% of humans, is usually acquired during early life and persists in a latent state for the life of the individual. In view of its previously described pro-angiogenic properties, we hypothesized that cytomegalovirus might be a novel risk factor for progression to an advanced form, neovascular AMD, which is characterized by choroidal neovascularization (CNV). The purpose of this study was to investigate if latent ocular murine cytomegalovirus (MCMV) infection exacerbated the development of CNV in vascular endothelial growth factor (VEGF)-overexpressing VEGF-Ahyper mice. Here we show that neonatal infection with MCMV resulted in dissemination of virus to various organs throughout the body including the eye, where it localized principally to the choroid in both VEGF-overexpressingVEGF-Ahyper and wild-type(WT) 129 mice. By 6 months post-infection, no replicating virus was detected in eyes and extraocular tissues, although virus DNA was still present in all eyes and extraocular tissues of both VEGF-Ahyper and WT mice. Expression of MCMV immediate early (IE) 1 mRNA was detected only in latently infected eyes of VEGF-Ahyper mice, but not in eyes of WT mice. Significantly increased CNV was observed in eyes of MCMV-infected VEGF-Ahyper mice compared to eyes of uninfected VEGF-Ahyper mice, while no CNV lesions were observed in eyes of either infected or uninfected WT mice. Protein levels of several inflammatory/angiogenic factors, particularly VEGF and IL-6, were significantly higher in eyes of MCMV-infected VEGF-Ahyper mice, compared to uninfected controls. Initial studies of ocular tissue from human cadavers revealed that HCMV DNA was present in four choroid/retinal pigment epithelium samples from 24 cadavers. Taken together, our data suggest that ocular HCMV latency could be a significant risk factor for the development of AMD. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Neovascularização de Coroide/virologia , Retinite por Citomegalovirus/virologia , Degeneração Macular/virologia , Muromegalovirus/patogenicidade , Retina/virologia , Latência Viral , Idoso , Idoso de 80 Anos ou mais , Animais , Neovascularização de Coroide/genética , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/patologia , Retinite por Citomegalovirus/genética , Retinite por Citomegalovirus/metabolismo , Retinite por Citomegalovirus/patologia , Modelos Animais de Doenças , Progressão da Doença , Feminino , Humanos , Proteínas Imediatamente Precoces/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Degeneração Macular/genética , Degeneração Macular/metabolismo , Degeneração Macular/patologia , Masculino , Camundongos da Linhagem 129 , Camundongos Transgênicos , Pessoa de Meia-Idade , Retina/metabolismo , Retina/ultraestrutura , Fatores de Risco , Transdução de Sinais , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
9.
PLoS One ; 15(4): e0231351, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32267887

RESUMO

PURPOSE: To investigate the association between different stages of posterior vitreous detachment (PVD) and macular microvasculature in the elderly. METHODS: Swept-source optical coherence tomography (OCT), OCT angiography, and color fundus images of 490 eyes without retinal pathologies of 322 participants aged ≥65 years were evaluated. PVD was classified using enhanced vitreous visualization mode as no apparent PVD (stage 0/1), vitreous adhesions at the fovea and optic disc (stage 2), adhesion at the optic disc (stage 3), or complete PVD (stage 4). Microvascular parameters, including foveal avascular zone (FAZ) and vessel density (VD), were analyzed for their associations with complete PVD. Additionally, the association between PVD and central retinal thickness (CRT) was also addressed. RESULTS: Overall, 80, 31, 31, and 349 eyes were categorized into stages 0/1, 2, 3, and 4, respectively. Using multivariate mixed-effects model, the mean superficial FAZ area was smaller in stage 4 compared with stages 0-3 (0.29 vs. 0.32 mm2; P = 0.014), and the mean superficial VD was lower in stage 4 compared with stages 0-3 (34.96% vs. 35.24%; P = 0.0089). However, PVD was not significantly associated with deep macular microvascular parameters or CRT. CONCLUSIONS: Complete PVD was associated with smaller FAZ area and lower VD in superficial macular microvasculature, while it was not associated with central retinal thickness.


Assuntos
Microvasos/fisiologia , Descolamento do Vítreo/diagnóstico , Idoso , Estudos Transversais , Olho/diagnóstico por imagem , Feminino , Angiofluoresceinografia , Humanos , Macula Lutea/irrigação sanguínea , Macula Lutea/diagnóstico por imagem , Macula Lutea/fisiologia , Degeneração Macular/diagnóstico , Degeneração Macular/patologia , Masculino , Microvasos/diagnóstico por imagem , Pessoa de Meia-Idade , Retina/fisiologia , Índice de Gravidade de Doença , Tomografia de Coerência Óptica , Descolamento do Vítreo/patologia
10.
Proc Natl Acad Sci U S A ; 117(18): 9942-9951, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32321835

RESUMO

Genetic variants within complement factor H (CFH), a major alternative complement pathway regulator, are associated with the development of age-related macular degeneration (AMD) and other complementopathies. This is explained with the reduced binding of CFH or its splice variant factor H-like protein 1 (FHL-1) to self-ligands or altered self-ligands (e.g., malondialdehyde [MDA]-modified molecules) involved in homeostasis, thereby causing impaired complement regulation. Considering the critical role of CFH in inhibiting alternative pathway activation on MDA-modified surfaces, we performed an unbiased genome-wide search for genetic variants that modify the ability of plasma CFH to bind MDA in 1,830 individuals and characterized the mechanistic basis and the functional consequences of this. In a cohort of healthy individuals, we identified rs1061170 in CFH and the deletion of CFHR3 and CFHR1 as dominant genetic variants that modify CFH/FHL-1 binding to MDA. We further demonstrated that FHR1 and FHR3 compete with CFH for binding to MDA-epitopes and that FHR1 displays the highest affinity toward MDA-epitopes compared to CFH and FHR3. Moreover, FHR1 bound to MDA-rich areas on necrotic cells and prevented CFH from mediating its cofactor activity on MDA-modified surfaces, resulting in enhanced complement activation. These findings provide a mechanistic explanation as to why the deletion of CFHR3 and CFHR1 is protective in AMD and highlight the importance of genetic variants within the CFH/CFHR3/CFHR1 locus in the recognition of altered-self in tissue homeostasis.


Assuntos
Proteínas Sanguíneas/genética , Proteínas Inativadoras do Complemento C3b/genética , Degeneração Macular/genética , Idoso , Fator H do Complemento/genética , Epitopos/genética , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Degeneração Macular/patologia , Masculino , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Ligação Proteica
11.
PLoS One ; 15(3): e0230305, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32168355

RESUMO

PURPOSE: To describe epidemiologic features of patients with presumed ocular histoplasmosis syndrome (POHS) in the United States using insurance claims data and compare POHS patients with and without choroidal neovascularization (CNV). DESIGN: Retrospective cohort study. METHODS: Patients with International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for histoplasmosis retinitis on an outpatient claim in the 2014 IBM® MarketScan® Commercial Database and the Medicare Supplemental Database who were enrolled for at least 2 years after the POHS code. MAIN OUTCOME MEASURES: Data related to testing, treatment, and direct medical costs. RESULTS: Among >50 million total MarketScan enrollees, 6,678 (13 per 100,000) had a POHS diagnosis code. Of those, 2,718 were enrolled for 2 years; 698 (25%) of whom had a CNV code. Eleven of the 13 states with the highest POHS rates bordered the Mississippi and Ohio rivers. CNV patients had significantly more eye care provider visits (mean 8.8 vs. 3.2, p<0.0001), more ophthalmic imaging tests, higher rates of treatment with anti-vascular endothelial growth factor injections (45% vs. 4%, p<0.0001), and incurred higher mean total yearly costs ($1,251.83 vs. $251.36, p<0.0001) than POHS patients without CNV. CONCLUSIONS: Although the relationship between Histoplasma and POHS remains controversial, geographic patterns of POHS patient residence were consistent with the traditionally reported range of the fungus. CNV in the context of POHS was associated with additional healthcare use and costs. Further research to understand POHS etiology, risk factors, prevalence, and complications is needed, along with early diagnosis and treatment strategies.


Assuntos
Neovascularização de Coroide/economia , Histoplasmose/economia , Seguro Saúde/economia , Degeneração Macular/economia , Retinite/economia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Neovascularização de Coroide/complicações , Neovascularização de Coroide/patologia , Neovascularização de Coroide/terapia , Olho/patologia , Oftalmopatias/economia , Oftalmopatias/epidemiologia , Feminino , Pessoal de Saúde , Histoplasmose/complicações , Histoplasmose/patologia , Histoplasmose/terapia , Humanos , Lactente , Recém-Nascido , Revisão da Utilização de Seguros , Degeneração Macular/patologia , Degeneração Macular/terapia , Masculino , Pessoa de Meia-Idade , Oftalmologia/economia , Retinite/complicações , Retinite/patologia , Retinite/terapia , Estados Unidos/epidemiologia , Visão Ocular/fisiologia , Adulto Jovem
12.
PLoS One ; 15(3): e0230344, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32214330

RESUMO

In age-related macular degeneration (AMD) or diabetic retinopathy (DR), hypoxia and inflammatory processes lead to an upregulation of the vascular endothelial growth factor (VEGF) expression and thereby to pathological neovascularisation with incorrectly formed vessels prone to damage, thus increasing the vascular permeability and the risk of bleeding and oedema in the retina. State of the art treatment is the repeated intraocular injection of anti-VEGF molecules. For developing improved individualized treatment approaches, a minimally invasive, repeatable method for in vivo quantification of VEGF in the eye is necessary. Therefore, we designed single molecule eBRET2 VEGF biosensors by directly fusing a Renilla luciferase mutant (Rluc8) N-terminal and a green fluorescent protein (GFP2) C-terminal to a VEGF binding domain. In total, 10 different VEGF biosensors (Re01- Re10) were generated based on either single domains or full length of VEGF receptor 1 or 2 extracellular regions as VEGF binding domains. Full length expression of the biosensors in HEK293-T cells was verified via Western Blot employing an anti-Rluc8-IgG. Expression of alternative splice variants was eliminated through the deletion of the donor splice site by introduction of a silent point mutation. In all ten biosensors the energy transfer from the Rluc8 to the GFP2 occurs and generates a measurable eBRET2 ratio. Four biosensors show a relevant change of the BRET ratio (ΔBR) after VEGF binding. Furthermore, each biosensor shows a unique detection range for VEGF quantification and especially Re06 and Re07 have a high sensitivity in the range of in vivo VEGF concentrations in the eye, previously measured by invasive methods. In conclusion, we generated several eBRET2 biosensors that are suitable for VEGF quantification in vitro and could identify two eBRET2 biosensors, which may be suitable for non-invasive in vivo VEGF quantification with an implantable device.


Assuntos
Técnicas Biossensoriais/instrumentação , Medições Luminescentes/instrumentação , Proteínas Recombinantes de Fusão/química , Fator A de Crescimento do Endotélio Vascular/análise , Animais , Córnea/patologia , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/patologia , Transferência de Energia , Proteínas de Fluorescência Verde/química , Proteínas de Fluorescência Verde/genética , Células HEK293 , Células Endoteliais da Veia Umbilical Humana , Humanos , Luciferases de Renilla/química , Luciferases de Renilla/genética , Degeneração Macular/diagnóstico , Degeneração Macular/patologia , Ligação Proteica , Domínios Proteicos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Retina/patologia , Transfecção , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo
13.
Expert Opin Pharmacother ; 21(7): 773-784, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32153203

RESUMO

INTRODUCTION: Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly in the industrialized world. While effective treatment is available for neovascular AMD, no therapy is successful for the non-neovascular form. Herein, the authors report the current knowledge on non-neovascular AMD pathogenesis and the promising research on treatments. AREAS COVERED: In the present review, the authors summarize the most recent advances in the treatment of non-neovascular AMD and provide an update on current treatment strategies. Evidence available from preclinical and clinical studies and from a selective literature search is reported. EXPERT OPINION: When investigating AMD, numerous pathological cascades and alterations of physiological processes have been investigated. It is well-known that AMD is a multifactorial disease, with environmental causes and genetics playing a role. Perturbations in multiple pathogenic pathways have been identified and this led to the development of several molecules directed at specific therapeutic targets. However, despite the huge research effort, the only proven approach so far is oral antioxidant supplementation. We believe that, in addition to successful advancement of promising drugs, further research should be directed at tailoring therapy to specific patient groups, eventually employing a combinational therapy strategy.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Degeneração Macular/tratamento farmacológico , Acuidade Visual/efeitos dos fármacos , Vitaminas/uso terapêutico , Idoso , Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Ensaios Clínicos como Assunto , Suplementos Nutricionais , Terapia Genética , Humanos , Degeneração Macular/metabolismo , Degeneração Macular/patologia , Transplante de Células-Tronco , Resultado do Tratamento , Vitaminas/administração & dosagem
14.
PLoS One ; 15(3): e0229342, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32155173

RESUMO

We aimed to construct a better model for predicting treatment outcomes of anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration (nAMD) using the concentrations of aqueous humour proteins at baseline and during treatment. From the data of 48 treatment-naïve nAMD eyes that received intravitreal ranibizumab pro re nata for up to 12 months, we used the aqueous humour concentrations of C-X-C motif chemokine ligand 1 (CXCL1), CXCL12, CXCL13, interferon-γ-induced protein 10, monocyte chemoattractant protein 1 (MCP-1), C-C motif chemokine ligand 11, interleukin 6 (IL-6), IL-10, and matrix metalloproteinase 9 (MMP-9). After stepwise regression, multivariate analysis was performed to identify which predictors were significantly associated with best-corrected visual acuity (BCVA) changes and the number of injections. The results demonstrated that besides male sex (ß coefficient = -0.088, P = 0.040) and central retinal thickness (ß coefficient = 0.00051 per µm, P = 0.027), MCP-1 (ß coefficient = 0.44, P < 0.001) and IL-10 (ß coefficient = -0.16, P = 0.033) were significantly correlated with baseline BCVA. Additionally, high MCP-1 at baseline (ß coefficient = -0.20, P = 0.015) and low CXCL13 at baseline (ß coefficient = 0.10, P = 0.0054) were independently associated with better BCVA change at 12 months. High MMP-9 at the first injection (ß coefficient = 0.56, P = 0.01), CXCL12 at the third injection (ß coefficient = 0.10, P = 0.0002), and IL-10 at the third injection (ß coefficient = 1.3, P = 0.001) were predictor variables associated with the increased number of injections. In conclusion, aqueous humour protein concentrations may have predictive abilities of BCVA change over 12 months and the number of injections in pro re nata treatment of exudative nAMD.


Assuntos
Humor Aquoso/metabolismo , Proteínas do Olho/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Degeneração Macular/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Ranibizumab/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Idoso , Inibidores da Angiogênese/uso terapêutico , Feminino , Humanos , Degeneração Macular/metabolismo , Degeneração Macular/patologia , Masculino , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Estudos Prospectivos , Resultado do Tratamento
15.
Invest Ophthalmol Vis Sci ; 61(3): 2, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32150251

RESUMO

Purpose: The purpose of this study was to examine changes in the ganglion cell layer (GCL) of individuals with intermediate age-related macular degeneration (AMD) using grid-wise analysis for macular optical coherence tomography (OCT) volume scans. We also aim to validate the use of age-correction functions for GCL thickness in diseased eyes. Methods: OCT macular cube scans covering 30° × 25° were acquired using Spectralis spectral-domain OCT for 87 eyes with intermediate AMD, 77 age-matched normal eyes, and 254 non-age-matched normal eyes. The thickness of the ganglion cell layer (GCL) was defined after segmentation at 60 locations across an 8 × 8 grid centered on the fovea, where each grid location covered 0.74 mm2 (approximately 3° × 3°) within the macula. Each GCL location of normal eyes (n = 77) were assigned to a specific iso-ganglion cell density cluster in the macula, based on patterns of age-related GCL thickness loss. Analyses were then performed comparing AMD GCL grid-wise data against corresponding spatial clusters, and significant AMD GCL thickness changes were denoted as values outside the 95% distribution limits. Results: Analysis of GCL thickness changes revealed significant differences between spatial clusters, with thinning toward the fovea, and thickening toward the peripheral macula. The direction of GCL thickness changes in AMD were associated more so with thickening than thinning in all analyses. Results were corroborated by the application of GCL thickness age-correction functions. Conclusions: GCL thickness changed significantly and nonuniformly within the macula of intermediate AMD eyes. Further characterization of these changes is critical to improve diagnoses and monitoring of GCL-altering pathologies.


Assuntos
Macula Lutea/patologia , Degeneração Macular/patologia , Células Ganglionares da Retina/patologia , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Estudos de Casos e Controles , Feminino , Humanos , Macula Lutea/diagnóstico por imagem , Degeneração Macular/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos
16.
PLoS One ; 15(2): e0229388, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32101581

RESUMO

Treatment of neovascular age-related macular degeneration (nAMD) with VEGF can be performed with several posologies. The purpose of our cross-sectional study was to analyze retinal vessel density by quantitative OCT-angiography (OCT-A) and to compare treat-and-extend (T&E) and fixed treatment protocols to a control group with dry AMD. Altogether 48 patients were enrolled: 13 eyes with T&E protocol ranibizumab treatment (group A) and 17 eyes with fixed regimen aflibercept therapy (group B), the control group comprised 18 eyes with dry AMD (group C). One year after the start of the treatment, quantitative OCT-A (AngioVue-Optovue, Fermont, USA) was performed: superficial and deep retinal vessel densities were analyzed in the foveal and parafoveal regions. Our results show, that the density of retinal superficial vasculature in the fovea was not different between the treatment groups (A: 25.9±9.1%; B: 24.3%±8.9), neither from group C (25.6±4.8%). Superficial parafoveal vascular density of the retina, however, was decreased in both treated groups (A: 46.7±9.1%, B: 42.9±6.1%, C: 49.7±4.9%). In the deep retinal plexus, vascular density was lower in both treatment groups compared to that of in controls in both the foveal and parafoveal area (A: 29.8±6.3%, B: 32.5±6.9%, C: 36.4±1.7% and A: 46.3±3.8%, B: 47.1±5.3%, C: 49.7±4.9%, foveal and parafoveal respectively). Our data suggest, that after one year of anti-VEGF treatment, reduced macular vessel density in three of the four examined vascular regions can be found independent of the treatment regimen.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Degeneração Macular/patologia , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Vasos Retinianos/patologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Idoso , Estudos de Casos e Controles , Estudos Transversais , Feminino , Fóvea Central/efeitos dos fármacos , Fóvea Central/patologia , Humanos , Degeneração Macular/tratamento farmacológico , Masculino , Estudos Prospectivos , Vasos Retinianos/efeitos dos fármacos , Retratamento , Fatores de Tempo
17.
Invest Ophthalmol Vis Sci ; 61(2): 9, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-32049341

RESUMO

Purpose: Variant B precursor cysteine protease inhibitor cystatin C, a known recessive risk factor for developing exudative age-related macular degeneration (AMD), presents altered intracellular trafficking and reduced secretion from retinal pigment epithelial (RPE) cells. Because cystatin C inhibits multiple extracellular matrix (ECM)-degrading cathepsins, this study evaluated the role of this mutation in inducing ECM-related functional changes in RPE cellular behavior. Methods: Induced pluripotent stem cells gene-edited bi-allelically by CRISPR/Cas9 to express the AMD-linked cystatin C variant were differentiated to RPE cells and assayed for their ability to degrade fluorescently labeled ECM proteins. Cellular migration and adhesion on multiple ECM proteins, differences in transepithelial resistance and polarized protein secretion were tested. Vessel formation induced by gene edited cells-conditioned media was quantified using primary human dermal microvascular epithelial cells. Results: Variant B cystatin C-expressing induced pluripotent stem cells-derived RPE cells displayed a significantly higher rate of laminin and fibronectin degradation 3 days after seeding on fluorescently labeled ECM (P < 0.05). Migration on matrigel, collagen IV and fibronectin was significantly faster for edited cells compared with wild-type (WT) cells. Both edited and WT cells displayed polarized secretion of cystatin C, but transepithelial resistance was lower in gene-edited cells after 6 weeks culture, with significantly lower expression of tight junction protein claudin-3. Media conditioned by gene-edited cells stimulated formation of significantly longer microvascular tubes (P < 0.05) compared with WT-conditioned media. Conclusions: Reduced levels of cystatin C lead to changes in the RPE ability to degrade, adhere, and migrate supporting increased invasiveness and angiogenesis relevant for AMD pathology.


Assuntos
Cistatina C/fisiologia , Células-Tronco Pluripotentes Induzidas/fisiologia , Degeneração Macular/patologia , Epitélio Pigmentado da Retina/citologia , Movimento Celular/fisiologia , Células Cultivadas , Cistatina C/genética , Cistatina C/metabolismo , Fibronectinas/metabolismo , Edição de Genes , Humanos , Laminina/metabolismo , Mutação Puntual/genética
18.
Nat Commun ; 11(1): 778, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034129

RESUMO

Age-related macular degeneration (AMD) is a leading cause of blindness. Genetic variants at the chromosome 1q31.3 encompassing the complement factor H (CFH, FH) and CFH related genes (CFHR1-5) are major determinants of AMD susceptibility, but their molecular consequences remain unclear. Here we demonstrate that FHR-4 plays a prominent role in AMD pathogenesis. We show that systemic FHR-4 levels are elevated in AMD (P-value = 7.1 × 10-6), whereas no difference is seen for FH. Furthermore, FHR-4 accumulates in the choriocapillaris, Bruch's membrane and drusen, and can compete with FH/FHL-1 for C3b binding, preventing FI-mediated C3b cleavage. Critically, the protective allele of the strongest AMD-associated CFH locus variant rs10922109 has the highest association with reduced FHR-4 levels (P-value = 2.2 × 10-56), independently of the AMD-protective CFHR1-3 deletion, and even in those individuals that carry the high-risk allele of rs1061170 (Y402H). Our findings identify FHR-4 as a key molecular player contributing to complement dysregulation in AMD.


Assuntos
Apolipoproteínas/genética , Apolipoproteínas/metabolismo , Degeneração Macular/sangue , Polimorfismo de Nucleotídeo Único , Idoso , Apolipoproteínas/sangue , Capilares/metabolismo , Estudos de Casos e Controles , Ativação do Complemento , Fator H do Complemento/metabolismo , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Haplótipos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas com Domínio LIM/metabolismo , Fígado/fisiologia , Degeneração Macular/genética , Degeneração Macular/patologia , Proteínas Musculares/metabolismo , Retina/metabolismo , Retina/patologia
19.
PLoS One ; 15(2): e0229504, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32106279

RESUMO

BACKGROUND/OBJECTIVE: A subset of neovascular age-related macular degeneration (nvAMD) subjects appears to be refractory to the effects of anti-VEGF treatment and require frequent intravitreal injections. The vascular phenotype of the choroidal neovascular (CNV) lesions may contribute to the resistance. Animal studies of CNV lesions have shown that cells originating from bone marrow are capable of forming varying cell types in the lesions. This raised the possibility of a similar cell population in human nvAMD subjects. MATERIALS AND METHODS: Blood draws were obtained from subjects with active nvAMD while patients were receiving standard of care anti-VEGF injections. Subjects were classified as refractory or non-refractory to anti-VEGF treatment based on previous number of injections in the preceding 12 months. Peripheral blood mononuclear cells (PBMCs) were isolated and CD34-positive cells purified using magnetic bead sorting. The isolated cells were expanded in StemSpan SFEM media to increase cell numbers. After expansion, the cells were split and plated in either endothelial or mesenchymal promoting conditions. Phenotype analysis was performed via qPCR. RESULTS: There was no significant difference in the number of PBMCs and CD34-positive cells between refractory and non-refractory nvAMD subjects. The growth pattern distribution between endothelial and mesenchymal media conditions were very similar between refractory and non-refractory subjects. qPCR and immunostaining demonstrated positive expression of endothelial markers in endothelial media, and markers such as NG2 and αSMA in mesenchymal media. However, analysis of subsequent samples from AMD subjects demonstrated high variability in both the numbers and differentiation properties of this cell population. CONCLUSIONS: CD34+ cells can be isolated from nvAMD subjects and show both endothelial and pericyte-like characteristics after differentiation in certain media conditions. However, nvAMD subjects show high variability in both numbers of cells and differentiation characteristics in repeat sampling. This variability highlights the importance of taking multiple samples from nvAMD subjects for any clinical trials focused on biomarkers for the disease.


Assuntos
Neovascularização de Coroide/sangue , Neovascularização de Coroide/patologia , Degeneração Macular/sangue , Degeneração Macular/patologia , Células-Tronco/patologia , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Antígenos CD34/sangue , Diferenciação Celular , Proliferação de Células , Separação Celular , Neovascularização de Coroide/tratamento farmacológico , Resistência a Medicamentos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Feminino , Humanos , Degeneração Macular/tratamento farmacológico , Masculino , Pericitos/metabolismo , Pericitos/patologia , Células-Tronco/metabolismo , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
20.
Invest Ophthalmol Vis Sci ; 61(2): 15, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-32053726

RESUMO

Purpose: To investigate the retinal sensitivity of highly myopic eyes with chorioretinal patchy atrophy (PA) using microperimetry. Methods: Fifty-two eyes of 32 patients with high myopia were prospectively included. Twenty-two eyes of 16 patients had PA lesions; eyes without PA were analyzed as controls. Testing points on microperimetry in eyes with PA were designated as 3 zones: zone 1 as the PA lesion including its borders; zone 2 including testing points adjoining PA; zone 3 including all other testing points. Results: In the PA group, the mean retinal sensitivity in zone 1 was 2.1 ± 2.8 dB, zone 2 = 8.3 ± 4.3 dB, and zone 3 = 9.4 ± 4.1 dB. Sensitivity in zone 1 was significantly reduced than zones 2 and 3 (P < 0.001). The mean retinal sensitivity in the PA group was lower than controls (6.5 ± 4.3 vs 13.9 ± 4.1 dB, P < 0.001), and combined zone 2 and 3 in the PA group also presented lower retinal sensitivity (8.8 ± 4.0 dB). Conclusions: Eyes with PA generate patchy scotoma in PA lesions and reduced retinal sensitivity in regions beyond atrophic lesion on microperimetry. The presence of PA may be an indicator to reflect both significantly anatomical and functional alterations on myopic macular degeneration.


Assuntos
Degeneração Macular/patologia , Miopia/patologia , Escotoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Lâmina Basilar da Corioide/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia de Coerência Óptica
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