RESUMO
The retina is increasingly recognised as a potential source of biomarkers for neurodegenerative diseases. Hallmark protein aggregates in the retinal neuronal tissue could be imaged through light non-invasively. Post-mortem studies have already shown the presence of specific hallmark proteins in Alzheimer's disease, primary tauopathies, synucleinopathies and frontotemporal lobar degeneration. This study aims to assess proteinopathy in a post-mortem cohort with different neurodegenerative diseases and assess the presence of the primary pathology in the retina. Post-mortem eyes were collected in collaboration with the Netherlands Brain Bank from donors with Alzheimer's disease (n = 17), primary tauopathies (n = 8), synucleinopathies (n = 27), frontotemporal lobar degeneration (n = 8), mixed pathology (n = 11), other neurodegenerative diseases (n = 6), and cognitively normal controls (n = 25). Multiple cross sections of the retina and optic nerve tissue were immunostained using antibodies against pTau Ser202/Thr205 (AT8), amyloid-beta (4G8), alpha-synuclein (LB509), pTDP-43 Ser409/410 and p62-lck ligand (p62) and were assessed for the presence of aggregates and inclusions. pTau pathology was observed as a diffuse signal in Alzheimer's disease, primary tauopathies and controls with Alzheimer's disease neuropathological changes. Amyloid-beta was observed in the vessel wall and as cytoplasmic granular deposits in all groups. Alpha-synuclein pathology was observed as Lewy neurites in the retina in synucleinopathies associated with Lewy pathology and as oligodendroglial cytoplasmic inclusions in the optic nerve in multiple system atrophy. Anti-pTDP-43 generally showed typical neuronal cytoplasmic inclusion bodies in cases with frontotemporal lobar degeneration with TDP-43 and also in cases with later stages of limbic-associated TDP-43 encephalopathy. P62 showed inclusion bodies similar to those seen with anti-pTDP-43. Furthermore, pTau and alpha-synuclein pathology were significantly associated with increasing Braak stages for neurofibrillary tangles and Lewy bodies, respectively. Mixed pathology cases in this cohort consisted of cases (n = 6) with high Braak LB stages (> 4) and low or moderate AD pathology, high AD pathology (n = 1, Braak NFT 6, Thal phase 5) with moderate LB pathology, or a combination of low/moderate scores for different pathology scores in the brain (n = 4). There were no cases with advanced co-pathologies. In seven cases with Braak LB ≥ 4, LB pathology was observed in the retina, while tau pathology in the retina in the mixed pathology group (n = 11) could not be observed. From this study, we conclude that the retina reflects the presence of the major hallmark proteins associated with neurodegenerative diseases. Although low or moderate levels of copathology were found in the brains of most cases, the retina primarily manifested protein aggregates associated with the main neurodegenerative disease. These findings indicate that with appropriate retinal imaging techniques, retinal biomarkers have the potential to become highly accurate indicators for diagnosing the major neurodegenerative diseases of the brain.
Assuntos
Doenças Neurodegenerativas , Retina , Proteínas tau , Humanos , Idoso , Feminino , Masculino , Retina/patologia , Retina/metabolismo , Idoso de 80 Anos ou mais , Doenças Neurodegenerativas/patologia , Doenças Neurodegenerativas/metabolismo , Proteínas tau/metabolismo , Pessoa de Meia-Idade , alfa-Sinucleína/metabolismo , Autopsia , Tauopatias/patologia , Tauopatias/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Proteínas de Ligação a DNA/metabolismoRESUMO
The retina is a potential source of biomarkers for the detection of neurodegenerative diseases. Accumulation of phosphorylated tau (p-tau) in the brain is a pathological feature characteristic for Alzheimer's disease (AD) and primary tauopathies. In this study the presence of p-tau in the retina in relation to tau pathology in the brain was assessed. Post-mortem eyes and brains were collected through the Netherlands Brain Bank from donors with AD (n = 17), primary tauopathies (n = 8), α-synucleinopathies (n = 13), other neurodegenerative diseases including non-tau frontotemporal lobar degeneration (FTLD) (n = 9), and controls (n = 15). Retina cross-sections were assessed by immunohistochemistry using antibodies directed against total tau (HT7), 3R and 4R tau isoforms (RD3, RD4), and phospho-epitopes Ser202/Thr205 (AT8), Thr217 (anti-T217), Thr212/Ser214 (AT100), Thr181 (AT270), Ser396 (anti-pS396) and Ser422 (anti-pS422). Retinal tau load was compared to p-tau Ser202/Thr205 and p-tau Thr217 load in various brain regions. Total tau, 3R and 4R tau isoforms were most prominently present in the inner plexiform layer (IPL) and outer plexiform layer (OPL) of the retina and were detected in all cases and controls as a diffuse and somatodendritic signal. Total tau, p-tau Ser202/Thr205 and p-tau Thr217 was observed in amacrine and horizontal cells of the inner nuclear layer (INL). Various antibodies directed against phospho-epitopes of tau showed immunoreactivity in the IPL, OPL, and INL. P-tau Ser202/Thr205 and Thr217 showed significant discrimination between AD and other tauopathies, and non-tauopathy cases including controls. Whilst immunopositivity was observed for p-tau Thr212/Ser214, Thr181 and Ser396, there were no group differences. P-tau Ser422 did not show any immunoreactivity in the retina. The presence of retinal p-tau Ser202/Thr205 and Thr217 correlated with Braak stage for NFTs and with the presence of p-tau Ser202/Thr205 in hippocampus and cortical brain regions. Depending on the phospho-epitope, p-tau in the retina is a potential biomarker for AD and primary tauopathies.
Assuntos
Doença de Alzheimer , Tauopatias , Humanos , Doença de Alzheimer/patologia , Fosforilação , Proteínas tau/metabolismo , Tauopatias/patologia , Encéfalo/patologia , Retina/patologia , EpitoposRESUMO
BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia, and due to increasing life expectancy the number of patients is expected to grow. The diagnosis of AD involves the use of biomarkers determined by an amyloid PET scan or cerebrospinal fluid analyses that are either invasive or expensive, and not available in each hospital, thus limiting their usage as a front-line screener. The TearAD study aims to use tear fluid as a potential source for AD biomarkers. In previous reports, we demonstrated that AD biomarkers amyloid-beta and tau, are measurable in tear fluid and are associated with disease severity and neurodegeration. This study aims to validate previous results in a larger cohort and evaluate the diagnostic accuracy of tear biomarkers to discriminate between individuals with and without neurodegeneration as determined by hippocampal atrophy. METHODS: The TearAD study is an observational longitudinal multi-center study that will enroll 50 cognitively healthy controls, 50 patients with subjective cognitive decline, 50 patients with mild cognitive impairment and 50 patients with AD dementia from the memory clinic. Participants will be examined at baseline, after one year, and after two years follow-up. Study assessments include neuropsychological tests and ophthalmic examination. All participants will receive a MRI scan, and a subset of the study population will undergo cerebral spinal fluid collection and an amyloid PET scan. Tear fluid will be collected with Schirmer strips and levels of Aß38, Aß40, Aß42, t-tau and p-tau in tear fluid will be determined using multiplex immunoassays. Blood samples will be collected from all participants. Images of the retina will be obtained with a standard, hyperspectral and ultra-wide field fundus camera. Additionally, macular pigment optical density will be measured with the macular pigment reflectometer, and cross-sectional images of the retina will be obtained through optical coherence tomography imaging. DISCUSSION: The TearAD study will provide insight into the potential diagnostic use of tear biomarkers as a minimally invasive and low cost tool for the screening and diagnosis of AD. TRIAL REGISTRATION: Retrospectively registered at clinicaltrials.gov (NCT05655793).
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Pigmento Macular , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Disfunção Cognitiva/psicologia , Biomarcadores/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Fragmentos de PeptídeosRESUMO
PURPOSE: To evaluate the impact of the COVID-19 pandemic lockdowns on the outcomes of eyes treated for neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion in eight countries. METHODS: A multicenter international database study of 5,782 eyes (4,708 patients) receiving intravitreal antivascular endothelial growth factor injections before, during, and after national lockdowns. The baseline visit was defined as the last visit within 3 months before lockdown, and prelockdown and postlockdown periods were defined as 6 months before and after the lockdown date. RESULTS: Eyes with neovascular age-related macular degeneration (n = 4,649) lost vision in all countries in proportion to the reduced number of injections. The mean visual acuity change postlockdown ranged from -0.4 to -3.8 logarithm of the minimum angle of resolution letters, and the median number of injections/visits decreased from 4-5/4-7 to 2-4/2-4 postlockdown. The diabetic macular edema (n = 654) and retinal vein occlusion (n = 479) eyes' mean visual acuity change ranged from -2.8 to +1.7 letters and -1.6 to +0.1 letters, and the median number of injections/visits decreased from 2.5-5/4-6 to 1-3/2-4 and from 3-5.5/4-5 to 1-3.5/2-3.5, respectively. The 6-month dropout rates postlockdown were 20% for neovascular age-related macular degeneration, 27% for diabetic macular edema, and 28% for retinal vein occlusion. CONCLUSION: This international study provides estimates of the impact of COVID-19 pandemic lockdown on intravitreal therapy and suggests that prioritizing neovascular age-related macular degeneration eyes seems appropriate.
Assuntos
COVID-19 , Retinopatia Diabética , Edema Macular , Inibidores da Angiogênese/uso terapêutico , Cegueira/tratamento farmacológico , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Retinopatia Diabética/complicações , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/epidemiologia , Humanos , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Edema Macular/epidemiologia , Pandemias , Ranibizumab/uso terapêutico , Sistema de Registros , Estudos Retrospectivos , Resultado do Tratamento , Fator A de Crescimento do Endotélio VascularRESUMO
PURPOSE: To determine which demographic and clinical characteristics are predictive of vision-related quality of life (VrQoL) and quality of life (QoL) in patients with macular oedema receiving intravitreal anti-vascular endothelial growth factor (VEGF) treatment. METHODS: Vision-related quality of life (VrQoL) and quality of life (QoL) were measured in 712 patients with retinal exudative disease receiving anti-VEGF treatment at baseline, 6 and 12 months. VrQoL was measured using an item-response theory based 47-question item bank (EyeQ), whereas QoL was measured using the EuroQol Five Dimensions (EQ-5D) questionnaire. The EQ-5D score was dichotomized into a perfect score of 1 and a suboptimal score of <1. Demographic and clinical patient characteristics were considered as possible predictors of (Vr)QoL. Prediction models for (Vr)QoL were created with linear mixed models and generalised estimating equations, using a forward selection procedure. RESULTS: A worse VrQoL was predicted by poorer LogMAR visual acuity of the better eye, female sex, single civil status, older age, longer length of anti-VEGF treatment at baseline and the presence of non-ocular and ocular comorbidities. Suboptimal EQ-5D scores were predicted by poorer LogMAR visual acuity of the better eye, female sex, single civil status, older age, the presence of non-ocular comorbidities and a lower educational background. CONCLUSIONS: Along with visual acuity of the better eye, which is the main factor used in clinical decision making, other patient characteristics should also be considered for the risk assessment of (Vr)QoL, such as sex, age, civil status, comorbidities and length of anti-VEGF treatment.
Assuntos
Edema Macular , Inibidores da Angiogênese/uso terapêutico , Feminino , Humanos , Injeções Intravítreas , Edema Macular/induzido quimicamente , Edema Macular/tratamento farmacológico , Qualidade de Vida , Ranibizumab/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Transtornos da Visão , Acuidade VisualRESUMO
PURPOSE: E-PsEYE is an internet-based, guided self-help course, following the principles of cognitive behavioural therapy, to reduce anxiety and depression in patients with retinal exudative diseases who receive anti-vascular endothelial growth factor (anti-VEGF) treatment. The purpose of this study was to determine the prevalence and related factors of anxiety and depression in this population and evaluate the usability and feasibility of E-PsEYE. METHODS: Symptoms of anxiety and depression and related factors were determined in 90 patients (mean age 77 years, 58% female), based on multiple logistic regression analysis. Five patients with mild to moderate depression/anxiety tested the usability of E-PsEYE. They were asked to think aloud while completing two modules of the intervention and freely explore system features. The feasibility of the total E-PsEYE intervention was tested in 14 patients with mild to moderate depression/anxiety, based on a single arm pre-post study with a follow-up of three months: fidelity, acceptability, feasibility of study methods and potential effectiveness were explored. RESULTS: Fifty-three percent of the total study population experienced at least mild anxiety and/or depression symptoms. Especially female patients (odds ratio (OR) 3.89, 95% confidence interval (CI) 1.33-11.40), those who experienced limitations in daily life activities due to vision loss (OR 9.67; 95% CI 3.18-29.45) and those who experienced loneliness (OR 3.53, 95% CI 1.14-10.95) were more likely to have anxiety/depression. The usability study raised several possibilities for improvement, based on which E-PsEYE was improved. The feasibility study showed adequate fidelity and acceptability. Most participants were satisfied with the results (79%). There was a high response rate, no loss to follow-up and mental health problems decreased in more than half of the patients. The Wilcoxon signed rank test indicated lower post-test ranks compared to pre-test ranks (depression Z -1.34, p = 0.18; anxiety Z -1.45, p = 0.15). CONCLUSIONS: Mental health problems are prevalent in patients who receive anti-VEGF treatment. Healthcare providers should recognise these problems and related factors in order to refer patients to appropriate care in a timely manner. Outcomes on the usability and feasibility of E-PsEYE are promising as a prelude to performing a randomised controlled trial, which will shed more light on its (cost-)effectiveness.
Assuntos
Depressão , Saúde Mental , Idoso , Ansiedade , Depressão/epidemiologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Projetos PilotoRESUMO
BACKGROUND: Ocular imaging receives much attention as a source of potential biomarkers for dementia. In the present study, we analyze these ocular biomarkers in cognitively impaired and healthy participants in a population aged over 90 years (= nonagenarian), and elucidate the effects of age on these biomarkers. METHODS: For this prospective cross-sectional study, we included individuals from the EMIF-AD 90+ study, consisting of a cognitively healthy (N = 67) and cognitively impaired group (N = 33), and the EMIF-AD PreclinAD study, consisting of cognitively healthy controls aged ≥60 (N = 198). Participants underwent Optical Coherence Tomography (OCT) and fundus photography of both eyes. OCT was used to asses total and individual inner retinal layer thickness in the macular region (Early Treatment Diabetic Retinopathy Study circles) as well as peripapillary retinal nerve fiber layer thickness, fundus images were analyzed with Singapore I Vessel Assessment to obtain 7 retinal vascular parameters. Values for both eyes were averaged. Differences in ocular biomarkers between the 2 nonagenarian groups were analyzed using linear regression, differences between the individual nonagenarian groups and controls were analyzed using generalized estimating equations. RESULTS: Ocular biomarkers did not differ between the healthy and cognitively impaired nonagenarian groups. 19 out of 22 ocular biomarkers assessed in this study differed between either nonagenarian group and the younger controls. CONCLUSION: The ocular biomarkers assessed in this study were not associated with cognitive impairment in nonagenarians, making their use as a screening tool for dementing disorders in this group limited. However, ocular biomarkers were significantly associated with chronological age, which were very similar to those ascribed to occur in Alzheimer's Disease.
Assuntos
Disfunção Cognitiva/complicações , Olho/diagnóstico por imagem , Doenças Retinianas/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Disfunção Cognitiva/diagnóstico por imagem , Estudos Transversais , Feminino , Fundo de Olho , Humanos , Masculino , Estudos Prospectivos , Retina/diagnóstico por imagem , SingapuraRESUMO
A new metric is used to improve the contrast of birefringent structures in biological tissue using polarization-sensitive optical coherence tomography. This metric, optic axis uniformity (OAxU), is based on the optic axis of birefringence and quantifies the uniformity of the optic axis direction. OAxU provides surprisingly strong contrast for fibrous structures such as muscle and the retinal nerve fiber layer (RNFL). We used OAxU for automatic segmentation of the RNFL in human eyes. From the segmentation, en face images of RNFL thickness and RNFL birefringence were created. The measured birefringence values are consistent with earlier reports.
RESUMO
Diabetic retinopathy (DR) has long been recognized as a microvasculopathy, but retinal diabetic neuropathy (RDN), characterized by inner retinal neurodegeneration, also occurs in people with diabetes mellitus (DM). We report that in 45 people with DM and no to minimal DR there was significant, progressive loss of the nerve fiber layer (NFL) (0.25 µm/y) and the ganglion cell (GC)/inner plexiform layer (0.29 µm/y) on optical coherence tomography analysis (OCT) over a 4-y period, independent of glycated hemoglobin, age, and sex. The NFL was significantly thinner (17.3 µm) in the eyes of six donors with DM than in the eyes of six similarly aged control donors (30.4 µm), although retinal capillary density did not differ in the two groups. We confirmed significant, progressive inner retinal thinning in streptozotocin-induced "type 1" and B6.BKS(D)-Lepr(db)/J "type 2" diabetic mouse models on OCT; immunohistochemistry in type 1 mice showed GC loss but no difference in pericyte density or acellular capillaries. The results suggest that RDN may precede the established clinical and morphometric vascular changes caused by DM and represent a paradigm shift in our understanding of ocular diabetic complications.
Assuntos
Retinopatia Diabética/patologia , Microvasos/patologia , Microvasos/fisiopatologia , Doenças Neurodegenerativas/patologia , Degeneração Retiniana/patologia , Adulto , Animais , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/fisiopatologia , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/fisiopatologia , Degeneração Retiniana/diagnóstico , Degeneração Retiniana/fisiopatologia , Especificidade da EspécieRESUMO
PURPOSE: To establish the predictive value of specific optical coherence tomography retinal features on visual outcomes and retinal thickness during anti-vascular endothelial growth factor treatment in patients with diabetic macular edema. METHODS: Post hoc analysis of compound data of a prospective, 6-month, multicenter, randomized controlled trial of 119 patients with diabetic macular edema receiving either intravitreal bevacizumab or ranibizumab were analyzed to assess the associations between baseline retinal morphologic parameters and change in best-corrected visual acuity and central subfield thickness. Based on the study protocol of the core study, best-corrected visual acuity and central subfield thickness were obtained before each mandatory monthly injection during 6 months. RESULTS: The presence of serous retinal detachment at baseline was associated with significant improvement in best-corrected visual acuity letter score at Month 3 and Month 6 (P < 0.001 and P = 0.01, respectively). In addition, the presence of disorganization of retinal inner layers was associated with lower best-corrected visual acuity letter score at Month 3 and Month 6 (P < 0.05 and P = 0.01, respectively). CONCLUSION: This study found that serous retinal detachment and disorganization of retinal inner layers were associated with different treatment responses to anti-vascular endothelial growth factor therapy in patients with diabetic macular edema.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Edema Macular/tratamento farmacológico , Ranibizumab/uso terapêutico , Tomografia de Coerência Óptica/normas , Idoso , Análise de Variância , Retinopatia Diabética/diagnóstico por imagem , Retinopatia Diabética/fisiopatologia , Feminino , Humanos , Injeções Intravítreas , Edema Macular/diagnóstico por imagem , Edema Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Acuidade VisualRESUMO
BACKGROUND: The oldest-old (subjects aged 90 years and older) population represents the fastest growing segment of society and shows a high dementia prevalence rate of up to 40%. Only a few studies have investigated protective factors for cognitive impairment in the oldest-old. The EMIF-AD 90+ Study aims to identify factors associated with resilience to cognitive impairment in the oldest-old. In this paper we reviewed previous studies on cognitive resilience in the oldest-old and described the design of the EMIF-AD 90+ Study. METHODS: The EMIF-AD 90+ Study aimed to enroll 80 cognitively normal subjects and 40 subjects with cognitive impairment aged 90 years or older. Cognitive impairment was operationalized as amnestic mild cognitive impairment (aMCI), or possible or probable Alzheimer's Disease (AD). The study was part of the European Medical Information Framework for AD (EMIF-AD) and was conducted at the Amsterdam University Medical Centers (UMC) and at the University of Manchester. We will test whether cognitive resilience is associated with cognitive reserve, vascular comorbidities, mood, sleep, sensory system capacity, physical performance and capacity, genetic risk factors, hallmarks of ageing, and markers of neurodegeneration. Markers of neurodegeneration included an amyloid positron emission tomography, amyloid ß and tau in cerebrospinal fluid/blood and neurophysiological measures. DISCUSSION: The EMIF-AD 90+ Study will extend our knowledge on resilience to cognitive impairment in the oldest-old by extensive phenotyping of the subjects and the measurement of a wide range of potential protective factors, hallmarks of aging and markers of neurodegeneration. TRIAL REGISTRATION: Nederlands Trial Register NTR5867 . Registered 20 May 2016.
Assuntos
Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/psicologia , Envelhecimento Saudável/psicologia , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Cognição/fisiologia , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/metabolismo , Feminino , Envelhecimento Saudável/metabolismo , Humanos , Masculino , Testes NeuropsicológicosRESUMO
BACKGROUND: Diabetic retinopathy (DRP) is a common microvascular complication seen in patients with type 1 diabetes mellitus (T1DM). The effects of T1DM and concomitant (proliferative) DRP on retinal blood flow are currently unclear. Therefore, we measured retinal vascular blood flow in T1DM patients with and without DRP and non-diabetic controls. We further assessed the acute effects of panretinal photocoagulation on retinal microvascular bloodflow in eight patients with diabetes. METHODS: Thirty-three T1DM patients with proliferative DRP, previously treated with panretinal photocoagulation (pDRP), 11 T1DM patients with untreated non-proliferative retinopathy (npDRP) and 32 T1DM patients without DRP (nDRP) were compared with 44 non-diabetic gender-matched controls. Using scanning laser Doppler flowmetry (HRF, Heidelberg) blood flow in the retinal microvasculature was measured temporal and nasal of the optic disc and averaged into one flow value per eye. The right eye was used as a default for further analyses. Eight patients with novel proliferative retinopathy (4 T1DM and 4 with type 2 diabetes) were measured before and several months after photocoagulation. Between-group differences in retinal blood flow were assessed using ANOVA corrected for multiple comparisons (Bonferroni). RESULTS: Retinal blood flow was higher in the treated pDRP compared with the nDRP group and controls (all P Bonferroni < 0.01). Furthermore, there was a positive linear trend for blood flow with lowest blood flow in the control group and highest in the pDRP group (P-for-trend < 0.01). In the eight patients with novel proliferative retinopathy, blood flow did not significantly change before and after panretinal photocoagulation (P > 0.05). Using regression analysis, no variables were found as predictors of retinal blood flow. CONCLUSIONS: In comparison with controls and nDRP patients, retinal blood flow significantly increased in the pDRP group, which previously underwent photocoagulation treatment, but not in the npDRP patients. These changes may be a consequence of a failing vascular autoregulation in advanced diabetic retinopathy.
Assuntos
Diabetes Mellitus Tipo 1/complicações , Retinopatia Diabética/fisiopatologia , Adulto , Retinopatia Diabética/cirurgia , Progressão da Doença , Feminino , Humanos , Fluxometria por Laser-Doppler , Fotocoagulação , Masculino , Microcirculação , Pessoa de Meia-Idade , Fluxo Sanguíneo RegionalRESUMO
PURPOSE: To characterize the relevance of macular thickness changes in the inner and outer rings in the progression of macular edema in eyes/patients with diabetes type 2. METHODS: A total of 374 type 2 diabetic patients with mild nonproliferative diabetic retinopathy (ETDRS levels 20-35) were included in a 12-month prospective observational study to identify retinopathy progression. Retinal thickness analyses were performed in 194 eyes/patients using Cirrus SD- OCT and 166 eyes/patients using Spectralis SD-OCT. The DRCR.net classification of subclinical and clinical macular edema was used. A composite grading of macular edema is proposed in this study. RESULTS: A total of 317 eyes/patients completed the study. SD-OCT identified clinical macular edema in 24 eyes/patients (6.7%) and subclinical macular edema in 104 eyes/patients (28.9%) at baseline. Increased thickness of the central subfield is the best predictor for the development of clinical macular edema, with 85.7% sensitivity and 71.9% specificity (OR: 2.57, 95% CI: 0.82-7.99). However, the involvement of the inner and outer rings is a cumulative predictor of progression to clinical macular edema (OR: 8.69, 95% CI: 2.85-26.52). CONCLUSIONS: A composite OCT grading of macular edema taking into account the retinal thickness changes in the inner and outer macular rings offers a simple way to characterize macular edema, with added clinical value.
Assuntos
Retinopatia Diabética/diagnóstico , Edema Macular/classificação , Edema Macular/diagnóstico , Retina/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/classificação , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos Prospectivos , Sensibilidade e Especificidade , Tomografia de Coerência Óptica , Acuidade Visual/fisiologiaRESUMO
PURPOSE: To identify the retinal layer predominantly affected in eyes with subclinical and clinical macular edema in diabetes type 2. METHODS: A cohort of 194 type 2 diabetic eyes/patients with mild nonproliferative diabetic retinopathy (ETDRS levels 20/35) were examined with Cirrus spectral-domain optical coherence tomography (OCT) at the baseline visit (ClinicalTrials.gov identifier: NCT01145599). Automated segmentation of the retinal layers of the eyes with subclinical and clinical macular edema was compared with a sample of 31 eyes from diabetic patients with normal OCT and an age-matched control group of 58 healthy eyes. RESULTS: From the 194 eyes in the study, 62 had subclinical macular edema and 12 had clinical macular edema. The highest increases in retinal thickness (RT) were found in the inner nuclear layer (INL; 33.6% in subclinical macular edema and 81.8% in clinical macular edema). Increases were also found in the neighboring layers. Thinning of the retina was registered in the retinal nerve fiber, ganglion cells and inner plexiform layers in the diabetic eyes without macular edema. CONCLUSIONS: The increase in RT occurring in diabetic eyes with macular edema is predominantly located in the INL but extends to neighboring retinal layers indicating that it may be due to extracellular fluid accumulation.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/etiologia , Edema Macular/etiologia , Neurônios Retinianos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Diabetes Mellitus Tipo 2/diagnóstico , Retinopatia Diabética/diagnóstico , Feminino , Humanos , Edema Macular/diagnóstico , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos Prospectivos , Tomografia de Coerência Óptica , Adulto JovemRESUMO
PURPOSE: To characterize the 1-year progression of retinal thickness (RT) increase occurring in eyes with subclinical macular edema in type 2 diabetes. METHODS: Forty-eight type 2 diabetic eyes/patients with mild nonproliferative diabetic retinopathy (NPDR; levels 20 and 35 in the Early Treatment Diabetic Retinopathy Study) classified as presenting subclinical macular edema at baseline completed the 1-year follow-up period, from a sample of 194 followed in a 12-month observational and prospective study (ClinicalTrials.gov identifier: NCT01145599). Automated segmentation of the retinal layers in these eyes was performed, followed by verification and correction by a human grader. RESULTS: The highest increase in RT over the 1-year follow-up period for the 48 eyes/patients with subclinical macular edema was found in the inner nuclear layer (INL). Progression to clinical macular edema was also associated with increased thickening of other retinal layers aside from the INL. The microvascular disease activity shown by microaneurysm (MA) turnover ≥6 was associated with progression from subclinical to clinical macular edema. CONCLUSIONS: Increases in RT occurring over a period of 1 year in diabetic eyes with mild NPDR and subclinical macular edema occur mainly in the INL. The development of clinical macular edema appears to be associated with increased thickening of other retinal layers and microvascular disease activity.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/diagnóstico , Edema Macular/diagnóstico , Neurônios Retinianos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos Prospectivos , Tomografia de Coerência ÓpticaRESUMO
Topic: The goal of this review was to summarize the current level of evidence on biomarkers to quantify diabetic retinal neurodegeneration (DRN) and diabetic macular edema (DME). Clinical relevance: With advances in retinal diagnostics, we have more data on patients with diabetes than ever before. However, the staging system for diabetic retinal disease is still based only on color fundus photographs and we do not have clear guidelines on how to incorporate data from the relatively newer modalities into clinical practice. Methods: In this review, we use a Delphi process with experts to identify the most promising modalities to identify DRN and DME. These included microperimetry, full-field flash electroretinogram, spectral-domain OCT, adaptive optics, and OCT angiography. We then used a previously published method of determining the evidence level to complete detailed evidence grids for each modality. Results: Our results showed that among the modalities evaluated, the level of evidence to quantify DRN and DME was highest for OCT (level 1) and lowest for adaptive optics (level 4). Conclusion: For most of the modalities evaluated, prospective studies are needed to elucidate their role in the management and outcomes of diabetic retinal diseases. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
RESUMO
BACKGROUND: Patients with brain, head, and neck tumors experience a decline in their quality of life due to radiation retinopathy and optic neuropathy. Little is known about the dose-response relationship and patient characteristics. We aimed to systematically review the prevalence of radiation retinopathy and optic neuropathy. METHOD: The primary outcome was the pooled prevalence of radiation retinopathy and optic neuropathy. The secondary outcome included the effect of the total radiation dose prescribed for the tumor according to the patient's characteristics. Furthermore, we aimed to evaluate the radiation dose parameters for organs at risk of radiation retinopathy and optic neuropathy. RESULTS: The pooled prevalence was 3.8%. No retinopathy was reported for the tumor's prescribed dose of <50 Gy. Optic neuropathy was more prevalent for a prescribed dose of >50 Gy than <50 Gy. We observed a higher prevalence rate for retinopathy (6.0%) than optic neuropathy (2.0%). Insufficient data on the dose for organs at risk were reported. CONCLUSION: The prevalence of radiation retinopathy was higher compared to optic neuropathy. This review emphasizes the need for future studies considering retinopathy and optic neuropathy as primary objective parameters.
RESUMO
In perinatally HIV-infected (PHIV) children, cross-sectional studies reported on subtle structural retinal differences and found associations between the retina and structural brain changes. Our objective is to investigate whether neuroretinal development in PHIV children is similar to the development in healthy matched controls and to explore associations with the brain structure. We measured RT using optical coherence tomography (OCT) on two occasions in 21 PHIV children or adolescents and 23 matched controls-all with good visual acuity-with a mean interval of 4.6 years (SD 0.3). We also included 22 participants (11 PHIV children and 11 controls) together with the follow-up group for a cross-sectional assessment using a different OCT device. Magnetic resonance imaging (MRI) was used to assess the white matter microstructure. We used linear (mixed) models to assess changes in RT and its determinants (over time), adjusting for age and sex. The development of the retina was similar between the PHIV adolescents and controls. In our cohort, we found that changes in the peripapillary RNFL was significantly associated with changes in WM microstructural makers: fractional anisotropy (coefficient = 0.030, p = 0.022) and radial diffusivity (coefficient = -0.568, p = 0.025). We found comparable RT between groups. A thinner pRNFL was associated with lower WM volume (coefficient = 0.117, p = 0.030). PHIV children or adolescents appear to have a similar development of the retinal structure. In our cohort, the associations between RT and MRI biomarkers underscore the relation between retina and brain.