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1.
Commun Med (Lond) ; 4(1): 50, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493237

RESUMO

BACKGROUND: The emerging use of biomarkers in research and tailored care introduces a need for information about the association between biomarkers and basic demographics and lifestyle factors revealing expectable concentrations in healthy individuals while considering general demographic differences. METHODS: A selection of 47 biomarkers, including markers of inflammation and vascular stress, were measured in plasma samples from 9876 Danish Blood Donor Study participants. Using regression models, we examined the association between biomarkers and sex, age, Body Mass Index (BMI), and smoking. RESULTS: Here we show that concentrations of inflammation and vascular stress biomarkers generally increase with higher age, BMI, and smoking. Sex-specific effects are observed for multiple biomarkers. CONCLUSION: This study provides comprehensive information on concentrations of 47 plasma biomarkers in healthy individuals. The study emphasizes that knowledge about biomarker concentrations in healthy individuals is critical for improved understanding of disease pathology and for tailored care and decision support tools.


Blood-based biomarkers are circulating molecules that can help to indicate health or disease. Biomarker levels may vary depending on demographic and lifestyle factors such as age, sex, smoking status, and body mass index. Here, we examine the effects of these demographic and lifestyle factors on levels of biomarkers related to activation of the immune system and cardiovascular stress. Measurements of 47 different proteins were performed on blood samples from nearly 10,000 healthy Danish blood donors. Measurement data were linked with questionnaire data to assess effects of lifestyle. We found that immune activation and vascular stress generally increased with age, BMI, and smoking. As these measurements are from healthy blood donors they can serve as a reference for expectable effects and inflammation levels in healthy individuals. Knowledge about the healthy state is important for understanding disease progression and optimizing care.

4.
Sci Rep ; 13(1): 19414, 2023 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-37940659

RESUMO

Age-related macular degeneration (AMD) is a common cause of visual loss among the elderly. Genetic variants in the gene encoding complement factor H (CFH) have been identified as an AMD susceptibility gene, however, the mechanistic link is debated. Here, we investigated the link between the CFH Y402H genotype and low-grade inflammation. We recruited 153 healthy individuals, 84 participants with dry stages of AMD, and 148 participants with neovascular AMD. All participants were subjected to detailed retinal examination, and interview regarding comorbidities and lifestyle. Blood samples were analyzed for level of C-Reactive Protein (CRP), white blood cell differential count, and stained with fluorescent antibodies to differentiate CD4+ and CD8+ T cells. CFH Y402H genotyping was performed using an allele-specific polymerase chain reaction genotyping assay. Splenocytes from young and aged wild type and Cfh null mutant C57BL/6J mice were examined for CD4+ and CD8+ T cells. Healthy individuals with the CFH Y402H at-risk polymorphism HH had higher levels of CRP and lower proportions of CD4+ T cells compared to persons with the YH or YY polymorphism (P = 0.037, Chi-square). Healthy individuals with the HH polymorphism displayed lower proportions of CD4+ T cells with ageing (P < 0.01, one-way ANOVA), whereas both young and aged Cfh null mutant mice displayed lower proportions of CD4+ T cells (P < 0.001 and P < 0.05; unpaired t test). Participants with dry AMD and the HH polymorphism had similarly lower proportions of CD4+ T cells (P = 0.024, one-way ANOVA), but no difference in CRP-levels. In the neovascular stage of AMD, there was no difference in proportion of CD4+ cells or CRP levels according to genotype. The risk-associated CFH genotype is associated with an age-related decrease in proportion of CD4+ T cells and increased levels of CRP in healthy individuals. This indicates that decreased complement regulation results in extensive changes in innate and adaptive immune compartments that precede development of AMD.


Assuntos
Proteína C-Reativa , Degeneração Macular Exsudativa , Idoso , Camundongos , Animais , Humanos , Proteína C-Reativa/metabolismo , Fator H do Complemento/genética , Fator H do Complemento/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Inibidores da Angiogênese , Polimorfismo de Nucleotídeo Único , Camundongos Endogâmicos C57BL , Acuidade Visual , Fator A de Crescimento do Endotélio Vascular/genética , Genótipo , Linfócitos T CD4-Positivos/metabolismo , Estudos de Casos e Controles
5.
Ugeskr Laeger ; 185(48)2023 11 27.
Artigo em Dinamarquês | MEDLINE | ID: mdl-38018728

RESUMO

This review investigates age-related macular degeneration (AMD) which is a degenerative retinal disease. The pathogenesis of the disease is unknown, but tobacco smoking is a significant risk factor for the development of the disease. The wet form of AMD can be treated by intraocular injection of an antibody that binds vascular endothelial growth factor (VEGF) which is involved in the disease process. The introduction of anti-VEGF treatment is a major reason why blindness secondary to wet AMD is now negligible. The demographic development can be expected to increase the demand for treatment of AMD considerably in the future.


Assuntos
Inibidores da Angiogênese , Degeneração Macular Exsudativa , Humanos , Inibidores da Angiogênese/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Injeções Intravítreas , Degeneração Macular Exsudativa/tratamento farmacológico , Retina
6.
BMJ Open ; 13(11): e077175, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-38016793

RESUMO

OBJECTIVES: This qualitative study aims to identify patient-reported barriers to treatment for neovascular age-related macular degeneration (nAMD) and investigate their impact on quality of life. DESIGN: Using a qualitative explorative design. SETTING: Semi-structured individual or dyadic interviews were conducted with patients and their relatives. PARTICIPANTS: Twenty-one patients completed the interview, with four of them having a relative present. INTERVENTIONS: Gadamer's hermeneutics guided the epistemological approach, and maximum variation sampling was employed to capture diverse patient experiences. An advisory board consisting of patients, relatives and ophthalmologists ensured the relevance of the study. Thematic analysis was conducted using NVivo software. PRIMARY AND SECONDARY OUTCOME MEASURES: To investigate patient-reported barriers to the recommended treatment for nAMD and impact on quality of life. RESULTS: The study included 21 patients with nAMD, with a median age of 79 years. Five themes emerged: (1) good compliance with intravitreal treatment, (2) the dual role of relatives, (3) treatment commute, (4) hospital barriers, (5) preventive health literacy. CONCLUSION: This study highlights the resilience and adherence of patients with nAMD in Denmark to their treatment despite various barriers. While the therapy may have negative effects on their well-being, patients do not opt out of treatment. These findings underscore the importance of personalised treatment plans that provide, for example, convenient access to care and clear future agreements at the hospital. By adopting more patient-centred approaches, healthcare providers can enhance patient satisfaction and improve treatment adherence, ultimately leading to better patient outcomes and quality of life.


Assuntos
Inibidores da Angiogênese , Degeneração Macular , Humanos , Idoso , Inibidores da Angiogênese/uso terapêutico , Qualidade de Vida , Satisfação do Paciente , Degeneração Macular/tratamento farmacológico , Dinamarca , Injeções Intravítreas , Ranibizumab
7.
Dan Med J ; 70(10)2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37897394

RESUMO

INTRODUCTION: Age-related macular degeneration (AMD) causes approximately 9% of all blindness worldwide. The introduction of optical coherence tomography angiography (OCT-A) has revealed a potential for non-invasive diagnosis of neovascular AMD (nAMD), but has yet to be proven an accurate method for nAMD diagnosis. The purpose of this study was to map the clinical use of OCT-A in nAMD diagnosis and to investigate the agreement between two consultants in diagnosing nAMD. METHODS: A survey was administered to assess Danish ophthalmologists in nAMD diagnostic modalities. Furthermore, a prospective observational cohort study was conducted in which two consultants graded Triton and Heidelberg OCT-A in patients with suspected nAMD. RESULTS: A total of 21 ophthalmologists completed the survey. OCT-A combined with structural OCT was the first choice for the majority (81%), whereas dye-based ophthalmic angiography was used when in doubt of the diagnosis. OCT-A was used to guide treatment decisions in 64% of patients. Some ophthalmologists (48%) had no formal OCT-A training. In the second part of the study, an agreement was recorded between the two consultants in 86% of the cases with Triton OCT-A and 66% with Heidelberg OCT-A. CONCLUSIONS: OCT-A with structural OCT has become a primary diagnostic method of nAMD, but national guidelines are lacking. Future implementation of new diagnostic technology of nAMD should include trial-based guidelines and physician training. FUNDING: None. TRIAL REGISTRATION: Not relevant.


Assuntos
Tomografia de Coerência Óptica , Degeneração Macular Exsudativa , Humanos , Tomografia de Coerência Óptica/métodos , Estudos Prospectivos , Inibidores da Angiogênese , Acuidade Visual , Fator A de Crescimento do Endotélio Vascular , Angiografia , Angiofluoresceinografia/métodos
8.
BMC Ophthalmol ; 23(1): 153, 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37041490

RESUMO

BACKGROUND: The atrophic late stage of age-related macular degeneration (AMD) is termed geographic atrophy (GA), and affects visual acuity (VA) as well as quality of life (QoL). Previous studies have found that best-corrected VA (BCVA), the standard vision assessment often underrepresents functional deficits. Therefore, the purpose of this study was to evaluate the correlation between atrophic lesion size, VA and QoL measured with the National Eye Institute Visual Function Questionnaire (VFQ-39) in a Danish population. Moreover, we wanted to evaluate the correlation between comorbidities, behavioural factors, and QoL. METHODS: This was prospective clinical study of 51 patients with GA in one or both eyes, of these 45 patients had bilateral GA. Patients were consecutively included between April 2021 and February 2022. All patients filled in the VFQ-39 questionnaire except the subscales "ocular pain" and "peripheral vision." Lesion size was measured from fundus autoflourescense images, and BCVA was assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. RESULTS: We found an overall low score in each VFQ-39 subscale scores reflected by GA. Lesion size and VA were both significantly associated with all VFQ-39 subscale scores except for "general health." VA showed a larger effect on QoL than lesion size. Chronic obstructive pulmonary disease (COPD) was associated with a lower score in the subscale score "general health" but none of the other subscale scores were affected. Cardiovascular disease (CVD) was associated with a lower BCVA as well as in QoL reflected in the subscale scores "poor general vision," "near activities," and "dependency" of VFQ-39. CONCLUSION: Both atrophic lesion size and visual acuity affects QoL in Danish patients with GA, who reports an overall poor QoL. CVD seems to have a negative effect on disease, as well as in VFQ-39 in several subscales, whereas COPD did not affect disease severity or vision-related subscales in VFQ-39.


Assuntos
Atrofia Geográfica , Doença Pulmonar Obstrutiva Crônica , Baixa Visão , Humanos , Qualidade de Vida , Estudos Prospectivos , Fundo de Olho
9.
Sci Rep ; 13(1): 4077, 2023 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-36906669

RESUMO

Immune responses play a key role in the pathogenesis and progression of myeloproliferative neoplasms (MPN) and age-related macular degeneration (AMD). Recent studies suggested using MPNs as a "Human Inflammation Model" of drusen development and previous results showed interleukin-4 (IL-4) dysregulation in MPN and AMD. IL-4, IL-13 and IL-33 are all cytokines involved in the type 2 inflammatory response. This study investigated the cytokine levels of IL-4, IL-13 and IL-33 in serum of MPN and AMD patients. This cross-sectional study included 35 patients with MPN with drusen (MPNd) and 27 with MPN and normal retinas (MPNn), 28 patients with intermediate AMD (iAMD) and 29 with neovascular AMD (nAMD). With immunoassays, we quantified and compared levels of IL-4, IL-13 and IL-33 in serum between the groups. The study was conducted at Zealand University Hospital, Roskilde, Denmark, between July 2018 and November 2020. The serum levels of IL-4 were significantly higher in the MPNd group than in the MPNn group (p = 0.003). In regard to IL-33, the difference between MPNd and MPNn was not significant (p = 0.069), however, when subdivided into subgroups, a significant difference was found between polycythemia vera patients with drusen and those without drusen (p = 0.005). We found no IL-13 difference between the MPNd and MPNn groups. Our data didn't show any significant IL-4 or IL-13 serum level difference between the MPNd and iAMD groups but in regard to IL-33, data recorded a significant serum level difference between the two groups. There was no statistically significant difference between the MPNn, iAMD and nAMD groups in levels of IL-4, IL-13 and IL-33. These findings suggested that the serum levels of IL-4 and IL-33 might play a role in drusen development in MPN patients. The results might represent the type 2 inflammatory arm of the disease. The findings support the association between chronic inflammation and drusen.


Assuntos
Neoplasias , Degeneração Macular Exsudativa , Humanos , Interleucina-4 , Interleucina-13 , Inibidores da Angiogênese , Interleucina-33 , Estudos Transversais , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual , Citocinas , Inflamação
10.
Acta Ophthalmol ; 101(2): 123-139, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36117281

RESUMO

Intravitreally injected anti-vascular endothelial growth factor (anti-VEGF) agents are first-line treatment for neovascular age-related macular degeneration (nAMD). Phase 3 trials demonstrated non-inferiority of anti-VEGF therapy with brolucizumab compared with aflibercept in best corrected visual acuity (BCVA) gains, with superior anatomical outcomes after brolucizumab. The purpose of the review was to summarize real-world efficacy and safety data on brolucizumab in patients with nAMD. The review protocol was registered with PROSPERO (ID: CRD42021290530). We conducted systematic searches in Embase, Medline and key ophthalmology congress websites (19 October 2021). Original reports of efficacy and/or safety in patients receiving brolucizumab to treat nAMD in clinical practice were eligible. The descriptive summary includes reports describing at least 10 brolucizumab-treated eyes. In total, 2907 brolucizumab-treated eyes from 26 studies were included. Outcomes were available for treatment-naive eyes (six studies), eyes switched to brolucizumab from other anti-VEGFs (16 studies), and/or treatment-naive and switch eyes combined (eight studies). Follow-up time points ranged from 4 weeks to 1 year post-brolucizumab initiation. For BCVA, significant improvements compared with brolucizumab initiation were reported in four of six studies in treatment-naive eyes (mean BCVA improvement, range: +3.7 to +11.9 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) and in three of 12 studies in switch eyes (range: +9.0 to +15 ETDRS letters) (all p < 0.05); remaining studies reported no significant post-brolucizumab BCVA changes. For central subfield thickness (CST), improvements post-brolucizumab initiation were reported in all six studies in treatment-naive eyes (mean CST improvement, range: -113.4 to -150.1 µm) and in eight of 11 studies in switch eyes (range: -26 to -185.7 µm) (all p < 0.05). The 14 studies reporting on intraretinal, subretinal and/or total fluid observed improvements post-brolucizumab initiation. The four studies comparing treatment intervals observed extension of the interval between injections after switching to brolucizumab from other anti-VEGFs. Incidence of intraocular inflammation ranged from 0% to 19%. In conclusion, real-world efficacy and safety data concur with brolucizumab pivotal trials. Additionally, reduction of disease activity in anti-VEGF switch eyes was demonstrated by fluid reduction and/or visual acuity gain, along with prolongation of the interval between injections.


Assuntos
Retinopatia Diabética , Degeneração Macular , Degeneração Macular Exsudativa , Humanos , Ranibizumab/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Proteínas Recombinantes de Fusão/uso terapêutico , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/tratamento farmacológico
11.
Acta Ophthalmol ; 100(7): e1503-e1509, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35611568

RESUMO

PURPOSE: Angiostatic agents have proven effective in the treatment of macular oedema in patients with branch retinal vein occlusion (BRVO). However, treatment is inconvenient and expensive, and novel treatment regimens are warranted. We aimed to evaluate if combination treatment of navigated central retinal laser and aflibercept lowered the treatment burden in these patients. METHODS: Treatment-naïve patients with BRVO and macular oedema were included at two centres and randomized 1:1 to three monthly injections of 2.0 mg aflibercept with (Group A) or without (Group B) navigated central laser, followed by aflibercept as needed from month 4 through 12. Re-treatment need was evaluated, and secondary endpoints included functional and anatomical outcomes and safety evaluated by retinal microperimetry. RESULTS: We evaluated 41 eyes of 41 patients with a mean age of 69.6 years. Baseline median best-corrected visual acuity (BCVA) was 70.0 letters, and median central retinal thickness (CRT) was 502 µm with no difference between Groups A (n = 21) and B (n = 20). Percentage of patients needing re-treatment after month three was 71% and 80% (p = 0.72). At month 12, groups did not differ in number of injections after loading (1 versus 2, p = 0.43), change in BCVA (+12.8 versus +15.1 letters, p = 0.48), CRT (-195 versus -181 µm, p = 0.82), or retinal sensitivity (+3.3 versus +4.1 dB, p = 0.67). CONCLUSION: In treatment-naïve BRVO patients, addition of navigated central laser to aflibercept did not lower treatment burden or affect functional or anatomical outcomes. A low number of intravitreal injections were needed for successful outcome in both treatment arms.


Assuntos
Edema Macular , Oclusão da Veia Retiniana , Idoso , Inibidores da Angiogênese , Humanos , Injeções Intravítreas , Lasers , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão/uso terapêutico , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/tratamento farmacológico , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual
12.
EClinicalMedicine ; 43: 101248, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35128362

RESUMO

BACKGROUND: The hematopoietic stem cell disorders, myeloproliferative neoplasms (MPNs), are characterised by chronic low-grade inflammation (CLI). Recently, we showed that patients with MPNs have an increased prevalence of drusen and age-related macular degeneration (AMD), and drusen prevalence seemed associated with higher CLI. Studying MPNs may reveal more about drusen pathophysiology. This study investigated CLI further by measuring cytokine levels and complement system markers, comparing these between patients with MPNs and AMD. METHODS: This cross-sectional study, between July 2018 and November 2020 conducted at Zealand University Hospital (ZUH) - Roskilde, Denmark, included 29 patients with neovascular AMD (nAMD), 28 with intermediate-stage AMD (iAMD), 62 with MPNs (35 with drusen - MPNd and 27 with healthy retinas - MPNn). With flow cytometry, we measured complement-regulatory-proteins (Cregs). With immunoassays, we investigated cytokine levels combined into a summary-inflammation-score (SIS). FINDINGS: The MPNd and nAMD groups had similar SIS, significantly higher than the MPNn and iAMD groups. Additionally, we found SIS to increase over the MPN biological continuum from early cancer stage, essential thrombocytaemia (ET), over polycythaemia vera (PV) to the late-stage primary myelofibrosis (PMF). MPNs showed signs of complement dysregulation, with Cregs expression lower in PV than ET and PMF and even lower in PV patients with drusen. INTERPRETATION: This study suggests that MPNd have a higher CLI than MPNn and may indicate systemic CLI to play a greater part in, and even initiate drusen formation. We suggest using MPNs as a "Human Inflammation Model" of drusen development. The CLI in MPNs elicits drusen formation, triggering more CLI creating a vicious cycle, increasing the risk of developing AMD. FUNDING: Fight for Sight, Denmark, and Region Zealand's research promotion fund.

13.
Aging (Albany NY) ; 13(24): 25763-25777, 2021 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-34954692

RESUMO

The cause of age-related macular degeneration (AMD) is unknown, but evidence indicates that both innate and adaptive immunity play a role in the pathogenesis. Our recent work has investigated AMD in patients with myeloproliferative neoplasms (MPNs) since they have increased drusen and AMD prevalence. We have previously found increased levels of chronic low-grade inflammation (CLI) in MPN patients with drusen (MPNd) compared to MPN patients with normal retinas (MPNn). CLI and AMD are both associated with aging, and we, therefore, wanted to study immunosenescence markers in MPNd, MPNn, and AMD. The purpose was to identify differences between MPNd and MPNn, which might reveal novel information relevant to drusen pathophysiology and thereby the AMD pathogenesis. Our results suggest that MPNd have a T cell differentiation profile resembling AMD and more effector memory T cells than MPNn. The senescence-associated-secretory-phenotype (SASP) is associated with effector T cells. SASP is thought to play a role in driving CLI seen with advancing age. Senescent cells with SASP may damage healthy tissue, including the eye tissues affected in AMD. The finding of increased effector cells in MPNd could implicate a role for adaptive immunity and senescent T cells together with increased CLI in drusen pathophysiology.


Assuntos
Degeneração Macular , Transtornos Mieloproliferativos , Neoplasias , Drusas Retinianas/fisiopatologia , Idoso , Biomarcadores/sangue , Diferenciação Celular , Senescência Celular , Feminino , Humanos , Sistema Imunitário/patologia , Imunossenescência/fisiologia , Degeneração Macular/epidemiologia , Degeneração Macular/patologia , Masculino , Células T de Memória/patologia , Transtornos Mieloproliferativos/sangue , Transtornos Mieloproliferativos/patologia , Neoplasias/sangue , Neoplasias/patologia
15.
Acta Ophthalmol ; 99(8): e1360-e1365, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33666364

RESUMO

PURPOSE: To report real-world experiences on driving vision in patients with neovascular age-related macular degeneration (AMD) undergoing intravitreal anti-VEGF treatment. METHODS: Retrospective cohort study of treatment-naïve patients with neovascular AMD commenced in anti-VEGF treatment (n = 416) and followed for 4 years in a pro re nata treatment regimen. Monocular best-corrected visual acuity (BCVA) measured using ETDRS was performed on the treatment eye at all visits and on the fellow eye at baseline, every 6 months, and upon any patient-reported change in vision. Driving vision was defined as BCVA in the best-seeing eye of ≥70 ETDRS letters (equivalent to ≥0.5 Snellen) corresponding to the minimum BCVA required in many countries. RESULTS: Driving vision was present in 280 patients (67%) and was sustained in 86%, 74%, 65% and 59% of the patients at 1, 2, 3 and 4 years, respectively. Lower BCVA in the best-seeing eye predicted loss of driving vision. In patients without driving vision at baseline, driving vision was regained in 29%, 36%, 39% and 41% of the patients at 1, 2, 3 and 4 years, respectively; but only 35% sustained driving vision after the first year. Lower age and higher BCVA in best-seeing eye predicted regain of driving vision. CONCLUSION: Driving vision can be sustained in the majority of the patients if they have driving vision at baseline. This study provides important prognostic information for patients with neovascular AMD.


Assuntos
Condução de Veículo , Ranibizumab/administração & dosagem , Acuidade Visual , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Masculino , Estudos Retrospectivos , Fatores de Tempo , Tomografia de Coerência Óptica , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Degeneração Macular Exsudativa/diagnóstico
16.
Acta Ophthalmol ; 99(5): 470-477, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33124181

RESUMO

Aetiological processes of polypoidal choroidal vasculopathy (PCV) remains poorly understood, but several studies indicate that immunity may play a role and report elevated levels of systemic C-reactive protein (CRP). In this systematic review and meta-analysis, we summarize available evidence in the field. We searched the databases PubMed/MEDLINE, EMBASE, Web of Science and the Cochrane Central on 19 March 2020. Two independent authors reviewed the studies and extracted data. Two independent authors reviewed the studies, extracted data and evaluated risk of bias within individual studies. Studies were reviewed in the text qualitatively and measures of association were included for quantitative analyses. Results from univariate analyses and multivariate-adjusted analyses were included for separate meta-analyses to evaluate whether the association was only due to factors associated with PCV. Four studies (246 patients with PCV and 2861 control individuals) were identified and included for a qualitative and quantitative analysis. Increased CRP was associated with PCV when pooling both univariate measures (OR 3.54, 95% CI: 2.13-5.89, p < 0.0001) and multivariate-adjusted measures (OR 3.05, 95% CI: 1.56-5.98, p = 0.0011). Sensitivity analyses confirmed robustness of the results. Increased CRP is associated to PCV, even after adjusting for demographics, lifestyle factors and co-morbidities. Clinical value of CRP in relation to PCV remains unclear, but the association gives much needed insight into the aetiology of a poorly understood disease.


Assuntos
Proteína C-Reativa/metabolismo , Doenças da Coroide/sangue , Corioide/irrigação sanguínea , Pólipos/sangue , Biomarcadores/sangue , Doenças da Coroide/diagnóstico , Angiofluoresceinografia , Fundo de Olho , Humanos , Pólipos/diagnóstico
17.
EClinicalMedicine ; 26: 100526, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33089124

RESUMO

BACKGROUND: Epidemiological data show that myeloproliferative neoplasms (MPNs) are associated with increased risk of neovascular age-related macular degeneration (AMD). However, knowledge about the retinal findings in these patients is lacking. This study was conducted to examine retinal ageing and the prevalence of a hallmark of AMD; drusen, in patients with MPNs. Further, we examine the role of chronic systemic inflammation, considered central in both AMD and MPNs. METHODS: In this single-centre cross-sectional study, we consecutively enrolled 200 patients with MPNs. The study was divided into three substudies. Firstly, we obtained colour fundus photographs from all patients to evaluate and compare the prevalence of drusen with the published estimates from three large population-based studies. Secondly, to evaluate age-related changes in the various retinal layers, optical coherence tomography images were obtained from 150 of the patients and compared to a healthy control group, from a previous study. Thirdly, venous blood was sampled from 63 patients to determine the JAK2V617F allele burden and neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, in MPN patients with and without drusen. FINDINGS: Patients with MPNs had an increased risk of having large drusen compared to the three population-based studies OR 5·7 (95%CI, 4·1-8·0), OR 6·0 (95%CI, 4·2-8·4) and OR 7·0 (95%CI, 5·0-9·7). Also, we found that the retinal site of drusen accumulation - the Bruch's-membrane-retinal-pigment-epithelium-complex was thicker compared to healthy controls, 0·43µm (95%CI 0·17-0·71, p = 0·0014), but there was no sign of accelerated retinal ageing in terms of thinning of the neuroretina. Further, we found that MPN patients with drusen had a higher level of systemic inflammation than MPN patients with no drusen (p = 0·0383). INTERPRETATION: Patients with MPNs suffer from accelerated accumulation of subretinal drusen and therefore AMD from an earlier age than healthy individuals. We find that the retinal changes are located only between the neuroretina and the choroidal bloodstream. Further, we find that the drusen accumulation is associated with a higher JAK2V617F allele burden and a higher NLR, suggesting that low-grade chronic inflammation is a part of the pathogenesis of drusen formation and AMD. FUNDING: Fight for Sight, Denmark and Region Zealand's research promotion fund.

18.
Ugeskr Laeger ; 182(44)2020 10 26.
Artigo em Dinamarquês | MEDLINE | ID: mdl-33118489

RESUMO

In a variety of corneal and retinal diseases, ocular ischaemia mediates vascular endothelial growth factor (VEGF) expression, which in turn causes angiogenesis and increased vascular permeability. Consequently, VEGF-inhibitory treatment has been introduced in different ocular diseases. Hypoxia-inducible factor (HIF)-1α is an upstream regulator of VEGF-A, and increased HIF-1α expression has been established in ocular animal models. Upcoming translational studies are expected to increase our understanding of the complex balance between pro- and anti-angiogenic factors in the eye.


Assuntos
Indutores da Angiogênese , Fator A de Crescimento do Endotélio Vascular , Animais
19.
Invest Ophthalmol Vis Sci ; 61(4): 28, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32324857

RESUMO

Purpose: Geographic atrophy (GA) secondary to age-related macular degeneration (AMD) is a progressive disease with no treatment option. Previous studies show chemokine-mediated recruitment of immune cells in the retina, and therefore we investigated systemic levels of chemokines and chemokine receptors in patients with GA. Methods: This observational prospective study was conducted at a single center. We included 122 participants with no immune disease: 41 participants with GA and no choroidal neovascularization, 51 patients with neovascular AMD, and 30 healthy control individuals. Flow cytometric analysis was used to detect expression level of C-C chemokine receptor (CCR)1, CCR2, CCR3, CCR5, and C-X-C motif chemokine receptor (CXCR)3 on peripheral blood mononuclear cells (CD14+ monocytes, CD4+ T cells, CD8+ T cells). Plasma levels of C-C motif ligand (CCL)11, C-X-C motif chemokine (CXCL)10, and CCL5 were measured by specific immunoassays. Enlargement rate of GA lesion was measured from autofluorescence images. Results: Participants with GA have a specific chemokine profile with a higher expression of CCR5 than healthy controls in peripheral blood mononuclear cells, and a higher plasma levels of CCL-5. Further, GA was associated with higher monocytic expression of CCR2 than in neovascular AMD. We found that a high expression level of CCR5 on CD8+ T cells was associated with slower enlargement rate of atrophic lesion. Conclusions: The study showed an association between systemic chemokine profile and GA formation. Further studies are needed to fully elucidate the possible role of systemic chemokine regulation in mediating pathogenesis of GA.


Assuntos
Quimiocina CCL5/genética , Regulação da Expressão Gênica , Atrofia Geográfica/genética , Receptores CCR5/genética , Degeneração Macular Exsudativa/genética , Idoso , Estudos de Casos e Controles , Neovascularização de Coroide/genética , Feminino , Atrofia Geográfica/diagnóstico , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Estudos Prospectivos , Valores de Referência , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Fator A de Crescimento do Endotélio Vascular/metabolismo
20.
Acta Ophthalmol ; 98(7): 693-700, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32275357

RESUMO

PURPOSE: Predicting the visual gain from cataract surgery when the main cause of vision loss is age-related macular degeneration may be difficult and warrants the need for an objective predictor of subjective outcome. Full-field electroretinography is an objective measure of overall retinal function. We therefore wanted to study if full-field electroretinography can predict subjective visual outcome using visual function questionnaire. METHODS: Thirty-one patients with age-related macular degeneration operated for bilateral cataract underwent full-field electroretinography preoperatively. Full-field electroretinography was performed according to International Society for the Clinical Electrophysiology of Vision standards using a Ganzfeld bowl (RETI-port/scan 21, Roland, Berlin) and Dawson-Trick-Litzkow fibre electrodes. Vision-related quality of life was measured using the National Eye Institute Visual Function Questionnaire-39 before first-eye surgery and 4.12 ± 2.11 months after second-eye surgery. RESULTS: Mean change in composite visual function questionnaire score after cataract surgery was 9.2 ± 11.9. The patients were divided into three groups: visual function questionnaire composite score increase >10 (n = 17); no change (n = 8); and decrease (n = 6). In the dark-adapted full-field electroretinography responses, we found a significant difference between the three groups in the 0.01 b-wave amplitude (p = 0.05), the 10.0 b-wave amplitude (p = 0.04) and a near-significant difference in 3.0 a-wave amplitude (p = 0.09). Other dark-adapted responses (the 3.0 b-wave and 10.0 a-wave) did not show any significant differences between the three groups, and neither did the light-adapted responses. CONCLUSION: Patients with low dark-adapted responses on full-field electroretinography preoperatively experience a decrease in subjective vision-related quality of life, suggesting that maintained rod function before cataract surgery may be important.


Assuntos
Extração de Catarata/métodos , Catarata/fisiopatologia , Eletrorretinografia/métodos , Degeneração Macular/fisiopatologia , Qualidade de Vida , Retina/fisiopatologia , Acuidade Visual , Idoso , Idoso de 80 Anos ou mais , Catarata/complicações , Feminino , Seguimentos , Humanos , Degeneração Macular/complicações , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
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