Age-related macular degeneration and myeloproliferative neoplasms - A common pathway.
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ABSTRACT:
SUBMITTER: Liisborg C
PROVIDER: S-EPMC9828081 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
Publications
Age-related macular degeneration and myeloproliferative neoplasms - A common pathway.
Acta ophthalmologica 20221001
DANSK RESUMÉ (DANISH SUMMARY): Aldersrelateret makuladegeneration (AMD) er den hyppigste årsag til uopretteligt synstab og blindhed i højindkomstlande. Det er en progredierende nethindesygdom som gradvist fører til ødelaeggelse af de celler som er ansvarlige for vores centralsyn. De tidlige stadier er ofte asymptomatiske, imens senstadie AMD, som opdeles i to former, neovaskulaer AMD (nAMD) og geografisk atrofi (GA), begge udviser gradvist synstab, dog generelt med forskellig hastighed. Tidlig A ...[more]
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Project description:ImportanceIt has been suggested that systemic inflammation increases the risk of age-related macular degeneration (AMD). Given that chronic immune modulation is present in patients with myeloproliferative neoplasms (MPNs), the risk of AMD in these patients may be increased.ObjectiveTo compare the risk of AMD in patients with MPNs with the risk of AMD in matched controls from the general population.Design, setting, and participantsA nationwide population-based cohort study using Danish registers was conducted of all patients in Denmark who received a diagnosis between January 1, 1994, and December 31, 2013, of essential thrombocythemia, polycythemia vera, myelofibrosis, or unclassifiable MPNs. For each patient, 10 age- and sex-matched controls were included. All patients without prior AMD were followed up from the date of diagnosis (or corresponding entry date for the controls) until the first AMD diagnosis, death or emigration, or December 31, 2013, whichever occurred first. Data analysis was performed from April 1, 2015, to October 31, 2016.Main outcomes and measuresIncidence of AMD recorded in specialized hospital-based care. The rates and absolute risk of AMD were calculated. Using Cox proportional hazards regression models, smoking and risk-time adjusted hazard ratios (HRs) between patients and controls were calculated. In addition, HRs of neovascular AMD after 2006 were calculated since antivascular endothelial growth factor treatment was introduced nationwide at hospitals thereafter.ResultsA total of 7958 patients with MPNs (4279 women [53.8%] and 3679 men [46.2%]; mean [SD] age at diagnosis, 66.4 [14.3] years) were included in the study. The rate of AMD per 1000 person-years at risk was 5.2 (95% CI, 4.6-5.9) for patients with MPNs (2628 with essential thrombocythemia, 3063 with polycythemia vera, 547 with myelofibrosis, and 1720 with unclassifiable MPNs) and 4.3 (95% CI, 4.1-4.4) for the 77 445 controls, while the 10-year risk of AMD was 2.4% (95% CI, 2.1%-2.8%) for patients with MPNs and 2.3% (95% CI, 2.2%-2.4%) for the controls. The risk of AMD was increased overall for patients with MPNs (adjusted HR, 1.3; 95% CI, 1.1-1.5), with adjusted HRs for the subtypes of 1.2 (95% CI, 1.0-1.6) for essential thrombocythemia, 1.4 (95% CI, 1.2-1.7) for polycythemia vera, 1.7 (95% CI, 0.8-4.0) for myelofibrosis, and 1.5 (95% CI, 1.1-2.1) for unclassifiable MPNs. In addition, patients with MPNs had a higher risk of neovascular AMD (adjusted HR, 1.4; 95% CI, 1.2-1.6).Conclusions and relevanceOur results suggest that patients with MPNs are at increased risk of AMD, supporting the possibility that systemic inflammation is involved in the pathogenesis of AMD.
| S-EPMC5710292 | biostudies-literature
Project description:BackgroundEpidemiological 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.MethodsIn 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.FindingsPatients 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).InterpretationPatients 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.FundingFight for Sight, Denmark and Region Zealand's research promotion fund.
| S-EPMC7565257 | biostudies-literature
Project description:In the age-related macular degeneration (AMD) 'inflammation model', local inflammation plus complement activation contributes to the pathogenesis and progression of the disease. Multiple genetic associations have now been established correlating the risk of development or progression of AMD. Stratifying patients by their AMD genetic profile may facilitate future AMD therapeutic trials resulting in meaningful clinical trial end points with smaller sample sizes and study duration.
| S-EPMC4709545 | biostudies-literature
Project description: Not available
| S-EPMC1125371 | biostudies-literature
Project description:CLINICAL QUESTION:Is there any new knowledge about the pathogenesis and treatment of age-related macular degeneration (AMD)? RESULTS:We now understand better the biochemical and pathological pathways involved in the genesis of AMD. Treatment of exudative AMD is based on intravitreal injection of new antivascular endothelial growth factor drugs for which there does not yet exist a unique recognized strategy of administration. No therapies are actually available for atrophic AMD, despite some experimental new pharmacological approaches. IMPLEMENTATION:strategy of administration, safety of intravitreal injection.
| S-EPMC3102591 | biostudies-literature
Project description: Not available
| S-EPMC2972328 | biostudies-literature
Project description:This SuperSeries is composed of the following subset Series: GSE28002: Gene expression of the whole mouse eye GSE28032: Epigenetic Regulation of IL17RC in Age-related Macular Degeneration (MeDIP-chip) Refer to individual Series
2011-03-22 | E-GEOD-28033 | biostudies-arrayexpress
Project description:Age-related macular degeneration (AMD) leads to irreversible visual loss, therefore, early intervention is desirable, but due to its multifactorial nature, diagnosis of early disease might be challenging. Identification of early markers for disease development and progression is key for disease diagnosis. Suitable biomarkers can potentially provide opportunities for clinical intervention at a stage of the disease when irreversible changes are yet to take place. One of the most metabolically active tissues in the human body is the retina, making the use of hypothesis-free techniques, like metabolomics, to measure molecular changes in AMD appealing. Indeed, there is increasing evidence that metabolic dysfunction has an important role in the development and progression of AMD. Therefore, metabolomics appears to be an appropriate platform to investigate disease-associated biomarkers. In this review, we explored what is known about metabolic changes in the retina, in conjunction with the emerging literature in AMD metabolomics research. Methods for metabolic biomarker identification in the eye have also been discussed, including the use of tears, vitreous, and aqueous humor, as well as imaging methods, like fluorescence lifetime imaging, that could be translated into a clinical diagnostic tool with molecular level resolution.
| S-EPMC6358913 | biostudies-other
Project description:Age-related macular degeneration (AMD), the most common form of irreversible blindness in the industrially developed world, can present years before a patient begins to lose vision. For most of these patients, AMD never progresses past its early stages to the advanced forms that are principally responsible for the vast majority of vision loss. Advanced AMD can manifest as either an advanced avascular form known as geographic atrophy (GA) marked by regional retinal pigment epithelium (RPE) cell death or as an advanced form known as neovascular AMD marked by the intrusion of fragile new blood vessels into the normally avascular retina. Physicians have several therapeutic interventions available to combat neovascular AMD, but GA has no approved effective therapies as of yet. In this chapter, we will discuss the current strategies for limiting dry AMD in patients. We will also discuss previous attempts at pharmacological intervention that were tested in a clinical setting and consider reasons why these putative therapeutics did not perform successfully in large-scale trials. Despite the number of unsuccessful past trials, new pharmacological interventions may succeed. These future therapies may aid millions of AMD patients worldwide.
| S-EPMC5472449 | biostudies-other
Project description:human gut sequencing Metagenome
| PRJNA791821 | ENA