Dataset Information

Age-Related Macular Degeneration in Patients With Chronic Myeloproliferative Neoplasms.

ABSTRACT:

Importance

It 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.

Objective

To compare the risk of AMD in patients with MPNs with the risk of AMD in matched controls from the general population.

Design, setting, and participants

A 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 measures

Incidence 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.

Results

A 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 relevance

Our 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.

SUBMITTER: Bak M

PROVIDER: S-EPMC5710292 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.