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Published on: July 14, 2016
Patients with myeloproliferative neoplasms and high levels of systemic inflammation develop age-related macular
Charlotte Liisborg1,2, Marie Krogh Nielsen1, Hans Carl Hasselbalch2,3
1Department of Ophthalmology, Zealand University Hospital, Vestermarksvej 23, 4000 Roskilde, Denmark.
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.
Insights
Patients with myeloproliferative neoplasms (MPNs) show increased drusen, a hallmark of age-related macular degeneration (AMD). This accumulation is linked to systemic inflammation, suggesting a shared pathway in MPN and AMD pathogenesis.
Area of Science:
- Ophthalmology
- Hematology
- Immunology
Background:
- Myeloproliferative neoplasms (MPNs) are linked to a higher risk of neovascular age-related macular degeneration (AMD).
- Retinal manifestations in MPN patients are not well understood.
- Chronic systemic inflammation plays a role in both MPNs and AMD.
Purpose of the Study:
- To investigate retinal aging and drusen prevalence in MPN patients.
- To explore the association between systemic inflammation and retinal changes in MPNs.
Main Methods:
- Cross-sectional study of 200 MPN patients.
- Color fundus photography to assess drusen prevalence compared to population studies.
- Optical coherence tomography (OCT) to evaluate retinal layers in 150 patients against healthy controls.
- Blood sampling for JAK2V617F allele burden and neutrophil-to-lymphocyte ratio (NLR) in 63 patients.
Main Results:
- MPN patients had a significantly increased risk of large drusen (ORs ranging from 5.7 to 7.0).
- The Bruch's-membrane-retinal-pigment-epithelium complex was thicker in MPN patients, but neuroretina showed no accelerated aging.
- MPN patients with drusen exhibited higher systemic inflammation (elevated NLR).
Conclusions:
- MPN patients experience accelerated subretinal drusen accumulation, contributing to earlier onset AMD.
- Retinal changes are localized to the neuroretina-choroidal interface.
- Drusen accumulation correlates with higher JAK2V617F allele burden and NLR, implicating chronic inflammation in AMD pathogenesis.
