Are Chronic Myeloproliferative Neoplasms Associated with Age-Related Macular Degeneration?
Authors: Bak Marie , Sørensen Torben Lykke , Flachs Esben Meulengracht , Zwisler Ann-Dorthe Olsen , Juel Knud , Frederiksen Henrik , Hasselbalch Hans 
Published: October 2019

Abstract
Background. Patients with Chronic Myeloproliferative Neoplasms (MPNs) already have increased comorbidity at time of diagnosis, and studies show association with ophthalmic manifestations. Retinal vascular symptoms including vascular occlusions and hemorrhages are present, but other manifestations of the eye have not been thoroughly investigated in these patients. Previously reported studies show signs of systemic inflammation in patients with MPN as well as in patients with Age-Related Macular Degeneration (AMD). Our hypothesis is that the presence of MPN predisposes some individuals to develop AMD and this might be explained by the degree of systemic inflammation.
Objective. To describe the prevalence of Age-Related Macular Degeneration in patients with Chronic Myeloproliferative cancer at time of diagnosis compared to the general population in Denmark.
Materials and Methods. We conducted a retrospective population-based matched cohort study using Danish registries. We included all patients age 18+ or older with a first listed diagnosis of MPN in the Danish National Patient Registry between 1994 and 2013. Patients with Essential Thrombocythemia (ET), Polycythemia Vera (PV), Myelofibrosis (MF), Unclassifiable MPN (MPN-U) and Chronic Myeloid Leukemia (CML) were included. To compare the prevalence of AMD with the general population we identified 10 sex-and-age matched individuals without MPN, for each corresponding patient. The controls were identified through the Danish Civil Registration System. Index date was defined as date of MPN diagnosis, and controls had to be alive at their corresponding patient's index date. We searched for all primary AMD diagnoses in the Danish National Patient Registry within a ten-year period preceding index date + 30 days. For all patients and controls, baseline characteristics, including smoking-related conditions (yes/no), were registered. We calculated number of events in all groups, including only patients' and controls' first AMD diagnosis. Prevalence of AMD at time of diagnosis was calculated using descriptive statistics.
Results. We included 9679 patients (ET=2714; PV=3170; MF=600; MPN-U=1839; CML=1356) and a total of 96737 sex-and-age matched controls in the study. Mean age of included patients with MPN at time of diagnosis was: 64 years (ET); 66 (PV); 71 (MF); 70 (MPN-U) and 61 (CML) − all with comparable age-distribution in the matched control groups. There was a higher percentage of females in the ET group (65%), an equal sex-distribution in PV (females 49 %) and MPN-U (females 51 %) and a higher percentage of men in the CML group (59 %). Significant more patients with ET, PV and MPN-U had smoking related diagnoses compared to controls (p<0.05), but no differences were seen for patients with CML and MF.
We found 220 MPN patients and 6 controls, who had AMD at time of diagnosis. Patients in all subgroups had a higher prevalence of AMD with 64 ET patients vs. 3 controls; 74 PV patients vs. 2 controls; 16 MF patients vs. 0 controls; 51 MPN-U patients vs. 1 control and 15 CML patients vs. 0 controls. Our results show that 2.3 % of all patients with MPN were diagnosed with AMD, including 2.6 % of Philadelphia-negative patients (ET, PV, MF and MPN-U) and 1.1 % of Philadelphia-positive CML patients. The corresponding values for controls with AMD diagnoses were: 0.006 % (Philadelphia-negative controls 0.007 % and CML controls 0 %). In summary, we found that the patients with MPN had a higher prevalence of AMD, at time of diagnosis, compared to the general population in Denmark.
Conclusion. Chronic Myeloproliferative cancers are associated with Age-Related Macular Degeneration at time of diagnosis. Patients with all MPN subtypes have an increased prevalence of AMD compared to the general population. Our results show the need for further studies to establish if the association is present, not only at time of diagnosis, but also during the course of the cancer diseases. We are currently analyzing incidence rates after diagnosis, and influence of potential confounders and effect modifiers. Our preliminary results suggest that the association between AMD and MPN is also present after diagnosis. Clinical studies are needed to investigate whether the association represents a causal relationship or if confounders are accountable for the findings.

Disclosures
Hasselbalch: Novartis: Research Funding.