Migraine May Represent an Independent Risk Factor for Retinal Stroke: A Population-Based Cohort Study.

Introduction: Migraine is an established risk factor for cerebral ischemic stroke, with an especially robust association in patients with migraine with aura. However, it is not known if migraine is a risk factor for retinal stroke (central or branch retinal artery occlusion; CRAO or BRAO).
Methods: We performed a retrospective, observational, cohort study using population-based data from the State Inpatient Databases and State Emergency Department Databases from New York (2006-2015), California (2003-2011), and Florida (2006-2015) to determine the association between hospital-documented migraine and retinal stroke. The primary exposure was hospital-documented migraine (ascertained from admission or emergency department diagnosis codes). The primary endpoint was time to hospital-documented CRAO (ICD-9-CM code 362.31 in the primary diagnosis position) and secondary endpoints included time to BRAO and any retinal artery occlusion (RAO). Cause-specific hazard models were used to model the association between migraine and subsequent CRAO.
Results: Of 39,835,024 patients included in the study, 1109,140 had migraine documented during our two year ascertainment window. Patients with migraine were younger (40.2±15.2 vs. 46.9±19.8, standardized difference (SD) 0.38), more likely to be female (81.4 % vs. 54.7 %, SD 0.6), and had a lower burden of atrial fibrillation (4.5 % vs. 6.9 %, SD 0.1), chronic kidney disease (1.9 % vs. 3.6 %, SD 0.2), and congestive cardiac failure (2.7 % vs. 5.1 %, SD 0.12). Migraine was not associated with CRAO in the primary diagnostic position (adjusted hazard rate (aHR) 1.15 (95 % CI: 0.79-1.67). However, it was associated with CRAO in any diagnostic position (aHR 1.39 (95 % CI: 1.08-1.78). As positive controls, we replicated previously established associations of migraine with cerebral ischemic stroke (aHR 1.35 (95 % CI: 1.32-1.38) and embolic ischemic stroke (aHR 1.15 (95 % CI: 1.08-1.22).
Conclusions: In a large, nationally-representative, claims-based study of patients from 3 regions in the United States (US), we did not find an adjusted association between migraine and a primary discharge diagnosis of CRAO. Our hypothesis-generating finding that migraine was associated with CRAO when using a broader definition sets the stage for future work leveraging both outpatient and pharmacy based claims to further explore this finding.
Competing Interests: Declaration of Competing Interest JL reported none. AS reported none. SU reported none. HRA reported none. ADH is supported by NIH-NINDS (K23NS105924), has received investigator initiated clinical research funding from the AAN, has received consultant fees from Integra and Novo Nordisk, has equity in TitinKM and Certus, and receives author fees from UpToDate. VB is supported by the National Institutes of Health’s National Eye Institute core grant P30-EY06360 (Department of Ophthalmology, Emory University School of Medicine) and by a departmental grant from Research to Prevent Blindness (New York, NY), and is a consultant for GenSight Biologics and Neurophoenix. MS is supported by the National Institutes of Health (R56AG074279, K76AG060001, R01AG078803, RF1NS129735, RF1NS130334 and R21AG070859). He has received fees from Labaton Sucharow and Raymond James and Associates for consulting unrelated to this work and receives a stipend for chairing the DSMB for the ongoing REVISION trial. ES reported none. SP received research support from BMS/Pfizer, Boehringer-Ingelheim, Daiichi Sankyo, European Union, German Federal Joint Committee Innovation Fund, and German Federal Ministry of Education and Research, Helena Laboratories and Werfen as well as speakers’ honoraria/consulting fees from Alexion, AstraZeneca, Bayer, Boehringer-Ingelheim, BMS/Pfizer, Daiichi Sankyo, Portola, and Werfen (all outside the submitted work). NOP reported none. YX is funded by the NIA (R01AG062770, R01AG066672), has research funding from the American Heart Association, Genentech, Daiichi Sankyo and Janssen and has received honoraria from Boehringer Ingelheim, and Portola. EO reported none. BMG is supported by the National Institutes of Health (K23HL161426) and the American Heart Association (23MRFSCD1077188).
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