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Evaluation of Risk Scores as Predictive Tools for Stroke in Patients with Retinal Artery Occlusion: A Danish Nationwide Cohort Study.

ABSTRACT: Purpose We investigated the 1-year risk of stroke in patients with retinal artery occlusion and evaluated the predictive and discriminating abilities of contemporary risk stratification models for embolic stroke. Methods This register-based cohort study included 7,906 patients with retinal artery occlusion from Danish nationwide patient registries between 1995 and 2018. The study population was stratified according to the number of points obtained in the stroke risk scores: the CHA ₂ DS ₂ -VASc score and the ESSEN Stroke Risk score. The 1-year risk of stroke within strata was evaluated and compared using the cox proportional hazards model. Furthermore, the discrimination of the risk scores as predictive tools for stroke risk assessment was investigated using C-statistics, Brier score, and the index of prediction accuracy. Results The stroke event rate in patients with retinal artery occlusion increased as the score increased for both risk scores, ranging from 3.62 (95% confidence interval [CI]: 2.46-5.31) per 100 person-years to 13.25 (95% CI: 11.78--14.89) per 100-person-years for increasing levels of the CHA ₂ DS ₂ -VASc score and from 3.97 (95% CI: 2.97-5.32) per 100 person-years to 16.43 (95% CI: 14.01-19.27) per 100 person-years for increasing levels of the ESSEN Stroke Risk score. Using a risk score of 0 as a reference, the difference was statistically significant for retinal artery occlusion patients with a CHA ₂ DS ₂ -VASc score of 2 or above and for all levels of the ESSEN Stroke Risk score. The C-statistics for the risk scores was 61% (95% CI: 58%-63%) and 62% (95% CI: 59-64%) for the CHA ₂ DS ₂ -VASc score and ESSEN Stroke Risk score, respectively. Conclusion The results suggested that the use of the CHA ₂ DS ₂ -VASc score and the ESSEN Stroke Risk score was applicable for risk stratification of stroke in patients with retinal artery occlusion, but discrimination was poor due to low specificity.

SUBMITTER: Orskov M

PROVIDER: S-EPMC9713298 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Evaluation of Risk Scores as Predictive Tools for Stroke in Patients with Retinal Artery Occlusion: A Danish Nationwide Cohort Study.

Ørskov Marie M Vorum Henrik H Larsen Torben Bjerregaard TB Skjøth Flemming F

TH open : companion journal to thrombosis and haemostasis 20221001 4

<b>Purpose</b> We investigated the 1-year risk of stroke in patients with retinal artery occlusion and evaluated the predictive and discriminating abilities of contemporary risk stratification models for embolic stroke. <b>Methods</b> This register-based cohort study included 7,906 patients with retinal artery occlusion from Danish nationwide patient registries between 1995 and 2018. The study population was stratified according to the number of points obtained in the stroke risk scores: the C ...[more]

PMID: 36632285

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Project description:ImportancePatients with retinal artery occlusions (RAOs) are recommended to have emergent stroke workup, although the true risk of death and subsequent vascular events post-RAO is not clear.ObjectiveTo determine short-term and long-term rates of stroke, myocardial infarction (MI), and death in patients after RAO compared with a control cohort.Design, setting, and participantsThis retrospective cohort study used aggregated electronic health records from January 1, 2003, through April 14, 2023, from TriNetX, a network with data from more than 111 million patients. Patients with RAO and a cataract control group were identified and matched for age, sex, race, and comorbidities, including hypertension, diabetes, hyperlipidemia, and smoking status. Patients were excluded if they had a stroke or MI within 2 years before the diagnosis of RAO or cataract.ExposureInternational Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis code for RAO or age-related cataract.Main outcomes and measuresRate of death, stroke, and MI at 2 weeks, 30 days, 1 year, 5 years, and 10 years after RAO compared with matched controls.ResultsThere were a total of 34 874 patients with at least 1 year of follow-up in the RAO cohort. The mean (SD) age at the RAO event was 66 (15.2) years. The rate of death after RAO diagnosis was higher than after cataract diagnosis at 2 weeks (0.14% vs 0.06%; relative risk [RR], 2.45; 95% CI, 1.46-4.12; risk difference [RD], 0.08%; 95% CI, 0.04%-0.13%; P < .001), 30 days (0.29% vs 0.14%; RR, 2.10; 95% CI, 1.49-2.97; RD, 0.15%; 95% CI, 0.08%-0.22%; P < .001), 1 year (3.51% vs 1.99%; RR, 1.78; 95% CI, 1.61-1.94; RD, 1.41%; 95% CI, 1.17%-1.66%; P < .001), 5 years (22.74% vs 17.82%; RR, 1.28; 95% CI, 1.23-1.33; RD, 4.93%; 95% CI, 4.17%-5.68%; P < .001), and 10 years (57.86% vs 55.38%; RR, 1.05; 95% CI, 1.02-1.07; RD, 2.47%; 95% CI, 1.25%-3.69%; P < .001). Risk of stroke after RAO was higher at 2 weeks (1.72% vs 0.08%; RR, 21.43; 95% CI, 14.67-31.29; RD, 1.64%; 95% CI, 1.50%-1.78%; P < .001), 30 days (2.48% vs 0.18%; RR, 14.18; 95% CI, 10.94-18.48; RD, 2.31%; 95% CI, 2.14%-2.47%; P < .001), 1 year (5.89% vs 1.13%; RR, 5.20; 95% CI, 4.67-5.79; RD, 4.64%; 95% CI, 4.37%-4.91%; P < .001), 5 years (10.85% vs 4.86%; RR, 2.24; 95% CI, 2.09-2.40; RD, 6.00%; 95% CI, 5.50%-6.50%; P < .001), and 10 years (14.59% vs 9.18%; RR, 1.59; 95% CI, 1.48-1.70; RD, 5.41%; 95% CI, 4.62%-6.21%; P < .001). Risk of MI after RAO was higher at 2 weeks (0.16% vs 0.06%; RR, 3.00; 95% CI, 1.79-5.04; RD, 0.11%; 95% CI, 0.06%-0.16%; P < .001), 30 days (0.27% vs 0.10%; RR, 2.61; 95% CI, 1.78-3.83; RD, 0.17%; 95% CI, 0.10%-0.23%; P < .001), 1 year (1.66% vs 0.97%; RR, 1.72; 95% CI, 1.51-1.97; RD, 0.59%; 95% CI, 0.42%-0.76%; P < .001), 5 years (6.06% vs 5.00%; RR, 1.21; 95% CI, 1.12-1.31; RD, 1.07%; 95% CI, 0.64%-1.50%; P < .001), and 10 years (10.55% vs 9.43%; RR, 1.12; 95% CI, 1.04-1.21; RD, 1.13%; 95% CI, 0.39%-1.87%; P = .003).Conclusions and relevanceThis study showed an increased risk of death, stroke, and MI in patients with RAO at both short-term and long-term intervals after RAO compared with a matched control population diagnosed with cataract. These findings suggest a potential need for multidisciplinary evaluation and long-term systemic follow-up of patients post-RAO.

Project description:PurposeThe transient middle cerebral artery occlusion (MCAO) model of stroke is one of the most commonly used models to study focal cerebral ischemia. This procedure also results in the simultaneous occlusion of the ophthalmic artery that supplies the retina. Retinal cell death is seen days after reperfusion and leads to functional deficits; however, the mechanism responsible for this injury has not been investigated. Given that the eye may have a unique ocular immune response to an ischemic challenge, this study examined the inflammatory response to retinal ischemia in the MCAO model.MethodsYoung male C57B/6 mice were subjected to 90-min transient MCAO and were euthanized at several time points up to 7 days. Transcription of inflammatory cytokines was measured with quantitative real-time PCR, and immune cell activation (e.g., phagocytosis) and migration were assessed with ophthalmoscopy and flow cytometry.ResultsObservation of the affected eye revealed symptoms consistent with Horner's syndrome. Light ophthalmoscopy confirmed the reduced blood flow of the retinal arteries during occlusion. CX3CR1-GFP reporter mice were then employed to evaluate the extent of the ocular microglia and monocyte activation. A significant increase in green fluorescent protein (GFP)-positive macrophages was seen throughout the ischemic area compared to the sham and contralateral control eyes. RT-PCR revealed enhanced expression of the monocyte chemotactic molecule CCL2 early after reperfusion followed by a delayed increase in the proinflammatory cytokine TNF-α. Further analysis of peripheral leukocyte recruitment by flow cytometry determined that monocytes and neutrophils were the predominant immune cells to infiltrate at 72 h. A transient reduction in retinal microglia numbers was also observed, demonstrating the ischemic sensitivity of these cells. Blood-eye barrier permeability to small and large tracer molecules was increased by 72 h. Retinal microglia exhibited enhanced phagocytic activity following MCAO; however, infiltrating myeloid cells were significantly more efficient at phagocytizing material at all time points. Immune homeostasis in the affected eye was largely restored by 7 days.ConclusionsThis work demonstrates that there is a robust inflammatory response in the eye following MCAO, which may contribute to a worsening of retinal injury and visual impairment. These results mirror what has been observed in the brain after MCAO, suggesting a conserved inflammatory signaling response to ischemia in the central nervous system. Imaging of the eye may therefore serve as a useful non-invasive prognostic indicator of brain injury after MCAO. Future studies are needed to determine whether this inflammatory response is a potential target for therapeutic manipulation in retinal ischemia.

Dataset Information

Evaluation of Risk Scores as Predictive Tools for Stroke in Patients with Retinal Artery Occlusion: A Danish Nationwide Cohort Study.

Publications

Evaluation of Risk Scores as Predictive Tools for Stroke in Patients with Retinal Artery Occlusion: A Danish Nationwide Cohort Study.

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