External Validation of the OAC3-PAD Bleeding Score in a Nationwide Population of Patients Undergoing Invasive Treatment for Peripheral Arterial Disease.

OBJECTIVE: The OAC3-PAD score was developed to predict bleeding risk in patients with lower extremity peripheral arterial disease (PAD), but its performance in concomitant international cohorts is largely unknown. This study aimed to validate the OAC3-PAD score in an unselected nationwide population of patients undergoing invasive treatment for symptomatic PAD. METHODS: This was a nationwide cohort study including all patients who underwent a first revascularisation procedure or major amputation for symptomatic PAD in Denmark from 2000 - 2021. The study population was stratified based on OAC3-PAD score, and the one year risk of major bleeding was assessed, accounting for the competing risk of death. The score performance was evaluated using calibration plots, C statistic, Brier score, and the index of prediction accuracy (IPA). RESULTS: A total of 52 016 patients were included (mean age 71 years, 43.8% female). The one year risk of major bleeding increased with higher OAC3-PAD score, ranging from 1.6% (95% confidence interval [CI] 1.4 - 1.8%) to 2.3% (95% CI 2.0 - 2.5%), 3.5% (95% CI 3.2 - 3.8%), and 5.2% (95% CI 4.8 - 5.6%) for patients with low, low moderate, moderate high, and high score, respectively. Using patients with low risk as reference, the OAC3-PAD score effectively categorised patients, demonstrating statistically significant differences in bleeding risk across strata. However, the score showed modest discriminative performance, with a C statistic of 65% (95% CI 63 - 66%) and a Brier score of 2.6% (95% CI 2.5 - 2.7%). Nevertheless, it performed significantly better than the null model, as indicated by an IPA of 3.1%. CONCLUSION: Among patients who underwent invasive treatment for symptomatic PAD in routine care, the OAC3-PAD score was associated with greater risk of major bleeding with increasing score level. However, its discriminatory ability was modest, and the clinical utility remains to be determined.

Similarities and differences in systemic risk factors for retinal artery occlusion and retinal vein occlusion: A nationwide case-control study.

BACKGROUND: To investigate the relationship between risk factors for retinal artery occlusion (RAO) and retinal vein occlusion (RVO) and thereby identify similarities and differences between the two types of retinal vascular occlusions. METHODS: In this case-control study, 5708 patients with RAO were included and matched with three patients with RVO each. The patients with RVO were matched on sex and age at index date. All patients, personal information, diagnoses, and prescriptions were obtained from the Danish nationwide registries. Adjusted conditional logistic regression was used to investigate the association of RAO and RVO with the included risk factors. RESULTS: RAO was stronger associated with arterial hypertension, heart failure, ischemic heart disease, peripheral artery disease, and stroke than RVO, with effect measures ranging from 1.10 to 2.21. RVO was associated with cataract and glaucoma with effect measures of 0.80 (95% CI 0.73-0.87) and 0.65 (95% CI 0.56-0.76), respectively. CONCLUSION: Differences in the level of associations with the included risk factors suggests differences in the pathophysiologies of the two diseases. The main pathophysiology associated with RAO was atherosclerosis, whereas the main pathophysiology associated with RVO was changes in the pressure gradients of the eyes.

Similarities and Differences in Systemic Risk Factors for Retinal Artery Occlusion and Stroke: A Nationwide Case-Control Study.

BACKGROUND: Retinal artery occlusion (RAO) has been considered a stroke equivalent. This study compares risk factor profiles for thromboembolism among patients with RAO and stroke, respectively. METHODS: This case-control study is based on 5683 RAO patients entered in the Danish National Patient Register between 1st of January 2000 and 31st of December 2018. Cases were matched on sex, year of birth, and age at event with 28,415 stroke patients. The Danish nationwide registries were used to collect information about age, sex, previous diagnoses, and drug prescriptions. Adjusted conditional logistic regression models were used to investigate the association between hypothesised risk factors and the patient outcome. RESULTS: For atrial fibrillation, a substantially stronger association to stroke was found, with an odds ratio (OR) of 0.52 (95% CI: 0.47-0.58) when comparing RAO patients with stroke patients. RAO was stronger associated with arterial hypertension, peripheral artery disease, retinal vein occlusion, cataract, and glaucoma with OR's ranging from 1.21-11.70. The identified effect measures reached equivalence or was close to equivalence for diabetes, heart failure, ischemic heart disease, and renal disease. CONCLUSION: The differences in risk factor profiles between RAO and stroke suggests differences in the pathophysiology of the two diseases. These variations in pathophysiologies between the two diseases may indicate that different interventions are needed to ensure the optimal long-term prognosis for the patients.

Clinical risk factors for retinal artery occlusions: a nationwide case-control study.

PURPOSE: This study seeks to examine potential risk factors for the development of retinal artery occlusions (RAO). METHODS: We used data obtained from Danish nationwide registries to evaluate potential risk factors for RAO present up to 5 years prior to the RAO diagnosis. The study included 5312 patients diagnosed with RAO registered in the Danish National Patient Register and 26,560 controls assessed from the general population matched on sex and age at index date. Adjusted conditional logistic regression was used to estimate the odds ratio of included risk factors for RAO diagnosis. We conducted supplementary analyses stratified on sex and age, and on RAO subtype. In addition, interaction analyses were performed between strata in the stratified analyses. RESULTS: Risk factors associated with the development of RAO included diabetes, arterial hypertension, ischemic heart disease, peripheral artery disease, stroke, renal disease, cataract, and glaucoma, with ORs ranging from 1.33 to 4.94. Atrial fibrillation and sleep apnea yielded effect measures close to equivalence. The presence of a risk factor was generally associated with higher odds of RAO among the population ≤ 55 of age. Arterial hypertension was stronger associated with RAO in male patients than in female patients. The association with arterial hypertension was stronger for CRAO than for BRAO subtype. CONCLUSION: The investigated risk factors suggest that atherosclerosis and conditions changing the intraocular pressure are involved in the pathophysiology of RAO.

Retinal Artery Occlusion as an Early Indicator of Macrovascular Complications in Diabetes.

BACKGROUND: A characteristic of the retinal circulation is that arterial occlusion is embolic or secondary to vasculitis but rarely or never due to in situ atherosclerosis. Therefore, retinal artery occlusion suggests the presence of cardiac or large-vessel disease outside the eye. This cohort study examined the general risk of macrovascular disease in individuals with diabetes, with or without retinal artery occlusion. METHODS: We retrieved data on 992 subjects with incident retinal artery occlusion and preexisting diabetes, registered in Denmark between January 1, 2000, and December 31, 2018. Each retinal artery occlusion subject was matched for age, sex, and diabetes duration, with 5 control subjects with diabetes but without retinal artery occlusion. We performed survival analyses to compare the risk of extraocular macrovascular disease between the 2 groups in a 5-year follow-up. RESULTS: After 1 year, the incidence of macrovascular disease in subjects with retinal artery occlusion was approximately 21 per 100 person-years (95% confidence interval [CI]: 18.11-24.29), compared to 6.25 per 100 patient-years (95% CI: 5.57-7.00) in those without retinal artery occlusion. After 5 years, the cumulative incidences of macrovascular disease were 51.2% (95% CI: 47.9-54.7%) and 29.4% (95% CI: 28.0-30.8%) in patients with diabetes with or without retinal artery occlusion, respectively. Hazard rate ratios were 3.36 (95% CI: 2.79-4.05) after 1 year and 2.27 (95% CI: 2.04-2.53) after 5 years. CONCLUSION: Among individuals with diabetes, those diagnosed with retinal artery occlusion had a higher general risk of macrovascular complications for at least 5 years after the occlusion event compared with those without retinal artery occlusion.

Positive Prediction Value of Retinal Artery Occlusion Diagnoses in the Danish National Patient Registry: A Validation Study.

PURPOSE: The hospital registration of retinal artery occlusions in the Danish National Patient Registry has not previously been validated. In this study, the diagnosis codes were validated to ensure the diagnoses had an acceptable validity for research. The validation was performed both for the overall diagnosis population and at the subtype diagnosis level. METHODS: The medical records for all patients with retinal artery occlusion with an incident hospital record in the years 2017-2019 in Northern Jutland (Denmark) were assessed in this population-based validation study. Furthermore, fundus images and two-person verification were assessed for the included patients when available. The positive prediction values for the overall diagnosis of retinal artery occlusion, as well as for the central or branch subtypes, were calculated. RESULTS: A total of 102 medical records were available for review. The overall positive prediction value for a retinal artery occlusion diagnosis was 79.4% (95% CI: 70.6-86.1%), while the overall positive prediction value at the subtype diagnosis level was 69.6% (95% CI: 60.1-77.7%), with 73.3% (95% CI: 58.1-85.4%) for branch retinal artery occlusion and 71.2% (95% CI: 56.9-82.9%) for central retinal artery occlusion. For the stratified analyses at the subtype diagnosis, age, sex, diagnosis year, and primary or secondary diagnosis, the positive prediction values ranged from 73.5 to 91.7%. In the stratified analyses at the subtype level, the positive prediction values ranged from 63.3 to 83.3%. The differences among the positive prediction values of the individual strata of both analyses were not statistically significant. CONCLUSIONS: the validities of the retinal artery occlusion and subtype level diagnoses are comparable to other validated diagnoses and considered acceptable for use in research.

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

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.

A review of risk factors for retinal vein occlusions.

INTRODUCTION: Risk factors for retinal vein occlusion have been extensively studied, with varying population sizes. Smaller populations result in less certain measures of associations. The present review included studies with a relevant population size to identify clinically relevant risk factors for retinal vein occlusion. Understanding the risk factors of retinal vein occlusion is important for the management of these patients. AREAS COVERED: A comprehensive literature review was conducted through a systematic literature search in PubMed and Embase. Additional studies were selected from cross references in the assessed studies. Weighted effect measures were calculated for all included risk factors.Risk factors associated with retinal vein occlusion included cardiovascular diseases, eye diseases, systemic diseases, medical interventions, and sociodemographic factors. EXPERT OPINION: This review provided an extensive overview of a wide variety of risk factors increasing the risk of developing retinal vein occlusion. The severity of the identified risk factors indicated that these patients have been in contact with the health care system before their retinal vein occlusion event. Therefore, the clinical course for patients with retinal vein occlusion may benefit from a multidisciplinary collaboration between ophthalmologists and especially cardiologists.