ASSOCIATION OF RETINAL VEIN OCCLUSION WITH CARDIOVASCULAR EVENTS AND MORTALITY: A Systematic Review and Meta-analysis.

PURPOSE: Previous studies examining the association of retinal vein occlusion (RVO) and cardiovascular events have been inconsistent and have mostly focused on stroke and myocardial infarction. The goal of this study is to use meta-analysis to examine the available evidence examining the association of RVO with incident cardiovascular events and mortality. METHODS: Systematic review and meta-analysis of all longitudinal cohort studies published in PubMed, Embase, and the Cochrane Library from inception to April 7, 2018, that evaluated the association of baseline RVO and incident cardiovascular events and/or mortality, that provided multivariate-adjusted risk estimates with 95% confidence intervals (95% CIs), and that had average follow-up ≥1 year. The Newcastle-Ottawa scale was used to assess study quality. Multivariate-adjusted risk estimates with 95% CI along with study characteristics were extracted from each study, and pooled risk ratios (RRs) with 95% CI were generated using a random-effects model with inverse-variance weighting to account for heterogeneity. Main outcomes were incident stroke (fatal or nonfatal), myocardial infarction, heart failure, peripheral arterial disease, all-cause mortality, and cardiovascular mortality. RESULTS: Fifteen cohort studies with a total of 474,466 patients (60,069 with RVO and 414,397 without RVO) were included. Each study had Newcastle-Ottawa scale score ≥6, indicating moderate-to-high quality. Retinal vein occlusion was associated with increased risk of stroke (RR = 1.45; 95% CI, 1.31-1.60), myocardial infarction (RR = 1.26; 95% CI, 1.17-1.37), heart failure (RR = 1.53; 95% CI, 1.22-1.92), peripheral arterial disease (RR = 1.26; 95% CI, 1.09-1.46), and all-cause mortality (RR = 1.36; 95% CI, 1.02-1.81), but was not associated with increased risk of cardiovascular mortality (RR = 1.78; 95% CI, 0.70-4.48). CONCLUSION: This review suggests patients with RVO have an increased risk of cardiovascular events and all-cause mortality. More studies are needed to determine the highest risk periods for cardiovascular events and mortality after RVO and whether immediate cardiovascular evaluation and intervention will improve outcomes.

Evaluation of the Association Between Retinal Vein Occlusion and the Risk of Atrial Fibrillation Development: A 12-Year, Retrospective Nationwide Cohort Study.

We aimed to evaluate the risk of atrial fibrillation (AF) development following retinal vein occlusion (RVO). We performed a nationwide propensity score-matched cohort study by retrospectively reviewing a database from the Korean National Health Insurance Service, comprising approximately 1 million random subjects. RVO and AF were diagnosed based on the Korean Classification of Disease codes. The RVO group was composed of patients with an initial diagnosis of RVO made between 2003 and 2007 (n = 1,801), excluding those who were diagnosed in 2002. The comparison group was composed of randomly selected patients (5 for each patient with RVO, n = 8,930) who were matched to the RVO group according to sociodemographic factors and the year of enrollment. Each sampled patient was tracked until 2013. The predictive value of RVO for AF was analyzed using Cox regression analysis with a hazard ratio (HR) and confidence interval (CI). AF developed in 6.5% of patients in the RVO group and 4.0% of those in the comparison group (p < 0.001). RVO was associated with a greater risk of AF development after adjusting for possible confounders (HR, 1.35; 95% CI, 1.09-1.67). An association between RVO and subsequent AF development was found after adjusting for possible confounding factors.

Associations of retinal artery occlusion and retinal vein occlusion to mortality, stroke, and myocardial infarction: a systematic review.

Retinal vascular events are perceived to be related to various cardiovascular complications. We conducted a systematic review to assess the relationship between retinal artery/vein occlusions (RAO/RVO) and the incidence of mortality, stroke, and myocardial infarction (MI). A comprehensive electronic literature search selected 93 relevant studies between 1992-2015: 16 articles qualified for inclusion (7 for mortality rate and MI, 11 for stroke). No published articles examined associations of RAO to mortality or MI, but only to stroke. Because of the heterogeneity of studies, no meta-analysis was performed. The association with mortality risk was highest at ~34.7% in RVO subgroup; whereas for MI, the risk was comparatively lower at 3.9-5.7% for RVO. There was no significant difference in stroke rate when comparing central and branch RVO subgroups (6.5%), but was significantly higher at 19.6-25% in RAO. There is a positive association of retinal vascular events to mortality, stroke, and MI. RAO is associated with a higher risk of stroke. Given that RAO and RVO patients would generally present to ophthalmologists, their high cardiovascular risk should include a referral for cardiovascular assessment as part of their management protocol.

Risk of Mortality and of Atherosclerotic Events Among Patients Who Underwent Hemodialysis and Subsequently Developed Retinal Vascular Occlusion: A Taiwanese Retrospective Cohort Study.

IMPORTANCE: Retinal vascular occlusion is considered a risk factor for cardiovascular diseases in the general population. However, the long-term outcomes of patients who undergo incident hemodialysis and subsequently develop retinal vascular occlusion have not been examined. OBJECTIVE: To determine the mortality rate and subsequent prevalence of systemic vascular diseases associated with retinal vascular occlusion among patients undergoing hemodialysis in Taiwan. DESIGN, SETTING, AND PARTICIPANTS: Data from the Taiwan National Health Institutes research database were used, and we identified 105,956 patients undergoing hemodialysis during the period from January 1997 to December 2008. In total, 113 patients with retinal artery occlusion and 463 patients with retinal vein occlusion were enrolled and matched for age, sex, and the duration of hemodialysis (at a 1:5 ratio) with patients without ocular disorders. MAIN OUTCOMES AND MEASURES: Mortality and atherosclerotic events. A multivariate Cox regression model for mortality and a competing risk regression model for atherosclerotic events were used for this population-based retrospective cohort study. RESULTS: Of 113 patients with retinal artery occlusion and 463 patients with retinal vein occlusion, 66 (58.4%) and 245 (52.9%) were females, respectively (ranging in age from ≤40 to 80 years). Our study showed there was a significant risk of mortality among patients undergoing hemodialysis who subsequently developed retinal artery occlusion or retinal vein occlusion compared with patients undergoing hemodialysis without ocular disorders. Patients with retinal artery occlusion had higher risks of ischemic stroke (adjusted hazard ratio [HR], 3.35 [95% CI, 2.00-5.59]; P < .001), coronary artery disease (adjusted HR, 1.70 [95% CI, 1.23-2.36]; P = .001), acute coronary syndrome (adjusted HR, 2.03 [95% CI, 1.24-3.33]; P = .002), and peripheral arterial occlusive disease (adjusted HR, 2.15 [95% CI, 1.26-3.66]; P = .002) than did patients without ocular disorders. Patients with retinal vein occlusion had higher risks of hemorrhagic stroke (adjusted HR, 2.54 [95% CI, 1.50-4.30]; P = .001), coronary artery disease (adjusted HR, 1.55 [95% CI, 1.31-1.83]; P < .001), and acute coronary syndrome (adjusted HR, 1.53 [95% CI, 1.14-2.06]; P = .002) than did patients without ocular disorders. CONCLUSIONS AND RELEVANCE: Our data demonstrate that the risks of mortality and atherosclerotic events were increased among patients undergoing incident hemodialysis who subsequently developed retinal vascular occlusion.

Retinal vein occlusion and the risk of stroke development: a 9-year nationwide population-based study.

PURPOSE: To evaluate the risk of stroke development after retinal vein occlusion (RVO). DESIGN: Nationwide, population-based 9-year longitudinal study. PARTICIPANTS: National registry data were collected from the Korean National Health Insurance Research Database, comprising 1 025 340 (∼2.2%) random subjects who were selected from 46 605 433 Korean residents in 2002. METHODS: Patients diagnosed with RVO or stroke in 2002 were excluded. The RVO group was composed of patients with an initial diagnosis of central or branch RVO between January 2003 and December 2005 (n = 344 in 2003, 375 in 2004, and 312 in 2005). The comparison group was composed of randomly selected patients (5 per patient with RVO; n = 1696 in 2003, 1854 in 2004, and 1524 in 2005) who were matched to the RVO group according to age, sex, residential area, household income, and year of RVO diagnosis. Each sampled patient was tracked until 2010. Cox proportional hazard regressions were used to calculate the overall survival rate for stroke development after adjusting for potential confounders, including hypertension, diabetes mellitus, and chronic kidney disease. MAIN OUTCOME MEASURES: Retinal vein occlusion and ischemic or hemorrhagic stroke based on the International Classification of Disease codes. RESULTS: Stroke developed in 16.8% of the RVO group and in 10.7% of the comparison group. Retinal vein occlusion was associated with an increased risk of stroke development (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.24-1.76). Hypertension, diabetes mellitus, and chronic kidney disease also increased the risk of stroke development. In addition, RVO increased the risk of both ischemic stroke (HR, 1.51; 95% CI, 1.24-1.84) and hemorrhagic stroke (HR, 1.30; 95% CI, 0.83-2.05), although this result was not significant for hemorrhagic stroke. In terms of age, the effect size of the HR was largest among younger adults, aged <50 years (HR, 2.69), compared with middle-aged adults, aged 50 to 69 years (HR, 1.33), and older adults, aged ≥70 years (HR, 1.46). CONCLUSIONS: Retinal vein occlusion was significantly associated with stroke development after adjusting for potential confounders. These findings are limited by uncontrolled confounding and need to be replicated by other observational studies.

Mortality in patients with central retinal vein occlusion.

PURPOSE: To assess mortality in patients with central retinal vein occlusion (CRVO). DESIGN: Registry-based cohort study. PARTICIPANTS AND CONTROLS: Four hundred thirty-nine photographically verified CRVO patients and a control cohort of 2195 unexposed subjects matched by age and gender and alive on the date CRVO was diagnosed in the corresponding case. METHODS: Data from nationwide registries were used to compare mortality rates in CRVO patients with a control cohort over a mean follow-up of 5.1 years for cases and of 5.7 years for controls. MAIN OUTCOME MEASURES: Hazard ratios (HRs) obtained by Cox regression and standardized mortality ratios (SMRs) stratified by age and gender served as measures of relative mortality risk. RESULTS: Mortality was higher in patients with CRVO (HR, 1.45; 95% confidence interval [CI], 1.19-1.76) than in the control cohort, adjusted for age, gender, and time of diagnosis. Mortality was comparable between the 2 groups (HR, 1.19; 95% CI, 0.96-1.46) when adjusting for overall occurrence of cardiovascular disease and diabetes. Subgroup analysis found that the age-stratified mortality rate was increased significantly in the total group of men (SMR, 1.27; 95% CI, 1.03-1.56) and in women 60 to 69 years of age (SMR, 1.94; 95% CI, 1.22-3.08). CONCLUSIONS: Central retinal vein occlusion was associated with an overall increase in mortality compared with controls that was attributed statistically to cardiovascular disorders and diabetes. We recommend treatment of hypertension and diabetes, if present, and referral of patients found to have CRVO who are not already being treated by a primary care physician.

Retinal vein occlusion: evaluation of "classic" and "emerging" risk factors and treatment.

Retinal vein occlusion (RVO) is the second most common retinal vein disease and an important cause of blindness and visual morbidity. Systemic risk factors are commonly associated with RVO, while unclear it is the role of the thrombophilic and coagulation disorders. To evaluate "classic" and "emerging" risk factors, and to establish a good treatment for RVO. Fifty patients, 31 males and 19 females, with RVO were selected for our study. RVO patients were divided into two groups: those with central retinal vein occlusion (CRVO) and those with branch retinal vein occlusion (BRVO). All patients were subjected to an anamnestic investigation and were tested for thrombophilia, coagulation disorders and hyperlipidemia. Treatment and prophylaxis were evaluated. We have named "classic" the systemic risk factors associated with RVO and "emerging" those risk factors, haemostasis related, not clearly associated with RVO. RVO occurs more commonly in patients aged over 50. "Emerging" risk factors were more frequent in CRVO, "classic" in BRVO. Hyperhomocysteinemia is the most common "emerging" risk factor related to RVO. 71.4% of tested patients had hypercholesterolemia. Treatment with LMWH would appear to be safe and effective, but the small number of patients considered not allow us a definitive evaluation of its efficacy. Although our study has shown the correlation between RVO and the "emerging" risk factors, more studies are necessary to better know the real role of thrombophilic and coagulation disorders in this disease and to determine a specific protocol for the treatment and prophylaxis of RVO.

Central retinal vein occlusion in a young Chinese population: risk factors and associated morbidity and mortality.

PURPOSE: The purpose of this study was to assess the risk factors for central retinal vein occlusion and associated morbidity and mortality in a Chinese population. METHODS: The participants included patients with central retinal vein occlusion 40 years old and younger. Predisposing factors, mortality, and systemic complications were examined in this group. RESULTS: Unilateral (n = 19) and bilateral (n = 3) central retinal vein occlusions were identified in a total of 22 patients (25 eyes), with a mean follow-up time of 37 months. Hypercholesterolemia (65%), hypertriglyceridemia (64%), and hyperhomocysteinemia (42%) were all identified as risk factors. Three patients (14%) developed stroke and 1 (5%) developed transient ischemic attacks during follow-up. Renal failure and pulmonary hypertension resulted in the death of two patients. The mean initial and final visual acuities (+ or - standard deviation) were 20/400 (+ or - 20/250) and 20/500 (+ or - 20/320), respectively, and treatments did not result in vision improvement (P = 0.57). The poor visual prognosis was likely due to macular edema in 7 eyes (28%), optic atrophy in 4 eyes (16%), and secondary glaucoma in 3 eyes (12%). CONCLUSION: Morbidity and mortality are high in young Chinese patients with central retinal vein occlusion who may have associated serious complications including stroke, blindness, and death. Central retinal vein occlusion may serve as an initial clinical presentation of serious systemic diseases.

Retinal vein occlusions and mortality: the Beijing Eye Study.

PURPOSE: To assess the association between retinal vein occlusion (RVO) and mortality in a population-based setting. DESIGN: Population-based, longitudinal study. METHODS: At baseline in 2001, the Beijing Eye Study examined 4,335 subjects for RVO with a frequency of detected vein occlusions of 61 (1.4%) in 4,335 subjects. In 2006, all study participants were invited for a follow-up examination. RESULTS: Of the 4,335 subjects, 3,195 (73.7%) returned for follow-up examination, whereas 132 (3.0%) subjects had died and 1,008 (23.3%) subjects declined to be re-examined or had moved away. For the subjects younger than 70 years or than 65 years, respectively, RVO was associated significantly with an increased mortality rate (P = .05; 95% confidence interval [CI], 0.995 to 8.26; and P = .001; 95% CI, 2.11 to 18.73, respectively). CONCLUSIONS: RVO in relatively young persons may signal a significant risk of mortality.

Mortality in patients with branch retinal vein occlusion.

PURPOSE: To assess the impact of branch retinal vein occlusion (BRVO), a condition related to arteriolar wall thickening, as a prognostic marker of mortality. DESIGN: Long-term follow-up study comparing cases with background population. PARTICIPANTS: Patients diagnosed with BRVO. METHODS: Diagnosis of BRVO confirmed by fundus photographic records including color diapositives and fluorescein angiograms. MAIN OUTCOME MEASURES: Observed and expected numbers of deaths determined from comprehensive civic records in cases compared with the background population (5.4 million). RESULTS: Branch retinal vein occlusion was found in 329 patients (173 women, 156 men) born between 1902 and 1956, who were 39 to 91 years old when diagnosed between 1973 and 1998. Follow-up was concluded on July 8, 2004, when 144 deaths were recorded in patients (74 women, 70 men), compared with an expected number of 145.5 deaths in the background population (standardized mortality rate, 0.99; 95% confidence interval, 0.84-1.16). Stratified analyses revealed no significant effect of age, gender, or time of diagnosis. CONCLUSIONS: In this study of 329 patients with BRVO, we found no significant difference in mortality between patients and the background population. An association between BRVO and cardiovascular/cerebrovascular risk factors has previously been documented in cross-sectional studies. The contrasting outcome in this longitudinal study may have been influenced by interventions instituted after the diagnosis of BRVO was made and by preferential survival before the diagnosis of BRVO of the more fit patients with the necessary precursor condition of having arteriovenous nicking, which is more prevalent in subjects with diabetes and hypertension.

Nine year follow-up study of morbidity and mortality in retinal vein occlusion.

PURPOSE: The aim of this study was to conduct a detailed retrospective follow-up of a large cohort of patients with retinal vein occlusion (RVO), examining morbidity and mortality, to investigate a possible relationship between RVO, large vessel disease and stroke, and to determine whether recurrence of RVO was influenced by treatment of associated medical conditions. METHODS: A follow-up study was undertaken in 1994 of all patients (n = 588) who presented to the medical ophthalmology clinics of the Birmingham and Midland Eye Hospital between 1982 and 1989 with a definitive diagnosis of RVO. RESULTS: Follow-up data were obtained on 549 patients (93%). Results showed that recurrence of RVO in the same or fellow eye was decreased by more than half in the follow-up group (3.3%) when compared with the known recurrence rate at initial presentation (8.8%). Comparison of the deceased with the survivors showed that the deceased patients were significantly older (mean age 70.2 vs 63.4 years). The prevalence of rubeosis iridis and smoking were statistically significantly increased when comparing the deceased with the survivors (p < 0.016 and p < 0.008 respectively). The deceased had a higher prevalence of diabetes (15.8% vs 10.1%), and there was a trend towards increased clinically evident macrovascular disease in those patients who had died (23.2% vs 19.5%). Neither hypertension nor hyperlipidaemia predicted death, as the prevalence rates of the two conditions were similar in survivors and those who had died (60.0% vs 60.6% and 48.4% vs 53.3%). The percentage of patients taking antiplatelet drug therapy was not different in the two groups (36.8% vs 38.3%). Analysis of the causes of death of the RVO population (n = 95) compared with the causes of death in the West Midlands population as a whole, showed that the percentage of deaths from myocardial infarction in the RVO population was significantly higher (23.1% vs 14.4%, p < 0.05). There was no statistical difference between the populations for ischaemic heart disease and stroke, although there was a trend for increased mortality from stroke (19% vs 13.5%). CONCLUSION: These data suggest a relationship between RVO, mortality and increased cardiovascular risk factors (smoking, diabetes and macrovascular disease), and support the possibility of an association between RVO and stroke. They also support the potential value of medical treatment of underlying medical conditions in preventing recurrence of RVO.

Mortality and morbidity in patients with central retinal vein occlusion.

We investigated the risk of mortality and morbidity in 78 patients with central retinal vein occlusion (CRVO) followed for more than 2 years (mean follow-up 7.2 years). Thirteen subjects died at an average of 7.0 years after CRVO. Five subjects developed myocardial infarction at an average of 2.8 years after CRVO, and 1 developed a cerebrovascular accident 3 years after CRVO. Patients with CRVO do not carry a higher risk of mortality and morbidity than matched controls derived from national surveys.

The risk for systemic vascular diseases and mortality in patients with central retinal vein occlusion.

In this cross-sectional study, the authors evaluated 197 patients diagnosed with central retinal vein occlusion (CRVO) at the Wilmer Ophthalmological Institute between 1980 and 1985 to determine the risk of systemic disease and mortality. Complete follow-up information for mortality was obtained in 191 (97%). National Health Interview Survey (NHIS) patients and Wilmer cataract patients formed two comparison groups. The prevalence of hypertension was significantly elevated in the CRVO cases when compared with both comparison groups (P less than 0.03, 0.005). The prevalence of diabetes mellitus was increased in CRVO cases in comparison with the NHIS group (P less than 0.005). The prevalence of cerebrovascular or cardiovascular disease was the same for all three groups, as was overall mortality. Mortality was not increased in CRVO cases as compared with United States mortality rates.