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Doug Davis, M.D. Scott & White Eye Institute 2013 Veirs Conference 2/27/2013 1 What to Remember: • 1) A annual general health assessment is reasonable advice whether or not the patient has a retinal vein occlusion. • 2) If the patient is young and without known systemic risk factors, it is potentially worthwhile to evaluate for systemic processes. o Possibile entities include elevated serum homocysteine levels or anti-phospholipid antibody syndrome. 2/27/2013 2 What to Remember: • 3) Patients with bilateral, simultaneous CRVO should undergo careful medical and hematologic evaluation assessing various blood rheologic parameters. o For most of us, this involves consultation with other physicians outside of Ophthalmology. 2/27/2013 3 Definitions 2/27/2013 4 Branch Retinal Vein Occlusion (BRVO) • Disruption of blood flow in a tributary of the central retinal vein invariably at an arteriovenous crossing. • Defined as Ischemic if 5 or more disc areas of capillary non-perfusion are identified on the FA. • Findings: o Intra-retinal hemorrhage o venous dilation and tortuosity o cotton-wool spots in the involved region 2/27/2013 5 Hemi- Retinal Vein Occlusion (HRVO) • Approximately 20% of eyes have been found to have retinal drainage through a dual-trunked central retinal vein (superior and inferior systems). • Disruption of blood flow through one of these trunks results in the clinical picture termed an HRVO. • These straddle the BRVO and CRVO clinical appearance. Progression to CRVO is possible. 2/27/2013 6 Central Retinal Vein Occlusion (CRVO) • Examination of enucleated eyes with this clinical picture has demonstrated interruption of blood flow at the lamina cribrosa. • Defined as Ischemic if 10 or more disc areas of capillary non-perfusion are demonstrated on FA. • Characteristics of Ischemic cases includes: o o o o Visual acuity of < 20/400 Presence of APD Extensive intra-retinal hemorrhage (Blood and Thunder) Anterior segment neovascularization 2/27/2013 7 Retinal Venous Occlusion (RVO) • Five population – based studies with incidence data out to as much as 10 years are in the literature: • 1) Beaver Dam Eye Study (BDES) • 2) Eye Disease Case – Control Study (EDCCS) • 3) Atherosclerosis Risk in Communities Study & Cardiovascular Health Study (ARIC / CHS) • 4) Blue Mountains Eye Study (BMES) • 5) Ocular Vascular Clinic at University of Iowa case series (Hayreh) 2/27/2013 8 Retinal Venous Occlusion (RVO) • Advanced Age and presence of Glaucoma are definite common risk factors • Second most common retinal vascular disorder behind Diabetic Retinopathy • Incidence of any RVO - 5.2 / 1000 • Incidence of CRVO - 0.8 / 1000 2/27/2013 9 Systemic Risk Factors for BRVO • Hypertension – significant risk factor in 4 out of the 5 studies • Diabetes - significant to a limited extent in only 2 of the 5 studies • Hx of CVD or MI – No significant association demonstrated • Tobacco use – Significant in only 1 of the 5 2/27/2013 10 Ocular Risk Factors for BRVO • Arterio-venous nicking - significant association • Focal arteriolar narrowing – significant association • Perfusion pressure – limited association 2/27/2013 11 Systemic Risk Factors for CRVO • Hypertension – odds ratio in the EDCCS was 2.9 (95% CI of 1.6 – 5.3) • Diabetes - odds ratio in the EDCCS was 2.4 (95% CI of 1.2 – 4.8) • Elevated ESR - odds ratio in EDCCS was 1.9 (95% CI of 1.1 - 3.4) • Estrogens, Alcohol, and increased activity - all found in the EDCCS to have a reduced OR (0.3 – 0.5) 2/27/2013 12 Effect of Systemic Factors on Risk RISK FACTOR BRVO CRVO HTN Worse Worse Diabetes Equivocal Worse MI / CVD Equivocal No change Stroke Hx Equivocal No change ESR elevation No change Worse BMI / Obesity Equivocal No change Tobacco Equivocal No change Alcohol Equivocal Better Activity No change Better Estrogens No change Better Renal disease Worse Worse 2/27/2013 13 Primary Thrombophilia Examples • Hyperhomocysteinemia (> 15 micro- mol / liter) o 9.5% of young CRVO patients (Lahey) o 5 – 10 % of Caucasians o RVO OR 3.76 (95% CI of 1.06 – 13.4) noted in BMES o May be managed with vitamin supplementation (Folate) 2/27/2013 14 Primary Thrombophilia Examples • Antiphospholipid Antibody syndrome o Lupus anticoagulant o Anticardiolipin antibodies o 10.8 % of young CVO patients (Lahey) o 2 – 4 % of the population 2/27/2013 15 Perspectives on Disease Associations • Systemic Diseases which are common in the populations at risk are, likewise, commonly seen in the case populations reported in the long term studies. • Presence of two uncommon diseases in one case is not necessarily evidence for association. 2/27/2013 16 Perspectives on Disease Associations • Little evidence is available for Primary Thrombophilia, Inflammatory disease, or other Hypercoagulable states in the Majority of patients with RVO. 2/27/2013 17 Anatomical Issues for RVO • Reports exist that document some patients have a congenital anomaly of the retinal vasculature (Kinky vein). • This alone can predispose an individual to experiencing an RVO. 2/27/2013 18 Testing Considerations • High Frequency testing for uncommon disease entities: o Reduces the test’s positive predictive value o Potentially results in unnecessary anxiety on the patients part o Likely is sub-optimal utilization of increasingly, limited resources allocated for medical care. 2/27/2013 19 Patient Modification of Risk Factors • For known cardiovascular risk factors, this may be an important component of their therapy. Examples include: o Diet selection o Exercise appropriate for their current health status o Medications known to favorably influence their cardiovascular health • May potentially reduce the progression from perfused to ischemic RVO’s. 2/27/2013 20 Patient Modification of Risk Factors • May influence the likelihood for manifestation of the RVO in the fellow eye as latency period between the eyes may be significant. • But, No proven Class I Rx benefit for efficacy. 2/27/2013 21 Patient Modification of Risk Factors • Current perspective for both the American Heart and American Stroke Association: o the Only Factor of significant benefit to reduce an individuals systemic stroke risk : Control of an individual’s Hypertension. 2/27/2013 22 Take Home Points • Increased age and Glaucoma are dominant risk factors for RVO. 2/27/2013 23 Take Home Points • Cardiovascular risk profile has strong predictive attributes: o Hypertension increases risk for BRVO or CRVO o Diabetes increases risk for CRVO o More physical activity decreases risk for CRVO o Moderate alcohol decreases risk for CRVO o Exogenous estrogens for post-menopausal women decreases risk for CRVO. 2/27/2013 24 Take Home Points • Hypercoagulability may play a role in limited cases: o Patients < 60 years of age o Bilateral, simultaneous CRVO cases 2/27/2013 25 Practice Guidelines to Consider • All patients with or without RVO should consider an annual general health assessment • Patients with bilateral, simultaneous CRVO: o Request comprehensive medical and hematologic evaluation o Whole blood viscosity and other rheologic assessments may be helpful 2/27/2013 26 Practice Guidelines to Consider • For patients without known risk factors: o Additional history of systemic thrombosis, rheumatic or inflammatory disease, and family history of thrombosis may be used to guide medical consultation o Medical consultation in young patients to assess for serum homocysteine levels and assay for anti-phospholipid antibody syndrome. 2/27/2013 27 Thanks to: • Dr. Howard Ying, MD, PhD of the Wilmer Eye Institute for some of the data and clinical correlations presented today. Footer Text 2/27/2013 28 References 1. 2. 3. 4. 5. Klein et al., Tr Am Ophth Soc. 2000; 98 :133 – 143. David et al., Ophthalmologica 1988; 197 : 69 – 74. Mitchell et al., Arch Ophth 1996; 114 : 1243 – 1247. Cugati et al., Arch. Ophth 2006; 124: 726 – 732. The Eye Disease Case – Control Study Group, AJO 1993; 116: 286 – 296. 6. Klein et al., AJO 2006; 141 : 859 – 862. 7. Chua et al., AJO 2005; 139 : 181 – 182. 8. Hayreh et al., AJO 2001;131: 61 – 77. 9. Wong et al, Ophthalmology 2005; 112 : 540 – 547. 10. Lahey et al., Ophthalmology 2002; 109: 126 – 131. 2/27/2013 29