Retinal Vein Occlusion: Do I Work-Up this Patient with an RVO?

R. Doug Davis, M.D.Scott & White Eye Institute2013 Veirs Conference2/27/2013 1

What to Remember:• 1) A annual general health assessment isreasonable advice whether or not the patient has aretinal vein occlusion.• 2) If the patient is young and without knownsystemic risk factors, it is potentially worthwhile toevaluate for systemic processes.o Possibile entities include elevated serumhomocysteine levels or anti-phospholipidantibody syndrome.2/27/2013 2

What to Remember:• 3) Patients with bilateral, simultaneous CRVO shouldundergo careful medical and hematologicevaluation assessing various blood rheologicparameters.o For most of us, this involves consultation withother physicians outside of Ophthalmology.2/27/20133

Definitions2/27/2013 4

Branch Retinal VeinOcclusion (BRVO)• Disruption of blood flow in a tributary of the centralretinal vein invariably at an arteriovenous crossing.• Defined as Ischemic if 5 or more disc areas ofcapillary non-perfusion are identified on the FA.• Findings:o Intra-retinal hemorrhageo venous dilation and tortuosityo cotton-wool spots in the involved region2/27/2013 5

Hemi- Retinal VeinOcclusion (HRVO)• Approximately 20% of eyes have been found tohave retinal drainage through a dual-trunkedcentral retinal vein (superior and inferior systems).• Disruption of blood flow through one of these trunksresults in the clinical picture termed an HRVO.• These straddle the BRVO and CRVO clinicalappearance. Progression to CRVO is possible.2/27/2013 6

Central Retinal VeinOcclusion (CRVO)• Examination of enucleated eyes with this clinical picturehas demonstrated interruption of blood flow at thelamina cribrosa.• Defined as Ischemic if 10 or more disc areas of capillarynon-perfusion are demonstrated on FA.• Characteristics of Ischemic cases includes:o Visual acuity of < 20/400o Presence of APDo Extensive intra-retinal hemorrhage (Blood and Thunder)o Anterior segment neovascularization2/27/2013 7

Retinal Venous Occlusion(RVO)• Advanced Age and presence of Glaucoma aredefinite common risk factors• Second most common retinal vascular disorderbehind Diabetic Retinopathy• Incidence of any RVO - 5.2 / 1000• Incidence of CRVO - 0.8 / 10002/27/2013 9

Systemic Risk Factors forBRVO• Hypertension – significant risk factor in 4 out of the 5studies• Diabetes - significant to a limited extent in only 2 ofthe 5 studies• Hx of CVD or MI – No significant associationdemonstrated• Tobacco use – Significant in only 1 of the 52/27/2013 10

Ocular Risk Factors forBRVO• Arterio-venous nicking - significant association• Focal arteriolar narrowing – significant association• Perfusion pressure – limited association2/27/2013 11

Systemic Risk Factors forCRVO• 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% CIof 1.2 – 4.8)• Elevated ESR - odds ratio in EDCCS was 1.9 (95% CIof 1.1 - 3.4)• Estrogens, Alcohol, and increased activity - allfound in the EDCCS to have a reduced OR (0.3 –0.5)2/27/2013 12

Effect of Systemic Factorson RiskRISK FACTOR BRVO CRVOHTN Worse WorseDiabetes Equivocal WorseMI / CVD Equivocal No changeStroke Hx Equivocal No changeESR elevation No change WorseBMI / Obesity Equivocal No changeTobacco Equivocal No changeAlcohol Equivocal BetterActivity No change BetterEstrogens No change BetterRenal disease Worse Worse2/27/2013 13

Primary ThrombophiliaExamples• Hyperhomocysteinemia (> 15 micro- mol / liter)o 9.5% of young CRVO patients (Lahey)o 5 – 10 % of Caucasianso RVO OR 3.76 (95% CI of 1.06 – 13.4) noted in BMESo May be managed with vitamin supplementation (Folate)2/27/2013 14

Primary ThrombophiliaExamples• Antiphospholipid Antibody syndromeo Lupus anticoagulanto Anticardiolipin antibodieso 10.8 % of young CVO patients (Lahey)o 2 – 4 % of the population2/27/2013 15

Perspectives on DiseaseAssociations• Systemic Diseases which are common in thepopulations at risk are, likewise, commonly seen inthe case populations reported in the long termstudies.• Presence of two uncommon diseases in one case isnot necessarily evidence for association.2/27/2013 16

Perspectives on DiseaseAssociations• Little evidence is available for PrimaryThrombophilia, Inflammatory disease, or otherHypercoagulable states in the Majority of patientswith RVO.2/27/2013 17

Anatomical Issues forRVO• Reports exist that document some patients have acongenital anomaly of the retinal vasculature(Kinky vein).• This alone can predispose an individual toexperiencing an RVO.2/27/2013 18

Testing Considerations• High Frequency testing for uncommon diseaseentities:o Reduces the test’s positive predictive valueo Potentially results in unnecessary anxiety on the patientsparto Likely is sub-optimal utilization of increasingly, limitedresources allocated for medical care.2/27/2013 19

Patient Modification ofRisk Factors• For known cardiovascular risk factors, this may bean important component of their therapy. Examplesinclude:o Diet selectiono Exercise appropriate for their current health statuso Medications known to favorably influence theircardiovascular health• May potentially reduce the progression fromperfused to ischemic RVO’s.2/27/2013 20

Patient Modification ofRisk Factors• May influence the likelihood for manifestation of theRVO in the fellow eye as latency period betweenthe eyes may be significant.• But, No proven Class I Rx benefit for efficacy.2/27/2013 21

Patient Modification ofRisk Factors• Current perspective for both the American Heartand American Stroke Association:o the Only Factor of significant benefit to reduce anindividuals systemic stroke risk : Control of an individual’sHypertension.2/27/2013 22

Take Home Points• Increased age and Glaucoma are dominant riskfactors for RVO.2/27/2013 23

Take Home Points• Cardiovascular risk profile has strong predictiveattributes:o Hypertension increases risk for BRVO or CRVOo Diabetes increases risk for CRVOo More physical activity decreases risk for CRVOo Moderate alcohol decreases risk for CRVOo Exogenous estrogens for post-menopausal womendecreases risk for CRVO.2/27/2013 24

Take Home Points• Hypercoagulability may play a role in limited cases:o Patients < 60 years of ageo Bilateral, simultaneous CRVO cases2/27/201325

Practice Guidelines toConsider• All patients with or without RVO should consider anannual general health assessment• Patients with bilateral, simultaneous CRVO:o Request comprehensive medical and hematologicevaluationo Whole blood viscosity and other rheologic assessmentsmay be helpful2/27/2013 26

Practice Guidelines toConsider• For patients without known risk factors:o Additional history of systemic thrombosis, rheumatic orinflammatory disease, and family history of thrombosis maybe used to guide medical consultationo Medical consultation in young patients to assess for serumhomocysteine levels and assay for anti-phospholipidantibody syndrome.2/27/2013 27

Thanks to:• Dr. Howard Ying, MD, PhD of the Wilmer Eye Institutefor some of the data and clinical correlationspresented today.Footer Text 2/27/2013 28

References1. Klein et al., Tr Am Ophth Soc. 2000; 98 :133 – 143.2. David et al., Ophthalmologica 1988; 197 : 69 – 74.3. Mitchell et al., Arch Ophth 1996; 114 : 1243 – 1247.4. Cugati et al., Arch. Ophth 2006; 124: 726 – 732.5. The Eye Disease Case – Control Study Group, AJO1993; 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