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Ischemic Ocular Disease

Vondolee Delgado-Nixon, PhD, FAAO

The Ohio State University College of Optometry

~Nothing to Disclose~

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What is Ischemia?

A restriction in blood supply• Decreased oxygen delivery

Generally caused by:• Vascular disease

• Hypercoagulopathies

Two major types of ischemia:1. Occlusive Ischemia

2. Hemorrhagic Ischemia

This image was originally published in the Retina Image Bank. Retina Image Bank. Apr 7 2018; © the American Society of Retina Specialists."

Occlusive Ischemia

Occlusion etiology:A. Thrombus in artery or arterioleB. Loss of fluid in vessel decreases 

flow downstream ‐ GCA

Appearance:• Pallor• Edema 

Cells my be injured or dead• Chronically injured cells accumulate water

• Sudden death of cells not visible until later

https://slideplayer.com/slide/13148712/

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Hemorrhagic Ischemia

Decreased oxygen delivery due to rupture of vessel

• High capillary pressure1. Hypertension

2. Venous occlusion/compression

Appearance:• Red!

• Blood obstructs view of ischemic area

https://webeye.ophth.uiowa.edu/eyeforum/cases/274‐branch‐retinal‐vein‐occlusion.htm

Case: Sudden loss of vision OS

• 81 year old white male • Presented with sudden, painless vision loss in left eye

• Sudden black spot in vision that spread out over his complete visual field within 15 min.• Drove himself to OD

• Review of systems• Denied: headache, jaw claudication, scalp tenderness, weight loss, or loss of appetite• CAD s/p CABG and balloon angioplasty• Right carotid endarterectomy (1980s)• Left carotid stenting (endovascular) recently with transient right hemiparesis (resolved)

• Rx• ASA• Plavix• Nitroglycerine PRN• Alfalfa pills

O’Malley, MD and Lee, MD 2005 – University of Iowa

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Examination Findings

• BCVA: 20/30 OD, and HM OS

• Pupils: greater than 2.5 LU RAPD OS

• GVF: full OD. Small inferior island of V4e OS.

• EOM: Full OU

• Anterior segment: mild nuclear sclerosis cataracts OU

• Fundus: Normal OD, cherry red spot OS

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Central Retinal Artery Occlusion

Incidence: 1‐2/100,000 in US

Where is the occlusion?1. Embolus lodged where the 

central retinal artery pierces the dural sheath of optic nerve

2. Thrombus formed immediately posterior to lamina cribosa

3. 5‐10% associated with GCA of ophthalmic artery

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Presentation of CRAO

Unilateral, painless loss of vision• Reduced visual acuity: variable 

• Afferent pupillary defect

• Whitening of the retina

• Macula appears as a cherry red spot

• Narrowing of the retinal arteries

• Sludging or segmentation of the blood in the arterioles

What are the risk factors for CRAO?

Atherosclerotic Risk Factors• Hypercholesterolemia• Diet • Lack of exercise• Diabetes mellitus (T1DM and T2DM)• Smoking• Hyperhomocystenemia

Carotid/Heart Disease• Stenting complications• Prior MI• TIA• Stroke

Coagulopathies:• Hereditary:

• Factor V Leiden Mutation• Prothrombin Mutation• Antithrombin III Mutation• Protein S deficiency• Protein C deficiency

• Acquired:• Estrogen/Progesterone• Obesity• Smoking • Cancer• Hyperhomocysteinemia• Antiphospholid Antibody Syndrome

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CRAO Classification

Non‐arteritic CRAO• 66% of the CRAO that occur

Non‐arteritic CRAO with cilioretinal artery sparing• 14% of the CRAO that occur

CRAO associated with giant cell arteritis • Less than 5% of all CRAO cases

Transient non‐arteritic CRAO• 15% of the CRAO that occur

Non‐Arteritic CRAO

Non‐Arteritic CRAO

• Retinal ischemia with cherry red spot

• FANG shows absent or poor retinal circulation

• Visual acuity ranges from 20/200‐NLP

• Women affected 42% of the time• Average age 67.7 • Amaurosis fugax seen 12% prior • Vision loss notice after waking 35%

Non‐Arteritic CRAO w/CilioretinalSparing

• Retinal ischemia with cilioretinalsparing

• Visual acuity ranges 20/30‐LP• VA depends on size of cilioretinalartery: larger artery better VA

• Women affected 46% of the time

• Average age 67.1

• Amaurosis fugax seen 12% prior 

• Vision loss notice after waking 29%

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Anatomy: Cilioretinal Artery

• ~35% population 

• Provide perfusion to maculopapillary tissue

Hayreh S.S. (2015) The Cilioretinal Arteries. In: Ocular Vascular Occlusive Disorders. Springer, Cham

Arterial occlusion after scleral bucklingBritish Journal of Ophthalmology 2010;94:523-524.

Where Do Clots Come From? 

Arise from:• Bifurcation of Common Carotid Artery

• 70‐90% 

• Heart (Cardiogenic)

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Bifurcation of Common Carotid Artery

• Atherosclerosis occurs at areas of turbulence

https://anatomy‐medicine.com/cardiovascular‐system/124‐blood‐vessels‐of‐the‐head‐and‐neck.html

How do clots form?

Atherosclerotic Emboli:

1. Artery Injury ‐ Turbulence

2. Cholesterol accumulation • Atheroma Formation

• Cholesterol Crystals

3. Calcification 

4. Rupture

5. Thrombus Formation

6. Embolization

Transferred from en.wikipedia to Commons. [CC BY‐SA 3.0 (http://creativecommons.org/licenses/by‐sa/3.0/)] 

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How do clots form? (cont.)

Actual clot composed of Platelets and Fibrin

How do clots form? (cont.)

Mechanism has 2 Parts:A. Platelet plug formation

B. Coagulation – fibrin

Clots:• Appear white when platelets > fibrin

• Appear red when fibrin > platelets

Damjanov, Pathology for the Health Professions, 2017

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Therapeutics

Change Life‐style

Statins 

Anti‐thrombotics• Anti‐platelet 

• NSAIDs• Plavix

• Anticoagulants• Warfarin• Coumadin• Xarelto

AntihypertensivesDiureticsCardioinibitoryVasodilators 

Thrombus

Platelets > Fibrin

The carotid artery during carotid surgery is shown. Photograph courtesy of Dr E. Gravereaux, Harvard Medical School, Boston, Mass., Published in Sobieszczyk and Beckman, Circulation, 2006, 114(7)

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Potential Effects of Carotid Artery Disease

Critical Stenosis

Thrombi in carotid• Friable

• Source for Thromboemboli 

Shedding of Calcium from atherosclerotic plaque

Dr. Todd Ragan, OD and Dr. Mario Matos‐Cruz, MD

Other Emboli Can Arise From AtherosclerosisThromboemboli

Hollenhorst PlaqueCalcium Crystals

Kanski’s Clinical Ophthalmology, 2015

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Balloon Angiography with Stenting of Carotid ArteryPros:

• Reperfuses vessel

• Not as invasive as endarterectomy

• Not as dangerous as endarterectomy

Cons:• Re‐stenose

• Trauma‐induced dissection

• Stroke 

Where Do Clots Come From? 

Arise from:• Bifurcation of Common Carotid Artery

• 70‐90% 

• Heart (Cardiogenic)

Ahuja RM et al Stroke 1999: 30(8); 1506‐1509Babikian V et al Cerebrovasc Dis 2001; 12:108‐113

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Cardiogenic Sources 

Etiologies:• Atrial Fibrillation

• Heart Valve Disease

• MI

How does MI cause Retinal Artery Occlusions?

Mechanism:Heart attacks kill heart muscle

Mural Thrombus• Clot on dead heart muscle

5X increased risk (stroke) 30 days after MI

• Ex. BRAO right eye

Kim et al, Invest. Ophthalmol. Vis. Sci.. 2018;59(11):4731-4737. doi:10.1167/iovs.18-23987

Dr. Rocke Robertson [CC BY‐SA 4.0 (https://creativecommons.org/licenses/by‐sa/4.0)]

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Work Up

• Blood draw• Immediate ESR, CRP, CBC with differential, PT/PTT

• Chem 7, lipid profile

• Carotid Doppler

• Electrocardiography

Treatment for CRAO

Medical Emergency• Early treatment is key for retinal recovery

• Acutely perform ocular‐digital massage (240 minutes complete and total optic atrophy and nerve damage)

• Anterior chamber paracentesis

• Acetazolamide 

• Increase O2 delivery [vasodilators, nitrodilators, hyperbaric, Carbogen therapy (CO2 + O2]

*Improved VA is rare

Hayreh, SS, et al, Exp Eye Res, 2004 78:728‐736Hayre SS, et al. Ophthalmology 2009 116(10); 1928‐1936

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CRAO Case Revisited

https://webeye.ophth.uiowa.edu/eyeforum/cases/case20.htm

Patient MHx:• CAD s/p bypass• Carotid vascular disease with right endarterectomy 1980s

• Carotid endovascular stenting left

Differential:• Carotid artery dissection• Stent thrombosis• Carotid artery restenosis• Cardiogenic

Plan: • Admitted patient• Angiogram for carotid evaluation• Left carotid dissection at the site of the stent

• Surgical implantation of telescoping stent

Case: Blurred vision

• 67 year old black female

• Presents with decreased vision OD • Blur is at distance and near

• Patient noticed the vision changes two weeks ago

• Vision has not gotten worse, nor has it gotten better

• Review of systems• Hypertension controlled with medication, BP at exam 140/86

• Hyperlipidemia controlled with medication

• Diabetes type II controlled with oral medication, BSL 128, HgA1c 6.0

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Exam

• Entrance visual acuities: 

• 20/100 OD, 20/25 OS

• Pupils: RRL –APD

Central Retinal Vein Occlusion

• Incidence: ~1/1000 worldwide

• Pathophysiology • Arteriosclerosis

• Blood stasis

• Hypercoagulability 

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CRVO Presentation

• Sudden, unilateral, painless vision loss

• Afferent Pupillary Defect

• Cotton wool spots

• Visual acuity: variable

• Retinal hemorrhages in four quadrants

• Blood vessel tortuosity and dilation in four quadrants

• Macular edema

• Optic disc edema

Who is at risk?

Wong, Tien Y., and Ingrid U. Scott. "Retinal‐vein occlusion." New England Journal of Medicine 363.22 (2010): 2135‐2144.

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CRVO Classifications

Non‐Ischemic

• 2/3 of the cases• Visual acuity 20/400 or better

• No afferent pupillary defect

• No cotton wool spots

• Capillary perfusion seen on FANG

Ischemic

• 1/3 of the cases• Visual acuity 20/400 or worse

• Visual field constriction

• Afferent pupillary defect

• Cotton wool spots

• No capillary perfusion seen on FANG

Differential Diagnosis: BRVO

Branch retinal vein occlusion• 4x more common than central retinal vein occlusion

• Commonly caused by hypertension

• Presentation• Blind spot in visual field or loss of vision

• Sectoral retinal hemorrhages

https://imagebank.asrs.org/file/184/branch‐retinal‐vein‐occlusion

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Differential Diagnosis: Ocular Ischemic Syndrome

• AKA Carotid Occlusive Disease

• Typically seen in patients 50‐80 years of age

• More common in men than women (2:1)

• Presentation• Mid peripheral retinal hemorrhages

• Dilated blood vessels without tortuosity

• Disc edema is absent

• Preceded by transient ischemic attacks

https://imagebank.asrs.org/file/3344/ocular‐ischaemic‐syndrome‐colour‐2Costa et al, Ophthalmology. Apr 1998;105(4):689‐693.

What Causes Venous Occlusions?

90‐95% Arteriosclerosis• A‐V Crossings

• Arterial disease occludes vein

5% Hypercoagulopathies• Not at A‐V Crossings

Beaumont PE, Kang HK. Clinical characteristics of retinal venous occlusions occuring at different sites. Br J Ophthalmol. 2002;86: 572-580

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Arteriosclerosis

Due to chronic hypertension

Thickening of arterial intima• Scarring

Narrowing of the lumen

Normal Arteriole Hyaline Arteriosclerosis

Kumar, V., Abbas, A. K., & Aster, J. C. (2015). Robbins and Cotran pathologic basis of disease (Ninth edition.). Philadelphia, PA: Elsevier/Saunders.

Venous Occlusions are Red Infarcts• Compression/Occlusion of vein

• Blood backs into capillary bed

• Capillaries rupture

http://www.scienceofrvo.org/learn/

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Hypercoagulation and Red InfarctsClots (red)

• Fibrin>Platelets• Occur in Veins or areas of stasis

Hypercoagulopathies:• Hereditary:

• Factor V Leiden Mutation• Prothrombin Mutation• Antithrombin III Mutation• Protein S deficiency• Protein C deficiency

• Acquired:• Estrogen/Progesterone• Obesity• Smoking Cancer• Hyperhomocysteinemia• Antiphospholipid Antibody Syndrome

Mark Braun, MD braunm@indiana.eduCopyright 1998, the Trustees of Indiana University

https://webeye.ophth.uiowa.edu/eyeforum/cases/274‐branch‐retinal‐vein‐occlusion.htm

Atherosclerosis vs Arteriosclerosis 

Arteriosclerosis ‐Hypertension

• BRVO and CRVO• Hemorrhage

Atherosclerosis – Cholesterol

• BRAO and CRAO• Thromoboembolism, Calcium and Hollenhorst

• Appear white

Kanski’s Clinical Ophthalmology, 2015

https://webeye.ophth.uiowa.edu/eyeforum/cases/274‐branch‐retinal‐vein‐occlusion.htm

This image was originally published in the Retina Image Bank. Retina Image Bank. Apr 7 2018; © the American Society of Retina Specialists."

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Work up

• Blood draw• Fasting blood glucose, Hemoglobin, CBC with differential, Platelets, PT/PTT, ESR, lipid profile, homocysteine, ANA, FTA‐ABS

• Blood pressure

• Cardiovascular work up

Complications

• Macular edema• Typically seen in the acute stage of CRVO with resolution seen within 2‐15 months

• Vitreous hemorrhage• 10% developing by 9 months

• Neovascularization• Incidence in Non‐ischemic CRVO is up to 33% over 12‐15 months

• Incidence in Ischemic CRVO is up to 20% over 8‐9 months

• Neovascular glaucoma• Occurs with Ischemic CRVO in up to 60% over 12‐15 months

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Treatments

For Neovascularization = no prophylactic PRP for CRVO• Central Retinal Vein Occlusion Study (CVOS)

Macular Edema Secondary to CRVO:• 1 mg triamcinolone should be considered

• SCORE study (Standard of Care Versus Corticosteroid for Retinal Vein Occlusion

• Intraocular injection of ranibizumab• CRUISE study

Macular Edema Secondary to BRVO:• Grid photocoagulation should remain standard of care

• SCORE study

• Intraocular injection of ranibizumab• BRAVO study

Thank you!