Retinal Vascular Occlusions

Joseph Sowka, OD, FAAO, Diplomate

Retinal Vascular Occlusive Disease

  • Second most prevalent retinopathy (behind diabetic retinopathy)
  • Strongly associated with systemic disease
  • Prominent morbidity and mortality

Anatomy

  • Central retinal vein
  • Single trunk in nerve, but may bifurcate within the substance of the nerve to a dual trunk.
  • Constrict within the lamina cribrosa in order to enter the globe.
  • Drains the retina through 4 tributaries
  • Central retinal artery
  • Feeds the inner 2/3rds of the retina
  • A branch of the ophthalmic artery
  • Parallels the venous arcades
  • Cilioretinal artery is truly a branch of the posterior ciliary artery and not a branch of the central retinal artery as most people think. This is why the cilioretinal artery fills before the central retinal artery on fluorescein angiography.

Venous Occlusive Disease

  • Central retinal vein occlusion (CRVO)
  • Hemi-retinal vein occlusion (HRVO)
  • Branch retinal vein occlusion (BRVO)

Central Retinal Vein Occlusion

  • Thrombotic phenomenon: Some property of the blood and central retinal vein act in concert to cause thrombotic occlusion. Causes partial or complete blockage of venous return
  • Vein inflammation
  • Vascular flow and/or vessel wall abnormalities stimulate vein thrombosis
  • Hypercoagulability states, elevated viscosity, and systemic states of decreased thrombolysis promote thrombus formation. (i.e., changes in blood constituents)
  • Turbulent blood flow causing thrombus formation at lamina
  • Laminar constriction site is the nidus for occlusion. Intraluminal pressure of the vein decreases, rendering it susceptible to collapse. Compression by an arteriolosclerotic CRA further affects flow and thrombus formation. CRV and CRA share common sheath passing through lamina cribrosa.
  • External factors such as increased IOP in POAG and papilledema (causing increased pressure in the optic nerve sheath) may cause further compression and contribute to occlusion.
  • Other factors that result in compression include: orbital tumor and abscesses, cavernous sinus thrombosis, and retrobulbar intranerve sheath injection.
  • Systemic diseases influence thrombus formation through:

1. External compression

2. Primary thrombus formation (Antiphospholipid antibodies)

3. Degenerative or inflammatory disorders of the vein itself

Central Retinal Vein Occlusion: Symptoms

  • Blurred vision
  • Loss of visual field
  • Photopsia, in rare cases
  • Asymptomatic (rare: more likely to have asymptomatic BRVO or HRVO)

Central Retinal Vein Occlusion: Clinical Signs

  • Dilated, tortuous veins
  • Deep and superficial hemorrhages
  • Disc edema
  • Macular edema
  • Posterior and anterior segment neovascularization
  • Collateral vessels
  • Pre-existing vascular anastomoses in vascular area
  • Collateral circulation is present to some degree in all organ systems. The extent to which collateral circulation prevents ischemia depends upon the time frame of the occlusion and the extent of collateral circulation for that organ and that individual.
  • Bypasses vascular bed occlusion
  • Beneficial- does not leak NaFl on FA
  • Larger caliber than neovascularization
  • Most commonly involves a communication between the retinal veins and the choroidal veins in response to retinal vascular occlusion

Clinical Pearl: Acute CRVO may cause angle closure glaucoma due to hemorrhagic choroidal expansion.

Central Retinal Vein Occlusion: Causes of Vision Loss

  • Macular edema: this is the prime cause of vision reduction in CRVO. Potentially reversible or treatable
  • RPE atrophy: occurs secondary to chronic macular edema and results in permanent vision reduction.
  • Macular ischemia: presents with severe, irreversible vision loss. This is often the cause when the vision loss is much more dramatic than the clinical picture.
  • Retinal hemorrhage (common)
  • Vitreous hemorrhage (rare)
  • Tractional retinal detachment (rare)
  • Neovascular glaucoma (common)

Central Retinal Vein Occlusion: Non-ischemic

  • Majority of cases (about 70%)
  • Acuity >20/200- low risk for neovascularization unless converts to ischemic form
  • Good prognosis
  • 5-20% progress from non-ischemic to ischemic CRVO
  • 83% of ‘indeterminate’ CRVO convert to ischemic CRVO over 4 months
  • Over 3 years, 34% of perfused eyes progressed to ischemic CRVO

Central Retinal Vein Occlusion: Ischemic

  • Minority of cases (about 30%)
  • Acuity < 20/200- high risk for neovascularization
  • Initial VA is typically count fingers
  • Extensive superficial hemorrhages
  • Multiple CWS
  • Poor capillary perfusion (10 or more cotton wool spots or 10 DD capillary non-perfusion on fluorescein angiography)
  • Turbid, orange, edematous retina
  • (+) RAPD
  • Poor prognosis
  • Very high risk of neovascularization or the iris and angle and a low/ moderate risk of disc/ retinal neovascularization.

Central Retinal Vein Occlusion: Ischemic Vs. Non-ischemic

  • Non-ischemic CRVO will have more dot & blot hemorrhages whereas ischemic will have retinal details obscured by flame-shaped hemorrhages. The presence of cotton wool spots indicates areas of retinal infarct and ischemia. The retina in non-ischemic CRVO will be relatively normal whereas it will be orange, turbid, edematous, and sick looking in ischemic CRVO.
  • Fluorescein angiography: 10 or more disc diameters of retinal non-perfusion on FA define ischemic CRVO. This does not guarantee that the patient will develop neovascular complications, but the odds are that they will.
  • Pupil defects: the ischemic CRVO will have a relative afferent pupillary defect due to destruction of the retina due to non-perfusion. Non-ischemic CRVO will typically not have an APD.
  • Visual acuity: Non-ischemic CRVO typically has acuity > 20/200; ischemic CRVO typically has acuity worse than 20/200 (i.e., finger counting at 2 feet).

Clinical Pearl: Most clinicians generally equate an ophthalmoscopically visible CWS with one DD of non-perfusion.

Clinical Pearl: Ischemic CRVO typically has vision in the CF range and an afferent pupil defect. If vision is better than 20/200, and there is no APD, then it most likely is non-ischemic.

Brain teaser: Why is neovascularization of the anterior segment so prevalent in ischemic CRVO while posterior segment neovascularization is so rare?

Central Retinal Vein Occlusion: Systemic Considerations

  • Hypertension*
  • Diabetes mellitus*
  • Elevated homocystein levels*
  • Cardiovascular disease (some studies feel that the CRVO pt. has no greater incidence of cardiovascular disease than age matched controls)
  • Hyperviscosity syndromes:
  • Hypergammaglobulinemia, paraproteinemia, hyperfibrinogenemia, cryofibrinogenemia
  • Hyperviscosity states:
  • Malignancy, paraproteinemia, nephrotic syndrome, chronic lung disease, Behcet's disease.
  • AIDS:
  • Infectious vasculitis
  • Collagen vascular disease:
  • Lupus and lupus-like diseases- Antiphospholipid antibodies, common in these diseases, interfere with endothelial cells and prevent interaction with platelets and anticoagulants, thus increasing thrombus formation.
  • Primary antiphospholipid antibody syndrome
  • Same reasons as collagen vascular disease, but phenomenon is primary entity
  • This is the most common cause of CRVO in young healthy adults (under age 50)
  • Syphilis:
  • Infectious vasculitis
  • Sarcoid:
  • Localized vein inflammation
  • Polycythemia (hyperviscosity)
  • Leukemia (blood dyscrasia-hyperviscosity)
  • Autoimmune disease:
  • Infectious vasculitis and antiphospholipid antibodies
  • Oral contraceptive use (causes a potentially hyperviscosity state)
  • Head injuries
  • Carotid artery disease:
  • Slow flow and increased viscosity
  • Hyperlipidemia
  • Mitral valve prolapse
  • Migraine
  • Pressure profusion abnormalities at ONH
  • Retrobulbar compression
  • Sickle cell disease (blood dyscrasia- hyperviscosity) - elevated hematocrit
  • Increased erythrocyte aggregation
  • Decreased plasma volume (causing increased viscosity and erythrocyte aggregation)

*Most experts feel that only these conditions must be examined for in the typical elderly vein occlusion patient and that more detailed evaluations should be reserved for special cases such as bilateral cases or in patients who are young (<50 yrs). In younger patients, testing for antiphospholipid antibodies is important.

Central Retinal Vein Occlusion: Management

  • Fluorescein angiography: questionable usage. Not appropriate early in the course as fluorescein is blocked by hemorrhage.
  • Pupil testing
  • Retinal photography
  • Gonioscopy to rule out angle neovascularization
  • IOP measurements
  • Co-management with primary care physician to identify and treat any underlying systemic disease
  • Referral to retinologist if NVD, NVE, NVI, NVG (for PRP), or unremitting macular edema develops.
  • Prophylactic PRP to prevent neovascularization inappropriate; therapeutic PRP once neovascularization develops very effective
  • Anti-angiogenic drugs such as Avastin being used successfully off label
  • Laser photocoagulation of macular edema (as for diabetic macular edema) not beneficial in cases of CRVO and hence not done
  • Newest treatment: intravitreal injection of steroids and anti-VEGF drugs (Avastin) for macular edema. Stabilizes vascular membranes and reduces vascular permeability. Very effective
  • Radial optic neurotomy – surgically cutting the nasal disc to decompress this “compartment syndrome” – very radical

Clinical Pearl: The main cause of vision reduction in CRVO is macular edema.

Clinical Pearl: The most common causes of severe, permanent vision loss in ischemic CRVO are macular infarct and neovascular glaucoma.

Clinical Pearl: Ischemic CRVO most commonly forms neovascularization of the iris and angle, and only rarely the posterior segment.

Clinical Pearl: A non-ischemic CRVO (or BRVO, HRVO) can convert during their clinical course from a non-ischemic event to an ischemic event.

Clinical Pearl: Intravitreal injections of steroids and anti-VEGF drugs are being investigated and used for edema secondary to vascular occlusions, diabetes, cystoid macular lesions, and wet age related macular degeneration.

Clinical Pearl: New understanding of autoimmunity suggests that young patients with CRVO be tested for primary antiphospholipid antibody syndrome, especially if there are no other concurrent conditions present

Hemi- Retinal Vein Occlusion

  • Historically has been considered a variant of branch retinal vein occlusion. Pathophysiologically, it most closely resembles CRVO. In terms of natural history and neovascular complications, it most closely resembles BRVO.
  • Involves superior or inferior drainage only
  • May be ischemic (23%), non-ischemic (67%), or indeterminate (10%)
  • Photograph and monitor q1mos until resolution
  • Fluorescein angiography: Not useful early in the course because fluorescein is blocked by the hemorrhage. Questionable usefulness.
  • Directed internal medicine consultation to evaluate systemic health. If patient has diseases known to be associated with vascular occlusive disease and patient is already being managed medically, send internist a letter detailing patient's ocular status.
  • Non-ischemic HRVO has very little propensity to develop neovascularization
  • Ischemic HRVO has a high propensity to develop neovascularization of the disc/ retina and a low/ moderate risk to develop neovascularization of the iris and angle.

Clinical Pearl: HRVO develops most like CRVO, but behaves most like BRVO.

Brain Teaser: Ischemic HRVO most typically develops neovascularization of the disc and retina and only rarely of the iris. Why is anterior segment neovascularization so rare in HRVO, while posterior segment neovascularization is much more so common?

Clinical Pearl: The main cause of vision reduction in HRVO is macular edema.

Clinical Pearl: The most common causes of severe, permanent vision loss in patients with HRVO are macular infarct and tractional retinal detachment.

Branch Retinal Vein Occlusion

  • Occurs at arteriovenous crossing
  • Most commonly superiotemporal
  • Arteriolosclerotic etiology: as the arteriole becomes sclerotic, it compresses the underlying venule leading to thrombus formation and leakage from the capillary beds draining into the venule. At no time in vascular occlusion does the vein or venule ever leak. All leakage is from the capillaries.
  • Vein compression will lead to turbulent blood flow, which damages the endothelium and sets the stage for platelets, thrombin, and fibrin to form a thrombus.
  • May present with loss of acuity and/or field, but may be asymptomatic
  • There are three location classification for BRVO

1. Hemispheric

Before the first bifurcation. Technically HRVO

2. Intermediate

After the first bifurcation. Typical BRVO appearance

3. Twig

Macular area only

Branch Retinal Vein Occlusion: Ischemic
  • 20-30% of cases
  • VA < 20/200 typically
  • Both blot and flame shaped hemorrhages
  • Cotton wool spots
  • Macular edema (this is the most common cause of vision loss in BRVO)
  • NVD; NVE; vitreous hemorrhage: tractional retinal detachment common (as cause of permanent severe vision loss).
  • NVI, NVG are rare in BRVO (for the same reasons as in HRVO).
  • Macular capillary non-perfusion may occur with devastating vision reduction which is irreversible
  • Ischemic BRVO is defined as 5 disc diameters of retinal capillary non-perfusion on fluorescein angiography.

Branch Retinal Vein Occlusion: Non-ischemic

  • 70-80% of cases
  • VA > 20/200 typically
  • Blot, flame shaped hemorrhages
  • Rare CWS
  • Mild macular edema
  • Collateral vessel formation

Branch Retinal Vein Occlusion: Causes of Vision Loss

  • Macular edema (most common cause and typically reversible)-any form
  • Macular capillary non-perfusion (perifoveal capillary loss) - ischemic
  • Vitreous hemorrhage- ischemic
  • Tractional retinal detachment- ischemic
  • Rarely NVG- ischemic
  • In terms of neovascularization, BRVO behaves most like HRVO in that the neovascularization is predominately in the posterior segment and rare in the anterior segment.

BRVO Study Group: Findings

  • Macular edema:
  • 3-18 month window of opportunity to treat
  • Do not treat macular hemorrhage
  • Treat only if VA < 20/40 and due to macular edema
  • Prophylactic treatment to avoid neovascularization not indicated- only treat with PRP after neovascularization forms.
  • As mentioned earlier, macular edema secondary to BRVO is increasingly being addressed by intravitreal steroid and anti-VEGF injections.

Clinical Pearl: The main cause of vision reduction in BRVO is macular edema.

Clinical Pearl: Ischemic BRVO most typically develops neovascularization of the disc and retina and only rarely of the iris.

Clinical Pearl: The most common causes of severe, permanent vision loss in patients with BRVO are macular infarct and tractional retinal detachment.

Clinical Pearl: You can have an ischemic BRVO (and possibly HRVO) with good acuity and no RAPD (but they aren’t common).

Branch Retinal Vein Occlusion: Systemic Associations

  • Hypertension: 70% of cases- most commonly associated medical condition
  • Diabetes
  • Atherosclerosis
  • Hyperlipidemia
  • Blood hyperviscosity
  • Carotid artery disease
  • Coronary artery disease

Branch Retinal Vein Occlusion: Management

  • Referral to internist for directed work-up
  • Monitor q1mos until resolution of hemorrhages
  • Monitor q4-6 months for the next three years
  • 50%-60% will have 20/40 or better vision without treatment
  • Possible fluorescein angiography
  • Retinal photography
  • Retinologist only if complications develop (neovascularization or unremitting macular edema with vision loss)
  • Laser photocoagulation for macular edema
  • Steroid/ anti-VEGF injection for macular edema
  • PRP/ anti-VEGF injection for neovascularization
  • Arteriovenous sheathotomy
  • The overlying artery is separated from the vein with a microvitreoretinal blade. A pars plana vitrectomy is first performed (surgical removal of the vitreous). An incision is then made in the adventitial sheath adjacent to the arteriovenous crossing, and is extended along the membrane that holds the blood vessels in position to the point where they cross. At this point, the blade is used to separate adhesions holding the artery to the vein. The artery is then lifted away from the vein.
  • Cutting the sheath around the vessels and physically separating them where they cross should improve blood flow through the vein.
  • Unanswered questions:
  • Timing?
  • Advantages of sheathotomy vs vitrectomy alone vs intravitreal injections vs natural untreated history?
  • An option for those patients with macular edema unremitting to other treatments

Clinical Pearl: In BRVO and HRVO, only treat macular edema if vision is worse than 20/40.

The Standard Care Vs. COrticosteroid for REtinal Vein Occlusion (SCORE) Study

  • The SCORE Study will compare the effectiveness and safety of standard care to intravitreal injection(s) of triamcinolone for treating macular edema associated with CRVO and BRVO.

Arterial Occlusive Disease

  • Central retinal artery occlusion (CRAO)
  • Ophthalmic artery occlusion
  • Cilioretinal artery occlusion
  • Branch retinal artery occlusion (BRAO)
  • Carotid artery disease (CAD) and Ocular Ischemic Syndrome (OIS)

Central Retinal Artery Occlusion: Clinical Picture

  • Painless, sudden loss of monocular vision
  • Vision is count fingers to hand motion to no light perception
  • Retinal edema causing white appearance to fundus
  • Mean age is 60's
  • Cherry red macula due to underlying choriocapillaris perfusion and lack of overlying structures within this area.
  • Optic atrophy ensues eventually

Central Retinal Artery Occlusion: Pathophysiology

  • Etiology is typically emboli from carotid artery or heart lodging in central retinal artery at laminar constriction. Emboli of cardiac origin are more likely than emboli of carotid origin to cause artery occlusion
  • Other possible etiologies:
  • Giant cell arteritis (GCA)
  • Intraluminal thrombosis
  • Hemorrhage under atherosclerotic plaque
  • Vasospasm
  • Dissecting aneurysm
  • Hypertensive arteriolar necrosis
  • Circulatory collapse

Clinical Pearl: In 2-10% of cases, the cause is thrombosis formation due to giant cell arteritis. If the cause is GCA, bilateral involvement can occur in hours to days. GCA must always be considered as a cause of CRAO in the elderly!

Ophthalmic Artery Occlusion: Compare and Contrastto CRAO

  • NLP vision
  • Cherry red spot not present
  • More severe retinal whitening
  • Systemic associations similar to CRAO, but much higher incidence of GCA

Cilioretinal Artery Occlusion:

  • Local infarcted area
  • Severe loss of central acuity with preservation of peripheral field
  • Systemic causes similar to CRAO
  • Higher incidence of GCA, especially if concurrent AION exists

Central Retinal Artery: Heroic Treatment

  • Paracentesis to reduce IOP and allow less compression on CRA to allow emboli to pass further.
  • Carbogen
  • Patient is hospitalized and breathes Carbogen 5-10 minutes every hour for 24 hours. Using pure oxygen is worse because there will be a reflex constriction of the blood vessels. Carbogen increases CO2 levels, which causes a rebound vasodilation.
  • Digital massage to transiently elevate IOP and have rebound IOP decrease and subsequent arterial dilation
  • Breathing into a brown paper bag in order to increase blood CO2 levels.
  • Fibrinolytic agents (clot-busters: urokinase, streptokinase)
  • 1-24 hour window of opportunity
  • Treatment vs no treatment: 1/4 line difference in Snellen acuity. Overall, heroic measures do not affect final visual acuity (only anecdotal success).
  • If the cause is inflammatory thrombosis from GCA, these heroic measures will do nothing because there is no embolus to dislodge.

Clinical Pearl: In patients over the age of 60 years, CRAO may be caused by giant cell arteritis. You must get an ESR and C-reactive protein on every patient over the age of 60 years with CRAO because if the cause is GCA, the patient will progress to bilateral vision loss in hours to days.