Lab and Imaging Interpretation Primary Eye Care · Lab and Imaging Interpretation Primary Eye Care practice, ... Visiting Professor of Clinical Medicine ... •Educate & Follow q

12/21/2013

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Lab and Imaging Interpretation Primary Eye Care

James L. Fanelli, OD, FAAO Visiting Professor of Clinical Medicine

Pa College of Optometry

[email protected]

[email protected]

AOA Meeting, 2014

Goals of the Presentation

• One Goal, and One Goal Only:

• To give you one nugget of information that you can take home and actually use in your practice, maybe two.

– Use that information to make you a better clinician

What the Goals are NOT:

• To have you become a hematologist

• To have you become a radiologist

This is a CEE/TQ Course

• It comes with an examination! – Exciting, yes?

• Pay attention to information presented in either red or gray font, as you may see that information again

• You can fill out your course evaluation at this point

Interpretation of Diagnostic Tests: A

Synopsis of Laboratory Medicine

Jacques Wallach MD

Little, Brown and Co

Clinical Implications of Laboratory

Tests

Tilkian, Conover & Tilkian

Mosby Co

mailto:[email protected]

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Interpreting Lab and Imaging Studies

• This is a Lab Study:

• This is an Imaging Study:

Why order Lab & Image Testing? • Objective measurment

• Helpful in DDx

• Dx confirmation

• Screening for unsupected illness

• Monitor compliance to therapy

• Monitor response to condition/treatment

• Medico-legal justification of Tx

Why Order Testing???

Clinical Confirmation

confirmatory diagnosis

Adjunct to Thorough Examination

covering the bases

Co-Management vs. Direct Involvement

refer vs. orchestrate

Can I Order Lab/Image Test? • Yes, most states allow ODs to order;

–Diagnostic Laboratory test for eye related conditions

–Radiological Imaging test for eye related conditions

What Are My Options?

• Hospital

• In-office

• Reference Laboratory

• Imaging Center

– Hospital based

– Private imaging center

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Typical Laboratory Tests • Complete Blood Count (CBC)

• Blood Chemistry/Profiles

• Urine Analysis

• Serology

Profile Examples

• Autoimmune Profile

– Anti-ANA antibodies, ANA, Complement C3

• Lipid Profile (VAP Cholesterol)

– Cholesterol, HDL, LDL,Triglycerides

• Thyroid Function Profile

– Free Thyroxin index (FTI), T4, T3 Uptake, Thyroid Stimulating Hormone (TSH)

Imaging Tests Available

• Plain Film X-Ray

• Computed Tomography (CT)

• CT Angiography (CTA)

• Magnetic Resonance Imaging (MRI)

• Magnetic Resonance Angiography (MRA)

• Magnetic resonance Venography (MRV)

• Carotid Doppler Ultrasonography

• Temporal Artery Ultrasonography

Lecture Format

Anatomy/Physiology Pathophysiology PEARLS

Lab/Image Results

Case Example SOAP

Lab/Image Test

Complete Blood Count (CBC) • WBC w/ Differential

• RBC Count

• Hematocrit

• Hemoglobin

• RBC Indices (MCV, MCH, MCHC)

• Peripheral Blood Smear

• Red Cell Distribution

• Reticulocyte Count

• Platelet Count

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CBC - Retinal Hemorrhage (Subjective)

• 41 YOWF secretary c/o Blur @ Near resulting in daily fatigue @ work

• First Eye Exam

• MHx: Unremarkable, 10 yrs since last physical

• Meds: None

• NKDA

CBC - Retinal Hemorrhage (Objective)

• BVA: 20/20 OD, OS w/ +1.00 ADD

• Neuro: PERRLA (-) APD; EOM-I

• SLE: Unremarkable

• DFE: Isolated Intraretinal Hemorrhage/CWS

• BP: 118/70

CBC - Retinal Hemorrhage (Objective)

CBC - Retinal Hemorrhage (Assessment)

1. Presbyopia

2. Retinal Hemorrhage with microinfarction

Additional History

• Fatigue also on weekends and has noted SOB and palpitations upon exertion

CBC - Retinal Hemorrhage (Plan)

1. Prescribe PAL w/ Adjustment to Work Station

2. -Physical Exam

-Laboratory Investigation ( Include CBC, SMA, ESR, ANA)

-RTC 1 month F/U DFE

CBC - Retinal Hemorrhage Lab Results/Final Assessment

Elevated

MCV

Low

RBCs

Hemoglobin

Hematocrit

Additional Labs

Low Fasting B12

(dietary lack or absorption?)

Normal Serum Folate (B8)

Schilling Test Stage I: known marked amount of B 12

ingested/excreted

Stage II: admin of ‘intrinsic factor’ followed by oral B12 ingestion and clearance

Final Dx: Pernicious Anemia

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CBC - Retinal Hemorrhage Discussion

Anatomy RBCs (erythrocytes)- # Red Cells in mL of Venous

Blood

Hemoglobin- O2 Carrying Pigment of RBCs

Hematocrit- Column of RBCs in 100 mL of Blood

MCV- Avg. Volume of individual cells in cubic Microns. Hematocrit X 10 divided by RBCs

Retinal NFL or capillary bed


Physiology • RBCs- Carries Hemoglobin

• Hemoglobin- Transports O2 to Tissue and CO2 to Lungs

• Hematocrit- measure of volume occupied by RBC’s

• MCV- individual cell volume elevated to increase O2 transport


• Physiology

–individual cellular effects occur at level of capillary bed

–Vitamin B-12

• co enzyme utilized in amino acid metabolism

• stimulates erythropoiesis


Pathophysiology • Pernicious anemia - precipitated by a gastric

condition that interferes with B12 absorption which results in ineffective erythropoiesis.

• Retinal hemorrhage/infarct from tissue hypoxia

• Decreased oxygen transport results in fatigue, dyspnea, angina, and syncope.


PEARLS

• 70-80% of Hematologic Disorders Dx by CBC

• B12 Absorption Defect not Dietary Lack

• Rare Before Age 35

• More Common in Scandinavian, English, and Irish. Rare in Orientals

• Treated w/ B12 (cyanocobalamin) Injections

Atherosclerosis Risk in Communities Study ARIC

• Initiated by the National Heart Blood and Lung Institute – Investigate factors that are involved with the

development of atherosclerosis and the incidence of CHD, stroke and other cardiovascular diseases

– Measure cardiovascular disease rates in communities over time

– 15,792 initial participants

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ARIC and Retinopathy

• What is incidence and prevalence of retinopathy?

– 3.8% chance of developing retinopathy

– 7.7% prevalence rate

– Retinopathy related to: • Fasting serum glucose

• Cholesterol

• Mean arterial blood pressure

• Plasma fibrinogen

• In non diabetics, incidence and prevalence are halved, with BP being the leading risk factor

Wong et al. Three-year incidence and cumulative prevalence of retinopathy: the atherosclerosis risk in communities study. Am J Ophthalmol. 2007 Jun;143(6):970-6. Epub 2007 Apr 2.


• ARIC (Atherosclerosis Risk in Communities) Study – Wong et al

– 1684 participants

– One arm of study compared MR findings with retinopathy in the context of STROKE

– retinopathy included: • microaneurysms, retinal hemorrhages, soft exudates, hard

exudates, macular edema and optic disc swelling

ARIC Prelim Results

• The overall incidence of stroke was found to be related to:

– 1: MR findings of white matter lesions

– 2: presence of “retinopathy”

Atherosclerosis Risk in Communities

• Findings:

– The 5-year cumulative incidence of clinical stroke:

– (-) white matter lesions 1.4%

– (+) white matter lesions 6.8%

– (-) retinopathy 1.4%

– (+) retinopathy 8.0%


• Higher Incidence of Clinical Stroke was related to ‘retinopathy’ and + MR findings independently.

• Was there a link between the two distinct clinical signs?


• Findings:

– No retinopathy:

• 9.9% chance of having MR lesions

• 1 out of 10

– With retinopathy:

• 22.9% chance of having MR lesions

• 1 out of 4 !!!

What about both together in a patient???

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• Findings: – 5year cumulative incidence of stroke:

• (-) white matter lesions and (-) retinopathy: 1.4%

• (+) white matter lesions and (+) retinopathy: 20.0%

– The study suggests that healthy people with white

matter lesions detected by MRI may benefit from a retinal examination to assess their risk of stroke.

Blood Chemistry (SMA or Profiles)

• Quick survey of body systems with an overall appreciation for the patients general condition as well as detection of abnormalities in specific systems

• Glucose, Lipid/Cholesterol, Electrolytes, Renal Function, Liver Function, Mineral/Bone Metabolism, Protein, Cardiac Function, Thyroid Profile, etc.

Blood Chemistry- Retinal Emboli (Subjective)

• 57 YOWM c/o decreased VA X 3 wks.

• POHx: Unremarkable; LEE: 2+ yrs.

• PMHx: S/P MI w/ CABG X 3, NIDDM X 16 mos.

• MEDS: Plavix, Lipitor, Glucophage

• NKDA

Blood Chemistry-Retinal Emboli (Objective)

• BVA: OD 20/30; OS 20/50 w/ -1.00 & -1.50 Refractive Shift

• Ta: OD 19 mmHg; OS 18 mmHg

• SLE: Clear OD, OS

• DFE: 1/3 AV with Nicking, Stage II AS, Multiple Arterial Plaques; Multiple Mid-peripheral Intraretinal Hemes.

• BP 140/85 LAS

Blood Chemistry- Retinal Emboli (Objective)

Blood Chemistry- Retinal Emboli (Assessment)

1. Asymptomatic Cholesterol Retinal Emboli

2. Suspected Diabetic VA Fluctuations

3. NPDR moderate

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Blood Chemistry- Retinal Emboli (Plan)

CBC w/ Diff, ESR, Diabetic Profile

VAP Cholesterol Profile

– Lipid profile (total, LDL, HDL, VLDL,triglycerides, cardio risks)

– Lipoprotein A Cholesterol

– Homocysteine levels

– CRP

VAP Cholesterol Test Vertical Auto Profile

http://www.atherotech.com

VAP Cholesterol

• Global Cardiometabolic Risk stratification

• Total, HDL, LDL, triglycerides

• Also measures cholesterol subclasses that play a major role in the development of ASCVD

• Benefits: – More accurate risk profile

– Provides basis for patient specific treatment

Blood Chemistry- Retinal Emboli (Plan)

• Carotid Doppler

• IM Communication

• Educate & Follow q 1 month

Blood Chemistry- Retinal Emboli Labs

High

• Fasting Glucose (133 mg/dl), Hgb A1C (10.2), Cholesterol (296 mg/dl), LDL, homocysteine

Low

• HDL

Risk 2.5/1

Doppler 80% Blockage @ Bifurcation

Blood Chemistry- Retinal Emboli Final Diagnosis/Plan

1. Hypercholesterolemia

2. Type II DM w/ NPDR

3. Carotid Occlusive Dz

4. Hyperhomocysteinemia

1. & 2. Medicate

3. Consider Endarterectomy

4. ????

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Blood Chemistry- Retinal Emboli Discussion

Anatomy/Physiology

• Carotid to Retinal Arteriole Vasculature & Blood Flow

• Serum Cholesterol, HDL, LDL,

Hgb A1C & Glucose



Pathophysiology • Hypercholesterolemia/Plaque Formation

• Arteriosclerosis

• Carotid Stenosis

• Hyperglycemia



PEARLS

• Moniter Hgb A1c

• Eye w/ MHx Significance

• Profile vs. Individual Test

• Systemic Risk of Retinal Emboli

• Hyperglycemia also Seen w/ Certain Medications(ie. Cortisone) and Trauma

Lipoproteins

• 5 categories

– HDL (high density lipoproteins)

– LDL (low density lipoproteins)

– Chylomicrons

– VLDL (very low density lipoproteins)

– IDL (intermediate density lipoproteins)

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Associated Markers of ASCVD

• Low density lipoproteins

• Lipoprotein (a)

• Apolipoprotein A1

• Apolipoprotein B

• Ratio of A1 / B

Low Density Lipoprotein

• One type of lipoprotein that transports cholesterol and triglycerides from liver to peripheral tissues

• Serum is water based; LDL’s allow fats and cholesterol to circulate

• LDL particles vary in size and density

– Subtype A • Larger, less dense

– Subtype B • Smaller, more dense

LDL Subtypes A and B

• Subtype B is more likely to penetrate vascular endothelium

– More highly associated with risk of CAD

• normal vascular endothelial gaps are about 26nm

Measurements of LDL

• Measurement of LDL is widely available and relatively inexpensive

• Not very well correlated with development of atherosclerosis

• Measurement of sub types of LDL are more correlated with cardiovascular disease

LDL and Cardiovascular Risk

• LDL may be low, but in presence of elevated LDL particles, AS increases

• LDL may be high, and in cases where LDL particles are low, so too is incidence of AS

• Typical lipid panels do NOT directly measure LDL; Friedenwald Formula is used to calculate LDL

Pathophysiology

• PDAYS Study

– Pathobiological Determinants of Atherosclerosis in Youth Study

– Lesions in the intimal lining of ALL the aortas and 50% of the Right Coronary Arteries are present by age 9

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A Rhetorical Question Homocysteine

• Homocysteine is: – 1: an amino acid that has protective properties in

patients at risk of cardiovascular disease

– 2: an amino acid that is a significant risk factor for MI, ischemic stroke, and thromboembolism

– 3: an amino acid whose levels are genetically determined and is not altered by dietary intake

– 4: an enzyme responsible for increased clotting times

Homocysteine

• Homocysteine is: – 1: an amino acid that has protective properties in

patients at risk of cardiovascular disease

– 2: an amino acid that is a significant risk factor for MI, ischemic stroke, and thromboembolism

– 3: an amino acid whose levels are genetically determined and is not altered by dietary intake

– 4: an enzyme responsible for increased clotting times

Homocysteine

• Elevated plasma levels of homocysteine is an established risk factor for ASCVD, Cerebrovascular disease, perpheral vascular occlusive disease

• Hcy levels are lower in premenopausal women than in men and post menopausal women

– May be related to the increased incidence of ASCVD in postmenopausal women

Homocysteine

• Elevated plasma levels of Hcy can be reduced by therapy with folate and vitamins B6 & B12

• Elevated Hcy levels are reduced by HRT, estrogens and tamoxifen

More to Think About

• Since elevated Hcy levels are associated with a significant increase in ASCVD and stroke:

– 1: lowering Hcy by folate and vitamins has a significant effect in lowering the risk of stroke

– 2: lowering of Hcy by folate and vitamins has a moderate effect in lowering the risk of stroke

– 3: lowering of Hcy by folate and vitamins has no clinical effect in lowering the risk of stroke

– 4: lowering Hcy by folate and vitamins further increases the risk of stroke

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More to Think About

• Since elevated Hcy levels are associated with a significant increase in ASCVD and stroke:

– 1: lowering Hcy by folate and vitamins has a significant effect in lowering the risk of stroke

– 2: lowering of Hcy by folate and vitamins has a moderate effect in lowering the risk of stroke

– 3: lowering of Hcy by folate and vitamins has no clinical effect in lowering the risk of stroke

– 4: lowering Hcy by folate and vitamins further increases the risk of stroke

VISP Study

• Vitamin Intervention for Stroke Prevention

• Double blind, randomized, controlled study

• 4000 participants

• Does administration of high doses of folate, B6 and B12 reduce the risk of stroke?

Vitamin in Stroke Prevention

• High doses or low doses of folate, B6 and B12 did not differ in effect on stroke outcomes

• Neither high nor low doses of folate, B6 and B12 had a clinically significant effect on vascular outcomes

2004, JAMA

Homocysteine and the Eye

• Include Hcy levels in work up of patients with:

– ASCVD

– emboli

– TIA, TVB

– retinal vascular disease,

– neuro visual field defects,

– vascular diplopia

Homocysteine and the Eye

• If clinical findings are present and Hcy levels elevated, IM prophylaxis with folate, B6 and B12 and anti-platelet therapy is warranted

Even More to Think About

• If lowering Hcy levels by supplementation does not decrease risk of stroke, why recommend it in patients at risk?

– 1: current research shows Hcy is intimately linked to vascular endothelial disease

– 2: high levels of folate increase libido in the elderly

– 3: high levels of folate are associated with a decreased incidence of Alzheimer’s Disease

– 4: two of the above

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Even More to Think About

• If lowering Hcy levels by supplementation does not decrease risk of stroke, why recommend it in patients at risk?

– 1: current research shows Hcy is intimately linked to vascular endothelial disease

– 2: high levels of folate increase libido in the elderly

– 3: high levels of folate are associated with a decreased incidence of Alzheimer’s Disease

– 4: two of the above

Homocysteine

• Elevated levels are associated with:

– Alzheimer’s Disease

– Neovascular AMD

• Not dry AMD

– Increased risk of cervical cancer

Serology for Inflammatory Disease

• Erythrocyte Sedimentation Rate (ESR, Sed Rate)

• C-Reactive Protein (CRP)

• Rheumatoid Factor (RF)

• Anti-Nuclear Antibody Titer (ANA)

• Human Leukocyte Antigen Test (HLA Typing)

• Immunoglobulins (IgM, IgG, IgA)

Inflammatory Disease - AION (Subjective)

• 61 YOWF c/o Sudden, Painless OD Decreased VA X 5 d, “Dimming of Vision”

• POHx: ? OS Problem 10+ yrs. Ago

• PMx: HTN, RA, Anxiety

• FMHx: Non-contributory

• Meds:Diazide, Macrobid, Naprosyn, Lorazepam

• NKDA

Inflammatory Disease - AION (Objective)

• BVA: 20/100 OD, 20/70 OS

• Neuro: PERRLA (-)APD; CF Constricted to 20 Degrees, EOM FROM, CV 4/10 OD, 8/10 OS w/ 25% Red Desatuation OD

• SLE: Unremarkable except 2+ NS OD, OS

• DFE: Moderate Sectoral Disc Edema w/ NFL Heme OD, Pale Atrophy OS

• Formal Visual Fields

Inflammatory Disease - AION (Objective)

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Inflammatory Disease - AION (Assessment)

1. AION OD

2. Optic Atrophy OS from Previous AION

(Foster-Kennedy Syndrome doubt)

Inflammatory Disease - AION (Plan)

1. STAT Laboratory Investigation

(CBC, SMA, ESR, CRP, RPR,RF, ANA, FTA-ABS)

2. STAT Imaging Study

(MRI of Head and Orbits R/O Mass Lesion)

Inflammatory Disease - AION Lab Results (Plan)

Lab Results

• Elevated ESR- 63 mm/hr

• Elevated CRP

Image Results

• Normal MRI

Plan Continued

• Schedule TA Biopsy

• Rx Prednisone 80mg po qd in Divided Doses (Co-Manage w/ IM/Rheumatologist)

• Follow ESR, VF, VA, CRP & ONH

Inflammatory Disease - AION Discussion

Anatomy/Physiology

• Optic Nerve Head

• Lamina Cribrosa

• Vasa Vasorum of Optic Nerve



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Ischemic Optic Neuropathy

Arteritic vs Non Arteritic

temporal artery biopsy

Arteritic

elevated sed rate (Westergren)

elevated CRP

associated symptoms of malaise, claudication, headache

Non-Arteritic

look for top 5 CV/IHD risk factors

C Reactive Protein

• C Reactive Protein levels:

– 1: are a marker of vascular inflammation

– 2: if elevated, are a risk factor for cardiovascular disease

– 3: if elevated, are more sensitive in determining AAION than ESR

– 4: all of the above

C Reactive Protein

• C reactive Protein levels:

– 1: are a marker of vascular inflammation

– 2: if elevated, are a risk factor for cardiovascular disease

– 3: if elevated, are more sensitive in determining AAION than ESR

– 4: all of the above


Hayreh et al

AJO March 1997

ascertained reliability, sensitivity and specificity of signs, symptoms and diagnostic tests for early diagnosis of GCA

Findings most strongly suggestive of GCA:

1: jaw claudication

2: C-reactive protein > 2.45mg/dl

3: neck pain

4: ESR > 47mm/hr


Hayreh et al, AJO March 1997

Sensitivity of CRP: 100%

Sensitivity of ESR: 90%

ESR + CRP gave best specificity (97%)

On to Part 2!

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Lab and Imaging Interpretation Primary Eye Care · Lab and Imaging Interpretation Primary Eye Care practice, ... Visiting Professor of Clinical Medicine ... •Educate & Follow q