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SECO 2011
DISCLOSURE STATEMENT March 2-6, 2011
Dr. Pizzimenti is CEO of Optometryboardcertified.com • The Eye is an extension of the brain
Dr. Pizzimenti has received honoaraia from Alcon, Reichert,
Zeavision, and Carl Zeiss Meditec retina”
• The anatomy of the eye is structured to serve the functions of the “ retina”
Dr. Pelino has received honoraria from Carl Zeiss Meditec
• The primary reason for dilation is to detect systemic disease
Essentials in Systemic Disease
Carlo J. Pelino, OD
Joseph J. Pizzimenti, OD
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Inner and Outer blood retinal barrier RPE and Choroidal pigmentation
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Choroid 80%
Sympathetic
Control
Retina 5 %
Autoregulate
Iris / Ciliary Body 15%
Classification of Blood Pressure (Adults 18 and older)
Clinical Ophthalmoscopic findings
Category Systolic Blood Pressure Diastolic Blood Pressure
Grading of Hypertensive Retinopathy
• Nomal < 120 mm Hg < 80 mm Hg
• Prehypertension 120-139 mm Hg 80-89 mm Hg
Grade 1 Retinal vessels narrowed > 90 and < 110 Diastolic BP
• Hypertension 140-159 mm Hg 90-99 mm Hg
Grade 2 Nicking of retinal vessels > 90 and <110 Diastolic BP
(Stage 1)
Grade 3 Hemes,
CWS, Hemes, Lipid exudates > 110 – 115 Diastolic BP
• Hypertension >160 mm Hg 100 mm Hg
(Stage 2) Grade 4 Grade 3 + Optic disc swelling > 130 Diastolic BP
Source: U.S. Department of Health Services; NIH no. 03-5231 May 2003 • Grades 3 and 4 = increase risk of cerebral, heart and kidney problems
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54 year old
+ Diabetes
+ HTN
+ Cholesterol
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4
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Grade 4 Hypertensive Retinopathy
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Malignant Hypertension Malignant Hypertension
Malignant Hypertension
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Hypertension:
Malignant Hypertension:
• Defined as Blood Pressure > 210 / 130
Presentation:
Ocular Presentation: May present with the following
• Disc Edema
• Arterio-venous crossing changes
• Nerve fiber layer infarcts (cotton wool spots)
• Macular edema
• Hard exudates
• Flame shaped hemorrhages
• Choroidal ischemia (usually seen in young patients)
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• Keith et al. found that ~ 80 % of patients with Grade 4 Hypertensive
Hypertension:
Malignant Hypertension: Systemic Presentation Retinopathy ( malignant hypertension ) died within 1 year
• Patient may be asymptomatic • Also, over a 3 year period, there was a 95% mortality for those with
• Patient may have encephalopathy, headaches, vomiting or coma malignant hypertension
• HLA B15 has been associated with malignant arterial hypertension.
Treatment of Malignant Hypertension:
• Blood pressure measurement
• Immediate referral to emergency room or primary care doctor for
slow lowering of the blood pressure !!!!!
• Visual field testing
• MRI – to rule out space occupying lesion
• MRV- to rule out “ venous sinus thrombosis ”
• Lumbar puncture if necessary
Hypertension:
Hypertension ~ 70 million Americans
Hypertension:
Secondary Hypertension:
• Malignant
• Essential Drugs / Toxins
Pheochromocytoma, stenosis,
• Secondary HTN ( Pheochromocytoma, renal artery stenosis, etc. )
Renal Disease Glomerulonephritis,
Glomerulonephritis, Diabetes, Chronic nephritis
Hypertension:
Essential Hypertension: defined as a blood pressure > 140 / 90
Vascular Coarctation of the aorta
age…
•During young adulthood /early middle age…HTN is more common in males
Neurologic Increased Intracranial Pressure, G-B syndrome
patients…
•Elderly patients…HTN is more common in women
Endocrine Pheochromocytoma,
Pheochromocytoma, Hypo-Hyperthyroidism
•A family history of HTN usually exists in essential HTN
•Essential HTN is usually controlled with one or two medications
Pregnancy
•Blood pressure does not progress to higher levels over a short period of time
Stress Postoperative, Burns, Alchohol withdrawal
Panel”
•Work Up = BUN/Cr, Lipid Profile, Glucose, CBC, EKG, “ Metabolic Panel”
Zoorob RJ, et al. Hypertension. Prim Care. 2000 Sep;27(3):589-614
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Always question the malignant hypertensive patient
Hypertensive encephalopathy
• Syncope 2 Months
• Seizures
• Focal weakness
• Paresthesias
• Speech problems
Hypertensive Cardiac involvement
• Chest pain
• Palpatations
• Cough
• Dyspnea
Hypertensive renal problems BP 125 / 82
• Change in renal volume RAS
Hematuria,
• Hematuria, abdominal pain
• Hypertensive Choroidopathy
Epiretinal Membrane formation
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Essential Hypertension – Long standing
Arteriosclerosis Grade 2-3
Retinal Arterial Macroaneurysm Retinal Arterial Macroaneurysm
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Central Retinal Vein Occlusion Branch Retinal Vein Occlusion
Ischemic”
“Non - Ischemic” Central Retinal Vein Occlusion
Valsalva Retinopathy
Valsalva Retinopathy
• Rupture of the superficial retinal capillaries
• Occurs when there is a rise in the intrathoracic or intra-abdominal
pressure
• There is then a rise in the intraocular venous pressure
• Increased pressure is generated by forceful exhalation against a closed
glottis
• Etiology may be from strenuous coughing, sneezing, vomiting,
straining or lifting
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1 Week
Day #1
BP 162 / 98
BP 135 / 90
RAS
RAS
35 yo AA male
Valsalva Retinopathy
4 Weeks Treatment:
Treatment:
• Usually observation – Most hemorrhages clear spontaneously and have
an excellent prognosis
• Vitrectomy
• Nd:YAG laser – disruption to the internal limiting membrane used to
disperse the dense hemorrhage into the inferior vitreous
Note:
Important Note:
• Toxic damage to the retina if contact with hemoglobin and iron for a
BP 140/90 long period of time
RAS
Evaluation:
Systemic Evaluation:
pressure, coagulopathy,
• A work up should include testing for high blood pressure, coagulopathy,
and blood dyscrasias especially if positive for a family history
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State:
Hypercoaguable State:
• It is a risk factor for artery and venous occlusions
• Has and association with coronary artery disease
• Has and association with cerebral vascular accidents (CVA)
• Hypercoaguable state is associated with peripheral vascular disease
State:
Primary State: State:
Secondary State:
• Protein C deficiency • Pregnancy
• Protein S deficiency • Malignancy
• Antithrombin III • Congestive Heart Failure
• Factor V Leiden • Immobility
• Hyperhomocysteinemia
• Prothrombin 20210 mutation
Anti-cardiolipin
• Antiphospholipid syndrome (Lupus anticoagulant / Anti-cardiolipin antibody)
• CBC c differential, Platelet count and PT / PTT
Coagulation Pathway
State:
Hypercoaguable State: Important Note
• Factor V Leiden is the most common hereditary blood coagulation
disorder in the United States ~10%
• Prothrombin 20210 mutation is the second most common inherited
clotting abnormality in the United States
Ophthalmic Presentations:
• Central Retinal Artery Occlusion
• Branch Retinal Artery Occlusion
• Central Retinal Vein Occlusion
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BRAO”
“BRAO” in a 42 yo AA female
Birth-control medication
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State:
Hypercoaguable State: Treatment
•Monitor patient closely with Primary Care Physician
Coumadin,
•Coumadin, Heparin, Aspirin therapy
•Treat ocular conditions accordingly
Dot and Blot hemes in mid-peripheral retina
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Syndrome:
Hypoperfusion Retinopathy / Ocular Ischemic Syndrome:
• Usually unilateral but may be bilateral in 20% of cases
• Males > Females by a 2 to 1 ratio
• Dot and blot hemes / microanuerysms found only in the mid-
peripheralretina = Hypoperfusion Retinopathy
• When the above is associated with neovascularization of the Disc,
Retina, Iris or Angle = Ocular Ischemic Syndrome
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Pathogenesis:
Pathogenesis: Ocular Ischemic Syndrome:
Symptoms:
Symptoms: Ocular Ischemic Syndrome
• Atheromatous ulceration and stenosis at the bifurcation of the
common carotid artery ( 90% occlusion has to be present )
Angina”
• Ocular and periorbital pain in 40% of cases = “Ocular Angina”
• Prolonged recovery of vision following exposure to bright light-
Amaurosis”
known as “ Light Induced Amaurosis”
• Amaurosis Fugax ( Transient Monocular Blindness ) in 5% of cases
• Transient Ischemic Attacks (TIA)
• Vision Loss ( 90% ) – Short Posterior Ciliary Arterial hypoperfusion
Carotid Doppler Carotid Bruit
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Symptoms: Ocular Ischemic Syndrome
Symptoms: Signs:
Ocular Signs: Ocular Ischemic Syndrome:
• Dilated but not tortuous retinal veins
• Retinal Hemorrhages in mid-peripheral retina (80%) of patients
Angina”
Ocular and periorbital pain in 40% of cases = “Ocular Angina” • Cotton Wool Spots (5%)
• Neovascularization of the Disc (35%)
• Neovascularization of the Retina (8%)
• Ischemia to the ophthalmic division of Cranial Nerve 5 • Rubeosis iridis (65%)
• Uveitis – mild anterior (20%)
• Anterior segment inflammation • Emboli (retinal)
• Lower IOP - initially
• Elevated intraocular pressure ( IOP ) from neovascular glaucoma
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Ocular Ischemic Syndrome
Cholesterol Plaques
55 yo AA male “BRAO” OD
55 yo AA male OS
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Cerebral Blood Supply Motor and Sensory Areas
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Ocular Ischemic Syndrome
Up:
Work Up:
• Carotid artery evaluation (Carotid – Duplex Scanning) – ICA, ECA,
CC
• Color Trans-cranial doppler (TCD) – ocular arteries
• Possible MRA (Magnetic Resonance Angiography)
• Computed Tomography (CT) angiography
• Cardiology work up (Echocardiogram) – Transesophogeal /
Transthoracic
Occipital Lobe Infarct • HTN, DM, Lipid Panel, ESR, C-reactive protein
Ocular Ischemic Syndrome Diabetes
Treatment:
Treatment:
Characteristics
(Endarterectomy)
• Consider carotid surgery if warranted (Endarterectomy)
European Carotid Surgery Trial (ECST)
North American Symptomatic Carotid End. Trial
( NASCET) • ~ 24 million American have Diabetes
• Therapeutic approach – Aspirin ( 325 mg QD or BID ) , Plavix • Most common retinal vasculature disease
• Control modifiable vascular risk factors ( HTN, DM, dyslipidemia )
• Stop smoking • Diabetes = leading cause of blindness in Americans between 20-74
• Panretinal photocoagulation (PRP) if neovascularization years old
Important Note:
Note: • African Americans, Hispanics and Native Americans are high risk groups
Leading cause of death = Ischemic heart disease
Second leading cause of death = Stroke • Non white females are at greatest risk for blindness
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Diabetes
The Prevalence of Diabetic Retinopathy
Classification of Diabetic Retinopathy
Non-Proliferative”
“Non-Proliferative” Proliferative”
“Proliferative”
• Hispanic population tends to have the highest prevalence rates of DR
• Mild Early
• African Americans tend to have highest rates of vision threatening DR
• Moderate High risk
• Severe (4-2-1 rule)
• No prominent difference between genders were seen in the prevalence of
• Very Severe
diabetic retinopathy
• The prevalence of diabetic retinopathy is in older age groups Other Ocular Complications:
• Clinically Significant Macular Edema
• Diabetic Papillopathy
• Cranial Nerve Palsy 3,4,6
• Cataract formation
Diabetes
Severe”
“Severe” Non-Proliferative Diabetic Retinopathy
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Diabetes
Proliferative”
“Proliferative” Diabetic Retinopathy
Diabetes
Diabetes
Dehemoglobinized Vitreal Heme Proliferative”
“Proliferative” Diabetic Retinopathy
Proliferative”
“Proliferative” Diabetic Retinopathy
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Diabetes Diabetes
Proliferative”
Fibrous Proliferation – “Proliferative” Diabetic Retinopathy
Proliferative”
“Proliferative” Diabetic Retinopathy
Diabetes 4-2-1 Rule
Severe NPDR
At least one of :
intraretinal hemorrhages in four quadrants
venous beading in two quadrants
intraretinal microvascular abnormalities in 1 quadrant
Standard photographs available at:
eyephoto.ophth.wisc.edu/ResearchAreas/Diabetes/DiabS
tds.htm
CSME”
“CSME” – Clinically Significant Macular Edema
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Intraretinal hemorrhages in four Venous Beading and Intraretinal
quadrants Microvascular Anomalies (IRMA)
Venous
beading IRMA
DIABETIC MACULAR EDEMA
CSME Defined
CSME, as defined by the ETDRS, exists
with any of the following findings:
Retinal thickening within 500 mm of the
center of the fovea
Hard exudates within 500 mm of the center of
the fovea with adjacent retinal thickening
At least 1 disc area of retinal thickening, any
part of which is within 1 disc diameter of the
center of the fovea
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Diabetic Macular Edema Management Guidelines: DME
More recently, laser out-performed
Kenalog.
intravitreal Kenalog.
Laser + Lucentis out-performed laser
alone.
+
Diabetes
Diabetes
#2 Anemia
Some important systemic effects of diabetes that affect retinopathy and • Gets more severe as renal disease worsens
Attack”
increase the risk of “Heart Attack”: Erythropoietin”
• Kidney production of “Erythropoietin” decrease, which means that less
reaches the bone marrow and less red blood cells are made
#1 Proteinuria • Measured by Hematocrit (HCT) and hemoglobin levels in a CBC
• First sign of renal disease If hemoglobin levels are less than 11g/dl = anemia
increases…
• As nephropathy increases…the glomerular filtration rate falls
• American Diabetes Association (ADA) recommends
yearly urinalysis Anemia may actually be making the retinopathy worse!!!
• Random Spot Urine or 24 hour collection
Normal <30
Procrit” dialysis…
Treat the patient with “Procrit” if patient is not on dialysis…also give iron
Microalbuminuria 30 mg – 299 mg
Albuminuria > 300 mg
Kidney Erythropoietin Bone Marrow RBC’
RBC’s
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Diabetes WBC’
WBC’s adhere to
and accumulate
within the retinal
#3 Hyperlipidemia
vasculature
• Cholesterol and triglyceride healthy levels should be < 200 mg/dl
ICAM
• PCP should consider Lipitor if cholesterol high
Further
#4 Hypertension breakdown
• Target blood pressure for diabetics with nephropathy is 130 /80 of the blood-
• ACE inhibitors should be given if blood pressure is high retinal barrier
anti-proteinuric
• ACE inhibitors are both renal-protective and anti-proteinuric
• Hypertension in diabetics is labile and only effectively
measured at home Release of VEGF
Vascular
#5 Hyperglycemia Endothelial
• Induces vasoconstriction = kidney ( glomerular ) damage Growth
• The Hemoglobin A1C should be as close to 7 % as possible Factor
#6. Obstructive Sleep Apnea Continuous Positive Airway Pressure
• Progressive relaxation of upper airway musculature in deeper stages of sleep
• Nocturnal Hypertension
REM
Sleep
Nasal Mask:
• Intimidating
• Cumbersome
• ? Poor Compliance
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DM + Smoking = Blindness
• Elevated morning BP by 20 -30 mmHg
• Elevated, resistant BP throughout the day
• Relationship: Congestive Heart Failure, Nocturnal MI / CVA, Nephropathy
#7. Smoking Smoking
• Severely worsens microangiopathy • Smoking is a risk factor for proteinuria and increased blood pressure
• Nicotine increases blood platelet viscosity which can increase retinopathy
• Smoking also causes arterial wall damage and constriction
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Moderate”
“Moderate” Non-Proliferative Diabetic Retinopathy
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ACCORD study Diabetes
• Patients with tightly controlled blood glucose (HbA1C < 6%) had a 22%
higher risk of death vs. those patients with less HbA1C control (7-8%) Home:
Take Home:
• The study was halted
• Diabetic Retinopathy is exacerbated by many concomitant conditions
ADVANCE study
• Had different results. Risk reduction by 10% in micro and macrovascular • Control of the systemic aspects of the disease improves the systemic
events. and ocular health
DPP (Diabetic Prevention Program) - Prediabetics
• Understand how Diabetic Retinopathy relates to the overall systemic
(metformin)
• Lifestyle intervention group vs. med group (metformin) vs. placebo health
• Lifestyle group showed the most decrease in diabetes risk
Cholesterol /
Cholesterol • Arcus Senilis
Triglycerides
< 200 mg/dl 990 mg/dl • Arcus Juvenilis
• 50% have high cholesterol levels
Triglycerides Triglyceride
> 2,500 mg/dl 7,200 mg/dl
• In younger people may lead to MI or
cardiovascular disease
• Arcus = “Bow like
• Hyperlipoproteinemia in younger pts.
Retinalis”
“Lipemia Retinalis”
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The Association of Corneal Arcus with Coronary Heart Disease and
Cardiovascular Disease Mortality in the Lipid Research Clinics Hyperlipidemia
Mortality Follow-up Study ( Am J Public Health 1990; 80:1200-1204 )
• Type 2 diabetics have elevated triglyceride levels
Prospective study of White men ( n = 3,930 )
and women non-hormone users ( n = 2139 ) • Type 2 diabetics have decreased high-density lipoprotein (HDL) levels
Followed for an average of 8.4 years
• Increases cardiovascular mortality risk = Coronary Artery Disease
Results:
Results:
Management:
• Corneal Arcus was strongly associated with CHD and CVD mortality
only in hyperlipidemic men ages 30-49 years. • Nutrition Therapy = lifestyle change
• Among 30-49 year old males, corneal arcus was a prognostic factor • Exercise = lifestyle change
for CHD independent of hyperlipidemia
• Drug Therapy (aka) HMG-CoA
Statins (aka) HMG-CoA reductase
inhibitors
Aspirin Use in Diabetes
• Aspirin use in diabetic patients is not associated with an
increased risk of hemorrhage or progression of retinopathy
or macular edema !!!
• Aspirin use may actually slow the progression of diabetic retinopathy ???
• Aspirin Therapy ( 81-325 mg/day): ADA recommendations
• Family History of coronary heart disease
• Cigarette smoking
• Hypertension
• Obesity
• Albuminuria
• Elevated lipid levels
• Age > 30 years
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29 year old AA female. Dry eye complaints
HIV Retinopathy – CD4 count 110
Cotton Wool Spots OU Pt. not on HAART
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• CD4 Count – Measure of T-cell count ( 600 – 1500 cell / m3 )
45 year old male. Diabetes history • CD4 / CD 8 Ratio ( Normal is 2.0 )
• Viral Load - # of HIV 1-RNA molecules / ml blood ( 10,000 low / 100,000 high )
Cytomegalo-virus (CMV)
CD 4 Count and Ocular Management of the HIV Patient Acquired Immune Deficiency Syndrome (AIDS)
Course of the Disease
CD4 Count Frequency of Examination
• Initial Stage – Influenza like illness ~ 4-12 weeks after becoming infected
> 250 cell / mm3 1 year
150 cell / mm3 6 months • Chronic Stage – Latent period ~ 10 years with minor immune dysfunction
50 -150 cell / mm3 3 months
• Final (Crisis) Stage – Weight loss, fever, skin rashes, opportunistic infections
< 50 cell / mm3 1 month and neoplasms
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disease:
Five drugs currently available to people with CMV disease: www.aidsmeds.com
Foscarnet (Foscavir®) Through an IV line
Ganciclovir (Cytovene®) Through an IV line followed by capsules
Cidofovir (Vistide®) Through an IV line
Valganciclovir (Valcyte®) Tablets that must be swallowed.
Ganciclovir implants (Vitrasert®) Surgically implanted directly into the eye.
Lupus Retinopathy
Fomivirsen (Vitravene®) A shot directly into the eye.
Sheathing of Blood Vessels
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Lupus Choroidopathy
Lupus Retinopathy and Optic Neuropathy
Systemic Lupus
Three forms of lupus are known
• Systemic lupus erythematosus
• Cutaneous lupus
• Drug-induced lupus
A multisystem autoimmune disorder
that commonly affects women of
childbearing age (women>>>men)
Common findings include malar rash,rash,
arthritis,
arthritis, oral ulcers, renal disease,
hematological,
hematological, seizures and psychosis,
pulmonary and GI Spot”
“Roth Spot”
Iritis
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Laboratory Testing in Systemic Lupus Erythematosus
Systemic Lupus Erythematosus
• Complete Blood Count (CBC)
• Lupus is more common in the African American,
Asian and native American populations • Platelet count
• Approximately 15 % of patients with Lupus will have retinal disease • Erythrocyte Sedimentation Rate (ESR) - Westergren
• Retinopathy can be associated with central nervous system • C-Reactive Protein (CRP)
complications such as cerebritis
• Antinuclear antibody (ANA) – screening test
Clinical Retinal Features
• Anti-n DNA ( ordered when ANA is positive )
• Cotton Wool Spots
• Retinal Hemorrhages • Urinalysis
Vaso-occlusive
• Vaso-occlusive disease
• Frosted branch periphlebitis • Complement ( C3 and C4 ) serum levels
Scleritis
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Feature Episcleritis Scleritis
Number of patients 37 97
Age 45 51
Gender 30% 29% men
70% 71% women
Race white 84% white 79%
Bitlateral 49% 51%
Systemic disease RA 18% RA
Scleral thinning and scleromalacia perforans
Scleritis:
Episcleritis and Scleritis: Clinical Features and Treatment Results. Doug Jabs, et al.
Ophthalmology 2000; 130:469-476.
Metastatic”
“Metastatic” Choroidal Tumor
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Choroidal Metastasis
Metastatic Tumors
• Lung cancer - #1 cause of death in males
• Breast cancer - #1 cause of death in females
• Prostate cancer – most common cancer in men
(More common and more aggressive in African Americans)
• Colon cancer – 3rd most common in men, 2nd most common in women
• Melanoma – skin most common site of cancer development
(Males = trunk) (Females = extremities)
• Ovarian cancer – disease of postmenopausal women
• Pancreatic cancer – usually >65 years old, wt. loss, jaundice, anorexia
• Uterine cancer – disease of postmenopausal women
(abnormal vaginal discharge or bleeding)
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Metastatic Tumors
• Choroidal Metastasis is the most common ocular tumor
• Most metastases found in the choroid are from the breast and lung
• Only ~ 65 % of patients with a choroidal metastasis have been
diagnosed with a form of systemic cancer
Ocular Presentation:
• Dome-shaped lesion yellow to orange in color
• Most often in the posterior pole but can be in iris and ciliary body
• They may be solitary or multifocal
• Bilateral in ~ 30 % of cases
Treatment:
• Observation, external beam radiation, radioactive plaque therapy
px’
• The goal of treatment is to save the px’s vision for the remainder of life
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Streaks:
Angioid Streaks:
• Alteration / break of the Retinal Pigment Epithelium (RPE),
Bruch’s membrane and Choriocapillaris
• Patient is usually asymptomatic
• Approximately 50% have associated systemic disease
• Decreased vision is secondary to choroidal neovascularization
membrane(CNVM) or a streak through the fovea
Etiology:
• Pseudoxanthoma elasticum (85%) Idiopathic
• Ehlers Danlos syndrome Lead Poisoning
• Paget’s Disease
• Sickle Cell Anemia
Appearance:
Fundus Appearance:
High Myopia Trauma
• Bilateral gray – red – brown linear bands radiating in a spoke wheel
pattern from the optic nerve
d’
• May have a peau d’orange fundus temporal to the macula
spots”
• May have peripheral round lesions caled “ salmon spots”
• Possibility of Optic nerve head drusen
Differential Diagnosis:
Diagnosis: Systems:
Affected Systems:
• Myopia (lacquer cracks) • Cardiovascular
• Choroidal Rupture HTN
Angina Pectoris
Mitral Valve Prolapse
• Skin • Lacquer Cracks • Choroidal Rupture
• Gastrointestinal
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Treatment:
Treatment: Angioid Streaks
Initial Presentation 3 weeks later
• Focal laser if (CNVM) is present
• Management of any underlying systemic disease
up:
Follow up:
• Twice a year with a dilated fundus examination
• Amsler Grid testing (~3 x week)
• Choroidal Ruture
The End !!!!
Any Questions ????
pizzimen@nova.edu
cpelino@pco.edu
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