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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 Please silence all mobile devices Welcome to SECO 2009 At the conclusion of this course, please properly dispose of your trash as you leave this room Inner and Outer blood retinal barrier RPE and Choroidal pigmentation 1 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 2 54 year old + Diabetes + HTN + Cholesterol 3 4 5 Grade 4 Hypertensive Retinopathy 6 Malignant Hypertension Malignant Hypertension Malignant Hypertension 7 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) 8 • 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 9 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 10 Essential Hypertension – Long standing Arteriosclerosis Grade 2-3 Retinal Arterial Macroaneurysm Retinal Arterial Macroaneurysm 11 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 12 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 13 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 14 BRAO” “BRAO” in a 42 yo AA female Birth-control medication 15 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 16 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 17 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 18 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 19 Ocular Ischemic Syndrome Cholesterol Plaques 55 yo AA male “BRAO” OD 55 yo AA male OS 20 Cerebral Blood Supply Motor and Sensory Areas 21 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 22 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 23 Diabetes Proliferative” “Proliferative” Diabetic Retinopathy Diabetes Diabetes Dehemoglobinized Vitreal Heme Proliferative” “Proliferative” Diabetic Retinopathy Proliferative” “Proliferative” Diabetic Retinopathy 24 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 25 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 26 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 27 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 28 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 29 Moderate” “Moderate” Non-Proliferative Diabetic Retinopathy 30 31 32 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” 33 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 34 29 year old AA female. Dry eye complaints HIV Retinopathy – CD4 count 110 Cotton Wool Spots OU Pt. not on HAART 35 • 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 36 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 37 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 38 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 39 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 40 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) 41 42 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 43 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 44 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 !!!! 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"Systemic Disease SECO"