Oculosystemic Disease Essentials

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Byron Hines
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1 Disclosures Oculosystemic Disease Essentials Steven Ferrucci, OD, FAAO Chief, Sepulveda VA Professor, MBKU/SCCO! Speakers bureau and/or Advisory Board for:! Alcon! Autogneomics! Macula Risk! MacuLogix! Nicox! Science-Based Health! ThromboGenics What is diabetes? Statistics DM is a chronic disorder characterized by a lack of insulin or increased resistance to insulin Insulin is needed for proper uptake of glucose Clinical result is hyperglycemia retinopathy nephropathy neuropathy Approximately 23.6 million Americans with diabetes 8.3% of total population 11.3 % of adults 25-30% undiagnosed ( 7 million) Another 79 million Americans have pre-diabetes and are likely to develop diabetes if do not change habits 35% of adults age 20 or older Statistics, cont. Statistics Globally, Type 2 DM affects 5.9% of adult population 46% ages Highest percentage in Eastern Mediterranean and Middle East (9.2%) and North America (8.4%) Total Numbers: 246 million Worldwide India 40.9 million China 39.8 million Then USA, Russia, Germany, Japan, Pakistan, Brazil, Mexico and Egypt! In 2007, medical expenditures for diabetes $116 billion! $27 B direct care! $58 B to treat diabetes related complications! $31 B in excess general medical costs! Costs: 2.3 x higher in diabetic vs non-diabetic pt! Actual national burden of diabetes likely exceeds $174 B when indirect costs considered! Seventh leading cause of death in

2 The Diabetes Epidemic The Diabetes Epidemic Incidence has increased 13.5% from 2005, and over 700% in last 40 years WHY?? Improvements in diabetes care Pts living longer with diabetes Growth in elderly populations: 10% > 60 vs 16-20% > 80 Increasing prevalence of obesity which causes increased insulin resistance Increased number or minority populations in US Rates of DM among minority populations are often 2-3 times greater TYPE 1 TYPE 2 Formerly IDDM or juvenile onset Prevalence: 0.2% 10% of all DM Most common age of onset < 30 Destruction of insulin producing B-cells in pancreas (autoimmune? viral?) Total lack of endogenous insulin Need to be on insulin to survive Formerly NIDDM or adult onset Prevalence: 3.1% 90% of all DM Most frequent age of onset > 40 Often asymptomatic Characterized by insulin resistance Strong genetic predisposition Gestational Diabetes Affects 4% of all pregnancies High risk populations: Pregnant woman greater than age 25 Abnormal body weight Have first degree relatives with diabetes Hispanic, Asian, Native American, African American descent Screen in 24th to 28th week of pregnancy Gestational Diabetes Plasma glucose concentration at or above any 2 of 4 values on OGTT 1. Fasting, 95 mg/dl 2. 1 hour, 180 mg/dl 3. 2 hour, 155 mg/dl 4. 3 hour, 140 mg/dl May be treated with diet changes or insulin if needed At higher risk for developing type 2 later in life 5 fold increase at 5 yrs, 9 fold after 5 years 2

3 Pre-Diabetes! Blood sugar levels higher than normal, but not yet high enough to be diagnosed with DM! FBS: mg/dl! A1c: ! ADA estimates 79 million Americans have prediabetes! 30 minutes of exercise combined with 5-10% reduction in body weight resulted in 58% reduction in diabetes Symptoms Often asymptomatic, especially Type 2 Classic symptoms polydipsia polyphagia polyurea Others: weight loss, delayed wound healing, dry mouth, dry skin, recurrent infections, refractive changes Risk Factors Traditional Diagnosis Criteria Family history Specific ethnic backgrounds African Americans Native Americans Hispanic Asian American Pacific islander Sedentary Lifestyle Pertinent medical history obesity cardiovascular disease HTN High cholesterol Polycystic ovarian syndrome Psychiatric illness Gestational DM IFG/IGT Fasting blood glucose > 126 mg/dl OGTT > 200 mg/dl (2 hour sample) Any random testing >200 mg/dl should be referred for further testing Random testing > 200 mg/dl with symptoms very suggestive of DM New Diagnosis Criteria! Panel of experts at ADA annual meeting are recommending A1C be used for diagnosis of diabetes! Glycosolated hemoglobin! Tells blood sugar control over 3 months! normal range 4% to 6% HgbA1c BS Level HgbA1c BS Level New Diagnosis Criteria! 6.5 would be indicative of DM! First major change in 30 years! In adults and children, not pregnant women! Advantages:! Convenience: no fasting! More accurate: average over 3 months! Disadvantage:! Cost? 3

4 Recommended Criteria for Screening Asymptomatic Individuals for Type 2 DM Treatment of Type 2 DM All pts >45 yrs at 3 yr intervals Younger age or more frequently in pts who: are obese have a first-degree relative with diabetes are members of high-risk ethnic population gestational diabetes or delivered a baby > 9 lbs are hypertensive HDL < 35mg/dl or triglycerides > 250 mg/dl have impaired glucose regulation! Goal: to produce desirable blood glucose levels with minimal adverse effects and maximal patient compliance! Treatment begins with diet and exercise and ends with insulin! Often, adequate control can be achieved with oral agents! If not, insulin is utilized Medical Management Medical Management! Sulfonylureas (glyburide, glipizide)! Often first line! Low cost, low side effects! Metformin (glucophage)! First line/second line to sulfonylureas or in combo! Glitazones (Avandia, Actos)! NEJM May, June 2007: Avandia has an increased cardiovascular risk! FDA Sept 2010: US patients can only take if unable to control blood sugar with any other drug! If already on drug, must sign statement that they understand risks if wish to continue! Aplha-glucosidase inhibitors! Acarbose (Precose) and Miglitol (Glyset)! Used alone or in combo with sulfonylureas! Meglitinides! Repaglanide (Prandin) and Nateglinide (Starlix)! Best used to control mealtime glucose! DPP-4 Inhibitors! Sitagliptin (Januvia) and Saxagliptin (Onglyza)! Relatively new class of meds! Only lower BS if levels are elevated Medical Management Newest meds! Exenatide (Byetta)! Injectable drug used to treat Type 2 DM! Pramlintide Acetate (Symlin)! Used as injection in Type 1 or Type 2 DM in conjunction with mealtime insulin! Liraglutide (Victoza)! Once daily injected medication for tx of type 2 DM! FDA Approved January 2010! Alogliptin ( Nesina, Takeda Pharmaceuticals)! DPP-4 Inhibitor! FDA approved January 2013! 14 clinical trials; 8,500 patients! Safe and effective! Reduced HbA1c at 6 mos by points! Kazano=alogliptin and metformin! Oseni=alogliptin and pioglitazone 4

5 Medical Management! Insulin! Replaces natural insulin in body! Used with type 2 patients who do not respond to oral agents! Long acting Insulins! Glargine (Lantus) and Detemir (Levemir)! Last 24 hrs with no peak! More expensive than traditional insulin! Inhaled insulin! FDA approved Jan 2006 (Exubera by Pfizer)! Removed from market 2010! Poor sales?! Lung CA?! Afreeza (MannKind) Current recommendations for Treatment of Type 2 DM Control BS: HgbA1c < 7 Control HTN: <120/80 Control Cholesterol levels: Total cholesterol < 200 No smoking Exercise Normal BMI Yearly foot exams, dental exams, and dilated retinal exams Diabetic Retinopathy Diabetic Retinopathy Leading cause of blindness year old 8-12% of all new cases of legal blindness 50,000 Americans legally blind Early diagnosis and treatment can decrease vision loss by 50-60% Factors which influence development of DR duration of disease control of BS Duration of Disease: Type 2 <10 years 1% years 23% > 16 years 60% Control of BS (UKPDS) for every 1% decrease in HgbA1C there is a 35% reduction in risk for retinopathy Diabetic Retinopathy Mild NPDR Non-proliferative Diabetic Retinopathy (NPDR) mild moderate severe very severe! Microaneurysms (ma)! Dot/blot hemorrhages! Follow Up: 1 year Proliferative Diabetic Retinopathy (PDR) Including high-risk 5

6 Moderate NPDR! Marked hemorrhages/ma! Cotton wool spots (CWS)! Venous beading (VB)! Intra-retinal microvascular abnormalities to mild degree (IRMA s)! Follow up: 6 months Severe/ Very Severe NPDR! Rule:! Marked hemes/ma in all 4 quadrants! VB in 2 or more quadrants! Marked IRMA s in one quadrant! Very severe: 2 of the 3 above criteria! Follow-up: 3-4 mos or refer to Retinal specialist Proliferative Diabetic Retinopathy (PDR) Hallmark is retinal neovascularization response to ischemia from capillary closure new vessels are fragile and easily rupture Neo divided into 2 categories NVD: on or within 2 DD of optic disc NVE: neovascularization elsewhere High Risk PDR! NVD >1/4 to 1/3 disc area! Any NVD with a PRH or VH! Moderate to severe NVE with VH or PRH! Poses very high risk of severe VH and vision loss within 2 years Follow-up: Retinal consult within 2 weeks! Follow-up: Retinal specialist hrs Risk of Progression to PDR Pan-Retinal Photocoagulation (PRP) 1 year 3 years Mild NPDR 5% 14% Moderate NPDR 12-26% 30-48% Severe NPDR 52% 71%! Traditional treatment for proliferative disease! Laser applied to retina, destroying parts! Eliminates need for oxygen, thereby decreasing vasoproliferative stimulus! Elimination of hypoxia causes regression of new vessel growth! Not without complications: decreased VF, decreased night vision, CME 6

7 ETDRS and DRS! Proved benefit of immediate PRP! Showed an overall reduction rate of severe vision loss (ie 5/200) of approximately 50% in treated vs. untreated eyes! <4% chance of severe vision loss in 5 years w/ tx! PRP in 2 to 3 sessions ( spots)! Treat CSME first, if present Clinically Significant Macular Edema(CSME)! Characteristics! retinal thickening at or within 500 microns (1/3 DD) of center of macula! hard exudates at or within 1/3 DD if associated with thickening of adjacent retina! thickening greater than 1 DD in size part of which is within 1 DD of center of macular! May occur at any stage of retinopathy! Treatment: retinal consult within 2 weeks CSME Focal Macular Laser (FML)! Level of Retinopathy! mild NPDR 3% incidence of DME! moderate to severe NPDR 40%! Proliferative 71%! Type 2: Duration and Insulin! no insulin! 10 years 5%! 20 years 15%! on insulin! 10 years 10%! 20 years 30-35%! Standard Treatment for CSME! ETDRS: proved benefit of FML in improving vision! Reduces the risk of moderate vision loss (doubling of the visual angle) from 30% to less than 15%! so 50% reduction in MVL after 3 years! Real goal is to prevent further loss, not to improve vision Anti-Vegf What is Hypertension?! RISE/RIDE studies! Pts with DME received intravitreal Lucentis 0.3 mg or 0.5 mg monthly for 2 years! 33.6% of pts receiving 0.3 mg gained > 15 letters! 45.7% of pts receiving 0.5 mg gained > 15 letters! Only 12.3% in placebo group gained > 15 letters! 3-4 fold increases in treated patients! Systolic BP > 140 or! Diastolic BP > 90! Affects 70 million Americans! Essential HTN SYSTOLIC DIASTOLIC! Malignant HTN Normal <120 <80! Secondary HTN Prehypertension Stage hypertension Stage 2 hypertension >160 >100 7

8 Essential HTN: >140/90 Secondary HTN! Most common type of HTN! 90-95%! Family History common! Risk Factors include:! Sedentary lifestyle, smoking, stress, alcohol intake, obesity, high sodium intake, vitamin D deficiency, aging! Usually controlled with 1 or 2 oral meds! By definition results from an identifiable cause! Cushings Syndrome! Hypo/hyperthyroidism! Kidney disease! Pregnancy (pre-eclampsia)! Coarctation of the aorta! Certain prescription and illegal dugs Malignant HTN: BP>210/130 Malignant HTN! Ocular findings! Papillidema! Exudates! CWS! FSH! AV changes! Systemic Findings! None! HA s! Vomiting! Coma! Immediate referral for BP lowering! ER or PCP! MRI to r/o space occupying lesion! MRA to r/o venous sinus thrombus! LP if needed Malignant HTN Hypertension! 80% of patients with malignant HTN die within 1 year! 95% mortality within 3 years! Other Complications! Retinopathy! Left ventricular Hypertrophy! Angina! Myocardial infarction! Heart Failure! Stroke! Peripheral vascular disease! Chronic kidney disease 8

Hypertension Hypertension Treatment! Risk! Each increase of 20 mmhg systolic or 10 mmhg diastolic doubles risk of complications! Risk reduction with treatment! 35-40% reduction in stroke!

9 Hypertension Hypertension Treatment! Risk! Each increase of 20 mmhg systolic or 10 mmhg diastolic doubles risk of complications! Risk reduction with treatment! 35-40% reduction in stroke! 20-25% reduction in myocardial infarction! >50% reduction in heart failure! Lifestyle! Weight reduction! BMI goal ! Diet! Sodium restriction! DASH diet! Dietary Approaches to Stop Hypertension! Physical activity! Moderation of alcohol consumption DASH Diet! Dietary Approaches to Stop Hypertension! Proven to lower BP in as little as 14 days! Best with moderate or less or pre-hypertension! Includes whole grains, poultry, fish, and nuts and has reduced amounts of fats, red meats, sweets, and sugared beverages.! Hypertension Treatment! Medical management! Thiazide diuretics (hydrochlorothiazide)! Work by helping body reduce sodium and water thereby decreasing blood volume! Beta blockers (atenolol)! Reduce workload on heart, causing decreased heart rate! Angiotensin-converting enzyme (ACE) inhibitors (lisinopril, captopril)! Help relax blood vessels by blocking the formation of enzymes which narrow blood vessels Hypertension Treatment! Medical management, cont! Angiotensin II receptor blockers (losartan)! Relax blood vessels by blocking action of the enzymes which narrow blood vessels! Calcium Channel Blockers (verapamil, diltiazem)! Help relax the smooth muscles of the arteries and heart, thereby decreasing blood pressure! Renin inhibitors (aliskiren)! Newer drug which works on renin, an enzyme produced in the kidneys which starts hypertensive cascade Hypertensive Retinopathy! Pts with HTN retinopathy suffer (obviously) from systemic HTN! However, at times, this may be first clue to pts underlying disease! Pts are almost always asymptomatic, unless they have rare finding of edema or papilladema, which would cause decreased acuity 9

10 Hypertensive Retinopathy Hypertensive Retinopathy! Typically pts with HTN retinopathy are middle aged or older! HTN more common in middle aged men than women! But more common in elderly woman than elderly men! Much more prevalent in African-Americans than Caucasians! Clinical findings include! Retinal artery narrowing and attenuation! Retinal artery nicking and crossing changes! Flame shaped hemes! Cotton wool spots! Rarely retinal or macula edema! May have macular star! Disc edema Hypertensive Retinopathy Hypertensive Retinopathy! Keith Wagner Baker Classification System! Grade 1 Hypertensive Retinopathy! Retinal arterial narrowing and straightening! Grade 2! AV Nicking! Keith Wagner Baker Classification System! Grade 3! Retinal hemorrhages! Cotton wool spots! Hard exudates! Macular star! Grade 4! Grade 3 with ONH edema Hypertensive Retinopathy Hypertensive Retinopathy! Rare to have either macula edema or optic disc edema unless there is malignant HTN, where BP is elevated in 250/130 range! However presentation of macular star and disc edema is almost pathognomonic for HTN crisis! CWS typically do not appear until diastolic BP is > 110! Monitor fundus q 12 months! Sooner if severe! Pt education! Management involves appropriate tx of underlying HTN, with referral to primary care physician or internist! If papilledema from HTN, consider medical emergency!!! Immediate referral and/or trip to ER!! 10

11 ! Several different types of plaques can often be visualized in the retinal vasculature! Pt is typically elderly, has HTN, CAD, hypercholesterolemia/hyperlipidemia, and/or atherosclerotic disease! Often totally asymptomatic and found on routine exam! May present with amarosis fugax, transient episodes of monocular blindness! Rarely, may report transient ischemic attack (TIA), which is above with hemiparesis, parasthesia or aphasia! Three different types of plaques, but all share strong association to significant cardiovascular disease! Cholesterol (Hollenhorst) plaque! shiny yellow-orange in appearance! typically from the ipsilateral carotid artery! Rarely causes occlusion, unless multiple! Typically occurs at bifurcations! Mobile in nature! Calcific! Appears more whitish than HH! Classically within arteriole, not at bifurcation! Typically immobile! Often causes BRAO! Often from cardiac arethromas of heart valves Retinal plaques! Fibrino-platelet! Appear as dull white to gray, long plugs! Typically within arterioles, not at bifurcations! May break-up and dissolve with time! May lead to BRAO or CRAO! Often associated with carotid disease or mitral valve insufficiency! No direct management of plaques is needed! Management is aimed at discovering source of embolus to decrease risk of other emboli, occlusion, or stroke! Pts need referral to internist for complete physical 11

12 ! Examination should include! Complete physical, including cardiac risk factors and BP evaluation! Carotid ultrasound! Stress echocardiogram! Fasting BS! Lipid profiles! Cardiac enzymes! After ruling out underlying etiology, see patient regularly, q 6-12 mos, to evaluate for additional plaques or other disease associated with vascular disease! BRVO/CRVO! BRAO/CRAO! NTG! If carotid stenosis or coronary artery disease is found treatment may include! Carotid endarterectomy! Angioplasty! Aspirin therapy! Other anti-coagulation therapy, such as coumadin! Pts with cholesterol HH emboli have 15% mortality at 1 yr, 29% by year 3, and 54% by 7 years! Mostly from cardiac disease Hyperlipidemia! Elevation of lipids in the bloodstream! Cholesterol and triglycerides are most commonly affected! High lipids causes accelerated atherosclerosis (hardening of the arteries)! Increased risk of plaque formation, heart disease, stroke, and other vascular disease! Can be genetic, but most often affected by lifestyle! Obesity, sedentary lifestyle, smoking! Also associated with diabetes, kidney disease, pregnancy, and hypo-thyroidism Hyperlipidemia Hyperlipidemia! Diagnosis! Fasting Lipid Profile! Total Cholesterol! LDL (low-density lipoproteins)! high levels associated with increased heart attack! HDL (high-density lipoproteins)! protective against heart attack! Triglycerides! Total Chol/HDL ratio! Total cholesterol! < 200 desirable! borderline high! > 240 high! HDL ( good cholesterol)! < 40 for men and < 50 for women is low! > 60 considered protective for heart disease! LDL ( bad cholesterol)! <100 desirable! borderline! borderline high! >160 high 12

13 Hyperlipidemia Hyperlipidemia! Triglycerides! < 150 is desirable! borderline high! > 200 is high! Total chol/hdl! 3.5:1 is optimal! Below 5:1 is acceptable! Above 5:1 unhealthy! National Cholesterol Education Program (NCEO) recommends cholesterol screenings for:! Males and females > 20 every 5 yrs! More often if risk factors! Diabetes! Obesity! Family history! > 65 years of age Hyperlipidemia What is Obesity?! Treatment! Exercise! Weight loss! Elimination of trans-fats! Increase omega-3 s! Identify and treat other risk factors! Hypertension! Diabetes! Smoking cessation! Increased body weight caused by excessive accumulation of fat! BMI defined as patient s weight (kg) divided by height (m 2 )! BMI categories of obesity! Normal ! Overweight ! Obesity ! Moderate obesity ! Extreme obesity over 40 What is Obesity? Body Mass Index BMI = Overweight BMI > 30 Obese BMI > 40 Morbidly Obese BMI = Weight in Kg (Height in Meters) 2 BMI > 50 Super Morbidly Obese 13

BMI Table Statistics! 1/3 of US adults are obese! 1 in 6 US children is overweight! #2 modifiable risk factor for death (tobacco)! May result in reduced life expectancy for the 1 st time in 200 years!

14 BMI Table Statistics! 1/3 of US adults are obese! 1 in 6 US children is overweight! #2 modifiable risk factor for death (tobacco)! May result in reduced life expectancy for the 1 st time in 200 years!! Obese patients have 6.7 years less life expectancy than non-obese patients! New England Journal of Medicine! 300,000 Deaths Each Year (Directly Related) Obesity: Ocular Complications Obesity: Systemic Complications! AMD! Diabetic retinopathy! Cataract! Pseudotumor cerebri (papilledema)! Floppy lid syndrome! Ocular hypertension! Exophthalmos/proptosis! HTN! Dyslipidemia! Type 2 DM! CAD! Stroke! Gall bladder disease! Osteoarthritis! Malignancies Other Scary Stuff! 165 Million Americans will be obese by 2030! ½ of all American men will be obese by 2030! US healthcare spending expected to increase $66 Billion per year by 2030 if this trend continues! 165 million obese Americans would correlate to an additional 8 million cases of DM, 6.8 million cases of heart disease and stroke, and 0.5 million cases of cancer! A 1% reduction in BMI would prevent as many as 2.4 million cases of DM and 1.7 million cases of heart disease and stroke 14

What is diabetes? Ocolusystemic Disease Essen6als. Statistics, cont. Statistics. Statistics. The Diabetes Epidemic 9/5/12

What is diabetes? Ocolusystemic Disease Essen6als Steven Ferrucci, OD, FAAO Chief, Optometry Sepulveda VA Associate Professor, SCCO DM is a chronic disorder characterized by a lack of insulin or increased