Medical Testing in Retinal Diseases Sherrol A. Reynolds O.D., FAAO

Associate Professor / NSU College of Optometry

Jay Harris Levy, MD Retina Macula Specialists of Miami

COURSE OUTLINE

I. Medical Testing

• Point of Care Testing (PCOT) o CLIA Regulations: Clinical Laboratory Improvement Amendments (CLIA)-Waived

tests- ensure the accuracy, quality, and reliability of laboratory test results o 120 CLIA-waived laboratory tests

§ Blood glucose § Hemoglobin A1C § Cholesterol § International normalized ratio (INR)

o Occupational Safety and Health Administration (OSHA)

II. Diabetes (DM) Test

• DM Problem (2019) o 30.3 million people in the US have diabetes (9.4%) National Diabetes Fact Sheet, 2018 o Diagnosed: 23.1 million people o Undiagnosed: 7.2. (23.8%) o Pre-diabetes: 84.1 million (33.95)/ 23.1 million 65 years or older

• Case presentations • POC Testing:

o Fingerstick

*Fasting is defined as no caloric intake for at least 8 h

A1C Fasting Plasma Glucose Test (FPG)

2-Hour Oral Glucose Challenge

Acceptable ≤5.6% Below 100 mg/dlBelow 140 mg/dl

Pre-Diabetes 5.7% - 6.4% 100-125 mg/dl (IFG) 140-199 mg/dl (IGT)

Diabetes ≥ 6.5% 126 mg/dl or above 200 mg/dl or above

American Diabetes Association. Diabetes Care 2010; 33;(Suppl.1):S11-61.

.

o Glycosylated hemoglobin is HbA1c. o Average blood glucose for the previous 3 months. Target AIC target hemoglobin HbA1C

£7 percent o HbAIC dependent on:

§ Life span of RBC’s § How long AIC is exposed to glucose § Conditions that affect erythrocyte turnover Anemia, hemolysis, blood loss, and

hemoglobin variants lower A1C (less HbA) § Permeability of RBC’s to Glucose permeability § $10.00/test

o HbAIC and retinopathy:

• Diabetic Retinopathy (DR)/DME

o ~8 Million Americans, but expected to increase to 11 million by 2030 o Combination of VEGF and inflammation o Prevention: good glycemic, blood pressure (£130/80), cholesterol control

• Management/ Treatment

II. Blood pressure • Problem- 103 million Americans (1 of every 3 adults)

o Risk for stroke, myocardial infarction (MI), vascular disease, and chronic kidney disease (CKD)

§ 69% of people who have a first heart attack (MI) § 77% of those who have a first stroke § 74% of those who have HF have a BP >140/90 mm Hg § Nearly half of people with high blood pressure (47.5 %) do not have it under control

• New Guidelines (Hypertension Clinical Practice Guidelines (2017) o Definition- The new guideline lowers the target for blood pressure treatment to 130/80 mmHg o Classification

§ Normal: Less than 120/80 mm Hg § Elevated: Systolic between 120-129 and diastolic less than 80 § Stage 1: Systolic between 130-139 or diastolic between 80-89 § Stage 2: Systolic at least 140 or diastolic at least 90 mm Hg

• Hypertensive crisis: Urgency versus Emergency o Systolic over 180 and/or diastolic over 120, with patients needing prompt changes in

medication if there are no other indications of problems, or immediate hospitalization if there are signs of organ damage.

Pivotal Diabetes Studies

DCCT. N Engl J Med. 1993;329:977-986UKPDS. Lancet. 1998;352:854-865.ACCORD Study Group. N Engl J Med. 2008;358:2545-2559ADVANCE Collaborative Group. N Engl J Med. 2008;358:2560-2572VADT N Engl J Med 2009; 360:129-139

o Malignant HTR- medical emergency o Mortality rate is 50% at 2 months and 90% at one year if untreated

III. Lipid Profile

o Total Cholesterol o Triglycerides (TGs) o LDL “bad” (low-density lipoproteins)- increase risk of heart disease o HDL “good” (high-density lipoproteins)- cardioprotective

• In-office testing

• Retinal vein occlusion (RVO) • Pathogenesis RVO

• Virchow’s triad- compression of the veins by arteries, degenerative changes within venous walls, and hypercoagulability

Central Retinal Vein Occlusion (CRVO) • Non-ischemic (83% of cases) Acuity >20/200

o Good prognosis o 5-20% progress from non-ischemic to ischemic CRVO

• Ischemic - greater than 10-disc areas of capillary non-perfusion observed on fluorescein angiography

§ (+) RAPD § Poor Prognosis § Risk for neovascularization (90day glaucoma)

Branch retinal vein occlusion (BRVO)- (Hayreh, 2014) • Latest classification:

§ Major BRVO- when one of the major branch retinal veins is occluded § Non-ischemic § Ischemic- 5 DD or more of capillary non-perfusion on FA, neovascularization

§ Macular BRVO-when one of the macular venules is occluded. § Macular edema (this is the most common cause of vision loss in BRVO)

o Macular edema at any point with RVO needs to be referred, have more detrimental impact in a shorter period of time (between 3-6 months)

• Retinal Artery Occlusion and Stroke Risk Update (2019) o Emboli (62% of eyes): Cholesterol (hollenhorst), calcific and platelet-fibrin, septic emboli

(Roth spot hemorrhage) IV drug use, or other emboli (tumors, migraines, parasitic or fungal injections, Susac syndrome)

o Non-embolic causes-thrombosis and atherosclerosis o Rule-out GCA in patients over 50 years of age o Treatment (1-24-hour window of opportunity)-retina can only survive 90-100 minutes of

ischemia prior to permanent damage. • Digital massage • Breathing into a brown paper bag in order to increase blood CO2 levels • Fibrinolytic agents (clot-busters)/ • Hyperbaric oxygen (HBO2) has demonstrated promise

§ CRAO/BRAO and Stroke Update • Because silent brain infarctions bear a high risk of future stroke, patients with

BRAO/CRAO, TIA or AF should undergo prompt neuroimaging and cardiovascular checkup, preferably on a stroke unit

• Diffusion-weighted magnetic resonance (DWI) • Carotid Artery Disease- Ocular Ischemic Syndrome (OIS)- Ocular hypoperfusion or “venous

stasis retinopathy” o Common (CCA) or internal (ICA) carotid arteries stenosis o Clinical case presentation o Rule-out GCA (Giant cell arteritis) o Carotid Artery Endarterectomy

IV. Inflammatory Markers • Erythrocyte sedimentation rate (ESR)

o Giant Cell Arteritis (GCA), infections, chronic inflammatory or connective tissue disease o ESR: Males- 0-15mm/hr

Female: 0-20 mm/hr • C-reactive protein (CRP)

o Inflammation (or infection) or Use in cardiovascular disease • CRP

o Low risk < 1.0 mg/L o Aver. risk 1.0-3.0 mg/L o High risk > 3.0 mg/L

• Antinuclear antibodies (ANA) o Sensitive test- lacks specificity o + ANA test= Autoimmune disease o Specific testing required= Final diagnosis

• Rheumatoid factor (RF) • Human leukocyte antigens (HLA)

o HLA-B27 o Ankylosing spondylitis o Reiter’s syndrome (reactive arthritis) o Crohn’s/ Ulcerative colitis

• Serum angiotensin-converting enzyme (ACE) o Sarcoidosis

§ Bilateral hilar lymphadenopathy

§ Pulmonary infiltration • Chest X-ray • Hilar lymphadenopathy • +PPD • Necessary to rule out TB with an Anergy panel

• Anti-Double Stranded DNA o Systemic lupus erythematosus o Correlate with disease activity

• Order in cases of uveitis or retinal vasculitis (sheathing) o GCA- giant cell arteritis o CRAO o Anterior ischemic optic neuropathy (AION) o Granulomatous anterior uveitis or vitritis- Syphilitic infection is commonly related to a

nonspecific iritis or iridocyclitis • Unexplained retinitis or neuritis • Chorioretinitis

V. Infectious Markers • Retinal cotton-wool spots

o ELISA and/or western blot in patients at risk for HIV § Rule-out in young patients with isolated CWS

• Enzyme-linked immunosorbent assays (ELISAs) o Human immunodeficiency virus (HIV), toxocariasis and Lyme disease

• A Western blot o Test for HIV

• VDRL/ PRP/ FTA-ABS o Screening tests for syphilis o Positive Test o Must be confirmed with a FTA-ABS test

VI. Hematological Testing • Antiphospholipid Syndrome

o Antiphospholipid antibodies § Play a crucial role in blood clotting

o Increase blood clots within the blood vessels (thrombosis)= strokes and MI o Narrowing and irregularity of the blood vessels (vasculopathy) o Blood Clotting- prothrombin time (PT) or “pro time” o Recurrent spontaneous abortions

• Patient’s on blood thinners POC o International normalized ratio (INR)

§ Measure the length of time platelet takes for a sample of blood to clot • Sickle cell retinopathy

o An autosomal recessive genetic disorder o Laboratory

§ Sickledex: in-office screening § Hemoglobin Electrophoresis- confirm the diagnosis and type of disease is present § DNA Analysis

o Anterior segment § Comma or "S"- shaped capillary segments in the bulbar conj. § Focal iris atrophy/ neovascularization

§ Subconjunctival hemorrhages/ spontaneous hyphemas o Sickle Cell Retinopathy

§ Non-proliferative Retinopathy § Proliferative Sickle Cell Retinopathy

• Neovascular and Fibrous Proliferations-Sea Fan formation *Auto-infarct or spontaneously regress (20-60%)

VII. Conclusion

• Medical testing is critical to the diagnosis and management of Retinal Diseases • Testing can greatly enhance the level of care provided to our patients.

References:

• Centers for Disease Control and Prevention. 2017 http://www.cdc.gov/diabetes/pdfs/library/diabetesreportcard2017.pdf.

• Hypertension. 2017.Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure

• Retinal and Ophthalmic Artery Occlusions Preferred Practice Pattern®. Ophthalmology. 2017.

• Retinal Vein Occlusions Preferred Practice Pattern®Guidelines. Ophthalmology. 2016