6/14/2021

Systemic Disease Straight Up…. AOA’s definition of Optometry approved Sept 2012 with a Twist of Neuro! Doctors of optometry (ODs) are the independent primary health care Beth A. Steele, OD, FAAO professionals for the eye. Optometrists examine, diagnose, treat, and [email protected] manage diseases, injuries, and disorders of the visual system, the eye, and associated structures as well as identify related systemic conditions affecting the eye.

PREVENTION Not just this…

TREATING THE WHOLE PATIENT But also this…

MEDICAL OPTOMETRY

…..where do we fit in?

1 6/14/2021

29 AA F Hx ESRD, on dialysis Blood Pressure Classifications and Referral Guidelines (adapted from the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure –JNC 7, no symptoms, visual or systemic 2003) Hypotension normal Pre‐ HTN Stage 1Stage 2 Critical High Point

Systolic < 90 < 120 120‐139 140‐ 159 ≥160 >180

Diastolic < 60 < 80 80 ‐ 89 90‐99 ≥100 >110

Refer Refer Evaluate or refer From: 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members within 2 within 1 immediately or BP 159/116 Appointed to the Eighth Joint National Committee (JNC 8) months month within 1 week

JNC vs. ACC/AHA Guidelines

All values ~10mmHg lower than JNC

• 2017 ACC/AHA Clinical Practice Guidelines lowered thresholds by 10mmHg for diagnosis and treatment goals! • 26% increase in US prevalence HTN • Very controversial

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Atherosclerotic cardiovascular disease (ASCVD) risk calculator • 10‐year risk of CVD • http://tools.acc.org/ASCVD‐Risk‐Estimator/

• age >65 • atherosclerosis or risk of developing it (e.g. total cholesterol, HDL, LDL; smoking history), • chronic kidney disease • diabetes

Number of deaths and age‐adjusted death rates for hypertension‐related and all Prevalence of Hypertension other causes of death combined: United States, 2000–2013

Overall 29.1 Sex Men 29.7 Women 28.5 Age (years) 18‐39 7.3 40‐59 32.4 60 and over 65 Race and Hispanic origin Non‐Hispanic white 28 Non‐Hispanic black 42.1 Non‐Hispanic Asian 24.7 Hispanic 26 0 10203040506070

Percent

Nwankwo. T., Yoon. S.S., Burt. V., Gu. Q. (2013). Hypertension among adults in the United States: National Health and Nutrition Examination Survey, 2011–2012. NCHS data brief, no 133. Hyattsville, MD: National Center for Health Statistics. CDC.gov

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“Hypertensive Crisis”

• URGENT vs. EMERGENT

Systolic >180 • JNC 7 “Evaluate and treat immediately or within 1 week depending on clinical Diastolic >110 situations and complications.”

• Systemic symptoms • Ocular findings

Meetz RE, Harris TA. The optometrist's role in the management of hypertensive crises. Optometry. 2011 Feb;82(2):108-16.

Hypertensive Crisis Emergencies – indicated Same BP –2 different situations end organ damage BP 190/112 BP 190/112 • Feeling “fine” • (+) “migraine” since yesterday • 1‐year death rate is >79% • Forgot his medicine • DFE: disc • today median survival is 10.4 months if edema, the emergency is left untreated • Denies H/A, etc flame • actual BP level may not be as heme • DFE: crossing important as the rate of BP rise changes

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Causes of Hypertensive Crisis

• Most have known Hx HTN • Compliance • Recent medication changes • Drug interactions

• Pregnancy • Recreational Drug Use (cocaine, amphetamines) • Head Trauma

Acute focal RPE lesions Vs…. Hypertensive leak on IVFA 32 year old with Hx kidney transplant Choroidopathy • Young patients • Acute HTN

• Elschnig Spots • Focal choriodal infarctions • Sign of past acute HTN episodes

• Siegrist Streaks • Linear areas of infarction and subsequent necrosis

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Diagnosis – Management 17 year old with adrenal carcinoma HTN Choroidopathy Choroidal Thickness

• SD‐OCT with EDI or SS‐ • SS‐OCT or SD‐OCT with OCT EDI • Choroidal thickening M. Rahhal‐Ortuño, A.S. et al. Archivos de la Sociedad initially Española de Oftalmología, 2019 Manjunath V, Am J Ophthalmol. 2010 • SRDs • vertical distance from RPE • Inner retinal thinning over ischemic areas and inner surface of the • OCT‐A : moth‐eaten sclera appearance of the • Subfoveally + parafoveally choriocapillaris • FAF: hypo of Elschnig spots

Tsukikawa M, Stacey AW. A Clin Optom 2020

SRDs, PEDs, can lead to RPE Tear

9 days after admission, BP lowering on board

Natsuki Matsubara, et al. AJOpht, 2019

6 6/14/2021

85 WM, HTN, Smoker

• Black circle over vision x 2 days Indirect manifestations of HTN: • FB vision Are we educating our Patients? • Pupils normal NAION Retinal Vein Occlusion Retinal Macroaneurysm

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• 52 Caucasian male • Never had an eye exam • No regular health care • Vision goes “out” when he turns his head

Vascular Supply Systems to Brain •≥70% blockage before ocular 1. Internal Carotid system manifestations  Supplies anterior and lateral portions of brain  Unilateral visual disturbances •5 year mortality rate – 40% 2. Vertebrobasilar system • MI is mc  Provides posterior brain  Bilateral visual symptoms • 4/5 strokes are causes by atherosclerosis at carotid bifurcation

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…as many diseases as she pleases…. Dr. Leo Semes

• Moderate NPDR –tough call

Carotid Artery Occlusion

• Associated with up to 20% of strokes • 4/5 strokes are causes by atherosclerotic disease at carotid bifurcation • Risk factors: • HTN • Smoking • Diabetes • High cholesterol (high LDL/triglyc) • Obesity • Sleep Apnea • Stroke • FHx • leading causes of death in US • 44WM, Type 1, A1C 8.3 • Age • 1/3 of cases are fatal Hb: 12.7 ‐ low • Lack of exercise • Survivors usually have irreversible • An easier call, but… damage HCT: 38% ‐ borderline Platelets: 157 –low

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• X 2 hours ago Intra‐arteriolar emboli • 62 year old white male “Vision went out, but • Heavy smoker, hx now it’s back” hypercholesterolemia, +HTN • Increased risk of stroke, mortality, co‐morbidity • 25% have carotid stenosis >40% (Bakri 2013) • Symptoms? Ocular signs of carotid • Often transient – plaques are pliable artery disease • Correlated with degree of occlusion? • Not predictive of future retinal events 1. Amaurosis Fugax – TMVL • Doppler 2. RAO 3. Hollenhorst Plaque • EKG/Angiography 4. Ocular Hypoperfusion Only 10% of emboli from ICA end up in OA .. ! (Kaufmann 2012)

81 Caucasian retinal heme and intra‐ And then there’s… female arteriolar plaque • Atrial fibrillation • 60 year old male longhaul trucker • Recent falls – due to TIA • Smoker, hx CVD • Sudden unilateral decrease vision • 2 hours of event Most common cardiac arrhythmia • Your staff suggests he come in Increased risk of mortality immediately  TIA, stroke (x5) and MI • Hx of 20/50 amblyopia in other Screen for with RAO patients eye   risk of stroke • LPO OS   need for anticoagulant

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tPA for CRAO New Guidelines • Dissolves embolism • Oral or IV • Some studies have shown tPA to be effective in improving VA for up • National Stroke Association, 2011 to 60‐70% cases • Other studies find no difference • American Heart Association, 2013 • Tx within 6 hours –better outcomes • Adverse events with tPA • Strokes of major arteries = must be sent immediately to an • Cerebral stroke and hemorrhage (10%) ER with stroke center • RAO • Transient monocular vision loss

3 categories of stroke

1. Ischemic (85%) All are medical 2. Hemorrhagic emergencies! 3. Transient Ischemic Attack • Temporary disruptions in blood flow ‐‐ no permanent damage • Symptoms last 30 min to 2 hrs ‐‐ often same symptoms as stroke • Risk of stroke if untreated • 10‐15% in 3 months – 50% of these within next 48 hours Take home: Spend the time to determine if most likely vascular….. • CDC 2015 33% in the next year AHA 2015 History, presentation, risk factors. Johnston WC, et al. Lancet. 2007; 369: 283‐ 292.

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• 48 WM 48 WM C/c: blurry vision, bumping into things C/c: blurry vision, bumping into things • Significance of Macular Sparing? • Never worn glasses • LEE, LPE: “over 10 years ago” • VA: 20/30 OD, 20/30‐2 OS • Pupils: normal, ‐APD • Confrontations: left field restricted OD, OS • Refraction: • OD +1.00 ‐0.50 x 175 20/15 • OS +1.25 –0.75 x 008 20/15

Kline L. Neuro-Ophthalmology Review • Normal IOP and ant/post seg exam Manual. 5th Edition.

50

Imaging considerations for this patient… And what about this one? • CT vs. MRI • ±contrast • ±angiography • Location to scan • ±urgency • CT with Diffuse Weighted Imaging (DWI) if acute

And… expect eventual structural loss

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Unexplained VF Loss

66 year old AA FM • Left eye: NLP due to old RD • Right eye:

MRA of Brain – Clear Silent Migraine ?

• Migraine VF Loss – Anything and Everything • Small peripheral scotomas, constricted fields, total loss…… • Can last up to 75 days

• Progressive cortical depression – associated with vascular changes • Leads to vasoconstriction, • Then vasodilation • Brief neuronal excitation, followed by prolonged inhibition • Triggers headache phase

• RNFL thinning around ONH , and faster progression of VF loss in NTG

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VF Loss – Migraine vs. Tension H/A Benign Episodic Pupillary Mydriasis

• women with migraines

• last minutes to one week; usually 12 hours

• may or may not react to light

http://www.nature.com/eye/journal/v21/n1/f ull/6702422a.html Yener. Neuro‐Ophthalmology, 2017.

76 Caucasian male Unexplained vascular changes.. ? 30% carotid occlusion, kidney disease

“Blood work‐up”….tests driven by differentials

 CBC with differential  Chem 7  Lipid Profile  ESR  C‐Reactive Protein

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CBC Index Clinical Significance Red Blood Count (RBC) Anemia and classification Platelet Count (PLT) Clotting disorders Mean Platelet Volume (MPV) Clotting disorders White Blood Count (WBC) ↑ in leukemia Test Ordered Results with Differential ↓ in leukopenia (granulomatous dz, meds, bacterial inf) FBS 107 mg/dl • neutrophils ↑ in bacterial infections A1C 5.6 • lymphocytes ↑in certain viral infections CBC Hb: 10 g/dl • monocytes ↑ in bacterial infections Hct: 32% Anemia • eosinophils Involved in allergic disorders and parasitic infections • basophils Immediate immune reactions Platelets: 100,000 cmm Thrombocytopenia Hemoglobin (Hb) Anemia and classification MCV: normal Hematocrit (Hct) ↑ in PCV, CHF, COPD, ↑altitude Normocytic ↓ in anemia, bleeding, sarcoidosis All other values normal RBC Indices Carotid Doppler 30% Carotid Occlusion both sides • Mean Corpuscular Volume ↑ in pernicious anemia (MCV) ↓ in Fe deficiency anemia • RBC Distribution Width (RDW) • Mean Corpuscular Hemoglobin (MCH) • Mean Corpuscular Hemoglobin ↑ Hyperchromic (B12 and Folic Acid Def) Concentration (MCHC) ↓ Hypochromic (Fe Def, thalassemia)

Chem 7 / Basic Metabolic Panel Severe anemia/thrombocytopenia due to ESRD

1. Creatinine • Screens for 2. Blood urea nitrogen • Kidney disease (BUN) • Liver Disease 3. Glucose • Diabetes and other blood sugar disorders 4. Carbon dioxide 5. Chloride 6. Sodium electrolytes 7. Potassium 8. (Sometimes Calcium)

15 6/14/2021

Factor V Leiden??? What’s that?!! Also Consider: Common Coagulopathies

Condition Name of Lab Test • Factor V – clotting protein Antiphospholipid Antibody / Antiphospholipid Antibody Panel • genec mutaon: ↑clong in veins Antiphospholipid Syndrome • Mc prothromobotic gene mutation in Caucasians –5% population • Caucasians of European descent Protein C and/or S deficiency Protein C and S Activity with Reflex to Protein C and/or S Antigen • Often undiagnosed, however…. • deep vein thrombosis Antithrombin III deficiency Antithrombin III Panel • pulmonary embolisms • CRVO Elevation of platelet factor 4 Platelet Factor 4 • 11% of ocular vasc occlusions assoc with FVL (Schockman 2015; Fegan 2002) 57 Caucasian female with Factor V Leiden Factor (V) Leiden Mutation Analysis borderline HTN and Factor V Zou Y et al. 2017 Manucci P, et al. Thrombosis and Haemostasis 2015 Leiden

double vision double vision

•Head injury 3 months ago 1⁰ gaze –note head –Imaging in ER all negative posture

•Vertical diplopia –Worse in down gaze –Right head tilt Under‐action LSO

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Torsion noted on DFEs! Use Double Maddox Rod to help Double Maddox Rod?? determine if SOP is bilateral ‐‐ often missed due to asymmetry

• Can help determine if SOP is bilateral • often missed due to asymmetry

• MR over both eyes • Small vertical prism over one eye • Cyclodeviated eye will report a “tilted” line

Rotating MR to straighten image of line

76 year old male with double vision SO Palsy

• Etiology • Trauma • Left‐sided headache • Decompensated congenital –slow onset • Denies Trauma • Least likely of EOM palsies to have underlying etiology, BUT…. Imaging, careful • Microvascular disease follow up • Brain abnormality • Treatment • Prism, surgery, botox

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If you want to find something wrong…. 1⁰ gaze

• MRI revealed small saccular aneurysm at Right MCA • Brain aneurysm: incidental finding? • Likelihood of relation to problem? • Size

• Unruptured smaIl aneurysms • 3 % of the population • Risk of rupture • Size • anatomical location

9 year EOM palsies: Do not assume…… old AAFM 1. Vasculopathic  16.5% thought to be ischemic had another cause (neoplasm, MS, GCA) Tamhankar, et al. Ophthalmology Nov 2013

2. True isolation • Left pupil larger than right And don’t forget about… • Left ptosis • GCA • No history birth trauma • Carotid Artery Dissection • Aneurysm • No heterochromia • …

18 6/14/2021

Pupils can be scary! 1 hour after 0.5% apraclonidine….

Little Pupil Problems Big Pupil Problems APD Horner’s Adie’s Optic nerve disease • Neck trauma/surgery • Idiopathic Vascular event • Lung tumor • Viral Demyelinating disease • Lesion sympathetic Brain tumor pathway 3rd Nerve • Ischemia Argyll – Robertson • Tumor • Tertiary syphilis • Aneurysm • Diabetic encephalopathy

Don’t forget – Pharmacologic Causes!

Carod Artery Dissecon → Painful Horner’s Carotid Artery Dissection • 48 year old male presents with a big pupil in the left eye. • Traumatic or spontaneous • ROS: right‐sided neck pain, headache • Cause of 2.5% of strokes • 10‐25% of ischemic events in • Exam patients <45 Rao, J Vasc Surg 2011 • Right eye – miosis, ptosis Lu A, et al. Emerg Radiol Feb 2015 • Dilates with 0.5% apraclonidine

• Horner’s • Can be subtle, transient, intermittent

http://www.cmaj.ca

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Carotid Artery Dissection

• Presentation • Headache –up to 69%‐ most common presenting • 43 AA FM symptom • History of • Unilateral neck pain –up to 49% recurring eye pain • Ipsilateral Horner’s –up to 60% • Visual manifestations associated with artery dissections • Joint pain • Photopsia • …lots of issues • VF defect • Mgmnt • Immediate Imaging: CT/CTA, MRI/A, T1W with contrast and fat suppression, Doppler • Anti‐platelets, anti‐coagulant tx

Kwak JH, et al. Neurointervention, 2011.

Laboratory Testing for Differentials – Sarcoidosis Inflammatory Conditions • ESR★ • C‐reactive protein★ • Multisystem granulomatous disease • Approach ? • Subacute/acute or chronic • Rh‐Factor★ • Unknown etiology ‐ Environmental, possibly • ANA★ infectious, and/or genetics • Order everything on the • ACE★ • Up to 40 per 100,000 in US menu? • 8:1 African Americans, and more virulent in • Lysozyme★ AA’s • PPD • 2:1 females • Non‐granulomatous vs. • Generally presenting 20‐30’s (40‐60’s) granulomatous? • Lyme titer • Symptom based? • VDRL, FT‐ABS • Diagnosis: sprojects.mmi.mcgill.ca • Serum ACE—90% with active disease (+) • HLA‐B27 • Serum Lysozyme, ESR • Calcium and liver function tests • …… • Chest xray

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Sarcoid: Ocular Manifestations in up to 50% Posterior Segment—up to

• Most common—granulomatous uveitis 25% • secondary glaucoma Vitritis, phlebitis • Posterior uveitis/vitritis/chorioretinitis Choroidal granulomas • Eyelid—up to 27% Retinal and ONH NV • Granulomatous lid lesion • Lacrimal gland enlargement Neuro‐ophthalmic – • Lid retraction 5‐10% • Conjunctival granuloma—up to 56% CN palsies • DES from lacrimal gland involvement—up to 66% Papilledema from intracranial lesions Direct ON infiltration –5% Optic Neuropthy / Neuritis

Optic Neuropathy

• Women • AA • 2 subtypes • Sub‐acute, neuritis • Progressive neuropathy • 2/3 are unilateral • 1/3 later involving other eye • 1/3 with intraocular inflammation • 1/3 with pain • OD: NLP • Treatment: steroids, immunosuppressants • OS: 20/80 with dense • Function varies inferior loss • Early treatment –better outcome

Kidd DP, et al. Am Academy Neurology 2016

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Vitritis Without Known Cause – Starting Point?

• Treatment? • Labs? • Imaging? • Consequences ?

Plaquenil Toxicity 2016 ‐ Revised Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy Marmor MF, et al. Ophth Feb 2011. Melles RB, Marmor MF. JAMA Ophthalmol 2014. Melles RB, Marmor MF. Ophthalmology 2015.

 Risk of toxicity increases sharply towards 1% after 5‐7 yrs of use, or cumulative

Rheumatolgist.com dose of 1000 g HCQ  Initial baseline exam, then annual screenings after 5 years  Screening:  Regular exams with DFE  10‐2 Nejm.org  24‐2 or 30‐2 for Asian patients  SD OCT*, FAF or mfERG

*most objective, lowest variability Melles RB, Marmor MF. Ophthalmology 2015.

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Damage is not always • 10% of patients with a parafoveal!! ring scotoma did NOT show damage with SD‐ Melles, OCT! Marmor, Ophthal Aug 2014

Marmor MF, Melles RB. Ophthalmology. Jan 2014.

FAF: Plaquenil Toxicity OCT –what to look for early

• May contribute to earlier detection • Scans • Before RPE degeneration develops • High resolution • Raster or radial • Early change: • Enhanced depth imaging (EDI) • hyper AF Normal parafoveal • Macular cube – quantifiable • 2‐6 degree ring around fovea • Early photoreceptor damage – subtle • Outer retinal thinning • Later change: • Disruption to PIL • hypo AF • Coalesces into dark absence of FAF‐ mixed pericentral cells are dead

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Toxicity is Dose‐Dependent 22 Venezuelan Female Type 1 Diabetic • Proper dose <1% with toxicity • 6.5mg/kg based on IDEAL weight • Typically 200mg BID –ok for normal size patient • Not ok if short/small • Not ok if obese • Not ok if kidney disease • Mostly clinically significant cases of toxicity are iatrogenic • Overdosing (>10%) • Lack of screening • Inadequate screening/missed findings • Damage can progress up to 3 years after discontinuation….

Browning DJ Hydroychloroquine and Chloroquine Retinopathy 2015

• BCVA OD 20/25 • PC cataracts OS>OD Procotol V: Other considerations

• Central thickness 400 : marker for more severe DME

• Applicable to all eyes with CI‐DME with good VA? • patients had well‐controlled diabetes with a mean A1c of 7.6, and • enrolled eyes had earlier stages of DR, mild DME

DRCR Net Protocol V: Ok to watch center involved DME with good VA

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44 year old OCT‐A for Diabetic Mexican FM Retinopathy

• CIDME, BCVA 20/25+ • Earlier, often sub‐clinical findings …..

• Earlier detection. • Microaneurysms • More aggressiveSuperficial f/u Retinal Plexus • Capillary nonperfusion • Small pockets of ischemia better visualized care, patient education. than with IVFA • Change in patient • Size/integrity of FAZ behavior. • Reduced vascular density • Localization/differentiation of vascular abnormalities –IRMA vs neo • Follow response to tx Superficial overlaid onto FA Deep Retinal Plexus

Zeiss.com

Superficial plexus: Deep plexus: vessel drop out, microaneurysms, non‐perfusion enlarged FAZ

Couturier Retina 2015

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37 y0, mild NPDR 43AA type 2

c

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