9/18/2018

Systemic Disease AOA’s definition of Optometry Straight Up…. approved Sept 2012 with a Twist of Neuro!

Doctors of optometry (ODs) are the independent primary health care professionals for the . Optometrists examine, diagnose, treat, and manage Beth A. Steele, OD, FAAO diseases, injuries, and disorders of the , the eye, and associated structures as well as identify [email protected] related systemic conditions affecting the eye. Disclosures: Member of Optos Advisory Board

PREVENTION Not just this…

WELLNESS

TREATING THE WHOLE PATIENT

MEDICAL OPTOMETRY

…..where do we fit in? But also this…

•≥70% blockage before ocular manifestations

•5 year mortality rate – 40% • MI is mc • 52 Caucasian male • 4/5 are causes • Never had an eye exam by at • No regular health care • Vision goes “out” when he carotid bifurcation turns his head up a certain way

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Vascular Supply Systems to Brain Ocular signs of carotid 1. Internal Carotid system artery disease  Supplies anterior and lateral portions of brain  Unilateral visual disturbances 1. Amaurosis Fugax 2. Vertebrobasilar system 2. CRAO  Provides posterior brain 3. Hollenhorst Plaque  Bilateral visual symptoms 4. Ocular Hypoperfusion

Intra‐arteriolar emboli

“Vision went out, but now it’s back” • Increased risk of , mortality, co‐morbidity • X 2 hours ago • 25% have carotid stenosis >40% • 62 year old white male (Bakri 2013) • Only 10% of emboli from ICA end up • Heavy smoker, hx in OA (Kaufmann 2012) hypercholesterolemia, +HTN • Symptoms? 11% with symptoms • Often transient – plaques are pliable had significant • Correlated with degree of occlusion? occlusion • Predictive of future events? Wakefield, et al • Doppler • EKG/Angiography 22% w/o symptoms had 30-60% occlusion Dunlap, et al

Carotid artery disease and 81 Caucasian female risk of stroke • Wants new glasses before a trip • 4/5 strokes are causes by atherosclerotic disease at to Paris carotid bifurcation • PMHx: • Atrial fibrillation • Stroke • Recent falls –due to TIA • leading causes of death in US • VA 20/30 due to • 1/3 of cases are fatal • DFE –retinal heme and intra‐ • Survivors usually have irreversible damage arteriolar plaque

Landwehr P, et al

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

Most common cardiac arrhythmia  CBC with differential  Chem 7 Increased risk of mortality by 40‐90%  Lipid Profile  TIA, stroke (x5) and MI  ESR Screen for with RAO patients  C‐Reactive Protein   risk of stroke   need for anticoagulant

Plunkett O, et al. BMJ Sept 2014 http://afib.utorontoeit.com/images/afibmain.png

CBC Index Clinical Significance Red Blood Count (RBC) Anemia and classification Platelet Count (PLT) Clotting disorders Chem 7 / Basic Metabolic Panel Mean Platelet Volume (MPV) Clotting disorders

White Blood Count (WBC) ↑ in leukemia with Differential ↓ in leukopenia (granulomatous dz, meds, bacterial inf) • Screens for • neutrophils ↑ in bacterial infections 1. Creatinine • Kidney disease • lymphocytes ↑in certain viral infections 2. Blood urea nitrogen • Liver Disease • monocytes ↑ in bacterial infections (BUN) • Diabetes and other • eosinophils Involved in allergic disorders and parasitic infections blood sugar disorders • basophils Immediate immune reactions 3. Glucose Hemoglobin (Hb) Anemia and classification Hematocrit (Hct) ↑ in PCV, CHF, COPD, ↑altitude 4. Carbon dioxide ↓ in anemia, bleeding, sarcoidosis RBC Indices 5. Chloride • Mean Corpuscular Volume ↑ in pernicious anemia 6. Sodium electrolytes (MCV) ↓ in Fe deficiency anemia • RBC Distribution Width (RDW) 7. Potassium • Mean Corpuscular Hemoglobin (MCH) 8. (Sometimes Calcium) • Mean Corpuscular Hemoglobin ↑ Hyperchromic (B12 and Folic Acid Def) Concentration (MCHC) ↓ Hypochromic (Fe Def, thalassemia)

End Stage Renal Disease

Test Ordered Results FBS 107 mg/dl A1C 5.6 CBC Hb: 10 g/dl Hct: 32% Anemia

Platelets: 100,000 cmm Thrombocytopenia

MCV: normal Normocytic

All other values normal 76 Caucasian male Bilateral blot hemes, all 4 Carotid Doppler 30% Carotid Occlusion both sides Hx severe anemia secondary quadrants to ESRD ‐disc edema, ‐tortuosity 30% carotid occlusion ‐artery attenuation

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

Condition Name of Lab Test • Factor V –clotting protein Antiphospholipid Antibody / Antiphospholipid Antibody Panel • genetic mutation: ↑clotting in veins Antiphospholipid Syndrome • Mc prothromobotic gene mutation in caucasians – 5% population

Protein C and/or S deficiency Protein C and S Activity with Reflex • Caucasians of European descent to Protein C and/or S Antigen • Often undiagnosed, however…. • deep vein thrombosis Antithrombin III deficiency Antithrombin III Panel • pulmonary embolisms

Elevation of platelet factor 4 Platelet Factor 4 • CRVO • 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 Leiden Manucci P, et al. Thrombosis and Haemostasis 2015

44 AA male c/o headaches

• VAs: 20/20 • CF: ↓ temporally OD, OS Some Cases Considering Diagnostic imaging CT vs. MRI ±contrast ±angiography Location to scan ±urgency Be prepared to give an ICD code Large pituitary adenoma

48 WM, c/o near blur Pituitary apoplexy • Heavy smoker • abrupt and sometimes • ‐Med Hx catastrophic hemorrhagic infarction • Needs a near add • headache, vomiting, visual • But… impairment • 2‐10% of pituitary tumor • patients Stroke of R posterior cerebral artery • More common in males, 5th • Imaging….. decade • MRI/MRA with DWI particularly if acute • Risk factors: HTN, anti‐ • CT/CTA coagulant tx, Sx, size of tumor

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57 WM

Patient complaining of  Reduced vision  Worsening headaches last 2 mos Hx:  Successful triple bypass  2 months prior, 20/20 VA

VA: 20/70 OD, OS

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26 WF, “blurry vision” Hx hydracephalous, multiple previous VA 20/40 OD, OS No other complaints

• Imaging….. • MRI of brain with and without contrast MRI “all clear” …. ICP was borderline

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32 AA FM Now what?

• Bilateral disc swelling with hx •Urgency ?? hydrocephalus •Emergency ?? • Presumed Recognize

• Reduced vision • H/A developing with more • Called Neurologist intensity Action • Scheduled MRI and LP • Outcome = shunt not draining, operated 2 days later

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Disc characteristics: • Tortuous vessels? • Mildly indistinct margins • Elevated topography Idiopathic Intracranial HTN • Paton’s folds? • SVP absent • (-) disc hemes • 90‐98% complain of headache • Nausea/vomiting/dizziness – 40% • Pulsatile tinnitus – 16‐60% • Visual disturbances – 30%

Severe headaches, BMI 42

Key features disc edema on OCT: Drusen or Disc Edema or….? • Smooth contour of elevation Qualitative and Quantitative Differentiation • Nasal RNFL >86um – 80% specificity Crowded nerves/ • Thick hyporeflective space adjacent to disc Papilledema Disc Drusen Anatomical Elevation “lazy V” – 90% specificity Johnson L. Archives of Ophth 2009. • Hyperemia, Dilated capillaries, Vessel • Non‐uniform elevation • No loss obscuration • Absence of physiologic cup • Normal RNFL thickness • Smooth, continuous elevation • Anomalous vessel branching • Narrow disc sheath • Thicker RNFL, especially nasal • Hyper‐reflectivity on B‐scan diameter • Thicker hypo‐reflective space between • Increased FAF • convexity (OCT) and RPE • SVP present • Bruch’s – anterior displacement / “forward bend” on OCT • ↑ ONH sheath diameter on B‐scan • Crescent shadow on B‐scan VF defects Elevation  RNFL thickening Optic atrophy  thinning

B‐scan Ultrasonography – Review of Tools

• ONH Sheath Diameter <5mm • Elevation of ONH <1mm • 30 degree test • Crescent sign

This patient: opening pressure =

28cm H20 Kimberly HH, et al. Acad Emerg Med. 2008.

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Those tools can miss subtle elevation….. • 21 AAF 3 years earlier, the was consistent with anatomical • High BMI elevation; then lost to f/u x 3 years • MRI clear • Initial opening pressure of 52

…3 years later patient decides to come back

IIH Treatment Trial – JAMA, April 2014 Acetazolamide + Low Sodium/Wt Loss Diet

• In patients with IIH and mild visual loss, the use of acetazolamide with a low‐sodium weight‐reduction diet compared with diet alone resulted in modest improvement in visual field function.

• Papilledema Outcomes from the Optical Coherence Tomography Substudy of the Idiopathic Intracranial Hypertension Treatment Trial. , Sept 2015. • Acetazolamide and weight loss effectively improve RNFL thickness, TRT, and ONH volume swelling measurements resulting from papilledema • RNFL and Total Retinal Thickness (TRT) useful in following and monitoring response to treatment The Idiopathic Intracranial Hypertension Treatment Trial. JAMA 2014

• 42 AA female • BVA 20/20 after corrected • R/v: headache significant cylinder • Father has • normal • ROS: arm weakness • Color (HRR) normal OD, OS • IOP 21, 20

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10‐2 10‐2

34% of the total macular volume is made up by GCL neurons

Optic Neuritis in MS Role of OCT in MS

• Autopsy studies –up to 99% • Earlier detection • Immediate treatment may improve prognosis • Often presenting sign—up to 30% • Confirmed with MRI with FLAIR (Fat suppression‐if acute ON) • Up to 70% develop ON throughout disease course • Identification of subtypes? • E.g. “macular thinning subtype” ‐‐ normal overall RNFL but • 92% have eye reduced macular volume •   • Abnormalities in retinal tissues w/ and w/o history of VEP –even without VA loss ( amp, ON latency) • Subclinical ON • Contrast sensitivity • Lesions distal to retina: retrograde degeneration • Prediction of disability • OCT?

Sakai, et al. J Neuroophthalmology, 2011 Sakai, et al. J Neuroophthalmology, 2011 Behbahani R. J Neurological Sciences 2015

OCT Findings 39 WM with progressive, relapsing MS

• Clinically Manifested ON: • Resistant to tx • Acute: thickening of RNFL, due to SEs IPL and GCL • • Atrophy in ≤2mos 20/60 OD, +APD thinning • RNFL and GCC • Disease activity associated thinning both with faster rates of GCL thinning

Sakai, et al. J Neuroophthalmology, 2011 Behbahani R. J Neurological Sciences 2015

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Optic Neuritis Treatment Trial, circa 1992

• IV steroids over oral • 1000mg IV methylpred x 3 days • Speeds recovery of vision; reduces recurrences • Alternative? Considerations? • Bioequivalent Oral Steroid– • oral prednisone (1250‐mg over 3 days ) vs. high dose IV over 3 days • No significant differences in VA, Contrast Sensitivity, VEP at 1 month or 6 months Morrow et al. JAMA Neurology 2018. • Steroid “Smoothie”

• 20/40 • (‐)APD double vision 1 month later – after steroid infusion • VF improved double vision

• Head injury 3 months ago – Imaging in ER all negative

• Vertical – Worse in down gaze – Right head tilt

Double Maddox Rod??

• Can help determine if SOP is bilateral • often missed due to asymmetry 1⁰ gaze –note head • MR over both eyes posture • Small vertical prism over one eye • Cyclodeviated eye will report a “tilted” line

Rotating MR to straighten image of line Under‐action LSO

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Torsion noted on DFEs! SO Palsy

• Etiology • Trauma • Decompensated congenital –slow onset

• Least likely of EOM palsies to have underlying etiology, BUT…. • Microvascular disease • Brain abnormality Imaging, careful follow up • Treatment • Prism, , botox

RSR, and other eye…

• ? • Trauma? • Giant Cell? • Myasthenia?

Giant cell arteritis Patient Labs Myasthenia suspicion… ? • Clinical presentations CBC – all normal ESR – 15 • Arteritic ION CRP ‐ < 1 • Tensilon Test – low sensitivity • CN palsies • Icepack Test • CRAO • Sustained upgaze x 2 min – 1 mm worse OU • Labs ‐ if suspected, send to ER and order all of the following: • ESR – 13% are normal • Bloodwork – high false negatives • C‐reactive protein • ACH, thymic panel, ANA, DM • Platelet count, CBC with differential (anemia often • Imaging – 70% have thymic hyperplasia (mediastinal imaging) present) • Biopsy indicated for anyone who is suspected, regardless of ESR

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VI Palsy – Pearls EOM palsies: Do not assume……

http://cim.ucdavis.edu/EyeRelease/Interface/TopFrame.htm 1. Vasculopathic  16.5% thought to be ischemic had another cause (neoplasm, MS, GCA) • Children Tamhankar, et al. Ophthalmology Nov 2013 • Frequently acquired and transient • Trauma, tumor, hydrocephalus 2. True isolation Significant risk of • Adults morbidity – imaging • Trauma even if other risk • Neoplasm factors present • Microvascular disease

Rutsein, Daum. Anomalies of

Carod Artery Dissecon → Painful Horner’s Carotid Artery Dissection

• 48 year old male presents with a big in the left eye. • ROS: right‐sided neck pain, headache

• Exam Lu A, et al. Emerg Radiol Feb 2015 • Right eye – , ptosis • Dilates with 0.5% apraclonidine

• Horner’s – 3rd order neuron defect along sympathetic pathway

http://www.cmaj.ca

Carotid Artery Dissection Big pupil problem  think 3rd N • Presentation • Headache – up to 69%‐ most common presenting symptom • • Parasympathetic pupillary fibers are Unilateral neck pain – up to 49% rd • Ipsilateral Horner’s – up to 50% located superficially along 3 CN • Visual manifestations associated with artery dissections • Likely to be affected early with compressive • Photopsia lesion • VF defect

Kanski. Clinical Ophthalmology, 4th Ed • Cause of 2.5% of strokes • • 10‐25% of ischemic events in patients <45 Anatomically at risk Rao, J Vasc Surg 2011 • 85% are within anterior Circle of Willis • Mgmnt • 30‐35% are adjacent to 3rd CN • Immediate Imaging: CT/CTA, MRI/A, T1W with contrast and fat suppression • Doppler • Imaging Considerations

Kwak JH, et al. Neurointervention, 2011.

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3rd Nerve –a nice overview 44 WM with bilateral ptosis Keane JR, Can J Neuro Sci. 2010 Sep;37(5):662-70. • POH and PMH: unremarkable when 1400 personally examined patients – 37 years questioned • FOH:  Presentation  Of 234 patients with diabetes  bilateral in 11%  2/3 due to microvascular ischemia • Ptosis  complete in 33%  53% had pupillary involvement-often bilateral • Cataracts : Father and  isolated in 36%  5 had aneurysms sister  Etiology  trauma (26%)  Only 2% of aneurysms spared the pupil. • “maybe” macular  tumor (12%) degeneration  diabetes (11%)  aneurysm (10%)  Painful onset • Exam:  surgery (10%)  94% of aneurysm  stroke (8%)  69% of diabetic cases. • Colorful nuclear opacities  infection (5%) • Macular stippling OS

Ptosis ‐‐ DDx

• 3rd Nerve Palsy • Horner’s Syndrome • Congenital ptosis • Levator Dehiscence • Myasthenia Gravis • Less commonly • Chronic progressive external ophthalmoplegia (CPEO) • Kearns Sayre syndrome • Ocularpharyngeal muscular dystrophy • Myotonic Dystrophy

Myotonic Frontal Balding Dystrophy Expressionless Face Back to case history…

• Family History: • AD w/variable • Sister had “muscular dystrophy” but died at age 45 before definitive dx penetrance • Father and both sisters also had droopy • 1 in 8000 • Patient history: (presenting age 20‐ • Multiple systems • Admits having difficulty writing, gripping and releasing his grip after 30) Endo, Resp, C/V handshakes • Myotonia: • ↓ intelligence, MH • ↑ muscle contraction with slow relaxation • Later involvement of • Distal muscles of larynx, vocal cords, limbs, face,neck pharynx

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Ocular manifestations Myotonia ‐ Dx and Mgmt • Ptosis (80%) • Dx • Ocular motility disturbances • Family history, clinical presentation • Orbicularis weakness • Creatine kinase (CK) levels • Hypotony (as low as 4mmHg) • Electromygraphy (EMG) • “Christmas Tree Cataracts” • Abnormal ERG (↓dark adaptation) • Muscle biopsy • Peripheral retinal changes—up to 50% • DNA testing • Macular involvement—20% • Treatment is palliative (Heat, cold avoidance, quinine) • Granular pigment changes with stellate pattern • Rarely, anti‐myotonic drugs are used • Genetic counseling

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