Ischemic Optic Neuropathy Ophthalmology & Neuro-ophthalmology Dr. Omer Y. Bialer

ION = Ischemic Optic Neuropathy Disclosure No conflict of interests I have nothing to disclose ION = Ischemic Optic Neuropathy

Presentation’s outline Introduction Terminology and Nosology Nonarteritic anterior ischemic optic neuropathy Arteritic ION Perioperative ION Radiation optic neuropathy “Take home massage” summary אנחנו נדבר רק על הסטנדרט אוף קר בעינים כיום ולא על התפתחויות חדשות ומחקרים הוסף SUMMARY

Introduction ION is the most common acute optic neuropathy > age 50 2nd most common optic neuropathy after glaucoma Relatively common neuro-ophthalmological disorder Visual loss is often severe No effective treatment or prevention

Introduction ION is due to: poor blood flow to the optic nerve Acute occlusion of the feeding arteries Ophthalmic artery Short posterior ciliary arteries

Terminology & Nosology ION Nonarteritic ION (cardiovascular risk factors) Arteritic ION (vasculitis) Nonarteritic Anterior ION (NAION) with swollen optic disc Nonarteritic Posterior ION (NA-PION) with normal optic disc Arteritic Anterior ION (AAION) with swollen optic disc Arteritic Posterior ION (APION) with normal optic disc

Terminology & Nosology ION Nonarteritic ION (cardiovascular risk factors) Arteritic ION (vasculitis) Nonarteritic Anterior ION (NAION) with swollen optic disc Nonarteritic Posterior ION (NA-PION) with normal optic disc Arteritic Anterior ION (AAION) with swollen optic disc Arteritic Posterior ION (APION) with normal optic disc הוסף ION תחת "אידיופאתי" Idiopathic ION Perioperative ION Radiation optic neuropathy GCA Other vasculitides

NAION (Nonarteritic Anterior Ischemic Optic Neuropathy)

NAION is the most common ION ~ 90% of ION Incidence: 1 / 10,000 / year (> 50 y.o) 0.5/ 100,000 / year (overall) Mean age at onset 57-65 Presentation: acute painless monocular visual field loss ± visual acuity loss Non arteritic posterior ischemic optic neuropathy is exceedingly rare and is a diagnosis of exclusion.

The most important risk factor is a crowded optic disc “disc at risk” = small optic disc + minimal cup crowded normal glaucoma

More risk factors for NAION Hypertension (50%) Diabetes mellitus (25%) Obstructive sleep apnea (55%) Hyperlipidemia Ischemic heart disease Obesity Tobacco use High intraocular pressure למעשה השכיחות של OSA ב NAION כפולה מהאוכלוסיה הכללית.

Several meds are associated with NAION Erectile dysfunction drugs Amiodarone Vasoconstrictors Cocaine (e.g. Viagra, Cialis) (e.g. nasal decongestants)

The pathogenesis of NAION differs from IHD or CVA Edema of optic disc Cardiovascular risk factors decrease in blood flow Compression of axons and blood vessels Crowded optic disc Blockage of axonal flow Necrosis and demyelination of nerve fibers

Eye Exam visual acuity & color vision can be normal A relative afferent pupillary defect Normal anterior segment Optic disc edema Crowded optic disc (fellow eye) Peripapillary hemorrhages Obscured borders Nerve fiber layer edema

The most common visual field defect is a superior or inferior scotoma Inferior altitudinal defect Superior arcuate defect Combined superior & inferior defect

NAION is a clinical diagnosis Elderly patient +/- cardiovascular risk factors Acute painless optic neuropathy + disc edema + crowded optic disc in fellow eye Rule out arteritic AION Do Humphrey visual fields Imaging is not in indicated Frequent follow-up נבצע גם את השאלון סקירה ל OSA (BERLIN QUESTIONNARE)

There is no proven treatment for NAION IONDT = ION decompression trial A multicenter randomized controlled clinical trial no efficacy for optic nerve fenestration Intravitreal steroids (triamcinolone acetate) Intravenous noradrenaline Warfarin TPA Levodopa + carbidopa

There is no proven treatment for NAION Oral prednisone 40-60mg daily – may hasten resolution of disc edema Some evidence for anti-VEGF intravitreal injections

Prophylaxis Control of cardio-vascular risk factors Aspirin 100 mg daily – limited evidence for second eye prophylaxis

Disc edema resolves in 1 month cup Optic atrophy with cupping Optic atrophy

Significant improvement is rare ~40% experience partial improvement Improvement may take up to 6 months 15% risk for fellow eye involvement in 2 years < 5 % recurrent AION (the same eye) A significant visual field defect persists

Arteritic ION And Giant Cell Arteritis (GCA)

>50% of Arteritic ION are d/t Giant Cell Arteritis Other etiologies include: Systemic Lupus Erythematosus Wegener’s granulomatosis Behcet’s disease Churg Strauss Polyarteritis Nodosa

* GCA = Giant Cell Arteritis (Temporal arteritis) GCA* - key facts Large vessel vasculitis Predilection for the aortic arch Incidence 20 / 100,000 / year (> age 50) 20% of GCA patients experience severe visual loss AION is the most common ophthalmic manifestation of GCA A-AION is an ophthalmic emergency ! * GCA = Giant Cell Arteritis (Temporal arteritis)

Arteritic ION presents like any ION, but . . . 75% have typical systemic symptoms 30% have preceding transient visual loss 54% have visual acuity of count-fingers  No light perception >50% second eye ION within hours -weeks (“amaurosis fugax”) (vs 26% in NAION)

There are specific funduscopic findings The involved swollen optic disc is acutely pale NAION

There are specific funduscopic findings Ischemic retina Cherry red spot Branch Retinal Artery Occlusion Central Retinal Artery Occlusion

There are specific funduscopic findings Lack of choroidal perfusion normal choroid Choroidal hypoperfusion indicates multifocal ischemia on Fluorescein angiography

The workup of suspected Arteritic ION GCA Symptoms / signs ? Do blood tests but yes no ESR, CRP, Hb, PLT, Fibrinogen IV Solomedrol  Prednisone + aspirin until biopsy results Iv Solomedrol  Prednisone + aspirin NAION high normal הרגישות המשולבת של ESR ו CRP היא מעל 97% בביופסיה חייבים לוודא שנלקח ספסימן מתאים – כלומר באורך 2 ס"מ לפחות , עורק ולא וריד ולא נמעך. במקרים של חשד קליני גבוה נפנה לביופסיה של הצד השני Urgent TAB* TAB* in 1 w * TAB = Temporal Artery Biopsy

“Ophthalmic GCA” should be treated with IV steroids Few studies evaluated treatment protocols Studies in ophthalmology differ from rheumatology We recommend: IV methylprednisolone 1000mg/d for 3 days followed by a very slow taper of oral prednisone Aspirin 100mg daily Rheumatology consultation & follow-up Tocilizumab (אנטי IL6) ומתוטרקסט לטיפול ב GCA

Perioperative ION (post operative AION and PION)

ION is a rare surgical complication ION is an uncommon but devastating complication after various types of surgeries Intraocular surgeries Intraocular injections Non-ocular surgeries ION may also occur after: renal dialysis cardiac catheterization d/t Elevated intraocular pressure

ION may complicate non-ocular surgeries The 2 most “classic” are : CABG Spinal surgery Commonly bilateral There is often profound visual loss Visual loss may be immediate or delayed (days) (mostly AION, 0.06%) (mostly PION, 0.2%)

The differential diagnosis of post-operative visual loss includes Ischemic optic neuropathy Retinal artery occlusion Angle closure glaucoma Cherry red spot Hazy cornea Unresponsive mid-dilated pupil Red “angry” eye

The differential diagnosis of post-operative visual loss includes Cortical blindness Corneal erosion Bilateral occipital stroke למחוק CORNEAL EROSION ולשים PITUITARY APOPLEXY עם תמונת MRI Epithelial irregularity

There is no prospective / controlled data regarding perioperative ION Risk factors: Obesity Male gender Prolonged surgical time Surgery in the prone position Large fluid shifts / severe blood loss

There is no effective treatment Prognosis is poor – significant improvement in minority of patients Should correct anemia, saturation & hypotension to improve perfusion No evidence for efficacy of : Aspirin Anti - coagulants Thrombolytics Anti-glaucoma drops 40 חווים איזה שהוא שיפור אך לא משמעותי. הוספה המילה saturation & הוספה השורה "anti glaucoma drops"

RON (Radiation Optic Neuropathy)

RON is a late complication Prevalence ~ 0.5% Mean interval 18 months The optic nerves must be in the radiation field (range: 3 months – 9 years)

The risk factors are: Radiation dosage Age Diabetes mellitus Presence of compressive optic neuropathy Concomitant chemotherapy Previous radiotherapy Multiple sclerosis (>total 50 Gy or single dose > 10 Gy)

RON mostly presents as PION May be monocular or binocular 45% have visual acuity of no light perception Diagnosis is one of exclusion: Suspected Optic neuropathy PMH of radiotherapy No other obvious explanation Optic nerve enhancement on MRI

Isolated enhancement on MRI optic nerve enhancement T1W with fat suppression + gadolinium

There are few treatment options Oral corticosteroids (prednisone 1mg/kg) Anticoagulants (heparin) Aspirin Hyperbaric oxygen (30-60min/day x 14-30 days) Intravenous Bevacizumab (2-4 cycles every 2 weeks)

Suspected RON ? Onset < 48-72 hours ? yes no VEP Look for other etiologies Brain+orbits MRI with gadolinium normal abnormal Hyperbaric oxygen VEP היא בדיקת עזר טובה לאבחן פגיעה בעצב הראיה בשלב מוקדם מאד - אפילו לפני הופעת הירידה בראיה. האפשרויות כוללות נוגדי קרישה (הפרין) סטרואידים , חמצן היפרבארי ואבסטין סיסטמי חמצן היפרבארי - יש 27 מקרים מתוארים בספרות – 30-40 טיפולים בני 30-60 דקות של חמצן 100% בלחץ 2-3 אטמוספירות. יש להתחיל בטיפול תוך 48-72 שעות. yes PO prednisone Enhancement ? Consider IV Bevacizumab Other optic neuropathy

Prognosis of RON is poor Spontaneous recovery is rare Treatment is mostly ineffective 85% visual acuity ≤ 20/200 Optic atrophy appear in 6-8 weeks Enhancement on MRI resolves after several months

Conclusions (the “take home massage”)

ION is an ophthalmic emergency  Patients with GCA+ION are in danger of catastrophic, irreversible, bilateral blindness that may be prevented by prompt treatment with corticosteroids Any patient > 50 presenting with ION  an immediate workup to rule out GCA

ION is not “another type of CVA” Although considered a “stroke of the optic nerve” and shares many risk factors with cerebrovascular disease, It cannot be directly compared to cerebral infarction, and therefore the evaluation should not be similar to that of cerebral infarction. Non arteritic anterior ischemic optic neuropathy is not an embolic disorder, but a small vessel disease. Evaluation of the internal carotid artery is not routinely indicated. There is also no definite increased risk of stroke in patients with nonarteritic anterior ischemic optic neuropathy, but vascular risk factors are common and should be controlled.

There is no effective treatment for ION there are no class I studies showing benefit from any medical or surgical treatments TPA Steroids Anti VEGF Heparin Aspirin Levodopa Erythropoietin Decompression surgery Hyperbaric oxygen Noradrenalin

Limited efficacy for prophylaxis Aspirin 100mg daily Control of cardiovascular risk factors suspect GCA !!! Avoid prolonged surgical time and dramatic shifts in body perfusion during surgrey Consider routine serial brain MRIs after brain radiotherapy to detect RON early

Thank you For listening

Acknowledgments Based on the chapter: Optic nerve: Ischemic. Bialer OY, Bruce BB, Biousse V, Newman NJ. Oxford textbook in Neuro-ophthalmology Oxford textbook in clinical neurology Editor: Bremner F. Publisher: Oxford University Press Gratitude to : Dr. Karin Mimoni Dr. Hadas Kalish-Stiebel Dr. Beau B. Bruce Dr. Nancy J. Newman Dr. Valérie Biousse

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