Acquired Optic Nerve Disorders

What is optic nerve head drusen?

Globular, hyaline bodies of degenerative axonal byproducts containing calcium located within the optic nerve head (anterior optic nerve)

What happens when optic nerve head drusen progresses?

• Progressive: calcification and growth, migration anteriorly

+/- Compression of RNFL leading to glaucoma-like damage

What causes optic nerve head drusen?

Unknown or hereditary

What are the signs of optic nerve head drusen?

• Bilateral 75%, asymmetric

• Overt (superficial, calcified, enlarged) vs. Covert (deep, buried)

• Scalloped, "lumpy-bumpy" appearance at disc margin

• Obscuration of cup (crowded disc)

• Pseudopapilledema (blurred, elevated disc margins)

• +/- angioid streaks

• +/- disc hemorrhages, ischemic optic neuropathy

What are the symptoms of ONH drusen?

• Asymptomatic (especially with deep, buried drusen)

• Transient visual obscurations (TVO) or dimming of vision (due to compression of RNFL

• Visual field defects (subjectively still may be asymptomatic; enlarged blindspot, generalized constriction, less commonly arcuate defects)

What is the management of ONH drusen?

• No treatment currently

• Patient education and routine testing

What testing should be done to evaluate ONH drusen?

• OCT

  • What to Order

    • EDI (enhanced depth imaging)

    • ONH radial

    • Neuroretinal rim RNFL

    • Peripapillary RNFL

    • Macular GCL

• FAF

• B-scan ultrasound

• IVFA (rarely ordered)

• CT

Why is it important to use EDI to observe ONH drusen?

Allows you to focus behind dense structures setting otherwise will be unable to differentiate from blood vessels

What do you expect to see on OCT with ONH drusen?

Hyperreflective, spherical/irregular anterior border with internal hyporeflective core

• Adjacent NRR RNFL and cpRNFL scan can detect RNFL loss/changes

What do you expect to see on FAF with ONH drusen?

• Only superficial/overt calcified drusen will hyperautofluoresce

  • If too deep, you will not be able to view on FAF

What do you expect to see on B scan with ONH drusen?

• Only calcified drusen will be observable

• Must be on low gain setting to see the intense signal of the calcified drusen at the ONH

What would you expect to see on IVFA with drusen?

• Would not typically order for ONHD

• Early diffuse hyperfluorescence, NO late leakage like seen with ONH edema

What would you expect to see on CT with ONH drusen?

• Would not typically order for ONHD

• Will be hyperreflective if calcified

What is optic nerve edema?

Swelling of the optic nerve

What are the 2 types of optic nerve edema?

Papillitis (unilateral) and papilledema (bilateral)

What are the causes of optic nerve edema (bilateral and unilateral?

What are the workup considerations for optic nerve edema?

• Vital signs

  • Blood pressure

  • Pulse

  • Height

  • Weight

  • BMI

• Complaint

  • Transient visual obscurations (especially with Valsalva or postural changes)

• Health history

  • Current or new medications

• Review of systems (When we see nerve edema, don't just refer straight to neuro - take these other conditions into considerations to manage/refer appropriately)

  • Recent headaches

  • Recent weight gain

  • Infectious concern:  recent tick bites, rashes, upper respiratory symptoms, gastroenteritis symptoms, new exposure to cats, sexually transmitted diseases

  • Inflammatory concern: jaw claudication, scalp tenderness, weight loss, arthralgias, myalgias, malaise

  • Demyelinating concern: numbness, tingling, daytime somnolence, intractable nausea, vomiting, hiccups

• Entrance tests

  • See optic nerve disease diagnostic testing (page 1)

  • Fundoscopy

• Diagnostic testing - OCT, Visual Field, Fundus photos, FAF, IVFA

  • OCT

    • Consider ONH radial, NRR RNFL thickness, cp RNFL thickness, m GCL thickness

• Consider 30-2, 24-2, 24-2C, or 10-2

• May observe: full field, enlarged blindspot, nasal step, arcuate defect, constriction 360, or paracentral defect

• Lab testing

• Brain imaging

What type of lab testing would you consider with optic nerve edema?

• CBC

• Heavy metals

• B12

• Folate

• FTA-ABS

• VDRL

• ANA

• Homocysteine

• ACE

• Antiphospholipid antibodies

• TORCH panel

What type of brain imaging would you order for optic nerve edema?

• CT

• MRI

• MRV

What is papilledema?

Bilateral disc swelling secondary to increased ICP (intracranial pressure) or CSF (cerebrospinal fluid) pressure - differentiates from optic nerve edema

What is the cause of papilledema?

Increased ICP (intracranial pressure) or CSF (cerebrospinal fluid) pressure

What is normal ICP?

Normal ICP: <250mm H2O in adults, <280mm H2O in children

What are causes of increased ICP?

• Brain tumor (compressive lesion)

• CNS inflammation (hydrocephalus, meningitis, etc.)

• Ventricular obstruction

• Cerebral venous thrombosis (blood clot in the brain's venous sinuses)

• Idiopathic intracranial hypertension/ IIH (most common cause of papilledema)

  • Mostly an ocular finding - neurology typically relies on this finding to help them diagnose

What are the signs of papilledema?

• Bilateral (can be asymmetric)

• Loss of SVP (ties back to earlier lecture) - increased ICP or OPP

• Optic nerve head

  • RNFL opacification

  • Elevation of margins

  • Hyperemia

  • Obliteration of cup

  • Obscuration of small blood vessels at disc margin

• Vascular congestion

  • Venous dilation

  • Vascular tortuosity

  • Hemorrhages

  • Cotton wool spots

  • Exudates

• Mechanical features

  • Retinal folds (Paton's lines: peripapillary RNFL ripples)

  • Choroidal folds (posterior globe deformation, extreme)

• Chronic papilledema

  • Rim pallor

  • Gliosis (greying of RNFL due to scarring)

  • Optociliary shunts

  • Refractile bodies

What is 0 on the Frisen scale for grading papilledema?

Normal Optic Disc or Pseudopapilledema

• Prominence of the RNFL

• Possibly some nasal blurring from smaller discs

What is Grade 1 on Frisen scale?

C shaped halo (typically nasal first)

What is Grade 2 on Frisen scale?

Circumferential blurred margins

What is Grade 3 on Frisen scale?

Obscuration of blood vessels (big difference between Stage 2) due to axon edema surrounding vessel in at least one segment

What is Grade 4 on Frisen scale?

Marked Degree of Edema

• Elevation of entire nerve and inability to see margins

What is Grade 5 on Frisen scale?

Obscuration of al vessels of the disc and obvious protrusing of dome shape

What is IIH?

Increased ICP of unknown cause that predominantly affects obese females of childbearing age

What are medication associations with IIH?

Tetracyclines, vitamin A, lithium, anabolic steroids, oral contraceptive pills, nalidixic acid, cyclosporine

What are some systemic illness associations with IIH?

Obstructive sleep apnea, hypothyroidism, anemia, Addison disease, systemic lupus erythematosus, Behcet's syndrome, polycystic ovary syndrome, coagulation disorders, uremia

What are symptoms of IIH?

• HA (most common): diffuse, non-specific; may be associated with vomiting; +/- retrobulbar pain/pressure

  • Also worse with Valsalva maneuver or postural changes

• Transient episodes of vision loss/blurring out: lasts seconds, associated with Valsalva maneuver or postural changes

• Pulsatile tinnitus: unilateral 'whooshing' sound exacerbated with postural change

  • Turbulent venous system pulsations from increased ICP

• Visual disturbance: peripheral field defects

• Horizontal diplopia: associated with unilateral or bilateral 6th cranial nerve palsy

What is the management for IIH?

• Diagnostic LP may provide transient symptomatic relief

• Weight loss (goal of 5-10% of body weight) provides long-term relief

• Oral CAIs provide short-term relief - reduce rate of CSF production

  • Acetazolamide (Diamox) 500mg BID, less dose can be considered

  • topiramate (Topamax), weaker effect

• Surgery for refractory cases

  • Optic nerve sheath fenestration

  • CSF shunt (LP or VP)

What is the prognosis for IIH?

• Can last weeks to years with variable outcomes

• Optic atrophy (permanent vision and field loss) especially without treatment

What testing should be done for IIH?

• OCT

  • OCT ONH- radial with enhanced depth imaging (R/O disc drusen)

  • OCT ONH - rim RNFL and CP RNFL thickness

  • OCT Mac - GCL thickness

  • HVF - 24-2C or 30-2 and/or 10-2

  • Photo - posterior pole (baseline)

• MRI (Magnetic Resonance Imaging) - ordered once you've determined cause is not drusen-related or pseudo-papilledema

  • Preferably gadolinium-enhanced (contrast medium/metal solution), fat-suppressed

• MRV (Magnetic Resonance Venography)

  • Absence of venous sinus thrombosis

  • Best way to diagnose Cerebral venous thrombosis

• Lumbar puncture/spinal tap

  • Detects opening pressure of CSF + retrieval of sample of CSF to send to lab for analysis (inflammation/infection/tumor cells)

What is the best way to diagnose cerebral venous thrombosis?

MRV

When is a lumbar puncture typically ordered?

Ordered if MRI and MRV is unremarkable to get CSF sample

Why is it important to order MRI before LP?

• Procedure is contraindicated if risk of herniation (i.e. Chiari malformation seen on MRI - brain extends lower than usual)

  • Important to run MRI before performing LP

  • Slight release of pressure from LP can drop the brain and crush the spinal cord

  • Ordered if the MRI and MRV comes back unremarkable

What opening pressure is diagnostic for IIH?

Opening pressure > 25 cm

T or F: IIH patients will have normal CSF composition

True

What the 5 criteria in Modified Dandy criteria?

1. Signs and symptoms of increased ICP (papilledema, headaches, TVOs)

2. Normal neurological exam except for cranial nerve abnormalities

3. Normal neuroimaging (no evidence of hydrocephalus, mass, structural or vascular lesion and no abnormal meningeal enhancement on MRI)

4. Normal CSF composition

5. Elevated lumbar puncture opening pressure (>25 cm H2O adults)

What is definite IIH?

All Dandy criteria met

What is probable IIH?

At least 4 criteria met (with papilledema being one of them)

What is optic neuritis?

Inflammation of the optic nerve

What are the etiologies of optic neuritis?

• Demyelinating (most common)

• Para-infectious (resolved infection)

• Infectious (active)

• Non-infectious (autoimmune)

T or F: Once ICP returns to normal, horizontal diplopia will resolve

True

What are the locations of optic neuritis?

• Retrobulbar

  • ONH appears normal (although pallor can appear later)

  • Commonly associated with multiple sclerosis (demyelinating)

• Papillitis

  • Swollen, hyperemic appearing ONH

• Neuroretinitis

  • Papillitis with retinal inflammation (i.e. circinate exudates)

    • Often has circinate exudates

What are the signs and symptoms of optic neuritis?

• Acute, painful unilateral (although can be bilateral) vision loss

• Periorbital pain, worsened with eye movements

• +/- RAPD (if severe unilateral or highly asymmetric)

• +/- decreased VA, VF, color vision

• +/- optic nerve swelling (may be retrobulbar)

What is demyelinating optic neuritis?

Immune-mediated inflammatory demyelination of the optic nerve

What is the most common type of optic neuritis?

Demyelinating

What is demyelinating optic neuritis often associated with?

MS

What are the signs of demyelinating optic neuritis?

• Acute, painful unilateral (although can be bilateral) vision loss

• Periorbital pain, worsened with eye movements

• +/- RAPD (if severe unilateral or highly asymmetric)

• +/- decreased VA, VF, color vision

• +/- optic nerve swelling (may be retrobulbar)

What are the symptoms of demyelinating optic neuritis?

• Prodromal viral illness

• Photopsias/phosphenes

• Uhthoff phenomenon 🌡: blurry vision when body temperature rises (I.e. exercise or bathing)

• Pulfrich phenomenon: altered perception of motion/2D images appear 3D due to delayed impulse from one affected optic nerve

What is used to diagnose demyelinating optic neuritis?

• OCT (signs of optic nerve edema unless retrobulbar)

• Serologic testing and CSF analysis (to rule out other causes)

• MRI of brain and orbit with gadolinium (may eliminate other causes and high prognostic value for MS)

  • Multiple Sclerosis (MS)

What is the study ONTT tell us?

Comparing treatments: oral prednisone vs. IV methylprednisolone followed by oral prednisone vs. Placebo

• Faster recovery - IV methylprednisolone followed by oral prednisone sped recovery by two weeks and delayed neurological signs/symptoms of MS by 2 years

• At 6 months, visual recover was the same for all 3 groups (87% 20/25 or better)

What is the percentage of MS patients that have asymptomatic white matter lesions?

72%

What are the causes of para-infectious optic neuritis?

• Viral

• After immunization/vaccines (1-3 weeks)

What are the causes of infectious optic neuritis?

• Sinus-related

• Cat-scratch disease

• Untreated syphilis

• Lyme disease

• Cryptococcal meningitis

• Varicella zoster virus

What is neuroretinitis?

 Inflammation of neural retina and optic nerve, commonly involving circinate exudates and optic nerve edema

Neuroretinitis

What are the etiologies of neuroretinitis?

• Infectious or para-infectious

• Hypertension grade 4 retinopathy

• Idiopathic (5%)

What is the prognosis of neuroretinitis?

• Typically resolves spontaneously

• Cause needs to be addressed

What are the etiologies of autoimmune optic neuritis?

• Sarcoid disease (granulomatous inflammatory disease)

• Sjogren syndrome

• Systemic lupus erythematosus (SLE)

• Rheumatoid arthritis (RA)

• Inflammatory bowel disease (IBD)

• Neuromyelitis optica

What is diabetic papillitis?

Rare ocular manifestation of diabetes

What are the etiologies of diabetic papillitis?

• Potentially due to rapid glycemic control

• Questionable if this is a form of NAION or malignant hypertension if other vascular issues exist

• Diagnosis of exclusion (rule out other causes)

What is the laterality of diabetic papillitis?

Unilateral optic nerve edema

What is the presentation of diabetic papillitis?

Unilateral, painless vision loss with DR and DME typically present

What is NAION?

Non-arteritic anterior ischemic optic neuropathy

• Occlusion of short posterior ciliary arterials (partial or total)

What is the average age of onset of NAION?

40-60 YOA

What are the risk factors of NAION?

• Poorly controlled vascular disease (hypertension, diabetes, hypercholesteremia)

• Hypotensive event (typically during nocturnal hypotension)

• Sleep apnea

• Medications (I.e. amiodarone, PDE-5 inhibitors)

• "disc at risk": small-sized optic disc with crowded rim tissue and minimal cup

What are the signs and symptoms?

• Unilateral (rarely bilateral)

• Painless (8-12% report headache or periocular pain)

• Visual acuity varies (typically better than 20/200)

  • >2/3 of patients notice it upon wakening

• Blurred margins or elevated margins/disc (diffuse or segmental)

• Hyperemic appearance (rarely pale) - nerve looks more reddish in color NOT typically pale

• Splinter hemorrhages (75% of patients) - superficial hemorrhages

• Altitudinal field loss (common, especially inferior; 25% central scotomas) - either the top or bottom half

What is the Management for NAION?

• No effective treatment

• Discuss modifiable vascular risk factors

What is the prognosis for NAION?

• Vision can worsen the first 2 weeks

• Vision stabilizes by 2 months

  • 50% of patients had VA 20/30 or better

  • Visual field defects can be permanent

  • Pallor (total or sectoral), cpRNFL/mGCL loss on OCT (total or sectoral)

• Fellow eye involvement

  • 15-24% in >5 years

NAION

Margins are blurred with hyperemia (reddish) of rim

Inferior altitudinal defect on 24-2 with paracentral defect

What is AAION?

Arteritic anterior ischemic optic neuropathy

• Inflammation and thrombosis of short posterior ciliary arteries

What is the age group of AAION

> 50 YOA

• Increasing incidence each decade

What are the most common causes of AAION?

Most commonly caused by giant cell arteritis (GCA), which is a form of vasculitis that most commonly affects the medium- to large-sized arteries in the temple (temporal arteritis)

• 1/3 to 1/2 of patients with GCA have polymyalgia rheumatica (PMR)

What are the signs and symptoms of AAION?

Acute, often painful, severe vision loss

• BCVA typically worse than 20/200

• Visual field defects, most commonly altitudinal

• Headache (most common), tenderness of scalp/temple, jaw claudication - pain or fatigue when chewing (specific to GCA), malaise, loss of appetite, weight loss, fever, joint and muscle pain, ear pain

• Chalky-white appearance of optic nerve, typically

• +/- APD

• Narrowed appearance of arteries around the nerve

What lab testing should be ordered for AAION?

• Erythrocyte sedimentation rate (ESR) - general inflammation

Westergren method

• Normal: males ≤ age / 2       females ≤ (age+10) / 2

• C reactive protein (CRP) - acute inflammation

  • Normal < 5mg/L (studies vary)

*97% specificity for temporal arteritis when ESR and CRP are both elevated

• Platelets (within CBC)

  • Normal: 150,000 – 400,000 /µL

• Leukocytes?

• Hemoglobin levels?

  • Normal: males: 13-17g/dL      females: 11.5-15.5g/dL

What is normal for ESR?

• Normal: males ≤ age / 2       females ≤ (age+10) / 2

What is normal for CRP?

• Normal < 5mg/L (studies vary)

What is normal for platelet count?

• Normal: 150,000 – 400,000 /µL

What diagnostic testing should be ordered for AAION?

• Biopsy

  • Superficial temporal artery biopsy (TAB) (gold standard, although negative biopsy could still mean "skip lesions" are present)

• Temporal artery ultrasound (superior alternative to biopsy but not widely available)

  • Dark wall swelling ("halo") and acute occlusions in active AAION

• MRI?

  • During acute stage, optic nerve head enhancement with AAION but not NAION

What is the treatment for AAION?

• IV methylprednisolone 1g/day for first three days, followed by oral prednisone 60-100mg/day; taper after several months or years

  • No long-term definitive studies to determine if this is the best line of treatment

• Tocilizumab (FDA approved 2017 for GCA)

  • Monoclonal antibody

What is the prognosis for AAION?

• Without treatment, 54-95% permanent vision loss within four months

• With steroid treatment, 13% permanent vision loss

• Untreated, other eye becomes involved in up to 50% of cases

AAION

Optic Atrophy

Atrophy of the optic nerve

• Possible end point for any of the optic nerve edematous conditions we've discussed

What is the presentation of optic atrophy?

Can be diffuse or sectoral, from insult

What are the findings of optic atrophy?

• +/- Optic nerve pallor

  • Total

  • Sectoral

  • Altitudinal

• OCT correlation

  • NRR RNFL thinning

  • cp RNFL thinning

  • mGCL atrophy

What are the symptoms of optic nerve atrophy?

• VA and VF correlation

• Possibly APD (if asymmetric damage)

What are the etiologies of optic atrophy?

• Chronic papilledema/optic nerve edema

• Optic neuropathy

• Optic neuritis

• Tumor (compressive)

• Trauma

• Cerebrovascular events/Strokes

  • CVA that affects any part of the visual pathway can cause visual field defects that correspond to thinning on the OCT (RNFL or GCL)

• Neurodegenerative disorder

  • Studies on Alzheimers shows thinning of RNFL on OCT

• Toxic or nutritional

  • I.e. alcohol overuse or vitamin B complex deficiency can lead to bitemporal pallor of the optic nerve head, leading to loss of visual acuity and/or a centrocecal scotoma

• Congenital (mitochondrial)/childhood disorder

  • Leber Hereditary Optic Neuropathy

  • Autosomal Dominant Optic Atrophy

Optic Atrophy

What two conditions can cause painful vision loss?

Optic neuritis and AAION

How would you describe the typically visual field defects you would see with NAION and AAION

Altitudinal