10/11/2017

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Neuro, Orbit, & Optic Nerve Brainteaser Cases……

Chris Borgman, OD, FAAO

Memphis, TN

Rules for this lecture…

• I have no disclaimers or conflict of interests to report…..

• Don’t look ahead!

• I’m not perfect…

• Some cases are more straight forward than others…

• I will email you my reference list if you want it….

• Email: cborgman@sco.edu

Case #1:“Doc, I have no visual problems, but my

daughter says I have trouble seeing things above me sometimes…”

Case History…

• 50 year old Hispanic Female

• OS blurrier than OD entire life per patient, (-)pain

• (+) Migraine HA---sees neurologist q6 months

• (+) DM Type 2

• Very short stature

• PCP recommended eye exam

Exam:• VA: 20/20- OD, 20/30- OS (cc)

• Pupils, EOM’s = WNL

• CVF = mild superior restriction OS>OD

• SLE = WNL OU

• IOP = 12 mmHg OU

• DFE = see photos

• MR: +1.00 - 0.50 x 140 20/20-

+1.75 - 3.50 x 165 20/30-

+2.00 Add

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Dx = Tilted Disc Syndrome

• Unilateral or bilateral congenital disc anomaly• Bilateral (60-80%) ; M=F

• 0.4-3.5% in general population

• Highly variable appearance

• Appears to be rotated by 90° about its Z-axis• Disc is not actually rotated/tilted = misnomer

• Situs inversus vascular anomaly common

• Conus inferior and inferior nasally (aka Fuch’s coloboma)• Retina/RPE/Choroidal thinning inferior = lighter fundus color

• Part of coloboma spectrum

• MOA: failure of the embryonic fissure to close in the 5th/6th weeks

• The coloboma can involve multiple layers of the globe, including the iris, lens, nerve, retina and retinal pigment epithelium (RPE).

Situs inversus = anomaly with no visual significance 70% of TDS, 5% of normals…

3 E C

Self-proclaimed: Borgman’s “3EC” Sign

Typical TDS Findings…

• Visual acuity = Normal or near normal• Myopic astigmatism with oblique axis

• Lenticular vs. Corneal Astigmatism?

• Recent studies = Corneal Astigmatism >>>>Lenticular

• CCT in TDS = CCT in normals

• Color vision abnormalities • ~50% of TDS cases

• Mixed (R,G) most common (70%)

• No correlation to severity of VA, VF defects

Visual field defects found in 92% of TDS….

• Possible VF Defects: Arcuate scotoma, blindspot enlargement, nasal contraction, superior temporal

• By far, most common is: superior temporal depression

• Superior temporal quadrantanopsia-like defects = 50-63% of TDS cases• Frequently misdiagnosed as tumor with chiasmal compression

• Be careful of unnecessary imaging…

• Non-progressive; congenital

• Within central 30 degrees

VF’s in neuro-optometry….Is testing the central 30° enough?

• “Humphrey SAP has replaced Goldmann perimetry in clinical practice despite fears that peripheral visual field defects may be missed. This fear seems unwarranted as only 1-2% of patients with nonglaucomatous VF defects have abnormalities in the peripheral field beyond 30° degrees in the absence of central field defect.”

• Alternatively said….98-99% of neurological VF defects will show up in the central 30° when tested….pretty good odds!

Kedar S, Ghate D, Corbett JJ. Visual fields in neuro-ophthalmology. Indian J Ophthalmol. 2011;59:103-109

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TDS Systemic Risks/Associations…

• Sellar and Endocrine abnormalities…

• Hormone deficiencies (TSH, GH, vasopressin)• Partial/complete absence of septum pellucidum

• Other midbrain abnormalities

• Hydrocephalus• DM

When should MRI/CT be performed?

• “However, regardless of the presence of TDS, any patient with bitemporal visual field defects suggestive of chiasmal compression should undergo neuroimaging in the event that a patient has both TDS and an underlying chiasmal mass lesion. However, if neuroimaging fails to reveal intracranial pathology, the genesis of the visual field defect can be ascribed to TDS.”---Joseph Sowka, OD

• “If one cannot confidently attribute monocular temporal field loss to tilted disk, or the field defect respects the vertical, neuroimaging of the anterior visual pathway and chiasm is in order.”---Witmer et al.

• Conclusion: Is vertical midline respected on HVF?• Yes = order MRI/CT• No = likely TDS and MRI/CT likely not needed; use your own discretion

• Sowka JW, Luong VV. Bitemporal visual field defects mimicking chiasmal compression in eyes with tilted disc syndrome. Optometry. 2009;80:232-242.

• Witmer MT, Margo CE, et al. Tilted Optic Disks. Surv Ophthalmol. 2010;55:403-428.

TDS Conclusions:

• No Treatment available congenital condition!

• Look for inferior changes to ON

• Get baseline 24-2 or 30-2 HVF’s• Superior temporal VF defects most common

• Avoid unnecessary investigations & common misdiagnoses:• Normal Tension Glaucoma

• Early Papilledema

• Chiasmal compression disease with VF defects

• TDS should be considered a form of ON hypoplasia on coloboma spectrum• Decreased axons entering all parts of optic nerves but GREATER reduction seen at

inferior location of ON

Case #2:

“Doc, my pupils look weird…”

Presentation…

• 38 year old white, female

• No systemic/ocular conditions

• Pupils are different sizes x 24 hours

• Left sided severe headache and neck pain; sudden onset 24 hours earlier

• (+) mild pulsatile noise inside head per patient?

• s/p short “run” (5 km) race 24 hours earlier

• PCP started azithromycin for potential sinus infection

• No diplopia, no blurry vision, no trauma, no eye drops used

Tests…• Uncorrected VA = 20/20 OD, OS, OU

• EOM’s = WNL

• CVF = WNL

• Pupils = 4 mm OD/ 3 mm OS (Bright) • 6 mm OD/ 3 mm OS (Dark)• no APD

• SLE = unremarkable, except mild left upper lid ptosis

• (IFW = 11 mm OD, 8 mm OS)

• IOP = 14 mmHg OD/ 14 mmHg OS

• DFE = unremarkable

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Dx = Painful Horner Syndrome OS

• Compromised sympathetic system on left side• Ptosis• Miosis• No Anhydrosis though…

• Highly suspected Internal Carotid Artery Dissection based on “painful” Horner’s!

• Thank you Dr. Len Messner!

• Emergent MRI/MRA ordered through PCP

Horner Syndrome 2° to ICAD

• ICAD = tear in lamina intima layer of blood vessel

• MOA: hematoma forms in space and can restrict or cut off blood flow to eyes and/or brain

• M=F

• 2.6-3.0 per 100,000 people

• Bilateral ICAD’s reported 20% of time

• Average age = 38-44 years old

• Motor vehicle accidents most common cause (whiplash)

• Other causes: chiropractor adjustments, Valsalva, sporting events, weight lifting, bar fights/strangulation, sexual intercourse, holding phone between ear and shoulder

General Sn/Sx of ICAD

• Ipsilateral Headache (68-92%)

• Cerebral Ischemia (49-67%)

• Horner Syndrome (36-58%)

• Subjective Bruit (21-39%)

• Cranial Nerve Palsies (12-14%)

• Death (<5%)

OCULAR Sn/Sx of ICAD’s…

• Painful Horner Syndrome (36-58%)

• Amaurosis Fugax (6-30%)

• Ophthalmic/Retinal Artery Occlusion (5%)

• Ischemic Optic Neuropathy (3.6%)

• Cranial Nerve Palsies (2.6%)

ICAD Associations…

• Vast majority are unknown/unclear

• Ehlers-Danlos Syndrome ***

• Fibromuscular dysplasia ***

• Marfan’s Syndrome

• Polycystic kidney disease

• Cystic medial necrosis

• Osteogenesis imperfecta } Only identified in 1-5% of cases

HS Diagnosis….

• 1) Cocaine 5-10%---------------- Is it a Horner’s?• MOA: Indirect-acting sympathomimetic; increases norepinephrine (NE) availability

• Horner’s pupil = no dilation

• Normal pupil = dilation

• Maintenance of anisocoria = Horner’s

• Bilateral Dilation = physiologic anisocoria

• 2) Hydroxyamphetamine 1%-----------Where is the lesion causing the HS?• MOA: indirect sympathomimetric; forces NE out of presynaptic terminal

• No dilation = post-ganglionic (3rd order neurons)

• Dilation = pre-ganglionic or central (1st or 2nd order neurons)

• Cocaine and Hydroxyamphetamine must be separated by 24-72 hours; cocaine interferes with hydroxyamphetamine

}Assess after 30-60 minutes

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Diagnosis continued…

• 3) Apraclonidine 0.5% or 1.0%• Weak alpha-one receptor agonist affinity• Reversal of anisocoria after 30-60 minutes if denervation

hypersensitivity is present• Horner’s pupil will dilate• Lid ptosis can also improve• Minimum 5-8 days needed for denervation hypersensitivity

• False negatives possible in early stages

• Apraclonidine effectively replaces cocaine to determine presence of HS

• Still need imaging and/or hydroxyamphetamine to determine location

Reversal of anisocoria with apraclonidine 0.5%

• Note the improved ptosis OD too

Imaging recommendations…

• Brain, neck, and superior portion of lungs and upper chest required…

• Pancoast tumor

• MRI/MRA = 95% sensitivity when used together

• Carotid duplex = identifies disrupted blood flow, does not visualize ICAD directly

• Conventional angiography = significant side effects possible…..like CVA

ICAD Treatment….

• Aggressive anti-coagulation/anti-platelet therapy:

• Warfarin***

• Heparin***

• Plavix (anti-platelets)

• ASA 325 mg

• Rarely, intravascular stents can be placed if needed…

• 85-90% complete resolution in 3-6 months; repeat MRI/MRA at this time

• 95% of associated headaches resolve in this time as well

• Recurrence rates are extremely low

• Death rates are ≤5%...

Patient Outcome…

• Patient was put on urgent Heparin, followed by Warfarin, and 20 mg oral Prednisone by neurologist

• Patient made full recovery in 3 months; no further Sn/Sx or Tx needed• Complete resolution of Horner’s findings

• PCP did not investigate into connective-tissue systemic conditions as recommended…

• Likely due to marathon run when patient bent over to tie shoes.

New Case #3

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Signal Strength:

OD: 9/10

OS: 9/10

Avg RNFL:

OD: 75 µm

OS: 95 µm

Pachymetry…

OD OS

CCT = 459 CCT = 471

Case #4 :

“Doc, my pupils are different sizes...”

Case history…

• 34 year old white female• Onset mid-morning that day…• Vision is mildly blurry; 20/25+ OD, 20/20 OS (sc)• (-) HA, (-) diplopia• (-) trauma• (-) eyedrops• (-) motion sickness patches (scopolamine)• (-) plants/flowers (atropine exposure)• (-) helping someone else with instilling eye drops• (-) systemic/ocular issues• (-) veterinarian/vet tech

Dr. Gregory House: “Everyone Lies!”

• “Oh yeah Doc, I forgot…… will these do anything?”

• Used 4-5 times throughout morning OD only b/c itchy OD with mild redness

• 100% back to normal following day

Pupillary dilation?

• Naphazoline

• Decongestant in sympathomimetic class

• Alpha-agonist activates iris dilator muscle

• Pheniramine

• Antihistamine with secondary anticholinergic properties

• Indirect/blocks acetylcholine binding (M receptor) iris sphincter muscle

• Both synergistically cause sympathetic response…hence dilation!

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Why are they available in combination?

• Naphazoline great at reducing redness, but NOT itching

• Pheniramine great at reducing itching but NOT redness

• Onset ≈ 3 minutes!

• Duration = up to 2.5 hours; means multiple dosings needed daily

• Abelson MB, et al. Effects of topically applied ocular decongestant and antihistamine. Am J Ophthalmol. 1980;90:254-57.

• Dockhorn RJ, Duckett TG. Comparison of Naphcon-A and its components (naphazoline and pheniramine) in a provocative model of allergic conjunctivitis. Curr Eye Res. 1994;319-24.

Case #5: “Doc, I have this rash on my forehead…”

Chief Complaint:

• 84 AAF presented to ER clinic

• Hospital ER referral from night before; Dx of Herpes Zoster Ophthalmicus (HZO)

• CC: “Soreness of eye lids”, blurry vision OS, never happened before, OS swollen x 2-3 days previous, concern over rash around OS, (+) mild ptosis LUL

• POH: (+)cataracts OU ECCE scheduled OU

• PMH: (+) HTN, (+)h/o breast cancer 2008, (+)↑ cholesterolemia

• PSH: unremarkable

• Meds: Nifedipine, Klor-con, Furosemide, Carvedilol, Tobramycin, APAP/codeine

• Allergies: NKMA, NKDA

Exam…

• VA’s: 20/50 PHNI OD, 20/60 PHNI OS

• Pupils: PERRL (-)APD

• EOM’s: FROM OU, (-)pain OU

• CVF: FTFC OD, mild superior defect 2º lid ptosis OS

• SLE: unremarkable; except for visually significant nuclear sclerosis OU

• IOP: 15 mmHg OD / 16 mmHg OS

• DFE: unremarkable

• Continue ACV 800mg 5x/day PO and RTC 1 week for follow up

Herpes Zoster Ophthalmicus

• Reactivation of varicella zoster virus along the ophthalmic division of CN V

• Typically unilateral vesicular rash along dermatome affected• Contagious until vesicles become crusted over

• CN V1 affected = HZO

• Any other nerves = shingles/herpes zoster

• HZO occurs in 10-20% of all zoster outbreaks

HZO in young people….

• Per Wills Eye Manual…….

• If HZO occurs in someone <40 years old be cautious of HIV/immunosuppression…..

• Has anyone ever done this?

• Anyone get positive results?

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HZ Ocular Complications…

1. Pseudo corneal-dendrites

2. Iritis/Uveitis

3. Glaucoma

4. Retinitis

5. Cranial Nerve Palsies

• Hutchinson’s Sign = nasociliary nerve involvement; means higher risk of ocular involvement

• (+)Hutchinson’s = 50-76% ocular involvement

• (-) Hutchinson’s = 34% ocular involvement

Seropositivity…

• 90% population ≥12 = seropositive for VZV

• 99% population ≥40 = seropositive for VZV• So everyone is at risk for a zoster outbreak…

• Older patients (≥60) = ↑risk and severity of HZ

• Lifetime risk = 25% in general pop.

= 50% in ≥85 YO

Herpes Antiviral Treatment…

Herpes Simplex Herpes Zoster

Acyclovir 400 mg 5x/day PO 800 mg 5x/day PO

Valacyclovir 500 mg TID PO 1000 mg TID PO

Famcyclovir 250 mg TID PO 500 mg TID PO

•Goal: Tx within 72 hours of Sn/Sx to ↓ risk of PHN and risk of ocular complications

•Ideally Tx with prodromal Sn/Sx (tingling, numbness along CN V1 dermatome) to achieve maximum benefit of Tx

1 week later…

• HZO vesicular rash completely gone but…

• “Doc, my eye lid is closed all the time…and I see double when I pick up my left lid…is something wrong?”

• “I have a headache, my jaw hurts, and my left temple is tender to the touch too”

• Immediate labwork and MRI ordered…• New neurologic deficit, GCA, HZO, history of breast cancer…

1 week later…

MRI and Labwork Results…

• MRI/MRA = negative; WNL; (-)masses

• ESR = 21 (>47 = high)

• CRP = <0.3

• RPR = negative

• HIV = negative

• CD3/CD4 = low immune suppression

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Dx= HZO Ophthalmoplegia of CN III…

• HZO occurs in 10-20% of all HZ outbreaks

• 13% of all HZO will result in CN palsies

• 1.3-2.6% of all HZ cases result in CN palsies of any kind

Incidence of Ophthalmoplegia Post-HZO…

• Total incidence = 13% of all HZO’s

• CN III = 47%

• CN IV = 10%

• CN VI = 23%

• Total Ophthalmoplegia = 20%

HZO Ophthalmoplegia Natural History…

• Onset = 9.5 days after HZO outbreak in 75% of cases• Range = 2-42 days • My patient = 8 days

• Self-Limited complete or near-complete resolution in 4.4 months in 65-76.5% of cases

• Range = 2 wks-1.5 years • My patient = 4.5 months

• Some EOM restriction and/or ptosis may last indefinitely

Mechanism of Action…

• Unproven at this point…

• Theory = 4 components1. Virus infection

2. Inflammatory/Immune Reactions

3. Vascular/Neural Inflammation4. Tissue Scarring

• Hence, benefit of concomitant antiviral and corticosteroid??? • Statistical evidence still elusive

Beware Post-Herpetic Neuralgia…

• Defn: “painful, abnormal sensations (allodynia or itch) that persist 3 months or more after rash onset.”

• Can be very severe; drastically ↓ QOL of pts

• More common in elderly populations…• 50% PHN in pts ≥60 years old• 75% PHN in pts ≥75 years old

PHN Incidence…

• No Antiviral Tx vs. Antiviral Tx:• 35% incidence with no antiviral med

• 15% incidence with antiviral med

• Responds poorly to Tx in general• Leads to ↑ rates of depression as ↓QOL

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PHN Treatment…(Combos of below meds work best)

• Oral Antivirals (mainstay of Tx)

• Tricyclic Antidepressants/SSRI’s

• Topical lidocaine patches

• Capsaicin creams

• Gabapentin (600 mg TID PO)

• Opioids

• NSAID’s----poor pain response overall

Herpes Zoster Vaccine (Zostavax®)• FDA approved, live attenuated vaccine

• Continued immunity through 7 years post-vaccine

• Current research projects 10 years benefit post vaccine

• Only ≥50 years old per FDA

• Decreased incidence of:

• herpes zoster (51%)

• PHN (67%)• Burden of Illness (61%)

• Severe pain (73%)

Is vaccine still needed after HZ outbreak?

• Some say “yes”• Will mute potential future outbreaks of HZ

• Some say “no”• Current outbreak may act as a “booster” itself

• Jury is still out…..

• Has anyone heard anything different?

• I usually leave the decision up to the PCP…

Case #6:“Doc, my eyelid is not getting better…”

Case History…

• 32 year old white male

• Referred for urgent eval. by PCP for swollen RUL/OD x 3-4 days

• PCP started on oral Augmentin 24 hours earlier

• Follow up with PCP showed no improvement so PCP referred to our clinic for second opinion

• (+)pain/tender to touch

• (-) fever

Exam:

• VA: 20/25 OD, 20/20 OS (sc)

• Pupils: PERLA, (-)APD

• CVF: OS FULL, OD mild superior restriction

• EOM’s: FULL, (-)pain

• Adnexa: see photos

• SLE: mild-moderate injection of conjunctiva OD, OS WNL

• IOP = 16 mmHg OU

• DFE = WNL OU

• No proptosis

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Ordered CT of orbits…

Sometimes it’s exactly what you think it is!

Continued Augmentin 875 mg TID PO x 10 days

Drastic improvement in another 24 hours…

Case #7:

“Doc, I have fluctuating double-vision in one eye…is that normal?”

Case History…

• 29 YO WF

• CC: “diplopia/quivering of vision”

• HPI: OD only/monocular, onset 8 years ago but worsening over past 10weeks post-partem, occurs multiple times per day with unpredictable onset, working on computer or reading makes things worse

• PMH: unremarkable

• FMH: unremarkable

• SH: unremarkable except for caffeine use daily

Exam…

• 20/20 OD, 20/20 OS (sc)• CVF: WNL OU• Pupils: equal, reactive, no anisocoria, no APD• EOM’s: full range of motion OU

• Cover test: orthophoric distance and near sc

• Manifest Refraction: +0.50 sph OD 20/20, plano OS 20/20

• SLE: unremarkable• Goldman Tonometry: 18 mmHg OU• DFE: unremarkable

• ONH OCT and macular OCT = WNL OU too

2nd Follow up (2 days later)

• OCT: macula and optic nerve WNL OU

• Park’s 3 Step: UTT (no hyper deviation)

• Maddox Rod 9 DAF’s: WNL OU

• Vertical Fusional Amps: WNL OU (rules out congenital 4th)

• MRD1/2: equal and WNL OU

• CN V1, V2, V3, VII intact

• BP: 118/68

• But finally……I saw it!!!

Diagnosis?

• Dx = Tentatively superior oblique myokymia…

• Other considerations: acquired/congenital nystagmus? Opsoclonus?

• And what treatment, if any, is available?

• Is further investigation necessary?

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Labs and Neurology Consult

• Lab tests ordered by me: • ANA (marginally elevated)

• Myasthenia panel----WNL• ESR----WNL

• Thyroid panel----WNL• RPR----WNL• ds-DNA---WNL

• Neurologist agreed with findings

• MRI/MRA imaging was performed: WNL OU

• Finally had a solid Dx!!!.....

Dx = Superior Oblique Myokymia

• First reported in 1906 by Duane “unilateral rotary nystagmus”

• In 1970, Hoyt coined term “superior oblique myokymia”

• Defn: monocular quivering/firing of superior oblique

• Sx: spontaneous monocular diplopia, quivering/jumping of vision, monocular oscillopsia, key is monocular nature

• Sn: low amplitude, high frequency intorsion of affected eye, intermittent/cyclic frequency, worse when looking down and in towards nose

• Most attacks last between 3-15 sec, rare cases of indefinite attacks

Pathogenesis Option #1

• Originally thought to be due to aberrant regeneration of nerves supplying superior oblique secondary to a trauma and/or inflammatory event1) Trochlear Nucleus

2) Trochlear Nerve3) Superior Oblique Muscle itself

• However none of these seem to adequately explain the “intermittent nature” of SOM

Pathogenesis Option #2

• Most currently accepted theory: microvascular compression

• Compression of dorsal root zone by superior cerebellar artery branches or posterior cerebral artery branches

• Based on 3 case reports involving microvascular decompression surgery

• Most recent case report----Fam et al. Br J Neurosurg. 2014.

Possible ominous causes…

• Tumors/Masses

• Strokes/CVA’s

• A/V malformations

• Multiple Sclerosis

• Hydrocephalus

• Arachnoid Cysts

Is imaging required?

• Older researchers = no

• Newer researchers = yes

• Lab tests?• Unsure…..not too many case reports have investigated

with bloodwork/labs• Most come back unremarkable/noncontributory• Small sample size though

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If imaging is now recommended…..where/what/how are we looking at things?

• Typically MRI’s use 5-10 mm slices

• In order to see compression on MRI’s with SOM the slices need to be 1-2 mm.

• Compression is then defined as “lack of a layer of cerebrospinal fluid between the trochlear nerve and adjacent blood vessels”

• Posterior Cerebral Artery• Superior Cerebellar Artery

• Begs the question, did the neurologist miss it?.....

What Tx is available?

1. Observation

2. Medical Management

3. Surgical Management

Medical Management

• Mixed results in general…

• Mainly domain of oral drugs:• Prismatic correction (BU over involved eye)

• Carbamazepine (historical gold standard)

Carbamazepine

• Historically the “go-to” drug for SOM

• Anticonvulsant which decreases nerve impulses that cause seizures and/or pain

• FDA category “D” drug

• However, has potential for serious side effects

• Leukopenia, renal failure, thromboembolism, and arrhythmias

• Highest rate of side effects and discontinuation of all the drugs, but seems to work the best according to 2007 study (Williams et al.)

• Other drugs have been investigated as a result….

Relief with New Meds…

• Gabapentin• Phenytoin

• Memantine• Baclofen

• Clonazepam

• Propranolol

• Botox?

• All have potential for some unwanted SE’s

Surgical Management

• Only indicated for absolutely intractable and unbearable Sx

1) Strabismus Surgery to weaken superior oblique

• Myectomy of ipsilateral inferior oblique and tenectomy of ipsilateral superior oblique

• Diplopia in down gaze (secondary to hyper phoria/tropia) likely side product of this procedure however it is very good at eliminating oscillopsia component

• Diplopia can be alleviated/eliminated with BD prism correction over affected eye

2) Cranial decompression of dorsal root exit zone of Trochlear nerve

• Based on 3 known cases

• Microvascular Decompression Surgery (MDS)

• Craniotomy Teflon pads between trochlear nerve and adjacent blood vessels causing compression

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New Tx?Topical Beta-blockers???

• Bibby et al. (1994) showed one case report of a patient’s SOM Sxbeing relieved with betaxolol glaucoma drops

• Based off of case reports which used oral propranolol

• Weak membrane stabilizing abilities of beta blockers = MOA

• MOA: hypothesized that enough drug was absorbed systemicallythrough conjunctival blood vessels to elicit its effect

• Systemic Theory

What did I do?

• Started topical timolol 0.5% drops BID OD!

• Patient reported 100% resolution of Sx after only 2 days of use!!!!

• Phone call 4 months later, still 100% resolution of Sx but only using drops QAM OD

• 12+ month later….still Sx-free on drops!

Story doesn’t end here…

• Given that numbers of SOM are low to begin with……cases reports of topical beta-blockers providing relief of Sx are even rarer

• Bibby et al……hypothesized “systemic theory”

• I developed my own theory……

• Chris Borgman’s “Localized Theory”

CB’s “Localized Theory”

• In SOM, when successfully treated with topical beta-blockers, the effect occurs locally at the trochlear nerve endings themselves and/or on the trochlear muscle itself, not systemically absorbed via the conjunctival blood vessels.

• I would argue AGAINST Bibby’s systemic absorption theory.

Proof of Localized Theory

• After successful Tx for 2+ months…

• Patient instructed to stop all drops

• Sx returned to pre-treatment severity in 2-3 days

• Patient instructed to instill drops in contralateral eye• No effect, Sx still remained

• Patient told to re-start drops in original/affected eye

• Sx disappeared in 1-2 days of use again• No recurrences since

What does this mean?

• Keep in mind…..this is only 1 case.

• Beta-blockers work locally on the ocular tissues themselves• Likely on superior oblique muscle itself or the trochlear nerve

endings

• Perhaps not on a systemic level like Bibby et al. hypothesized…

• “Localized theory” holds water!• However, still unproven…needs more research

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Potential New Associations Noted By Author/Presenter

• Compression/trauma are two separate causes that share final common pathways leading to SOM?

• Females: pregnancy induced/associated?• MOA: unknown….hormones?

• Males: trauma induced?

• Would explain female:male ratio of 3:1

Superior Oblique Myokymia

• Monocular oscillopsia???….think SOM

• Seal diagnosis with attentive slit lamp exam and case Hx

• Imaging to rule out ominous causes; majority are benign!

• Consider topical beta-blocker trial

• Dirt cheap!

• If no response then refer to neurology for trial of oral medications• Gold Standard = Carbamazepine

• Surgery….last resort only….rarely should be employed

Case #8:“Doc, where am I at?”

Case History…

• 33 year old white female

• Bicycle accident with concussion 3 days prior, (+)loss of consciousness, amnesia x 2 weeks afterwards

• CT WNL OU, (-)orbital/skull/maxillofacial fractures per radiologist

• (+) moderate HA

• (-) prior systemic issues or meds

• Vision blurry OD>OS per patient

Exam…

• VA = 20/20-2 OD, 20/20-2 OS (sc)

• Pupils: traumatic iridoplegia OD, 6 mm OD fixed, (+) reverse APD OD?

• CVF: restricted right side OU

• EOM’s: Full, (-)diplopia

• Adnexa: see picture

• SLE: Subconj Hemorrhage OD, (-) hyphema, (-)iritis

• IOP = 12 mmHg OU

• DFE = (-)H,T,D OU ; see posterior pole pictures OU

MRI ordered…

• Ordered MRI with contrast ; concentrated in orbits, optic tracts, and occipital lobes.

• MRI WNL per radiology report

• Dx = Traumatic Optic Neuropathy with bilateral right-sided hemianopic VF defects

• Unfortunately, patient never returned for future appointments

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Traumatic Optic Neuropathy…

• Decreased VA or VF after a traumatic injury to eye or periocular area • Typical scenario = patient awakes and notices vision loss

• New APD in traumatized eye that cannot be accounted for by prev. pathology

• Other Sn/Sx: decreased color vision, VF defect, optic nerve pallor or may be normal in acute stages

• Optic atrophy usually occurs after 3-6 weeks.

• TON often associated with intracranial/closed head injuries: 0.5%-5%

• M>F, 90% unilateral, 10% bilateral, avg 33.5 YO

• MVA’s (49%) most commonly followed by falls (27%) and assaults (13%)

Types of Trauma:

1. Direct• Penetrating injury; less common

2. Indirect• Trauma to: forehead, supraorbital ridge, less commonly temporal

region ; shockwave transferred to optic canal

• Most common• Loss of consciousness is very common

Indirect Trauma to ONH• Superior orbital rim or fronto-temporal region of the cranium,

compression forces are transmitted to the orbital apex and optic canal.

• LOCATION = OPTIC CANAL; 71% of the time

• Primary indirect = blood vessel and nerve shearing

• Secondary indirect = edema from injury causes decreased blood flow to nerve as nerve swells in optic nerve canal

TON Treatment Options…

1. Observation

2. IV Steroids

3. Optic Canal Decompression

• MOA: medically or surgically reduce edema/choking effect of optic canal on the optic nerve

• Which Tx is best?

• When do I choose which one to use?

Landmark TON Treatment Studies…

1. National Acute Spinal Cord Injury Study 2 (NASCIS 2) • (1990)

2. National Acute Spinal Cord Injury Study 3 (NASCIS 3) • (1997)

3. International Optic Nerve Trauma Study (IONTS) • (1999)

4. Corticosteroid Randomization After Significant Head Injury (CRASH) • (2004)

NASCIS 2 & 3 Studies (1990/1997)…

• Studied acute spinal cord injury

• Extrapolated to eyes…

• Option A: IV High dose steroids x 24-48 hours post acute injury

• Option B: IV Naloxone x 24-48 hours

• Option C: IV Placebo x 24-48 hours

• Conclusion: IV steroids <8 hours of injury = greatest chance of motor/sensory improvement in comparison to placebo and naloxone

• IV steroids >8 hours was detrimental to outcomes

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NASCIS Conundrums…

1. Optic Nerve vs. Spinal Cord• Optic Nerve = white matter/axons only

• Spinal Cord = mix of white/grey matter

• Will these respond the same since they have different make ups?

2. Timing of eye exam post-trauma• Priorities: Life > Eyes

• The ability to stabilize patients post-trauma commonly takes much longer than 8 hours

• Steroids beyond 8 hours found to be detrimental

International Optic Nerve Trauma Study (1999)• Largest TON study to date…

• N=133 patients1. Observation alone vs….2. High-dose steroids within 7 days of injury vs….3. Optic canal decompression (+/- steroids) within 7 days of injury

• 57% of observation group showed 3+ lines of acuity improvement

• 52% of steroid group showed 3+ lines of acuity improvement

• 32% of decompression group showed 3+ lines of acuity improvement

• No clear statistical benefit between any of the treatment groups

CRASH Study (2004)

• High-dose IV steroids or IV placebo for 48 hours post head trauma

• Plan = enroll 20,000 pts

• Study was halted at 10,008 patients

• Safety monitoring found increased risk of death in steroid group!

• “The CRASH trial has immediate implications for treating TON given the high incidence of concomitant head trauma.”

---Steinsapir et al. (2011)

• Relevancy to TON = 40%-72% of TON cases involve loss of consciousness

Landmark TON Treatment Outcomes…

1. National Acute Spinal Cord Injury Study 2 (NASCIS 2) (1990)• High-dose steroids = greater chance of motor/sensor improvement• Extrapolated to eyes…..(eyes not actually involved in study!)

2. National Acute Spinal Cord Injury Study 3 (NASCIS 3) (1997)• High-dose steroids within 8 hours of injury = greatest recovery chance• Increased risk of sepsis and pneumonia with high-dose steroids in these patients

3. International Optic Nerve Trauma Study (IONTS) (1999)• Observation = same outcome as decompression and/or steroids

4. Corticosteroid Randomization After Significant Head Injury (CRASH) (2004)• Increased risk of death in patients within 2 weeks of head trauma with steroid Tx compared to

observation alone ; (Eyes were not studied!)

Where does all this leave us now?

1. Observation is best option currently• 57% of TON spontaneous improve on there own at least somewhat

2. Optic Canal Decompression • (with or without fenestration both are equal)

3. High-Dose IV Steroids } Both Tx are NOT yet proven better than observation alone

Notable quotes…

• “These clinical findings, together with the newer experimental data, provide a very cogent rationale for with-holding high-dose methylprednisolone in TON.”

---Kenneth Steinsapir, MD (2006)

• “There is sufficient evidence to conclude that neither corticosteroids nor optic canal surgery should be considered the standard of care for patients with TON.”

---Levin et al. (IONTS study) (1999)

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Future TON Treatments?

• Hypothermia• Glutamate inhibitors• Erythropoetin• Progesterone• Crystalline• Neurotrophic factors (BDNF, CNTF, Fibroblast growth factors)• Transplantations• Nitrous oxide inhibition• Tumor necrosis factor-alpha inhibition• Umbilical cord blood stem cells• A2A Adenosine Receptor Agonists

• Promising for sure, not proven yet…

•Thank you!!!• Questions?

• cborgman@sco.edu