10/11/2017
1
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: [email protected]
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
10/11/2017
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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?