1. Back to Basics: Diplopia
Michael Dollin
PGY2 University of Ottawa Eye Institute
University of Ottawa Meds Year 4 LMCC review course
April 2, 2009

2. Outline What is diplopia? Important questions to ask
Important causes of diplopia
Monocular
Binocular
Investigations
Management
Summary

3. What is diplopia?
Double vision

4. Important questions
Does the diplopia resolve when 1 eye is covered? (i.e. monocular vs. binocular)
Is it the same in all fields gaze (comitant) or does it vary with gaze direction (incomitant)?
Is it horizontal, vertical, or oblique?
Is it constant, intermittent, or variable?

5. Causes of diplopia Monocular causes Binocular causes
Start with question #1:
Does the diplopia resolve when 1 eye
(either eye) is covered?
(If not, the diplopia is monocular)

6. Monocular causes (1) Abnormalities of the refractive media
High astigmatism
Corneal irregularity (e.g. scar, k’conus)
Lens opacities (e.g. cataract)
(2) Retinal pathology
Maculopathy (fluid, Hgb, fibrosis)
The diplopia will persist when the unaffected eye is covered, but resolve when the affected eye is covered

7. Binocular diplopia will resolve by covering either eye
Binocular causes
Binocular diplopia will resolve by covering either eye
Now question #2:
Is the diplopia the same in all fields gaze (comitant) or does it vary with gaze direction (incomitant)?

8. Comitant deviations
Characteristic of congenital or early-onset strabismus
Typically do not cause diplopia although diplopia may develop later in life
e.g. patient with long-standing exophoria whose accommodation and convergence capacities wane in 5th decade of life
Divergence insufficiency
Manifests as esodeviation greater at distance than at near; comitant in right and left gaze
Benign syndrome, resolves spontaneously
Rule out incipient or resolving U/L CN6 palsy or highly symmetric B/L CN6 palsy (consider MRI)

9. Incomitant deviations
More likely acquired and usually cause diplopia
Think of…
Paretic etiologies
Neural (CN 3, 4, and 6 palsies)
Neuromuscular junction (MG)
Restrictive etiologies
Trapped or fibrotic EOM

10. Incomitant deviations
Approach to these etiologies…
Question #3:
Is it horizontal, vertical, or oblique?
Tells you which extra-ocular muscle(s) might be involved
Question #4:
Is it constant, intermittent, or variable?
Constant: paretic (neural) or restricted
Intermittent, variable: paretic (neuromuscular; MG)

11. Way back to basics!
Let’s review the actions and innervations of the extra-ocular muscles (EOM)

12. EOM “LR6SO4” 4 rectus muscles 2 oblique muscles Innervation:
Lateral (LR), Medial (MR), Superior (SR), Inferior (IR)
2 oblique muscles
Superior (SO), Inferior (IO)
Innervation:
CN3  SR (+ levator), MR, IR, IO
CN4  SO
CN6  LR
“LR6SO4”

13. AAO, Neuro-Ophthalmology
EOM
10 action
20 action
30 action LR MR SR IR SO IO
ABduction
ADduction
Elevation
Depression
Intorsion
Extorsion
None

14. Back to incomitant deviations…

15. Neural (paretic) causes
Oculomotor nerve palsies
CN3 (Oculomotor)
CN4 (Trochlear)
CN6 (Abducens)
Internuclear ophthalmoplegia (INO)

16. AAO, Neuro-Ophthalmology

17. CN3 palsy Exits ventrally from midbrain
Motor innervation to levator, SR, IR, MR, IO
Parasympathetic innervation to pupillary sphincter (constrictor) and ciliary muscles
Reference 3

18. Causes of 3rd nerve palsy
Ischemic (DM, HTN) – most common
Brain stem lesion (infarct, MS)
Compression (P comm aneurysm, uncus)
Tumour
Inflammation (Sarcoid, vasculitis)
Infection (meningitis)
Infiltration (lymphoma, carcinoma)
Trauma

19. AAO, Neuro-Ophthalmology
Complete 3rd nerve palsy
Severe ptosis
Eye positioned “down and out”
Dilated pupil that responds poorly to light
Partial 3rd nerve palsy
Mild or moderate limitation
AAO, Neuro-Ophthalmology

20. Always check pupils! “Pupil-involving”
Dilated pupil that responds poorly to light
Due to loss of parasympathetic input
These fibers travel along the medial superficial surface of CN3
Susceptible to direct compression by an aneurysm of the posterior communicating artery (P comm)
Assumed to be secondary to an aneurysm until proven otherwise  must image
Gold standard is catheter angiography
CTA or MRA can reliably detect 2-3 mm aneurysms

21. AAO, Neuro-Ophthalmology

22. Always check pupils! “Pupil-sparing”
Normal pupillary function but complete loss of lid and ocular motor function
Almost always ischemic (DM)
May be painful
Resolves within 3 months (if not  image)
If partial w/o pupillary involvement or young and no ischemic risk factors  follow closely (may evolve)
Older patients  consider GCA

23. CN4 palsy Crosses in the brainstem Exits dorsally
Nucleus innervates contralateral SO
Exits dorsally
Longest intracranial course
Reference 3

24. Palsy typically causes diplopia that is worse in downgaze
“Double vision is worse while reading”
Motility testing often appears normal
Identify using Parks-Bielchowsky 3-step test
Look for: ipsilateral hypertropia and compensatory contralateral head tilt

25. Left 4th nerve palsy

26. Causes of 4th nerve palsy
Congenital
Asymptomatic until 40-60yo (↓ fusional amplitudes)
Chronic head tilt – check old photographs
Ischemic
Patients older than 50yo with ischemic risk factors
Expect resolution within 3 months
Trauma
MS, tumour, hydrocephalus, aneurysm
Idiopathic
Consider Graves and Myasthenia

27. Investigations Neuroimaging Medical work-up
Usually of little diagnostic value
Lack of recovery after 3 months  MRI
Medical work-up
Patients in vasculopathic age group
BP, fasting BG, lipid profile

28. CN6 palsy Exits brainstem at ponto-medullary junction
Travels ventrally up the clivus
Crosses over the apex of the petrous bone
Enters the cavernous sinus
Reference 3

29. AAO, Neuro-Ophthalmology
Typically presents as horizontal diplopia that worsens on ipsilateral gaze and when viewing at a distance
Patient appears esodeviated
AAO, Neuro-Ophthalmology

30. Causes of 6th nerve palsy
Ischemic – most common
Patients older than 50yo with ischemic risk factors
Expect resolution within 3 months
CPA tumours (e.g. acoustic neuroma)
CN 5, 6, 7, and 8 usually also affected
Trauma
Raised intracranial pressure
Gradenigo syndrome (mastoiditis)
Consider leukemia or brain stem glioma (children)
Consider MS (adolescents and young adults)

31. Investigations Adults > 50yo Patients < 50yo
Medical work-up (BP, fasting BG, lipid profile)
Lack of recovery after 3 months  MRI
Patients < 50yo
Rarely ischemic  must image (MRI/FLAIR)
Consider LP, Tensilon test

32. INO
Secondary to brainstem lesion of the medial longitudinal fasciculus (MLF)
Bundle of fibers connecting 6th nerve nucleus on one side to the MR (3rd nerve) subnucleus on the opposite side

33. AAO, Neuro-Ophthalmology
Cardinal feature: slowed ADducting saccadic velocity in eye ipsilateral to lesion
INO = Insufficient Nasal Output
Associated ABducting nystagmus of contralateral eye
Most common causes:
Adults: MS, brain stem stroke
Children: post-viral, brain stem tumour
Myasthenia gravis: pseudo-INO
AAO, Neuro-Ophthalmology

34. Neuromuscular (paretic) causes
Problem at the neuromuscular junction (e.g. Myasthenia Gravis)

35. Myasthenia Gravis
Immunologic disorder characterized by weakness which worsens with use (end of day) and improves with rest
Pathophysiology: anti-acetylcholine receptor antibodies
Hallmark features: fluctuation and fatiguability
Common clinical presentation:
Ptosis (worsens with sustained upgaze)
Diplopia (especially changing pattern of diplopia)
Cogan eyelid twitch
Pseudo-INO
Absence of pupil or sensory abnormalities

36. Why is this diagnosis important to make? Systemic involvement:
Dyspnea, dysphagia  life-threatening!
Muscle weakness (masticators, extensors)
Hoarseness
Dysarthria

37. Diagnosing MG Clinical exam Tensilon test
Edrophonium chloride (Ach-esterase inhibitor)
Document baseline deficit (e.g. ptosis)
2 mg test dose (observe 60 sec) 4 mg  4 mg
Positive response dramatic if deficit was severe
Potential side effects: bradycardia, respiratory arrest, bronchospasm, syncope, cholinergic crisis
Pulse and BP monitoring; Atropine and crash cart ready
Alternatives: sleep test, ice test

38. Other diagnostic tests: Serology:
Anti-Ach receptor antibodies
Anti-muscle specific kinase
Test for thyroid dysfunction (5%) and Lupus
Single fiber EMG: decremental response
CT chest: malignant thymoma (10%)
Treatment:
Mestinon (Pyridostigmine)
+/- Thymectomy

39. Restrictive causes Most common causes:
Thyroid-Associated Orbitopathy (Graves)
Orbital trauma (blow-out fracture)
Other causes:
Orbital inflammation (myositis)
Orbital infection (orbital cellulitis)
Orbital tumour (EOM infiltration or metastases)

40. Thyroid-Associated Orbitopathy (Graves’ disease)
Autoimmune inflammatory disorder
Usually hyperthyroid (can be euthyroid)
Eye disease does not necessarily parallel thyroid gland activity
Clinical signs:
Eyelid retraction
Lid lag
Proptosis (exophthalmos)
Restrictive EOM ( diplopia)
Compressive optic neuropathy

42. Orbital wall (blow-out) fracture
Typically orbital floor or medial wall
Mechanism: blunt trauma
Diplopia 20 EOM or fascia entrapment

43. Check motility (esp. up and lateral gaze) Other signs:
Enophthalmos (affected eye sunken in)
V2 numbness (over cheek bone)
Subcutaneous emphysema

44. Summary Remember the 4 questions Determine onset and course
Check pupils in CN3 palsy
Pupil-involving needs imaging (CTA or MRI)
Other indications for imaging
Non-resolving (presumed ischemic) CN palsy
Younger patients (< 50yo)
Value of a Tensilon test in MG
In older patients, consider GCA (ESR, CRP)

45. References AAO BCSC 2007-2008 Section 5, Neuro-Ophthalmology.
Kanski JJ. Clinical Ophthalmology: A Systematic Approach, 6th ed. Philadelphia, PA: Elsevier Limited; 2007.
Patel V. Efferent Neuroanatomy. Neuro-Ophthalmology teaching block, 2009, University of Ottawa Eye Institute.
(March 17, 2009)

46. Thank you
Any questions?

47. Good luck on the exam! (Enjoy your summer)