Google doc row 18 OPHTHALMOLOGY S ACCADIC PERFORMANCE CAN BE - - PDF document

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OPHTHALMOLOGY

B Y E R S E Y E I N S T I T U T E

Heather E. Moss, MD, PhD

EFFERENT PATHWAY INVOLVEMENT OF

NEURODEGENERATIVE DISEASE SCIENTIFIC PERSPECTIVE

NANOS ANNUAL MEETING 2018

OPHTHALMOLOGY

DISCLOSURES

— National Eye Institute — Research to Prevent Blindness

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OPHTHALMOLOGY

THE FOLLOWING HORIZONTAL SACCADE TEST IS SIMILAR

IN PSP AND NORMAL CONTROL SUBJECTS

• 1. anti-saccades
• 2. saccade latency
• 3. saccade velocity
• 4. saccade gain

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OPHTHALMOLOGY

SACCADIC PERFORMANCE CAN BE AFFECTED BY:

• 1. executive function
• 2. attention
• 3. oculomotor pathways
• 4. language function
• 5. afferent visual function
• 6. all of the above Google doc row 18

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OPHTHALMOLOGY

OVERVIEW

— Implications of abnormal eye movements — Afferent impacts on eye movement measures — Leveraging eye movements as a marker of non-

• cular motor pathology

OPHTHALMOLOGY

tests

diagnosis risk assessment monitoring & prognosis

Prevention

• pportunity

Personalized Treatment

• pportunity

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OPHTHALMOLOGY

SMOOTH PURSUITS ARE QUANTITATIVELY DIFFERENT

BETWEEN DISEASES

MSA gains < PD gains < Control gains with significant overlap

Pinkhardt et al, 2009 Subjects:

— 23

controls

— 27 PD — 11 MSA-P — 8 MSA-C

OPHTHALMOLOGY

SMOOTH PURSUITS ARE QUALITATIVELY DIFFERENT

BETWEEN DISEASES — MSA patients with

catch up saccades

— PD patients with

anticipatory saccades

MSA MSA PD PD Target Eyes Pinkhardt et al, 2009

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OPHTHALMOLOGY

SACCADES ARE QUALITATIVELY DIFFERENT BETWEEN

DISEASES

Garbutt et al, Brain 2008

Eye position vs. time

OPHTHALMOLOGY

SACCADES ARE QUANTITATIVELY DIFFERENCE BETWEEN

DISEASES

Boxer et al, 2012 latency velocity gain FTD-TDP-43 (12) control (27) PSP (8) CBD (4) Pick, FTP-17 (3) AD (10)

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OPHTHALMOLOGY

FIXATION STABILITY IS DIFFERENT BETWEEN DISEASES

• T. Shakespeare, 2015

Square wave jerks (in AD) à cerebellar volume

OPHTHALMOLOGY

EYE MOVEMENT ABNORMALITIES CORRELATE WITH

REGIONAL BRAIN ATROPHY

Boxer et al, 2012 Midbrain volume

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OPHTHALMOLOGY

MOTILITY MAY BE HELPFUL FOR DIAGNOSIS

Garbutt et al, Brain 2008

OPHTHALMOLOGY

ROLE OF ELEMENTARY EYE MOVEMENT RECORDINGS IN

NEURODEGENERATIVE DISEASE

— Marker of anatomic site of degeneration — Diagnostic feature of disease (mainly for PSP)

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OPHTHALMOLOGY

BEYOND SIMPLE EYE MOVEMENTS

OPHTHALMOLOGY

SCAN PATHS REQUIRE EYE MOVEMENTS

Looking at a scene

• T. Shakespeare (2015), J. Liao

Reading

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OPHTHALMOLOGY

LEFT TO RIGHT READING TASK IN PERSON WITH

PARKINSON’S DISEASE

• Dr. Joyce Liao, Stanford Ophthalmology

No neurological disease (12 seconds) Parkinson’s disease (21 seconds)

OPHTHALMOLOGY

COMPARISON OF READING PATHS

No neurological disease (12 seconds) Parkinson’s disease (21 seconds)

• Dr. Joyce Liao, Stanford Neuro-Ophthalmology

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OPHTHALMOLOGY

SCAN PATHS MIGHT ACCOUNT FOR SYMPTOMS (E.G. DIFFICULTY READING)

No neurological disease (12 seconds) Parkinson’s disease (21 seconds) Parkinson’s disease (119 seconds) Jehangir et al (2017), J. Liao PD (n=42) slower than controls (n=80) p < 0.05

OPHTHALMOLOGY

ROLE OF EYE MOVEMENT RECORDINGS IN

NEURODEGENERATIVE DISEASE

— Marker of anatomic site of degeneration — Diagnostic feature of disease (mainly for PSP) — Scan path analysis may have diagnostic and

counselling implications

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OPHTHALMOLOGY

EYE MOVEMENT TESTS REFLECT MORE THAN

OCULAR MOTILITY PATHWAYS

OPHTHALMOLOGY

TASK DEPENDENT SCAN PATHS ARE AFFECTED IN PCA

Non-search task Search task (look at trees) Shakespeare et al, 2015

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OPHTHALMOLOGY

VISUALLY GUIDED SACCADES ARE AFFECTED IN PCA

• T. Shakespeare, 2015

OPHTHALMOLOGY

SACCADE TIME CORRELATES WITH PARIETAL AND

OCCIPITAL THICKNESS (IN PCA AND AD)

• T. Shakespeare, 2015

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OPHTHALMOLOGY

ROLE OF EYE MOVEMENT RECORDINGS IN

NEURODEGENERATIVE DISEASE

— Marker of anatomic site of degeneration — Diagnostic feature of disease (mainly for PSP) — Scan path analysis may have diagnostic and

counselling implications

— Afferent visual pathway pathology affects eye

movement task performance in a task dependent manner

OPHTHALMOLOGY

LEVERAGING EYE MOVEMENTS FOR TESTING

COGNITIVE DOMAINS

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OPHTHALMOLOGY

ANTI-SACCADES ARE IMPAIRED IN AD

Heuer et al, 2013 Normal (118) Mild cognitive impairment (26) Alzheimers disease (18)

OPHTHALMOLOGY

SACCADES AS A TEST OF LANGUAGE

Seckin et al, 2016

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OPHTHALMOLOGY

SACCADE BASED SPATIAL ANTICIPATION TEST (INSPIRED BY BRIXTON TEST)

Primitivo et al, 2017 Sequence of targets Anticipatory saccades Correct incorrect

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OPHTHALMOLOGY

ROLE OF EYE MOVEMENT RECORDINGS IN

NEURODEGENERATIVE DISEASE

— Marker of anatomic site of degeneration — Diagnostic feature of disease (mainly for PSP) — Scan path analysis may have diagnostic and counselling

implications

— Afferent visual pathway and neuro-cognitive

dysfunction affect eye movement task performance in a task dependent manner

— Potentially useful for testing non-ocular motility

domains

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OPHTHALMOLOGY

EYE MOVEMENT ABNORMALITIES IN ALS?

— Poor anti-saccades — Saccadic intrusions into smooth pursuit — Gaze impersistence — Voluntary saccade palsy (supranuclear) — Reduced Bell’s phenomenon — Eyelid opening apraxia

• Correlated with reduced forced vital capacity

Moss et al, 2012

OPHTHALMOLOGY

A PROPOSED STAGING SCHEME IN ALS BASED ON

OCULAR MOTILITY TESTING

Gorges et al, 2015

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OPHTHALMOLOGY

ALS PATIENTS WITH NORMAL PRO-SACCADES HAVE

ABNORMAL EXECUTIVE FUNCTION

Proudfoot et al, 2015 antisaccade Correlates with motor score (ALS-FRS) Trail making task control ALS No deterioration over 2 years in 6 subjects