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

3/14/18 E FFERENT PATHWAY INVOLVEMENT OF NEURODEGENERATIVE DISEASE SCIENTIFIC PERSPECTIVE Heather E. Moss, MD, PhD NANOS A NNUAL MEETING 2018 OPHTHALMOLOGY B Y E R S E Y E I N S T I T U T E D ISCLOSURES — National Eye Institute — Research to Prevent Blindness OPHTHALMOLOGY 1

3/14/18 T HE FOLLOWING HORIZONTAL SACCADE TEST IS SIMILAR IN PSP AND NORMAL CONTROL SUBJECTS 1. anti-saccades 2. saccade latency 3. saccade velocity 4. saccade gain Google doc row 18 OPHTHALMOLOGY S ACCADIC 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 OPHTHALMOLOGY 2

3/14/18 O VERVIEW — Implications of abnormal eye movements — Afferent impacts on eye movement measures — Leveraging eye movements as a marker of non- ocular motor pathology OPHTHALMOLOGY diagnosis Personalized Prevention Treatment opportunity opportunity tests monitoring risk & assessment prognosis OPHTHALMOLOGY 3

3/14/18 S MOOTH PURSUITS ARE QUANTITATIVELY DIFFERENT BETWEEN DISEASES Subjects: — 23 controls — 27 PD — 11 MSA-P — 8 MSA-C MSA gains < PD gains < Control gains with significant overlap Pinkhardt et al, 2009 OPHTHALMOLOGY S MOOTH PURSUITS ARE QUALITATIVELY DIFFERENT BETWEEN DISEASES MSA Target Eyes — MSA patients with catch up saccades MSA — PD patients with PD anticipatory saccades PD Pinkhardt et al, 2009 OPHTHALMOLOGY 4

3/14/18 S ACCADES ARE QUALITATIVELY DIFFERENT BETWEEN DISEASES Eye position vs. time Garbutt et al, Brain 2008 OPHTHALMOLOGY S ACCADES ARE QUANTITATIVELY DIFFERENCE BETWEEN DISEASES velocity latency gain control (27) Pick, FTP-17 (3) FTD-TDP-43 (12) PSP (8) CBD (4) AD (10) Boxer et al, 2012 OPHTHALMOLOGY 5

3/14/18 F IXATION STABILITY IS DIFFERENT BETWEEN DISEASES Square wave jerks (in AD) à cerebellar volume T. Shakespeare, 2015 OPHTHALMOLOGY E YE MOVEMENT ABNORMALITIES CORRELATE WITH REGIONAL BRAIN ATROPHY Midbrain volume Boxer et al, 2012 OPHTHALMOLOGY 6

3/14/18 M OTILITY MAY BE HELPFUL FOR DIAGNOSIS Garbutt et al, Brain 2008 OPHTHALMOLOGY R OLE OF ELEMENTARY EYE MOVEMENT RECORDINGS IN NEURODEGENERATIVE DISEASE — Marker of anatomic site of degeneration — Diagnostic feature of disease (mainly for PSP) OPHTHALMOLOGY 7

3/14/18 B EYOND SIMPLE EYE MOVEMENTS OPHTHALMOLOGY SCAN PATHS REQUIRE EYE MOVEMENTS Looking at a scene Reading T. Shakespeare (2015), J. Liao OPHTHALMOLOGY 8

3/14/18 L EFT TO RIGHT READING TASK IN PERSON WITH PARKINSON ’ S DISEASE No neurological disease Parkinson’s disease (12 seconds) (21 seconds) Dr. Joyce Liao, Stanford Ophthalmology OPHTHALMOLOGY C OMPARISON OF READING PATHS No neurological disease Parkinson’s disease (12 seconds) (21 seconds) Dr. Joyce Liao, Stanford Neuro-Ophthalmology OPHTHALMOLOGY 9

3/14/18 S CAN PATHS MIGHT ACCOUNT FOR SYMPTOMS ( E . G . DIFFICULTY READING ) No neurological disease Parkinson’s disease Parkinson’s disease (12 seconds) (21 seconds) (119 seconds) PD (n=42) slower than controls (n=80) p < 0.05 Jehangir et al (2017), J. Liao OPHTHALMOLOGY R OLE 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 OPHTHALMOLOGY 10

3/14/18 E YE MOVEMENT TESTS REFLECT MORE THAN OCULAR MOTILITY PATHWAYS OPHTHALMOLOGY T ASK DEPENDENT SCAN PATHS ARE AFFECTED IN PCA Non-search task Search task (look at trees) Shakespeare et al, 2015 OPHTHALMOLOGY 11

3/14/18 V ISUALLY GUIDED SACCADES ARE AFFECTED IN PCA T. Shakespeare, 2015 OPHTHALMOLOGY S ACCADE TIME CORRELATES WITH PARIETAL AND OCCIPITAL THICKNESS ( IN PCA AND AD) T. Shakespeare, 2015 OPHTHALMOLOGY 12

3/14/18 R OLE 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 L EVERAGING EYE MOVEMENTS FOR TESTING COGNITIVE DOMAINS OPHTHALMOLOGY 13

3/14/18 A NTI - SACCADES ARE IMPAIRED IN AD Normal (118) Mild cognitive impairment (26) Alzheimers disease (18) Heuer et al, 2013 OPHTHALMOLOGY S ACCADES AS A TEST OF LANGUAGE Seckin et al, 2016 OPHTHALMOLOGY 14

3/14/18 S ACCADE BASED SPATIAL ANTICIPATION TEST ( INSPIRED BY BRIXTON TEST ) 36 12 6 Sequence of targets Anticipatory saccades Correct incorrect Primitivo et al, 2017 OPHTHALMOLOGY R OLE 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 OPHTHALMOLOGY 15

3/14/18 E YE M OVEMENT 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 P ROPOSED STAGING SCHEME IN ALS BASED ON OCULAR MOTILITY TESTING Gorges et al, 2015 OPHTHALMOLOGY 16

3/14/18 ALS PATIENTS WITH NORMAL PRO - SACCADES HAVE ABNORMAL EXECUTIVE FUNCTION antisaccade Trail making task control ALS Correlates with motor score (ALS-FRS) No deterioration over 2 years in 6 subjects Proudfoot et al, 2015 OPHTHALMOLOGY 17