Deficient Low-Contrast Visual Sensitivity Occurs in Patients with Multiple Sclerosis: May Degrade Gait Performance, Possible Modification Utilizing High Contrast Visual Aids.

Rachel TripoliKelly SchwirianDr. C.G. Maitland

Background & Hypothesis

Balcer in 2000 (Balcer et al 2000) observed deficient low-contrast sensitivity in M.S. patients with and without optic neuropathy.

The impact of deficient low contrast sensitivity has not yet been explained in patients with M.S. to any degree.– Since optic neuropathy is found in over 80% of patients

with M.S., it seems prudent to investigate any mechanism that might improve the function of affected individuals.

The application of high-contrast, blue-blocking yellow lenses was investigated in hopes of improving vision in low-contrast environments, and thus possibly allowing for better obstacle discrimination.

Methodology Four parameters were used to stage

the degree of pathology of patients with multiple sclerosis and age matched controls

– Estimated Disability Severity Scale Ten-point scoring system that evaluates

visual, motor, brainstem, sensory, and cognitive dimensions of patients with M.S.

– Low Contrast Sloan Letter Chart– Optical Coherence Tomography– Gait Pad Measurement

Methodology

Patients tested with both eyes first, then right and left eye individually first at 100% efficiency, then at 2.5%, and then at 1.25% efficiency.

The Snellen visual acuity equivalent will be determined by the lowest line read on the 100% chart.

Low Contrast Sloan Chart

Methodology

To ensure a complete assessment of optic nerve topography, patients were examined using optical coherence tomography to assess thickness of the optic nerve fiber bundle.

Optic Coherence Tomography

Methodology

Patients were asked to walk on a 22 foot gait pad that measures 102 parameters of gait

The GaitRite pad (CIR Systems, Inc.) contains six sensor pads that extract readings from over 16,000 sensors embedded within a carpet that record patient data in an area 24 inches wide and 1400 inches long.

Ambulation time, velocity, right and left footfall pressure and duration, and Functional Ambulation Performance (FAP) scores were calculated for each patient.

GaitRite Pad Measurement

http://www.gaitrite.com/Products/index-new.html

Methodology

EDSS Assessment– Evaluated on a scale of 0 – 10 based on

disease progression

Visual Acuity– Measured using the Sloan chart at 100%,

2.5%, and 1.25%– Contrast vision measured with both eyes, the

right eye, and the left eye

OCT– Used to measure optic nerve thickness

Our study consisted of 22 MS patients and 22 age-matched controls

Methodology GaitRite Pad 8 randomized walking trials per patient

– 4 in high illumination (> 80 candela) 2 with obstacles

– 1 with lenses and 1 without 2 without obstacles

– 1 with lenses and 1 without– 4 in dim illumination (< 4 candela)

2 with obstacles– 1 with lenses and 1 without

2 without obstacles– 1 with lenses and 1 without

– MEASUREMENTS Functional ambulation profile (FAP) Step number, normalized velocity, step length, step length

differential, stride length, and cadence

Significant Findings*Evaluated using paired T-testing

Poorer contrast visual acuity in MS patients– Measured using the Sloan chart– Significant difference at 100%, 2.5%, and 1.25%

MS patients had thinner optic nerves– Measured using OCT

Thinner optic nerves correlated negatively with visual acuity– Patients with thinner optic nerves (measured using OCT) had

poorer performance on the Sloan chart

Significant Findings Visual deficiency significantly degraded motor performance in dim

illumination– Especially seen with complicated walking (obstacles)– Significant differences seen in FAP, velocity, normalized velocity,

cadence, step length, and stride length– No deficiency seen in high illumination

Negative correlation between FAP and EDSS scores– MS patients with an EDSS score of 4 or less had significantly worse FAP

scores than those with a score of 4 or greater

Yellow lenses improved FAP scores of MS patients in dim illumination – Especially significant with complicated walking (obstacles)– No significant differences seen between MS patients and controls in dim

illumination with lenses

Conclusion Contrast sensitivity deficits degrade motor

performance in MS patients in dim illumination– These deficits are presumably the result of

optic neuropathy– MS patients have decreased FAP scores

Low FAP scores correlate highly with increased fall risk

High-contrast yellow lenses improve low-contrast vision in MS patients– These lenses increase obstacle discrimination,

and could potentially result in a reduction in risk of injury from falls

References Balcer LJ , Baier ML , Pelak VS , et al. (2000). New low-

contrast vision charts (reliability and test characteristics in patients with multiple sclerosis). Mult Scler. 6,163–171

Frohman, E. M., Fujimoto, J. G., Frohman, T. C., Calabresi, P. A., Cutter, G., & Balcer, L. J. (2008). Optical coherence tomography: a window into the mechanisms of multiple sclerosis. [10.1038/ncpneuro0950]. Nat Clin Pract Neuro, 4(12), 664-675.

FUNDING FOR THIS RESEARCH PROVIDED BY: FSU College of Medicine TMH Foundation

Contrast sensitivity Definition: Spacial contrast.

A physical dimension referring to the light dark transition at a border or an edge of an image that delineates the existence of a pattern or object.

Spacial Contrast

Contrast is expressed as a percentage from 0 to 100%. When contrast is 0% there is no edge between the two adjacent areas ie no pattern is physically present.

Spacial Contrast

For any value greater than 0%, an edge exists even though it may or may not be visible, depending on the image processing capabilities of the detector.

Contrast Sensitivity The amount of contrast a person

needs to see a target is called contrast threshold . In clinical research, it is expressed as contrast senstivity which is simply the reciprocal of threshold.

Visual Testing by SLOAN charts

Measure of visual acuity through standardized charts descending in contrast sensitivity – Begins with 100%

contrast to measure directive visual acuity

– 2.5% and 1.25% contrast used as a measure of low contrast sensitivity

Why Bother ?

CS may uncover a hidden dysfunction not apparent by other visual evaluations.

Optic neuritis Cerebral lesions Age related cataract

Why Bother?

Provides another visual parameter to monitor the impact of treatment

interventions. MS platform and novel therapies. Rasagaline

Why Bother?

Provides insights into the extent of functional performance problems.

Difficulties: mobility driving reading using tools

Parkinson’s and contrast sensitivity

What are the clinical implications of deficit in contrast sensitivity visual acuity in Parkinson’s disease?

Parkinson’s and CSVAHistory

Bodis Wolner (1987): Loss of spaciotemporal contrast sensitivity Frederick (1982): Dopaminergic amacrine neurons in human

retina Harnois: (1990): Decreased dopamine/metabolites in retina

in Parkinsonism Ikeda (1994): Electroretinographic evidence of retinal

dopamine deficiency Ghilardi (1988): Pattern ERG same in idiopathic PD and

monkey model Inzelberg (2004): OCT and retinal NFB thinning Hajee (2009): Inner retinal layer thinning ( Optovue )

History of PD Contrast Sensitivity

Contrast sensitivity is deficient in Parkinson’s Can be identified with CS wall charts

(Sheriff et al –NANOS 2009) Limited functional studies of effects on motor

performance:– Rizzo (2009):Driving under low-contrast

visibility conditions – Owsley (1987):The perception of “real world”

targets– Moes (2009):Contrast sensitivity, gait and

reading speed

Hypotheses1. Compared with controls, patients will

exhibit a deficiency in contrast sensitivity as measured with simple wall charts (SLOAN)

2. Patients walking performance will degrade significantly in low contrast conditions compared to controls

3. There will be a correlation between poorer performance on the SLOAN and walking performance in dim illumination.

ParkinsonismDemographics:

-51 Patients -30 Controls

-Mean Age: 70 -Mean Age: 65-Mean UPDRS: 24

***All on some dopaminergic medication; no anticholinergics with exception of Amantadine

Exclusions:-Inability to walk independently

Canes and walkers allowed-Known treated glaucoma or macular disease-VA < 20/50-Significant comorbid cardiovascular or neurologic disease-Dementia (MOCA)

• 8 Male• 22 Female

• 31 Male• 20 Female

Methodology A general neurologic examination including

standardized scoring for Parkinson’s severity (UPDRS)

Directive and contrast visual acuity tests utilizing SLOAN wall charts at 80 candela at 100%, 2.5%, 1.25% efficiency

Participants walked 18 feet on a gait pad measuring 102 parameters of gait (GAITRite) in randomized conditions of high and dim illumination.

Parkinson’s UPDRSII. ACTIVITIES OF DAILY LIVING (for both "on" and "off") 8. Handwriting0 = Normal.1 = Slightly slow or small.2 = Moderately slow or small; all words are legible.3 = Severely affected; not all words are legible.4 = The majority of words are not legible. 9. Cutting food and handling utensils0 = Normal.1 = Somewhat slow and clumsy, but no help needed.2 = Can cut most foods, although clumsy and slow; some help

needed.3 = Food must be cut by someone, but can still feed slowly.4 = Needs to be fed. 10. Dressing0 = Normal.1 = Somewhat slow, but no help needed.2 = Occasional assistance with buttoning, getting arms in

sleeves.3 = Considerable help required, but can do some things alone.4 = Helpless. 11. Hygiene0 = Normal.1 = Somewhat slow, but no help needed.2 = Needs help to shower or bathe; or very slow in hygienic

care.3 = Requires assistance for washing, brushing teeth, combing

hair, going to bathroom.4 = Foley catheter or other mechanical aids.

III. MOTOR EXAMINATION 

22. Rigidity (Judged on passive movement of major joints with patient relaxed in sitting position. Cogwheeling to be ignored.)

0 = Absent.1 = Slight or detectable only when activated by mirror or other

movements.2 = Mild to moderate.3 = Marked, but full range of motion easily achieved.4 = Severe, range of motion achieved with difficulty. 23. Finger Taps (Patient taps thumb with index finger in rapid

succession.)0 = Normal.1 = Mild slowing and/or reduction in amplitude.2 = Moderately impaired. Definite and early fatiguing. May have

occasional arrests in movement.3 = Severely impaired. Frequent hesitation in initiating movements

or arrests in ongoing movement.4 = Can barely perform the task. 24. Hand Movements (Patient opens and closes hands in rapid

succesion.)0 = Normal.1 = Mild slowing and/or reduction in amplitude.2 = Moderately impaired. Definite and early fatiguing. May have

occasional arrests in movement.3 = Severely impaired. Frequent hesitation in initiating movements

or arrests in ongoing movement.4 = Can barely perform the task. 

Parkinson’s GaitFunctional Ambulation Performance

(FAP) Scoring system that integrates

selected time and distance parameters to provide a single, numerical representation of gait

Consists of a linear relationship of step length/ leg length ratio to step time when velocity is normalized to leg length

GAITRITE SYSTEM

Measure the overall Functional Ambulatory Score (FAP) and its main parameters – Cadence– Velocity– Step Length– Step Time

SLOAN Contrast Sensitivity Comparison

100.00%

2.50%

1.25%

0 10 20 30 40 50 60 70

Pt vs Control OU Contrast Sensitivity

PatientControl

Number of Correct Letters

Cont

rast

%

P= 4.33E-05

P= 8.44E-06

P= 5.04E-05

Parkinson’s 100% SLOAN

40 50 60 70 80 90 1000

10

20

30

40

50

60

70

Pt vs Control 100% OU SLOAN

ControlLinear (Control)PatientLinear (Patient)

Age

Num

ber

of C

orre

ct L

ette

rs

Parkinson’s 2.5% SLOAN

40 50 60 70 80 90 10005

101520253035404550

Pt vs Control 2.5% SLOAN

ControlLinear (Control)PatientLinear (Patient)

Age

Num

ber

of C

orre

ct L

ette

rs

Parkinson’s 1.25% SLOAN

40 50 60 70 80 90 1000

5

10

15

20

25

30

35

40

45

Pt vs Control 1.25% SLOAN

ControlLinear (Control)PatientLinear (Patient)

Age

Num

ber

of C

orre

ct L

ette

rs

Parkinson’s Gait Data

LC Pt

LC C

HC Pt

HC C

0 10 20 30 40 50 60 70 80 90 100

PD FAP Pt vs Control

Series1

Avg FAP Score

Gai

t Tr

ial

P=2.35E-09

Parkinson’s GaitResults

– Confirms contrast sensitivity defects– Motor performance degrades in dim

illumination even in early stages of Parkinsonism

– Deficient contrast sensitivity heightens fall risk likely due to retinal dopamine deficiency

Parkinson’s and CS The clinical significance of a

degraded FAP score rests in well documented correlations between FAP and fall risk.

Parkinson’s patients fall at start and when cadence is interrupted.

Contrast sensitivity disrupts cadence.

Parkinson’s GaitResults

Plausible correlation between CS and FAP No correlation between CS and age No correlation between UPDRS and CS

– Might reflect discrepancy between part II and III of UPDRS

– Might reflect drug affect (peak/trough)

Two Questions1. What about yellow lenses?

– 39 patients vs 30 age matched controls

2. How early does CS deficiency develop in parkinsonism?

Lenses

No Lenses

70 75 80 85 90 95

LC FAP Pt vs Control

ControlPatient

FAP

• No statistical significance between control data

• Patient significance: p-value = 0.04