Visual Development & Amblyopia Adlers Physiology of the

Visual Development & Amblyopia Adlers Physiology of the

Visual Development & Amblyopia Adlers Physiology of the Eye 10th Ed. Chapter 21- Development of Vision in Infancy Chapter 27 - Activity-Dependent Development of Retinogeniculate Projections Chapter 31 - Visual Deprivation Human Amblyopia - Some current issues Visual Development: Hierarchical Model of Vision

Visual Development: Development of Contrast Sensitivity Peak temporal frequency (low spatial frequency) VEP DEM FPL

Visual Development: Development of Contrast Sensitivity Peak spatial frequency (low temporal frequency) Sweep VEP Grating Acuity Visual Development:

Temporal Acuity Precedes Spatial VEP Temporal Spatial Adult Adult 4 years

psychophysically 6 years psychophysically Visual Development: Response Latency Shows Rapid Change VEP 125 msec difference at 5 mo

50 msec difference in adults Visual Development: OKN Asymmetry Nasal precedes temporal Improves rapidly over 6 mo DEM VEP

Visual Development: Vernier Acuity FPL FPL Sweep VEP (filled) Visual Development: Binocular Vision

FPL (open) VEP (solid) Visual Development: Binocular Vision FPL Global stereopsis emerges at 3-5 mo

Global stereopsis improves 8 fold in first year Protracted development of adult values Facts and Figures Brain Weight: Doubles in 9 mo/90% by 6 yr

Cortical Thickness: Neuronal Density: V1 6 mo/parietal 12 yr/temporal 16 yr V1 5 mo/frontal 7 yr Synaptic Density: V1 peaks 4 mo then declines to 11yr frontal peaks 1 yr then declines to 16yr

Cortical Metabolism: Peaks 4 yr then declines to 15yr White Matter: Peaks 2 yr and continues to 30 yrs Regionally Specific and Non-Linear Gross Cortical Development lissencephalic

Regionally Specific Growth loss Ages 5-11 gain Sowell ER, Thompson PM, Leonard CM, Welcome SE, Kan E, Toga AW.

Longitudinal mapping of cortical thickness and brain growth in normal children. J Neurosci. 2004 Sep 22;24(38):8223-31. Visual Behaviors Follow Distinct Time Courses Critical periods Visual Cortex Development: Multiple Stages

Light Light First Binocular Stage Visual Cortex Development: Retinal Waves

Serve to fine tune local specificy For eye of origin, retinotopy, on/off Visual Cortex Development: Retinogeniculate Prenatal, uses Spontaneous activity Visual Cortex Development:

Geniculocortical Postnatal, experience dependent Visual Cortex Development: Ocular Dominance Layer 4c

Visual Cortex Development: Ocular Dominance Columns In normal development each eye acquires an equal amount of territory Visual Cortex Development: Postnatal Development of ODC

Visual Cortex Development: Competitive Model Competition, with a little help from your friends Visual Cortex Development: Competitive Model Normal Development

Monoc. Deprivation present at birth X X X

X Layer 4c Normally, it is useful to be able to fine tune eye alignment after birth X Visual Cortex Development: Three-Eyed Frog Tectum

Columns seem to be a general consequence of competition for connections Visual Cortex Development: Spontaneous Activity Correlated neural activity is important

Visual Cortex Development: Cooperative Model Hebbs Rule winner-take-all cooperation between similar inputs in a positive feedback cycle Visual Cortex Development:

Mechanism for Cooperation/Competition Neurotransmitter Postsynaptic target cell Neural growth factor Developmental Plasticity: Monocular Deprivation

* Retina and LGN quite normal * Actually more severe than binocular deprivation * Minimal effect if done to adults Developmental Plasticity: Experimental Strabismus ODC sharper than normal

No binocular integration Developmental Plasticity: Cytochrome Oxidase Weak Fixation Preference Strong Fixation Preference Developmental Plasticity:

Summary for Review This is for layer 4c Human Amblyopia Lazy Eye

Relatively common developmental visual disorder Reduced visual acuity in an otherwise healthy and properly corrected eye

Associated with interruption of normal early visual experience Affects at least 2% of North American population Most common cause of vision loss in children

Well characterized behaviorally, not neurologically Treated by patching in children Visual Deficits in Amblyopia Reduced visual acuity - defining feature

Impaired contrast sensitivity Prominent at high spatial frequencies Central visual field is generally most affected Contrast Sensitivity

Usually 20/30 - 20/60 Spatial Frequency Moderate deficits in object segmentation/recognition and spatial localization Severe deficits in binocular interactions Subtypes of Amblyopia

Anisometropic Unequal refractive error between the two eyes Strabismic Deviated eye that may or may not have unbalanced refraction Deprivation Congenital cataract; corneal opacity; eyelid masses

Mechanisms of Amblyopia 1. Form deprivation Sharp image is not formed at the retina 2. Abnormal binocular vision

Binocularity is often changed or lost in amblyopia Suppression may be necessary to avoid double vision Models of Amblyopia Competition hypothesis originated with experiments in kittens in the 1960s by Hubel and Wiesel Monocular deprivation of retinal input during critical

developmental periods leads to striking abnormalities in the physiology of visual cortical neurons Binocular deprivation actually leads to less severe abnormalities Amblyopia may be a form of activity-dependent deprivation, modulated by competitive interactions Site of abnormality Primary visual cortex and beyond

Loss of disparity sensitivity and binocular suppression in V1 (primary visual cortex) Although loss in V1 cant explain the full abnormality - extrastriate is implicated. Barnes et al. showed with fMRI abnormalities in many visual areas beyond V1. Hypothesized that feedback connections from extrastriate

to V1 may be a primary source of abnormality. Current Issues Abiding debate about how the strabismic and anisometropic subtypes differ from each other. Chicken and egg situation : Is amblyopia a consequence or a cause of strabismus/ anisometropia ? The relationship between performance on monocular versus binocular tests has not been well-studied.

Hypothesis Impairment in binocular functions may predict the pattern of monocular deficits, and thereby help explain the mechanisms (McKee, Movshon & Levi, 2003). Subjects 20 adults (age 19-35) N

Age Years of education Near acuity normal or fellow

Near acuity amblyopia Control 7 25.1 13.7

20/18 - Strabismics 6 26.3

13.5 20/20 61*^ Anisometropes 7

28 14.9 20/23 61*^ Most Subjects have a history of patch treatment in their childhood.

Complete ophthalmologic examination was done to confirm diagnosis General Methods Seven psychophysical Tests Monocular Tests Amblyopic and fellow eye of amblyopic subjects tested separately Stronger and weaker eye of normal subjects tested separately Binocular Tests Both eyes tested simultaneously - required careful stimulus alignment

It is difficult to achieve precise alignment of stimuli in the two eyes, and we pioneered new methods for achieving this using methods that are compatible with fMRI. Experiments Monocular tests

Snellen acuity Grating acuity Vernier acuity Contrast sensitivity Binocular tests Randot stereotest Binocular motion integration

Binocular contrast integration Summary - Monocular Functions Amblyopic eyes showed a deficit for all the monocular functions tested. Strabismic amblyopes are distinguished from anisometropic amblyopes by their severe loss of Vernier acuity. Vernier acuity

Measures the relative position of an object Much finer than Snellen or grating acuity (6-10 arc-sec of visual angle) In our normal subjects Vernier is 12 times better than grating acuity A type of hyperacuity Hyperacuity

photoreceptor = www.cnl.salk.edu/~thomas/ vernier.html Binocular Tests - Methods Dichoptic Stimulation with Avotec Eye Tracking with Avotec/SMI

System Stimulus Alignment Via Perceptual Report Stimulus Alignment Via Fovea Reflex Dual Eye Tracking Alternate Cover Test Summary - Binocular Functions

Stereopsis Reduced in amblyopes, especially strabismics Binocular motion integration Binocular perception impaired in amblyopes, especially strabismics Can binocularity predict Vernier acuity?

Re-classification We reclassified amblyopes based on binocular properties. A simple pass/fail criterion was used to classify. The subjects who passed both randot stereoacuity test and binocular motion integration were assigned binocular (33% strabismics and 57% anisometropes passed the criteria). Those who couldnt pass were assigned non-binocular Result

Deficits in Vernier acuity are much more severe in non-binocular group as compared to binocular. Performance in non-binocular subgroup can not be predicted the by snellen/grating acuities - suggesting additional factors. Implications Vernier performance is better predicted by residual binocularity than by clinical subtype.

Interocular suppression may be an important etiological factor in the development of amblyopia (e.g., Sireteanu, 1980; Agrawal et al., 2006). Future Directions fMRI experiments that study amblyopic binocular suppression directly, perhaps in comparison with binocular rivalry in normal subjects.

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