Visual Development Amblyopia Adlers Physiology of the Eye
Visual Development & Amblyopia Adler’s Physiology of the Eye 10 th 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 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 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: V 1 6 mo/parietal 12 yr/temporal 16 yr V 1 5 mo/frontal 7 yr Synaptic Density: V 1 peaks 4 mo then declines to 11 yr frontal peaks 1 yr then declines to 16 yr Cortical Metabolism: Peaks 4 yr then declines to 15 yr 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 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 4 c
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 Layer 4 c 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 Hebb’s 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 4 c
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
• Reduced visual acuity - defining feature – Usually 20/30 - 20/60 – • Impaired contrast sensitivity – Prominent at high – spatial frequencies – Central visual field is generally most affected Contrast Sensitivity Visual Deficits in Amblyopia 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 1960 s 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 V 1 (primary visual cortex) • Although loss in V 1 can’t explain the full abnormality - extrastriate is implicated. • Barnes et al. showed with f. MRI abnormalities in many visual areas beyond V 1. Hypothesized that feedback connections from extrastriate to V 1 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 (Mc. Kee, 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 f. MRI.
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 couldn’t 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 • f. MRI experiments that study amblyopic binocular suppression directly, perhaps in comparison with binocular rivalry in normal subjects.
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