Visual Development & Amblyopia

1. Visual Development &Amblyopia Adler’s 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

2. Visual Development: Hierarchical Model of Vision

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

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

5. Visual Development: Temporal Acuity Precedes Spatial VEP Temporal Spatial Adult Adult 6 years psychophysically 4 years psychophysically

6. Visual Development: Response Latency Shows Rapid Change VEP 125 msec difference at 5 mo 50 msec difference in adults

7. Visual Development: OKN Asymmetry Improves rapidly over 6 mo Nasal precedes temporal DEM VEP

8. Visual Development: Vernier Acuity FPL FPL Sweep VEP (filled)

9. Visual Development: Binocular Vision FPL (open) VEP (solid)

10. 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

11. Facts and Figures Brain Weight: Doubles in 9 mo/90% by 6 yrCortical Thickness: V1 6 mo/parietal 12 yr/temporal 16 yrNeuronal Density: V1 5 mo/frontal 7 yrSynaptic Density: V1 peaks 4 mo then declines to 11yrfrontal peaks 1 yr then declines to 16yrCortical Metabolism: Peaks 4 yr then declines to 15yr White Matter: Peaks 2 yr and continues to 30 yrsRegionally Specific and Non-Linear

12. Gross Cortical Development lissencephalic

13. Regionally Specific Growth Ages 5-11 loss 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.

14. Visual Behaviors Follow Distinct Time Courses Critical periods

15. Visual Cortex Development: Multiple Stages Light Light First Binocular Stage

16. Visual Cortex Development: Retinal Waves Serve to fine tune local specificy For eye of origin, retinotopy, on/off

17. Visual Cortex Development: Retinogeniculate Prenatal, uses Spontaneous activity

18. Visual Cortex Development: Geniculocortical Postnatal, experience dependent

19. Visual Cortex Development: Ocular Dominance Layer 4c

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

21. Visual Cortex Development: Postnatal Development of ODC

22. Visual Cortex Development: Competitive Model Competition, with ‘ a little help from your friends’

23. Visual Cortex Development: Competitive Model Normal Development Monoc. Deprivation present at birth X X X X X Layer 4c Normally, it is useful to be able to fine tune eye alignment after birth

24. Visual Cortex Development: Three-Eyed Frog Tectum Columns seem to be a general consequence of competition for connections

25. Visual Cortex Development: Spontaneous Activity Correlated neural activity is important

26. Visual Cortex Development: Cooperative Model Hebb’s Rule ‘winner-take-all’ cooperation between similar inputs in a positive feedback cycle

27. Visual Cortex Development: Mechanism for Cooperation/Competition Neurotransmitter Postsynaptic target cell Neural growth factor

28. Developmental Plasticity: Monocular Deprivation * Retina and LGN quite normal * Actually more severe than binocular deprivation * Minimal effect if done to adults

29. Developmental Plasticity: Experimental Strabismus ODC sharper than normal No binocular integration

30. Developmental Plasticity: Cytochrome Oxidase Weak Fixation Preference Strong Fixation Preference

31. Developmental Plasticity: Summary for Review This is for layer 4c

32. 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

33. Visual Deficits in Amblyopia • 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 • Moderate deficits in object segmentation/recognition and spatial localization • Severe deficits in binocular interactions Contrast Sensitivity Spatial Frequency

34. 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

35. 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’

36. 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

37. Site of abnormality

38. Primary visual cortex and beyond • Loss of disparity sensitivity and binocular suppression in V1 (primary visual cortex) • Although loss in V1 can’t 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.

39. Current Issues • Abiding debate about how the strabismic and anisometropicsubtypes 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.

40. Hypothesis • Impairment in binocular functions may predict the pattern of monocular deficits, and thereby help explain the mechanisms (McKee, Movshon & Levi, 2003).

41. Subjects • 20 adults (age 19-35) Most Subjects have a history of patch treatment in their childhood. Complete ophthalmologic examination was done to confirm diagnosis

42. General Methods • Seven psychophysical Tests • Monocular Tests • Binocular Tests Amblyopic and fellow eye of amblyopic subjects tested separately Stronger and weaker eye of normal subjects tested separately 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.

43. Experiments • Monocular tests • Snellen acuity • Grating acuity • Vernier acuity • Contrast sensitivity • Binocular tests • Randot stereotest • Binocular motion integration • Binocular contrast integration

44. 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.

45. 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

46. Hyperacuity photoreceptor = • www.cnl.salk.edu/~thomas/ vernier.html

47. Binocular Tests - Methods Dichoptic Stimulation with Avotec Eye Tracking with Avotec/SMI System

48. Stimulus Alignment Via Perceptual Report

49. Stimulus Alignment Via Fovea Reflex Dual Eye Tracking Alternate Cover Test

50. Summary - Binocular Functions • Stereopsis • Reduced in amblyopes, especially strabismics • Binocular motion integration • Binocular perception impaired in amblyopes, especially strabismics