Developmental Visual Deprivation

Perceptual deficits

All binocular functions including local/global stereopsis and binocular summation of contrast sensitivity are severely compromised or lost following early monocular form deprivation. ^, The visual sensitivity of the deprived eye is dramatically reduced or virtually lost, form deprivation amblyopia ( Fig. 40.1A ). Importantly, the severity of the contrast sensitivity loss resulting from monocular form deprivation is directly related to the degree of retinal image degradation during early infancy ( Fig. 40.1B ).

Monocular deprivation also leads to an abnormal elongation of the eyes, hence, the development of myopic refractive errors. The deleterious effects of early monocular deprivation on spatial vision development are generally far more severe than the anomalies resulting from form deprivation in both eyes, bilateral form deprivation ( Fig. 40.2 ). ^, As in monkeys with monocular form deprivation, bilateral form deprivation leads to a significant loss of binocular functions including the detection of stereoscopic cues and binocular summation of contrast sensitivity ( Fig. 40.2 ). In these binocularly deprived monkeys, the binocular contrast sensitivity function (square symbols) overlaps with the better monocular sensitivity function (open circles).

Neural changes

The most consistent effect of early monocular form deprivation on development is anomalous changes in the ocular dominance distribution of V1 neurons ( ocular dominance plasticity ). During the critical period of development, the afferent fibers from the LGN representing the two eyes compete for consolidation of functional connections in V1 ( binocular competition ). ^, This early binocular competition is activity dependent; hence, depriving normal signals from one eye puts the affected eye into a competitive disadvantage and leads to a severe loss of functional connections in V1 from the deprived eye. The ocular dominance columns of the input layer in V1 (layer IVC) representing the deprived eye exhibit a substantial shrinkage. The axon arbors of the afferent fibers from the LGN in the deprived columns show abnormal structural changes and the intrinsic long-range horizontal connections extending over multiple ocular dominance columns reorganize their wiring pattern in the cat primary visual cortex. ^,

Electrophysiological studies consistently report the severe loss of binocularly driven cells, i.e. neurons that can be activated by stimulation of either eye. In addition, there is a clear shift in the ocular dominance distribution of cortical neurons away from the deprived eye. Specifically, the percentage of V1 neurons that can be activated or dominated by stimulation of the deprived eye is significantly decreased ( Fig. 40.3 ). The reduced functional innervation from the deprived eye is, at least in part, the neural basis for “undersampling” of visual scenes by the affected eye in form deprivation amblyopia.

For subcortical structures, there is a mild shrinkage of cell bodies of LGN neurons that receive input signals from the deprived eye. However, the response properties of these primate LGN neurons are largely unaffected by early monocular form deprivation. Interestingly, there is considerable evidence for functional alterations in the cat LGN due to early abnormal visual experience. For the primate retina there are no significant structural or functional abnormalities due to early monocular form deprivation. Together, major neural changes resulting from early monocular form deprivations in primates occur beyond the LGN, i.e. begins in the primary visual cortex.

Alternating monocular deprivation

Daily alternations of form deprivation between the two eyes have very little impact on the perceptual development of either eye in cats. ^, Consistent with this observation, the spatial receptive-field properties such as orientation selectivity are normal. However, the same daily alternating deprivation devastates the development of binocular vision. Local stereopsis is lost and the proportion of binocularly driven neurons in area 17 is severely reduced. In monkeys, daily alternating monocular occlusion beginning at birth leads to a variety of abnormal eye positions and eye movements including strabismus and/or saccadic disconjugacy, i.e. the amplitudes of saccades in the occluded eye are less than that in the viewing eye. ^,

Reverse occlusion

The effects of constant form deprivation in one eye, including spatial contrast sensitivity loss and ocular dominance shift in V1 away from the deprived eye, can be reversed if vision of the originally deprived eye is restored early in development and the fellow non-deprived eye is occluded, reverse occlusion ^, ( Fig. 40.4 ). The timing of the reverse occlusion is critical in determining the effectiveness of this procedure because the “recovery” of functions in the originally deprived eye may occur at the expense of the originally non-deprived eye. For example, contrast sensitivity can be restored if reverse occlusion occurs relatively early in the critical period, i.e. if the original deprivation is short. However, this early reversal leads to a loss of contrast sensitivity in the newly deprived (or originally non-deprived) eye (red circles in Fig. 40.4A ) and causes a corresponding shift in the ocular dominance distribution of V1 neurons favoring the initially deprived eye. There is an optimal time for the reversal of monocular occlusion in order to achieve near normal contrast sensitivity for both eyes ( Fig. 40.4B ). ^, In all cases, the binocular functions are diminished. Similar effects of reverse occlusion have been extensively studied in cats, and the results have contributed in advancing our understanding of the neural mechanisms underlying the breakdown and recovery of visual functions from early monocular form deprivation.

The clinical significance of these findings is that this kind of animal study can provide key information for developing an effective clinical strategy for treating amblyopia with various patching regimens .

Brief unrestricted vision during monocular deprivation

Providing brief daily periods of normal vision to the deprived eye during early monocular deprivation prevents or reduces the severity of form deprivation amblyopia in monkeys ( Fig. 40.5A ). Constant form deprivation (0 hour of unrestricted vision), as previously described, causes severe amblyopia of the deprived eye and a large shift in the ocular dominance of V1 neurons away from the deprived eye ( Fig. 40.5B ). However, only one hour of unrestricted (normal) vision every day during the deprivation period (12 hours/day) dramatically improves the contrast sensitivity of the deprived eye, hence reducing the severity of form deprivation amblyopia. In these monkeys the extent of abnormal ocular dominance shift in V1 is significantly reduced ( Fig. 40.5B ). In stark contrast, the same “preventive” measure, even with 4 hours of daily unrestricted vision during the 12-hour deprivation period, does not prevent a severe loss of disparity sensitive neurons, highlighting the extremely fragile nature of developing binocular connections in V1. However, one hour of unrestricted vision is effective in reducing binocular suppression in V1 (i.e. the binocular responses of V1 neurons are less than monocular responses) that is prevalent in monkeys reared with constant form deprivation ( Fig. 40.5C ).

Constant monocular form deprivation leads to an elongation of the eye, and hence, the development of myopic refractive errors in the deprived eye. However, a brief period of unrestricted vision during the deprivation period reduces the degree of myopic refractive error.

The clinical relevance of these studies is that the timely removal of the conditions that produce degradation of images or image occlusion (e.g. severe hyperopic anisometropia, cataract, or ptosis) is critically important for the prevention of amblyopia. If that is not immediately possible, stop-gap manipulations such as lifting a drooping eyelid or keeping corrective lenses even for a short period of time every day are likely to have preventive effects against form deprivation amblyopia and development of myopic refractive errors. Taken together, studies of this kind and those on the effects of temporal variations in image quality, e.g. alternating or reverse occlusion, can provide key information in developing effective clinical strategies for the management of amblyopia in human infants. ^,