APRECIACIÓN DEL COMPONENTE ESTRATÉGICO DE LOS

development. It is derived from the Greek word for 'dullness of vision' and may be unilateral or bilateral. Von Noorden (1974) proposed a classification of amblyopia based on developmental factors. The main subgroups based on his classification were amblyopia occurring in association with strabismus, anisometropia and form vision deprivation.

Strabismic amblyopia is thought to develop as an adaptive mechanism against visual conflict caused by diplopia and overlap of mis-aligned images. In anisometropic amblyopia, the images falling on the two foveae originate from the same visual object, however, they are of different sharpness, or if the refractive error is corrected, of different size (aniseikonia). The dissimilarity between the two foveal images is incompatible with foveal fusion, and the adaptive mechanism is to suppress the image at the cortical level from one eye (usually the more ametropic eye). Form vision deprivation amblyopia occurs as a result of deprivation of normal visual experience early in life. This most commonly is due to comeal opacities, congenital cataracts, ptosis or other visual obstacles to normal retinal stimulation. The amblyopia is more severe after unilateral than after bilateral visual deprivation.

Clinical observations indicate plasticity associated with maturation of the visual process. It is during the maturational period for stereopsis that the young strabismic patient has the neural plasticity of sensory adaptation. After the age of about 9 years, suppression of vision from the amblyopic eye does not occur and patients can suffer persistent double vision. Thus visual abnormalities that have their onset in the first few months of life have the capability of being partly or wholly reversed, but for a limited period only (so called the critical or sensitive period).

The accepted treatment for amblyopia is occlusion of the fellow, better vision eye; thereby encouraging visual improvement in the weaker amblyopic eye. The best acuity results tend to be achieved by children who are occluded before the age of 4 years. The

treatment is less effective between 4 and 9 years of age and relatively ineffective after the age of 9 years. A possible complication of early patching is the development of occlusion amblyopia in the better vision eye, however this is usually reversible.

There have been numerous psychophysical studies of amblyopes to investigate their subnormal visual performance. For example, amblyopes commonly have elevated contrast thresholds for grating detection (Hess and Howell, 1977; Levi and Harwerth, 1977; Bradley and Freeman, 1981, Holpigian et al., 1986) and poor vernier acuity (Levi and Klein, 1982; Bradley and Freeman, 1985). Psychophysical investigations of amblyopic subjects (e.g. using random dot stereograms) have demonstrated impaired stereopsis, and other aspects of binocularity (e.g. Cooper and Feldman, 1978; Henson and Williams; 1980; Schor et al.,

1983; Holopigian et al., 1986).

6.1.3 Neuro-anatomical and physiological basis of amblyopia

Much of our knowledge conceming basic physiological mechanisms in amblyopia have been derived from experimental studies, single unit electrophysiological recordings and neurohistological studies, mainly in cat and monkey.

During the first months after birth, binocular connections are very vulnerable and can be dismpted by visual inequalities between the two eyes. In experiments involving lid suturing at an early age, Hubei and Wiesel (1963) found that very few cortical cells were driven by the sutured eye, with the great majority being activated by the unsutured eye. Binocular deprivation caused less disruption of cortical connections than did monocular deprivation, and binocularity still persisted.

Hubei & Wiesel (1965) produced divergent squints in kittens by sectioning the medial rectus muscle in one eye at about 8-10 days after birth. Single cell recordings revealed that there was a severe decline in the number of cells in striate area 17 that were driven from

both eyes. They concluded that this loss was due, not to loss of cells but rather to changes in the overall ocular dominance distribution. It was apparently the lack of synergy between the afferents from the two eyes that caused the ocular dominance of the cells to change with an overall increase in the numbers in monocularly driven cortical cells. Despite the marked loss o f binocular activation by neurons in area 17, the cats with divergent squint showed no behavioural abnormalities suggestive of defective vision. It is presumed that this was because the squint was divergent and the cats developed the ability to fixate with either eye alternately.

Ikeda et al (1974) suggested that it is particularly the sustained retinal neurons that have been deprived from adequate stimulation during early development, and the sustained pathway becomes less effective. Ikeda and Tremain (1978, 1979, 1980) studied the sustained X cells in the area centralis of the retina and the binocular properties of visual cortical cells in control cats and in cats reared with divergent or convergent squint of one eye, or defocused with atropine in one or both eyes. Recordings were made from both the striate cortex, to give an estimate of the proportion of binocularly innervated cortical cells, and from the lateral geniculate nucleus so as to compare the spatial resolving power (acuities) of geniculate neurons receiving their input from the normal retina with that of cells stimulated by the equivalent area of the retina in the squinting eye. Poor responsiveness of X cells was found only in the amblyopic deviating eye. These sustained X cells showed poor contrast sensitivity. Analysis of the sensitivity loss at different spatial frequencies showed that the higher spatial frequencies showed the greatest deficits - a result similar to that found for strabismic amblyopia in humans. In the atropinized kittens, Ikeda & Tremain (1980) simulated the effects of anisometopia. Atropine dilates the pupil and paralyses accommodation, so that the image received is blurred. Atropinized eyes produced less intense responsiveness by the sustained X cells in the area centralis. These results indicated

that amblyopia occurred in the esotropic eye when there was no alternating fixation, and in all atropinized eyes. Comparison of the number of cells driven by each eye showed that in normals the numbers were very similar as they were in cats with convergent or divergent squints with alternating fixation and no amblyopia. But in cats with amblyopia, the number of cortical cells driven by the normal eye was greater than that driven by the amblyopic eye.

Ikeda and Tremain (1978) and Ikeda and W right (1976) proposed that protracted exposure of the fovea or area centralis to defocused images during the sensitive period is the common factor responsible for the effects of visual deprivation and strabismus. They argue that the defocused image provides an inappropriate stimulus for sustained ganglion cells in the central retina. The weak (or absent) firing of these ganglion cells leads to retarded or arrested growth of LGN cells. The geniculate cells therefore lose normal contrast sensitivity and visual acuity response properties. The inadequate growth and development of the geniculate cells leads to a deficiency in the normal development of the axon terminals at the visual cortex thus allowing input from the normal eye to dominate.

Macaque monkeys appear to have a similar visual system to that of humans and many studies have now used the monkey to provide a closer model. Blakemore, Garey and Vital- Durand (1978), and Crawford et al (1975), studied macaque monkeys and noted that monocular lid suture at about 4 weeks of age for periods of 2 to 4 weeks, caused a marked shift in ocular dominance towards the non-deprived eye at all layers of the striate cortex. Extension of the period of deprivation accentuates the shift in eye dominance, and, with prolonged monocular deprivation for the first two years of life, dominance by the normal eye is virtually complete. When the start of monocular deprivation is delayed until 11 to 16 months of age, there is no detectable influence on layer IVC, but outside IVC there still appears to be a small shift in ocular dominance. Prolonged deprivation in adults has no detectable effect.

Work by Von-Noorden (1970), Baker et al (1974) and Hubei et al (1977), have shown that prolonged monocular lid suturing in monkeys, during the first few weeks of life, leads to cell shrinkage in the layers of the LGN associated with the deprived eye. Furthermore a clear change in the relative sizes of the ocular dominance strips in layer IVC, with a shrinkage of stripes receiving input from the deprived eye and a corresponding expansion of those associated with the normal eye also occurs. These changes appear more marked when deprivation is instigated at 2 weeks of age rather than later.

Many factors have been proposed to account for the effects of visual deprivation. It has been postulated that during the critical period the afferent paths from the two eyes compete for control over cortical cells (Guillery, 1972, 1973; Wiesel & Hubei 1965, Hubei et al, 1977). Geniculocortical axons arising from adjacent laminae are thought to compete for synaptic access to binocular cortical neurones. Unilateral visual deprivation upsets this balance of competition and the reduced cell growth in the LGN is a consequence of the unbalanced axonal development and the smaller numbers of active synapses made by each axon. Hubei et al (1977) have suggested that the same competition mechanism may also explain the deprivation effects that occur in layer IV. The end result of deprivation depends on the amount of overlap of the terminals that still existed at the time of eye closure. This explains the greater severity of the effects of early closures and indicates that once the process of segregation is complete, eye closure will have little or no effect. This competition hypothesis predicts that bilateral lid suture should be less effective than monocular lid suture, since in the former case all the geniculate laminae would be deprived equally.

Sloper (1987) questioned the assumption that cells related to the open, normal eye are unaffected by the closure of the other eye. He compared the sizes of cells of both deprived and undeprived laminae of experimental animals with corresponding LGN cells in normal animals. The LGN in rhesus monkey consists of 6 laminae of which the inner two

consist of larger cells (magnocellular laminae) compared with the outer four laminae which contain smaller cells (the parvocellular laminae). These two sets of cells have been found to react differently to visual deprivation under certain conditions (Schiller and Colby, 1983; Shapley et al., 1980; Sloper, 1987). Sloper found that the initial effect on LGN cells following monocular lid closure at birth was not shrinkage of deprived parvocellular cells, but enlargement of cells in the undeprived laminae. This hypertrophy was responsible for the apparent difference in size seen between deprived and undeprived parvocellular cells. Less hypertrophy occurs in magnocellular laminae. The increased size of the undeprived parvocellular cells is maintained until about 8 weeks of age, when the undeprived parvocellular cells shrink back to normal size. However, the deprived parvocellular cells now also shrink in parallel and so little change in relative size is apparent. By 3 months of age the undeprived cells are of normal size and the deprived cells are very shrunken. This parallel shrinkage has not been seen in the magnocellular cells.