perhaps it is more important to recognize that patients with MFS indeed have binocular correspondence, rather than how we label that correspondence. Either way, as discussed earlier, animal studies are beginning to reveal a possible anatomical basis for the clinical observations described in MFS. Until these anomalous neural connections can be shown in a human subject with the clinical features of MFS, the debate remains unresolved.

4.3MFS with Manifest Strabismus

The majority of patients with MFS have a manifest strabismus, and esotropia is the most prevalent form by a wide margin. The prevalence of micro-esotropia in several large series of primary and secondary MFS has been reported from 61 to 90% [1, 15]. MFS with small angle exotropia is less common, occurring in 8–21% [1, 15, 16]. The prevalence of MFS associated with small angle vertical strabismus is extremely low at 0–3% in large series [1, 15, 16]. Choi and Isenberg described 40 cases of MFS with a vertical tropia; however, the prevalence of this variety of MFS cannot be determined from their report [17].

4.3.1Esotropia is the Most Common Form of MFS

Apparently, monofixation can be achieved and maintained with any type of strabismus. However, the esotropic variety of MFS is so prevalent it is unlikely that this occurs by chance. New evidence suggests that a convergent deviation may be the default position if orthotropia with bifixation is not possible [6].

As discussed in Sect. 4.2, studies comparing normal and strabismic monkeys have found that an early onset unrepaired strabismus will deplete the supply of binocular connections in area V1, as well as cause low metabolic activity (suppression) in ocular dominance columns corresponding to the deviating eye [3, 6, 18]. Binocular processing begins in the layers above and below input layer 4 of area V1 in the striate cortex, but continues in several di erent populations of binocular cells within and beyond area V1 that are sensitive to either relative or absolute retinal image disparity. These cell groups give rise to stereopsis or fusional vergence, respectively [19]. Vergence neurons sensitive to crossed disparity (convergence) appear to be naturally more numerous than those coding for uncrossed disparity (divergence) in normal monkeys [6]. It is possible that more convergence neurons survive the early insult simply because there is a preponderance of them to begin with.

The timing of the insult is probably also contributory to the prevalence of small angle esotropia in MFS. Eye

alignment and fusional vergence is immature in neonates, but more often results in transient over-convergence as opposed to over-divergence [20]. Pathways for nasally directed pursuit are more developed at birth compared with those for temporally directed pursuit. Interruption of maturation due to an insult such as early-onset,unrepaired strabismus, leads to permanent monocular naso-temporal pursuit asymmetry [21]. It may also lead to latent nystagmus, which typically features a pathologic nasally directed pursuit movement of the fixating eye, followed by a physiologic temporal-ward refixation saccade [18]. These motor findings associated with infantile esotropia seem to suggest that the infant visual system is biased to convergent alignment when normal development is interrupted.

4.3.2Esotropia Allows for Better Binocular Vision

Fusion and stereopsis may be more likely to develop if the ocular deviation is less than 9D though presumably, the greater the number of cortical neurons necessary to link nonadjacent ocular dominance columns, the poorer the quality of the resulting binocular vision. Deviations up to 20D have been shown to support peripheral sensory fusion [14], if not stereopsis, so it is no surprise that peripheral fusion is a feature of MFS. However, in a recent study, the maximum angle of horizontal strabismus consistent with true stereopsis was found to be only 4D [16], which happens to correspond with the approximate length of one cortical neuron.

The maximum angle of strabismus that still allows for fusional vergence is not yet known,though the most robust convergence response to binocular image disparity in monkeys with MFS occurs at 4.0–4.5D of crossed disparity [22], once again corresponding with the length of the average cortical neuron. The motor fusion amplitudes of human subjects with MFS have been found to be within the normal range by some [1, 13, 23], and present but subnormal by others [24]. Though patients with MFS often have fusional vergence su cient to overcome small angles of strabismus, most patients with MFS maintain a manifest strabismus. The logical conclusion is that, in patients with MFS, there is a greater functional benefit to keeping the eyes slightly misaligned, particularly on the esotropic side.

MFS with esotropia di ers slightly from MFS with exoor hypertropia. Not only is it more common, but it is the form that allows for the best binocular vision. In a large series, the micro-ET group out-performed the other two alignment categories by a wide margin in each of the three sensory categories: sensory fusion, motor fusion, and stereopsis [15]. The most striking di erence in the sensory exam was found in the motor fusion category.