Both primary and secondary micro-esotropes were significantly more likely to have disparity vergence than the exotropes or hypertropes.

Why might binocular vision be better in MFS with

4esotropia? In esotropia, the fovea of the fixating eye must communicate with a nonfoveal point on the nasal retina of the deviating eye to achieve fusion. In exotropia, the fixating fovea must link with a point on the temporal retina of the deviating eye. However, not all areas of the retina are created equal. Temporal retina is at a competitive disadvantage, even in the normal, nonstrabismic visual system. Cones and ganglion cells are 1.5-fold less numerous in the temporal retina [25–28]. LGN layers receiving input from the ipsilateral temporal retina have fewer cells and less volume [29].And in the visual cortex, temporal ocular dominance columns occupy less territory than nasal columns, with the di erence increasing dramatically with retinal eccentricity [30]. Temporal retina matures slower than nasal retina in normal human infants [31]. Spatial resolution and vernier acuity are poorer in the temporal retina of normal eyes [32–34]. The critical period for the development of the temporal retina and its connections in the visual cortex begins later and takes longer to complete than that for nasal retina [31]. And finally, the neural mechanisms underlying disparity detection from uncrossed disparity (as would occur in exotropia) are naturally more sensitive to image decorrelation than those from crossed disparity [35]. If the critical period is interrupted by strabismus, the temporal retina should be selectively penalized, potentially magnifying the anatomic and physiological asymmetry.

This presents a particular problem for exotropia. If inputs from the temporal retina are less numerous, delayed in development, relatively suppressed, and more vulnerable to the deleterious e ects of image decorrelation, the foveal cortical neurons of the dominant eye would have comparatively few neurons from the deviated eye with which to work. The larger the angle of exotropia, the fewer are the temporal cortical neurons available to link with the columns of the dominant eye because of the increase in the ratio of dominance with retinal eccentricity. The relative suppression of these temporal neurons may result in poor quality communication, even if a link could be established.

4.3.3Esotropia is the Most Stable Form

Good binocular vision is associated with stability, but does not guarantee lasting alignment. Studies have found that stability of alignment in microtropia is not permanent,

even in the presence of high-quality binocular vision [15, 36, 37]. Twenty-four to 26% of MFS cases deteriorate over a period of 5.5–17.5 years [15, 36, 37]. In these studies, deterioration was not the result of loss of sensory status. Following treatment, 48–80% of subjects were able to regain monofixation status.

Stability of MFS with exoor hypertropia appears to be more vulnerable to insults to the visual system such as dense amblyopia or a significant change in the refractive error over time [15]. Dense amblyopia appears to be disruptive to an already fragile binocular connection in exotropia, and may contribute to instability in the majority of exotropic patients. Drastic changes in refractive error in MFS with exotropia appear to have a similar destabilizing e ect. Neither of these factors appears to have an e ect on long-term stability in micro-esotropia, however.

Instability of alignment in MFS is also associated with the presence of vertically incomitant horizontal strabismus, oblique dysfunction, and a history of large-angle infantile esotropia. Micro-esotropes were statistically less likely to have a history of any of these associated motility disorders in one study [15].

4.4Repairing and Producing MFS

Any mechanic will tell you that one of the best ways to understand something is to take it apart and reassemble it. Can MFS be“taken apart”or cured? Curing MFS means elimination of the foveal suppression scotoma, which is relatively simple to accomplish, and restoring bifixation with fusion and high grade stereopsis, which is considerably more di cult. Most researchers (including Parks) believe that a patient with MFS cannot be restored to bifixation [1, 13, 38, 39]. There is also very little in the current literature to suggest that this is possible. A single study claims to have cured MFS in nine patients [40], and another reports a spontaneous resolution of MFS and amblyopia in a small group of older children and teenagers [41]. In the former study, of 30 patients with amblyopia and eccentric fixation, nine improved stereoacuity below the threshold for MFS (60 s of arc or better) that coincided with improvement in visual acuity. However, since stereoacuity is dependent on spatial resolution as well as alignment, and at least seven of these patients had no manifest strabismus prior to occlusion therapy, it may be that the treatment simply cured amblyopia, rather than MFS.

To the contrary, there seems to be opinion backed by evidence to suggest that MFS cannot be cured, but more importantly, a cure should not be attempted [42].

Antisuppression and treatment of ARC typically lead to insuperable diplopia (see Case 4.1) [39, 43]. For those with an associated small tropia, nothing is gained by attempted correction of the deviation with surgery or prism, because the monofixation persists and the deviation recurs. Normal or near-normal fusional vergence in these patients assures that alignment will be maintained at the visual system’s preferred angle, regardless of attempts at intervention. In addition, patients with MFS are typically asymptomatic and already enjoy high quality binocular vision. If bifixation could be restored, it may not result in a significant improvement in quality of life.

Can MFS be restored once deconstructed? If it is possible to lose the suppression ability due to trauma, occlusion or loss of vision in the preferred eye, or therapeutic intervention, might it be possible to restore it? Very little has been published in this area. The cases in the literature suggest that suppression cannot be relearned once unlearned [43]. However, the prognosis may depend on what caused the loss of suppression, as Case 4.2 shows.

Because MFS cannot or perhaps should not be cured once established, a better question might be “Can MFS be prevented in favor of bifixation?” Parks hypothesized that, for those cases of secondary MFS, correction of the underlying pathology, whether strabismus or anisometropia, before 6 months of age may be the answer. This is a challenging hypothesis to study in human subjects; such early intervention is often logistically di cult. An animal model is better suited to answer this question.

4.4.1Animal Models for the Study of MFS

There are several valid methods for creating the clinical conditions associated with the development of MFS. Large angle esotropia has been surgically induced in infant monkeys [23], or simulated with the use of prism glasses [18, 21]. One can create large angle sensory strabismus through monocular or binocular occlusion early in life [44–46]. One can also create an animal model for anisometropia by using optical defocus with minus lenses [47, 48]. With each of these methods, the timing of the repair of the induced strabismus or anisometropia determines the sensory outcome. If the image decorrelation is repaired in the infant monkey by 3 weeks of age (correlates to 3 months in human infants), bifixation can result in some animals [3, 6]. If delayed for up to 24 weeks, bifixation is not possible, but MFS can result. If delayed longer than 24 months, not only do the monkeys show a lack of sensory fusion, motor fusion and stereopsis, but they tend to develop latent nystagmus, asymmetry of pursuit and OKN, A- and V- pattern incomitance, and

Case 4.1

A 5-year old female was diagnosed with monofixation syndrome following a failed pre-school vision screening. The patient completed a course of optometric vision training designed to eliminate the foveal suppression scotoma in the left eye. Once constant, intractable diplopia was present, and the patient was referred to an orthoptist and pediatric ophthalmologist for the management of diplopia. The patient was 6-years old when presented to the ophthalmologist.

Vsc: 20/20

20/25

Motility:

Dsc

LET 5Δ with simultaneous prism and cover test Builds to E 20Δ with prism and alternate cover Nsc

LET 5Δ with simultaneous prism and cover Builds to E(T) 20Δ with prism and alternate cover

Sensory:

Constant, uncrossed diplopia at distance and near, unrelieved with any combination of prism.

Amblyoscope examination:

Objective angle (Grade I target) = +20 Subjective angle (Grade I target) = +5

Grade II: constant, variable diplopia, no sensory fusion, no suppression; as image approaches +5 on amblyoscope,diplopia converts from uncrossed to crossed.

Management:

Bilateral medial rectus recessions were done for the decompensating near deviation. At the 1-day postoperative visit, the diplopia was unchanged. Examination results at that visit are as follows.

Post-op Motility: Dsc:

LET 5Δ with simultaneous prism and cover test Builds to E 20Δ with prism and alternate cover test Nsc:

LET 5Δ with simultaneous prism and cover test Builds to E 20Δ with prism and alternate cover test

Post-op Exam 2:

At 1 month following surgery, the motility and sensory examinations were unchanged from presentation. The patient was o ered an occlusion foil to alleviate the diplopia. The mother declined as she viewed this as “a step backwards” after all the vision therapy that was done.

Case 4.2

A 16-year old female with a history of monofixation syndrome presents with a 3-month history of constant hori-

4zontal diplopia. The onset of the diplopia was abrupt, following closed head trauma without loss of consciousness, secondary to a motor vehicle accident. The patient reports that the diplopic image is always present, but is not always in the same location relative to fixation and appears to be constantly moving. Previous records document a stable RET 6Δ, with a superimposed phoria of up to 18Δ in addition to the sensory features of monofixation syndrome.

Motility:

Dcc:

RET variable from 8Δ to 25Δ

Ncc:

RET variable from 10Δ to 25Δ

Sensory:

Constant uncrossed horizontal diplopia of variable magnitude, unrelieved with prism. The addition of base-out prism in free space appears to cause an increase in the esodeviation, with diplopia.

Amblyoscope examination:

Objective angle (Grade I targets) = +25

T ereh was no subjective angle at which the patient could appreciate sensory fusion with either Grade I or II targets.

Management:

T ehpatient was prescribed a dense occlusion foil (Bangerter Light Perception foil) for the right lens of the glasses. At her 2-week follow-up, the filter strength was reduced to Bangerter 0.2. Two weeks later, the strength was reduced again to Bangerter 0.4. The filter was discontinued 1 month later, with complete resolution of the diplopia. Her sensory and motor examination returned to baseline level, and has been stable for over 2 years.

dissociated vertical deviation [18, 21, 45, 46]. Research shows that in the animal model, shorter durations of image decorrelation result in better sensory outcomes. These results imply that excellent outcomes may be possible in the human if alignment is restored within 90 days of the onset of strabismus. This suggests that, if monofixation is to be prevented in favor of bifixation, very early detection and intervention is necessary.

4.5Primary MFS (Sensory Signs

of Infantile-Onset Image Decorrelation)

The problem of primary MFS is one that has perplexed Parks and others. Primary MFS accounts for 16–19% of all cases of monofixation [1, 15]. This subpopulation is interesting, as it may represent the visual cortex’s active choice when bifoveal fixation is not possible for some reason. But what is that reason? One theory that has been debated for decades is the possibility that some individuals have an inherent inability to bi-fixate. However, no evidence of a genetic absence of disparity detectors has been uncovered thus far. In a recent study, there was no data found to support the hypothesis that MFS is a motor adaptation to an inherent ARC [13].

To the contrary, since animal studies have demonstrated that even a brief interval of image decorrelation early in the critical period of development can lead to MFS, one answer may be that the patient had strabismus or anisometropia that spontaneously resolved in early infancy. In a recent study, the presence of image decorrelation for only 3 days, if occurring at the height of the critical period, was found to cause dramatic changes in cortical processing of binocular input in monkeys [49]. The first change caused by early image decorrelation is suppression in area V1, beyond the input level in layer four. Apparently, once begun, this process of low metabolic activity spreads quickly. The longer the period of image decorrelation, the more prevalent the suppression becomes in all layers of V1. Once suppression is established, the developing cortex may have no choice but to work around it to achieve the best binocular vision possible under the circumstances.

4.5.1Motor Signs of Infantile-Onset Image Decorrelation

Secondary abnormalities of ocular motility associated with early-onset image decorrelation are well documented. Patients with uncorrected infantile-onset strabismus often develop latent nystagmus, dissociated vertical deviation, and A- or V-pattern incomitance, as well as demonstrate persistent naso-temporal pursuit and OKN asymmetry (see Sect. 4.5). The age of onset of binocular decorrelation appears to determine whether these signs will be present, and the duration of binocular decorrelation determines the severity [18, 21, 44–46]. Occasionally these motor signs may be observed in cases of secondary MFS (see Sect. 4.3.3) following strabismus repair, but they are particularly rare in primary MFS. The only secondary abnormality that has been found consistently thus far is