Correlation of Cross-Axis Eye Movements and Motoneuron Activity in Non-Human Primates with “A” Pattern Strabismus

Binocular alignment and binocular coordination of eye movements are important in primates, who have frontal vision and foveae to direct gaze at a particular object.1,2 Loss of sensory or motor fusion early in postnatal development leads to binocular misalignment (strabismus). Various studies conclude that infantile forms of strabismus occur in as many as 5% of all children.3 Incomitant strabismus is one in which ocular misalignment varies with gaze position. A relatively common form of incomitant strabismus is A/V pattern strabismus.4,5 An increase in esotropia or a decrease in exotropia in supraduction and an increase in exotropia or a decrease in esotropia in infraduction is called an “A” pattern. Similarly, an increase in exotropia or a decrease in esotropia in supraduction and an increase in esotropia or a decrease in exotropia in infraduction is called a “V” pattern.6,7 One study suggests that more than 50% of patients with horizontal misalignment also show A/V pattern incomitance.5 Though the nomenclature primarily refers to variation of horizontal misalignment with vertical gaze position, often a vertical misalignment that changes with horizontal gaze position is present as well. Earlier we showed that we are able to reproduce these properties of strabismus in monkeys reared using visual sensory deprivation paradigms.8 Our animals also displayed dissociated vertical deviation (DVD), another common disorder observed in humans with strabismus, by which the nonfixating eye is elevated compared with the fixating eye. In our published study, we measured binocular eye movements in these animals and showed that static alignment patterns were reflected in their eye movements. Thus, during monocular viewing, the animal was able to track a horizontally or vertically moving pursuit or saccadic target with purely horizontal or vertical eye movements of the viewing eye. However, the nonviewing eye displayed significant cross-axis components (i.e., vertical components during horizontal tracking and horizontal components during vertical tracking; see Figs. ​Figs.11 and ​and22).8 Figure 1 Hess screen chart showing alignment patterns during monocular viewing in strabismic monkeys S1, S2, and S3. Left: alignment data collected during right eye viewing; right: alignment data collected during left eye viewing. Abduction is positive, and adduction ... Figure 2 Raw data plot of eye movements in animal S2 during horizontal and vertical smooth pursuit. Target amplitude was ±15°. The viewing eye (right eye, black trace) makes purely horizontal or vertical tracking eye movements. However, the nonviewing ... There are at least two possible sources for the abnormal cross-axis eye movements associated with A/V pattern strabismus and DVD. One possibility involves only the periphery and is what we refer to as the mechanical hypothesis. Thus, in the mechanical hypothesis, either static malpositioning of extraocular rectus muscle pulleys or sideslip of extraocular muscle because of dynamic instability of muscle pulleys could result in A/V patterns and associated eye movements. This hypothesis has support from human MRI studies that examined patients with incomitant strabismus and showed pulley location problems and problems with muscle stability.9-12 Another hypothesis is that disruptive changes in neural circuits result from visual sensory deprivation rearing, leading to an inappropriate neural drive to extraocular muscles that leads to cross-axis eye movements and the A/V patterns and DVD observed in the strabismic animals. We refer to this as the neural hypothesis. Though the neural hypothesis may be attractive for animals with sensory induced strabismus that were part of this study (given that the rearing paradigm putatively does not interfere with extraocular muscle), a few studies have provided genetic/molecular evidence that suggests visual sensory deprivation may alter the development of extraocular muscle structure.13,14 In this study we report results from experiments aimed at testing the neural hypothesis for generating cross-axis eye movements leading to A/V patterns and DVD in our animals. We recorded from extraocular motoneurons in the oculomotor nucleus and analyzed neuronal activity when the animals attempted a sinusoidal smooth pursuit task with either eye viewing. We focused this study on vertical motoneurons. The question we asked was whether neuronal responses of the oculomotor neurons could account for the abnormal cross-axis movements observed in our animals. Our working hypothesis was that if there were a neural source for the inappropriate cross-axis movements, the relationship between motoneuron unit activity and eye motion should remain consistent during purposeful tracking and during cross-axis eye movements. On the other hand, if the A/V patterns and associated cross-axis eye movements were caused by nonneural sources (for example, mechanical problems at the periphery), the lawful relationship between the neuronal responses and eye movements should break down during the inappropriate cross-axis eye movements. It is important to note that we were not investigating the source of the horizontal or vertical misalignment. Rather, our goal was to determine whether the change in ocular misalignment with eye position was caused by a neuronal drive. Some of the results have appeared before in abstract form (Das VE, et al. IOVS 2004;45:ARVO E-Abstract 2545).15