Cross-coupled eye movement supports neural origin of pattern strabismus.

Pattern strabismus describes horizontal strabismus that is vertically incomitant. Historically, pattern strabismus is attributed to the oblique muscle dysfunction.1 Little is known about the etiology of isolated primary oblique overaction. Clinical observations have suggested that a torsional offset due to loss of fusion might alter the direction of the recti muscle action, hence causing the pattern strabismus.2,3 For example, excyclotorsion of the globe will result in medial rectus becoming a partial elevator leading to overelevation during adduction, and inferior rectus becoming a partial adductor and superior rectus a partial abductor causing a V-pattern. Correlation between the fundus torsion and static eye fixation in patients with pattern strabismus further supported the viewpoint emphasizing altered recti pull.4 Subsequent studies suggested that oblique overaction is a clinical description rather than an actual mechanism of the pattern strabismus.5 Static malposition or dynamic instability of the extraocular muscle pulleys in patients with craniofacial dysmorphism causes pattern strabismus.6 Neurophysiology experiments in nonhuman primates reared with alternate monocular occlusion suggested a neural basis for pattern strabismus.7–9 These animals had cross-axis eye movements; for example, intended horizontal saccades were associated with cross-axis vertical eye movement and vice versa. Neural recordings from ocular motor neurons have shown that horizontal cross-coupled movement corresponds to increased firing rate of horizontal motor neurons, whereas vertical cross-coupled movement corresponds to increased firing rate of vertical motor neurons. The presence of the neural correlate of cross-coupled movements in animal models suggested that abnormal central innervations might cause the pattern strabismus.7–9 These principles describing the pathophysiology of pattern strabismus are based on subjective clinical impression, orbital imaging, and neurophysiology in animal models. There is a paucity of investigations of objective eye movement assessments in human patients with pattern strabismus. We aimed to quantify eye movements and fundus torsion in patients with infantile and late onset pattern strabismus without craniofacial abnormalities. We hypothesized that overaction of the oblique muscles, as previously predicted in pattern strabismus, should be reflected in the static misalignment as well as dynamic disconjugacy of saccades. For example, inferior oblique overaction should cause an upward deviation of the adducting eye during a horizontal saccade, and the oblique upward saccade would have greater amplitude in the adducting than the abducting eye. It is unknown whether patients with pattern strabismus have cross-coupling of the eye movement, as described in the nonhuman primate model. If, indeed, animal models are analogous to the patients with pattern strabismus, we should also see cross-coupled eye movements in these patients. We quantitatively assessed the presence of cross-coupling of saccades in patients with pattern strabismus. There are several possible explanations for cross-coupled responses. Mechanical factors, such as an abnormal fundus torsion or inappropriate innervations, and consequent cross-talk between horizontal and vertical saccade generators, can result in cross-coupling. The torsion hypothesis predicts a correlation between the severity of cross-coupled saccades and the static fundus torsion. According to the torsion hypothesis, patients with greater static torsion will have larger cross-coupling of saccades. The absence of such a correlation would suggest that abnormal static torsion is not the exclusive cause of pattern strabismus.