Fatema F. Ghasia

Abnormal Fixational Eye Movements in Amblyopia

Purpose Fixational saccades shift the foveal image to counteract visual fading related to neural adaptation. Drifts are slow eye movements between two adjacent fixational saccades. We quantified fixational saccades and asked whether their changes could be attributed to pathologic drifts seen in amblyopia, one of the most common causes of blindness in childhood. Methods Thirty-six pediatric subjects with varying severity of amblyopia and eleven healthy age-matched controls held their gaze on a visual target. Eye movements were measured with high-resolution video-oculography during fellow eye-viewing and amblyopic eye-viewing conditions. Fixational saccades and drifts were analyzed in the amblyopic and fellow eye and compared with controls. Results We found an increase in the amplitude with decreased frequency of fixational saccades in children with amblyopia. These alterations in fixational eye movements correlated with the severity of their amblyopia. There was also an increase in eye position variance during drifts in amblyopes. There was no correlation between the eye position variance or the eye velocity during ocular drifts and the amplitude of subsequent fixational saccade. Our findings suggest that abnormalities in fixational saccades in amblyopia are independent of the ocular drift. Discussion This investigation of amblyopia in pediatric age group quantitatively characterizes the fixation instability. Impaired properties of fixational saccades could be the consequence of abnormal processing and reorganization of the visual system in amblyopia. Paucity in the visual feedback during amblyopic eye-viewing condition can attribute to the increased eye position variance and drift velocity.

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

PURPOSE Pattern strabismus describes vertically incomitant horizontal strabismus. Conventional theories emphasized the role of orbital etiologies, such as abnormal fundus torsion and misaligned orbital pulleys as a cause of the pattern strabismus. Experiments in animal models, however, suggested the role of abnormal cross-connections between the neural circuits. We quantitatively assessed eye movements in patients with pattern strabismus with a goal to delineate the role of neural circuits versus orbital etiologies. METHODS We measured saccadic eye movements with high-precision video-oculography in 14 subjects with pattern strabismus, 5 with comitant strabismus, and 15 healthy controls. We assessed change in eye position in the direction orthogonal to that of the desired eye movement (cross-coupled responses). We used fundus photography to quantify the fundus torsion. RESULTS We found cross-coupling of saccades in all patients with pattern strabismus. The cross-coupled responses were in the same direction in both eyes, but larger in the nonviewing eye. All patients had clinically apparent inferior oblique overaction with abnormal excylotorsion. There was no correlation between the amount of the fundus torsion or the grade of oblique overaction and the severity of cross-coupling. The disconjugacy in the saccade direction and amplitude in pattern strabismics did not have characteristics predicted by clinically apparent inferior oblique overaction. CONCLUSIONS Our results validated primate models of pattern strabismus in human patients. We found no correlation between ocular torsion or oblique overaction and cross-coupling. Therefore, we could not ascribe cross-coupling exclusively to the orbital etiology. Patients with pattern strabismus could have abnormalities in the saccade generators.

Uncorrected Myopic Refractive Error Increases Microsaccade Amplitude

PURPOSE Human brain generates miniature eye movements, such as microsaccades, to counteract image fading due to visual adaptation. Generation of microsaccade relies on the amount of retinal error or acuity demand for a desired visual task. The goal of this study was to assess the influence of visual blur, induced by uncorrected refractive error on microsaccades and saccades. METHODS Ten subjects with myopia held their gaze on a visual target during two experiment conditions: corrected refractive error and uncorrected refractive error. Eye movements were measured with high-resolution video oculography under binocular viewing conditions during both tasks. Gaze holding function, microsaccades, and visually guided saccades were analyzed and compared during both tasks. RESULTS We found an increase in the amplitude of microsaccades in the presence of uncorrected refractive error, but the microsaccade frequency and velocity remained unchanged. The microsaccade amplitude systematically increased with an increase in uncorrected refractive error. The main sequence relationship relating the saccade amplitude with respective peak velocity was not significantly different between two conditions. The onset latency, peak velocities, and accuracy of visually guided saccades also were unchanged between the two conditions. CONCLUSIONS These results suggest that visual blur, hence the precision of an image on the fovea, has an important role in calibrating the amplitude of fixational eye movements, such as microsaccades.

Viewing condition dependence of the gaze-evoked nystagmus in Arnold Chiari type 1 malformation

Saccadic eye movements rapidly shift gaze to the target of interest. Once the eyes reach a given target, the brainstem ocular motor integrator utilizes feedback from various sources to assure steady gaze. One of such sources is cerebellum whose lesion can impair neural integration leading to gaze-evoked nystagmus. The gaze evoked nystagmus is characterized by drifts moving the eyes away from the target and a null position where the drifts are absent. The extent of impairment in the neural integration for two opposite eccentricities might determine the location of the null position. Eye in the orbit position might also determine the location of the null. We report this phenomenon in a patient with Arnold Chiari type 1 malformation who had intermittent esotropia and horizontal gaze-evoked nystagmus with a shift in the null position. During binocular viewing, the null was shifted to the right. During monocular viewing, when the eye under cover drifted nasally (secondary to the esotropia), the null of the gaze-evoked nystagmus reorganized toward the center. We speculate that the output of the neural integrator is altered from the bilateral conflicting eye in the orbit position secondary to the strabismus. This could possibly explain the reorganization of the location of the null position.

Experimental tests of hypotheses for microsaccade generation

Fixational eye movements such as microsaccades are important to prevent fading. These miniature eye movements are also necessary to redirect gaze to the target after a drift. Generation of saccades and microsaccades utilizes common neural substrates. We, therefore, hypothesized that physiological modulators of saccades should also affect microsaccades. Test of this hypothesis will also provide support for the models of a microsaccade generation. We performed two experiments. In the first experiment, complete darkness led to a decrease in the frequency and velocity, but increased the amplitude of microsaccades. In the second experiment, active eyelid closure further reduced the velocity and frequency of microsaccades, but increased their amplitude. Darkness reduces the superior colliculus activity leading to a reduction in the velocity and frequency of microsaccades. Eye closure might cause sustained inhibition of the omnipause neurons. Subsequent disinhibition of the burst neurons might cause a reduction in the post-inhibitory rebound firing resulting in a decreased velocity of microsaccades. Sustained inhibition of the omnipause neurons could also reduce the inhibitory drive that would otherwise abort microsaccades. Hence, by inhibiting the activity of omnipause neurons, the eye closure could increase the amplitude of microsaccades.

Ocular Palatal Tremor Plus Dystonia: New Syndromic Association

Ocular palatal tremor (OPT) typically develops after a breach in the Guillian‐Mollaret triangle. We herein describe a variant of this syndrome in which dystonia is also present, hence called, here, ocular palatal tremor plus dystonia.

Head oscillations in infantile nystagmus syndrome

PURPOSE To quantitatively characterize eye and head oscillations in patients with infantile nystagmus syndrome (INS). METHODS Vertical and horizontal eye and head position in INS patients were measured simultaneously at a sampling frequency of 500 Hz. Eye and head movements were measured continuously for 180 seconds. The data was calibrated and converted to angular vectors, which were further analyzed with custom software. RESULTS A total of 10 patients with INS were included: 3 with pseudo-jerk, 3 with pure-jerk, 2 with pseudo-pendular with foveating saccade form of jerk, 1 with bidirectional jerk, and 1 with asymmetric pendular nystagmus waveforms. None of the patients had periodic, aperiodic, or a superimposed latent nystagmus component. Two types of head oscillations were observed: one with a frequency of 1-3 Hz, present in all patients; and another with a frequency range of 5-8 Hz, present in only 7 patients. High-frequency oscillations were episodic, whereas low-frequency oscillations were constantly present. Peak velocity of the high-frequency head oscillations and eye velocity of nystagmus were not correlated, suggesting that these oscillations did not influence foveation. CONCLUSIONS Two types of head oscillations were found in INS patients: a constant, low-frequency and an episodic, high-frequency. Lack of correlation between the foveation period of nystagmus and peak head velocity during high-frequency oscillations suggests a coexisting pathological phenomenon rather than a compensatory mechanism used to improve the visual acuity.

Neuro-ophthalmology of type 1 Chiari malformation

Chiari malformation is a congenital deformity leading to herniation of cerebellar tonsils. Headache is a typical symptom of this condition, but patients with Chiari malformation often present with double vision and vertigo. Examination of eye movements in such patients often reveals nystagmus and strabismus. Eye movement deficits in the context of typical symptomatic presentation are critical clinical markers for the diagnosis of Chiari malformation. We will review eye movement deficits that are seen in patients with type 1 Chiari malformation. We will then discuss the underlying pathophysiology and therapeutic options for such deficits.

Acute onset of upbeat nystagmus, exotropia, and internuclear ophthalmoplegia—A tell-tale of ponto-mesencephalic infarct

Two patients were assessed for acute onset of diplopia. Clinical examination revealed upbeat nystagmus, exotropia, and internuclear ophthalmoplegia (INO). Both patients had vascular risk factors; acute ischemic stroke affecting ponto-mesencephalic junction was suspected. Magnetic resonance imaging confirmed strategic location of the acute infarct affecting the medial longitudinal fasciculus, adjacent occulomotor nuclei, and paramedian tract. We propose that constellation of acute onset of upbeat nystagmus, INO, and exotropia in patients with vascular risk factors might be unequivocal manifestation of the ponto-mesencephalic stroke.

Misdirected horizontal saccades in pan-cerebellar atrophy.

Saccadic dysmetria is a sensitive marker of cerebellar dysfunction. We discovered misdirected horizontal saccades due to cross-coupled orthogonal (vertical) saccades in siblings with pan-cerebellar atrophy. There was an upward drift in vertical eye position after each cross-coupled downward saccade. Such drifts brought the eyes back to the desired target. Due to strong upward bias, downward compensatory slow movements did not follow cross-coupled upward saccades. There was minimal horizontal cross-coupling associated with vertical saccades. There was a reduced gain of horizontal pursuit causing lag in the horizontal eye movement and subsequent catch-up horizontal saccades. The horizontal catch-up saccades were also associated with vertical cross-coupled eye movements and subsequent drifts. There was no cross-coupling of pursuit eye movements. Our results support the hypothesis emphasizing adaptive cerebellar control of saccade direction. Commands for horizontal saccades trigger not only the activity of the horizontal burst generators, but also the vertical burst neurons. The activity of orthogonal (vertical) burst neurons is canceled by opposing signals under cerebellar supervision. Cerebellar lesions could disrupt such balance between opposing orthogonal signals leading to vertical cross-coupling during horizontal saccade. We speculate that upward drift might result from an imbalance in opposing orthogonal signals at the level of neural integrators.