This case report presents a rare case of infantile nystagmus syndrome (INS) in which the direction of infantile nystagmus (IN) was vertical. A 66-year-old woman was referred to our department for investigation of abnormal eye movements. She showed a disordered field of view with a homonymous hemianopia in the lower left quadrant and vertical gaze-evoked nystagmus, but there were no other abnormal neurological findings. She did not complain of an oscillopsia. Imaging revealed that the cause of hemianopia was atrophy and low cerebral blood flow in the right occipital lobe. The vertical nystagmus became strong when attempting to fixate to stationary targets. A reversed optokinetic nystagmus response was observed in the vertical optokinetic nystagmus test. From these eye movements, we diagnosed her nystagmus as vertical IN. Patients with INS see everything by saccades. IN consists of the alternate appearance of saccades and preceding slow eye movements. For these eye movements, a wide visual field is necessary. In this case, vertical IN was caused by the wider vertical than horizontal visual field resulting from homonymous hemianopia. Therefore, the direction of IN is horizontal in most patients with INS because their horizontal visual field is the widest field.

UNASSIGNED: Research on infantile nystagmus syndrome (INS) and visual search is limited. Conducting this research could assist practitioners in understanding how INS affects the real-life visual activities of patients and aid in developing new clinical visual function assessments for INS.
UNASSIGNED: The aim of this work is to investigate how subjects with INS perform visual search tasks, and, particularly, to assess how INS subjects perform when targets are located at their null position or away from it, and when under additional cognitive demands.
UNASSIGNED: INS subjects (N = 15) and controls (N = 20) performed conjunction and feature search tasks, both with and without mental arithmetic. Search performance was assessed using log-transformed total search time, gaze-dependent search time, and accuracy. Cognitive demand was quantified by pupil size and the NASA task-load index score.
UNASSIGNED: INS subjects showed longer search times compared to controls in conjunction search (P < 0.01), but not in feature search. Within INS and control subjects, the total search times were significantly increased by the addition of mental arithmetic (P < 0.0001). There was no difference in gaze-dependent search times between null target position and 15° away from null target position of subjects in conjunction search (P > 0.05). Accuracies were 100% for both control and INS subjects in both conjunction and feature search.
UNASSIGNED: Conjunction visual search was impaired in adult INS subjects, and further worsened under increased cognitive demand. The null position did not affect the visual search performance in INS.

Spastic paraplegia is a neurodegenerative disorder characterized by progressive leg weakness and spasticity due to degeneration of corticospinal axons. SPG7 encodes paraplegin, and pathogenic variants in the gene cause hereditary spastic paraplegia as an autosomal recessive trait. Various ophthalmological findings including optic atrophy, ophthalmoplegia, or nystagmus have been reported in patients with spastic paraplegia type 7. We report a 15-year-old male patient with a novel heterozygous variant, c.1224T>G:p.(Asp408Glu) in SPG7 (NM_003119.3) causing early onset isolated optic atrophy and infantile nystagmus prior to the onset of neurological symptoms. Therefore, SPG7 should be considered a cause of infantile nystagmus with optic atrophy.

Infantile nystagmus syndrome (INS) is often characterized by an identifiable null zone. When the null zone is not in the straight-ahead gaze, a compensatory head posture (CHP) is adopted by the patient to achieve best possible vision. Various surgical procedures have been recommended to correct a CHP which is clinically predominant in one dimension of yaw (lateral rotation), pitch (anterior or posterior flexion/extension) or roll (lateral flexion). However, the presence of a complex CHP which is clinically evident in more than one dimension, warrants either a combination of multiple techniques or a stepwise approach. We report the case of a 26-year-old male with INS with an eccentric null and a multi-dimensional complex CHP of 30º left face turn, 20º right head tilt and 10º chin depression. The patient was managed by all four horizontal rectus muscle recession and resection with full tendon vertical transposition to address the face turn and head tilt. He underwent lateral rectus muscle (LR) recession with upward transposition and medial rectus muscle (MR) resection with downward transposition in the right eye. MR recession with upward transposition and LR resection with downward transposition were performed in the left eye. Postoperatively. the head posture improved significantly for both distance and near viewing. The chin depression also reduced after the procedure. He developed transient diplopia due to a small vertical deviation after the surgery, which was managed by prisms and fusional exercises. Thus, horizontal rectus muscle recession and resection combined with vertical transposition may be helpful to simultaneously improve the head tilt associated with the face turn, obviating the need for vertical rectus muscle or oblique muscle surgery.

UNASSIGNED: To report the results of plication augmentation of the augmented Anderson procedure in patients with infantile nystagmus syndrome and face turn.
UNASSIGNED: In this retrospective study, all patients who underwent plication augmentation of the augmented Anderson procedure between August 2015 and November 2018 were included. Our study included patients older than 6 years with a face turn >25°. We also included patients with residual face turns ≥15° after Anderson-type procedures. The face turn was measured by a goniometer and also quantified with prisms placed with apex in the direction of the face turn. We plicated the medial rectus of one eye by 5.0 mm and lateral rectus of the fellow eye by 7.0 mm based on the direction of the face turn in addition to the augmented Anderson procedure. Patients were reviewed on the 1st postoperative day, 1st month, and every 6 months thereafter.
UNASSIGNED: Eight patients with a mean face turn of 27.5° ± 6.5° underwent plication augmentation of the augmented Anderson procedure. Two patients had residual face turns after a previous Anderson-type procedure. We obtained a mean correction of 25° ± 6.5° with a median prismatic correction of 45 prism diopters (PD) for each eye. The median face turn at the last review was 2.5°, and all patients were corrected to within 10°. Excluding patients operated for residual face turns, we had a mean dose response of 2.7 PD/mm and 1.7°/mm of surgery on each eye. Five patients had an improvement in null zone visual acuity. Two patients had a restriction in ocular motility of -2 in the direction of the recessed extraocular muscle at the last review, and the remaining had a -1 restriction.
UNASSIGNED: Plication augmentation of the augmentation Anderson procedure appears to be a safe and effective procedure for patients with infantile nystagmus syndrome and a face turn more than 25°. It may also be used for residual face turns more than 15°.

Background: Infantile nystagmus syndrome (INS) is a genetically heterogeneous disorder. Identifying genetic causes of INS would help clinicians to facilitate clinical diagnosis and provide appropriate treatment. The aim of this study was to determine the diagnostic utility of targeted next-generation sequencing (NGS) for INS.Materials and methods: We recruited 37 patients who were referred to the Neuro-ophthalmology clinics for evaluations of INS. NGS was performed using a targeted panel that included 98 candidate genes associated with INS. We identified pathogenic variants according to guidelines of the American College of Medical Genetics and Genomics. We also calculated the sensitivity and specificity of each clinical sign to assess the diagnostic yield of our gene panel.Results: After variant filtering, annotation, and interpretation, the potential pathogenic variants were detected in 13 of the 37 patients, achieving a molecular diagnostic rate of 35%. The identified genes were PAX6 (n = 4), FRMD7 (n = 4), GPR143 (n = 2), CACNA1F (n = 1), CNGA3 (n = 1) and GUCY2D (n = 1). In approximately 30% (n = 4) of the patients, the initial clinical diagnosis was revised after a molecular diagnosis was performed. The presence of a family history had the highest predictive power for a molecular diagnosis (sensitivity = 61.5%, specificity = 91.7%), and the sensitivity increased when the family history was considered together with one of two clinical signs such as pendular nystagmus waveforms or anterior segment dysgenesis.Conclusions: Our study shows that targeted NGS can be useful to determine a molecular diagnosis for patients with INS. Targeted NGS also helps to confirm a clinical diagnosis in atypical phenotypes or unresolved cases.

To evaluate foveation dynamics and characteristics of vergence eye movements during fixation of static targets at different distances and while tracking a target moving in depth in a subject with congenital nystagmus (CN).
Eye movements of a well-studied subject with CN were recorded using the magnetic search coil technique and analyzed using the OMtools software, including the eXpanded Nystagmus Acuity Function (NAFX).
Both the phase planes and NAFX values during fixation of targets at various near distances were equivalent to those during fixation of a far target. When applied to vergence data, the NAFX values (\"binocular\" NAFX) were higher than for the individual eye data. Vergence tracking of targets moving in depth was demonstrated and was accurate for targets moving at speeds up to ~ 35°/sec.
Target foveation qualities during fixation of targets at various near distances were equivalent to that during fixation of a far target. Stereo discrimination was limited by the foveation quality of the eye with the higher NAFX waveform. Foveation period slopes during vergence tracking demonstrated vergence movements despite the ongoing CN oscillation. Similar to what we found with fixation, pursuit, and the vestibulo-ocular systems, these findings establish that vergence in both static and dynamic viewing conditions functions normally in the presence of the CN oscillation.

Albinism patients have poor visual acuity in addition to hypopigmentation. Their foveal anatomy is abnormal, but correlation with function is incompletely understood. This study correlates retinal electrophysiology, visual acuity and optical coherence tomography (OCT) anatomy in albinism patients and compares with age-similar controls.
Institutional Review Board approval was obtained (IRB# 201408782). Patients were recruited from clinical practice. Inclusion criteria were at least three clinical features of albinism including iris transillumination, nystagmus, fundus hypopigmentation, or foveal hypoplasia on OCT and/or molecular genetic confirmation. Diagnosys (Lowell, Mass) full-field ERG (ffERG) and VERIS multifocal ERG (mfERG; Electro-Diagnostic Imaging, Milpitas, California) were obtained using standard International Society for Clinical Electrophysiology of Vision protocols. The mfERG protocol was a 4-min 103-hexagon protocol covering approximately 40° in diameter of central retina. Control subjects without albinism were recruited by in-hospital notices and invitations in clinic. OCT central thickness was recorded, and an OCT foveal score was calculated. Nonparametric permutation testing was utilized to determine the statistical significance.
A total of 16 albinism patients and 19 age-similar controls were recruited. Four of 16 albinism patients had no nystagmus. Seventeen non-albinism controls had no ocular disorder other than refractive error. Two controls had infantile nystagmus with normal maculas on OCT. There was no statistically significant difference in mfERG amplitude or latency between albinism patients with or without nystagmus (lowest p = 0.68; 0.54, respectively). mfERG: 12 of 16 (75%) albinism patients had average ring 1 amplitudes within one standard deviation of controls despite having abnormal foveal anatomy on OCT. Patients averaged shorter latencies in rings 1 and 2 than controls (p = 0.005, p = 0.02). Patients averaged higher amplitudes than controls in rings 4, 5 and 6 (p = 0.03, p = 0.006, p = 0.004). There was no significant correlation between visual acuity and mfERG amplitudes in any ring (smallest p = 0.15). ffERG: Patients averaged higher amplitudes on 30 Hz flicker (p = 0.008). In all conditions, albinism patients had higher amplitude a-waves (p ≤ 0.03). B-waves were higher amplitude than controls in light-adapted 3.0 (p = 0.03). There was no statistical correlation between ffERG amplitudes and visual acuity (smallest p = 0.45). OCT: In albinism patients, thicker central macula on OCT correlated with lower mfERG amplitudes in all rings except for ring 1 (p < 0.05) and lower ffERG a-wave amplitudes on dark-adapted 0.01 (p = 0.003). Macular thickness on OCT did not correlate with visual acuity (p = 0.51); OCT foveal score did (p = 0.0004).
Amplitude of mfERG does not correlate with visual acuity in any ring in patients with albinism. The slope of the change in amplitude from central to peripheral rings on the mferg is significantly different in albinism patients versus controls whether or not nystagmus is present. The decreased slope of change in amplitudes from center to periphery of the macula in albinism patients indicates changes in macular topography that are more important to visual deficits than the foveal depression.

To demonstrate the utility of using eye-movement data to reveal the diagnostic characteristics of infantile nystagmus syndrome (INS), determine treatment, and both estimate and document therapeutic improvements in three patients with well-developed foveation periods, fairly broad, lateral gaze \"nulls,\" head turns, strabismus, and complex, multiplanar nystagmus.
Infrared reflection, magnetic search coil, and high-speed digital video systems were used to record the eye movements of INS patients, pre- and post-Kestenbaum null-point correction surgery (horizontal or vertical). Data were analyzed and estimations made, using the eXpanded Nystagmus Acuity Function (NAFX) that is part of the OMtools toolbox for MATLAB.
In all three subjects (S1-S3), both peak NAFX and longest foveation domain (LFD) improved from their pre-Kestenbaum values. S1: 0.700-0.745 (6.4%) and 25-34° (36%), respectively. S2: 0.445-0.633 (42.4%) and >40° to >50° (10%), respectively. S3: 0.250-0.300 (20%) and 13° to ≫18° (see text), respectively.
S1: Even at the high ends of the pre-therapy NAFX and LFD spectra, INS foveation (and therefore, visual-function) improvements may be adequate to justify nystagmus surgery and provide clinical improvements beneficial to the patient. S2: INS foveation improvements in the vertical plane are equal to those originally estimated using the horizontal data in prior patients. S3: Two apparent NAFX peaks can be converted into a very broad peak by surgery based on the preferred lower peak.

Abnormal projection of the optic nerves to the wrong cerebral hemisphere transforms the optokinetic system from its usual negative feedback loop to a positive feedback loop with characteristic ocular motor instabilities including directional reversal of the optokinetic nystagmus (OKN) and spontaneous nystagmus, which are common features of infantile nystagmus syndrome (INS). Visual input plays a critical role in INS linked to an underlying optic nerve misprojection such as that often seen in albinism. However, spontaneous nystagmus often continues in darkness, making the visual, sensory-driven etiology questionable. We propose that sensorimotor adaptation during the constant nystagmus of patients in the light could account for continuing nystagmus in the dark. The OKN is a stereotyped reflexive eye movement in response to motion in the surround and serves to stabilize the visual image on the retina, allowing high resolution vision. Robust negative optokinetic afternystagmus (negative OKAN), referring to the continuous nystagmus in the dark with opposite beating direction of the preceding OKN, has been identified in various non-foveated animals. In humans, a robust afternystagmus in the same direction as previous smooth-pursuit movements (the eye\'s continuous tracking and foveation of a moving target) induced by visual stimuli has been known to commonly mask negative OKAN. Some INS patients are often associated with ocular hypopigmentation, foveal hypoplasia, and compromised smooth pursuit. We identified an INS case with negative OKAN in the dark, in contrast to the positive afternystagmus in healthy subjects. We hypothesize that spontaneous nystagmus in the dark in INS patients may be attributable to sensory adaptation in the optokinetic system after a sustained period of spontaneous nystagmus with directional visual input in light.