ERG Responses in Albinism, Idiopathic Infantile Nystagmus, and Controls.

Purpose: Our primary aim was to compare adult full-field ERG (ffERG) responses in albinism, idiopathic infantile nystagmus (IIN), and controls. A secondary aim was to investigate the effect of within-subject changes in nystagmus eye movements on ffERG responses. Methods: Dilated Ganzfeld flash ffERG responses were recorded using DTL electrodes under conditions of dark (standard and dim flash) and light adaptation in 68 participants with albinism, 43 with IIN, and 24 controls. For the primary aim, the effect of group and age on ffERG responses was investigated. For the secondary aim, null region characteristics were determined using eye movements recorded prior to ffERG recordings. ffERG responses were recorded near and away from the null regions of 18 participants also measuring the success rate of recordings. Results: For the primary aim, age-adjusted photopic a- and b-wave amplitudes were consistently smaller in IIN compared with controls (P < 0.0001), with responses in both groups decreasing with age. In contrast, photopic a-wave amplitudes increased with age in albinism (P = 0.0035). For the secondary aim, more intense nystagmus significantly reduced the success rate of measurable responses. Within-subject changes in nystagmus intensity generated small, borderline significant differences in photopic b-wave peak times and a-and b-wave amplitudes under scotopic conditions with standard flash. Conclusions: Age-adjusted photopic ffERG responses are significantly reduced in IIN adding to the growing body of evidence of retinal abnormalities in IIN. Differences between photopic responses in albinism and controls depend on age. Success at obtaining ffERG responses could be improved by recording responses at the null region.

[A comparative study of rigid gas permeable corneal contact lenses versus frame glasses for refractive correction of postoperative aphakic eyes after congenital cataract surgery in infants and children].

Objective: The aim of this paper is to compare the refractive correction effects of rigid gas permeable contact lenses (RGPCL) and spectacle correction in children with aphakia after congenital cataract surgery. Methods: This was a prospective non-randomized controlled trial. Children with aphakic eyes after congenital cataract surgery, who underwent vision correction in the Strabismus and Pediatric Ophthalmology Clinic of Beijing Tongren Hospital affiliated with Capital Medical University from April 2012 to November 2019, were continuously collected. Those who voluntarily chose to wear RGPCL for refractive correction were included in the experimental group. Patients with monocular disease were in trial group 1, and patients with binocular disease were in trial group 2. Patients who chose to wear frame glasses for refractive correction were included in the control group. Patients with monocular disease were in control group 1, and patients with binocular disease were in control group 2. Regional origin, medical history, and family information were collected at the first diagnosis. During the follow-up, adverse reactions occurring during the process of wearing glasses were recorded. The Teller acuity card was used for visual examination to obtain the best-corrected visual acuity and convert it into the logarithm of the minimum resolution angle. The degree of nystagmus was determined according to the amplitude and frequency of nystagmus. Treatment cost, treatment compliance, and the reasons for adopting or not adopting RGPCL were analyzed through a questionnaire completed by the parents of children with RGPCL. Results: A total of 203 children (344 eyes) who underwent congenital cataract surgery were included, including 124 males (210 eyes) and 79 females (134 eyes). The age range was 3 to 36 months. There were 28 cases in the experimental group, including 19 cases in trial group 1 and 9 cases in trial group 2. There were 175 cases in the control group, including 43 cases in control group 1 and 132 cases in control group 2. Except for 6 months of age, the visual acuity of the experimental group was better than that of the control group, and the differences were statistically significant (P<0.05). The visual acuity of children in trial group 1 was better than that of children in control group 1 at the same age. Among them, at 12 months of age [1.54 (1.27, 1.97), 1.84 (0.97, 2.12)], 18 months of age [1.27 (0.97, 1.84), 1.84 (0.97, 2.12)], 24 months of age [1.54 (1.27, 1.84), 1.84 (0.97, 2.12)], and 30 months old [0.97 (0.66, 1.27), 1.54 (0.66, 2.12)], the difference was statistically significant (P<0.001). The visual acuity of children in trial group 2 was better than that in control group 2 at the same age. Among them, at 18 months old [1.27 (0.97, 1.54), 1.27 (0.66, 2.12)], 24 months old [0.97 (0.66, 1.27), 1.27 (0.66, 2.12)], and 30 months old [1.27 (0.66, 2.12)], the difference was statistically significant (P<0.05). The remission rate of nystagmus in the experimental group was 8/9 (8 cases), the remission rate of nystagmus in the control group was 34.40% (32 cases), and the exacerbation rate was 29.03% (27 cases). The average annual cost of the experimental group was 25 125 yuan, and that of the control group was 2 511 yuan. Conclusions: RGPCL is a well-tolerated, safe, and effective treatment for infants and young children. The visual acuity and degree of nystagmus were significantly improved in children who wore RGPCL for aphakia refractive correction after congenital cataract surgery compared with spectacle correction.

Clinical and mutational characteristics of oculocutaneous albinism type 7.

The purpose of this paper is to expand on the phenotype of oculocutaneous albinism type 7 (OCA7). We described three patients with OCA7: two from a consanguineous family of Kurdish origin and one patient of Dutch origin. We compared them with all patients described to date in the literature. All newly described patients had severely reduced visual acuity (VA), nystagmus, hypopigmentation of the fundus, severe foveal hypoplasia, and chiasmal misrouting. None had iris translucency. All patients had normal pigmentation of skin and hair. We found one novel mutation in the Dutch patient: c.565G > A; p.(Gly189Ser). We compared our patients to the 15 described in the literature to date. All 18 patients had substantially pigmented skin and hair, very poor VA (0.4-1.3 logMAR), nystagmus, (mild) ocular hypopigmentation, foveal hypoplasia, and misrouting. Although pigmentation levels were mildly affected in OCA7, patients had a severe ocular phenotype with VA at the poorer end of the albinism spectrum, severe foveal hypoplasia, and chiasmal misrouting. OCA7 patients had a phenotype restricted to the eyes, and similar to that of X-linked ocular albinism. We therefore propose to rename the disorder in ocular albinism type 2. Unfolding the role of LRMDA in OCA7, may bring us a step closer in identifying the responsible factors for the co-occurrence of foveal hypoplasia and misrouting.

GAA-FGF14 disease: defining its frequency, molecular basis, and 4-aminopyridine response in a large downbeat nystagmus cohort.

BACKGROUND: GAA-FGF14 disease/spinocerebellar ataxia 27B is a recently described neurodegenerative disease caused by (GAA)≥250 expansions in the fibroblast growth factor 14 (FGF14) gene, but its phenotypic spectrum, pathogenic threshold, and evidence-based treatability remain to be established. We report on the frequency of FGF14 (GAA)≥250 and (GAA)200-249 expansions in a large cohort of patients with idiopathic downbeat nystagmus (DBN) and their response to 4-aminopyridine. METHODS: Retrospective cohort study of 170 patients with idiopathic DBN, comprising in-depth phenotyping and assessment of 4-aminopyridine treatment response, including re-analysis of placebo-controlled video-oculography treatment response data from a previous randomised double-blind 4-aminopyridine trial. FINDINGS: Frequency of FGF14 (GAA)≥250 expansions was 48% (82/170) in patients with idiopathic DBN. Additional cerebellar ocular motor signs were observed in 100% (82/82) and cerebellar ataxia in 43% (35/82) of patients carrying an FGF14 (GAA)≥250 expansion. FGF14 (GAA)200-249 alleles were enriched in patients with DBN (12%; 20/170) compared to controls (0.87%; 19/2191; OR, 15.20; 95% CI, 7.52-30.80; p < 0.0001). The phenotype of patients carrying a (GAA)200-249 allele closely mirrored that of patients carrying a (GAA)≥250 allele. Patients carrying a (GAA)≥250 or a (GAA)200-249 allele had a significantly greater clinician-reported (80%, 33/41 vs 31%, 5/16; RR, 2.58; 95% CI, 1.23-5.41; Fisher's exact test, p = 0.0011) and self-reported (59%, 32/54 vs 11%, 2/19; RR, 5.63; 95% CI, 1.49-21.27; Fisher's exact test, p = 0.00033) response to 4-aminopyridine treatment compared to patients carrying a (GAA)<200 allele. Placebo-controlled video-oculography data, available for four patients carrying an FGF14 (GAA)≥250 expansion, showed a significant decrease in slow phase velocity of DBN with 4-aminopyridine, but not placebo. INTERPRETATION: This study confirms that FGF14 GAA expansions are a frequent cause of DBN syndromes. It provides preliminary evidence that (GAA)200-249 alleles might be pathogenic. Finally, it provides large real-world and preliminary piloting placebo-controlled evidence for the efficacy of 4-aminopyridine in GAA-FGF14 disease. FUNDING: This work was supported by the Clinician Scientist program "PRECISE.net" funded by the Else Kröner-Fresenius-Stiftung (to CW, AT, and MSy), the grant 779257 "Solve-RD" from the European's Union Horizon 2020 research and innovation program (to MSy), and the grant 01EO 1401 by the German Federal Ministry of Education and Research (BMBF) (to MSt). This work was also supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) N° 441409627, as part of the PROSPAX consortium under the frame of EJP RD, the European Joint Programme on Rare Diseases, under the EJP RD COFUND-EJP N° 825575 (to MSy, BB and-as associated partner-SZ), the NIH National Institute of Neurological Disorders and Stroke (grant 2R01NS072248-11A1 to SZ), the Fondation Groupe Monaco (to BB), and the Montreal General Hospital Foundation (grant PT79418 to BB). The Care4Rare Canada Consortium is funded in part by Genome Canada and the Ontario Genomics Institute (OGI-147 to KMB), the Canadian Institutes of Health Research (CIHR GP1-155867 to KMB), Ontario Research Foundation, Genome Quebec, and the Children's Hospital of Eastern Ontario Foundation. The funders had no role in the conduct of this study.

Multimodal deep learning-based diagnostic model for BPPV.

BACKGROUND: Benign paroxysmal positional vertigo (BPPV) is a prevalent form of vertigo that necessitates a skilled physician to diagnose by observing the nystagmus and vertigo resulting from specific changes in the patient's position. In this study, we aim to explore the integration of eye movement video and position information for BPPV diagnosis and apply artificial intelligence (AI) methods to improve the accuracy of BPPV diagnosis. METHODS: We collected eye movement video and diagnostic data from 518 patients with BPPV who visited the hospital for examination from January to March 2021 and developed a BPPV dataset. Based on the characteristics of the dataset, we propose a multimodal deep learning diagnostic model, which combines a video understanding model, self-encoder, and cross-attention mechanism structure. RESULT: Our validation test on the test set showed that the average accuracy of the model reached 81.7%, demonstrating the effectiveness of the proposed multimodal deep learning method for BPPV diagnosis. Furthermore, our study highlights the significance of combining head position information and eye movement information in BPPV diagnosis. We also found that postural and eye movement information plays a critical role in the diagnosis of BPPV, as demonstrated by exploring the necessity of postural information for the diagnostic model and the contribution of cross-attention mechanisms to the fusion of postural and oculomotor information. Our results underscore the potential of AI-based methods for improving the accuracy of BPPV diagnosis and the importance of considering both postural and oculomotor information in BPPV diagnosis.

Red flags alerting a posterior cranial fossa tumor from audiovestibular perspectives - a review.

BACKGROUND: There is no comprehensive and up-to-date overview of audiovestibular approach to the posterior fossa tumors in the literature. OBJECTIVE: This paper reviewed the literature relating to tumors at the posterior cranial fossa to find red flags alerting a posterior fossa lesion from audiovestibular perspectives. METHODS: This review was developed from articles published in those journals listed on the journal citation reports. Through the PubMed database, Embase, Google Scholar, and Cochrane library, 60 articles were finally obtained based on the PRISMA guidelines for reporting reviews. RESULTS: The presence of one red flag indicates a positive predictive value of 33% for detecting a posterior fossa lesion. Clinical features, namely, 1) mid-frequency sudden sensorineural hearing loss (SNHL), 2) bilateral sudden SNHL, and 3) rebound nystagmus may indicate a posterior fossa lesion, representing one, two, and three red flags, respectively. CONCLUSION: Those with 1) mid-frequency sudden SNHL, 2) bilateral sudden SNHL, and 3) rebound nystagmus trigger one, two, and three red flags, respectively, alerting clinicians the possibility of a posterior fossa lesion, which warrant MR imaging to exclude life-threatening or treatable conditions. SIGNIFICANCE: Patients with posterior fossa tumors may have potential life-threatening outcome.

Alström syndrome mimicking spasmus nutans: report of a novel ALMS1 variant.

We report the case of an otherwise healthy 6-year-old girl presenting with poor visual acuity, photophobia, and abnormal eye and head movements who was initially diagnosed with spasmus nutans. A remote history of presumed viral cardiomyopathy and further electroretinography testing raised suspicion for Alström syndrome. She was diagnosed with a novel ALMS1 variant.

Videoocular assessment of eye movement activity in an ataxia-telangiectasia: a case study.

PURPOSE: Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by progressive neurological deficits, including prominent oculomotor dysfunction. We report 5 cases of eye movement assessment in children 9-15 years old with A-T. METHODS: Three different oculomotor tasks (gaze holding, visually guided saccades and visual search) were used, and video-oculography was performed. Additionally, the scale for the assessment and rating of ataxia (SARA) score was used to assess severity of the cerebellar ataxia. RESULTS: Unstable gaze holding, nystagmus and saccadic intrusions were found. In addition to psychophysiological assessment results, we provide quantitative analysis of oculomotor activity, revealing a specific abnormal oculomotor pattern, consisting of (i) marked saccade hypermetria, (ii) unstable gaze holding, and (iii) gaze-evoked nystagmus. CONCLUSION: Our study opens the prospect to evaluate efficacy and safety of alternative methods for supporting the patient and improving his/her life quality.

Pearls & Oy-sters: Ocular Myasthenia Gravis: Central Ocular Motor Signs and Unilateral Visual Loss Caused by the Great Neuro-Ophthalmologic Impersonator.

Myasthenia gravis (MG) has been described as a great mimicker of other neurologic and ocular motility disorders, including centrally mediated ophthalmoplegia. For example, ocular myasthenia gravis (ocular MG) may cause impaired binocular visual acuity for near vision due to reduced accommodation or for distance vision due to accommodative excess. Notably, accommodative excess due to ocular MG is rare, but may occur with exotropia, with or without diplopia. We report 2 cases of ocular MG: First, a 32-year-old man with exotropia, bilateral hypometric and slowed adducting saccades with dissociated abducting nystagmus, miosis, and decreased distance vision in his right eye; second, a 45-year-old man with similar ocular motor deficits, miosis, and myopia. Both patients showed ocular motor deficits which appeared to localize to the pons but were instead due to ocular MG. Ocular MG should be considered in patients who present with reduced visual acuities due to any disruption in accommodation. Any ocular motor deficit, even if appearing to be centrally mediated or occurring without ptosis, may be caused by ocular MG.

Nystagmus in a child with nephrotic syndrome.

We report a child with steroid-dependent nephrotic syndrome presenting with excessive irritability, double vision and inability to walk for 5 days. On examination, the child was irritable with Glasgow coma sccale (GCS of 12/15, had bilateral convergent squint (R>L), vertical nystagmus, ataxia without any focal neurological deficits and normal fundus. MRI brain with venogram showed bilateral symmetric FLAIR hyperintensity in the medial thalamus and periaqueductal grey matter showing diffuse restriction with normal venogram. A possibility of Wernicke encephalopathy (WE) was considered and the child was started on thiamine supplementation, following which he had significant improvement in his symptoms. His irritability reduced with significant improvement in the range of eye movements and vertical nystagmus. At 3-month follow-up, the child is asymptomatic with normal gait. Although WE is uncommon in children with nephrotic syndrome, the possibility has to be kept in mind when a child presents with atypical neurological symptoms.

Nystagmus in the B6(CG)Tyr(c-2J)/J Albino Mouse: A Functional and RNA-Seq Analysis.

Purpose: Infantile nystagmus syndrome (INS) is a gaze-holding disorder characterized by conjugate, uncontrolled eye oscillations that can result in significant visual acuity loss. INS is often associated with albinism, but the mechanism is unclear. Albino mice have nystagmus; however, a pigmented mouse with a tyr mutation making it phenotypically albino, the B6(CG)-Tyr(c-2J)/J (B6 albino), had not been tested. We tested optokinetic response (OKR) in B6 albino and control mice. RNA-Seq was performed on extraocular muscles (EOM), tibialis anterior (TA) muscle, abducens (CN6), and oculomotor (CN3) neurons to uncover molecular differences that may contribute to nystagmus. Methods: OKR was measured using an ISCAN system. RNA was isolated from four tissues to identify differentially expressed genes and validated with qPCR and immunohistochemistry. Ingenuity pathway analyses identified top biological pathways. Results: All B6 albino mice tested had nystagmus. Differential RNA expression analysis showed 383 genes differentially expressed in EOM, 70 in CN3, 20 in CN6, and 639 in the TA. Two genes were differentially expressed in all four tissues: wdfy1 and nnt. Differences were validated by qPCR and immunostaining. Conclusions: The tyr mutation in B6 albino mice, genotypically pigmented and phenotypically albino, is sufficient to result in spontaneous nystagmus. The two genes with decreased expression in the B6 albino tissues examined, wdfy1 and nnt, have been implicated in mitochondrial dysfunction and stem cell maintenance in other systems. Their function in extraocular muscle is unknown. These studies suggest that this mouse model of nystagmus may allow molecular identification of candidate nystagmus-related genes.

Visual acuity improvement in children with albinism beyond the first decade of life.

PURPOSE: To determine if visual maturation continues beyond the first decade of life in children with albinism and whether this is related to albinism type, presence of nystagmus, eye muscle surgery or refractive errors. DESIGN: Case series based on retrospective study of children with confirmed genetic diagnosis of albinism. METHODS: Clinical data were obtained from medical files of children examined during school years, including albinism type, visual acuity, eye muscle surgery, nystagmus, and others on different visits (Visit 1: ages 7-9; Visit 2: ages: 10-12; Visit 3: ages 13-16; Visit 4: ages >16). RESULTS: Seventy-five children with albinism were included in the study. Patients were divided into different groups according to the albinism type including OCA1A: 17; OCA1B: 28; OCA2: 26; HPS: 3; OCA4: 1. Follow-up ranged from 3-13 years. Progressive visual acuity improvement was seen in all three main groups. T-test paired samples showed a statistically significant improvement when comparing vision from Visit 1 and Visit 3 in both OCA1A and OCA2 groups, with a mean vision improvement of 2 lines. There was no correlation between visual improvement and refractive error, eye muscle surgery or nystagmus. CONCLUSION: An improved visual performance was seen in a large percentage of children with albinism during the second decade of life. The reason for this late improvement in vision is not clear but may be related to late foveal maturation or improvement in nystagmus with time. This information is useful for clinicians of these patients and when counseling parents.

Teaching Video NeuroImage: Monocular Rotational Nystagmus Caused by Superior Oblique Myokymia.

A 61-year-old man presented with 2 days of "flickering" vision. The symptom resolved with closure of the left eye. Examination demonstrated involuntary high-frequency, low-amplitude intorting movements of the left eye, consistent with superior oblique myokymia (Video 1). Ocular ductions were full, and there were no abnormal movements of the right eye.

Post-transfusion severe headache in a patient with thalassemia with superficial siderosis of the central nervous system: a case report and literature review.

BACKGROUND: Patients with severe thalassemia may experience adverse effects from transfusion such as fever, rash, and iron overload after long-term transfusion therapy. Severe headaches as a side effect of blood transfusion in patients with thalassemia are not commonly observed, especially when combined with superficial siderosis of the central nervous system, which is easily misdiagnosed and requires excessive examination and treatment. CASE PRESENTATION: A 31-year-old woman was admitted with severe headache and vomiting over 3 days following blood transfusion. She was diagnosed with intermediate α-thalassemia at 2 years of age and had a history of irregular blood transfusions. Physical examination revealed horizontal nystagmus with no other abnormal neurological signs. Magnetic resonance (MR) imaging, MR venography, MR arteriography, and cerebrospinal fluid analysis were normal. However, susceptibility-weighted imaging showed abnormal signals in the bilateral and fourth ventricles. Initial antibiotics, antivirals, decompression of intracranial pressure, iron chelation, and symptomatic treatments were administered; subsequently, small intermittent blood transfusions were cautiously administered for severe anemia. The patient's headache was gradually relieved, and she was discharged on day 9. At the 5-month follow-up, the patient's headache recurred following another transfusion. CONCLUSIONS: Severe post-transfusion headache in patients with thalassemia has not been fully recognized and is easily misdiagnosed, leading to excessive examination and treatment. Understanding the clinical features of transfusion-related headaches can help identify this complication, but the exact pathophysiological mechanism requires further research.

Preliminary study on the computer-based optokinetic nystagmus analyzer to detect the visual acuity of preschool children.

The purpose of this study is to examine the viability, precision, and consistency of a computer-based optokinetic nystagmus analyzer (nystagmus meter) for diagnosing eyesight in preschoolers. A total of 59 subjects who could pass the log of minimum angle of resolution (LogMAR) visual acuity chart were divided into three groups by age, 4-, 5-, and 6-year-old groups, and their visual acuity was tested with nystagmus meter. The percentage of children in each age group that could be detected by nystagmus was recorded along with the differences between these groups. The correlation between the test results from the two methods was found for each age group using the correlation coefficient method. Repeated measurements were used to assess the two visual acuity values of the measured nystagmus, and the repeatability of the two measurement techniques for different age groups was compared. The overall measurability of the visual acuity detected by nystagmus was 93.22%, and the measurability of the 4-, 5-, and 6-year-old groups was 90%, 95%, and 94.74%, respectively. There was no statistically significant difference in the measurability of subjects among all age groups (P = 1.0). The outcomes of the LogMAR visual acuity chart had a negative correlation with the visual acuity measured by the nystagmus meter. The overall correlation coefficient R value was -0.80, and the correlation coefficient R value of the 4-, 5-, and 6-year-old groups was -0.79, -0.76, and -0.87, respectively. The nystagmus meter has good feasibility, accuracy, and stability in visual acuity testing and can be used for visual acuity testing in children.