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Resume Introduction Les affections neuro-ophtalmologiques necessitent une prise en charge transdisciplinaire specialisee prenant en charge sur le plan medical et chirurgical des personnes atteintes de deficience visuelle en rapport avec une pathologie du systeme nerveux. L’objectif principal de cette etude est de definir la specificite de la neuro-ophtalmologie dans le domaine de la sante visuelle. L’objectif secondaire est de reconstituer le parcours de soins du patient, en etudiant l’organisation de la prise en charge, en termes d’accessibilite aux soins et de personnalisation du parcours. Patients et methodes Une etude de terrain a ete menee de fevrier a juin 2015, au sein du service d’ophtalmologie du CHU Pitie-Salpetriere a Paris. Un entretien de 30 minutes avec le patient avant ou apres sa consultation de neuro-ophtalmologie a ete realise afin de reconstituer le parcours de soins. Les dossiers medicaux des patients interroges ont egalement ete analyses. Resultats Dix-sept parcours de soins (10 femmes et 7 hommes) ont ete reconstitues. L’âge moyen du debut d’apparition des atteintes visuelles etait de 44,5 ans (± 8,4 ans). Si l’on exclut 3 patients de plus de 66 ans a la retraite, 35,71 % etaient en activite, 35,71 % etaient en invalidite et 28,57 % etait en arret maladie. Dix patients (58,82 %) correspondent aux criteres d’admission en affection longue duree (ALD). La premiere demarche avait ete effectuee aupres de professionnels de proximite exercant en liberal. Le premier medecin consulte etant le medecin generaliste (59 %), puis l’ophtalmologiste liberal en urgence (17 %). En moyenne, les patients ont suivi 8 etapes durant leur parcours de soins (de 6 a 10 etapes) et 14 departements medicaux etaient susceptibles d’intervenir. L’etude a montre qu’il existait une collaboration avec les autres structures du departement hospitalo-universitaire (DHU) vision et handicaps (notamment avec la Fondation Rothschild, le CHNO des Quinze-Vingts, la Fondation Sainte-Marie). Outre les services de reeducation, les professionnels de sante participant au suivi du patient a l’exterieur de l’hopital comportaient une orthoptiste (11,7 %), un psychologue (11,7 %), un opticien specialise en basse vision pour les aides visuelles. Enfin, les associations de patients, AFM-Telethon (myasthenie) et l’association ARIBa (deficience visuelle) ont ete sollicitees par 2 patients pour les accompagner. Une gene fonctionnelle dans des activites de la vie quotidienne entrainant des incapacites avec repercussion psychologique etait notee par de nombreux patients. Les plaintes les plus frequentes concernent les deplacements (29,41 %) et la lecture (23,52 %). Au total, 77 % des personnes se disent affectees dans leur bien-etre et inquietes sur l’evolution de la maladie. Discussion et conclusions La reconstitution du parcours de soins du patient atteint d’affections neuro-ophtalmologiques montre que ces pathologies sont d’une part souvent meconnues, d’autre part complexes, aboutissant a un nombre d’etapes souvent importantes pour le patient. Ceci souligne egalement la necessite d’un reseau de soin specialise et structure pour ameliorer l’efficacite de cette prise en charge. Enfin, ces resultats montrent l’existence d’un handicap tres frequent, pouvant retentir dans toutes les spheres de la vie du patient, soulignant l’importance des structures de reeducation et des acteurs participant au suivi de ces patients en aval des soins aigus.

Purpose: To evaluate functional vision in patients with CHARGE syndrome (coloboma, heart defects, atresia of the choanae, retardation of growth and development, genital and urinary anomalies, and ear anomalies) by using a new questionnaire entitled VISIOCHARGE. Methods: Ophthalmological data including fundus description and visual acuity, when available, were extracted from the charts of 83 patients with CHARGE syndrome, and the VISIOCHARGE questionnaire was prospectively mailed to 55 of those patients. The answers from the 36 responders (18 males) allowed for the calculation of three scores that assessed distance vision, near vision, and overall ability scores. Results: Visual acuity measurements were extracted from the charts of 20 of the 36 patients. The mean visual acuity was 20/50. The mean distance vision score of 0.62 ± 0.30 and near vision score of 0.78 ± 0.23 were correlated with visual acuity in the 20 patients (ρ = 0.64, P = .002 and ρ = 0.61, P = .005, respectively) and were associated with the severity of colobomatous malformation ( P = .049 and P = .008, respectively). Severity of the ocular malformation was not associated with the overall ability score ( P = .64). Conclusions: The VISIOCHARGE questionnaire is feasible for patients with CHARGE syndrome and may help in the assessment of visual function. The mean visual acuity and answers to the VISIOCHARGE questionnaire showed relatively good visual skills in patients with CHARGE syndrome in everyday life, even in those with bilateral colobomas, which contrasts with the pessimistic conclusions usually resulting from the initial fundus examination. [ J Pediatr Ophthalmol Strabismus . 2020;57(2):120–128.]

Hearing loss and visual impairment in childhood have mostly genetic origins, some of them being related to sensorial neuronal defects. Here, we report on eight subjects from four independent families affected by auditory neuropathy and optic atrophy. Whole-exome sequencing revealed biallelic mutations in FDXR in affected subjects of each family. FDXR encodes the mitochondrial ferredoxin reductase, the sole human ferredoxin reductase implicated in the biosynthesis of iron-sulfur clusters (ISCs) and in heme formation. ISC proteins are involved in enzymatic catalysis, gene expression, and DNA replication and repair. We observed deregulated iron homeostasis in FDXR mutant fibroblasts and indirect evidence of mitochondrial iron overload. Functional complementation in a yeast strain in which ARH1, the human FDXR ortholog, was deleted established the pathogenicity of these mutations. These data highlight the wide clinical heterogeneity of mitochondrial disorders related to ISC synthesis.

Summary Introduction Neuro-ophthalmologic conditions require specialized multidisciplinary management, both medical and surgical, for patients affected by visual loss due to nervous system disease. The primary goal of this study is to define the specificity of neuro-ophthalmology within the realm of visual health. The secondary goal is to review clinical care pathways by studying the organization of management, in terms of accessibility to care and personalization of the care pathway. Patients and methods A field study was carried out from February to June 2015, within the ophthalmology service of the Pitie-Salpetriere University Medical Center in Paris. A 30-minute interview with the patient before or after his or her neuro-ophthalmology consultation was performed, to describe the clinical care pathway. The medical records of interviewed patients were also analyzed. Results Seventeen care pathways (10 women and 7 men) were reviewed. The mean age at appearance of visual involvement was 44.5 years (± 8.4 years). If we exclude 3 patients over 66 years and retired, 35.71% were active, 35.71% were disabled, and 28.57% were on sick leave. Ten patients (58.82%) met the criteria for admission to long-term care. The first step had been carried out by local private practitioners. The first physician seen was the general medicine physician (59%), then the private ophthalmologist on an emergency basis (17%). On average, patients went through 8 steps during their care pathway (from 6 to 10 steps) and 14 medical departments were involved. The study showed collaboration with the other services of the University Hospital Department of Vision and Disabilities (notably with the Fondation Rothschild, the Quinze-Vingts National Ophthalmology Hospital, and the Fondation Sainte-Marie). In addition to rehabilitation services, health care professionals participating in the outpatient care of the patients included an orthoptist (11.7%), a psychologist (11.7%), and an optician specializing in low vision for visual aids. Finally, patient support groups, AFM-Telethon (myasthenia) and the ARIBa association (visual disability) were solicited by 2 patients for their involvement. A disturbance in activities of daily living leading to disabilities with psychological repercussions was noted by a number of patients. The most frequent complaints involve mobility (29.41%) and reading (23.52%). In total, 77% of patients state that their well-being has been affected, and they are disturbed by the progression of their disease. Discussion and conclusions The review of the clinical care pathway of patients affected by neuro-ophthalmological conditions shows that these pathologies are, on the one hand, often poorly understood, and on the other hand complex, leading to an often significant number of steps for the patient. This also emphasizes the necessity of a care network, specialized and structured to improve the efficiency of this management. Finally, these results demonstrate the existence of a very frequent disability, which may affect all aspects of the patients’ lives, highlighting the importance of rehabilitation services and individuals participating in the follow-up of these patients beyond their acute care.

Although visual function is thought to be preserved in patients with locked-in syndrome (LIS), enabling them to communicate through vertical or lateral eye movements or blinking of the upper eyelid, nothing is known about the actual visual function of patients with LIS. The goal of this study is to evaluate the visual function of patients with LIS which may enable better evaluation of the state of consciousness of these patients. Patients with LIS seen in a single neurovascular unit of a tertiary center between 1997 and 2013 were retrospectively reviewed. Each patient had a specialized neuro-ophthalmological evaluation under optimal environmental conditions (light, contrast, examination distance, head position, best ergonomic adaptation, and establishment of a means of communication with help from the patient's friends/family). Visual acuity, extraocular eye movements, confrontational visual field, slit lamp and fundus examination were performed. Thirteen patients (6M/7F) were included in this study. Mean visual acuity was 20/60. Oculomotor examination was abnormal in 77%. Forty-six percent of patients presented binocular diplopia mainly related to a VIth nerve palsy. One patient presented complete ophthalmoplegia. Forty-six percent of patients had nystagmus responsible for oscillopsia (oculopalatal tremor). An abnormal visual field was observed in 17% of patients, and abnormal pupillary light response leading to photophobia was present in 22% of patients. Keratitis or dry eye syndrome was present in most patients and was a major cause of pain and visual impairment. Our results suggest that the visual function is impaired in all patients with LIS. This impairment is multifactorial including mostly binocular diplopia or oscillopsia but also refractive errors, dry eye syndrome, keratitis or visual field defect. This altered visual function may alter the ability of the patient to interact with his environment and lead to underestimation of their state of consciousness. An ophthalmologic evaluation would allow for improvement of these patients' comfort, their ability to communicate, and the assessment of their state of consciousness.

Mutations in the spastic paraplegia 7 (SPG7) gene encoding paraplegin are responsible for autosomal recessive hereditary spasticity. We screened 135 unrelated index cases, selected in five different settings: SPG7-positive patients detected during SPG31 analysis using SPG31/SPG7 multiplex ligation-dependent probe amplification (n = 7); previously reported ambiguous SPG7 cases (n = 5); patients carefully selected on the basis of their phenotype (spasticity of the lower limbs with cerebellar signs and/or cerebellar atrophy on magnetic resonance imaging/computer tomography scan and/or optic neuropathy and without other signs) (n = 24); patients with hereditary spastic paraparesis referred consecutively from attending neurologists and the national reference centre in a diagnostic setting (n = 98); and the index case of a four-generation family with autosomal dominant optic neuropathy but no spasticity linked to the SPG7 locus. We identified two SPG7 mutations in 23/134 spastic patients, 21% of the patients selected according to phenotype but only 8% of those referred directly. Our results confirm the pathogenicity of Ala510Val, which was the most frequent mutation in our series (65%) and segregated at the homozygous state with spastic paraparesis in a large family with autosomal recessive inheritance. All SPG7-positive patients tested had optic neuropathy or abnormalities revealed by optical coherence tomography, indicating that abnormalities in optical coherence tomography could be a clinical biomarker for SPG7 testing. In addition, the presence of late-onset very slowly progressive spastic gait (median age 39 years, range 18-52 years) associated with cerebellar ataxia (39%) or cerebellar atrophy (47%) constitute, with abnormal optical coherence tomography, key features pointing towards SPG7-testing. Interestingly, three relatives of patients with heterozygote SPG7 mutations had cerebellar signs and atrophy, or peripheral neuropathy, but no spasticity of the lower limbs, suggesting that SPG7 mutations at the heterozygous state might predispose to late-onset neurodegenerative disorders, mimicking autosomal dominant inheritance. Finally, a novel missense SPG7 mutation at the heterozygous state (Asp411Ala) was identified as the cause of autosomal dominant optic neuropathy in a large family, indicating that some SPG7 mutations can occasionally be dominantly inherited and be an uncommon cause of isolated optic neuropathy. Altogether, these results emphasize the clinical variability associated with SPG7 mutations, ranging from optic neuropathy to spastic paraplegia, and support the view that SPG7 screening should be carried out in both conditions.

Background Usher syndrome (USH) combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3). Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool. Methods We sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3). Results Biallelic mutations were detected in 39 patients (72%) and monoallelic mutations in an additional 10 patients (18.5%). In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%), and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48%) were novel. Conclusions Based on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy.