Case of acute zonal occult outer retinopathy with abnormal pattern visual evoked potentials

Electrophysiological and morphological findings were studied in a case of acute zonal occult outer retinopathy (AZOOR) showing abnormal pattern visual evoked potentials (VEPs) at the onset and significant functional recovery in the natural course. A 21-year-old woman presented with acute onset of photopsia and a large scotoma in the right eye of 2 weeks duration. Her visual acuity was 20/20 in both eyes with no ophthalmoscopic and fluorescein angiographic abnormalities. However, a relative afferent pupillary defect and an enlarged blind spot were found in the right eye. The pattern VEPs were severely reduced when the right eye was stimulated. The amplitudes of both rod and cone full-field electroretinographics (ERGs) were reduced in the right eye. The amplitudes of the multifocal ERGs were reduced in the area of the enlarged blind spot. Irregularities in the inner segment/outer segment (IS/OS) line of the photoreceptors were observed over the nasal fovea by optical coherence tomography (OCT). The patient was followed without treatment. The enlarged blind spot disappeared in 3 months after the onset. At 5 months, reappearance of the IS/OS line was detected by OCT. At 6 months, the P100 recovered to normal values. At 1 year, the reduced full-field ERGs were almost normal size and the multifocal ERGs in the area corresponding to the enlarged blind spot were also improved. ERG findings are crucial for differentiating AZOOR from retrobulbar neuritis, especially in patients with abnormal pattern VEPs. The pattern VEPs, full-field ERGs, multifocal ERGs, and OCT images can be abnormal in the early phase of AZOOR, but they can all improve during the natural course

Stargardt macular dystrophy and therapeutic approaches

Stargardt macular dystrophy (Stargardt disease; STGD1; OMIM 248200) is the most prevalent inherited macular dystrophy. STGD1 is an autosomal recessive disorder caused by multiple pathogenic sequence variants in the large ABCA4 gene (OMIM 601691). Major advances in understanding both the clinical and molecular features, as well as the underlying pathophysiology, have culminated in many completed, ongoing and planned human clinical trials of novel therapies.The aims of this concise review are to describe (1) the detailed phenotypic and genotypic characteristics of the disease, multimodal imaging findings, natural history of the disease, and pathogenesis, (2) the multiple avenues of research and therapeutic intervention, including pharmacological, cellular therapies and diverse types of genetic therapies that have either been investigated or are under investigation and (3) the exciting novel therapeutic approaches on the translational horizon that aim to treat STGD1 by replacing the entire 6.8 kb ABCA4 open reading frame

CRB1-associated Retinal Dystrophies: Genetics, Clinical Characteristics and Natural History

PURPOSE: To analyse the clinical characteristics, natural history, and genetics of CRB1-associated retinal dystrophies. DESIGN: Multicenter international retrospective cohort study. METHODS: Review of clinical notes, ophthalmic images, and genetic testing results of 104 patients (91 probands) with disease-causing CRB1 variants. Macular optical coherence tomography (OCT) parameters, visual function, fundus characteristics, and associations between variables were our main outcome measures. RESULTS: The mean age of the cohort at the first visit was 19.8 ± 16.1 (median 15) years of age, with a mean follow-up of 9.6 ± 10 years. Based on history, imaging, and clinical examination, 26 individuals were diagnosed with retinitis pigmentosa (RP, 26%), 54 with early-onset severe retinal dystrophy/Leber Congenital Amaurosis (EOSRD/LCA, 51%), and 24 with macular dystrophy (MD, 23%). Severe visual impairment was most frequent after 40 years of age for patients with RP and after 20 years of age for EOSRD/LCA. Longitudinal analysis revealed a significant difference between baseline and follow up best corrected visual acuity in the three sub-cohorts. Macular thickness decreased in most patients with EOSRD/LCA and MD, whereas the majority of patients with RP had increased perifoveal thickness. CONCLUSIONS: A subset of individuals with CRB1 variants present with mild, adult-onset RP. EOSRD/LCA phenotype was significantly associated with null variants, and 167_169 deletion was exclusively present in the MD cohort. The poor OCT lamination may have a degenerative component, as well as being congenital. Disease symmetry and reasonable window for intervention highlight CRB1 retinal dystrophies as a promising target for trials of novel therapeutics

CERKL-associated retinal dystrophy: Genetics, Phenotype and Natural History

PURPOSE: To analyze the clinical characteristics, natural history, and genetics of CERKL-associated retinal dystrophy in the largest series to date. DESIGN: Multicenter retrospective cohort study. SUBJECTS: 47 patients (37 families) with likely disease-causing CERKL variants METHODS: Review of clinical notes, ophthalmic images, and molecular diagnosis from two international centres. MAIN OUTCOME MEASURES: Visual function, retinal imaging and characteristics were evaluated and correlated. RESULTS: The mean age at the first visit was 29.6 + 13.9 years and the mean follow-up time was 9.1 + 7.4 years. The most frequent initial symptom was central vision loss (40%) and the most common retinal feature was well-demarcated areas of macular atrophy (57%). Seventy percent of the participants had double-null genotypes and 64% had electrophysiological assessment. Amongst the latter, 53% showed similar severity of rod and cone dysfunction, 27% revealed a rod-cone, 10% a cone-rod, and 10% a macular dystrophy dysfunction pattern. Patients without double-null genotypes tended to have fewer pigment deposits and included a higher proportion of older patients with a relatively mild electrophysiological phenotype. Longitudinal analysis showed that over half of the cohort lost 15 ETDRS letters or more in at least one eye during the first 5 years of follow up. CONCLUSIONS: The phenotype of CERKL-retinal dystrophy is broad, encompassing isolated macular disease to severe retina-wide involvement, with a range of functional phenotypes, generally not fitting in the rod-cone/cone-rod dichotomy. Disease onset is often earlier, with more severe retinal degenerative changes and photoreceptor dysfunction, in nullizygous cases

RBP3-retinopathy - inherited high myopia and retinal dystrophy: Genetic Characterization, Natural History, and Deep Phenotyping

Objective: To examine the genetic and clinical features and the natural history of RBP3-associated retinopathy. // Design: Multi-center international, retrospective, case series. // Setting: Three tertiary referral centers. // Participants: Adults and children, with molecularly confirmed RBP3-associated retinopathy. // Main Outcomes and Measures: Multi-center, international, retrospective, consecutive observational study in three tertiary referral centers of adults and children, with molecularly confirmed RBP3-retinopathy. The genetic, clinical and retinal imaging findings, including optical coherence tomography (OCT) and fundus autofluorescence (FAF), were investigated both cross-sectionally and longitudinally. The results of International standard full-field and pattern electroretinography (ERG; PERG) were reviewed. // Results: We ascertained 12 patients (5 females), from 10 families, with four patients previously reported. Eight novel disease-causing RBP3 variants were identified. Ten patients were homozygous. The mean age (±SD, range) of the group was 21.4 years (±19.1, 2.9-60.5 years) at baseline evaluation. All 12 patients were highly myopic with a mean spherical equivalent of -16.0D (range; -7.0D to -33.0D). Visual acuity was not significantly different between eyes and no significant anisometropia was observed. Mean best corrected visual acuity (BCVA) was 0.48 LogMAR (range; 0.2-1.35, SD; ± 0.29 LogMAR) at baseline. Eleven patients had longitudinal BCVA assessment, with a mean BCVA of 0.46 LogMAR after a mean follow-up of 12.6 years. All patients were symptomatic with reduced VA and myopia by the age of 7 years. All patients had myopic fundi and features in keeping with high myopia on OCT, including choroidal thinning. The 4 youngest patients had no fundus pigmentary changes, with the rest presenting with a variable degree of mid-peripheral pigmentation and macular changes. FAF showed variable phenotypes, ranging from areas of increased signal to advanced atrophy in older patients. OCT showed cystoid macular edema at presentation in three patients, which persisted during follow-up in two patients and resolved to atrophy for the third patient. The ERGs were abnormal in 9 of 9 cases, revealing variable relative involvement of rod and cone photoreceptors with additional milder dysfunction post-phototransduction in some. All but one had PERG evidence of macular dysfunction, severe in most. // Conclusions: This study details the clinical and functional phenotype of RBP3-retinopathy in the largest cohort reported to date. RBP3-retinopathy is a disease characterized by early onset, slow progression over decades, and high myopia. The phenotypic spectrum and natural history as described herein has prognostic and counselling implications. RBP3-related disease should be considered in children with high myopia and retinal dystrophy

Genetic and Phenotypic Landscape of PRPH2-Associated Retinal Dystrophy in Japan

Peripherin-2 (PRPH2) is one of the causative genes of inherited retinal dystrophy. While the gene is relatively common in Caucasians, reports from Asian ethnicities are limited. In the present study, we report 40 Japanese patients from 30 families with PRPH2-associated retinal dystrophy. We identified 17 distinct pathogenic or likely pathogenic variants using next-generation sequencing. Variants p.R142W and p.V200E were relatively common in the cohort. The age of onset was generally in the 40’s; however, some patients had earlier onset (age: 5 years). Visual acuity of the patients ranged from hand motion to 1.5 (Snellen equivalent 20/13). The patients showed variable phenotypes such as retinitis pigmentosa, cone-rod dystrophy, and macular dystrophy. Additionally, intrafamilial phenotypic variability was observed. Choroidal neovascularization was observed in three eyes of two patients with retinitis pigmentosa. The results demonstrate the genotypic and phenotypic variations of the disease in the Asian cohort

KCNV2-associated retinopathy: genotype–phenotype correlations – KCNV2 study group report 3

BACKGROUND/AIMS: To investigate genotype–phenotype associations in patients withKCNV2retinopathy. METHODS: Review of clinical notes, best-corrected visual acuity (BCVA), molecular variants, electroretinography (ERG) and retinal imaging. Subjects were grouped according to the combination ofKCNV2variants—two loss-of-function (TLOF), two missense (TM) or one of each (MLOF)—and parameters were compared. RESULTS: Ninety-two patients were included. The mean age of onset (mean±SD) in TLOF (n=55), TM (n=23) and MLOF (n=14) groups was 3.51±0.58, 4.07±2.76 and 5.54±3.38 years, respectively. The mean LogMAR BCVA (±SD) at baseline in TLOF, TM and MLOF groups was 0.89±0.25, 0.67±0.38 and 0.81±0.35 for right, and 0.88±0.26, 0.69±0.33 and 0.78±0.33 for left eyes, respectively. The difference in BCVA between groups at baseline was significant in right (p=0.03) and left eyes (p=0.035). Mean outer nuclear layer thickness (±SD) at baseline in TLOF, MLOF and TM groups was 37.07±15.20 µm, 40.67±12.53 and 40.38±18.67, respectively, which was not significantly different (p=0.85). The mean ellipsoid zone width (EZW) loss (±SD) was 2051 µm (±1318) for patients in the TLOF, and 1314 µm (±965) for MLOF. Only one patient in the TM group had EZW loss at presentation. There was considerable overlap in ERG findings, although the largest DA 10 ERG b-waves were associated with TLOF and the smallest with TM variants. CONCLUSIONS: Patients with missense alterations had better BCVA and greater structural integrity. This is important for patient prognostication and counselling, as well as stratification for future gene therapy trials

Can artificial intelligence accelerate the diagnosis of inherited retinal diseases? Protocol for a data-only retrospective cohort study (Eye2Gene)

INTRODUCTION: Inherited retinal diseases (IRD) are a leading cause of visual impairment and blindness in the working age population. Mutations in over 300 genes have been found to be associated with IRDs and identifying the affected gene in patients by molecular genetic testing is the first step towards effective care and patient management. However, genetic diagnosis is currently slow, expensive and not widely accessible. The aim of the current project is to address the evidence gap in IRD diagnosis with an AI algorithm, Eye2Gene, to accelerate and democratise the IRD diagnosis service. METHODS AND ANALYSIS: The data-only retrospective cohort study involves a target sample size of 10 000 participants, which has been derived based on the number of participants with IRD at three leading UK eye hospitals: Moorfields Eye Hospital (MEH), Oxford University Hospital (OUH) and Liverpool University Hospital (LUH), as well as a Japanese hospital, the Tokyo Medical Centre (TMC). Eye2Gene aims to predict causative genes from retinal images of patients with a diagnosis of IRD. For this purpose, 36 most common causative IRD genes have been selected to develop a training dataset for the software to have enough examples for training and validation for detection of each gene. The Eye2Gene algorithm is composed of multiple deep convolutional neural networks, which will be trained on MEH IRD datasets, and externally validated on OUH, LUH and TMC. ETHICS AND DISSEMINATION: This research was approved by the IRB and the UK Health Research Authority (Research Ethics Committee reference 22/WA/0049) 'Eye2Gene: accelerating the diagnosis of IRDs' Integrated Research Application System (IRAS) project ID: 242050. All research adhered to the tenets of the Declaration of Helsinki. Findings will be reported in an open-access format

Characteristics of Training Center for Nurses Pertaining to Specified Medical Practice at Seirei Christopher University

P(論文)本学は2018 年に看護師特定行為研修指定研修機関に指定され、2019 年から研修を開始した。開講区分は「栄養及び水分管理に係る薬剤投与関連」の1 区分で、4 年間で16 名の修了者（見込み含む） を輩出した。2023 年度からは「在宅・慢性期領域パッケージ」が追加となる。本報告では、本学における特定行為研修の実際と特色についてまとめ、高度実践看護師育成に向けた今後の課題、方向性について述べる。紀要委員会企画Special Articlesdepartmental bulletin pape