scholarly journals Ocular Characteristics of Patients with Leber Congenital Amaurosis 6 Caused by Pathogenic RPGRIP1 Gene Variation in a Chinese Cohort

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Yumei Mao ◽  
Yanling Long ◽  
Bo Liu ◽  
Qingling Cao ◽  
Yijian Li ◽  
...  
Keyword(s):  
Fundus Autofluorescence ◽  
Chinese Patients ◽  
Fundus Photography ◽  
System Response ◽  
Autofluorescence Imaging ◽  
Genetic Characteristics ◽  
Full Field ◽  
Leber Congenital Amaurosis ◽  
Gene Variation ◽  
Rod System

Purpose. To delineate the clinical and genetic characteristics of Chinese patients with RPGRIP1-associated Leber congenital amaurosis 6 (LCA6). Methods. After screening 352 unrelated families with clinically diagnosed RP, five LCA6 patients with RPGRIP1 variations from unrelated Chinese families were identified. Full ophthalmology examinations, including decimal best-corrected visual acuity (BCVA), fundus photography, fundus autofluorescence imaging, spectral-domain optical coherence tomography (SD-OCT), full-field electroretinography (ffERG), multifocal electroretinography (mfERG), perimetry, and flash visual evoked potential (FVEP), were performed. Target next-generation sequencing (NGS) and Sanger sequencing were performed for the five patients to identify and to validate candidate disease-causing variants. Results. Five patients were molecularly diagnosed as the LCA6 associated with RPGRIP1 variation, with typical clinical characteristics including congenital night blindness, nystagmus, and visual defect, at an early age. Interestingly, LCA6 exhibited extensive clinical heterogeneity and the changes in the morphology and function were not completely consistent in the five LCA6 patients. Case 1 showed extensive inferior-nasal retinal atrophy with a corresponding area of hypofluorescence in fundus autofluorescence, and the fundus photograph was nearly normal in cases 2 and 3. The ERG results displayed a moderately reduced rod-system response in cases 1 and 2 and a significant reduced rod-system response in case 3. Both case 4 and case 5 showed mottled pigmentation in fundi and an unrecordable rod and cone-system response in ERG. Moreover, we identified eight compound variants and one homozygous variant in the five patients with RPGRIP1. Conclusions. This is the largest report focused on the clinical electrophysiological features of patients with associated LCA6 caused by the variation in the RPGRIP1 gene in the Chinese population with an enriched phenotypic and genotypic background of LCA6 to improve future gene therapies.

scholarly journals Expanding the Mutation Spectrum in ABCA4: Sixty Novel Disease Causing Variants and Their Associated Phenotype in a Large French Stargardt Cohort

2018 ◽  
Vol 19 (8) ◽  
pp. 2196 ◽  
Author(s):  
Marco Nassisi ◽  
Saddek Mohand-Saïd ◽  
Claire-Marie Dhaenens ◽  
Fiona Boyard ◽  
Vanessa Démontant ◽  
...  
Keyword(s):  
Near Infrared ◽  
Age Of Onset ◽  
Fundus Autofluorescence ◽  
Mutation Spectrum ◽  
Fundus Photography ◽  
Heterozygous Mutation ◽  
Autofluorescence Imaging ◽  
Stargardt Disease ◽  
Full Field ◽  
Uncertain Significance

Here we report novel mutations in ABCA4 with the underlying phenotype in a large French cohort with autosomal recessive Stargardt disease. The DNA samples of 397 index subjects were analyzed in exons and flanking intronic regions of ABCA4 (NM_000350.2) by microarray analysis and direct Sanger sequencing. At the end of the screening, at least two likely pathogenic mutations were found in 302 patients (76.1%) while 95 remained unsolved: 40 (10.1%) with no variants identified, 52 (13.1%) with one heterozygous mutation, and 3 (0.7%) with at least one variant of uncertain significance (VUS). Sixty-three novel variants were identified in the cohort. Three of them were variants of uncertain significance. The other 60 mutations were classified as likely pathogenic or pathogenic, and were identified in 61 patients (15.4%). The majority of those were missense (55%) followed by frameshift and nonsense (30%), intronic (11.7%) variants, and in-frame deletions (3.3%). Only patients with variants never reported in literature were further analyzed herein. Recruited subjects underwent complete ophthalmic examination including best corrected visual acuity, kinetic and static perimetry, color vision test, full-field and multifocal electroretinography, color fundus photography, short-wavelength and near-infrared fundus autofluorescence imaging, and spectral domain optical coherence tomography. Clinical evaluation of each subject confirms the tendency that truncating mutations lead to a more severe phenotype with electroretinogram (ERG) impairment (p = 0.002) and an earlier age of onset (p = 0.037). Our study further expands the mutation spectrum in the exonic and flanking regions of ABCA4 underlying Stargardt disease.

scholarly journals Clinical Phenotype of PDE6B-Associated Retinitis Pigmentosa

2021 ◽  
Vol 22 (5) ◽  
pp. 2374
Author(s):  
Laura Kuehlewein ◽  
Ditta Zobor ◽  
Katarina Stingl ◽  
Melanie Kempf ◽  
Fadi Nasser ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Genetic Testing ◽  
Retinitis Pigmentosa ◽  
Fundus Autofluorescence ◽  
Retinal Disease ◽  
New Drugs ◽  
Autofluorescence Imaging ◽  
Full Field ◽  
Tertiary Referral Center ◽  
The Right

In this retrospective, longitudinal, observational cohort study, we investigated the phenotypic and genotypic features of retinitis pigmentosa associated with variants in the PDE6B gene. Patients underwent clinical examination and genetic testing at a single tertiary referral center, including best-corrected visual acuity (BCVA), kinetic visual field (VF), full-field electroretinography, full-field stimulus threshold, spectral domain optical coherence tomography, and fundus autofluorescence imaging. The genetic testing comprised candidate gene sequencing, inherited retinal disease gene panel sequencing, whole-genome sequencing, and testing for familial variants by Sanger sequencing. Twenty-four patients with mutations in PDE6B from 21 families were included in the study (mean age at the first visit: 32.1 ± 13.5 years). The majority of variants were putative splicing defects (8/23) and missense (7/23) mutations. Seventy-nine percent (38/48) of eyes had no visual acuity impairment at the first visit. Visual acuity impairment was mild in 4% (2/48), moderate in 13% (6/48), and severe in 4% (2/48). BCVA was symmetrical in the right and left eyes. The kinetic VF measurements were highly symmetrical in the right and left eyes, as was the horizontal ellipsoid zone (EZ) width. Regarding the genetic findings, 43% of the PDE6B variants found in our patients were novel. Thus, this study contributed substantially to the PDE6B mutation spectrum. The visual acuity impairment was mild in 83% of eyes, providing a window of opportunity for investigational new drugs. The EZ width was reduced in all patients and was highly symmetric between the eyes, making it a promising outcome measure. We expect these findings to have implications on the design of future PDE6B-related retinitis pigmentosa (RP) clinical trials.

scholarly journals Structural evaluation in inherited retinal diseases

2021 ◽  
pp. bjophthalmol-2021-319228
Author(s):  
Malena Daich Varela ◽  
Burak Esener ◽  
Shaima A Hashem ◽  
Thales Antonio Cabral de Guimaraes ◽  
Michalis Georgiou ◽  
...  
Keyword(s):  
Adaptive Optics ◽  
Fundus Autofluorescence ◽  
Standard Of Care ◽  
Laser Speckle ◽  
Fundus Photography ◽  
Laser Speckle Flowgraphy ◽  
Retinal Diseases ◽  
Autofluorescence Imaging ◽  
Structural Evaluation ◽  
Fundus Imaging

Ophthalmic genetics is a field that has been rapidly evolving over the last decade, mainly due to the flourishing of translational medicine for inherited retinal diseases (IRD). In this review, we will address the different methods by which retinal structure can be objectively and accurately assessed in IRD. We review standard-of-care imaging for these patients: colour fundus photography, fundus autofluorescence imaging and optical coherence tomography (OCT), as well as higher-resolution and/or newer technologies including OCT angiography, adaptive optics imaging, fundus imaging using a range of wavelengths, magnetic resonance imaging, laser speckle flowgraphy and retinal oximetry, illustrating their utility using paradigm genotypes with on-going therapeutic efforts/trials.

Best Clinical Practice for Age-Related Macular Degeneration Imaging

2019 ◽  
Vol 3 (3) ◽  
pp. 167-171 ◽  
Author(s):  
K. Bailey Freund ◽  
Cynthia Toth ◽  
Marco Zarbin
Keyword(s):  
Optical Coherence Tomography ◽  
Macular Degeneration ◽  
Fundus Autofluorescence ◽  
Age Related Macular Degeneration ◽  
Fundus Photography ◽  
Optical Coherence ◽  
Autofluorescence Imaging ◽  
Clinical Practices ◽  
Age Related

Purpose: To identify best clinical practices for macular degeneration imaging. Methods: We reviewed best clinical practices for imaging patients with age-related macular degeneration. These recommendations are based on different levels of evidence (I-III). Results: The type of imaging needed depends to some degree on the clinical scenario: first visit vs follow-up visit vs poorly responsive patient. Conclusions: Imaging technologies that may be useful include optical coherence tomography, fundus photography, fundus autofluorescence imaging, fluorescein angiography, indocyanine green angiography, and optical coherence tomography angiography.

scholarly journals Clinical characterisation and the improved molecular diagnosis of autosomal dominant cone-rod dystrophy in patients with SCA7

2020 ◽  
Author(s):  
Xuan Zou ◽  
Fengxia Yao ◽  
Fengrong Li ◽  
Shijing Wu ◽  
Hui Li ◽  
...  
Keyword(s):  
Trinucleotide Repeat ◽  
Fundus Autofluorescence ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Cag Repeats ◽  
Chinese Patients ◽  
Fundus Photography ◽  
Spinocerebellar Ataxia Type ◽  
Optic Coherence Tomography ◽  
Spinocerebellar Ataxia Type 7

Abstract Purpose To evaluate the retinal phenotype and genetic features of Chinese patients with spinocerebellar ataxia type 7 (SCA7). Methods Detailed ophthalmic examinations, including electroretinograms, fundus photography, fundus autofluorescence and optical coherence tomography, were performed to analyse the retinal lesions of patients with SCA7. A molecular genetic analysis was completed to confirm the number of CAG repeats in ATXN7 gene on the patients and their family members. Results Eight patients from three families with SCA7 were included in this study. Trinucleotide repeat was expanded from 43 to 113 in the affected patients. The affected patients were characterised by different degrees of cone-rod dystrophy, which is positively related to the number of CAG repeats and age. All patients complained of progressive bilateral visual loss, and most cases reported visual disturbance earlier than gait movement or dysarthria. A coarse granular appearance of the macular region on scanning laser ophthalmoscopy, hypofluorescence in the macula on autofluorescence, retinal atrophy on optic coherence tomography, depression of multifocal electroretinograms and prominent abnormalities in cone-mediated responses on electrograms are the general features of SCA7-related retinopathy. Hyperreflective dots in the outer retinal layers and choroidal vessel layers are a common sign in optic coherence tomography in the advanced stage. Conclusions SCA shows a cone-rod dystrophy phenotype. The multimodal imaging of the retina is beneficial to detect the early lesions of cone-rod dystrophy related to SCA7.

scholarly journals Ocular Characteristics of Patients With Bardet–Biedl Syndrome Caused by Pathogenic BBS Gene Variation in a Chinese Cohort

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaohong Meng ◽  
Yanling Long ◽  
Jiayun Ren ◽  
Gang Wang ◽  
Xin Yin ◽  
...  
Keyword(s):  
Visual Function ◽  
Early Adulthood ◽  
Fundus Photography ◽  
Chinese Families ◽  
Bardet Biedl Syndrome ◽  
Full Field ◽  
Gene Variation ◽  
Multiple Organs ◽  
Flash Visual Evoked Potentials ◽  
Visual Evoked

Bardet–Biedl syndrome (BBS; OMIM 209900) is a rare genetic disease causing damage to multiple organs and affecting patients’ quality of life in late adolescence or early adulthood. In this study, the ocular characteristics including morphology and function, were analyzed in 12 BBS patients from 10 Chinese families by molecular diagnostics. A total of five known and twelve novel variants in four BBS genes (BBS2, 58.33%; BBS4, 8.33%; BBS7, 16.67%; and BBS9, 16.67%) were identified in 10 Chinese families with BBS. All patients had typical phenotypes of retinitis pigmentosa with unrecordable or severely damaged cone and rod responses on full-field flash electroretinography (ffERG). Most of the patients showed unremarkable reactions in pattern visual evoked potential (PVEP) and multifocal electroretinography (mfERG), while their flash visual evoked potentials (FVEP) indicated display residual visual function. Changes in the fundus morphology, including color fundus photography and autofluorescence (AF) imaging, were heterogeneous and not consistent with the patients’ functional tests. Overall, our study expands the variation spectrum of the BBS gene, showing that the ocular characteristics of BBS patients are clinically highly heterogeneous, and demonstrates the usefulness of a combination of the ffERG and FVEP assessments of visual function in the advanced stage of retinopathy in BBS.

scholarly journals Prediction of causative genes in inherited retinal disorder from fundus photography and autofluorescence imaging using deep learning techniques

2021 ◽  
pp. bjophthalmol-2020-318544
Author(s):  
Yu Fujinami-Yokokawa ◽  
Hideki Ninomiya ◽  
Xiao Liu ◽  
Lizhu Yang ◽  
Nikolas Pontikos ◽  
...  
Keyword(s):  
Deep Learning ◽  
Fundus Autofluorescence ◽  
Genetic Diagnosis ◽  
Fundus Photography ◽  
Macular Dystrophy ◽  
Test Accuracy ◽  
Autofluorescence Imaging ◽  
The Mean ◽  
Fundus Photographs ◽  
Retinal Disorder

Background/AimsTo investigate the utility of a data-driven deep learning approach in patients with inherited retinal disorder (IRD) and to predict the causative genes based on fundus photography and fundus autofluorescence (FAF) imaging.MethodsClinical and genetic data from 1302 subjects from 729 genetically confirmed families with IRD registered with the Japan Eye Genetics Consortium were reviewed. Three categories of genetic diagnosis were selected, based on the high prevalence of their causative genes: Stargardt disease (ABCA4), retinitis pigmentosa (EYS) and occult macular dystrophy (RP1L1). Fundus photographs and FAF images were cropped in a standardised manner with a macro algorithm. Images for training/testing were selected using a randomised, fourfold cross-validation method. The application program interface was established to reach the learning accuracy of concordance (target: >80%) between the genetic diagnosis and the machine diagnosis (ABCA4, EYS, RP1L1 and normal).ResultsA total of 417 images from 156 Japanese subjects were examined, including 115 genetically confirmed patients caused by the three prevalent causative genes and 41 normal subjects. The mean overall test accuracy for fundus photographs and FAF images was 88.2% and 81.3%, respectively. The mean overall sensitivity/specificity values for fundus photographs and FAF images were 88.3%/97.4% and 81.8%/95.5%, respectively.ConclusionA novel application of deep neural networks in the prediction of the causative IRD genes from fundus photographs and FAF, with a high prediction accuracy of over 80%, was highlighted. These achievements will extensively promote the quality of medical care by facilitating early diagnosis, especially by non-specialists, access to care, reducing the cost of referrals, and preventing unnecessary clinical and genetic testing.

Choroidal Manifestation of Systemic Non-Tuberculous Mycobacterial Infection: A Case Series

2020 ◽  
Vol 237 (04) ◽  
pp. 493-496
Author(s):  
Veronika Sinner ◽  
Reinhard Rüesch ◽  
Christophe Valmaggia ◽  
Margarita Todorova
Keyword(s):  
Indocyanine Green ◽  
Indocyanine Green Angiography ◽  
Fundus Autofluorescence ◽  
Systemic Disease ◽  
Graft Infection ◽  
Case Series ◽  
Mycobacterial Infection ◽  
Fundus Photography ◽  
Fluorescence Angiography ◽  
Autofluorescence Imaging

Abstract Purpose To describe choroidal findings associated with disseminated systemic non-mycobacterial infection. Methods A retrospective observational case series included two patients (four eyes) with non-tuberculous mycobacterial disease. The activity of choroidal lesions was assessed by clinical examination, supported by colour fundus photography, fundus autofluorescence imaging, indocyanine green angiography, fluorescence angiography, and optical coherence tomography (OCT) angiography. The relationships between clinical symptomatology, choroidal findings, and systemic disease activity were evaluated. Results One subject diagnosed with aortic graft infection showed positive cultures for Mycobacterium chimaera. One HIV-positive subject showed a positive saliva culture for Mycobacterium avium. At presentation, all subjects showed chorioretinal manifestation. In one patient, the lesions were active and in the other patient, the lesions appeared inactive. With activity of disseminated chorioretinitis, the lesions had indistinct, blurred borders on fluorescence angiography and indocyanine green angiography and were hyporeflective with well-defined borders on OCT imaging. Conclusion Multimodal imaging enables distinction between active and inactive lesions, thus supporting therapeutic management. Choroidal presentation of active disseminated mycobacterium infection indicates activity of systemic disease. Thus, even if the patient is not immunocompromised, an underlying systemic involvement should be ruled out.

Cone dystrophy with supernormal rod responses: A rare KCNV2 gene variant

2021 ◽  
pp. 112067212110000
Author(s):  
João Esteves-Leandro ◽  
Sónia Torres-Costa ◽  
Sérgio Estrela-Silva ◽  
Renato Santos-Silva ◽  
Elisete Brandão ◽  
...  
Keyword(s):  
Rare Variant ◽  
Pigment Epithelium ◽  
Fundus Autofluorescence ◽  
Retinal Pigment ◽  
Pattern Electroretinogram ◽  
Fundus Photography ◽  
Cone Dystrophy ◽  
Ophthalmological Examination ◽  
Full Field ◽  
Visual Acuity Loss

Purpose: To describe the clinical, electrophysiological, and genetic findings of three Portuguese families with a rare variant in the KCNV2 gene resulting in “cone dystrophy with supernormal rod responses” (CDSRR). Methods: Retrospective clinical revision of five individuals from three unrelated families with CDSRR. Ophthalmological examination was described in all patients and included color vision testing, fundus photography, fundus autofluorescence (FAF) imaging, spectral domain-optical coherence tomography (SD-OCT), pattern electroretinogram (ERG), and full-field ERG. The mutational screening of the KCNV2 gene was performed with Sanger and Next Generation Sequencing. Results: All patients showed childhood-onset photophobia and progressive visual acuity loss with varying degrees of severity. In multimodal imaging, various degrees of retinal pigment epithelium disturbances and outer retinal atrophy, which tend to be worst with advancing age, were observed. Molecular screening identified a rare presumed truncating variant (p.Glu209Ter) in homozygosity in two families and in compound heterozygosity in a third family. Three patients showed ERG changes characteristic of CDSRR, however, two patients presented with incomplete electrophysiological features of the disease. Conclusion: A rare variant in the KCNV2 gene was identified in five patients from three Portuguese families. This variant often leads to a severe and progressive form of retinopathy. Considerable variability in the ERG responses among patients with this KCNV2 variant was observed.

Sign in / Sign up

Export Citation Format

Share Document