scholarly journals Clinical polymorphism and genetic heterogeneity of inherited retinal diseases

2020 ◽  
pp. 42-43
Author(s):  
И.В. Зольникова ◽  
В.В. Кадышев ◽  
А.В. Марахонов ◽  
Р.А. Зинченко
Keyword(s):  
Molecular Genetics ◽  
Genetic Heterogeneity ◽  
Retinal Disease ◽  
Retinal Diseases ◽  
Inherited Retinal Disease ◽  
Rod System ◽  
Cone System ◽  
Clinical Molecular Genetics

Наследственные заболевания сетчатки (НЗС) представляют собой класс офтальмологических болезней, в котором выделяют заболевания с преимущественным поражением палочковой системы и заболевания с преимущественным поражением колбочковой системы, включающие макулярные дистрофии. В представленном сообщении описана структура спектра НЗС в клинически полиморфной выборке на основании данных клинических, инструментальных (оптической когерентной томографии, аутофлюоресценции, электроретинографии) и молекулярно-генетических методов диагностики (NGS, секвенирование по Сэнгеру). Inherited retinal disease (IRD) is a class of ophthalmic disorders in which can be classified into diseases of primarily of rod system and with primarily of cone system, which include macular dystrophies. In the presented report the structure of spectrum of IRD in clinically polymorphic is presented on the base of clinical, molecular-genetics and instrumental (OCТ, autofluorescencе, eletroretinography).

scholarly journals Balancing the Photoreceptor Proteome: Proteostasis Network Therapeutics for Inherited Retinal Disease

Genes ◽  
2019 ◽  
Vol 10 (8) ◽  
pp. 557 ◽  
Author(s):  
Siebren Faber ◽  
Ronald Roepman
Keyword(s):  
Retinal Disease ◽  
Protein Accumulation ◽  
Retinal Diseases ◽  
High Turnover ◽  
Protein Balance ◽  
Light Sensing ◽  
Outer Segments ◽  
Inherited Retinal Disease ◽  
Tremendous Amount ◽  
Therapeutic Compounds

The light sensing outer segments of photoreceptors (PRs) are renewed every ten days due to their high photoactivity, especially of the cones during daytime vision. This demands a tremendous amount of energy, as well as a high turnover of their main biosynthetic compounds, membranes, and proteins. Therefore, a refined proteostasis network (PN), regulating the protein balance, is crucial for PR viability. In many inherited retinal diseases (IRDs) this balance is disrupted leading to protein accumulation in the inner segment and eventually the death of PRs. Various studies have been focusing on therapeutically targeting the different branches of the PR PN to restore the protein balance and ultimately to treat inherited blindness. This review first describes the different branches of the PN in detail. Subsequently, insights are provided on how therapeutic compounds directed against the different PN branches might slow down or even arrest the appalling, progressive blinding conditions. These insights are supported by findings of PN modulators in other research disciplines.

scholarly journals Functional evaluation in inherited retinal disease

2021 ◽  
pp. bjophthalmol-2021-319994
Author(s):  
Malena Daich Varela ◽  
Michalis Georgiou ◽  
Shaima A Hashem ◽  
Richard G Weleber ◽  
Michel Michaelides
Keyword(s):  
Clinical Trials ◽  
Primary Outcome ◽  
Retinal Disease ◽  
Functional Evaluation ◽  
Retinal Diseases ◽  
Full Field ◽  
Inherited Retinal Disease ◽  
Wide Range ◽  
Functional Assessments ◽  
Field Static

Functional assessments are a fundamental part of the clinical evaluation of patients with inherited retinal diseases (IRDs). Their importance and impact have become increasingly notable, given the significant breadth and number of clinical trials and studies investigating multiple avenues of intervention across a wide range of IRDs, including gene, pharmacological and cellular therapies. Moreover, the fact that many clinical trials are reporting improvements in vision, rather than the previously anticipated structural stability/slowing of degeneration, makes functional evaluation of primary relevance. In this review, we will describe a range of methods employed to characterise retinal function and functional vision, beginning with tests variably included in the clinic, such as visual acuity, electrophysiological assessment and colour discrimination, and then discussing assessments often reserved for clinical trials/research studies such as photoaversion testing, full-field static perimetry and microperimetry, and vision-guided mobility testing; addressing perimetry in greatest detail, given it is commonly a primary outcome metric. We will focus on how these tests can help diagnose and monitor particular genotypes, also noting their limitations/challenges and exploring analytical methodologies for better exploiting functional measurements, as well as how they facilitate patient inclusion and stratification in clinical trials and serve as outcome measures.

A nationwide genetic analysis of inherited retinal diseases in Israel as assessed by the Israeli inherited retinal disease consortium (IIRDC)

2019 ◽  
Vol 41 (1) ◽  
pp. 140-149 ◽  
Author(s):  
Dror Sharon ◽  
Tamar Ben‐Yosef ◽  
Nitza Goldenberg‐Cohen ◽  
Eran Pras ◽  
Libe Gradstein ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Retinal Disease ◽  
Retinal Diseases ◽  
Inherited Retinal Disease

scholarly journals Trial Interventions in ABCA4- Retinopathy

2020 ◽  
Author(s):  
Majid Al Breiki
Keyword(s):  
Clinical Trials ◽  
Literature Review ◽  
Visual Impairment ◽  
Retinal Disease ◽  
Retinal Diseases ◽  
Research Opportunities ◽  
Treatment Trials ◽  
Inherited Retinal Disease ◽  
Intervention Trials ◽  
The Moment

Abstract: Inherited retinal diseases collectively are one of the leading causes of visual impairment worldwide. ABCA4 retinopathy is the most common inherited retinal disease. In the last few years, there are many advances in the understanding of this disease, which led to many interventional trials with promising results at the moment. This paper is going to present a brief background up to date knowledge in the context of the disease pathophysiology, the main mechanisms involved in this disease and related diseases, and different approaches of the intervention trials. I will be using a literature review to highlight the main structural, physiological, chemical, functional characteristics of ABCA4 transporter physiology. This will be followed by a brief discussion about pathophysiology. Next, analysing, extracting and comparing different interventional options and presenting the current clinical trials for each will be done. This paper expected to discusses and rationally compare between different treatment trials approaches their advantages over others and challenges. A sensible, possible application from current trials from different diseases with similar pathogenesis and possible research opportunities will be discussed.

scholarly journals Deep Learning-Based Classification of Inherited Retinal Diseases Using Fundus Autofluorescence

2020 ◽  
Vol 9 (10) ◽  
pp. 3303
Author(s):  
Alexandra Miere ◽  
Thomas Le Meur ◽  
Karen Bitton ◽  
Carlotta Pallone ◽  
Oudy Semoun ◽  
...  
Keyword(s):  
Deep Learning ◽  
Learning Algorithm ◽  
Fundus Autofluorescence ◽  
Area Under The Curve ◽  
Retinal Disease ◽  
Relevant Information ◽  
Retinal Diseases ◽  
Autofluorescence Imaging ◽  
Comparable Group ◽  
Inherited Retinal Disease

Background. In recent years, deep learning has been increasingly applied to a vast array of ophthalmological diseases. Inherited retinal diseases (IRD) are rare genetic conditions with a distinctive phenotype on fundus autofluorescence imaging (FAF). Our purpose was to automatically classify different IRDs by means of FAF images using a deep learning algorithm. Methods. In this study, FAF images of patients with retinitis pigmentosa (RP), Best disease (BD), Stargardt disease (STGD), as well as a healthy comparable group were used to train a multilayer deep convolutional neural network (CNN) to differentiate FAF images between each type of IRD and normal FAF. The CNN was trained and validated with 389 FAF images. Established augmentation techniques were used. An Adam optimizer was used for training. For subsequent testing, the built classifiers were then tested with 94 untrained FAF images. Results. For the inherited retinal disease classifiers, global accuracy was 0.95. The precision-recall area under the curve (PRC-AUC) averaged 0.988 for BD, 0.999 for RP, 0.996 for STGD, and 0.989 for healthy controls. Conclusions. This study describes the use of a deep learning-based algorithm to automatically detect and classify inherited retinal disease in FAF. Hereby, the created classifiers showed excellent results. With further developments, this model may be a diagnostic tool and may give relevant information for future therapeutic approaches.

scholarly journals Development of a Fundus Image-Based Deep Learning Diagnostic Tool for Various Retinal Diseases

2021 ◽  
Vol 11 (5) ◽  
pp. 321
Author(s):  
Kyoung Min Kim ◽  
Tae-Young Heo ◽  
Aesul Kim ◽  
Joohee Kim ◽  
Kyu Jin Han ◽  
...  
Keyword(s):  
Network Models ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Diagnostic Tools ◽  
Retinal Images ◽  
Dense Layer ◽  
Retinal Diseases ◽  
Fundus Image ◽  
Neural Network Models ◽  
Age Related

Artificial intelligence (AI)-based diagnostic tools have been accepted in ophthalmology. The use of retinal images, such as fundus photographs, is a promising approach for the development of AI-based diagnostic platforms. Retinal pathologies usually occur in a broad spectrum of eye diseases, including neovascular or dry age-related macular degeneration, epiretinal membrane, rhegmatogenous retinal detachment, retinitis pigmentosa, macular hole, retinal vein occlusions, and diabetic retinopathy. Here, we report a fundus image-based AI model for differential diagnosis of retinal diseases. We classified retinal images with three convolutional neural network models: ResNet50, VGG19, and Inception v3. Furthermore, the performance of several dense (fully connected) layers was compared. The prediction accuracy for diagnosis of nine classes of eight retinal diseases and normal control was 87.42% in the ResNet50 model, which added a dense layer with 128 nodes. Furthermore, our AI tool augments ophthalmologist’s performance in the diagnosis of retinal disease. These results suggested that the fundus image-based AI tool is applicable for the medical diagnosis process of retinal diseases.

scholarly journals Paternal Uniparental Isodisomy of Chromosome 2 in a Patient with CNGA3-Associated Autosomal Recessive Achromatopsia

2021 ◽  
Vol 22 (15) ◽  
pp. 7842
Author(s):  
Susanne Kohl ◽  
Britta Baumann ◽  
Francesca Dassie ◽  
Anja K. Mayer ◽  
Maria Solaki ◽  
...  
Keyword(s):  
Segregation Analysis ◽  
Molecular Genetic ◽  
Retinal Disease ◽  
Underlying Mechanism ◽  
Recurrence Risk ◽  
Molecular Genetic Analysis ◽  
Recessive Mutation ◽  
Chromosome 2 ◽  
Inherited Retinal Disease ◽  
Uniparental Isodisomy

Achromatopsia (ACHM) is a rare autosomal recessively inherited retinal disease characterized by congenital photophobia, nystagmus, low visual acuity, and absence of color vision. ACHM is genetically heterogeneous and can be caused by biallelic mutations in the genes CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, or ATF6. We undertook molecular genetic analysis in a single female patient with a clinical diagnosis of ACHM and identified the homozygous variant c.778G>C;p.(D260H) in the CNGA3 gene. While segregation analysis in the father, as expected, identified the CNGA3 variant in a heterozygous state, it could not be displayed in the mother. Microsatellite marker analysis provided evidence that the homozygosity of the CNGA3 variant is due to partial or complete paternal uniparental isodisomy (UPD) of chromosome 2 in the patient. Apart from the ACHM phenotype, the patient was clinically unsuspicious and healthy. This is one of few examples proving UPD as the underlying mechanism for the clinical manifestation of a recessive mutation in a patient with inherited retinal disease. It also highlights the importance of segregation analysis in both parents of a given patient or especially in cases of homozygous recessive mutations, as UPD has significant implications for genetic counseling with a very low recurrence risk assessment in such families.

scholarly journals A qualitative study among patients with an inherited retinal disease on the meaning of genomic unsolicited findings

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marlies Saelaert ◽  
Heidi Mertes ◽  
Tania Moerenhout ◽  
Caroline Van Cauwenbergh ◽  
Bart P. Leroy ◽  
...  
Keyword(s):  
Qualitative Study ◽  
Interpretative Phenomenological Analysis ◽  
Age Of Onset ◽  
Genetic Diseases ◽  
Retinal Disease ◽  
Clinical Approach ◽  
Inherited Retinal Disease ◽  
Illness Experiences ◽  
Meaning Structure ◽  
Main Components

AbstractExome-based testing for genetic diseases can reveal unsolicited findings (UFs), i.e. predispositions for diseases that exceed the diagnostic question. Knowledge of patients’ interpretation of possible UFs and of motives for (not) wanting to know UFs is still limited. This lacking knowledge may impede effective counselling that meets patients’ needs. Therefore, this article examines the meaning of UFs from a patient perspective. A qualitative study was conducted and an interpretative phenomenological analysis was made of 14 interviews with patients with an inherited retinal disease. Patients assign a complex meaning to UFs, including three main components. The first component focuses on result-specific qualities, i.e. the characteristics of an UF (inclusive of actionability, penetrance, severity and age of onset) and the consequences of disclosure; the second component applies to a patient’s lived illness experiences and to the way these contrast with reflections on presymptomatic UFs; the third component addresses a patient’s family embedding and its effect on concerns about disease prognosis and genetic information’s family relevance. The complex meaning structure of UFs suggests the need for counselling procedures that transcend a strictly clinical approach. Counselling should be personalised and consider patients’ lived illness experiences and family context.

scholarly journals Methodological Challenges in the Economic Evaluation of a Gene Therapy for RPE65-Mediated Inherited Retinal Disease: The Value of Vision

2021 ◽  
Vol 39 (4) ◽  
pp. 383-397
Author(s):  
Simone A. Huygens ◽  
Matthijs M. Versteegh ◽  
Stefan Vegter ◽  
L. Jan Schouten ◽  
Tim A. Kanters
Keyword(s):  
Gene Therapy ◽  
Economic Evaluation ◽  
Retinal Disease ◽  
Inherited Retinal Disease ◽  
Methodological Challenges
Sign in / Sign up

Export Citation Format

Share Document