Validation of Standardized Tasks and Questionnaires to Evaluate and Understand the Impact of Age-related Macular Degeneration on Daily Living Activitie

The complex and variable course of age-related diseases makes it all the more necessary to carry out personalised, reasoning-based examinations to improve the personalised assessment and management of AMD. However, functional assessment of AMD is most often based solely on visual acuity, and classifications of AMD are based solely on structural markers. There is therefore a need to improve the detection and functional assessment of this vision-threatening eye disease, by complementing and extending the standard assessments of clinical outcomes (COA)

开始日期2024-06-01

申办/合作机构

Centre Hospitalier National dOphtalmologie des Quinze

NCT06185517 / Not yet recruitingN/AIIT

French Translation and Validation of the Michigan Retinal Degeneration Questionnaire and the Michigan Vision-Related Anxiety Questionnaire in a Cohort of People With Hereditary Retinal Degeneration.

While inherited retinal diseases are well characterized anatomically and functionally, it is also essential to understand their impact on patients' quality of life, from their ability to perform the tasks of daily living to the psychological impact of the disease on patients. Questionnaires (PRO, Patient-Reported Outcomes) are important tools for assessing this impact. However, PROs validated in French are rare, and often poorly adapted to populations with hereditary retinal degeneration. New PROs particularly adapted to retinal degeneration have recently been validated in English: the Michigan Retinal Degeneration Questionnaire (MRDQ) and the Michigan Vision-Related Anxiety Questionnaire (MVAQ). Validation of a French translation will provide a standardized, reliable tool for French-speaking patients, and enable these questionnaires to be used in gene therapy clinical trials, to assess the efficacy of treatments and their impact on patients' quality of life.

开始日期2024-01-01

申办/合作机构

Centre Hospitalier National dOphtalmologie des Quinze

NCT06168617 / Not yet recruitingN/AIIT

Feasibility Study of Tests, on the Model of Real-life Daily Tasks, Measuring the Performance of Different Vision Restoration Strategies, After Cataract Surgical Treatment With Different Types of Intraocular Lens Implants.

Prospective, interventional, non-invasive, monocentric, longitudinal, non-randomized study

开始日期2024-01-01

申办/合作机构

Centre Hospitalier National dOphtalmologie des Quinze

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2021-04-01·Human Mutation2区 · 医学

CHM mutation spectrum and disease: An update at the time of human therapeutic trials

2区 · 医学

Review

作者: Roux, Anne‐Françoise ; Meunier, Isabelle ; Antonio, Aline ; El‐Shamieh, Said ; Sahel, José‐Alain ; Nassisi, Marco ; Kloeckener‐Gruissem, Barbara ; Laurent‐Coriat, Caroline ; Mohand‐Saïd, Saddek ; Andrieu, Camille ; Zanlonghi, Xavier ; Audo, Isabelle ; Zeitz, Christina ; Frederiksen, Helen ; Condroyer, Christel ; Boyard, Fiona ; Lancelot, Marie‐Elise ; Démontant, Vanessa

Choroideremia is an X-linked inherited retinal disorder (IRD) characterized by the degeneration of retinal pigment epithelium, photoreceptors, choriocapillaris and choroid affecting males with variable phenotypes in female carriers. Unlike other IRD, characterized by a large clinical and genetic heterogeneity, choroideremia shows a specific phenotype with causative mutations in only one gene, CHM. Ongoing gene replacement trials raise further interests in this disorder. We describe here the clinical and genetic data from a French cohort of 45 families, 25 of which carry novel variants, in the context of 822 previously reported choroideremia families. Most of the variants represent loss-of-function mutations with eleven families having large (i.e. ≥6 kb) genomic deletions, 18 small insertions, deletions or insertion deletions, six showing nonsense variants, eight splice site variants and two missense variants likely to affect splicing. Similarly, 822 previously published families carry mostly loss-of-function variants. Recurrent variants are observed worldwide, some of which linked to a common ancestor, others arisen independently in specific CHM regions prone to mutations. Since all exons of CHM may harbor variants, Sanger sequencing combined with quantitative polymerase chain reaction or multiplex ligation-dependent probe amplification experiments are efficient to achieve the molecular diagnosis in patients with typical choroideremia features.

2021-03-01·BioDrugs3区 · 医学

Safety of Intravitreal Gene Therapy for Treatment of Subjects with Leber Hereditary Optic Neuropathy due to Mutations in the Mitochondrial ND4 Gene: The REVEAL Study

3区 · 医学

Article

作者: Girmens, Jean-François ; Plaine, Lise ; Taiel, Magali ; Audo, Isabelle ; Errera, Marie-Hélène ; Said, Saddek Mohand ; Sahel, José-Alain ; Vignal-Clermont, Catherine ; O'Shaughnessy, Denis

BACKGROUNDLeber hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disease whose primary clinical manifestation is bilateral visual loss. Only a single therapy, idebenone, is approved in Europe for use in exceptional circumstances and no therapy is currently approved in the USA. LHON remains a disease with a high unmet medical need.OBJECTIVEThis is a report of an open-label, single-center, dose-escalation study that evaluated the safety and tolerability of lenadogene nolparvovec in 15 subjects with LHON for up to 5 years following a single intravitreal injection at four dose levels.METHODSSubjects were enrolled sequentially in four cohorts followed by an additional cohort at the dose selected, and safety was assessed by an independent data safety monitoring board (DSMB) prior to any dose escalation.RESULTSOverall, the treatment was well tolerated during the 5-year follow-up. No serious adverse events were considered related to treatment, no unexpected adverse events occurred, and no grade 3 or 4 Common Terminology Criteria for Adverse Events were reported. Anterior chamber inflammation and vitritis were mostly managed with topical steroids, and ocular inflammation was considered to be dose limiting by the DSMB based on the benefits/risks for the subjects. Analysis of the logarithm of the minimal angle of resolution (LogMAR) visual acuity in both treated and untreated eyes showed clinically relevant and durable improvements compared with baseline. Mean improvements of - 0.44 and - 0.49 LogMAR for treated and untreated eyes, respectively, were noted, with a mean (± standard deviation) final value of LogMAR + 1.96 ± 0.60 and + 1.65 ± 0.34, respectively, at 5 years post-treatment administration. For the six subjects treated with the optimal dose level (9 × 10¹⁰ viral genomes [vg]/eye), the mean visual acuity improvement from baseline reached - 0.68 LogMAR for treated eyes and - 0.64 LogMAR for untreated eyes, with a mean final value of LogMAR + 1.77 ± 0.52 and + 1.78 ± 0.34, respectively. While there was a meaningful improvement in visual acuity for REVEAL subjects, the final visual acuity was less favorable than that seen in the two subsequent pivotal phase III studies in which subjects were treated earlier during the course of their disease.CONCLUSIONLenadogene nolparvovec was well tolerated with a good safety profile during 5 years of follow-up and may offer meaningful lasting improvements in vision for this LHON population.CLINICAL TRIAL NUMBEREUDRACT N° 2013-001405-90.

2019-06-01·Human Mutation2区 · 医学

Where are the missing gene defects in inherited retinal disorders? Intronic and synonymous variants contribute at least to 4% of CACNA1F ‐mediated inherited retinal disorders

2区 · 医学

Article

作者: Perdomo‐Trujillo, Yaumara ; Bouzidi, Nassima ; Condroyer, Christel ; Casteels, Ingele ; Milicevic, Diana ; Balikova, Irina ; Zeitz, Christina ; Kohl, Susanne ; Deleuze, Jean‐François ; Lorenz, Birgit ; Dollfus, Hélène ; Laffargue, Fanny ; Banin, Eyal ; Boland, Anne ; McKibbin, Martin ; Meunier, Isabelle ; Blanchard, Steven ; Jurklies, Bernhard ; Zanlonghi, Xavier ; Pelletier, Valerie ; Seneina, Imene ; Foussard, Marine ; Saraiva, Jean‐Paul ; Antonio, Aline ; Andrieu, Camille ; Neuillé, Marion ; McLean, Rebecca ; Mesrob, Lilia ; Drumare, Isabelle ; Wissinger, Bernd ; Blanché, Hélène ; Meyer, Vincent ; Michiels, Christelle ; Veaux, Robin ; Zrenner, Eberhart ; Audo, Isabelle ; Bonneau, Dominique ; Ravel, Thomy J. ; N. Preising, Markus ; Baere, Elfride ; L. Munier, Francis ; Zoumba, Axelle ; Leroy, Bart P. ; Tourville, Aurore ; Sharon, Dror ; Jubin, Claire ; Friedburg, Christoph ; Koenekoop, Rob K. ; Defoort‐Dhellemmes, Sabine ; Prescott, Katrina ; Gottlob, Irene ; Faure, Céline ; Sahel, José‐Alain ; Le Floch, Edith ; Reiff, Charlotte ; Schorderet, Daniel F. ; Boyard, Fiona

Inherited retinal disorders (IRD) represent clinically and genetically heterogeneous diseases. To date, pathogenic variants have been identified in ~260 genes. Albeit that many genes are implicated in IRD, for 30-50% of the cases, the gene defect is unknown. These cases may be explained by novel gene defects, by overlooked structural variants, by variants in intronic, promoter or more distant regulatory regions, and represent synonymous variants of known genes contributing to the dysfunction of the respective proteins. Patients with one subgroup of IRD, namely incomplete congenital stationary night blindness (icCSNB), show a very specific phenotype. The major cause of this condition is the presence of a hemizygous pathogenic variant in CACNA1F. A comprehensive study applying direct Sanger sequencing of the gene-coding regions, exome and genome sequencing applied to a large cohort of patients with a clinical diagnosis of icCSNB revealed indeed that seven of the 189 CACNA1F-related cases have intronic and synonymous disease-causing variants leading to missplicing as validated by minigene approaches. These findings highlight that gene-locus sequencing may be a very efficient method in detecting disease-causing variants in clinically well-characterized patients with a diagnosis of IRD, like icCSNB.

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