PRO29 COST-EFFECTIVENESS OF VORETIGENE NEPARVOVEC FOR VISION LOSS DUE TO BIALLELIC RPE65-MEDIATED INHERITED RETINAL DISEASE IN A DANISH SETTING

Background/aimsIn rare diseases, health-related quality of life (HRQL) data can be difficult to capture. Given the ultrarare nature of RPE65-mediated inherited retinal disease (IRD), it was not feasible to recruit a patient sample and collect HRQL data prospectively. The objectives of this study were to develop health state descriptions of RPE65-mediated IRD, and to estimate associated patient utilities.MethodsVignette descriptions of IRD states were developed and then assessed to elicit utilities. The vignettes ranged from moderate vision loss through to hand motion to no light perception (NLP). Six retina specialists with additional expertise in IRDs provided a proxy valuation of the vignettes using generic measures of health—the 5-level version of EQ-5D-5L and Health Utility Index 3 (HUI3). The data were then scored using standard methods for each instrument.ResultsWeights from both HRQL measures revealed a large decline in scores with vision loss. The EQ-5D-5L weights ranged from 0.709 for moderate vision loss to 0.152 for hand motion to NLP. The HUI3 weights ranged from 0.519 to − 0.039, respectively. A decline was seen on both measures, and the degree of decline from moderate vision loss to NLP was identical on both (−0.56).ConclusionThis is the first study to report HRQL weights (or utilities) for health states describing different levels of vision loss in patients with IRD, specifically those with RPE65-mediated disease. The parallel decline in scores from the EQ-5D and HUI3 corroborates the substantial impact of progressive vision loss on HRQL.

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Deep learning segmentation of hyperautofluorescent fleck lesions in Stargardt disease

Scientific Reports ◽

10.1038/s41598-020-73339-y ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Jason Charng ◽

Di Xiao ◽

Maryam Mehdizadeh ◽

Mary S. Attia ◽

Sukanya Arunachalam ◽

...

Keyword(s):

Deep Learning ◽

Vision Loss ◽

Fundus Autofluorescence ◽

Retinal Disease ◽

Diagnostic Feature ◽

Stargardt Disease ◽

Inherited Retinal Disease ◽

Trial Endpoint ◽

Disease Testing

Abstract Stargardt disease is one of the most common forms of inherited retinal disease and leads to permanent vision loss. A diagnostic feature of the disease is retinal flecks, which appear hyperautofluorescent in fundus autofluorescence (FAF) imaging. The size and number of these flecks increase with disease progression. Manual segmentation of flecks allows monitoring of disease, but is time-consuming. Herein, we have developed and validated a deep learning approach for segmenting these Stargardt flecks (1750 training and 100 validation FAF patches from 37 eyes with Stargardt disease). Testing was done in 10 separate Stargardt FAF images and we observed a good overall agreement between manual and deep learning in both fleck count and fleck area. Longitudinal data were available in both eyes from 6 patients (average total follow-up time 4.2 years), with both manual and deep learning segmentation performed on all (n = 82) images. Both methods detected a similar upward trend in fleck number and area over time. In conclusion, we demonstrated the feasibility of utilizing deep learning to segment and quantify FAF lesions, laying the foundation for future studies using fleck parameters as a trial endpoint.

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Cost-effectiveness of Voretigene Neparvovec-rzyl vs Standard Care for RPE65-Mediated Inherited Retinal Disease

JAMA Ophthalmology ◽

10.1001/jamaophthalmol.2019.2512 ◽

2019 ◽

Vol 137 (10) ◽

pp. 1115 ◽

Cited By ~ 13

Author(s):

Scott Johnson ◽

Marric Buessing ◽

Thomas O’Connell ◽

Sarah Pitluck ◽

Thomas A. Ciulla

Keyword(s):

Cost Effectiveness ◽

Standard Care ◽

Retinal Disease ◽

Inherited Retinal Disease

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Integrative Biology of Diabetic Retinal Disease: Lessons from Diabetic Kidney Disease

Journal of Clinical Medicine ◽

10.3390/jcm10061254 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1254

Author(s):

Warren W. Pan ◽

Thomas W. Gardner ◽

Jennifer L. Harder

Keyword(s):

Systems Biology ◽

Kidney Disease ◽

Diabetic Kidney Disease ◽

Vision Loss ◽

Retinal Disease ◽

Diabetic Kidney ◽

New Therapies ◽

Traditional Research ◽

Working Age ◽

Culture Models

Diabetic retinal disease (DRD) remains the most common cause of vision loss in adults of working age. Progress on the development of new therapies for DRD has been limited by the complexity of the human eye, which constrains the utility of traditional research techniques, including animal and tissue culture models—a problem shared by those in the field of kidney disease research. By contrast, significant progress in the study of diabetic kidney disease (DKD) has resulted from the successful employment of systems biology approaches. Systems biology is widely used to comprehensively understand complex human diseases through the unbiased integration of genetic, environmental, and phenotypic aspects of the disease with the functional and structural manifestations of the disease. The application of a systems biology approach to DRD may help to clarify the molecular basis of the disease and its progression. Acquiring this type of information might enable the development of personalized treatment approaches, with the goal of discovering new therapies targeted to an individual’s specific DRD pathophysiology and phenotype. Furthermore, recent efforts have revealed shared and distinct pathways and molecular targets of DRD and DKD, highlighting the complex pathophysiology of these diseases and raising the possibility of therapeutics beneficial to both organs. The objective of this review is to survey the current understanding of DRD pathophysiology and to demonstrate the investigative approaches currently applied to DKD that could promote a more thorough understanding of the structure, function, and progression of DRD.

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

International Journal of Molecular Sciences ◽

10.3390/ijms22157842 ◽

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.

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

Scientific Reports ◽

10.1038/s41598-021-95258-2 ◽

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.

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