The Diagnostic Yield of Next Generation Sequencing in Inherited Retinal Diseases: A Systematic Review and Meta-analysis

Britten‐Jones, Alexis Ceecee; Gocuk, Sena A; Goh, Kai Lyn; Huq, Aamira; Edwards, Thomas; Ayton, Lauren N

doi:10.1016/j.ajo.2022.12.027

Cited by 34 publications

(18 citation statements)

References 135 publications

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“…36,37 Our findings highlighted several knowledge gaps in primary eye care, including awareness of genetic testing outcomes, as only 20% of optometrists knew that approximately 1 in 3 ocular genetic tests may return an inconclusive result; practical considerations (cost, ways to access, impact on health and medical insurance); and knowledge of gene therapy clinical trial results to date. In this study, we considered 1 in 3 ocular genetic tests being inconclusive as the correct answer to reflect the approximate number of cases in whom a candidate pathogenic variant can be identified as being causative of their IRD, based on data from next generation sequencing studies 11 and Australian IRD registries. 12,38 However, in practice, the interpretation of genetic testing results is complex, often requiring additional testing (e.g., to determine phase or to evaluate additional variants) and multidisciplinary team input.…”

Section: Discussionmentioning

confidence: 99%

“…The uptake of IRD genetic testing in Australian private ophthalmology clinics is currently estimated to be around 10%, reflecting historic management patterns and access to genetic services 10 . Currently, the likelihood that a genetic test will provide an IRD diagnosis is approximately 60% 11 . However, with the increasing availability of sponsored genetic testing programs, 12–14 it's likely that diagnostic genetic testing will be available to more patients with retinal diseases.…”

Section: Introductionmentioning

confidence: 99%

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Genetic testing and gene therapy in retinal diseases: Knowledge and perceptions of optometrists in Australia and New Zealand

et al. 2023

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With advances in gene‐based therapies for heritable retinal diseases, primary eye care clinicians should be informed on ocular genetics topics. This cross‐sectional survey evaluated knowledge, attitudes, and concerns regarding genetic testing and gene therapy for retinal diseases among optometrists in Australia and New Zealand. Survey data included practitioner background, attitudes and practices towards genetic testing for monogenic inherited retinal disease (IRDs) and age‐related macular degeneration, and knowledge of ocular genetics and gene therapy. Responses were received from 516 optometrists between 1 April and 31 December 2022. Key perceived barriers to accessing genetic testing were lack of clarity on referral pathways (81%), cost (65%), and lack of treatment options if a genetic cause is identified (50%). Almost all respondents (98%) believed that ophthalmologists should initiate genetic testing for IRDs and fewer understood the role of genetic counsellors and clinical geneticists. This study found that optometrists in Australia and New Zealand have a high level of interest in ocular genetics topics. However, knowledge gaps include referral pathways and awareness of genetic testing and gene therapy outcomes. Addressing perceived barriers to access and promoting sharing of knowledge between interdisciplinary networks can set the foundation for genetic education agendas in primary eye care.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genetic testing and gene therapy in retinal diseases: Knowledge and perceptions of optometrists in Australia and New Zealand

et al. 2023

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“…In our case, the cost per positive diagnosis would be approximately 734 USD considering our diagnostic yield of 62%. When taking into account a high diagnostic yield of 80% for inherited dystrophies (23), the cost would be 659.11 USD. The more expertise gained, the lower the nal cost and the greater the test's clinical utility over time.…”

Section: Discussionmentioning

confidence: 99%

The Cost of Hereditary Pediatric Cataract's Clinical and Genetic Diagnosis With Whole Exome Sequencing From a Middle-income Country Perspective: Can We See Any Gains?

Neves,

Pinto,

Zin

et al. 2023

Preprint

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Up to 25% of pediatric cataract cases are inherited. There is scarce information in the literature regarding the cost of whole exome sequencing (WES) for hereditary pediatric cataract. Molecular diagnosis of hereditary pediatric cataract is important for a comprehensive genetic counseling. We performed a partial economic evaluation using a microcosting approach with a bottom-up technique to estimate the cost of clinical and genetic diagnosis using WES for hereditary pediatric cataract under the Brazilian governmental healthcare system’s perspective. One hundred and ten participants from twenty-nine families from Rio de Janeiro city (RJ) were included. Direct costs of consumables, staff and equipment were used. Two scenarios were created: 1. Reference scenario included patients with hereditary pediatric cataract plus two family members in RJ. 2. Alternative scenario considered other genetic diseases resulting in 5,280 exams per month. Sensitivity analysis was performed. In the reference scenario the total cost per exam (clinical and genetic) was 609.51 United State Dollars (USD) and in the alternative scenario it was 541.20 USD. Considering only WES, its cost per exam was 455.29 USD in the reference and 386.98USD in the alternative scenarios. Sensitivity analysis showed that the most important costs were consumables in both scenarios. Economic evaluations can help inform policy decisions specially in middle-income countries such as Brazil.

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“…18 Without predefined guidelines, variant interpretation can differ substantially between institutes, which may contribute to the variability in genetic interpretation of a given variant. 19 Japan has a different genetic architecture of IRD compared to Western countries and even neighboring countries, 14 20 21 leading the Japanese Retina and Vitreous Society to publish a modified set of guidelines, the Japanese inherited retinal dystrophy variant interpretation (J-IRD-VI) guidelines. These guidelines are built upon predefined ACMG/AMP rules based on a thorough discussion among the expert members of key genetic laboratories and allow a uniform interpretation of variants tailored specifically for Japanese patients.…”

Section: Introductionmentioning

confidence: 99%

Disease-specific variant interpretation highlighted the genetic findings in 2325 Japanese patients with retinitis pigmentosa and allied diseases

Goto,

Koyanagi,

Akiyama

et al. 2023

Preprint

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BackgroundAs gene-specific therapy for inherited retinal dystrophy (IRD) advances, unified variant interpretation across institutes is becoming increasingly important. This study aims to update the genetic findings of 86 retinitis pigmentosa (RP)–related genes in a large number of Japanese RP patients by applying the standardized variant interpretation guidelines for Japanese IRD patients (J-IRD-VI guidelines) built upon ACMG/AMP rules and assess the contribution of these genes in RP-allied diseases.MethodsWe assessed 2325 probands with RP (n=2155, including n=1204 sequenced previously with the same sequencing panel) and allied diseases (n=170, all newly analyzed), including Usher syndrome, Leber congenital amaurosis, and cone-rod dystrophy (CRD). Target sequencing using a panel of 86 genes was performed. The variants were interpreted according to the J-IRD-VI guidelines.ResultsA total of 3564 variants were detected, of which 524 variants were interpreted as pathogenic or likely pathogenic. Among these 524 variants, 280 (53.4%) had been either undetected or interpreted as variants of unknown significance or benign variants in our earlier study of 1204 RP patients. This led to a genetic diagnostic rate in 38.6% of RP patients, withEYSaccounting for 46.7% of the genetically solved patients, showing a 9% increase in diagnostic rate from our earlier study. The genetic diagnostic rate for CRD patients was 28.2%, with RP-related genes significantly contributing over other allied diseases.ConclusionA large-scale genetic analysis using the J-IRD-VI guidelines highlighted the unique genetic findings for Japanese IRD patients; these findings serve as a foundation for the clinical application of gene-specific therapies.

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The Diagnostic Yield of Next Generation Sequencing in Inherited Retinal Diseases: A Systematic Review and Meta-analysis

Cited by 34 publications

References 135 publications

Genetic testing and gene therapy in retinal diseases: Knowledge and perceptions of optometrists in Australia and New Zealand

Genetic testing and gene therapy in retinal diseases: Knowledge and perceptions of optometrists in Australia and New Zealand

The Cost of Hereditary Pediatric Cataract's Clinical and Genetic Diagnosis With Whole Exome Sequencing From a Middle-income Country Perspective: Can We See Any Gains?

Disease-specific variant interpretation highlighted the genetic findings in 2325 Japanese patients with retinitis pigmentosa and allied diseases

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