Abstract
BackgroundThis research aimed to establish recommendations on the clinical and genetic characteristics necessary to confirm patient eligibility for gene supplementation with voretigene neparvovec.MethodsAn expert steering committee comprising an interdisciplinary panel of Italian experts in the three fields of medical specialisation involved in the management of RPE65-associated inherited retinal disease (IRD) (medical retina, genetics, vitreoretinal surgery) proposed clinical questions necessary to determine the correct identification of patients with the disease, determine the fundamental clinical and genetics tests to reach the correct diagnosis and to evaluate the urgency to treat patients eligible to receive treatment with voretigene neparvovec. Supported by an extensive review of the literature, a series of statements were developed and refined to prepare precisely constructed questionnaires that were circulated among an external panel of experts comprising ophthalmologists (retina specialists, vitreoretinal surgeons) and geneticists with extensive experience in IRDs in Italy in a two-round Delphi process.ResultsThe categories addressed in the questionnaires included clinical manifestations of RPE65-related IRD, IRD screening and diagnosis, gene testing and genotyping, ocular gene therapy for IRDs, patient eligibility and prioritisation and surgical issues. Response rates by the survey participants were over 90% for the majority of items in both Delphi rounds. The steering committee developed the key consensus recommendations on each category that came from the two Delphi rounds into a simple and linear diagnostic algorithm designed to illustrate the patient pathway leading from the patient’s referral centre to the retinal specialist centre.ConclusionsConsensus guidelines were developed to guide paediatricians and general ophthalmologists to arrive at the correct diagnosis of RPE65-associated IRD and make informed clinical decisions regarding eligibility for a gene therapy approach to RPE65-associated IRD. The guidelines aim to ensure the best outcome for the patient, based on expert opinion, the published literature, and practical experience in the field of IRDs.
Highlights
This research aimed to establish recommendations on the clinical and genetic characteristics necessary to confirm patient eligibility for gene supplementation with voretigene neparvovec
RPE65-associated inherited retinal disease (IRD) should be suspected in individuals with the following clinical findings: Table 1 Summary of the key consensus recommendations regarding anamnesis and genetic testing
To summarise, this paper provides robust, evidencebased and consensus-driven guidelines that can be used by ophthalmologists and paediatricians to arrive at the correct diagnosis of RPE65-associated IRD and to make informed clinical decisions about eligibility for gene supplementation with voretigene neparvovec
Summary
This research aimed to establish recommendations on the clinical and genetic characteristics necessary to confirm patient eligibility for gene supplementation with voretigene neparvovec. Inherited retinal diseases (inherited retinal dystrophies; IRDs) are a heterogeneous group of ocular neurodegenerative disorders resulting from mutations in any one of over 250 causative genes [1] They are mostly characterised by progressive retinal degeneration that leads to severe visual impairment and blindness [2,3,4,5,6]. Depending on the time of disease onset, severity, rate of progression and presenting phenotype, the most common diagnoses are Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EOSRD) [5, 8] These forms are thought to be responsible for approximately 5% of cases of severe IRDs [7]. A smaller proportion of patients exhibit a milder phenotype with a slower progression, possibly associated with hypomorphic alleles [11,12,13]
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