这项研究旨在建立有关临床和遗传特征的建议,以确认患者补充voretigeneneparvovec基因的资格。
一个专家指导委员会,由意大利三个医学专业领域的跨学科专家组成,涉及RPE65相关遗传性视网膜疾病(IRD)的管理(医学视网膜,遗传学,玻璃体视网膜手术)提出了确定正确识别该疾病患者所必需的临床问题,确定基本的临床和遗传学测试,以达到正确的诊断,并评估治疗有资格接受voretigeneneparvovec治疗的患者的紧迫性。在广泛的文献综述的支持下,开发和完善了一系列声明,以准备精确构造的问卷,这些问卷在由眼科医生组成的外部专家小组(视网膜专家,玻璃体视网膜外科医生)和遗传学家在意大利的IRD中有丰富的经验,进行了两轮Delphi过程。
问卷中涉及的类别包括与RPE65相关的IRD的临床表现,IRD筛查和诊断,基因检测和基因分型,IRD的眼部基因治疗,患者资格和优先次序和手术问题。在两个Delphi回合中,调查参与者对大多数项目的响应率都超过90%。指导委员会将来自两次Delphi回合的每个类别的关键共识建议开发为一种简单且线性的诊断算法,旨在说明从患者转诊中心到视网膜专科中心的患者路径。
制定了共识指南,以指导儿科医生和普通眼科医生正确诊断RPE65相关IRD,并就RPE65相关IRD的基因治疗方法的资格做出明智的临床决定。该指南旨在确保患者的最佳结果,根据专家意见,出版的文献,以及IRD领域的实践经验。
This research aimed to establish recommendations on the clinical and genetic characteristics necessary to confirm patient eligibility for gene supplementation with voretigene neparvovec.
An 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.
The 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.
Consensus 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.