A Description of the Yield of Genetic Reinvestigation in Patients with Inherited Retinal Dystrophies and Previous Inconclusive Genetic Testing.

In the present era of evolving gene-based therapies for inherited retinal dystrophies (IRDs), it has become increasingly important to verify the genotype in every case, to identify all subjects eligible for treatment. Moreover, combined insight concerning phenotypes and genotypes is crucial for improved understanding of thevisual impairment, prognosis, and inheritance. The objective of this study was to investigate to what extent renewed comprehensive genetic testing of patients diagnosed with IRD but with previously inconclusive DNA test results can verify the genotype, if confirmation of the genotype has an impact on the understanding of the clinical picture, and, to describe the genetic spectrum encountered in a Swedish IRD cohort. The study included 279 patients from the retinitis pigmentosa research registry (comprising diagnosis within the whole IRD spectrum), hosted at the Department of Ophthalmology, Skåne University hospital, Sweden. The phenotypes had already been evaluated with electrophysiology and other clinical tests, e.g., visual acuity, Goldmann perimetry, and fundus imaging at the first visit, sometime between 1988-2015 and the previous-in many cases, multiple-genetic testing, performed between 1995 and 2020 had been inconclusive. All patients were aged 0-25 years at the time of their first visit. Renewed genetic testing was performed using a next generation sequencing (NGS) IRD panel including 322 genes (Blueprint Genetics). Class 5 and 4 variants, according to ACMG guidelines, were considered pathogenic. Of the 279 samples tested, a confirmed genotype was determined in 182 (65%). The cohort was genetically heterogenous, including 65 different genes. The most prevailing were ABCA4 (16.5%), RPGR (6%), CEP290 (6%), and RS1 (5.5%). Other prevalent genes were CACNA1F (3%), PROM1 (3%), CHM (3%), and NYX (3%). In 7% of the patients there was a discrepancy between the diagnosis made based on phenotypical or genotypical findings alone. To conclude, repeated DNA-analysis was beneficial also in previously tested patients and improved our ability to verify the genotype-phenotype association increasing the understanding of how visual impairment manifests, prognosis, and the inheritance pattern. Moreover, repeated testing using a widely available method could identify additional patients eligible for future gene-based therapies.

Randomized crossover study in patients with neuroendocrine tumors to assess patient preference for lanreotide Autogel(®) given by either self/partner or a health care professional.

BACKGROUND: Lanreotide Autogel(®) is supplied in prefilled syringes. Therefore, it is possible for patients with neuroendocrine tumors to use self-/partner-administered injections. The primary objective of this study was to assess the proportion of patients preferring self/partner injections over injections administered by health care professionals, and to describe the impact of self/partner administration on efficacy, safety, and costs. METHODS: Of 62 eligible patients, 26 (42%) patients with neuroendocrine tumors treated with a stable dose of lanreotide Autogel 90 mg or 120 mg every 4 weeks agreed to participate in this Phase IV, international, open-label, crossover study, conducted at hospitals in Sweden, Norway, and Denmark. Patients were randomized to two blocks, starting with administration of lanreotide Autogel by either self/partner or a health care professional. Preference for injections administered by self/partner or health care professionals was measured, as well as efficacy, safety, and health care resource utilization (both direct and indirect costs). RESULTS: Of 25 evaluable patients, 22 (88%) preferred self/partner injections, mainly because they experienced increased independence. Based on all patients asked to participate (n = 62), 35% preferred self/partner injections on a regular basis. There was no difference in efficacy or safety between the two administration blocks. CONCLUSION: Many patients with neuroendocrine tumors prefer self/partner injection of lanreotide Autogel, and are able to self/partner inject without any impact on efficacy or safety. This administration method seems to provide a good alternative for suitable patients to increase patient independence and reduce the number of clinic visits.