Electrophysiology-Guided Genetic Characterisation Maximises Molecular Diagnosis in an Irish Paediatric Inherited Retinal Degeneration Population.

Inherited retinal degenerations (IRDs) account for over one third of the underlying causes of blindness in the paediatric population. Patients with IRDs often experience long delays prior to reaching a definitive diagnosis. Children attending a tertiary care paediatric ophthalmology department with phenotypic (i.e., clinical and/or electrophysiologic) evidence suggestive of IRD were contacted for genetic testing during the SARS-CoV-2-19 pandemic using a "telegenetics" approach. Genetic testing approach was panel-based next generation sequencing (351 genes) via a commercial laboratory (Blueprint Genetics, Helsinki, Finland). Of 70 patient samples from 57 pedigrees undergoing genetic testing, a causative genetic variant(s) was detected for 60 patients (85.7%) from 47 (82.5%) pedigrees. Of the 60 genetically resolved IRD patients, 5% (n = 3) are eligible for approved therapies (RPE65) and 38.3% (n = 23) are eligible for clinical trial-based gene therapies including CEP290 (n = 2), CNGA3 (n = 3), CNGB3 (n = 6), RPGR (n = 5) and RS1 (n = 7). The early introduction of genetic testing in the diagnostic/care pathway for children with IRDs is critical for genetic counselling of these families prior to upcoming gene therapy trials. Herein, we describe the pathway used, the clinical and genetic findings, and the therapeutic implications of the first systematic coordinated round of genetic testing of a paediatric IRD cohort in Ireland.

COVID-19 Vaccines in Inherited Retinal Degenerations (IRD), Fears, Ideas and Real Interactions.

Purpose: In the COVID-19 pandemic era, vaccines are one of the most efficient weapons, as well established by WHO, that humans have, in all their variants (mRNA, AAV or others). Unfortunately, in western nations skepticism within different groups has been generated by the fast approval processes, driven by the urgent need to confront the rapid increase of hospitalized patients and number of deaths by regulation authorities as FDA and EMA. Moreover, several scientific and non-scientific perplexity, also amplified by the media, created hard no-vax strategies, that lead many patients to refuse vaccine administration. Also in this selected population higher rate of COVID-19 infections and severe diseases are registered and consequently there was an increase of death number. Furthermore, to avoid vaccine shots, people frequently ask exemption querying ophthalmological and systemic diseases, in this situation most patients affected with orphan ophthalmological conditions as inherited retinal degenerations have profound fears and doubt. The goal of our study was to ascertain if these fears are based on real facts and if there are interactions or severe visual impairment after each shot of vaccinations. Methods: Five hundred randomically selected patients affected by IRD at each patient was asked anonymously, number of vaccine administrations and eventually reported side effects. Results: Of 500 selected patients 61 (12,2%) did not underwent to Covid-19 vaccination, reasons were various (fear, laziness, caregiver unavailability etc.). Remaining 439 patients (87,8%) had first shot of vaccine. Only 30% of patients complained side effects of vaccine, none of them was serious. Conclusion: The number of patients is wide enough to draw some considerations: In IRD vaccination is safe, in all doses ocular side effects were reported only in one third of subjects and this is not different from the percentage shown by normal people, COVID-19 effects may be more dangerous than vaccine.