Francesca Simonelli

Professor of Ophtalmology

Name Francesca
Surname Simonelli
Institution Università degli Studi della Campania Luigi Vanvitelli
E-Mail francesca.simonelli@unicampania.it
Address Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
Francesca Simonelli

Member PUBLICATIONS

  • Clinical and Genetic Evaluation of a Cohort of Pediatric Patients with Severe Inherited Retinal Dystrophies.

    Publication Date: 20/10/2017 on Genes
    by Di Iorio V, Karali M, Brunetti-Pierri R, Filippelli M, Di Fruscio G, Pizzo M, Mutarelli M, Nigro V, Testa F, Banfi S, Simonelli F
    DOI: 10.3390/genes8100280

    We performed a clinical and genetic characterization of a pediatric cohort of patients with inherited retinal dystrophy (IRD) to identify the most suitable cases for gene therapy. The cohort comprised 43 patients, aged between 2 and 18 years, with severe isolated IRD at the time of presentation. The ophthalmological characterization also included assessment of the photoreceptor layer integrity in the macular region (ellipsoid zone (EZ) band). In parallel, we carried out a targeted, next-generation sequencing (NGS)-based analysis using a panel that covers over 150 genes with either an established or a candidate role in IRD pathogenesis. Based on the ophthalmological assessment, the cohort was composed of 24 Leber congenital amaurosis, 14 early onset retinitis pigmentosa, and 5 achromatopsia patients. We identified causative mutations in 58.1% of the cases. We also found novel genotype-phenotype correlations in patients harboring mutations in the CEP290 and CNGB3 genes. The EZ band was detectable in 40% of the analyzed cases, also in patients with genotypes usually associated with severe clinical manifestations. This study provides the first detailed clinical-genetic assessment of severe IRDs with infantile onset and lays the foundation of a standardized protocol for the selection of patients that are more likely to benefit from gene replacement therapeutic approaches.

  • Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial.

    Publication Date: 26/08/2017 on Lancet (London, England)
    by Russell S, Bennett J, Wellman JA, Chung DC, Yu ZF, Tillman A, Wittes J, Pappas J, Elci O, McCague S, Cross D, Marshall KA, Walshire J, Kehoe TL, Reichert H, Davis M, Raffini L, George LA, Hudson FP, Dingfield L, Zhu X, Haller JA, Sohn EH, Mahajan VB, Pfeifer W, Weckmann M, Johnson C, Gewaily D, Drack A, Stone E, Wachtel K, Simonelli F, Leroy BP, Wright JF, High KA, Maguire AM
    DOI: 10.1016/S0140-6736(17)31868-8

    Phase 1 studies have shown potential benefit of gene replacement in RPE65-mediated inherited retinal dystrophy. This phase 3 study assessed the efficacy and safety of voretigene neparvovec in participants whose inherited retinal dystrophy would otherwise progress to complete blindness.

  • Prevalence of macular abnormalities assessed by optical coherence tomography in patients with Usher syndrome.

    Publication Date: 13/07/2017 on Ophthalmic genetics
    by Testa F, Melillo P, Rossi S, Marcelli V, de Benedictis A, Colucci R, Gallo B, Brunetti-Pierri R, Donati S, Azzolini C, Marciano E, Simonelli F
    DOI: 10.1080/13816810.2017.1329445

    To investigate the prevalence of macular abnormalities in patients affected by Usher syndrome (USH), by comparing the clinical findings between two types (i.e., USH1 and USH2).

  • Wearable Improved Vision System for Color Vision Deficiency Correction.

    Publication Date: 02/05/2017 on IEEE journal of translational engineering in health and medicine
    by Melillo P, Riccio D, Di Perna L, Sanniti Di Baja G, De Nino M, Rossi S, Testa F, Simonelli F, Frucci M
    DOI: 10.1109/JTEHM.2017.2679746

    Color vision deficiency (CVD) is an extremely frequent vision impairment that compromises the ability to recognize colors. In order to improve color vision in a subject with CVD, we designed and developed a wearable improved vision system based on an augmented reality device. The system was validated in a clinical pilot study on 24 subjects with CVD (18 males and 6 females, aged 37.4 ± 14.2 years). The primary outcome was the improvement in the Ishihara Vision Test score with the correction proposed by our system. The Ishihara test score significantly improved ([Formula: see text]) from 5.8 ± 3.0 without correction to 14.8 ± 5.0 with correction. Almost all patients showed an improvement in color vision, as shown by the increased test scores. Moreover, with our system, 12 subjects (50%) passed the vision color test as normal vision subjects. The development and preliminary validation of the proposed platform confirm that a wearable augmented-reality device could be an effective aid to improve color vision in subjects with CVD.

  • Mutations in the PCYT1A gene are responsible for isolated forms of retinal dystrophy.

    Publication Date: 01/05/2017 on European journal of human genetics : EJHG
    by Testa F, Filippelli M, Brunetti-Pierri R, Di Fruscio G, Di Iorio V, Pizzo M, Torella A, Barillari MR, Nigro V, Brunetti-Pierri N, Simonelli F, Banfi S
    DOI: 10.1038/ejhg.2017.23

    Mutations in the PCYT1A gene have been recently linked to two different phenotypes: one characterized by spondylometaphyseal dysplasia and cone-rod dystrophy (SMD-CRD) and the other by congenital lipodystrophy, severe fatty liver disease, and reduced HDL cholesterol without any retinal or skeletal involvement. Here, we identified, by next generation sequencing, sequence variants affecting function in the PCYT1A gene in three young patients with isolated retinal dystrophy from two different Italian families. A thorough clinical evaluation of the patients, with whole skeleton X-ray, metabolic assessment and liver ultrasound failed to reveal signs of skeletal dysplasia, metabolic and hepatic alterations. This is the first report showing that the PCYT1A gene can be responsible for isolated forms of retinal dystrophy, particularly without any skeletal involvement, thus further expanding the phenotypic spectrum induced by mutations in this gene.

  • Identifying fallers among ophthalmic patients using classification tree methodology.

    Publication Date: 23/03/2017 on PloS one
    by Melillo P, Orrico A, Chirico F, Pecchia L, Rossi S, Testa F, Simonelli F
    DOI: 10.1371/journal.pone.0174083

    To develop and validate a tool aiming to support ophthalmologists in identifying, during routine ophthalmologic visits, patients at higher risk of falling in the following year.

  • Genetic characterization of Italian patients with Bardet-Biedl syndrome and correlation to ocular, renal and audio-vestibular phenotype: identification of eleven novel pathogenic sequence variants.

    Publication Date: 01/02/2017 on BMC medical genetics
    by Esposito G, Testa F, Zacchia M, Crispo AA, Di Iorio V, Capolongo G, Rinaldi L, D'Antonio M, Fioretti T, Iadicicco P, Rossi S, Franzè A, Marciano E, Capasso G, Simonelli F, Salvatore F
    DOI: 10.1186/s12881-017-0372-0

    Bardet-Biedl syndrome (BBS) is a rare genetic disorder that features retinal degeneration, obesity, polydactyly, learning disabilities and renal abnormalities. The diagnosis is often missed at birth, the median age at diagnosis being 9 years. In the attempt to shed light on BBS and improve its diagnosis and treatment, we evaluated the genotype-phenotype relationship in patients with a molecular diagnosis of BBS.

  • Melanocortin receptor agonists MCR<sub>1-5</sub> protect photoreceptors from high-glucose damage and restore antioxidant enzymes in primary retinal cell culture.

    Publication Date: 20/12/2016 on Journal of cellular and molecular medicine
    by Maisto R, Gesualdo C, Trotta MC, Grieco P, Testa F, Simonelli F, Barcia JM, D'Amico M, Di Filippo C, Rossi S
    DOI: 10.1111/jcmm.13036

    Retinal photoreceptors are particularly vulnerable to local high-glucose concentrations. Oxidative stress is a risk factor for diabetic retinopathy development. Melanocortin receptors represent a family of G-protein-coupled receptors classified in five subtypes and are expressed in retina. Our previous data indicate that subtypes 1 and 5 receptor agonists exert a protective role on experimental diabetic retinopathy. This study focuses on their role in primary retinal cell cultures in high-glucose concentrations. After eye enucleation from wild-type male C57BL/6 mice, retinal cells were isolated, plated in high-glucose concentration and treated with melanocortin receptors 1 and 5 agonists and antagonists. Immunocytochemical and biochemical analysis showed that treatment with melanocortin receptors 1 and 5 agonists reduced anti-inflammatory cytokines and chemokines and enhanced manganese superoxide dismutase and glutathione peroxidase levels, preserving photoreceptor integrity. According with these evidences, we propose a major role of melanocortin receptors 1 and 5 on primary retinal cell response against high glucose or oxidative insults.

  • An innovative strategy for the molecular diagnosis of Usher syndrome identifies causal biallelic mutations in 93% of European patients.

    Publication Date: 01/12/2016 on European journal of human genetics : EJHG
    by Bonnet C, Riahi Z, Chantot-Bastaraud S, Smagghe L, Letexier M, Marcaillou C, Lefèvre GM, Hardelin JP, El-Amraoui A, Singh-Estivalet A, Mohand-Saïd S, Kohl S, Kurtenbach A, Sliesoraityte I, Zobor D, Gherbi S, Testa F, Simonelli F, Banfi S, Fakin A, Glavač D, Jarc-Vidmar M, Zupan A, Battelino S, Martorell Sampol L, Claveria MA, Catala Mora J, Dad S, Møller LB, Rodriguez Jorge J, Hawlina M, Auricchio A, Sahel JA, Marlin S, Zrenner E, Audo I, Petit C
    DOI: 10.1038/ejhg.2016.99

    Usher syndrome (USH), the most prevalent cause of hereditary deafness-blindness, is an autosomal recessive and genetically heterogeneous disorder. Three clinical subtypes (USH1-3) are distinguishable based on the severity of the sensorineural hearing impairment, the presence or absence of vestibular dysfunction, and the age of onset of the retinitis pigmentosa. A total of 10 causal genes, 6 for USH1, 3 for USH2, and 1 for USH3, and an USH2 modifier gene, have been identified. A robust molecular diagnosis is required not only to improve genetic counseling, but also to advance gene therapy in USH patients. Here, we present an improved diagnostic strategy that is both cost- and time-effective. It relies on the sequential use of three different techniques to analyze selected genomic regions: targeted exome sequencing, comparative genome hybridization, and quantitative exon amplification. We screened a large cohort of 427 patients (139 USH1, 282 USH2, and six of undefined clinical subtype) from various European medical centers for mutations in all USH genes and the modifier gene. We identified a total of 421 different sequence variants predicted to be pathogenic, about half of which had not been previously reported. Remarkably, we detected large genomic rearrangements, most of which were novel and unique, in 9% of the patients. Thus, our strategy led to the identification of biallelic and monoallelic mutations in 92.7% and 5.8% of the USH patients, respectively. With an overall 98.5% mutation characterization rate, the diagnosis efficiency was substantially improved compared with previously reported methods.

  • Systematic screening of Retinopathy in Diabetes (REaD project): an Italian implementation campaign.

    Publication Date: 21/11/2016 on European journal of ophthalmology
    by Porta M, Boscia F, Lanzetta P, Mannucci E, Menchini U, Simonelli F
    DOI: 10.5301/ejo.5000912

    To evaluate the use of telemedicine retinal screening in Italy and to identify potential elements of implementation of this system.