Settimio Rossi

Professor of Ophtalmology

Name Settimio
Surname Rossi
Institution Università degli Studi della Campania Luigi Vanvitelli
E-Mail settimio.rossi@unicampania.it
Address Ophtalmology at 'Dipartimento Multidisciplinare di Specialità Medico-Chirurgiche e Odontoiatriche' Department of Medical Surgical, Neurological, Metabolic Sciences, and Aging, University of Campania Luigi Vanvitelli, Edificio 10 Via Sergio Pansini, 580131 Naples, Italy

Member PUBLICATIONS

  • Next Generation Molecular Diagnosis of Hereditary Spastic Paraplegias: An Italian Cross-Sectional Study.

    Publication Date: 04/12/2018 on Frontiers in neurology
    by D'Amore A, Tessa A, Casali C, Dotti MT, Filla A, Silvestri G, Antenora A, Astrea G, Barghigiani M, Battini R, Battisti C, Bruno I, Cereda C, Dato C, Di Iorio G, Donadio V, Felicori M, Fini N, Fiorillo C, Gallone S, Gemignani F, Gigli GL, Graziano C, Guerrini R, Gurrieri F, Kariminejad A, Lieto M, Marques LourenḈo C, Malandrini A, Mandich P, Marcotulli C, Mari F, Massacesi L, Melone MAB, Mignarri A, Milone R, Musumeci O, Pegoraro E, Perna A, Petrucci A, Pini A, Pochiero F, Pons MR, Ricca I, Rossi S, Seri M, Stanzial F, Tinelli F, Toscano A, Valente M, Federico A, Rubegni A, Santorelli FM
    DOI: 10.3389/fneur.2018.00981

    Hereditary spastic paraplegia (HSP) refers to a group of genetically heterogeneous neurodegenerative motor neuron disorders characterized by progressive age-dependent loss of corticospinal motor tract function, lower limb spasticity, and weakness. Recent clinical use of next generation sequencing (NGS) methodologies suggests that they facilitate the diagnostic approach to HSP, but the power of NGS as a first-tier diagnostic procedure is unclear. The larger-than-expected genetic heterogeneity-there are over 80 potential disease-associated genes-and frequent overlap with other clinical conditions affecting the motor system make a molecular diagnosis in HSP cumbersome and time consuming. In a single-center, cross-sectional study, spanning 4 years, 239 subjects with a clinical diagnosis of HSP underwent molecular screening of a large set of genes, using two different customized NGS panels. The latest version of our targeted sequencing panel () comprises 118 genes known to be associated with HSP. Using an in-house validated bioinformatics pipeline and several tools to predict mutation pathogenicity, we obtained a positive diagnostic yield of 29% (70/239), whereas variants of unknown significance (VUS) were found in 86 patients (36%), and 83 cases remained unsolved. This study is among the largest screenings of consecutive HSP index cases enrolled in real-life clinical-diagnostic settings. Its results corroborate NGS as a modern, first-step procedure for molecular diagnosis of HSP. It also disclosed a significant number of new mutations in ultra-rare genes, expanding the clinical spectrum, and genetic landscape of HSP, at least in Italy.

  • Determinants of therapy switch in multiple sclerosis treatment-naïve patients: A real-life study.

    Publication Date: 25/07/2018 on Multiple sclerosis (Houndmills, Basingstoke, England)
    by Saccà F, Lanzillo R, Signori A, Maniscalco GT, Signoriello E, Lo Fermo S, Repice A, Annovazzi P, Baroncini D, Clerico M, Binello E, Cerqua R, Mataluni G, Bonavita S, Lavorgna L, Zarbo IR, Laroni A, Rossi S, Pareja Gutierrez L, La Gioia S, Frigeni B, Barcella V, Frau J, Cocco E, Fenu G, Torri Clerici V, Sartori A, Rasia S, Cordioli C, Di Sapio A, Pontecorvo S, Grasso R, Barrilà C, Russo CV, Esposito S, Ippolito D, Bovis F, Gallo F, Sormani MP,
    DOI: 10.1177/1352458518790390

    With many options now available, first therapy choice is challenging in multiple sclerosis (MS) and depends mainly on neurologist and patient preferences.

  • Clinical activity after fingolimod cessation: disease reactivation or rebound?

    Publication Date: 31/05/2018 on European journal of neurology
    by Frau J, Sormani MP, Signori A, Realmuto S, Baroncini D, Annovazzi P, Signoriello E, Maniscalco G, La Gioia S, Cordioli C, Frigeni B, Rasia S, Fenu G, Grasso R, Sartori A, Lanzillo R, Stromillo ML, Rossi S, Forci B, Cocco E,
    DOI: 10.1111/ene.13694

    There is debate as to whether the apparent rebound after fingolimod discontinuation is related to the discontinuation itself, or if it is due to the natural course of highly active multiple sclerosis (MS). We aimed to survey the prevalence of severe reactivation and rebound after discontinuation of fingolimod in a cohort of Italian patients with MS.

  • ASSOCIATION BETWEEN GENOTYPE AND DISEASE PROGRESSION IN ITALIAN STARGARDT PATIENTS: A Retrospective Natural History Study.

    Publication Date: 10/04/2018 on Retina (Philadelphia, Pa.)
    by Di Iorio V, Orrico A, Esposito G, Melillo P, Rossi S, Sbordone S, Auricchio A, Testa F, Simonelli F
    DOI: 10.1097/IAE.0000000000002151

    To investigate the natural history of Stargardt disease over a multiyear follow-up.

  • Targeting and silencing of rhodopsin by ectopic expression of the transcription factor KLF15.

    Publication Date: 21/12/2017 on JCI insight
    by Botta S, de Prisco N, Marrocco E, Renda M, Sofia M, Curion F, Bacci ML, Ventrella D, Wilson C, Gesualdo C, Rossi S, Simonelli F, Surace EM
    DOI: 10.1172/jci.insight.96560

    The genome-wide activity of transcription factors (TFs) on multiple regulatory elements precludes their use as gene-specific regulators. Here we show that ectopic expression of a TF in a cell-specific context can be used to silence the expression of a specific gene as a therapeutic approach to regulate gene expression in human disease. We selected the TF Krüppel-like factor 15 (KLF15) based on its putative ability to recognize a specific DNA sequence motif present in the rhodopsin (RHO) promoter and its lack of expression in terminally differentiated rod photoreceptors (the RHO-expressing cells). Adeno-associated virus (AAV) vector-mediated ectopic expression of KLF15 in rod photoreceptors of pigs enables Rho silencing with limited genome-wide transcriptional perturbations. Suppression of a RHO mutant allele by KLF15 corrects the phenotype of a mouse model of retinitis pigmentosa with no observed toxicity. Cell-specific-context conditioning of TF activity may prove a novel mode for somatic gene-targeted manipulation.

  • Triple Vectors Expand AAV Transfer Capacity in the Retina.

    Publication Date: 05/12/2017 on Molecular therapy : the journal of the American Society of Gene Therapy
    by Maddalena A, Tornabene P, Tiberi P, Minopoli R, Manfredi A, Mutarelli M, Rossi S, Simonelli F, Naggert JK, Cacchiarelli D, Auricchio A
    DOI: 10.1016/j.ymthe.2017.11.019

    Retinal gene transfer with adeno-associated viral (AAV) vectors holds great promise for the treatment of inherited retinal degenerations (IRDs). One limit of AAV is its transfer capacity of about 5 kb, which can be expanded to about 9 kb, using dual AAV vectors. This strategy would still not suffice for treatment of IRDs such as Usher syndrome type 1D or Alström syndrome type I (ALMS) due to mutations in CDH23 or ALMS1, respectively. To overcome this limitation, we generated triple AAV vectors, with a maximal transfer capacity of about 14 kb. Transcriptomic analysis following triple AAV transduction showed the expected full-length products along a number of aberrant transcripts. However, only the full-length transcripts are efficiently translated in vivo. We additionally showed that approximately 4% of mouse photoreceptors are transduced by triple AAV vectors and showed correct localization of recombinant ALMS1. The low-photoreceptor transduction levels might justify the modest and transient improvement we observe in the retina of a mouse model of ALMS. However, the levels of transduction mediated by triple AAV vectors in pig retina reached 40% of those observed with single vectors, and this bodes well for further improving the efficiency of triple AAV vectors in the retina.

  • Assessing association of comorbidities with treatment choice and persistence in MS: A real-life multicenter study.

    Publication Date: 28/11/2017 on Neurology
    by Laroni A, Signori A, Maniscalco GT, Lanzillo R, Russo CV, Binello E, Lo Fermo S, Repice A, Annovazzi P, Bonavita S, Clerico M, Baroncini D, Prosperini L, La Gioia S, Rossi S, Cocco E, Frau J, Torri Clerici V, Signoriello E, Sartori A, Zarbo IR, Rasia S, Cordioli C, Cerqua R, Di Sapio A, Lavorgna L, Pontecorvo S, Barrilà C, Saccà F, Frigeni B, Esposito S, Ippolito D, Gallo F, Sormani MP,
    DOI: 10.1212/WNL.0000000000004686

    To assess whether the presence of concomitant diseases at multiple sclerosis (MS) diagnosis is associated with the choice and the treatment persistence in an Italian MS cohort.

  • Standard, transepithelial and iontophoresis corneal cross-linking: clinical analysis of three surgical techniques.

    Publication Date: 28/11/2017 on International ophthalmology
    by Rossi S, Santamaria C, Boccia R, De Rosa L, D'Alterio FM, Simonelli F, De Rosa G
    DOI: 10.1007/s10792-017-0772-3

    To evaluate the clinical results of standard, transepithelial (TE) and iontophoresis (I) corneal cross-linking (CXL), in patients with progressive keratoconus.

  • 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.