159 results on '"Ziccardi, L."'
Search Results
2. Genetic characteristics of 234 Italian patients with macular and cone/cone-rod dystrophy
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Falsini, Benedetto, Placidi, Giorgio, De Siena, E., Chiurazzi, Pietro, Minnella, Angelo Maria, Savastano, Maria Cristina, Ziccardi, L., Parisi, V., Iarossi, G., Percio, M., Pitekova, B., Marceddu, G., Maltese, Paolo Enrico, Bertelli, M., Falsini B. (ORCID:0000-0002-3569-4968), Placidi G., Chiurazzi P. (ORCID:0000-0001-5104-1521), Minnella A. M. (ORCID:0000-0001-5896-5313), Savastano M. C. (ORCID:0000-0003-1397-4333), Maltese P. E., Falsini, Benedetto, Placidi, Giorgio, De Siena, E., Chiurazzi, Pietro, Minnella, Angelo Maria, Savastano, Maria Cristina, Ziccardi, L., Parisi, V., Iarossi, G., Percio, M., Pitekova, B., Marceddu, G., Maltese, Paolo Enrico, Bertelli, M., Falsini B. (ORCID:0000-0002-3569-4968), Placidi G., Chiurazzi P. (ORCID:0000-0001-5104-1521), Minnella A. M. (ORCID:0000-0001-5896-5313), Savastano M. C. (ORCID:0000-0003-1397-4333), and Maltese P. E.
- Abstract
Two-hundred and thirty-four Italian patients with a clinical diagnosis of macular, cone and cone-rod dystrophies (MD, CD, and CRD) were examined using next-generation sequencing (NGS) and gene sequencing panels targeting a specific set of genes, Sanger sequencing and—when necessary—multiplex ligation-dependent probe amplification (MLPA) to diagnose the molecular cause of the aforementioned diseases. When possible, segregation analysis was performed in order to confirm unsolved cases. Each patient’s retinal phenotypic characteristics were determined using focal and full-field ERGs, perimetry, spectral domain optical coherence tomography and fundus autofluorescence. We identified 236 potentially causative variants in 136 patients representing the 58.1% of the total cohort, 43 of which were unpublished. After stratifying the patients according to their clinical suspicion, the diagnostic yield was 62.5% and 53.8% for patients with MD and for those with CD/CRD, respectively. The mode of inheritance of all cases confirmed by genetic analysis was 70% autosomal recessive, 26% dominant, and 4% X-linked. The main cause (59%) of both MD and CD/CRD cases was the presence of variants in the ABCA4 gene, followed by variants in PRPH2 (9%) and BEST1 (6%). A careful morpho-functional evaluation of the phenotype, together with genetic counselling, resulted in an acceptable diagnostic yield in a large cohort of Italian patients. Our study emphasizes the role of targeted NGS to diagnose MDs, CDs, and CRDs, as well as the clinical usefulness of segregation analysis for patients with unsolved diagnosis.
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- 2022
3. Neural Conduction Along Postretinal Visual Pathways in Glaucoma
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Oddone, F, Rossetti, L, Parravano, M, Sbardella, D, Coletta, M, Ziccardi, L, Roberti, G, Carnevale, C, Romano, D, Manni, G, and Parisi, V
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Aging ,medicine.medical_specialty ,genetic structures ,PERG ,Cognitive Neuroscience ,Nerve fiber layer ,Glaucoma ,Neurosciences. Biological psychiatry. Neuropsychiatry ,Visual system ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Ophthalmology ,Settore MED/30 ,medicine ,OCT imaging ,Original Research ,Neural Conduction ,business.industry ,Retinal ,medicine.disease ,visual pathways ,eye diseases ,Visual field ,medicine.anatomical_structure ,glaucoma ,chemistry ,Retinal ganglion cell ,030221 ophthalmology & optometry ,Analysis of variance ,sense organs ,business ,VEP ,030217 neurology & neurosurgery ,RC321-571 ,Neuroscience - Abstract
Purpose: This study was conducted in order to evaluate retinal ganglion cell (RCG) function and the neural conduction along the postretinal large and small axons and its correlation with retinal nerve fiber layer thickness (RNFL-T) in open-angle glaucoma (OAG) eyes.Methods: Thirty-seven OAG patients (mean age: 51.68 ± 9.83 years) with 24–2 Humphrey mean deviation (MD) between −2.5 and −20 dB and IOP Results: In the OAG group, a significant (ANOVA, p < 0.01) reduction of 60′ and 15′ PERG P50-N95 and VEP N75-P100 amplitudes and of RNFL-T [overall (average of all quadrants) or temporal] with respect to controls was found; the values of 60′ and 15′ PERG P50 and VEP P100 implicit times and of retinocortical time (RCT; difference between VEP P100 and PERG P50 implicit times) were significantly (p < 0.01) increased with respect to control ones. The observed increased RCTs were significantly linearly correlated (Pearson’s test, p < 0.01) with the reduced PERG amplitude and MD values, whereas no significant linear correlation (p < 0.01) with RNFL-T (overall or temporal) values was detected.Conclusions: In OAG, there is an impaired postretinal neural conduction along both large and small axons (increased 60′ and 15′ RCTs) that is related to RGC dysfunction, but independent from the RNFL morphology. This implies that, in OAG, the impairment of postretinal neural structures can be electrophysiologically identified and may contribute to the visual field defects, as suggested by the linear correlation between the increase of RCT and MD reduction.
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- 2021
4. Pseudoxanthoma elasticum overlaps hereditary spastic paraplegia type 56
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Legrand, A., primary, Pujol, C., additional, Durand, C. M., additional, Mesnil, A., additional, Rubera, I., additional, Duranton, C., additional, Zuily, S., additional, Sousa, A. B., additional, Renaud, M., additional, Boucher, J. L., additional, Pietrancosta, N., additional, Adham, S., additional, Orssaud, C., additional, Marelli, C., additional, Casali, C., additional, Ziccardi, L., additional, Villain, N., additional, Ewenczyk, C., additional, Durr, A., additional, Mignot, C., additional, Stevanin, G., additional, Billon, C., additional, Hureaux, M., additional, Jeunemaitre, X., additional, Goizet, C., additional, and Albuisson, J., additional
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- 2021
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5. Next generation sequencing analysis of patients with Mendelian obesity
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Paolacci, S., primary, Maltese, P.E., additional, Manara, E., additional, Iarossi, G., additional, Ziccardi, L., additional, Colombo, L., additional, Falsini, B., additional, and Bertelli, M., additional
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- 2019
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6. Electrophysiological assessment of visual function in patients with non-arteritic ischaemic optic neuropathy
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Parisi, V., Gallinaro, G., Ziccardi, L., and Coppola, G.
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- 2008
7. Cytidine-5′-diphosphocholine (Citicoline): a pilot study in patients with non-arteritic ischaemic optic neuropathy
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Parisi, V., Coppola, G., Ziccardi, L., Gallinaro, G., and Falsini, B.
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- 2008
8. Penetrating keratoplasty in a newborn: Case report and analysis of current surgical trends in Italy
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RICCI, B., COPPOLA, G., CAPOBIANCO, A., and ZICCARDI, L.
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- 2008
9. Enhancement of Retinal Function and of Neural Conduction Along the Visual Pathway Induced by Treatment with Citicoline Eye Drops in Liposomal Formulation in Open Angle Glaucoma
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Parisi, V, Oddone, F, Roberti, G, Tanga, L, Carnevale, C, Ziccardi, L, and Manni, G
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Settore MED/30 - Published
- 2019
10. Mutation profile of BBS genes in patients with Bardet-Biedl syndrome: An Italian study
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Manara, E., Paolacci, S., D'Esposito, F., Abeshi, A., Ziccardi, L., Falsini, Benedetto, Colombo, L., Iarossi, G., Pilotta, A., Boccone, L., Guerri, Giulia, Monica, M., Marta, B., Maltese, P. E., Buzzonetti, Luca, Rossetti, Lodovico, Bertelli, M., Falsini B. (ORCID:0000-0002-3569-4968), Guerri G., Buzzonetti L. (ORCID:0000-0002-3200-3260), Rossetti L., Manara, E., Paolacci, S., D'Esposito, F., Abeshi, A., Ziccardi, L., Falsini, Benedetto, Colombo, L., Iarossi, G., Pilotta, A., Boccone, L., Guerri, Giulia, Monica, M., Marta, B., Maltese, P. E., Buzzonetti, Luca, Rossetti, Lodovico, Bertelli, M., Falsini B. (ORCID:0000-0002-3569-4968), Guerri G., Buzzonetti L. (ORCID:0000-0002-3200-3260), and Rossetti L.
- Abstract
Background: Bardet-Biedl syndrome (BBS) is a rare inherited multisystemic disorder with autosomal recessive or complex digenic triallelic inheritance. There is currently no treatment for BBS, but some morbidities can be managed. Accurate molecular diagnosis is often crucial for the definition of appropriate patient management and for the development of a potential personalized therapy. Methods: We developed a next-generation-sequencing (NGS) protocol for the screening of the 18 most frequently mutated genes to define the genotype and clarify the mutation spectrum of a cohort of 20 BBS Italian patients. Results: We defined the causative variants in 60% of patients; four of those are novel. 33% of patients also harboured variants in additional gene/s, suggesting possible oligogenic inheritance. To explore the function of different genes, we looked for correlations between genotype and phenotype in our cohort. Hypogonadism was more frequently detected in patients with variants in BBSome proteins, while renal abnormalities in patients with variations in BBSome chaperonin genes. Conclusions: NGS is a powerful tool that can help understanding BBS patients' phenotype through the identification of mutations that could explain differences in phenotype severity and could provide insights for the development of targeted therapy. Furthermore, our results support the existence of additional BBS loci yet to be identified.
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- 2019
11. Pathogenicity of new BEST1 variants identified in Italian patients with best vitelliform macular dystrophy assessed by computational structural biology
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Frecer, V., Iarossi, G., Salvetti, A. P., Maltese, P. E., Delledonne, G., Oldani, M., Staurenghi, G., Falsini, Benedetto, Minnella, Angelo Maria, Ziccardi, L., Magli, A., Colombo, L., D'Esposito, F., Miertus, J., Viola, F., Attanasio, M., Maggio, E., Bertelli, M., Falsini B. (ORCID:0000-0002-3569-4968), Minnella A. M. (ORCID:0000-0001-5896-5313), Frecer, V., Iarossi, G., Salvetti, A. P., Maltese, P. E., Delledonne, G., Oldani, M., Staurenghi, G., Falsini, Benedetto, Minnella, Angelo Maria, Ziccardi, L., Magli, A., Colombo, L., D'Esposito, F., Miertus, J., Viola, F., Attanasio, M., Maggio, E., Bertelli, M., Falsini B. (ORCID:0000-0002-3569-4968), and Minnella A. M. (ORCID:0000-0001-5896-5313)
- Abstract
Background: Best vitelliform macular dystrophy (BVMD) is an autosomal dominant macular degeneration. The typical central yellowish yolk-like lesion usually appears in childhood and gradually worsens. Most cases are caused by variants in the BEST1 gene which encodes bestrophin-1, an integral membrane protein found primarily in the retinal pigment epithelium. Methods: Here we describe the spectrum of BEST1 variants identified in a cohort of 57 Italian patients analyzed by Sanger sequencing. In 13 cases, the study also included segregation analysis in affected and unaffected relatives. We used molecular mechanics to calculate two quantitative parameters related to calcium-activated chloride channel (CaCC composed of 5 BEST1 subunits) stability and calcium-dependent activation and related them to the potential pathogenicity of individual missense variants detected in the probands. Results: Thirty-six out of 57 probands (63% positivity) and 16 out of 18 relatives proved positive to genetic testing. Family study confirmed the variable penetrance and expressivity of the disease. Six of the 27 genetic variants discovered were novel: p.(Val9Gly), p.(Ser108Arg), p.(Asn179Asp), p.(Trp182Arg), p.(Glu292Gln) and p.(Asn296Lys). All BEST1 variants were assessed in silico for potential pathogenicity. Our computational structural biology approach based on 3D model structure of the CaCC showed that individual amino acid replacements may affect channel shape, stability, activation, gating, selectivity and throughput, and possibly also other features, depending on where the individual mutated amino acid residues are located in the tertiary structure of BEST1. Statistically significant correlations between mean logMAR best-corrected visual acuity (BCVA), age and modulus of computed BEST1 dimerization energies, which reflect variations in the in CaCC stability due to amino acid changes, permitted us to assess the pathogenicity of individual BEST1 variants. Conclusions: Using this computa
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- 2019
12. Central retina functional damage in usher syndrome type 2: 22 years of focal macular ERG analysis in a patient population from central and southern Italy
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Galli-Resta, L., Placidi, Giorgio, Campagna, Francesca, Ziccardi, L., Piccardi, Marco, Minnella, Angelo Maria, Abed, E., Iovine, S., Maltese, P., Bertelli, M., Falsini, Benedetto, Placidi G., Campagna F., Piccardi M., Minnella A. (ORCID:0000-0001-5896-5313), Falsini B. (ORCID:0000-0002-3569-4968), Galli-Resta, L., Placidi, Giorgio, Campagna, Francesca, Ziccardi, L., Piccardi, Marco, Minnella, Angelo Maria, Abed, E., Iovine, S., Maltese, P., Bertelli, M., Falsini, Benedetto, Placidi G., Campagna F., Piccardi M., Minnella A. (ORCID:0000-0001-5896-5313), and Falsini B. (ORCID:0000-0002-3569-4968)
- Abstract
PURPOSE. Recent studies show that patients with Usher syndrome type 2 (USH2) have abnormal cone structure and density in the central retina. This occurs in the presence of normal acuity, opening the quest for additional sensitive functional measures of central cone function in USH. We tested here whether focal macular cone electroretinogram (fERG) could be such a tool. METHODS. This retrospective study of central cone function loss was based on data from 47 patients with USH2 from the Ophthalmology Department of the Policlinico Gemelli/Catholic University in Rome. The analysis focused on the decrease of the fERG, obtained in response to a 41-Hz sinusoidal modulation of a uniform field presented to the central 18°, generated by red light-emitting diodes (LEDs) and superimposed on an equiluminant steady adapting background. fERG decrease was compared with the decrease of best-corrected visual acuity and Goldmann kinetic perimetry V4E field. RESULTS. fERG follow-up data document a severe and precocious loss of central cone function in USH2 patients, preceding losses in other measures of cone function. fERG is already reduced to 40% of control at the beginning of the second decade of life, and by 25 years of age, all USH2 patients have fERGs less than 30% of control values. CONCLUSIONS. fERG represents a sensitive tool to evaluate central cone function in USH2, anticipating the decline of other central cone function measures, such as visual acuity and Goldmann perimetry.
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- 2018
13. Neuroretinal dysfunction is associated with early peripheral motor unit loss in type 1 diabetes
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Ylli, D, Picconi, F, Mataluni, G, Parravano, M, Ziccardi, L, Di Renzo, A, Coluzzi, S, Pasqualetti, P, Chioma, L, Malandrucco, I, Lauro, D, Marfia, G, and Frontoni, S
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Settore MED/26 - Neurologia - Published
- 2017
14. Neuroretinal Dysfunction Is Associated with Early Peripheral Motor Unit Loss in Type 1 Diabetes Mellitus
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Picconi, F, Mataluni, G, Ziccardi, L, Di Renzo, A, Parravano, M, Coluzzi, S, Ylli, D, Pasqualetti, P, Chioma, L, Malandrucco, I, Lauro, D, Marfia, G, and Frontoni, S
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Settore MED/26 - Neurologia - Published
- 2017
15. 6133Takotsubo syndrome in patients with malignancies: a metanalysis
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Tarantino, N, primary, Santoro, F, additional, Guastafierro, F, additional, Di Terlizzi, V, additional, Formica, S E, additional, Ieva, R, additional, D'Arienzo, G, additional, Pellegrino, P L, additional, Ziccardi, L C, additional, Di Biase, M, additional, and Brunetti, N D, additional
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- 2018
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16. Genotype-Phenotype Characterization of Novel Variants in Six Italian Patients with Familial Exudative Vitreoretinopathy
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Iarossi, G., Bertelli, M., Maltese, P. E., Gusson, E., Marchini, G., Bruson, A., Benedetti, S., Volpetti, S., Catena, G., Buzzonetti, L., Ziccardi, L., Buzzonetti L. (ORCID:0000-0002-3200-3260), Iarossi, G., Bertelli, M., Maltese, P. E., Gusson, E., Marchini, G., Bruson, A., Benedetti, S., Volpetti, S., Catena, G., Buzzonetti, L., Ziccardi, L., and Buzzonetti L. (ORCID:0000-0002-3200-3260)
- Abstract
Familial exudative vitreoretinopathy (FEVR) is a complex disorder characterized by incomplete development of the retinal vasculature. Here, we report the results obtained on the spectrum of genetic variations and correlated phenotypes found in a cohort of Italian FEVR patients. Eight probands (age range 7-19 years) were assessed by genetic analysis and comprehensive age-appropriate ophthalmic examination. Genetic testing investigated the genes most widely associated in literature with FEVR: FZD4, LRP5, TSPAN12, and NDP. Clinical and genetic evaluations were extended to relatives of probands positive to genetic testing. Six out of eight probands (75%) showed a genetic variation probably related to the phenotype. We identified four novel genetic variants, one variant already described in association with Norrie disease and one previously described linked to autosomal dominant FEVR. Pedigree analysis of patients led to the classification of four autosomal dominant cases of FEVR (caused by FZD4 and TSPAN12 variants) and two X-linked FEVR probands (NDP variants). None of the patients showed variants in the LRP5 gene. This study represents the largest cohort study in Italian FEVR patients. Our findings are in agreement with the previous literature confirming that FEVR is a clinically and genetically heterogeneous retinal disorder, even when it manifests in the same family.
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- 2017
17. Short-term effects of vision trainer rehabilitation in patients affected by anisometropic amblyopia: electrofunctional evaluation
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Esposito Veneruso, P, Ziccardi, L, Magli, G, Falsini, Benedetto, Magli, A., Falsini, Benedetto (ORCID:0000-0002-3569-4968), Esposito Veneruso, P, Ziccardi, L, Magli, G, Falsini, Benedetto, Magli, A., and Falsini, Benedetto (ORCID:0000-0002-3569-4968)
- Abstract
The aim of the present study was to evaluate the short-term effects of the vision trainer rehabilitation technique on retinal and post-retinal function in young amblyopic patients outside the critical visual developmental period.
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- 2014
18. Sequential spectral domain optical coherence tomography imaging of an eye after successful removal of subfoveal perfluorcarbon liquid collection
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Savastano, Maria Cristina, Ziccardi, L, Zinzanella, G, Falsini, Benedetto, Minnella, Angelo Maria, Savastano, Mc (ORCID:0000-0003-1397-4333), Falsini, Benedetto (ORCID:0000-0002-3569-4968), Minnella, Angelo Maria (ORCID:0000-0001-5896-5313), Savastano, Maria Cristina, Ziccardi, L, Zinzanella, G, Falsini, Benedetto, Minnella, Angelo Maria, Savastano, Mc (ORCID:0000-0003-1397-4333), Falsini, Benedetto (ORCID:0000-0002-3569-4968), and Minnella, Angelo Maria (ORCID:0000-0001-5896-5313)
- Abstract
To evaluate retinal restoration after subfoveal perfluorcarbon liquid (PFCL) bubble removal by means of autofluorescence, infrared, and spectral domain optical coherence tomography over 2 years of follow-up.
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- 2014
19. Evidence of the neuroprotective role of the citicoline in glaucoma patients
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Parisi, V., Coppola, G., Centofanti, M., Oddone, F., Angrisani, M. A., Ziccardi, L., Ricci, B., Quaranta, Luciano, and Manni, G.
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genetic structures ,neuroprotection ,eye diseases - Published
- 2008
20. Early Detection of Central Visual Function Decline in Cone-Rod Dystrophy by the Use of Macular Focal Cone Electroretinogram
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Galli Resta, L, Piccardi, M, Ziccardi, L, Fadda, A, Minnella, Angelo Maria (ORCID:0000-0001-5896-5313), Marangoni, D, Placidi, G, Resta, G, Falsini, B. (ORCID:0000-0002-3569-4968), Galli Resta, L, Piccardi, M, Ziccardi, L, Fadda, A, Minnella, Angelo Maria (ORCID:0000-0001-5896-5313), Marangoni, D, Placidi, G, Resta, G, and Falsini, B. (ORCID:0000-0002-3569-4968)
- Abstract
PURPOSE. To evaluate macular focal cone ERG (fERG) as a tool for reliable and early detection of central retinal function decay in cone-rod dystrophy (CRD). METHODS. A retrospective study of the time course of fERG amplitude and its relation to visual acuity alterations was performed in 47 CRD patients followed yearly for 6.0 +/- 3.1 years. Macular focal cone ERG was evoked by a flickering uniform red field overlaying the central 188 of visual field. RESULTS. Macular focal cone ERG follow-up allowed a clear-cut identification of CRD patients as stationary or progressive, in agreement with visual acuity follow-up. In all progressive patients, fERG declined whenever visual acuity declined, and-in 50% of the cases-fERG loss anticipated acuity loss of several years. CONCLUSIONS. Macular focal cone ERG represents a sensitive assay to detect, categorize, and follow the progression of central retinal dysfunction in CRD. Its use as a diagnostic tool in CRD may help anticipate, for an individual patient, the likelihood and rate of further disease progression before visual acuity loss has occurred.
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- 2013
21. Retinal function following transpupillary thermotherapy for occult choroidal neovascularization in age-related macular degeneration: A short-term study by focal electroretinography
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Pirozzi, E., Manganelli, Chiara, Piccardi, Marco, Minnella, Angelo Maria, Fadda, A., Ziccardi, L., Coccimiglio, F., Falsini, Benedetto, Manganelli C. (ORCID:0000-0001-5246-3590), Piccardi M., Minnella A. (ORCID:0000-0001-5896-5313), Falsini B. (ORCID:0000-0002-3569-4968), Pirozzi, E., Manganelli, Chiara, Piccardi, Marco, Minnella, Angelo Maria, Fadda, A., Ziccardi, L., Coccimiglio, F., Falsini, Benedetto, Manganelli C. (ORCID:0000-0001-5246-3590), Piccardi M., Minnella A. (ORCID:0000-0001-5896-5313), and Falsini B. (ORCID:0000-0002-3569-4968)
- Abstract
Purpose: To assess short-term changes in macular function after transpupillary thermotherapy (TTT) in patients with occult subfoveal choroidal neovascularization (CNV) secondary to agerelated macular degeneration (AMD), using focal electroretinography (FERG). Methods: Twenty-five patients with occult subfoveal CNV due to AMD were treated with TTT delivered using an infrared (810 nm) diode laser (spot size 3.0 mm, laser power 400-600 mW, duration 60 seconds). All patients were clinically evaluated before, 1 and 6 weeks after treatment. Snellen visual acuity (VA) was measured at each visit. Fluorescein angiography (FA) was performed at baseline and 6 weeks after TTT. Focal ERGs were recorded in all patients immediately before and 1 week after TTT in response to an 18-degree diameter, 41 Hz flickering spot (630 nm) centred on the fovea, presented on a steady background in Maxwellian view. A subgroup of 12 patients was also re-tested by FERG at 6-weeks post-TTT. Results: No significant changes in mean FERG amplitude and phase were observed across the different recording sessions before and after TTT. One week after TTT, four patients had significant (>2 SD from baseline variability) increases in FERG amplitude and/or phase advances, one had a decrease in amplitude and four had phase delays, compared to baseline. The remaining 15 patients had stable FERGs. Six weeks after TTT, four patients had significant increases in FERG amplitude and/or phase advances, four had decreases in amplitude and/or phase delays, and four had stable FERGs, compared to baseline. Improvement in FERG parameters after TTT was always associated with an improvement in VA and a decrease in exudation. Patients with post-TTT FERG deterioration had stable or deteriorated clinical pictures. At either 1 or 6 weeks post-TTT, the FERG amplitude increase was inverselycorrelated (p < 0.05) with the baseline FERG amplitude and VA. Conclusions: Three major conclusions can be drawn: in a short-term follow
- Published
- 2006
22. Loss of Retinoschisin (RS1) Cell Surface Protein in Maturing Mouse Rod Photoreceptors Elevates the Luminance Threshold for Light-Driven Translocation of Transducin But Not Arrestin
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Ziccardi, L., primary, Vijayasarathy, C., additional, Bush, R. A., additional, and Sieving, P. A., additional
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- 2012
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23. Longitudinal assessment of childhood optic gliomas: Relationship between brain imaging and optic pathway function
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Falsini, B., primary, Lazzareschi, I., additional, Ruggiero, A., additional, Ziccardi, L., additional, Placentino, L., additional, Colosimo, C., additional, Di Rocco, C., additional, and Riccardi, R., additional
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- 2007
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24. Outer retina dysfunction and choriocapillaris impairment in type 1 diabetes
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Simona Frontoni, Giuseppe Querques, Riccardo Sacconi, Fabiana Picconi, Eliana Costanzo, V. Parisi, Monica Varano, A Di Renzo, Enrico Borrelli, Mariacristina Parravano, Lucia Ziccardi, Parravano, M., Ziccardi, L., Borrelli, E., Costanzo, E., Frontoni, S., Picconi, F., Parisi, V., Sacconi, R., Di Renzo, A., Varano, M., and Querques, G.
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Male ,0301 basic medicine ,genetic structures ,chemistry.chemical_compound ,Settore MED/13 ,0302 clinical medicine ,Medicine ,Tomography ,Multidisciplinary ,Angiography ,Diabetic retinopathy ,Middle Aged ,Reflectivity ,Retinal diseases ,Type 1 diabetes ,medicine.anatomical_structure ,Female ,Perfusion ,Tomography, Optical Coherence ,Type 1 ,Adult ,medicine.medical_specialty ,Science ,Article ,Retina ,Young Adult ,03 medical and health sciences ,Ophthalmology ,Diabetes Mellitus ,Electroretinography ,Humans ,Response Amplitude ,Aged ,Diabetic Retinopathy ,Choroid ,business.industry ,Retinal Vessels ,Retinal ,Optical coherence tomography angiography ,medicine.disease ,eye diseases ,Cross-Sectional Studies ,Diabetes Mellitus, Type 1 ,030104 developmental biology ,chemistry ,Optical Coherence ,Case-Control Studies ,030221 ophthalmology & optometry ,sense organs ,business - Abstract
To study the outer retina morpho-functional characteristics and the choriocapillaris (CC) features in type 1 diabetic (T1D) patients, with and without signs of diabetic retinopathy (NPDR and NoDR). Twenty-five NPDR and 18 NoDR eyes were imaged by Optical Coherence Tomography Angiography. Ellipsoid zone (EZ) “normalized” reflectivity and CC perfusion density parameters, as flow deficits number (FDn), flow deficit average area (FDa) and flow deficit percentage (FD%), were analysed. Multifocal electroretinogram (mfERG) response amplitude densities (RADs) were measured. Mean EZ “normalized” reflectivity, CC FDn and FD% values, were similar (p > 0.05) in both groups, FDa was significant greater (p > 0.05) in NPDR compared with NoDR eyes. MfERG-RADs were similar in both groups. NPDR eyes showed a significant (p
- Published
- 2021
25. Functional Changes of Retinal Ganglion Cells and Visual Pathways in Patients with Chronic Leber's Hereditary Optic Neuropathy during One Year of Follow-up
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Vincenzo Parisi, Anna Maria De Negri, Lucia Ziccardi, Lucilla Barbano, Piero Barboni, Federico Sadun, Valerio Carelli, Chiara La Morgia, Parisi V., Ziccardi L., Sadun F., De Negri A.M., La Morgia C., Barbano L., Carelli V., and Barboni P.
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Adult ,Male ,Retinal Ganglion Cells ,medicine.medical_specialty ,genetic structures ,Optic Atrophy, Hereditary, Leber ,Visual system ,Retinal ganglion ,Optic neuropathy ,03 medical and health sciences ,LHON ,0302 clinical medicine ,Ophthalmology ,medicine ,follow-up ,Electroretinography ,Humans ,Visual Pathways ,retinal ganglion cell ,030304 developmental biology ,0303 health sciences ,Analysis of Variance ,medicine.diagnostic_test ,business.industry ,Leber's hereditary optic neuropathy ,Case-control study ,Middle Aged ,medicine.disease ,eye diseases ,Confidence interval ,Case-Control Studies ,030221 ophthalmology & optometry ,Evoked Potentials, Visual ,Female ,sense organs ,Analysis of variance ,business - Abstract
Purpose: To assess changes of retinal ganglion cells (RGCs) and visual pathways’ function in patients with Leber's hereditary optic neuropathy (LHON) during 12 months of follow-up of the chronic phase. Design: Retrospective case series. Participants: Twenty-two patients with LHON (mean age, 36.3±9.3 years) in the “chronic phase” of the disease, providing 42 eyes (LHON group) with different pathogenic mitochondrial DNA mutations (group 11778: 21 eyes; group 3460: 4 eyes; group 14484: 13 eyes; and group 14568: 4 eyes) were enrolled. Twenty-five age-similar healthy participants, providing 25 eyes, served as controls. Methods: Pattern electroretinogram (PERG) and visual evoked potentials (VEP), in response to 60ʹ and 15ʹ checks visual stimuli, were recorded at baseline in all subjects and after 6 and 12 months of follow-up in patients with LHON. At baseline, in all LHON eyes for each PERG and VEP parameter (amplitude and implicit time), the 95% confidence limit (CL) of test–retest variability was calculated. The PERG and VEP mean values observed in LHON eyes were compared (1-way analysis of variance [ANOVA]) with those of controls. During the follow-up, the PERG and VEP differences observed with respect to baseline were evaluated by ANOVA. Main Outcome Measures: Changes of individual and mean absolute values of 60ʹ and 15ʹ PERG amplitude and VEP amplitude and implicit time at each time point compared with baseline values in the LHON group. Results: At baseline, mean values of PERG and VEP parameters detected in the LHON group were significantly (P < 0.01) different with respect to control values. In the LHON group, at 6 and 12 months of follow-up, the majority of eyes showed unmodified (within 95% CL) PERG and VEP values, and mean absolute values of these measures were not significantly (P > 0.01) different from baseline values. Conclusions: In our untreated patients with chronic LHON, with different specific pathogenic mutations, RGCs and visual pathways function were not significantly modified during 12 months of follow-up. This should be considered in the disease natural history when attempts for treatments are proposed in chronic LHON.
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- 2018
26. Retinal AAV8-RS1 Gene Therapy for X-Linked Retinoschisis: Initial Findings from a Phase I/IIa Trial by Intravitreal Delivery
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Sten Kjellstrom, Paul A. Sieving, Lisa L. Wei, Camasamudram Vijayasarathy, Yong Zeng, H. Nida Sen, Zhijian Wu, Henry E. Wiley, Brett G. Jeffrey, Peter Colosi, J. Fraser Wright, Suja Hiriyanna, Ronald A. Bush, Catherine A Cukras, Amy Turriff, Tae Kwon Park, Dario Marangoni, Lucia Ziccardi, Cukras, C, Wiley, He, Jeffrey, Bg, Sen, Hn, Turriff, A, Zeng, Y, Vijayasarathy, C, Marangoni, D, Ziccardi, L, Kjellstrom, S, Park, Tk, Hiriyanna, S, Wright, Jf, Colosi, P, Wu, Z, Bush, Ra, Wei, Ll, and Sieving, Pa.
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Male ,0301 basic medicine ,Technology ,genetic structures ,Genetic enhancement ,Retinoschisin Protein ,Retinoschisis ,Eye ,Medical and Health Sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Drug Discovery ,Retinal detachment ,clinical trial ,Middle Aged ,Biological Sciences ,gene therapy ,AAV vector ,medicine.anatomical_structure ,Tolerability ,6.1 Pharmaceuticals ,Intravitreal Injections ,Molecular Medicine ,Female ,X-linked retinoschisis ,Biotechnology ,Adult ,medicine.medical_specialty ,Clinical Trials and Supportive Activities ,X-linked retinoschisi ,Retina ,ocular disease ,retinal disease ,Young Adult ,03 medical and health sciences ,Clinical Research ,Ophthalmology ,Genetics ,medicine ,Humans ,Eye Proteins ,Eye Disease and Disorders of Vision ,Molecular Biology ,Aged ,Pharmacology ,business.industry ,Neurosciences ,Evaluation of treatments and therapeutic interventions ,Retinal ,Genetic Therapy ,medicine.disease ,eye diseases ,Clinical trial ,030104 developmental biology ,chemistry ,Mutation ,030221 ophthalmology & optometry ,business - Abstract
This study evaluated the safety and tolerability of ocular RS1 adeno-associated virus (AAV8-RS1) gene augmentation therapy to the retina of participants with X-linked retinoschisis (XLRS). XLRS is a monogenic trait affecting only males, caused by mutations in the RS1 gene. Retinoschisin protein is secreted principally in the outer retina, and its absence results in retinal cavities, synaptic dysfunction, reduced visual acuity, and susceptibility to retinal detachment. This phase I/IIa single-center, prospective, open-label, three-dose-escalation clinical trial administered vector to nine participants with pathogenic RS1 mutations. The eye of each participant with worse acuity (≤63 letters; Snellen 20/63) received the AAV8-RS1 gene vector by intravitreal injection. Three participants were assigned to each of three dosage groups: 1e9 vector genomes (vg)/eye, 1e10 vg/eye, and 1e11 vg/eye. The investigational product was generally well tolerated in all but one individual. Ocular events included dose-related inflammation that resolved with topical and oral corticosteroids. Systemic antibodies against AAV8 increased in a dose-related fashion, but no antibodies against RS1 were observed. Retinal cavities closed transiently in one participant. Additional doses and immunosuppressive regimens are being explored to pursue evidence of safety and efficacy (ClinicalTrials.gov: NCT02317887).
- Published
- 2018
27. Bilateral Symmetry of Visual Function Loss in Cone-Rod Dystrophies
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Marco Piccardi, Angelo Maria Minnella, Giorgio Placidi, Antonello Fadda, Lucia Galli-Resta, Matteo Bertelli, Benedetto Falsini, Giovanni Resta, Edoardo Abed, Giuseppe Rossi, Monia Zuntini, Lucia Ziccardi, Dario Marangoni, Francesca Campagna, Galli-Resta, L, Falsini, B, Rossi, G, Piccardi, M, Ziccardi, L, Fadda, A, Minnella, A, Marangoni, D, Placidi, G, Campagna, F, Abed, E, Bertelli, M, Zuntini, M, and Resta, G.
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0301 basic medicine ,Male ,Visual acuity ,genetic structures ,Intraclass correlation ,Visual Acuity ,ABCA4 ,interocular ,Blindness ,0302 clinical medicine ,Cone dystrophy ,Child ,Aged, 80 and over ,Observer Variation ,Clinical Trials as Topic ,medicine.diagnostic_test ,biology ,Settore MED/30 - MALATTIE APPARATO VISIVO ,Middle Aged ,Sensory Systems ,Child, Preschool ,Disease Progression ,Female ,medicine.symptom ,Adult ,medicine.medical_specialty ,Electroretinography ,Interocular ,Visual function ,Ophthalmology ,Cellular and Molecular Neuroscience ,Adolescent ,Visual impairment ,03 medical and health sciences ,Young Adult ,Retinitis pigmentosa ,medicine ,visual function ,Humans ,cone dystrophy ,Aged ,Retrospective Studies ,business.industry ,medicine.disease ,eye diseases ,Clinical trial ,030104 developmental biology ,Mutation ,030221 ophthalmology & optometry ,biology.protein ,Feasibility Studies ,ATP-Binding Cassette Transporters ,sense organs ,business ,Cone-Rod Dystrophies - Abstract
PURPOSE: To investigate bilateral symmetry of visual impairment in cone-rod dystrophy (CRD) patients and understand the feasibility of clinical trial designs treating one eye and using the untreated eye as an internal control. METHODS: This was a retrospective study of visual function loss measures in 436 CRD patients followed at the Ophthalmology Department of the Catholic University in Rome. Clinical measures considered were best-corrected visual acuity, focal macular cone electroretinogram (fERG), and Ganzfeld cone-mediated and rod-mediated electroretinograms. Interocular agreement in each of these clinical indexes was assessed by t- and Wilcoxon tests for paired samples, structural (Deming) regression analysis, and intraclass correlation. Baseline and follow-up measures were analyzed. A separate analysis was performed on the subset of 61 CRD patients carrying likely disease-causing mutations in the ABCA4 gene. RESULTS: Statistical tests show a very high degree of bilateral symmetry in the extent and progression of visual impairment in the fellow eyes of CRD patients. CONCLUSIONS: These data contribute to a better understanding of CRDs and support the feasibility of clinical trial designs involving unilateral eye treatment with the use of fellow eye as internal control.
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- 2016
28. Ocular and Systemic Safety of a Recombinant AAV8 Vector for X-linked Retinoschisis Gene Therapy: GLP studies in rabbits and Rs1-KO mice
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Joshua T. Bartoe, Lucia Ziccardi, Zhijian Wu, Camasamudram Vijayasarathy, Paul A. Sieving, Kiran Palyada, Lisa L. Wei, Dario Marangoni, Ronald A. Bush, Maria José Santos, Suja Hiriyanna, Peter Colosi, Yong Zeng, Marangoni, D, Bush, Ra, Zeng, Y, Wei, Ll, Ziccardi, L, Vijayasarathy, C, Bartoe, Jt, Palyada, K, Santos, M, Hiriyanna, S, Wu, Z, Colosi, P, and Sieving, Pa.
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,lcsh:QH426-470 ,Genetic enhancement ,Retinoschisis ,Inflammation ,Eye ,Article ,Viral vector ,03 medical and health sciences ,chemistry.chemical_compound ,Genetics ,medicine ,lcsh:QH573-671 ,Eye Disease and Disorders of Vision ,Molecular Biology ,lcsh:Cytology ,business.industry ,Neurosciences ,Retinal detachment ,Retinal ,Gene Therapy ,Macular degeneration ,medicine.disease ,eye diseases ,lcsh:Genetics ,030104 developmental biology ,chemistry ,Molecular Medicine ,sense organs ,medicine.symptom ,business ,RETINOSCHISIN ,Biotechnology - Abstract
X-linked retinoschisis (XLRS) is a retinal disease caused by mutations in the gene encoding the protein retinoschisin (RS1) and is one of the most common causes of macular degeneration in young men. Our therapeutic approach for XLRS is based on the administration of AAV8-scRS/IRBPhRS, an adeno-associated viral vector coding the human RS1 protein, via the intravitreal (IVT) route. Two Good Laboratory Practice studies, a 9-month study in New Zealand White rabbits (n = 124) injected with AAV8-scRS/IRBPhRS at doses of 2E9, 2E10, 2E11, and 1.5E12 vector genomes/eye (vg/eye), and a 6-month study in Rs1-KO mice (n = 162) dosed with 2E9 and 2E10 vg/eye of the same vector were conducted to assess ocular and systemic safety. A self-resolving, dose-dependent vitreal inflammation was the main ocular finding, and except for a single rabbit dosed with 1.5E12 vg/eye, which showed a retinal detachment, no other ocular adverse event was reported. Systemic toxicity was not identified in either species. Biodistribution analysis in Rs1-KO mice detected spread of vector genome in extraocular tissues, but no evidence of organ or tissues damage was found. These studies indicate that IVT administration of AAV8-scRS/IRBPhRS is safe and well tolerated and support its advancement into a phase 1/2a clinical trial for XLRS.
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- 2016
29. Synaptic pathology and therapeutic repair in adult retinoschisis mouse by AAV-RS1 transfer
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Ou, Jingxing, Vijayasarathy, Camasamudram, Ziccardi, Lucia, Chen, Shan, Zeng, Yong, Marangoni, Dario, Pope, Jodie G, Bush, Ronald A, Wu, Zhijian, Li, Wei, Sieving, Paul A, Ou, J, Vijayasarathy, C, Ziccardi, L, Chen, S, Zeng, Y, Marangoni, D, Pope, Jg, Bush, Ra, Wu, Z, Li, W, and Sieving, Pa.
- Subjects
Male ,Retinoschisis ,Knockout ,Genetic Vectors ,Immunology ,TRPM Cation Channels ,Inbred C57BL ,Eye ,Medical and Health Sciences ,Mice ,Receptors ,Metabotropic Glutamate ,Electroretinography ,Genetics ,Animals ,Humans ,2.1 Biological and endogenous factors ,Photoreceptor Cells ,Calcium Signaling ,Aetiology ,Eye Proteins ,Eye Disease and Disorders of Vision ,Neuronal Plasticity ,Animal ,Vertebrate ,Neurosciences ,Genetic Therapy ,Dependovirus ,Synapses ,Disease Models ,Neurological ,Cell Adhesion Molecules - Abstract
Strategies aimed at invoking synaptic plasticity have therapeutic potential for several neurological conditions. The human retinal synaptic disease X-linked retinoschisis (XLRS) is characterized by impaired visual signal transmission through the retina and progressive visual acuity loss, and mice lacking retinoschisin (RS1) recapitulate human disease. Here, we demonstrate that restoration of RS1 via retina-specific delivery of adeno-associated virus type 8-RS1 (AAV8-RS1) vector rescues molecular pathology at the photoreceptor-depolarizing bipolar cell (photoreceptor-DBC) synapse and restores function in adult Rs1-KO animals. Initial development of the photoreceptor-DBC synapse was normal in the Rs1-KO retina; however, the metabotropic glutamate receptor 6/transient receptor potential melastatin subfamily M member 1-signaling (mGluR6/TRPM1-signaling) cascade was not properly maintained. Specifically, the TRPM1 channel and G proteins Gαo, Gβ5, and RGS11 were progressively lost from postsynaptic DBC dendritic tips, whereas the mGluR6 receptor and RGS7 maintained proper synaptic position. This postsynaptic disruption differed from other murine night-blindness models with an electronegative electroretinogram response, which is also characteristic of murine and human XLRS disease. Upon AAV8-RS1 gene transfer to the retina of adult XLRS mice, TRPM1 and the signaling molecules returned to their proper dendritic tip location, and the DBC resting membrane potential was restored. These findings provide insight into the molecular plasticity of a critical synapse in the visual system and demonstrate potential therapeutic avenues for some diseases involving synaptic pathology.
- Published
- 2015
30. Whole Genome Sequencing Solves an Atypical Form of Bardet-Biedl Syndrome: Identification of Novel Pathogenic Variants of BBS9 .
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Stellacci E, Niceta M, Bruselles A, Straface E, Tatti M, Carvetta M, Mancini C, Cecchetti S, Parravano M, Barbano L, Varano M, Tartaglia M, Ziccardi L, and Cordeddu V
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- Humans, Male, Adolescent, Cilia pathology, Cilia genetics, Cytoskeletal Proteins, Bardet-Biedl Syndrome genetics, Bardet-Biedl Syndrome diagnosis, Whole Genome Sequencing
- Abstract
Bardet-Biedl syndrome (BBS) is a rare recessive multisystem disorder characterized by retinitis pigmentosa, obesity, postaxial polydactyly, cognitive deficits, and genitourinary defects. BBS is clinically variable and genetically heterogeneous, with 26 genes identified to contribute to the disorder when mutated, the majority encoding proteins playing role in primary cilium biogenesis, intraflagellar transport, and ciliary trafficking. Here, we report on an 18-year-old boy with features including severe photophobia and central vision loss since childhood, hexadactyly of the right foot and a supernumerary nipple, which were suggestive of BBS. Genetic analyses using targeted resequencing and exome sequencing failed to provide a conclusive genetic diagnosis. Whole-genome sequencing (WGS) allowed us to identify compound heterozygosity for a missense variant and a large intragenic deletion encompassing exon 12 in BBS9 as underlying the condition. We assessed the functional impact of the identified variants and demonstrated that they impair BBS9 function, with significant consequences for primary cilium formation and morphology. Overall, this study further highlights the usefulness of WGS in the diagnostic workflow of rare diseases to reach a definitive diagnosis. This report also remarks on a requirement for functional validation analyses to more effectively classify variants that are identified in the frame of the diagnostic workflow.
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- 2024
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31. Retraction Note: Autoantibodies detection in patients affected by autoimmune retinopathies.
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Ceccarini MR, Medori MC, Dhuli K, Tezzele S, Bonetti G, Micheletti C, Maltese PE, Cecchin S, Donato K, Colombo L, Rossetti L, Staurenghi G, Salvetti AP, Oldani M, Ziccardi L, Marangoni D, Iarossi G, Falsini B, Placidi G, D'Esposito F, Viola F, Nassisi M, Leone G, Cimino L, De Simone L, Mastrofilippo V, Beccari T, and Bertelli M
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- Humans, Retinal Diseases immunology, Retinal Diseases diagnosis, Retraction of Publication as Topic, Autoantibodies blood, Autoantibodies immunology, Autoimmune Diseases immunology, Autoimmune Diseases diagnosis
- Abstract
The article "Autoantibodies detection in patients affected by autoimmune retinopathies", by M.R. Ceccarini, M.C. Medori, K. Dhuli, S. Tezzele, G. Bonetti, C. Micheletti, P.E. Maltese, S. Cecchin, K. Donato, L. Colombo, L. Rossetti, G. Staurenghi, A.P. Salvetti, M. Oldani, L. Ziccardi, D. Marangoni, G. Iarossi, B. Falsini, G. Placidi, F. D'Esposito, F. Viola, M. Nassisi, G. Leone, L. Cimino, L. De Simone, V. Mastrofilippo, T. Beccari, M. Bertelli, published in Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 57-63-DOI: 10.26355/eurrev_202312_34690-PMID: 38112948 has been retracted by the Editor in Chief for the following reasons. Following some concerns raised on PubPeer, the Editor in Chief has started an investigation to assess the validity of the results. The outcome of the investigation revealed that the manuscript presented major flaws in the following: - Issues with ethical approval - Undeclared conflict of interest In light of concerns regarding the potential manipulation of Supplementary Figure 2, the journal's inquiry has been unable to conclusively determine whether the alterations noted on PubPeer constitute figure manipulation. The investigation yielded divergent evaluations. However, given the aforementioned concerns, the Editor in Chief doubts the integrity of the findings presented and thus, has opted to retract the article. The authors disagree with this retraction. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/34690.
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- 2024
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32. Retinal Dystrophies Associated With Peripherin-2: Genetic Spectrum and Novel Clinical Observations in 241 Patients.
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Heath Jeffery RC, Thompson JA, Lo J, Chelva ES, Armstrong S, Pulido JS, Procopio R, Vincent AL, Bianco L, Battaglia Parodi M, Ziccardi L, Antonelli G, Barbano L, Marques JP, Geada S, Carvalho AL, Tang WC, Chan CM, Boon CJF, Hensman J, Chen TC, Lin CY, Chen PL, Vincent A, Tumber A, Heon E, Grigg JR, Jamieson RV, Cornish EE, Nash BM, Borooah S, Ayton LN, Britten-Jones AC, Edwards TL, Ruddle JB, Sharma A, Porter RG, Lamey TM, McLaren TL, McLenachan S, Roshandel D, and Chen FK
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- Humans, Middle Aged, Adult, Male, Female, Adolescent, Aged, Child, Young Adult, Child, Preschool, Tomography, Optical Coherence, Mutation, Fluorescein Angiography, Genetic Association Studies, Retrospective Studies, DNA Mutational Analysis, DNA genetics, Pedigree, Peripherins genetics, Retinal Dystrophies genetics, Retinal Dystrophies physiopathology, Retinal Dystrophies diagnosis, Visual Acuity physiology, Electroretinography, Phenotype
- Abstract
Purpose: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene., Methods: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype-phenotype correlations., Results: The median age at symptom onset was 40 years (range, 4-78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, or vitelliform macular dystrophy (11%), central areolar choroidal dystrophy (28%), pseudo-Stargardt pattern dystrophy (41%), and retinitis pigmentosa (25%). Symptom onset was earlier in retinitis pigmentosa as compared with pseudo-Stargardt pattern dystrophy (34 vs 44 years; P = 0.004). The median visual acuity was 0.18 logMAR (interquartile range, 0-0.54 logMAR) and 0.18 logMAR (interquartile range 0-0.42 logMAR) in the right and left eyes, respectively. ERG showed a significantly reduced amplitude across all components (P < 0.001) and a peak time delay in the light-adapted 30-Hz flicker and single-flash b-wave (P < 0.001). Twenty-two variants were novel. The central areolar choroidal dystrophy phenotype was associated with 13 missense variants. The remaining variants showed marked phenotypic variability., Conclusions: We described six distinct FAF phenotypes associated with variants in the PRPH2 gene. One FAF phenotype may have multiple ERG phenotypes, demonstrating a discordance between structure and function. Given the vast spectrum of PRPH2 disease our findings are useful for future clinical trials.
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- 2024
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33. Bi-allelic variants in SNF8 cause a disease spectrum ranging from severe developmental and epileptic encephalopathy to syndromic optic atrophy.
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Brugger M, Lauri A, Zhen Y, Gramegna LL, Zott B, Sekulić N, Fasano G, Kopajtich R, Cordeddu V, Radio FC, Mancini C, Pizzi S, Paradisi G, Zanni G, Vasco G, Carrozzo R, Palombo F, Tonon C, Lodi R, La Morgia C, Arelin M, Blechschmidt C, Finck T, Sørensen V, Kreiser K, Strobl-Wildemann G, Daum H, Michaelson-Cohen R, Ziccardi L, Zampino G, Prokisch H, Abou Jamra R, Fiorini C, Arzberger T, Winkelmann J, Caporali L, Carelli V, Stenmark H, Tartaglia M, and Wagner M
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- Animals, Humans, Child, Zebrafish genetics, Phenotype, Endosomal Sorting Complexes Required for Transport genetics, Optic Atrophy genetics, Epilepsy, Generalized
- Abstract
The endosomal sorting complex required for transport (ESCRT) machinery is essential for membrane remodeling and autophagy and it comprises three multi-subunit complexes (ESCRT I-III). We report nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8 (GenBank: NM_007241.4), encoding the ESCRT-II subunit SNF8. The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile). In patient-derived fibroblasts, bi-allelic SNF8 variants cause loss of ESCRT-II subunits. Snf8 loss of function in zebrafish results in global developmental delay and altered embryo morphology, impaired optic nerve development, and reduced forebrain size. In vivo experiments corroborated the pathogenicity of the tested SNF8 variants and their variable impact on embryo development, validating the observed clinical heterogeneity. Taken together, we conclude that loss of ESCRT-II due to bi-allelic SNF8 variants is associated with a spectrum of neurodevelopmental/neurodegenerative phenotypes mediated likely via impairment of the autophagic flux., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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34. Visual System Abnormalities in a Case of Nonsyndromic, Complete, Isolated Corpus Callosum Agenesis.
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Barbano L, Ziccardi L, Antonelli G, Tinelli E, and Parisi V
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- Humans, Magnetic Resonance Imaging, Agenesis of Corpus Callosum diagnosis, Corpus Callosum diagnostic imaging
- Abstract
Competing Interests: The authors report no conflicts of interest.
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- 2024
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35. Genotypic and Phenotypic Characterization of a Cohort of Patients Affected by Rod Cyclic Nucleotide Channel-Associated Retinitis Pigmentosa.
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Colombo L, Bonetti G, Maltese PE, Iarossi G, Ziccardi L, Fogagnolo P, De Ruvo V, Murro V, Giorgio D, Falsini B, Placidi G, Martella S, Galantin E, Bertelli M, and Rossetti L
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- Humans, Male, Female, Retrospective Studies, Middle Aged, Adult, Young Adult, Adolescent, Electroretinography, Tomography, Optical Coherence methods, Aged, Mutation, Child, Retinal Rod Photoreceptor Cells metabolism, Fluorescein Angiography methods, Genetic Association Studies, DNA Mutational Analysis, Pedigree, DNA genetics, Retinitis Pigmentosa genetics, Retinitis Pigmentosa diagnosis, Retinitis Pigmentosa physiopathology, Cyclic Nucleotide-Gated Cation Channels genetics, Visual Acuity, Phenotype, Genotype
- Abstract
Introduction: Retinitis pigmentosa (RP), a heterogeneous inherited retinal disorder causing gradual vision loss, affects over 1 million people worldwide. Pathogenic variants in CNGA1 and CNGB1 genes, respectively, accounting for 1% and 4% of cases, impact the cyclic nucleotide-gated channel in rod photoreceptor cells. The aim of this study was to describe and compare genotypic and clinical characteristics of a cohort of patients with CNGA1- or CNGB1-related RP and to explore potential genotype-phenotype correlations., Methods: The following data from patients with CNGA1- or CNGB1-related RP, followed in five Italian inherited retinal degenerations services, were retrospectively collected: genetic variants in CNGA1 and CNGB1, best-corrected visual acuity (BCVA), ellipsoid zone (EZ) width, fundus photographs, and short-wavelength fundus autofluorescence (SW-AF) images. Comparisons and correlation analyses were performed by first dividing the cohort in two groups according to the gene responsible for the disease (CNGA1 and CNGB1 groups). In parallel, the whole cohort of RP patients was divided into two other groups, according to the expected impact of the variants at protein level (low and high group)., Results: In total, 29 patients were recruited, 11 with CNGA1- and 18 with CNGB1-related RP. In both CNGA1 and CNGB1, 5 novel variants in CNGA1 and 5 in CNGB1 were found. BCVA was comparable between CNGA1 and CNGB1 groups, as well as between low and high groups. CNGA1 group had a larger mean EZ width compared to CNGB1 group, albeit not statistically significant, while EZ width did not differ between low and high groups A statistically significant correlation between EZ width and BCVA as well as between EZ width and age were observed in the whole cohort of RP patients. Fundus photographs of all patients in the cohort showed classic RP pattern, and in SW-AF images an hyperautofluorescent ring was observed in 14/21 patients., Conclusion: Rod CNG channel-associated RP was demonstrated to be a slowly progressive disease in both CNGA1- and CNGB1-related forms, making it an ideal candidate for gene augmentation therapies., (© 2024 The Author(s). Published by S. Karger AG, Basel.)
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- 2024
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36. Autoantibodies detection in patients affected by autoimmune retinopathies.
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Ceccarini MR, Medori MC, Dhuli K, Tezzele S, Bonetti G, Micheletti C, Maltese PE, Cecchin S, Donato K, Colombo L, Rossetti L, Staurenghi G, Salvetti AP, Oldani M, Ziccardi L, Marangoni D, Iarossi G, Falsini B, Placidi G, D'Esposito F, Viola F, Nassisi M, Leone G, Cimino L, De Simone L, Mastrofilippo V, Beccari T, and Bertelli M
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- Humans, Middle Aged, Autoantibodies, Autoantigens, Autoimmune Diseases diagnosis, Retinal Diseases diagnosis, Neoplasms
- Abstract
Objective: Autoimmune retinopathies (ARs) encompass a spectrum of immune diseases that are characterized by the presence of autoantibodies against retinal proteins in the bloodstream. These autoantibodies (AAbs) lead to a progressive and sometimes rapid loss of vision. ARs commonly affect subjects over 50 years of age, but also rare cases of kids under 3 years of age have been reported., Patients and Methods: In this study, 47 unrelated Caucasian patients were enrolled. All subjects showed negative cancer diagnoses and negative results in their genetic screenings. We studied 8 confirmed retinal antigens using Western blotting analysis, with α-enolase followed by carbonic anhydrase II being the two most frequently found in the patients' sera., Results: Nineteen patients were positive (40.4%), thirteen uncertain (27.7%), and fifteen were negative (31.9%). Their gender did not correlate with the presence of AAbs (p=0.409)., Conclusions: AAbs are responsible for retinal degeneration in some cases, while in others, they contribute to exacerbating the progression of the disease; however, their detection is crucial to reaching a better diagnosis and developing more effective treatments for these conditions. Moreover, finding good biomarkers is important not only for AR monitoring and prognosis, but also for helping with early cancer diagnosis.
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- 2023
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37. Topographical Correlation between Structural and Functional Impairment of the Macular Inner Retinal Layers in Multiple Sclerosis Eyes with a History of Optic Neuropathy.
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Parisi V, Barbano L, Antonelli G, Nicoletti CG, Landi D, Mataluni G, Di Renzo A, Buttari F, Marfia GA, Centonze D, and Ziccardi L
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We investigated the potential correlation between morphological and functional parameters describing the rarefaction and dysfunction of retinal ganglion cells (RGCs), located in the macula, in multiple sclerosis eyes with a history of optic neuritis (MS-ON). A total of 19 MS-ON eyes from 19 MS patients (mean age: 44.16 ± 4.66 years; 11 females and 8 males), with a mean disease duration of 10.06 ± 6.12 years and full recovery of visual acuity, and 30 age-similar (mean age: 45.09 ± 5.08 years) healthy eyes were submitted for ophthalmological evaluation using swept-source optical coherence tomography (SS-OCT) and multifocal photopic negative response (mfPhNR) to study the structural and functional features of localized RGCs. Both GCL+ thickness (via SS-OCT) and response amplitude density (RAD) (via mfPhNR) measurements were obtained from annular regions and ETDRS sectors. Morphological and electrophysiological data from the control and MS groups were compared by using an ANOVA test. GCL+ values were correlated with the corresponding RADs derived from almost superimposable areas using Pearson's tests ( p < 0.01). In MS-ON eyes, the mean values of macular GCL+-T and mfPhNR RAD detected in all rings and ETDRS sectors were significantly reduced ( p < 0.01) when compared with control ones. In addition, when plotting the GCL+-T and mfPhNR RAD individual data from MS-ON eyes, we found statistically significant linear correlations ( p < 0.01) when considering responses from both rings and sectors. In conclusion, in MS-ON eyes, a topographical correlation between structural and functional impairment of macular RGCs occurs.
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- 2023
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38. Morpho-Functional Assessment of Retinal Ganglion Cells and Visual Pathways in Patients with Optic Disc Drusen: Superficial Drusen Visible Height as a Marker of Impairment.
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Antonelli G, Ziccardi L, Barbano L, Di Renzo A, and Parisi V
- Abstract
The aim of this study was to assess the morpho-functional involvement of the retinal ganglion cells (RGCs) and of the visual pathways in patients with superficial (ODD-S) or deep (ODD-D) optic disc drusen. This study enrolled 17 patients with ODD (mean age of 59.10 ± 12.68 years) providing 19 eyes and 20 control subjects (mean age 58.62 ± 8.77 years) providing 20 eyes. We evaluated the following: best-corrected visual acuity, visual field mean deviation (MD), the amplitude (A) of Pattern Electroretinogram (PERG), the implicit time (IT) and A of Visual Evoked Potentials (VEPs), retinal nerve fiber layer thickness (RNFL-T) and ganglion cell thickness (GC-T). In ODD-S eyes, the drusen visible height was measured. ODD-D and ODD-S were detected in 26.3% and 73.7% of ODD eyes, respectively. Significantly ( p < 0.01) reduced MD, PERG A, VEP amplitude, RNFL-T and GC-T values and significantly ( p < 0.01) increased VEP IT values were found in the ODD Group as compared to the Control one. In the ODD Group, no significant correlation ( p > 0.01) between PERG As and VEP ITs was found. In ODD-S, the visible height was significantly correlated ( p < 0.01) with reduced MD, PERG As and RNFL-T and with increased PSD and VEP IT values. Our findings suggest that ODD might induce morpho-functional changes in RGCs and their fibers and an unrelated visual pathway dysfunction leading or not leading to visual field defects. The observed morpho-functional impairment should be ascribed to an alteration in retrograde (from the axons to the RGCs) and anterograde (from the RGCs up to the visual cortex) axoplasmic transport. In ODD-S eyes, a minimum visible height of 300 microns represented the threshold for the abnormalities, suggesting that "the higher the ODD, the worse the impairment".
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- 2023
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39. Retinitis Pigmentosa Associated with EYS Gene Mutations: Disease Severity Staging and Central Retina Atrophy.
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Placidi G, Maltese PE, Savastano MC, D'Agostino E, Cestrone V, Bertelli M, Chiurazzi P, Maceroni M, Minnella AM, Ziccardi L, Parisi V, Rizzo S, and Falsini B
- Abstract
Background: Eyes shut homolog (EYS) gene mutations are estimated to affect at least 5% of patients with autosomal recessive retinitis pigmentosa. Since there is no mammalian model of human EYS disease, it is important to investigate its age-related changes and the degree of central retinal impairment., Methods: A cohort of EYS patients was studied. They underwent full ophthalmic examination as well as assessment of retinal function and structure, by full-field and focal electroretinograms (ERGs) and spectral domain optical coherence tomography (OCT), respectively. The disease severity stage was determined by the RP stage scoring system (RP-SSS). Central retina atrophy (CRA) was estimated from the automatically calculated area of the sub-retinal pigment epithelium (RPE) illumination (SRI)., Results: The RP-SSS was positively correlated with age, showing an advanced severity score (≥8) at an age of 45 and a disease duration of 15 years. The RP-SSS was positively correlated with the CRA area. LogMAR visual acuity and ellipsoid zone width, but not ERG, were correlated with CRA., Conclusions: In EYS-related disease, the RP-SSS showed advanced severity at a relative early age and was correlated with the central area of the RPE/photoreceptor atrophy. These correlations may be relevant in view of therapeutic interventions aimed at rescuing rods and cones in EYS-retinopathy.
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- 2023
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40. Retinal and Visual Pathways Involvement in Carriers of Friedreich's Ataxia.
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Ziccardi L, Barbano L, Antonelli G, Cioffi E, Di Renzo A, Gioiosa V, Marcotulli C, Grzybowski A, Casali C, and Parisi V
- Abstract
Friedreich’s ataxia (FRDA) is a rare autosomal recessive neurodegenerative disorder due to the homozygous pathological expansion of guanine-adenine-adenine (GAA) triplet repeats in the first intron of the FXN gene, which encodes for the mitochondrial protein frataxin. In the visual system, the typical manifestations are ocular motility abnormality, optic neuropathy, and retinopathy. Despite the evidence of ophthalmological impairment in FRDA patients, there is a lack of information about the morpho-functional condition of the retina and of the optic pathways in healthy heterozygous carriers of Friedreich’s ataxia (C-FRDA). Ten C-FRDA subjects (providing 20 eyes) and thirty-five Controls (providing 70 eyes) underwent a complete neurological and ophthalmological examination comprehensive of functional (full-field Electroretinogram (ffERG), multifocal Electroretinogram (mfERG), Visual Evoked Potential (VEP), and Pattern Reversal Electroretinogram (PERG)) and morphological assessments (Optical Coherence Tomography, OCT) of the retina, macula, retinal ganglion cells, and visual pathways. The groups’ data were compared using a two-sample t-test. Pearson’s test was used to investigate the morpho-functional correlations. Statistically significant differences (p < 0.01) between C-FRDA and Control eyes for the values of the following parameters were found: ffERG b-wave amplitude, mfERG Response Amplitude Densities, PERG P50 implicit time and P50-N95 amplitude, VEP P100 implicit time, Retinal Nerve Fiber Layer (RNFL) Overall, and Nasal thickness. The values of the OCT macular volume were not statistically different (p > 0.01) between the two Groups. Therefore, our data suggest that, in C-FRDA, a dysfunction of retinal elements without morphological macular impairment may occur. In addition, a morphological impairment of RNFL associated with an abnormal neural conduction along the visual pathways can be also detected.
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- 2022
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41. Morpho-Functional Macular Assessment in a Case of Facioscapulohumeral Muscular Dystrophy: Photoreceptor Degeneration as Possible Cause for Reduced Visual Acuity over Three Years of Follow-Up.
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Parravano M, Costanzo E, Barbano L, Viggiano P, De Geronimo D, Antonelli G, Parisi V, Varano M, and Ziccardi L
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Background: Autosomal-dominant facioscapulohumeral muscular dystrophy (FSHD) is a muscular dystrophy with associated retinal abnormalities such as retinal vessel tortuosity, focal retinal pigment epithelium defect and large telangiectasia vessels., Methods: Case report of an FSHD 16-year-old female referred for blurred vision in both eyes (20/40), evening fever and shoulder muscle weakness over the past month preceding assessment. A multimodal assessment including visual acuity (VA), microperimetry (MP), multifocal electroretinogram (mfERG), optical coherence tomography (OCT), fluorescein angiography (FA) and fundus autofluorescence (FAF) was performed., Results: OCT showed pseudocyst macular abnormalities and disruption of the photoreceptor layer with no signs of macular ischemia/exudation. Macular function showed foveal impairment recorded by mfERG and MP as a reduction of the response amplitude density and retinal sensitivity, respectively. No medical treatment was prescribed. After three years, patient's VA slightly improved to 20/32. OCT showed resolution of bilateral pseudocyst macular changes and persistence of photoreceptor disruption. By contrast, mfERG recordings remained abnormal for impaired foveal function and microperimetry mean sensitivity was reduced as well., Conclusions: This multimodal assessment showed persistent VA impairment at three years follow-up associated to abnormal foveal function and reduced retinal sensitivity, with spontaneous resolution of morphological macular changes, suggesting a retinal neurodegenerative process on the basis of the disease.
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- 2022
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42. Biallelic Inactivating TUB Variants Cause Retinal Ciliopathy Impairing Biogenesis and the Structure of the Primary Cilium.
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Ziccardi L, Niceta M, Stellacci E, Ciolfi A, Tatti M, Bruselles A, Mancini C, Barbano L, Cecchetti S, Costanzo E, Cappa M, Parravano M, Varano M, Tartaglia M, and Cordeddu V
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- Humans, Adult, Cilia genetics, Retina, Proteins genetics, Obesity, Mutation, Pedigree, Ciliopathies genetics, Retinal Dystrophies genetics
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Inherited retinal degeneration (IRD) represents a clinically variable and genetically heterogeneous group of disorders characterized by photoreceptor dysfunction. These diseases typically present with progressive severe vision loss and variable onset, ranging from birth to adulthood. Genomic sequencing has allowed to identify novel IRD-related genes, most of which encode proteins contributing to photoreceptor-cilia biogenesis and/or function. Despite these insights, knowledge gaps hamper a molecular diagnosis in one-third of IRD cases. By exome sequencing in a cohort of molecularly unsolved individuals with IRD, we identified a homozygous splice site variant affecting the transcript processing of TUB, encoding the first member of the Tubby family of bipartite transcription factors, in a sporadic case with retinal dystrophy. A truncating homozygous variant in this gene had previously been reported in a single family with three subjects sharing retinal dystrophy and obesity. The clinical assessment of the present patient documented a slightly increased body mass index and no changes in metabolic markers of obesity, but confirmed the occurrence of retinal detachment. In vitro studies using patient-derived fibroblasts showed the accelerated degradation of the encoded protein and aberrant cilium morphology and biogenesis. These findings definitely link impaired TUB function to retinal dystrophy and provide new data on the clinical characterization of this ultra-rare retinal ciliopathy.
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- 2022
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43. Middle-Inner Macular Layers Dysfunction in a Case of Stellate Foveomacular Retinoschisis Detected by Abnormal Multifocal Photopic Negative Response Recordings.
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Barbano L, Antonelli G, Parravano M, Costanzo E, Parisi V, and Ziccardi L
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We describe the macular morpho-functional assessment of a 65-year-old man affected by stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR), studied by visual field, SD-OCT, autofluorescence, full-field electroretinogram (ffERG), multifocal electroretinogram (mfERG) and multifocal Photopic Negative Response (mfPhNR) recordings. The typical presentation consists of the foveal appearance of radial cartwheel pattern for the splitting of the retinal layers at the level of the Henle fiber layer (HFL) and the outer plexiform layer (OPL), perfectly seen by Spectral Domain-Optical Coherence Tomography (SD-OCT). Despite a normal function of the outer retina of the peripheral and central retina evaluated by ffERG and mfERG respectively, we observed a reduced function of the retinal elements involved in the retinoschisis by recording mfPhNR that assesses mainly inner retina function (retinal ganglion cells and their axons). Therefore, it is likely that the observed impaired mfPhNR responses reflect the signaling defects derived from the delaminated middle retina and transmitted to the innermost retinal layers., Competing Interests: The authors declare no conflict of interest.
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- 2022
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44. Multimodal Study of PRPH2 Gene-Related Retinal Phenotypes.
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Antonelli G, Parravano M, Barbano L, Costanzo E, Bertelli M, Medori MC, Parisi V, and Ziccardi L
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PRPH2 gene mutations are frequently found in inherited retinal dystrophies (IRD) and are associated with a wide spectrum of clinical phenotypes. We studied 28 subjects affected by IRD carrying pathogenic PRPH2 mutations, belonging to 11 unrelated families. Functional tests (best-corrected visual acuity measurement, chromatic test, visual field, full-field, 30 Hz flicker, and multifocal electroretinogram), morphological retino-choroidal imaging (optical coherence tomography, optical coherence tomography angiography, and fundus autofluorescence), and clinical data were collected and analyzed. Common primary complaints, with onset in their 40s, were visual acuity reduction and abnormal dark adaptation. Visual acuity ranged from light perception to 20/20 Snellen. Visual field peripheral constriction and central scotoma were found. Chromatic sense was reduced in one third of patients. Electrophysiological tests were abnormal in most of the patients. Choroidal neovascular lesions were detected in five patients. Three novel PRPH2 variants were found in four different families. Based on the present multimodal study, we identified seven distinct PRPH2 phenotypes in 11 unrelated families carrying either different mutations or the same mutation, both within the same family or among them. Fundus autofluorescence modality turned out to be the most adequate imaging method for early recognition of this dystrophy, and the optical coherence tomography angiography was highly informative to promptly detect choroidal neovascularization, even in the presence of the extensive chorioretinal atrophy phenotype.
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- 2022
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45. Multifocal Electroretinogram Photopic Negative Response: A Reliable Paradigm to Detect Localized Retinal Ganglion Cells' Impairment in Retrobulbar Optic Neuritis Due to Multiple Sclerosis as a Model of Retinal Neurodegeneration.
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Barbano L, Ziccardi L, Antonelli G, Nicoletti CG, Landi D, Mataluni G, Falsini B, Marfia GA, Centonze D, and Parisi V
- Abstract
The measure of the full-field photopic negative response (ff-PhNR) of light-adapted full-field electroretinogram (ff-ERG) allows to evaluate the function of the innermost retinal layers (IRL) containing primarily retinal ganglion cells (RGCs) and other non-neuronal elements of the entire retina. The aim of this study was to acquire functional information of localized IRL by measuring the PhNR in response to multifocal stimuli (mfPhNR). In this case-control observational and retrospective study, we assessed mfPhNR responses from 25 healthy controls and from 20 patients with multiple sclerosis with previous history of optic neuritis (MS-ON), with full recovery of visual acuity, IRL morphological impairment, and absence of morpho-functional involvement of outer retinal layers (ORL). MfPhNR response amplitude densities (RADs) were measured from concentric rings (R) with increasing foveal eccentricity: 0−5° (R1), 5−10° (R2), 10−15° (R3), 15−20° (R4), and 20−25° (R5) from retinal sectors (superior-temporal (ST), superior-nasal (SN), inferior-nasal (IN), and inferior-temporal (IT)); between 5° and 20° and from retinal sectors (superior (S), temporal (T), inferior (I), and nasal (N)); and within 5° to 10° and within 10° and 20° from the fovea. The mfPhNR RAD values observed in all rings or sectors in MS-ON eyes were significantly reduced (p < 0.01) with respect to control ones. Our results suggest that mfPhNR recordings may detect localized IRL dysfunction in the pathologic condition of selective RGCs neurodegeneration.
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- 2022
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46. Choroidal vascularity index in eyes with central macular atrophy secondary to age-related macular degeneration and Stargardt disease.
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Corbelli E, Sacconi R, Battista M, Bacherini D, Miere A, Borrelli E, Costanzo E, Vella G, Parravano M, Ziccardi L, Sodi A, Rizzo S, Souied EH, Bandello F, and Querques G
- Subjects
- Adult, Aged, Aged, 80 and over, Atrophy diagnosis, Choroid pathology, Fluorescein Angiography methods, Humans, Middle Aged, Retrospective Studies, Stargardt Disease, Macular Degeneration complications, Macular Degeneration diagnosis, Macular Degeneration pathology, Tomography, Optical Coherence methods
- Abstract
Purpose: To compare macular atrophy (MA) secondary to age-related macular degeneration (AMD) and Stargardt disease (STGD) using the choroidal vascularity index (CVI)., Methods: In this multicentric retrospective study, two distinct cohorts were collected: patients with MA secondary to AMD and MA secondary to STGD. All patients were investigated using a multimodal imaging approach, including CVI in the subfoveal 1000 μm area. Of note, the CVI is not influenced by aging, which allows comparisons between different cohorts., Results: Seventy eyes were included: 35 eyes of 35 patients (mean age 78 ± 7 years) in the AMD group and 35 eyes of 35 patients (mean age 41 ± 16 years, p < 0.001) in the STGD group. Choroidal thickness was significantly lower in the AMD group in comparison to the STGD group (151 ± 80 μm vs 353 ± 105 μm, p < 0.001). The total choroidal area (TCA) was significantly greater in the STGD group in comparison to the AMD group (1.734 ± 0.958 mm
2 vs 0.538 ± 0.391 mm2 , respectively, p < 0.001). Interestingly, the CVI was significantly lower in AMD patients in comparison to STGD patients (27.322 ± 15.320% vs 49.880 ± 7.217%, respectively, p < 0.001), and this difference was confirmed in the subgroup of patients over 50 years old., Conclusion: Our results corroborate the hypothesis that large choroidal vessels were impaired to a greater extent in AMD than in STGD. CVI may help in differentiating AMD from STGD in the presence of MA, better understanding of the pathogenesis, and monitoring of therapeutic response., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2022
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47. Genetic characteristics of 234 Italian patients with macular and cone/cone-rod dystrophy.
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Falsini B, Placidi G, De Siena E, Chiurazzi P, Minnella AM, Savastano MC, Ziccardi L, Parisi V, Iarossi G, Percio M, Piteková B, Marceddu G, Maltese PE, and Bertelli M
- Subjects
- ATP-Binding Cassette Transporters genetics, Bestrophins genetics, Electroretinography, Humans, Mutation, Pedigree, Phenotype, Tomography, Optical Coherence, Cone-Rod Dystrophies diagnosis, Cone-Rod Dystrophies genetics, Retinitis Pigmentosa genetics
- Abstract
Two-hundred and thirty-four Italian patients with a clinical diagnosis of macular, cone and cone-rod dystrophies (MD, CD, and CRD) were examined using next-generation sequencing (NGS) and gene sequencing panels targeting a specific set of genes, Sanger sequencing and-when necessary-multiplex ligation-dependent probe amplification (MLPA) to diagnose the molecular cause of the aforementioned diseases. When possible, segregation analysis was performed in order to confirm unsolved cases. Each patient's retinal phenotypic characteristics were determined using focal and full-field ERGs, perimetry, spectral domain optical coherence tomography and fundus autofluorescence. We identified 236 potentially causative variants in 136 patients representing the 58.1% of the total cohort, 43 of which were unpublished. After stratifying the patients according to their clinical suspicion, the diagnostic yield was 62.5% and 53.8% for patients with MD and for those with CD/CRD, respectively. The mode of inheritance of all cases confirmed by genetic analysis was 70% autosomal recessive, 26% dominant, and 4% X-linked. The main cause (59%) of both MD and CD/CRD cases was the presence of variants in the ABCA4 gene, followed by variants in PRPH2 (9%) and BEST1 (6%). A careful morpho-functional evaluation of the phenotype, together with genetic counselling, resulted in an acceptable diagnostic yield in a large cohort of Italian patients. Our study emphasizes the role of targeted NGS to diagnose MDs, CDs, and CRDs, as well as the clinical usefulness of segregation analysis for patients with unsolved diagnosis., (© 2022. The Author(s).)
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- 2022
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48. Macular Morpho-Functional and Visual Pathways Functional Assessment in Patients with Spinocerebellar Type 1 Ataxia with or without Neurological Signs.
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Ziccardi L, Cioffi E, Barbano L, Gioiosa V, Falsini B, Casali C, and Parisi V
- Abstract
Spinocerebellar ataxia type 1 (SCA-ATXN1) is an autosomal dominant, neurodegenerative disease, caused by CAG repeat expansion in the ataxin-1 gene ( ATXN1 ). In isolated reports of patients with neurological signs [symptomatic patients (SP)], macular abnormalities have been described. However, no reports exist about macular anomalies in SCA1 subjects carrying the ATXN1 mutation without neurological signs [not symptomatic carriers (NSC)]. Therefore, the main aim of our work was to evaluate whether the macular functional and morphological abnormalities could be detectable in SP, genetically confirmed and with neurological signs, as well as in SCA-ATXN1-NSC, harboring pathogenic CAG expansion in ATXN1. In addition, we investigated whether the macular involvement could be associated or not to an impairment of RGCs and of their fibers and of the neural conduction along the visual pathways. Herein, nine SCA-ATXN1 subjects (6 SP and 3 NSC) underwent the following examinations: visual acuity and chromatic test assessments, fundus oculi (FO) examination, macular and peripapillary retinal nerve fiber layer thickness (RNFL-T) analysis by Spectral domain-Optical Coherence Tomography (Sd-OCT) acquisition, multifocal electroretinogram (mfERG), pattern reversal electroretinogram (PERG) and visual evoked potentials (VEP) recordings. In four eyes of two SP, visual acuity reduction and chromatic abnormalities were observed; in three of them FO changes associated with macular thinning and outer retinal defects were also detected. In three NSC eyes, slight FO abnormalities were associated with qualitative macular morphological changes. By contrast, abnormal mfERG responses (exclusively from foveal and parafoveal areas) were detected in all SP and NSC (18 eyes). No abnormalities of PERG values, RNFL-T, and VEP responses were found, but in one SP, presenting abnormal papillo-macular bundle neural conduction. Results from our SCA-ATXN1 cohort suggest that a macular dysfunction, detectable by mfERG recordings, may occur in the overt disorder, and unexpectedly in the stage of the disease in which there is still an absence of neurological signs. In NSC, an exclusive dysfunction of preganglionic macular elements can be observed, and this is associated with both normal RGCs function and neural conduction along the visual pathways.
- Published
- 2021
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49. Fampridine improves acute optic neuritis contributing to a long-lasting recovery of nerve function.
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Boffa L, Albanese M, Ziccardi L, Aiello F, Cesareo M, Parisi V, and Mercuri NB
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- 4-Aminopyridine, Humans, Optic Nerve, Optic Neuritis drug therapy
- Published
- 2021
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50. Neural Conduction Along Postretinal Visual Pathways in Glaucoma.
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Parisi V, Ziccardi L, Tanga L, Roberti G, Barbano L, Carnevale C, Manni G, and Oddone F
- Abstract
Purpose : This study was conducted in order to evaluate retinal ganglion cell (RCG) function and the neural conduction along the postretinal large and small axons and its correlation with retinal nerve fiber layer thickness (RNFL-T) in open-angle glaucoma (OAG) eyes. Methods : Thirty-seven OAG patients (mean age: 51.68 ± 9.83 years) with 24-2 Humphrey mean deviation (MD) between -2.5 and -20 dB and IOP <21 mmHg on pharmacological treatment (OAG group) and 20 age-matched controls (control group) were enrolled. In both groups, simultaneous pattern electroretinograms (PERG) and visual evoked potentials (VEP), in response to checks stimulating macular or extramacular areas (the check edge subtended 15' and 60' of visual arc, respectively), and RNFL-T (measured in superior, inferior, nasal, and temporal quadrants) were assessed. Results : In the OAG group, a significant (ANOVA, p < 0.01) reduction of 60' and 15' PERG P50-N95 and VEP N75-P100 amplitudes and of RNFL-T [overall (average of all quadrants) or temporal] with respect to controls was found; the values of 60' and 15' PERG P50 and VEP P100 implicit times and of retinocortical time (RCT; difference between VEP P100 and PERG P50 implicit times) were significantly ( p < 0.01) increased with respect to control ones. The observed increased RCTs were significantly linearly correlated (Pearson's test, p < 0.01) with the reduced PERG amplitude and MD values, whereas no significant linear correlation ( p < 0.01) with RNFL-T (overall or temporal) values was detected. Conclusions : In OAG, there is an impaired postretinal neural conduction along both large and small axons (increased 60' and 15' RCTs) that is related to RGC dysfunction, but independent from the RNFL morphology. This implies that, in OAG, the impairment of postretinal neural structures can be electrophysiologically identified and may contribute to the visual field defects, as suggested by the linear correlation between the increase of RCT and MD reduction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Parisi, Ziccardi, Tanga, Roberti, Barbano, Carnevale, Manni and Oddone.)
- Published
- 2021
- Full Text
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