Francesca Simonelli

Università degli Studi della Campania "Luigi Vanvitelli

Biallelic mutations in the RPE65 gene affect nearly 8% of Leber Congenital Amaurosis and 2% of Retinitis Pigmentosa cases. Voretigene neparvovec (VN) is the first gene therapy approach approved for their treatment. To date, real life experience has demonstrated functional improvements following VN treatment, which are consistent with the clinical t...

Introduction The purine analog 6-thioguanine (6TG), an old drug approved in the 60s to treat acute myeloid leukemia (AML), was tested in the diabetic retinopathy (DR) experimental in vivo setting along with a molecular modeling approach. Methods A computational analysis was performed to investigate the interaction of 6TG with MC1R and MC5R. This w...

Voretigene neparvovec (VN) is the first available gene therapy for patients with biallelic RPE65-mediated inherited retinal dystrophy who have sufficient viable retinal cells. PERCEIVE is an ongoing, post-authorization, prospective, multicenter, registry-based observational study and is the largest study assessing the real-world, long-term safety a...

Background and Objectives: The role and the levels of ghrelin in diabetes-induced retinal damage have not yet been explored. The present study aimed to measure the serum levels of total ghrelin (TG), and its acylated (AG) and des-acylated (DAG) forms in patients with the two stages of diabetic retinopathy (DR), non-proliferative (NPDR) and prolifer...

Mucopolysaccharidosis type IIIA (MPS IIIA or Sanfilippo syndrome type A) is an autosomal recessive lysosomal storage disorder caused by pathogenic variants in the SGSH gene encoding N ‐sulfoglucosamine sulfohydrolase, an enzyme involved in the degradation of heparan sulfate. MPS IIIA is typically characterized by neurocognitive decline and hepatosp...

Purpose To report the efficacy and safety of navigated 577nm yellow subthreshold micropulse laser (YSML) treatment in a case of refractory cystoid macular edema (CME) following combined phaco-vitrectomy for rhegmatogenous retinal detachment (RRD). Observations A 69-year-old male patient complained a slow and progressive visual loss in the right ey...

Background Individuals with thiamine-responsive megaloblastic anemia (TRMA) mainly manifest macrocytic anemia, sensorineural deafness, ocular complications, and nonautoimmune diabetes. Macrocytic anemia and diabetes may be responsive to high-dosage thiamine treatment, in contrast to sensorineural deafness. Little is known about the efficacy of thia...

Background and Objectives: Since the protective role of ghrelin against high glucose-induced retinal damage was not yet explored, we aimed to investigate the serum levels of total ghrelin (TG), its acylated (AG) and des-acylated (DAG) forms in diabetic retinopathy (DR) patients. Moreover, the correlation between serum ghrelin and neutrophil elastas...

Background Non-syndromic inherited retinal dystrophies (IRDs) such as retinitis pigmentosa or Leber congenital amaurosis generally manifest between early childhood and late adolescence, imposing profound long-term impacts as a result of vision impairment or blindness. IRDs are highly heterogeneous, with often overlapping symptoms among different IR...

Background: The prevalence of refractive errors has sharply risen over recent decades. Despite the established role of genetics in the onset and progression of such conditions, the environment was also shown to play a pivotal role. Indeed, the COVID-19 pandemic has majorly impacted people's lifestyles and healthy habits, especially among the youth...

Background: To perform a multimodal assessment of the ectopic inner foveal layers' (EIFL) prognostic role on idiopathic epiretinal membrane (ERM) surgery. Methods: We retrospectively followed-up for 12 months 27 patients who underwent ERM surgery and stratified them based on EIFL presence (group 1) or absence (group 2) at baseline. Central Retin...

Background and Objectives: To report the real-life Brolucizumab therapeutical outcomes of treatment-naïve and non-treatment-naïve eyes with neovascular age-related macular degeneration (nAMD) and to analyze the incidence of therapy-related adverse events. Materials and Methods: A total of 56 eyes of 54 patients diagnosed with nAMD were retrospectiv...

Diabetic retinopathy (DR) is the most frequent microvascular retinal complication of diabetic patients, contributing to loss of vision. Recently, retinal neuroinflammation and neurodegeneration have emerged as key players in DR progression, and therefore, this review examines the neuroinflammatory molecular basis of DR. We focus on four important a...

Inherited retinal diseases (IRDs) are a group of clinically and genetically heterogeneous disorders that may be complicated by several vitreoretinal conditions requiring a surgical approach. Pars plana vitrectomy (PPV) stands as a valuable treatment option in these cases, but its application in eyes with such severely impaired chorioretinal archite...

Background: Next-generation sequencing (NGS) technology is revolutionizing diagnostic screening for mitochondrial diseases (MDs). Moreover, an investigation by NGS still requires analyzing the mitochondrial genome and nuclear genes separately, with limitations in terms of time and costs. We describe the validation and implementation of a custom bl...

Optical coherence tomography angiography (OCT-A) is a valuable imaging technique, allowing non-invasive, depth-resolved, motion-contrast, high-resolution images of both retinal and choroidal vascular networks. The imaging capabilities of OCT-A have enhanced our understanding of the retinal and choroidal alterations that occur in inherited retinal d...

Background: To evaluate corneal deformation in Maturity Onset Diabetes of the Young type 2 (MODY2), paediatric subjects were analysed using a Scheimpflug-based device. The purpose of this analysis was to find new biomarkers for MODY2 disease and to gain a better understanding of the pathogenesis of the disease. Methods: A total of 15 patients wi...

Background: Leber congenital amaurosis is the first form of inherited retinal dystrophy (IRD) treated with a gene therapy approach using voretigene neparvovec (VN). To date, 42 patients have been treated, 25 of whom, treated at Clinica Oculistica Vanvitelli (Naples), have shown – after 45 days of treatment – a significant increase in dim-light visu...

Background: Vitamin D deficiency has been associated with dry eye development during Sjögren's syndrome (SS). Here, we investigated whether repeated oral vitamin D3 supplementation could prevent the corneal epithelium damage in an SS mouse model. Methods: 30 female mouse knock-out for the thrombospondin 1 gene were randomized (six per group) in...

Introduction: Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are two groups of inherited retinal diseases (IRDs) where the rod photoreceptors degenerate followed by the cone photoreceptors of the retina. A genetic diagnosis for IRDs is challenging since >280 genes are associated with these conditions. While whole exome sequencing (W...

Gene therapy of Usher syndrome type 1B (USH1B) due to mutations in the large Myosin VIIA (MYO7A) gene is limited by the packaging capacity of adeno-associated viral (AAV) vectors. To overcome this, we have previously developed dual AAV8 vectors which encode human MYO7A (dual AAV8.MYO7A). Here we show that subretinal administration of 1.37E+9 to 1.3...

Background: To evaluate how Ectopic Inner Foveal Layers (EIFL) affect macular morphology and function after idiopathic Epiretinal Membrane (ERM) and internal limiting membrane (ILM) peeling by the means of Best-Corrected Visual Acuity (BCVA), Optical Coherence Tomography (OCT), Microperimetry (MP-1) and Multifocal Electroretinogram (mfERG). Methods...

Inherited retinal diseases (IRDs) are the leading cause of vision loss in the working-age population. We performed a retrospective epidemiological study to determine the genetic basis of IRDs in a large Italian cohort (n = 2790) followed at a single referral center. We provided, mainly by next generation sequencing, potentially conclusive molecular...

Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are two groups of inherited retinal diseases (IRDs) where the rod photoreceptors degenerate followed by the cone photoreceptors of the retina. A genetic diagnosis for IRDs is challenging since >280 genes are associated with these conditions. While whole exome sequencing (WES) is commonl...

Purpose To report a case of peripapillary pachychoroid syndrome (PPS) successfully treated with navigated subthreshold micropulse laser (SML). Observations A 65-year-old male was referred to our retina service complaining a worsening vision in the left eye over the past 6 months. A complete ophthalmological evaluation including best corrected visu...

To report quantitative retinal changes assessed by spectral-domain optical coherence tomography (SD-OCT) in children treated with voretigene neparvovec (VN) at a single center in Italy. Retrospective review of six consecutive pediatric patients with biallelic RPE65 -related dystrophy treated bilaterally with VN. SD-OCT scans were analyzed to extrac...

Background: To investigate the efficacy interval of the topical therapies available for primary open-angle glaucoma (POAG) and the ocular and systemic features potentially associated. Methods: This retrospective study included 190 patients with POAG undergoing first topical therapy, throughout a follow-up of 15 years. The patients started one to...

UNSTRUCTURED Telemedicine is conceived as physicians who manage and treat patients remotely. However, transversal telemedicine practice also exists among healthcare professionals (HCPs). We present details of our telemedicine practice among HCPs in the last 10 years. A web-based informatic platform was developed, with a continuously updated hyperte...

Background Telemedicine, a term that encompasses several applications and tasks, generally involves the remote management and treatment of patients by physicians. It is known as transversal telemedicine when practiced among health care professionals (HCPs). Objective We describe the experience of implementing our telemedicine Eumeda platform for H...

Objectives Although inherited retinal disorders (IRDs) related to the gene encoding the retinal pigment epithelium 65kD protein (RPE65) significantly impact the vision-related quality of life (VRQoL), their emotional and social aspects remain poorly investigated in Italy. Narrative Medicine (NM) reveals the more intimate aspects of the illness expe...

Background: Diabetic retinopathy (DR) is a neurovascular disease, characterized by a deficiency of brain-derived neurotrophic factor (BDNF), a regulator of autophagy. Beta-hydroxybutyrate (BHB), previously reported as a protective agent in DR, has been associated with BDNF promotion. Here, we investigated whether systemic BHB affects the retinal le...

Chronic kidney disease (CKD) is a major clinical sign of patients with Bardet-Biedl syndrome (BBS), especially in those carrying BBS10 mutations. Twenty-nine BBS patients and 30 controls underwent a serum targeted metabolomic analysis. In vitro studies were conducted in two kidney-derived epithelial cell lines, where Bbs10 was stably deleted (IMCD3...

Objectives To compare choroidal vascularity index (CVI) measurements using the automated image binarization algorithm in healthy subjects with two Spectralis spectral-domain optical coherence tomography (SD-OCT) protocol scans. Methods Sixty-nine eyes of 69 healthy volunteers were included in this cross-sectional prospective study. Two subsequent...

Over the past couple of years, Transformers became increasingly popular within the deep learning community. Initially designed for Natural Language Processing tasks, Transformers were then tailored to fit to the Image Analysis field. The self-attention mechanism behind Transformers immediately appeared a promising, although computationally expensiv...

Anti-vascular endothelial growth factor nowdays represents the standard of care for diabetic macular edema (DME). Nevertheless, the burden of injections worldwide has created tremendous stress on the healthcare system during the COVID-19 pandemic. The aim of this study was to investigate the effects of the oral administration of Curcuma longa and B...

Purpose: To assess the accuracy of the following intraocular lens (IOL) power formulas: Barrett True-K No History (BTKNH), Emmetropia Verifying Optical 2.0 Post Myopic LASIK/PRK (EVO 2.0), Haigis-L, American Society of Cataract and Refractive Surgery (ASCRS) average, and Shammas, designed for patients who have undergone previous myopic refractive...

The most frequent retinal diseases, such as diabetic retinopathy, age-related macular degeneration and posterior uveitis, are underlined by oxidative stress or aging-induced retinal inflammation, which contributes to vision impairing or loss. Resolution of inflammation is emerging as a critical phase able to counteract the inflammatory process lead...

Precis: All devices evaluated in this study showed a significant underestimation in intraocular pressure measurement after myopic PRK, Goldmann tonometer more than others. Corneal biomechanics indicated a different influence on the different kinds of tonometry. Purpose: To investigate the reliability of Goldmann applanation tonometry (GAT), rebo...

Background Corneal collagen cross-linking (CXL) is considered an effective procedure for slowing down or eliminating the progression of keratoconus. New techniques, in combination with CXL, have been proposed to stop the evolution of keratoconus and improve the visual function. Objective To evaluate the effectiveness of combined photorefractive ke...

Purpose: This study explored the possibility of highlighting early retinal neurovascular alterations of diabetic retinopathy (DR) by monitoring in DR patients the serum levels of microglial biomarkers ionized calcium-binding adapter molecule 1 (Iba-1), glucose transporter 5 (GLUT5), and translocator protein (TSPO), along with serum changes of the...

Purpose: Retinol dehydrogenase (RDH)5 related fundus albipunctatus (FAP) can present with phenotypic variability. Our purpose was to investigate new clinical characteristics and multimodal imaging findings in patients from different ethnic origins, carrying different mutations. Methods: Multicenter international retrospective case series. 18 pat...

Purpose: To investigate the course of inherited retinal degenerations (IRD) due to mutations in the RPE65 gene. Methods: This longitudinal multicentric retrospective chart-review study was designed to collect best corrected visual acuity (BCVA), Goldman visual field, optical coherence tomography (OCT), and electroretinography (ERG) measurements....

Introduction: Müller glial cells typically activate to react to hypoxic tissue damage in several retinal diseases. We evaluated the in vitro response to a hypoxia-mimicking stimulus on the expression of a set of genes, known to contribute to eye morphogenesis and cell differentiation. Materials and methods: A MIO-M1 Müller cell line was cultured...

Purpose Timely detection and multidisciplinary management of RPE65-related inherited retinal disorders (IRDs) can significantly improve both disease management and patient care. Thus, this Narrative Medicine (NM) project aimed to investigate the evolution of the care pathway and the expectations on genetic counseling and gene therapy by patients, c...

Background This research aimed to establish recommendations on the clinical and genetic characteristics necessary to confirm patient eligibility for gene supplementation with voretigene neparvovec. Methods An expert steering committee comprising an interdisciplinary panel of Italian experts in the three fields of medical specialisation involved in...

Background: Artificial intelligence (AI) is becoming ever more frequently applied in medicine and, consequently, also in ophthalmology to improve both the quality of work for physicians and the quality of care for patients. The aim of this study is to use AI, in particular classification tree, for the evaluation of both ocular and systemic feature...

Split intein-mediated protein trans-splicing expands AAV transfer capacity, thus overcoming the limited AAV cargo. However, non-mammalian inteins persist as trans-splicing by-products, and this could raise safety concerns for AAV intein clinical applications. In this study, we tested the ability of several degrons to selectively decrease levels of...

In contrast to USH2A, variants in ADGRV1 are a minor cause of Usher syndrome type 2, and the associated phenotype is less known. The purpose of the study was to characterize the retinal phenotype of 18 ADGRV1 patients (9 male, 9 female; median age 52 years) and compare it with that of 204 USH2A patients (111 male, 93 female; median age 43 years) in...

Purpose: To present visual outcomes of the first two Italian patients with RPE65-related inherited retinal dystrophy (RPE65-IRD) treated with voretigene neparvovec (VN). Methods: Two pediatric patients with RPE65-IRD were treated with VN in both eyes. Patients were evaluated by best-corrected visual acuity (BCVA), full-field stimulus threshold (...

This study aimed to investigate the interactions between fingolimod, a sphingosine 1-phosphate receptor (S1PR) agonist, and melanocortin receptors 1 and 5 (MCR1, MCR5). In particular, we investigated the effects of fingolimod, a drug approved to treat relapsing-remitting multiple sclerosis, on retinal angiogenesis in a mouse model of diabetic retin...

IntroductionTo compare the functional and anatomic outcomes between eyes in patients with diabetic macular edema (DME) who underwent a complete anti-vascular endothelial growth factor (VEGF) loading dose with aflibercept and those who were switched to dexamethasone intravitreal (DEX) implant after an incomplete anti-VEGF treatment regimen during th...

Aim To evaluate the real utilization of ranibizumab and aflibercept in the daily management of patients with neovascular age-related macular degeneration (nAMD) treated at the Eye Clinic of Campania University L.Vanvitelli. Background Therapy with anti-vascular endothelial growth factor represents the gold standard in wet age-related macular degen...

Choroideremia (CHM) is a X-linked recessive chorioretinal dystrophy due to deficiency of the CHM gene product, i.e., Rab escort protein isoform 1 (REP1). To date, gene therapy for CHM has shown variable effectiveness, likely because the underlying pathogenic mechanisms as well as genotype-phenotype correlation are not yet fully known. Small nucleot...

Pathogenic variants in the MKS1 gene are responsible for a ciliopathy with a wide spectrum of clinical manifestations ranging from Meckel and Joubert syndrome (JBTS) to Bardet-Biedl syndrome, and involving the central nervous system, liver, kidney, skeleton, and retina. We report a 39-year-old male individual presenting with isolated Retinitis Pigm...

Purpose: The purpose of this study was to perform a detailed longitudinal phenotyping and genetic characterization of 32 Italian patients with a nonsyndromic retinal dystrophy and mutations in the CEP290 gene. Methods: We reviewed the clinical history and examinations of 32 patients with a nonsyndromic retinal dystrophy due to mutations in the C...

Purpose: The purpose of this study was to investigate the relationship between perfusion of the choriocapillaris (CC) and retinal sensitivity in eyes with intermediate age-related macular degeneration (iAMD). Methods: This prospective study included patients with iAMD and healthy controls. All enrolled subjects underwent optical coherence tomogr...

The photopupillary reflex regulates the pupil reaction to changing light conditions. Being controlled by the autonomic nervous system, it is a proxy for brain trauma and for the conditions of patients in critical care. A prompt evaluation of brain traumas can save lives. With a simple penlight, skilled clinicians can do that, whereas less specializ...

Background Genetic testing of patients with inherited kidney diseases has emerged as a tool of clinical utility by improving the patients’ diagnosis, prognosis, surveillance and therapy. Methods The present study applied a Next Generation Sequencing (NGS)-based panel, named NephroPlex, testing 115 genes causing renal diseases, to 119 individuals,...

Wolfram syndrome (WFS) is a rare autosomal recessive neurodegenerative disease whose diagnosis requires diabetes mellitus and optic atrophy (OA). WFS includes a wide spectrum of other possible complications such as diabetes insipidus, sensorineural deafness, urinary tract problems, neurological and psychiatric disorders. Most WFS patients show type...

Aims: To evaluate both donor and recipient features involved in visual acuity restoring and complication insurgence in eyes that have undergone Descemet stripping automated endothelial keratoplasty (DSAEK). Methods: In this retrospective study, charts of 111 eyes of 96 patients (mean age 70.25 ± 8.58 years) that underwent DSAEK were evaluated. Only...

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The use of chromatic pupil responses may be a novel way to diagnose and monitor diseases affecting either the outer or inner retina.

Background/objectives To compare the number of eye surgical procedures performed in Italy in the 2 months following the beginning of lockdown (study period) because of COVID-19 epidemic with those performed in the two earlier months of the same year (intra-year control) and in the period of 2019 corresponding to the lockdown (inter-year control)....

Objective To determine whether functional vision and visual function improvements after voretigene neparvovec (VN; LUXTURNA®, Spark Therapeutics, Inc.) administration in subjects with biallelic RPE65 mutation-associated inherited retinal disease are maintained at 3–4 years, and to review safety outcomes. Design Open-label, randomized, controlled p...

Cystoid spaces (CSs) are a common retinal finding in choroideremia (CHM) patients. The aim of this study was to analyze the vascular features of the choroid associated with the presence of CSs in patients with confirmed genetic diagnosis of CHM. A total of 33 patients (33 eyes) were enrolled in this retrospective cross-sectional study and divided i...

Achromatopsia (ACHM) is a rare genetic disorder of infantile onset affecting cone photoreceptors. To determine the extent of progressive retinal changes in achromatopsia, we performed a detailed longitudinal phenotyping and genetic characterization of an Italian cohort comprising 21 ACHM patients (17 unrelated families). Molecular genetic testing i...

In this study we analyzed the expression of circulating miRNAs, in the serum of diabetic retinopathy (DR) patients. Five miRNAs (hsa-miR-195-5p, hsa-miR-20a-5p, hsa-miR-20b-5p, hsa-miR-27b-3p and hsa-miR-451a) were validated as biomarkers for stratification of DR stages, from the early non-proliferative (NPDR) to the late proliferative (PDR) phase....

Purpose: The purpose of this study was to perform a detailed longitudinal phenotyping of X-linked retinitis pigmentosa (RP) caused by mutations in the RPGR gene during a long follow-up period. Methods: An Italian cohort of 48 male patients (from 31 unrelated families) with RPGR-associated RP was clinically assessed at a single center (mean follo...

The purpose of the study is to evaluate the corneal biomechanical properties (CBP) and their behaviors after myopic refractive surgery both with Ocular Response Analyzer (ORA) and Corvis ST (CST). This retrospective study included 145 eyes of 145 patients with a mean age of 33.13 ± 9.24 years, who underwent myopic photorefractive keratectomy (PRK)...

Aims: To evaluate the ocular and systemic factors involved in cataract surgery complications in a teaching hospital using artificial intelligence. Methods: One eye of 1,229 patients with a mean age of 70.2 ± 10.3 years old that underwent cataract surgery was selected for this study. Ocular and systemic details of the patients were recorded and then...

Background Urine concentrating defect is a common dysfunction in ciliopathies, even though its underlying mechanism and its prognostic meaning are largely unknown. This study assesses renal function in a cohort of 54 Bardet–Biedl syndrome (BBS) individuals and analyses whether renal hyposthenuria is the result of specific tubule dysfunction and pre...

Background: Fingolimod (FNG) is associated with the development of symptomatic macular edema (ME) in a small subset of multiple sclerosis (MS) patients. By using spectral domain optical coherence tomography (SD-OCT), an increase in the total macular volume (TMV) was rarely detected during the first months of treatment. Objectives: The objective...

Peroxisomal biogenesis disorders (PBD) are rare autosomal recessive disorders with various degrees of severity caused by hypomorphic mutations in 13 different peroxin (PEX) genes. In this study, we report the clinical and molecular characterization of a 9-years-old female presenting an apparently isolated pre-lingual sensorineural hearing loss (SNH...

Background: Sialidosis is a rare genetic lysosomal storage disorder caused by a deficit of neuraminidase enzyme activity. Patients with sialidosis present various neurological disorders such as: myoclonic epilepsy and hypotonia, often associated with visual impairment. A typical aspect of sialidosis is the finding of a macular cherry-red spot on o...

We investigated the genetic origin of the phenotype of three children from two unrelated Italian families presenting with a previously-unrecognized, seemingly autosomal recessive disorder that included a severe form of spondylo-epiphyseal dysplasia, sensorineural hearing loss, intellectual disability, and Leber congenital amaurosis (SHILCA), as wel...

Purpose: to evaluate the effect of biofeedback (BF) rehabilitation on the visual function and on the activity of primary visual cortex (PVC) in patients with Stargardt's disease owing to mutations in the ABCA4 gene (STGD1). Methods: This was a single-center, controlled, randomized study. Twenty-four patients with STGD1 were randomized into two g...

Missing heritability in human diseases represents a major challenge, and this is particularly true for ABCA4-associated Stargardt disease (STGD1). We aimed to elucidate the genomic and transcriptomic variation in 1054 unsolved STGD and STGD-like probands. Sequencing of the complete 128-kb ABCA4 gene was performed using single-molecule molecular inv...