Based on phenotypic similarities between age-related macular degeneration and the autosomal disorder Doyne honeycomb retinal dystrophy, we report on a single nanolaser treatment of a patient with genotype Doyne honeycomb retinal dystrophy confirmation and evidence of disease progression over 12 months. The case study is the first report of short-term results of subthreshold nanolaser treatment in a patient with Doyne honeycomb retinal dystrophy. A 43-year-old Caucasian man with moderate loss of visual acuity in his left eye (20/40) and normal visual acuity in his right eye (20/20), with clinical Doyne honeycomb retinal dystrophy diagnosis and genetic confirmation of the common heterozygous mutation (EFEMP1) by genetic testing, underwent nanopulse subthreshold laser treatment in his left eye. A safety examination, carried out 7 days after treatment, and clinical follow-up, conducted 60 days following laser treatment, showed improvement of visual acuity from baseline by two letters and a subjective improvement of blurring. While no apparent morphological changes were found on fundoscopy, increased autofluorescence in the treated eye was observed on imaging. In addition, 2 months after nanopulse subthreshold laser treatment, rod-mediated and cone-mediated full-field electroretinography b-wave amplitudes showed an increase from baseline in both the treated eye (300%) and untreated eye (50%). At 2 months after nanopulse subthreshold laser treatment, multifocal electroretinograms showed improvement. Acuity and full-field electroretinography improvement persisted at 6-month follow-up. Sustained improvements in retinal function on electroretinography persisted in both eyes 6 months after treatment, suggesting an enhancement of phototransduction and retinoid recycling induced by nanopulse subthreshold laser treatment. The functional improvement observed in the untreated eye is hypothesized to arise from an increased expression and release of metalloproteinases that circulate systemically.

Stargardt macular dystrophy is a genetic disorder, but in many cases, the causative gene remains unrevealed. Through a combined approach (whole-exome sequencing and phenotype/family-driven filtering algorithm) and a multilevel validation (international database searching, prediction scores calculation, splicing analysis assay, segregation analyses), a biallelic mutation in the RDH8 gene was identified to be responsible for Stargardt macular dystrophy in a consanguineous Italian family. This paper is a report on the first family in which a biallelic deleterious mutation in RDH8 is detected. The disease phenotype is consistent with the expected phenotype hypothesized in previous studies on murine models. The application of the combined approach to genetic data and the multilevel validation allowed the identification of a splicing mutation in a gene that has never been reported before in human disorders.

Background: Retinal dystrophies related to damaging variants in the cadherin-related family member 1 (CDHR1) gene are rare and phenotypically heterogeneous. Here, we report a longitudinal (three-year) structure–function evaluation of a patient with a CDHR1-related retinal dystrophy. Methods: A 14-year-old girl was evaluated between 2019 and 2022. An ophthalmological assessment, including color vision, perimetry, electroretinography, and multimodal imaging of the retina, was performed periodically every six months. Next-generation sequencing disclosed two likely pathogenic/pathogenic variants in the CDHR1 gene, in compound heterozygosity, confirmed by segregation analysis. Results: At first examination, the patient showed a cone–rod pattern retinal dystrophy. Over follow-up, there was a decline of visual acuity and perimetric sensitivity (by ≥0.3 and 0.6 log units, respectively). Visual loss was associated with a progressive increase in inner retinal thickness (by 30%). Outer retina showed no detectable changes over the follow-up. Conclusions: The results indicate that, in this patient with a CDHR1-related cone–rod dystrophy, the progression to severe visual loss was paralleled by a progressive inner retinal thickening, likely a reflection of remodeling. Inner retinal changes over time may be functionally relevant in view of the therapeutic attempts based on gene therapy or stem cells to mitigate photoreceptor loss.

Given the multifactorial features characterizing age-related macular degeneration (AMD), the availability of a tool able to provide the individual risk profile is extremely helpful for personalizing the follow-up and treatment protocols of patients. To this purpose, we developed an open-source computational tool named WARE (Wet AMD Risk Evaluation), able to assess the individual risk profile for wet AMD based on genetic and non-genetic factors. In particular, the tool uses genetic risk measures normalized for their relative frequencies in the general population and disease prevalence. WARE is characterized by a user-friendly web page interface that is intended to assist clinicians in reporting risk assessment upon patient evaluation. When using the tool, plots of population risk distribution highlight a “low-risk zone” and a “high-risk zone” into which subjects can fall depending on their risk-assessment result. WARE represents a reliable population-specific computational system for wet AMD risk evaluation that can be exploited to promote preventive actions and personalized medicine approach for affected patients or at-risk individuals. This tool can be suitable to compute the disease risk adjusted to different populations considering their specific genetic factors and related frequencies, non-genetic factors, and the disease prevalence.

Background: INPP5E-related retinopathy (INPP5E-RR) is a rare genetic disorder caused by biallelic pathogenic variants in the INPP5E gene, which encodes an enzyme critical for phosphoinositide signaling. While early-onset rod–cone dystrophy is a hallmark feature, detailed longitudinal data on the phenotype are scarce. This study aims to report a 6-year longitudinal assessment of retinal structure and function in a case of non-syndromic INPP5E-RR. Methods: A 42-year-old female proband with compound heterozygous pathogenic missense variants in INPP5E (p.Arg486Cys and p.Arg378Cys) was monitored from 2019 to 2025. She underwent serial comprehensive ophthalmologic evaluations, including optical coherence tomography (OCT), fundus autofluorescence, adaptive optics transscleral flood illumination, full-field 30Hz flicker electroretinography (ERG), and macular frequency-doubling technology perimetry. Results: Over the 6-year follow-up, OCT imaging revealed a progressive decline in the ellipsoid zone (EZ) width, from 1220 µm to 720 µm (~80 µm/year), and in the inner nuclear layer (INL) thickness. The central outer nuclear layer (ONL) thickness was preserved, but intraretinal cysts developed. Functional testing revealed a progressive decline in cone flicker ERG amplitudes, while visual acuity and macular perimetry remained stable. Conclusions: In this genotypically confirmed case, the longitudinal data identify EZ width, INL thickness, and cone flicker ERG as robust biomarkers of disease progression in INPP5E-RR. These parameters are ideal candidates for monitoring therapeutic outcomes in future clinical trials.

The main aim of this work is to present the electrical analysis of the Acepack ^TM Drive housing an half bridge configuration with 8 SiC MOSFET per switch. The analysis is performed by means of SPICE model simulation setup and the results have been compared with experimental measurements. The experimentally validated simulation model can be exploited to investigate the electrical behavior of the power module in a wider operating range, by considering different working conditions and applications.