Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases characterized by the progressive loss of photoreceptor function, visual impairment, and, ultimately, blindness. While gene therapy has emerged as a promising therapy, it is currently available only for the RPE65 gene mutation, leaving many patients without targeted genetic treatments. Non-surgical interventions may help in managing the progression of RP and improving patients’ quality of life. Visual training and rehabilitation, maximizing residual vision, have shown potential in improving mobility and patients’ ability to perform daily activities. Visual aids enhance visual function. Moreover, photo-protection demonstrated effectiveness in mitigating light-induced damage and improving visual comfort. Alternative therapies (i.e., electrostimulation, acupuncture, and ozone therapy) are being explored to preserve retinal function and reduce disease progression. Pharmacological interventions supported by nutritional and psychological counseling play a role in slowing retinal degeneration while managing the emotional burden of progressive vision loss. Although for these interventions, further validation is required, their potential benefits make them valuable additions to care for RP patients. The integration of these interventions into a multidisciplinary care approach—including ophthalmologists, orthoptist, dietitians, and psychologists—is essential for providing comprehensive, personalized care to RP patients while awaiting more widespread gene therapy solutions.

Sequencing of the low-complexity ORF15 exon of RPGR, a gene correlated with retinitis pigmentosa and cone dystrophy, is difficult to achieve with NGS and Sanger sequencing. False results could lead to the inaccurate annotation of genetic variants in dbSNP and ClinVar databases, tools on which HGMD and Ensembl rely, finally resulting in incorrect genetic variants interpretation. This paper aims to propose PacBio sequencing as a feasible method to correctly detect genetic variants in low-complexity regions, such as the ORF15 exon of RPGR, and interpret their pathogenicity by structural studies. Biological samples from 75 patients affected by retinitis pigmentosa or cone dystrophy were analyzed with NGS and repeated with PacBio. The results showed that NGS has a low coverage of the ORF15 region, while PacBio was able to sequence the region of interest and detect eight genetic variants, of which four are likely pathogenic. Furthermore, molecular modeling and dynamics of the RPGR Glu-Gly repeats binding to TTLL5 allowed for the structural evaluation of the variants, providing a way to predict their pathogenicity. Therefore, we propose PacBio sequencing as a standard procedure in diagnostic research for sequencing low-complexity regions such as RPGR^ORF15, aiding in the correct annotation of genetic variants in online databases.

Introduction: Non-arteritic anterior ischemic optic neuropathy (NAION) is a major cause of vision loss in middle-aged and elderly populations, with no effective treatment currently available. Electrical stimulation (ES) has shown potential in preserving and restoring neural function in optic neuropathies. This study investigates the efficacy of transpalpebral ES in improving visual function in a patient with long-term visual impairment due to NAION. Methods: A 62-year-old male patient with sequential NAION in both eyes underwent a 60-day transpalpebral ES for 20 min daily. Visual function was assessed at baseline and after 30 and 60 days of treatment, including best-corrected visual acuity (BCVA), contrast sensitivity, visual field (VF) analysis, and microperimetry. Results: Significant improvements in BCVA were detected, with an overall increase of 11 ETDRS letters in the right eye and 18 in the left eye after 60 days of treatment. Contrast sensitivity also improved in both eyes. Visual field parameters, including mean deviation, pattern standard deviation and visual field index, showed notable enhancements. Microperimetry revealed increased macular sensitivity and improved fixation stability. The patient also reported subjective improvements. No adverse events were noted. Discussion: ES has been shown to enhance retinal function by modulating neuronal excitability, activating neuroprotective signaling pathways, and potentially supporting neural regeneration. In our case, transpalpebral ES was associated with meaningful improvements in visual function in a patient with long-term NAION-related visual impairment. These results suggest ES as a promising approach for NAION, though further research is needed to confirm these results and optimize treatment protocols.

Introduction: Concomitant manifestation of PPRCA in one eye and RP-like retinopathy in the fellow eye is a rare clinical entity, with limited published descriptions to date. The aim of this study is to describe comprehensive clinical evaluations and long-term follow-up of three patients affected by this clinical picture. Methods: Three patients with concurrent PPRCA and RP-like retinopathy were prospectively re-evaluated and comprehensive assessments were performed. The progression of disease was assessed by comparing best corrected visual acuity (BCVA) and ellipsoid zone (EZ) width with data available from each patient's medical charts and previous SD-OCT scans. Blood samples were collected and tested to rule out autoimmune or infectious ocular diseases, for testing anti-retinal autoantibodies (ARAs) and for genetic analysis. Results: Reduction in BCVA and a progressive concentric loss of the EZ band over time were detected in the eye with RP-like phenotype in all three patients, while in the eye with PPRCA none of the patients showed significant changes in BCVA and only one patient showed a progressive reduction of the EZ width. No clear etiology has been identified. Two or more ARAs subtypes were detected in two out of three patients. Conclusions: PPRCA was demonstrated to be a non-progressive or slowly progressive disease, instead the eye with RP-like phenotype showed a progressive visual impairment, highlighting the importance of shedding light on this condition. Its etiology remains unclear: a genetic trait with different phenotype between the two eyes is conceivable, as well as a potential role of ARAs.

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Background/Objectives: Retinitis pigmentosa (RP) is characterized by progressive degeneration of photoreceptors, with increasing evidence supporting the involvement of inflammation in disease progression. Aqueous humor (AH) reflects the intraocular microenvironment and represents an accessible source for biochemical analysis. This study aimed to characterize the profile of the main inflammatory proteins and bioactive lipids in the AH of RP patients and to compare it with healthy subjects. Methods: The AH was analyzed for cytokines using multiplex immunoassays and for lipid species using liquid chromatography–mass spectrometry. The concentrations of the analyzed molecules were compared between RP patients and the control group and then correlated with age and ellipsoid zone (EZ) width in RP patients. Results: A total of 26 RP patients and 13 controls were recruited. Significantly elevated levels of the pro-inflammatory IL-6 and a significant decrease in vascular endothelial growth factor (VEGF) were found in RP patients compared to controls. In RP patients, lipidomic analysis demonstrated significant increases in medium- and long-chain sphingomyelins (SMs) and very-long-chain unsaturated phosphatidylcholines (PCs). Higher levels of Cer 16:0, PC 32:0, and PC 34:0 were significantly associated with greater EZ preservation in RP patients. Additionally, in RP patients, VEGF and GM-CSF levels increased significantly with age, while IL-8 showed a non-significant decreasing trend. Conclusions: By integrating proteomic and, for the first time, lipidomic analyses of AH, we identified significant alterations in pro-inflammatory cytokines and bioactive lipid species in RP patients compared to controls, further highlighting a link between inflammatory activity, patient age, and disease stage. These preliminary findings need further validation in larger longitudinal cohorts to confirm the clinical utility of these bioactive mediators as potential disease biomarkers.