Background and Objectives. Retinitis pigmentosa (RP) is the most common inherited rod–cone dystrophy (RCD), resulting in nyctalopia, progressive visual field, and visual acuity decay in the late stages. The autosomal dominant form (ADRP) accounts for about 20% of RPs. Among the over 30 genes found to date related to ADRP, RP1 pathogenic variants have been identified in 5–10% of cases. In a cohort of RCD patients from the Palermo province on the island of Sicily, we identified a prevalent nonsense variant in RP1, which was associated with ADRP. The objective of our study was to analyse the clinical and molecular data of this patient cohort and to evaluate the potential presence of a founder effect. Materials and Methods. From 2005 to January 2023, 84 probands originating from Western Sicily (Italy) with a diagnosis of RCD or RP and their relatives underwent deep phenotyping, which was performed in various Italian clinical institutions. Molecular characterisation of patients and familial segregation of pathogenic variants were carried out in different laboratories using Sanger and/or next-generation sequencing (NGS). Results. Among 84 probands with RCD/RP, we found 28 heterozygotes for the RP1 variant c.2219C>G, p.Ser740* ((NM_006269.2)*, which was therefore significantly prevalent in this patient cohort. After a careful interview process, we ascertained that some of these patients shared the same pedigree. Therefore, we were ultimately able to define 20 independent family groups with no traceable consanguinity. Lastly, analysis of clinical data showed, in our patients, that the p.Ser740* nonsense variant was often associated with a late-onset and relatively mild phenotype. Conclusions. The high prevalence of the p.Ser740* variant in ADRP patients from Western Sicily suggests the presence of a founder effect, which has useful implications for the molecular diagnosis of RCD in patients coming from this Italian region. This variant can be primarily searched for in RP-affected subjects displaying compatible modes of transmission and phenotypes, with an advantage in terms of the required costs and time for analysis. Moreover, given its high prevalence, the RP1 p.Ser740* variant could represent a potential candidate for the development of therapeutic strategies based on gene editing or translational read-through therapy for suppression of nonsense variants.

Purpose: The purpose of the study is to show the excellent anatomical result of the inverted flap-assisted technique with platelet-rich plasma under air for retinitis pigmentosa complicated with macular hole. Methods: A 32-year-old woman, previously diagnosed with retinitis pigmentosa, was referred to our department complaining of decreased central vision in her left eye for 4 weeks. At the time of presentation, the optical coherence tomography and fundoscopy examination showed the presence of a macular hole of 620 μm in diameter. The closure of the macular hole was observed after the surgical procedure, but endophthalmitis occurred 5 days, postoperatively. Results: In our presented case, the cover flap-assisted technique with platelet-rich plasma under air for retinitis pigmentosa complicated with macular hole resulted in excellent anatomical outcomes with unremarkable visual recovery. Conclusion: The physiopathology of full-thickness macular holes in retinitis pigmentosa patients remains still not fully elucidated. Pars plana vitrectomy with the adjunct of highly concentrated pure platelet-rich plasma have shown successful results.

Background: Inherited retinal dystrophies (IRDs) include a clinically and genetically diverse array of conditions resulting in progressive visual impairment. The PROM1 gene is crucial for the development and maintenance of photoreceptors. Variants in PROM1 are linked to a wide phenotypic spectra of IRDs; however, the correlation between genotype and phenotype is not fully elucidated. Comprehending these relationships is essential for enhanced diagnostic precision, patient guidance, and formulation of focused treatments. Objective: This study aims to examine the genotype–phenotype associations in patients with PROM1-associated IRDs. Clinical variability and inheritance patterns linked to different pathogenic variants are examined, aiming to clarify their different behaviors. Methods: We performed a retrospective investigation of patients identified as affected by PROM1-related IRDs. Thorough ophthalmologic assessments, including retinography, fundus autofluorescence, optical coherence tomography (OCT), and electrodiagnostic testing (EDT), were conducted. Genetic testing was performed via targeted gene panels or whole-exome sequencing. Variants were categorized based on ACMG criteria, and inheritance patterns were determined by familial segregation analysis. Clinical characteristics were analyzed among genotypic groups to ascertain potential phenotype–genotype relationships. Results: All patients had pathogenic or likely pathogenic PROM1 mutations. Both autosomal dominant and autosomal recessive inheritance patterns were identified. Dominant pathogenic variants were predominantly linked to late-onset cone-rod dystrophy or macular dystrophy, whereas biallelic variants frequently resulted in early-onset severe rod–cone dystrophy characterized by fast vision deterioration. A group of patients with the same genotypes displayed significant phenotypic variability, indicating the potential impact of modifier genes or environmental influences. Truncating mutations in the N-terminal region were significantly associated with earlier illness onset and greater functional impairment. Conclusions: PROM1-related IRDs demonstrated significant clinical and genetic heterogeneity, with the route of inheritance and type of variant affecting disease severity and progression. Our findings underscore the significance of thorough genotypic and phenotypic characterization in afflicted individuals. A deeper comprehension of PROM1-related IRD disease pathways can enhance prognosis, direct clinical care, and facilitate the advancement of genotype-based therapy strategies.

This case report describes the possibility of XEN63 lumen obstruction at the middle of the device and emphasizes the potential to restore its flow using an ab-externo revision technique involving a 10-0 nylon suture probe, before considering more aggressive surgical interventions. A 55-year-old female with uveitic glaucoma underwent XEN63 implantation but experienced elevated intraocular pressure (IOP) (35 mm Hg) 1 month after the operation, despite medical therapy. A flat bleb, lack of response to medication, yttrium aluminum garnet (YAG) laser treatment, and slit-lamp needling necessitated revision. An ab-externo surgical procedure was performed using a 10-0 nylon probe to release the obstruction, followed by the application of mitomycin C and removal of fibrous tissue and subconjunctival Tenon's capsule. Intraoperatively, flow was observed only after probing with the 10-0 nylon. Postoperatively, the patient's IOP decreased immediately and remained well-controlled at 2 months (8 mm Hg) without requiring further medication. For patients experiencing increased inflammatory response, the XEN63 gel stent may develop deep lumen occlusion that is unresponsive to conventional treatments. This case report introduces a novel surgical technique applicable to various glaucoma devices, utilizing an ab-externo approach with a 10-0 nylon probe. The demonstrated success in reducing IOP suggests its potential as a less invasive alternative to consider before resorting to more aggressive surgical interventions. Marchese V, Randazzo V, Badalamenti R, et al. Reviving XEN63 Gel Stent Patency in Uveitic Glaucoma: A Novel Approach Using 10-0 Nylon Probe. J Curr Glaucoma Pract 2024;18(2):74-78.

BACKGROUND AND OBJECTIVES. Rod-Cone Dystrophies (RCDs) are genetically determined retinal dystrophies, resulting in nyctalopia, visual field progressive reduction and visual acuity decay in the late stages. Retinitis Pigmentosa (RP) is the most described type. All modes of transmission can be identified in RP, with the autosomal dominant form (ADRP) accounting for about 20% of cases. To date, over 30 genes have been related to ADRP, with RP1 gene estimated to be involved in 5-10% of cases. In a cohort of patients affected by RCD and sharing the same geographic origin from Palermo province in Western Sicily, we identified a prevalent causative variant in the RP1 gene (NM_006269.2; c.2219C>G, p.Ser740*). Objective of our study was to analyse clinical and molecular data of this population and define the entity and the meaning of this finding. MATERIALS AND METHODS. Eighty-four patients with a diagnosis of RCD or RP underwent deep phenotyping, pedigree definition and molecular characterization, mostly by Next Generation Sequencing (NGS). All potentially pathogenic variants have been confirmed through direct sequencing and familial segregation. Statistical evaluation of resulting data has been performed. RESULTS. In 28 probands we identified a pathogenic variant (p.Ser740*) in the RP1 gene that resulted significantly prevalent. Some patients, after careful interviewing, were found to share the same pedigree; we ultimately defined 20 family groups with no traceable consanguinity. CONCLUSIONS. The high prevalence of the p.Ser740* variant in RP patients from Western Sicily unveils the presence of a founder effect, which has implications for the molecular diagnosis of RCD in patients coming from this Italian region. This variant can be primarily searched in RP affected subjects displaying compatible mode of transmission and phenotype, with an advantage in terms of costs and analysis time. Moreover, given its high prevalence, RP1 p.Ser740* variant could represent a potential candidate for the development of therapeutic strategies based on gene editing or translational read-through therapy for suppression of nonsense variants.

Purpose: To introduce a novel surgical technique for repositioning a dislocated XEN63^® gel stent in patients with open-angle glaucoma, to synthesize contemporary findings on complications associated with stent dislocation, and to comment on related management strategies. Methods: A 75-year-old male with primary open-angle glaucoma experiencing XEN63 dislocation underwent this new surgical procedure. Key steps included identifying the scleral leakage site with Trypan Blue, performing precise scleral incisions, and careful stent repositioning. A mini-review on XEN dislocation was conducted through literature searches using PubMed, Embase, Medline, Web of Science, and Google Scholar, focusing on causes, complications, and management strategies. Relevant studies were selected based on specific inclusion criteria and a consensus process involving multiple reviewers. Results: The technique successfully repositioned the stent, with postoperative recovery indicating normal intraocular pressure and correct stent positioning. Initial postsurgery assessments confirmed stent functionality and correct placement. Pathophysiological mechanisms related to dislocation, type of dislocation, and relative management was also presented summarizing the findings based on current literature. Conclusions: The study presents an effective, conservative management method for repositioning dislocated XEN63 gel stents using an ab externo approach. This technique offers a less traumatic alternative to current practices by avoiding the need for additional devices or scleral pocket creation. The accompanying mini-review provides a comprehensive overview of XEN dislocation, enhancing the strategy for managing such complications. Further research, including broader case series or comparative studies, is essential to solidify these findings.