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Purpose: Women with hypertensive disorders of pregnancy (HDP) are at increased risk of developing premature cardiovascular disease (CVD). The mechanisms behind this are not fully understood, but microvascular alterations have been documented in retinal arterioles and venules. The aim of this study was to use non‐invasive retinal imaging to investigate the structural and functional properties of arterioles, venules and capillaries in this patient group. Methods: We examined 27 women with previous HDP and 23 controls at 3 years postpartum. The retinal microvasculature was assessed by vessel calibre measurements, retinal oximetry and optical coherence tomography angiography. Differences were analysed using non‐parametric tests and multiple regression analyses, adjusted for age and body mass index. Results: Median arteriolar oxygen saturation (SaO2; 94.2% vs. 93.0%), venular oxygen saturation (SvO2; 60.1% vs. 62.4%) and arteriovenous saturation difference (AV‐difference; 32.8% vs. 32.3%) were similar across groups. Capillary vessel density (VD; 46.2% vs. 46.3%), skeletonised VD (VSD; 21.3 vs. 21.1 mm/mm2) and vessel diameter index (21.65 vs. 21.86) were also comparable. In the HDP group, mean arterial pressure (MAP) was positively correlated with AV‐difference (R2 = 0.209) and negatively correlated with arteriolar diameter (CRAE; r2 = 0.382). Conclusions: Structural microvascular alterations appear not to be key biomarkers for CVD risk after HDP as early as 3 years postpartum in otherwise healthy women. Further studies are needed to evaluate whether such changes occur later in life. MAP was associated with AV‐difference only in the HDP group, suggesting specific mechanisms affecting functional microvascular properties in these women. [ABSTRACT FROM AUTHOR]

Background: Retinitis pigmentosa (RP) is a group of hereditary retinal dystrophies characterized by progressive degeneration of photoreceptor cells, which results in debilitating visual impairment. This systematic review aims to evaluate the efficacy and safety of emerging treatment modalities for RP, including gene therapy, mesenchymal-cell-based approaches, and supplementary interventions. Methods: A comprehensive search of electronic databases was conducted to identify relevant studies published up to February 2024. Studies reporting outcomes of treatment interventions for RP, including randomized controlled trials, non-randomized studies, and case series, were included. Data extraction and synthesis were performed according to predefined criteria, focusing on assessing the quality of evidence and summarizing key findings. Results: The search yielded 13 studies meeting inclusion criteria, encompassing diverse treatment modalities and study designs. Gene therapy emerged as a promising therapeutic approach, with several studies reporting favorable outcomes regarding visual function preservation and disease stabilization. Mesenchymal-cell-based therapies also demonstrated potential benefits, although evidence remains limited and heterogeneous. Supplementary interventions, including nutritional supplements and neuroprotective agents, exhibited variable efficacy, with conflicting findings across studies. Conclusions: Despite the lack of definitive curative treatments, emerging therapeutic modalities promise to slow disease progression and preserve visual function in individuals with RP. However, substantial gaps in evidence and heterogeneity in study methodologies underscore the need for further research to elucidate optimal treatment strategies, refine patient selection criteria, and enhance long-term outcomes. This systematic review provides a comprehensive synthesis of current evidence and highlights directions for future research to advance the care and management of individuals with RP. [ABSTRACT FROM AUTHOR]

Purpose: To assess the safety and feasibility of direct vitrectomy-sparing subretinal injection for gene delivery in a large animal model. Methods: The experimental Liběchov minipigs were used for subretinal delivery of a plasmid DNA vector (pS/MAR-CMV-copGFP) with cytomegalovirus (CMV) promoter, green fluorescent protein (GFP) reporter (copGFP) and a scaffold/matrix attachment region (S/MAR) sequence. The eyes were randomized to subretinal injection of the vector following pars plana vitrectomy (control group) or a direct injection without prior vitrectomy surgery (experimental group). Intra- and post-operative observations up to 30 days after surgery were compared. Results: Six eyes of three mini-pigs underwent surgery for delivery into the subretinal space. Two eyes in the control group were operated with a classical approach (lens-sparing vitrectomy and posterior hyaloid detachment). The other four eyes in the experimental group were injected directly with a subretinal cannula without vitrectomy surgery. No adverse events, such as endophthalmitis, retinal detachment and intraocular pressure elevation were observed post-operatively. The eyes in the experimental group had both shorter surgical time and recovery while achieving the same surgical goal. Conclusions: This pilot study demonstrates that successful subretinal delivery of gene therapy vectors is achievable using a direct injection without prior vitrectomy surgery. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF), also known as mucoviscidosis, is the most common autosomal recessive genetic disease in the Caucasian population, with an estimated frequency of 1:2000–3000 live births. CF results from the mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene localized in the long arm of chromosome 7. The product of CFTR gene expression is CFTR protein, an adenosine triphosphate (ATP)-binding cassette (ABC) transporter that regulates the transport of chloride ions (Cl−) across the apical cell membrane. Primary manifestations of CF include chronic lung and pancreas function impairment secondary to the production of thick, sticky mucus resulting from dehydrated secretions. It is well known that CF can cause both anterior and posterior ocular abnormalities. Conjunctival and corneal xerosis and dry eye disease symptoms are the most characteristic manifestations in the anterior segment. In contrast, the most typical anatomical and functional changes relating to the posterior segment of the eye include defects in the retinal nerve fiber layer (RNFL), vascular abnormalities, and visual disturbances, such as reduced contrast sensitivity and abnormal dark adaptation. However, the complete background of ophthalmic manifestations in the course of CF has yet to be discovered. This review summarizes the current knowledge regarding ocular changes in cystic fibrosis. [ABSTRACT FROM AUTHOR]

We explored differences in the DNA methylation statuses of PSMA6, PSMB5, HIF1A, and KEAP1 gene promoter regions in patients with type 1 diabetes and different diabetic retinopathy (DR) stages. Study subjects included individuals with no DR (NDR, n = 41), those with non-proliferative DR (NPDR, n = 27), and individuals with proliferative DR or those who underwent laser photocoagulation (PDR/LPC, n = 46). DNA methylation was determined by Zymo OneStep qMethyl technique. The methylation of PSMA6 (NDR 5.9 (3.9–8.7) %, NPDR 4.5 (3.8–5.7) %, PDR/LPC 6.6 (4.7–10.7) %, p = 0.003) and PSMB5 (NDR 2.2 (1.9–3.7) %, NPDR 2.2 (1.9–3.0) %, PDR/LPC 3.2 (2.5–7.1) %, p < 0.01) differed across the groups. Consistent correlations were observed between the methylation levels of HIF1A and PSMA6 in all study groups. DNA methylation levels of PSMA6, PSMB5, and HIF1A genes were positively correlated with the duration of diabetes, HbA1c, and albuminuria in certain study groups. Univariate regression models revealed a significant association between the methylation level z-scores of PSMA6, PSMB5, and HIF1A and severe DR (PSMA6: OR = 1.96 (1.15; 3.33), p = 0.013; PSMB5: OR = 1.90 (1.14; 3.16), p = 0.013; HIF1A: OR = 3.19 (1.26; 8.06), p = 0.014). PSMB5 remained significantly associated with DR in multivariate analysis. Our findings suggest significant associations between the severity of DR and the DNA methylation levels of the genes PSMA6, PSMB5, and HIF1A, but not KEAP1 gene. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is the most frequent cause of blindness in developed countries. The replacement of dysfunctional human retinal pigment epithelium (hRPE) cells by the transplantation of in vitro-cultivated hRPE cells to the affected area emerges as a feasible strategy for regenerative therapy. Synthetic biomimetic membranes arise as powerful hRPE cell carriers, but as biodegradability is a requirement, it also poses a challenge due to its limited durability. hRPE cells exhibit several characteristics that putatively respond to the type of membrane carrier, and they can be used as biomarkers to evaluate and further optimize such membranes. Here, we analyze the pigmentation, transepithelial resistance, genome integrity, and maturation markers of hRPE cells plated on commercial polycarbonate (PC) versus in-house electrospun polylactide-based (PLA) membranes, both enabling separate apical/basolateral compartments. Our results show that PLA is superior to PC-based membranes for the cultivation of hRPEs, and the BEST1/RPE65 maturation markers emerge as the best biomarkers for addressing the quality of hRPE cultivated in vitro. The stability of the cultures was observed to be affected by PLA aging, which is an effect that could be partially palliated by the coating of the PLA membranes. [ABSTRACT FROM AUTHOR]

Aim: To report on the effectiveness and safety of the MiniMed 780G automated insulin delivery system in real‐world users during the month of Ramadan. Materials and Methods: CareLink Personal data were extracted from MiniMed 780G system users from the Gulf region. Users were included if they had ≥10 days of sensor glucose data during the month of Ramadan 2022 as well as in the month before and after. For the main analysis, continuous glucose monitoring endpoints were aggregated per month and were reported by time of day (daytime: 05.31‐18.00 h, and night‐time). Additional analyses were performed to study the pace at which the algorithm adapts. Results: Glycaemic control was well kept in the 449 included users (mean sensor glucose = 152.6 ± 18.7 mg/dl, glucose management indicator = 7.0 ± 0.4%, time in range = 70.7 ± 11.0%, time below 70 mg/dl = 2.3 ± 2.3%). Albeit some metrics differed from the month before (p <.0001 for all), absolute differences were very small and considered clinically irrelevant. During Ramadan, there was no increased risk of hypoglycaemia during daytime (time below 70 mg/dl = 2.3 ± 2.4%), time in range was highest during daytime (80.0 ± 10.7%, night: 60.4 ± 15.3%), while time above 180 mg/dl was highest during night‐time (37.3 ± 16.3%, day: 17.7 ± 10.7%). The algorithm adapted immediately upon lifestyle change. Conclusion: The MiniMed 780G automated insulin delivery system is effective, safe and fast in adapting to the substantial changes that occur in the lifestyle of people with type 1 diabetes during Ramadan. [ABSTRACT FROM AUTHOR]