bluuebunny/crossref_metadata_2025_split huggingface dataset:
Up to 10‐month outcomes of faricimab in treating treatment‐refractory wet age‐related macular degeneration
Authors: Tay Nicole , Milczynska Wiktoria , Kogiantis Alexandros 
Published: January 2025

Aims/Purpose: Wet Age‐Related Macular Degeneration (ARMD) represents a significant irreversible cause of blindness worldwide. Current treatment options are limited to anti‐VEGF therapy, which has shown limited success in halting disease progression. A novel anti‐VEGF therapy, Faricimab, has been suggested to revolutionise these outcomes. This study aimed to evaluate the effectiveness of Faricimab in treating Wet ARMD.Methods: This retrospective cohort study was conducted. Inclusion criteria: all patients with a diagnosis of Wet ARMD who received at least 4 loading‐doses of Faricimab between January 2023 and May 2024 at Watford General Hospital, United Kingdom. Exclusion criteria: Patients who did not receive any anti‐VEGF treatments prior to starting Faricimab. Data on visual acuity (VA) and OCT images were collected for their first and last injections. OCTs were analysed to evaluate the thickness of central retinal fluid (CRF), pigment epithelial detachment (PED) and sub‐retinal fluid (SRF). Data was compared between increasing number of Faricimab injections, OCT thicknesses and visual outcomes.Results: 40 patients (45 eyes) were identified and included in the study. The mean change of thickness between first and last injections in patients were: +1.18 ± 35.7 % increase in CRF, ‐1.65 ± 39.7 % decrease in PED, and ‐40.053 ± 52.4 % of the patients who had SRF. There was no significant difference in CRF or PED thickness changes between 4‐6 injections compared to 8‐10 injections (p: 0.39 and p: 0.17). Average VA worsened, with a mean of 0.065 ± 0.475 increase in LogMAR.Conclusions: This study demonstrates the limited effectiveness of Faricimab in treating wet ARMD. There was no significant decrease in CRF and PED. However, there was a 40% decrease in SRF for patients affected by pre‐existing SRF before the 4th injection. Current literature indicates a link between a reduction in SRF and a subsequent worsening in VA1, as seen in our study. Further data needs to be collected to assess the effectiveness of Faricimab in treating ARMD.References: 1 Siedlecki J et al. Impact of Sub‐Retinal Fluid on the Long‐Term Incidence of Macular Atrophy in Neovascular Age‐related Macular Degeneration under Treat & Extend Anti‐Vascular Endothelial Growth Factor Inhibitors. Sci Rep. 2020 May 15; 10(1): 8036. doi: 10.1038/s41598‐020‐64901‐9.
Regarding a case, can hypertrophy of the retinal pigment epithelium be the first sign of familial adenomatous polyposis?
Authors: Rafecas Ariadna Garreta 
Published: January 2025

Aims/Purpose: Congenital Hypertrophy of the Retinal Pigment Epithelium (CHRPE) is a benign ocular condition characterized by well‐demarcated, flat, pigmented lesions in the retinal pigment epithelium. The primary aim of studying CHRPE is to understand its prevalence, features, and potential associations with other conditions, particularly familial adenomatous polyposis coli (FAP), which can have significant health implications.Methods: With an example clinical case, methods for studying CHRPE often involve comprehensive eye examinations using tools like the Optomap imaging system, which provides ultra‐wide‐field views of the retina, enabling detailed observation of the lesions.Results: Results from studies have shown that CHRPE has a low prevalence rate and is typically found temporally to the optic disc within the peripheral fundus. The lesions are usually monocular and exhibit a range of documented shapes and sizes. Some lesions present with depigmented haloes and lacunae, which are atrophied window‐like defects. The progression of CHRPE is not well‐documented due to the lack of longitudinal follow‐up in most studies. However, there is evidence suggesting that the lesions may increase in size due to atrophy over time. Conclusions drawn from the research indicate that CHRPE is generally not associated with symptoms or visual impairment, and its presence does not necessarily indicate a link with syndromes like FAP, Gardner's, or Turcot's.Conclusions: This conclusion is significant as it helps differentiate CHRPE from similar retinal conditions that may have more serious implications. For further reading on the prevalence and ocular features of CHRPE in the optometric population, one can refer to the study by Coleman and Barnard. Additionally, the imaging characteristics of CHRPE have been described in detail in a retrospective observational case series, which provides insights into the lesion's features as analyzed by enhanced‐depth imaging optical coherence tomography.References: Deibert B, Ferris L, Sanchez N, Weishaar P. The link between colon cancer and congenital hypertrophy of the retinal pigment epithelium (CHRPE). Am J Ophthalmol Case Rep. 2019 Sep; 15: 100524.
Treatment of polypoidal choroidal vasculopathy in the real world and its underlying mechanisms
Authors: Chao Howard Wen‐Haur , Chao Hsiao‐Ming 
Published: January 2025

Aims/Purpose: To evaluate the efficacy of combined therapy (verteporfin PDT plus anti‐VEGF) vs. anti‐VEGF monotherapy in symptomatic macular polypoidal choroidal vasculopathy (PCV) and its underlying therapeutic mechanisms.Methods: In this retrospective indocyanine green angiography (ICG)–proved PCV study, 21 Chinese (mean age: 67.50 ± 2.22 years; 17 males; 4 females; 11 left eyes) were treated randomized to mainly verteporfin PDT (standard fluence) + anti‐VEGF, or anti‐VEGF monotherapy. Patients were followed monthly by 3D OCT and re‐treated if signs/symptoms (e.g. cystoid macular edema/deteriorated best corrected vision, BCVA) recurred or persisted. Patients were evaluated with ICG to observe the regression of polyps. Change in BCVA/central retinal thickness, CRT, and safety were also included.Results: The mean follow‐up period (37.04 ± 7.74 months) showed that verteporfin PDT combined with antibodies (bevacizumab, ranibizumab or aflibercept) was compared to anti‐VEGF monotherapy in reducing the CRT (151.75 ± 40.37μm vs. 151.00 ± 58.83); BCVA changes (LogMAR) were ‐0.01 ± 0.21 (verteporfin PDT+antibodies) vs. 0.08 ± 0.09 (anti‐VEGF monotherapy). The mean injection numbers are 1.1# PDT+2# anti‐VEGF agents for combined therapy; 4.6 ± 1.2 anti‐VEGF agents for monotherapy. Three patients of PCV (30%) were recurrent and averaged 18.50 ± 9.26 months. Incomplete remission of polyps/BVN were observed in all eyes. There were no new safety issues with defined therapies. The PCV/nvAMD (control) levels of PLGF, VEGF, HIF1α and Wnt were 3.60 ± 1.48 (n = 8)/32.45 ± 10.53 (n = 28), 105.52 ± 16.15 (n = 8)/235.38 ± 42.13 (n = 27), 2.78 ± 1.40 (n = 3)/2.27 ± 0.43 (n = 63) and 2.13 ± 1.22 (n = 5)/2.40 ± 0.34 (n = 20). As compared to nvAMD, those concentrations of PLGF and VEGF in PCV were much lower.Conclusions: Verteporfin PDT plus antibodies was compared to anti‐VEGF monotherapy in achieving less number of visits/injections in this study in symptomatic macular PCV. However, BCVA was only stable (‐0.01 ± 0.21) but not improved, which was not correlating to the anatomic improvement. All treatments were well tolerated over the around 2‐year follow‐up period. As shown by various biomarkers, PCV should be a variant of nvAMD. It might therefore explain dissimilarity in response to anti‐VEGF and/or PDT treatment.
Vascular density and metamorphopsia after successful repair of rhegmatogenous retinal detachment. comparison between macula‐on and macula‐off eyes
Authors: Xirou Tina , Smoustopoulos Georgios , Kontou Evgenia , Garnavou‐Xirou Christina , Gkizis Ilias , Bontzos George 
Published: January 2025

Purpose: To analyze vascular changes such as the postoperative foveal avascular zone (FAZ) area, the superficial vessel density (sVD) and deep vessel density (dVD) and their correlation with functional (best‐corrected visual acuity, metamorphopsia) and anatomical variables (foveal macular thickness, FMT) after successful repair of a rhegmatogenous retinal detachment (RRD) repair.Methods: Patients with RRD eyes, successfully treated with a single pars plana vitrectomy (PPV) with gas or silicone oil tamponade and a minimum 6 months follow‐up, were re‐examined. For patients where silicone oil was applied, measures were taken after its removal. Foveal avascular zone (FAZ) area, sVD, dVD and FAZ area were evaluated by using optical coherence tomography angiography (OCTA) and compared to fellow eye. Moreover, anatomical association was tested between areas of reported metamorphopsias and vascular changes in the corresponding area.Results: Twenty‐one patients with macula‐on and 24 with macula‐off RRD were included in the study. In both groups, no significant difference in macular thickness and FAZ area was found compared to fellow eyes. In macula‐on RRD eyes, a lower total dVD (p < 0.05) was detected; FAZ area was not related to FMT, and the postoperative BCVA was correlated with FAZ area and dDV (p < 0.05). In macula‐off RRD eyes, lower sDV (p = 0.05), and dVD (p < 0.05, respectively) were observed when compared to fellow eyes. The prevalence of metamorphopsia in macula‐on group was 42.86% (9/21), whereas in macula ‐off this number increased to 62.5% (15/24). For both of these groups we found significant association between sDV and presence of metamorphopsia but only in the inferior paramacular area (p = 0.01).Conclusions: Rhegmatogenous retinal detachment eyes successfully treated with PPV had lower vessel density in the superficial and deep retinal plexus compared to fellow healthy eyes; final BCVA was related to vessel density and FAZ area. Metamorphopsias were also related to superficial vessel density inferiorly of the macula.
Advanced glycation end products association with diabetic retinopathy severity
Authors: Varoniukaite Aiste , Verkauskiene Rasa , Simoniene Diana , Paskeviciene Deimante , Balciuniene Vilma 
Published: January 2025

Aims/Purpose: Advanced glycation end products (AGEs) are proteins or lipids that become glycated as a result to exposure to sugars and diabetes (DM) can accelerate its usually slow accumulation. Higher levels of AGEs are associated with microvascular complications as diabetic retinopathy (DR). AGEs can be measured in human skin using ultra‐violet light to excite autofluorescence. The purpose of this study was to determine the association between AGEs levels and DR severity.Methods: A total of 152 patients were enrolled. DR severity was determined by an ophthalmologist. AGEs concentrations were measured with non‐invasive AGE Reader device.Results: 69 men and 83 women with type 1 (50.7%) and type 2 (49.3%) diabetes were included in the analysis. Age median was 51.85 (min.18, max. 85) years with duration of diabetes 15.99 ± 11.18 years. Mean HbA1C was 8.34 ± 1.99%. 43.7% had no signs of DR, 40.4% had non‐proliferative DR (NPDR), 15.9% – proliferative DR (PDR). Age and HbA1C did not differ between different severity DR groups (p = 0.081 and p = 0.196). AGEs concentration increases with age (r = 0.498, p < 0.001) and duration of diabetes (r = 0.308, p < 0.001). Mean concentration of AGEs were higher in type 2 DM group (p = 0.015). The concentration of AGEs did not differ between DR groups (p = 0.473), thought in type 1 DM subgroup mean concentration of AGEs was higher in PDR patients compared to no DR patients (1.89 vs. 2.43, p = 0.006), whereas no significant difference was found between type 2 DM patients in different DR groups (p = 0.343). There was no significant correlation between HbA1C and AGEs concentration (p = 0246) in all DM patients, but in type 1 DM, AGEs concentration significantly increases with higher HbA1C values (r = 0.309, p = 0.007), but not significantly in type 2 DM (p = 0.282).Conclusions: The levels of AGEs might have association with the severity of DR in type 1 diabetes, but not type 2. More investigations regarding the association of AGEs and DR severity should be performed.
Neovascular age‐related macular degeneration on three nationwide survey and register data in Finland during 2000–2017
Authors: Purola Petri , Koskinen Seppo , Kaarniranta Kai , Uusitalo Hannu 
Published: January 2025

AbstractPurposeTo evaluate time trends in the incidence and prevalence of neovascular age‐related macular degeneration (nAMD) and its treatments, associated factors, and effects on vision in Finland during 2000–2017.MethodsWe used three nationwide health examination surveys representing the Finnish population aged 30 years or older. All three surveys were linked to the national care register covering nAMD diagnoses and intravitreal injections between 2000 and 2017. All three surveys included a health examination in which distance and near visual acuity (VA) were measured, as well as self‐reported and register‐based information on socio‐demographic status and lifestyle, health care use, co‐morbidities, and quality of life. The data included two cross‐sectional time points in 2011 and 2017 and two 11 year longitudinal follow‐ups during 2000–2011 and 2006–2017.ResultsThe incidence and prevalence of nAMD were two times higher in women than in men. The annual prevalence of nAMD increased from 0.51% to 0.70% and from 0.22% to 0.46% in treated nAMD between 2011 and 2017. Treated nAMD patients had an average of 4 intravitreal injections per treatment year. nAMD patients showed significantly poorer distance and near VA than persons without any AMD in 2011 and 2017 (p < 0.001). However, near VA was significantly better in 2017 than in 2011 among nAMD patients (p = 0.036). The duration of nAMD showed weak negative correlation with distance and near VA. After adjusting for age and sex, nAMD patients showed significantly higher univariable odds ratios for lower distance VA, low consumption of vegetables, living in central Finland, a higher number of hospitalisations per year, and older age compared with persons without any AMD.ConclusionSince nAMD is an increasing burden for public health with gender discrepancy and a detrimental impact on vision, we should better find patients who have a high risk of developing nAMD and try to optimise their preventive intervention. Once nAMD is developed, we should understand treatment and follow‐up demands at the personalised level. The nationwide register data help us in those challenges.
A Phase I, First‐In‐Human Study of CBA‐1205, an Anti‐DLK1 Monoclonal Antibody, in Patients With Advanced Solid Tumors
Authors: Katsuya Yuki , Ikeda Masafumi , Koyama Takafumi , Sato Jun , Okada Mao , Matsubara Nobuaki , Kondoh Chihiro , Mukohara Toru , Watanabe Kazuo , Kotani Daisuke , Ogawa Yoshimi , Taoka Shose , Yamamoto Noboru 
Published: January 2025

ABSTRACTCBA‐1205 is a novel humanized antibody targeting delta‐like 1 homolog (DLK1) that enhances antibody‐dependent cellular cytotoxicity activity. DLK1 overexpression has been reported in various cancer types, such as hepatocellular carcinoma and neuroblastoma. CBA‐1205 demonstrates potent antitumor activity in multiple tumor models, making it a potential treatment option for DLK1‐expressing cancers. This first‐in‐human, open‐label Phase I study includes three parts. Part 1, the dose‐escalation phase, primarily evaluates the safety profile, tolerability, and maximum tolerated dose of CBA‐1205. The drug is administered intravenously every 2 weeks in a 28‐day cycle. A standard 3 + 3 dose‐escalation design was used across seven cohorts. In a cohort of 22 Japanese patients, over 80% had undergone three or more prior treatments. CBA‐1205 was well tolerated, with no dose‐limiting toxicity observed at doses ranging from 0.1 to 30 mg/kg, the planned highest dose. There were no treatment‐related serious adverse events or trial‐related deaths. CBA‐1205 exposure, as measured by Cmax, AUC0–14, and AUC0–∞, increased in a dose‐dependent manner. No serum anti‐CBA‐1205 antibodies were detected. Serum DLK1 concentrations were found in 6 out of 22 patients. Stable disease for over 6 months was observed in six patients, with progression‐free survival ranging from 29 to 144 weeks. CBA‐1205 was well tolerated, showing no severe toxicity in patients with advanced or recurrent solid tumors. The favorable safety profile and indications of potential activity support further investigation in Parts 2 and 3 of this Phase I study to evaluate the safety, tolerability, and preliminary efficacy of CBA‐1205.
Promoting Identity Development, Multicultural Attitudes, and Civic Engagement Through Ethnic Studies: Evidence From a Natural Experiment
Authors: Gillespie Sarah , Morency Mirinda M. , Fajemirokun Elizabeth , Ferguson Gail M. 
Published: January 2025

ABSTRACTThis study used a natural experiment design to examine the impact of ethnic studies courses on students' ethnic‐racial identity (ERI) development, multicultural attitudes, and civic engagement during the 2021–2022 school year in Minneapolis, MN (N = 535; 33.5% White, 29.5% Black, 21.1% Latine, 10.7% multi‐racial; 44.7% female, 7.1% non‐binary). Compared to students who were quasi‐randomly assigned to a control class, 9th graders taking an ethnic studies class (treatment group) engaged in significantly more midpoint ERI exploration (β = 0.12), resulting in stronger endpoint ERI resolution (β = 0.48–0.57). Increased exploration mediated more favorable attitudes toward multiculturalism (indirect effect = 0.05) and more frequent civic engagement activities (indirect effect = 0.02). Results have implications for policy efforts to expand ethnic studies.
Trajectories of Maternal Urinary Iodine Concentration Are Associated With Gestational Diabetes Mellitus
Authors: Li Yahui , Gu Simeng , Mo Zhe , Li Xueqing , Jiang Yujie , Liu Chenyang , Guo Fanjia , Mao Guangming , Wang Yuanyang , Huang Xuemin , Li Hong , Chen Zhijian , Wang Xiaofeng , Lou Xiaoming 
Published: January 2025

ABSTRACTObjectivesThe relationship between iodine status and gestational diabetes mellitus (GDM) is inconclusive. This study aimed to explore the trajectories of urinary iodine concentrations (UIC) in pregnant women before GDM diagnosis and to assess the associations between maternal UIC trajectories and the risk of developing GDM.MethodsA prospective cohort study was conducted in China. Data from 1076 pregnant women who were recruited between August 2019 and December 2021 were analyzed. GDM screening was performed at the 28th week of pregnancy. Arsenic and cerium catalysis spectrophotometry was used to measure UIC. The latent class model was used to identify distinct UIC trajectories in pregnant women, using multiple urine specimens. We evaluated the association of UIC trajectories with the risk of GDM by logistic regression analysis.ResultsThree maternal UIC trajectories were identified: (1) high‐stable trajectory (72.12%), (2) high‐decreasing trajectory (3.07%), and (3) low‐stable trajectory (24.81%). Compared with the pregnant women in high‐stable trajectory group, women in the low‐stable UIC trajectory group showed an increased risk of GDM before adjustment of covariates (OR: 1.58, 95% CI: 1.08–2.27). After adjusting for different covariates, a statistically significant association was observed only between low‐stable trajectory trajectories and GDM.ConclusionsThis study highlights a relationship between UIC and the risk of GDM. To better prevent iodine deficiency and GDM, persistent sufficient iodine status from pregnancy to delivery, should be emphasized.
Ravulizumab in juvenile myasthenia gravis: An effective treatment in a 17‐year‐old girl
Authors: Vecchio Domizia , Papa Amanda , Filisetti Giada , Brustia Francesca , Comi Cristoforo , Cantello Roberto 
Published: January 2025

AbstractBackgroundRavulizumab, a monoclonal antibody against C5, is not currently approved for juvenile myasthenia gravis (MG).Case PresentationWe are presenting a 14‐year‐old Moroccan girl diagnosed with antibody‐positive generalized MG first treated with pyridostigmine 240 mg, prednisone 1 mg/kg/day, and thymectomy. Her clinical status remained unchanged (MG Foundation of America Clinical Classification: IIIa) with azathioprine 3 mg/kg, and steroids up to 2 mg/kg/day. She also required three rescue therapies over the subsequent 8 months, gained 10 kg, and had insomnia. We started compassionate ravulizumab treatment, as part of Alexion Pharmaceuticals expanded access program. At screening, the Myasthenia Gravis–Activities of Daily Living scale total score was 4, and Quantitative Myasthenia Gravis total scores were 13 (handgrip and forced vital capacity not performed). She continued her treatment every 8 weeks, and, at week 60, her Myasthenia Gravis–Activities of Daily Living scale total score was 0, and Quantitative Myasthenia Gravis total score was 1. This status was achieved despite an ongoing steroid tapering, that was possibly allowed using a rapidly‐acting treatment. No significant infection or adverse effects were collected.ConclusionsWe are presenting the first case of juvenile MG treated with ravulizumab. Clinical assessment showed at week 60 an improvement of 12 points according to the Quantitative Myasthenia Gravis scoring system, and 3 points to the Myasthenia Gravis–Activities of Daily Living scale total score. This case report supports the efficacy and safety of ravulizumab in MG patients aged <18 years.
SNV/Indel and CNV Analysis in Trio‐WES for Intellectual and Developmental Disabilities: Diagnostic Yield & Cost‐Effectiveness
Authors: Qian Guanhua , Yang Nanyan , Deng Fang , Zhang Mingze , Pan Xin , Tan Bo , Liu Li , Zhang Xu , Yao Hong , Dong Xiaojing 
Published: January 2025

ABSTRACTIntellectual and developmental disabilities (IDD) are clinically and genetically heterogeneous disorders of global concern. While whole exome sequencing (WES) is used to identify single nucleotide variants (SNVs) and small insertions/deletions (Indels) in IDD patients, its detection rate is limited. This study evaluated the value of integrating copy number variation (CNV) analysis into traditional SNV/Indel analysis based on trio‐WES. One hundred eighty seven patients with IDD in 140 families from southwest China were incorporated into the study cohort. The overall diagnostic rate was 40.11% (75/187), with 33.16% (62/187) from SNV/Indel analysis and 6.95% (13/187) from CNV analysis. SNV/Indel analysis identified 52 variants in 42 genes, including 30 novel and 22 reported variants; CNV analysis identified 11 CNVs, comprising 1 repeat and 10 deletions, with sizes ranging from 1313 to 55 184 kb. 39.29% (55/140) families benefited from this study for their clinical diagnosis, treatment, and reproduction. Furthermore, our strategy, with an incremental cost‐effectiveness ratio (ICER) of $2546.22/diagnosis, had demonstrated significant advantages in terms of cost‐effectiveness and detection speed compared to previous methods. In general, by incorporating SNV/Indel and CNV analysis based on trio‐WES, a robust, cost‐effective, and time‐saving approach for diagnosing IDD has been developed.