bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipoic acid's impact on retinitis pigmentosa: Partial protection of photoreceptors and müller cells
Authors: Almansa Inmaculada , López‐Pedrajas Rosa , Valero Javier , Cantó Antolin , Martínez‐González Javier , Hernández‐Rabaza Vicente , Olivar Teresa , Sanz María Miranda 
Published: January 2025

Aims/Purpose: Retinitis Pigmentosa (RP) describes a group of hereditary retinopathies. Traditionally, therapeutic approaches have assumed that inner retinal neurons retain function, properties, and connectivity after photoreceptor degeneration. However, it is known that photoreceptor degeneration leads to dramatic changes in second‐ and third‐order neurons, such as amacrine cells and horizontal cells. In the present study, the main objective is to evaluate not only the protective capacity of lipoic acid against photoreceptor death but also its protective effect on these neurons and Müller cells.Methods: Rd1 mice were treated in accordance with the ARVO statement for the use of animals in ophthalmic and vision research. Mice were sacrificed at different postnatal days (11, 13, 17). Lipoic acid was administered orally (100 mg/kg). It was administered every two days, starting at PN7. The neuroprotective effect of this treatment was analyzed using the TUNEL assay. Müller cells, amacrine cells, and horizontal cells were studied by immunohistochemistry.Results: Lipoic acid treatment reduced photoreceptor death at PN11 and PN13, with no differences observed at PN17 in rd1 mice, demonstrating a partial treatment effect. The expression of GFAP was increased in the retinas at PN11, 13, and 17 rd1 mice, and lipoic acid treatment significantly reversed this effect.Regarding second‐ and third‐order neurons, there was an increase in amacrine cells at PN13 and PN17 in rd1 mice, but lipoic acid had no effect on this increase. As for horizontal cells, no changes were observed at PN13, but at PN17, there was a decrease in these cells that lipoic acid could not reverse.Conclusions: Lipoic acid partially protects photoreceptor death. However, no effect was seen on the studied amacrine and horizontal cells. Further research is necessary to deepen our understanding of RP, specifically examining the remaining neuronal populations.
Fundus autofluorescence patterns in retinitis pigmentosa
Authors: Sahli Esra , Atilla Huban 
Published: January 2025

Aims/Purpose: To evaluate the fundus autofluorescence (AF) patterns in retinitis pigmentosa (RP) patients at different clinical stages.Methods: Patients with a diagnosis of RP confirmed by fundus examination, visual field (VF) and ERG with visual acuity of 20/200 and above were included in the study. Fundus AF imaging was used to evaluate the AF patterns in the macula.Results: Seventy eyes of 36 RP patients were included in the study. Twelve eyes of 6 patients had no hyperautofluorescent ring on fundus AF imaging (type 1). A hyperautofluorescent ring was observed in 22 eyes of 11 patients (type 2). Double hyperautofluorescent rings were present in 4 eyes of 2 patients (type 3). The fovea was hyperautofluorescent in 8 eyes (type 4). In 24 eyes, the macula was completely hypoautofluorescent (type 5). Excluding type 3 with double hyperautofluorescent rings, there was a weak negative correlation between AF typing and visual acuity and a very weak positive correlation between AF typing and VF MD index (correlation coefficients 0.31 and 0.13, respectively).Conclusions: The genetic test results of the patients with double hyperautofluorescent rings were compatible with USH2A gene mutation in accordance with the literature. We believe that patterns other than the double hyperfluorescent ring appearance, which was attributed to a specific genotype in previous studies, are related to the severity or stage of the disease. Type 1 AF suggests early stage disease where the hyperautofluorescent ring does not fall within the area tested in the visual field test, while type 2 AF suggests more advanced disease with a hyperautofluorescent ring. In type 4 AF, only enough retinal pigment epithelium is preserved to give AF in the foveal region. In type 5 AF, there is extensive degeneration involving the fovea. Since the different AF patterns are related to the macular involvement of the disease and the involvement of the cone cells, some correlation with visual acuity has been found.
Macular and optic nerve microvascular changes in patients with type 1 diabetes mellitus
Authors: Chatziralli Irini , Risi‐Koziona Alexia , Agapitou Chrysa , Lampsas Stamatios , Kyratzidis Fotis , Pappelis Konstantinos , Theodossiadis Panagiotis 
Published: January 2025

Aims/Purpose: The purpose of this study was to evaluate the changes of foveal avascular zone (FAZ) area and vessel density (VD) in superficial (SCP) and deep capillary plexus (DCP), as well as changes in optic nerve VD, in association with functional changes in patients with type 1 diabetes mellitus (DM) with and without retinopathy.Methods: The study included 23 patients (23 eyes) with type 1 DM, and 20 control subjects without DM (20 eyes). All participants underwent best‐corrected visual acuity (BCVA) measurement, optical coherence tomography (OCT) and OCT angiography (OCTA) of the macular and optic nerve. Comparison of OCTA parameters between eyes of DM patients and controls was performed.Results: There was a statistically significant decrease in vessel density (VD) in the foveal and parafoveal area in the SCP and DCP in eyes with DM compared to control eyes (p = 0.019 for SCP and p < 0.001 for DCP). The two groups did not differ in FAZ area, FAZ perimeter and FAZ circularity. The change in VD was associated with the severity of diabetic retinopathy (DR) in these patients. There was also a decrease in VD in the optic nerve in patients with DM compared to controls (p = 0.018)Conclusions: The OCTA reveals that the macular and optic nerve was early‐altered in type 1 DM and the alterations were associated with DR severity.
Clinical spectrum of retinal dystrophy caused by pathogenic variants in the cerkl gene
Authors: Paavo Maarjaliis , Sankila Eeva‐Marja , Seitsonen Sanna , Majander Anna , Krootila Julia , Turunen Joni 
Published: January 2025

Aims/Purpose: Two disease‐causing variants of the CERKL gene, (c.375C > G, c.193G > T), are enriched in the Finnish population due to the specific population history. Here we present a large patient cohort with biallelic pathogenic variants in CERKL with long follow‐up time and a reduced spectrum of pathogenic variants.Methods: In this retrospective cohort study medical record data were collected from 50 patients with CERKL‐associated retinopathy followed in the Department of Ophthalmology, Helsinki University Hospital. The age, sex, symptoms, onset of symptoms, best corrected visual acuity (BCVA), colour fundus photography, spectral‐domain optical coherence tomography (SD‐OCT), fundus autofluorescence (AF) and genetic data were collected.Results: The median age at the first visit was 24 years (range 5‐51), and the follow‐up time was 12 years (median, range 0,8‐19). The most common symptoms were nyctalopia (33 patients), reduced BCVA (25 patients) and glare (24 patients). In 11 patients, the disease manifested in the macular area ranging from mild bull's eye maculopathy to geographic atrophy. In 28 patients, both macular and peripheral retina were affected. Eleven patients had severe panretinal degeneration. The median age at onset of visual impairment according to the WHO classification was 38 years (range 23‐60), which corresponds to a 14‐year period (median; range 7‐27) after receiving the diagnosis. Forty‐three (88 %) patients carried at least one allele of the most common pathogenic variant c.375C > G, and 34 (69 %) were homozygous for this variant. Twelve patients (24 %) carried at least one allele of the second most common variant, c.193G > T.Conclusions: The disease spectrum is broad in this large CERKL‐associated retinopathy cohort ranging from macular disease to severe panretinal degeneration. The over a decade period from diagnosis to visual impairment provides an optimal time window for future therapeutic interventions.
Aged‐related changes in connexins‐based mediated intercellular channels in retina
Authors: Domenech‐Bendaña Alicia , Ponce‐Mora Alejandro , Locascio Antonella , Salazar Nicolle , Mallench Lucía Gimeno , Bejarano Eloy 
Published: January 2025

Aims/Purpose: Connexins (Cxs) are a family of structurally‐related transmembrane proteins that form gap junction channels. These channels are essential for direct intercellular communication in many tissues. Cxs play a crucial role in retina homeostasis and visual information processing. Cxs connect photoreceptors, horizontal cells, bipolar cells, amacrine cells and ganglion cells in the mammalian retina. They are proposed as therapeutic targets for several retinal diseases. Although retinal aging is considered a risk factor for different retinal disorders, it remains unclear if the retinal connectome changes with age. This study systematically analyzes the relationship between retinal Cxs isoforms and age.Methods: Retinas from C57BL/6J mice were harvested at 1‐, 4‐, 12‐ and 24 months. Immunohistochemical and qPCR analysis for various retinal Cxs isoforms were performed, including Cx50, Cx43, Cx36 and Cx57. Colocalization analysis was carried out using antibodies against different retinal layers or retinal cell types. Images were captured using the EVOS M7000 microscope, and 3D modelling was performed using the Celleste 3D Deconvolution Module.Results: Differences in expression and location were found in different aged‐groups in an isoform‐dependent manner. For example, Cx50 is expressed in ganglion cell layer in young retina and, as mice aged, Cx50 is highly expressed in Müller cells. Cx36 is highly expressed in both OPL and IPL; higher levels and accumulation of Cx36 are found in aged retina.Conclusions: This study provides new pieces of evidence about the impact of aging in the retinal connexins‐based connectome. A comprehensive understanding of the impact of aging on the retinal connectome is imperative for the design of connexins‐mimetic peptides as therapeutic tools in the treatment of connexin‐related retinal diseases.Funding: RYC 2018‐024434‐I, MINECO PID 2020‐119466RB‐I00, and FUSP‐PPC‐19‐B53C4C64.
Pseudoxanthoma elasticum: A case study of three family members
Authors: Laguna Candela Congost , Gil Romana García , Sánchez Anselmo Feliciano , Peláez Blanca Casado , Moreno Sergio Inat 
Published: January 2025

Aims/Purpose: To evaluate the evolution and various clinical presentations of pseudoxanthoma elasticum in three family members.Methods: Continuous follow‐up was conducted in the outpatient ophthalmology clinics at our hospital. Clinical characteristics, including the presence of exudation, neovascular membranes, angioid streaks, and posterior pole atrophy, were documented and analyzed through detailed ophthalmological examinations and imaging tests. Visual acuity was assessed, and autofluorescence imaging was performed. Additionally, optical coherence tomography (OCT) and OCT angiography (OCT‐A) were utilized to obtain high‐resolution images of the retina and its blood flow.Results: One daughter presented with exudation accompanied by a neovascular membrane, which was treated with intravitreal anti‐VEGF injections. The other daughter maintains good vision and shows angioid streaks in the fundus without macular involvement. The mother is in an advanced stage of the disease, with significant retinoschisis and posterior pole atrophy.Conclusions: This case study highlights the variability in the presentation and progression of pseudoxanthoma elasticum within the same family. Continuous and personalized follow‐ up is crucial for the appropriate management and early detection of complications in PXE patients.
Macular thicknesses of the outer retinal and choroid layers measured by automatic segmentation with artificial inteligence in non‐pathological high myopia
Authors: Darriba David Blanco , Cedrun‐Sanchez Juan , Peña Monica Narvaez , Santos Maria Jimenez , López Juan Donate , Puell María 
Published: January 2025

Aims/Purpose: To compare structural changes in photoreceptor sublayers, retinal pigment epithelium and choroid using optical coherence tomography (OCT) with artificial intelligence‐based automatic segmentation between subjects with simple myopia and non‐pathological high myopia.Methods: This observational case‐control study included a total of 45 eyes of 45 subjects comprised of n = 22 eyes with simple myopia (axial length between 24.00mm and 25.50mm; spherical equivalent between ‐0.50D and ‐4.50D) and n = 23 eyes with non‐pathological high myopia (axial length greater than or equal to 26.00mm; spherical equivalent less than or equal to ‐6.00D). Images were obtained from OCT Spectralis® HRA/OCT2 (Heidelberg Engineering Inc. Heidelberg, Germany) and sublayers were analysed: outer nuclear layer + Henle's fiber layer (ONL+HFL), myoid zone (MZ), ellipsoid zone (EZ)+outer photoreceptor layer (OPR)+interdigitation zone (IZ), retinal pigment epithelium (RPE), choriocapillaris (CC) + stromal choroid (CS) sectorially from the Early Treatment Diabetic Retinopathy Study (ETDRS) 1, 3, 6 mm grid using automatic segmentation by artificial intelligence based software (Discovery® 4.1, RetinAI, Switzerland).Results: Subjects with non‐pathological high myopia showed greater mean thinning in the ONL+HFL (p = 0.001), MZ (p = 0.003), EZ+OPR+IZ (p = 0.001), EPR (p = 0.003) and CC+CS (p < 0.001) sublayers. Specifically, the external regions at the nasal level were the segmentation values with the greatest thinning. Axial length showed a negative correlation in all sublayers analysed (rONL+HFL = ‐0.469, p = 0.001; rMZ = ‐0.535, p ≤ 0.001; rEZ+OPR+IZ = ‐0.549, p ≤ 0.001; rRPE = ‐0.333, p = 0.025; rCC+CS = ‐0.667, p ≤ 0.001).Conclusions: There is greater thinning of the different outer layers of the retina and choroid in non‐pathological high myopia than in simple myopia. The increase in axial length in non‐pathological high myopia may be the determining factor in the presence of these changes. Automatic segmentation using artificial intelligence may be a useful tool in the characterisation and analysis of these layers.
Is intravitreal faricimab an effective treatment for diabetic macular oedema not‐responsive to aflibercept? An audit of treated patients at the princess alexandra eye pavilion
Authors: Lowe Cameron , Das Meghomala 
Published: January 2025

Aims/Purpose: We aim to evaluate both functional and anatomical outcomes of patients switched from aflibercept to faricimab for management of treatment‐resistant diabetic macular oedema (DMO) in a real‐world environment, and the proportion of patients who achieved improvement, stability or deterioration.Methods: Casenotes of 20 eyes not responding to aflibercept, then switched to faricimab were reviewed. Patient demographics, best‐corrected visual acuity (BCVA) and presence of macular oedema on OCT pre‐switch and at post‐treatment clinic review, and injection intervals were recorded. We then categorised whether there was an improvement, stability or deterioration in both BCVA and presence of macular oedema on OCT.Results: Of 16 eyes where analysis was complete for BCVA, there was improvement in 31% (n = 5), stability in 19% (n = 3) and deterioration in 50% (n = 8). Of the eyes where there was deterioration, 4 had other co‐morbidity which affected BCVA. Of 17 eyes with pre‐ and post‐switch macular OCT, there was improvement in macular oedema in 71% (n = 12), stability in 24% (n = 4) and deterioration in 6% (n = 1). The mean injection interval where prescribed 4x 1 monthly (n = 13) was 61 days, with a range from 35 – 138 days.Conclusions: In this real‐world setting with challenges providing patients with regular monthly treatment, faricimab demonstrates the ability to improve DMO in chronic disease with sub‐optimal dosing regimens. A majority of patients demonstrated anatomical improvements, and functional stability or improvement was seen in half of treated eyes. Though the anatomical outcomes were more positive than the functional outcomes on BCVA, this likely reflects the chronicity of DMO in affected eyes, and notably in half of the eyes treated where BCVA deteriorated, there was an alternative cause for this. Given the poorer prognosis of treatment non‐responsive DMO, faricimab is promising as a further option for these harder to treat patients. Overall, there would appear to be a role for faricimab to be a treatment option in chronic‐DMO, and its increased durability is beneficial in busy centres where it is challenging to provide patients with 1‐monthly dosing. This could be further supported by investigating outcomes in patients with treatment‐naive disease.
Comparative retinal study by OCT in Alzheimer's disease: Insights from the APP NL‐F/NL‐F model
Authors: Sanchez‐Puebla Lidia , López‐Cuenca Inés , Vázquez Alberto Arias , Salobrar‐Garcia Elena , Matamoros José A. , Lozano María Pilar Rojas , Fernández‐Albarral José A. , Elvira‐Hurtado Lorena , Ramirez Ana Isabel , Salazar Juan Jose , Saido Takaomi , Saito Takashi , Nieto‐Vaquero Carmen , Cuartero María Isabel , Moro María Ángeles , de Hoz Rosa , Ramirez Jose Manuel 
Published: January 2025

Aims/Purpose: Transgenic mouse models of Alzheimer's disease (AD) have shown a correlation between retinal abnormalities and brain pathology. The APPNL‐F/NL‐F murine humanized AD model accurately replicates many pathological features seen in AD patients. This study aims to analyze, using manual retinal segmentation by optical coherence tomography (OCT), the changes occurring in several retinal layers in the APPNL‐F/NL‐F AD model at 6, 9, 12, 15, 17, and 20 months of age, in comparison to C57BL/6J mice (WT).Methods: A diachronic study was conducted using OCT for manual retinal segmentation to evaluate changes in retinal layers. The analysis focused on retinal thickness in the retinal nerve fiber layer (RNFL)‐ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), and outer nuclear layer (ONL) based on Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. The study included both the APPNL‐F/NL‐F AD model and age‐matched WT controls, with measurements taken at 6, 9, 12, 15, 17, and 20 months.Results: Both the APPNL‐F/NL‐F model and WT animals exhibited changes in retinal thickness at various study time points. WT mice showed significant changes in the INL, OPL, and ONL. In contrast, the AD model exhibited significant changes in all analyzed retinal layers except for the IPL. The APPNL‐F/NL‐F model displayed significant thickness variations in the retinal layers analyzed, which closely resemble those found in humans during pre‐clinical, as well as mild and moderate stages of AD.Conclusions: The study identifies early retinal vascular and structural changes in the APPNL‐F/NL‐F model that precede cognitive changes observed at later stages. These findings suggest that the retinal changes in this model more closely resemble those in human AD compared to other transgenic models, highlighting the potential of retinal assessments in early AD diagnosis.
Comparing membrane peeling techniques in lamellar macular hole surgery: A systematic review and meta‐analysis
Authors: Abu‐Dieh Anas , Er‐Reguyeg Yosra , Rhalem Elyazid , You Eunice , Hébert Mélanie , Dirani Ali 
Published: January 2025

Aims: To compare outcomes of standard and alternative membrane peeling techniques in LMH surgery.Methods: A systematic review and meta‐analysis was performed per the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Pairwise meta‐analysis of mean change in best corrected visual acuity (BCVA as logMAR) and LMH closure rate between flap embedding (FE) and standard peeling (ST) were conducted. A proportional meta‐analysis evaluated FTMH prevalence for each technique.Results: 36 studies of 1200 eyes were included. Three techniques were identified: ST (29 studies), FE (7 studies) and fovea‐sparing peeling (4 studies). FE was superior to ST in BCVA change (MD ‐0.21; CI ‐0.33 to ‐0.10), LMH closure (RR 1.53; CI 1.23–1.90) and postoperative FTMH (RR 0.08; CI 0.01 to 0.58). LMH closure rate was higher (0.97; CI 0.88 to 0.99 vs. 0.81; CI 0.70 to 0.88) in alternative vs. ST, with postoperative FTMH occurring only in ST peelings (0.026; CI 0.013‐0.054).Conclusions: Alternative peeling techniques have superior outcomes. Further randomized controlled studies are needed to confirm their efficacy and innocuity.
Progression of diabetic retinopathy during pregnancy: Retrospective study from birmingham and solihull
Authors: Khalifa Ahmad , Sobha Joseph 
Published: January 2025

Aims/Purpose: To assess the progression of diabetic retinopathy (DR) in pregnant women with pre‐existing diabetes in the Birmingham and Solihull area and to evaluate adherence to recommended screening guidelines.Methods: A retrospective review was conducted over 12 months (01/09/2022‐31/08/2023) using data from the Diabetic Eye Screening Program (DESP) and hospital records (Medisoft, OCT, and retina images). The study included pregnant women with pre‐existing diabetes who received maternity services at University Hospitals Birmingham (UHB) and were referred to DESP. Patients with gestational diabetes were excluded. Data collected included demographics, DR screening attendance, progression rates, and clinical outcomes.Results: Out of 149 pregnant women with pre‐existing diabetes, 54 (36.2%) were not referred for initial screening by 12 weeks due to late presentation and delayed diabetes status confirmation. Of the total, 88 (59%) missed the 12‐week screening, 57 (40%) missed the 16‐20 week screening, and 67 (48%) missed the 28‐week screening. At 12 weeks, 27% were R0M0, 9% R1M0, 3% R1M1, and 1% R2M0/R2M1, with 8 referred to HES. At 16‐20 weeks, 43% were R0M0, 16% R1M0, 1% R3SM0, and 1% were unable to assess, with 2 referred to HES. By 28 weeks, 37% were R0M0, 12% R1M0, 1% R3SM1, and 2% were still being graded, with 1 referred to HES. The study highlighted significant cases, including one patient who progressed to severe NPDR and required bilateral PRP and Ozurdex treatment, and another who developed DMO treated with Ozurdex.Conclusions: Diabetic retinopathy progression during pregnancy remains a significant concern, with many patients missing critical screening appointments, leading to advanced DR stages and severe visual impairment. Despite adherence to screening guidelines, patient non‐compliance and late referrals hinder effective management. Improved patient education and follow‐up strategies are essential to enhance screening attendance and outcomes, thereby preventing severe DR progression during pregnancy. Further research is necessary to develop targeted interventions for better compliance and timely treatment.
Anti‐Youth Ageism: What It Is and Why It Matters
Authors: Wray‐Lake Laura , Rottenberg Julia , Kennedy Heather 
Published: January 2025

ABSTRACTAgeism against older adults has been well studied, yet adolescents also experience ageism in pervasive and harmful ways. In this article, we describe anti‐youth ageism as a system of oppression that encompasses negative stereotypes, prejudices, and discrimination against adolescents that uphold power hierarchies and marginalize young people based on their age. Drawing from interdisciplinary theory and research, we examine adolescents' experiences of anti‐youth ageism at interpersonal, cultural, and institutional levels, and consider the ways anti‐youth ageism is internalized. Across many levels, anti‐youth ageism is understood in concert with other systems of oppression such as racism and cis‐heterosexism. The field needs a new wave of anti‐oppressive developmental science to understand the multilayered, intersectional manifestations of anti‐youth ageism and the impacts of anti‐youth ageism on various domains of development. Research can help foster the creation of intervention strategies to reduce harm to adolescents and their development.