bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular vesicles from retinal pigment epithelium: Key players in the outer blood‐retinal barrier disruption and choroidal neovascularization in age‐related macular degeneration
Authors: Martins Beatriz , Rodrigues Teresa , Boia Raquel , Ramalho José , Ambrósio António Francisco , Girão Henrique , Fernandes Rosa 
Published: January 2025

Aims/Purpose: Age‐related macular degeneration (AMD), a degenerative disease causing irreversible central vision loss in the elderly, is characterized by dysregulation of the retinal pigment epithelium (RPE). During AMD, stressed RPE releases extracellular vesicles (EVs) carrying bioactive cargo, potentially disrupting the outer blood‐retinal barrier (oBRB) and accelerating AMD progression. Mechanisms behind EV‐induced oBRB disruption and their role in choroidal neovascularization (CNV) are unclear. Our study aims to assess how RPE‐derived EVs under inflammatory conditions impact oBRB integrity and CNV in AMD.Methods: We used highly polarized primary cultures of porcine RPE (pRPE), porcine eyecups with the RPE exposed, and human umbilical vein endothelial cells (HUVEC). RPE and HUVEC cells were treated with TNF, LPS, or EVs derived from inflamed RPE cells. Additionally, Balb/c mice were intravitreally injected with RPE‐derived EVs.Results: Treatment with TNF or LPS reduced the transepithelial resistance (TER) of pRPE cells monolayer and disrupted the tight junction complexes. Although inflammatory stimuli reduced EVs release from the apical membrane of RPE cells, increased CD63 levels and MMPs levels and activity were found in EVs. Moreover, these EVs led to the disruption of the RPE monolayer. In the Matrigel assay of HUVEC, angiogenesis was induced by both TNF and LPS, and by RPE‐derived EVs isolated after the LPS stimulus. At seven days following intravitreal injection, EVs induced outer retinal structural changes in the Balb/c mice.Conclusions: Our study indicates that EVs released from RPE cells following an inflammatory insult contribute to the oBRB disruption and induce neovascularization, indicating that EVs may play a key role in the onset and progression of AMD.Support: GOAP, Bayer; FCT, Portugal: 2020.04811.BD (to BM), PEst UIDB/04539/Base/2020 and UIDP/04539/Programatico/2020 through POCI‐01‐0145‐FEDER‐007440, CENTRO‐01‐0145‐FEDER‐000008: BRAINHEALTH2020
Correlation of biomarkers of oxidative stress and inflammation in tears and aqueous humor of primary open‐angle glaucoma patients
Authors: Sanchez Javier Benitez‐del‐Castillo , Duran Maria Dolores Pinazo , Sáez Sara Mora , Ruiz David Peña , Zanon‐Moreno Vicente , Ramos‐Lopez Juan Francisco , Galarreta‐Mira David 
Published: January 2025

Aims/Purpose: Biomarkers improve our knowledge of the risk factors and pathogenic mechanisms of eye disorders. Validation of biomarkers is crucial for addressing an effective translation to the clinical practice. We aimed to find the correlation between oxidative stress (OS) and inflammation (INF) biomarkers obtained from two commonly sampled ocular fluids: tears and aqueous humor.Methods: A longitudinal, prospective, case‐control study was conducted in 220 participants that were divided into: patients diagnosed of primary open‐angle glaucoma (POAG; n = 115), and patients diagnosed of cataracts, as the comparative group (CG; n = 105). All participants underwent an interview and standardized ophthalmological examination. Reflex tears were collected from the inferior meniscus by capillarity. Aqueous humor was collected at the onset of the programmed glaucoma or cataract surgery. Both samples were stored at ‐80°, until processing to enzyme‐linked immunosorbent assay (ELISA) technique, to determine OS by products (malondialdehyde ‐MDA‐/4 hydroxynonenal ‐4HNE‐/total antioxidant capacity ‐TAC‐) and INF mediators (IL1b, IL6, TNFa, INFg). The R‐core team statistical program was used for data processing.Results: Mean age was 72 + 9 years in the POAG group and 65 + 10 years in the CG. Gender distribution was homogeneous in both groups of participants. Significantly higher MDA, 4HNE, IL1b, IL6, TNFa, and INFg and lower TAC, were found in tears from the POAG group respect to the CG (p < 0.001). Also, a statistically significant differential profile of OS (MDA, 4HNE, TAC) and INF (IL1b, IL6, TNFa, and INFg) molecules was detected in the aqueous humor of the POAG patients versus the CG (p < 0.001). Specific significant correlations were found between the above molecules and the imaging data regarding disease stages, as well as, importantly, between the tears and aqueous humor results.Conclusions: We described a series of OS and INF biomarkers that can provide information of the disease severity. Furthermore, the OS and INF biomarker levels in tears have been shown to correlate with the aqueous humor in POAG patients, but not in the CG. These data enhance the value of non‐invasive tear collection for biomarkers analyses, that may be one useful driver of glaucoma molecular diagnosis and prognosis.
Is there a common factor for vision?
Authors: Herzog Michael , Garobbio Simona , Pfau Maximilian , Scholl Hendrik 
Published: January 2025

Aims/Purpose: Eye diseases are implicitly assumed to affect vision generally. However, only visual acuity and contrast sensitivity are usually measured to determine perceptual deficits. What about orientation and motion perception?Methods: To address these questions, we first conducted 19 visual tests, including visual acuity (determined by Landolt Cs and verniers), various motion tests, etc., in a large sample of 104 young and 92 older healthy participants. Second, we investigated 50 patients with age‐related macular degeneration (AMD) and 49 age matched controls, administering a battery of six perceptual tests. In addition, OCT images of the retina, choroid, and optic nerve were recorded.Results: Surprisingly, in the young and old healthy population, the tests correlated only weakly, and the factor structure was rather flat. Hence, single eye tests tell very little about vision in the healthy population. What about disease? AMD patients were impaired in all perceptual tests compared to age matched controls, except for motion perception. Detailed OCT analysis and retinal layer segmentation showed that the thickness of the retinal pigment epithelium drusen complex (RPEDC) determines deficits most strongly (r=0.40). We found moderate correlations between the tests, which we attribute to the thickness of the RPEDC layer. However, motion perception was independent of RPEDC thickness, suggesting that AMD does not affect all visual abilities equally.Conclusions: Our results show the need to investigate healthy and clinical vision with batteries of tests rather than with a single contrast or spatial acuity measure.
The effect of peri‐ and preoperative anxiety on cardio‐vascular parameters and intraocular pressure of patients awaiting cataract surgery
Authors: Dimitrova Galina , Gjorgjiovska Ana , Ljubic Antonela , Jordanovska Sofija Milanovska 
Published: January 2025

Aims/Purpose: To evaluate peri‐ and preoperative anxiety in patients scheduled for cataract surgery and its effect and correlation with cardio‐vascular parameters and intraocular pressure (IOP).Methods: Thirty patients scheduled for cataract surgery were included in the study. Exclusion criteria were any previous ocular surgery on both eyes, glaucoma and any sign of acute or chronic ocular inflammation. In addition to the general ophthalmic examination at the initial evaluation patients were asked to define their level of anxiety using a visual facial anxiety scale (VFAS). Systemic blood pressure (BP) and heart rate (HR) were measured using an automated brachial sphygmomanometer and IOP was measured using an air‐puff tonometer. Mean of three measurements was calculated for both BP, HR and IOP. VFAS, BP, HR and IOP measurements were repeated on the day of surgery. T test was used to compare the peri‐ and preoperative parameters and Pearson's coefficient of correlation was used to study correlation between VFAS, BP, HR and IOP.Results: The mean level of anxiety according to patients’ self‐evaluation was mild to moderate both at the peri‐ and at the preoperative day. The cardio‐vascular parameters and IOP were not significantly different at the peri‐ and preoperative days. IOP was significantly correlated to HR in the perioperative period (R=0.62, p < 0.001), whereas in the pre‐operative day it was significantly correlated with systolic BP (R=0.47, p = 0.009) and with level of anxiety (R=0.29, p = 0.04). Patients with moderate to high levels of anxiety (grades 3‐5) had significantly higher IOP (17.06 ± 1.69 mmHg) than patients with none to mild/moderate anxiety (grades 0‐2) (14.74 ± 2.41 mmHg; p = 0.006).Conclusions: Systemic cardio‐vascular parameters are correlated with IOP and the level of anxiety in patients scheduled for cataract surgery. IOP is higher in patients with higher degrees of anxiety.
Congenital aniridia: Experience of 26 years in the department of pediatric ophtalmology of Casablanca, Morocco
Authors: Daghouj Ghizlane , Ettouri Sara , Rokaya Chahir , Rami Ali , El Maaloum Loubna , Allali Bouchra , El Kettani Asmaa 
Published: January 2025

Aims/Purpose: Report the experience of 26 years in the department of pediatric ophthalmology in Casablanca.Methods: Retrospective study from 1996 to 2022 about 30 eyes with congenital aniridia.Results: The average age is 83.35 months. Male at 53% and female at 47% .46% with nystagmus. 20% of the eyes were with corneal involvement. 56.6% of the lenses are cataract. 30% of lenses were dislocated. 30% of aniridia were associated with glaucoma .33.3% of fundus where passage were possible: 22% were normal and the rest pathological. Glaucoma: 2 of the 9 eyes with glaucoma were operated on and the rest under hypotonic medical treatment. Cataract: 13 operated eyes. All children received optical correction and amblyopia treatment. All abdominal ultrasounds were normal. The gain in visual acuity on average was 1 line after therapeutic measures.Conclusions: Aniridia is rare but can significantly and progressively impair vision by reaching the entire eyeball with polymorphic manifestations. Management of aniridia remains difficult, it must be both proactive and responsive, with medical or surgical management or both of them. In sporadic forms an abdominal ultrasound is necessary to rule out the presence of Wilms tumor.References
Efficacy and Safety of Plasma Rich in Growth Factor in Patients with Congenital Aniridia and Dry Eye Disease. Lozano‐Sanroma J, Barros A, Alcalde I, Alvarado‐Villacorta R, Sánchez‐Ávila RM, Queiruga‐Piñeiro J, Cueto LF, Anitua E, Merayo‐Lloves J.Diseases. 2024 Apr 11;12(4):76. doi: 10.3390/diseases12040076.
Epidemiology of PAX6 Gene Pathogenic Variants and Expected Prevalence of PAX6‐Associated Congenital Aniridia across the Russian Federation: A Nationwide Study. Vasilyeva TA, Marakhonov AV, Voskresenskaya AA, Kadyshev VV, Sukhanova NV, Minzhenkova ME, Shilova NV, Latyshova AA, Ginter EK, Kutsev SI, Zinchenko RA.Genes (Basel). 2023 Nov 4;14(11):2041. doi: 10.3390/genes14112041.
Congenital aniridia and cataract. C. Speeg‐Schatz. Journal francais d’ophtalmologie, Volume35‐ N°4, Avril 2012. Doi: 10.1016/j.jfo.2011.04.017
Retinal ischemia: Therapeutic effects and mechanisms of paeoniflorin
Authors: Chao Winsdor Wen‐Jin , Chao Howard Wen‐Haur , Chao Hsiao‐Ming 
Published: January 2025

Aims/Purpose: Retinal ischemia‐associated ocular disorders are vision threatening. The aim of the present study is to assess the potential of paeoniflorin in alleviating retinal ischemic injury and to uncover the mechanisms involved.Methods: Cultured retinal cells were subjected to oxygen glucose deprivation (OGD; N2/CO2/O2: 95 %/5 %/1 %) with pre‐OGD (1h) administration of paeoniflorin (0.25/0.5 mM). The cell viability were evaluated by MTT assay.High intraocular pressure‐induced retinal ischemia (I) was established by raising IOP to 120 mmHg for 60 minutes followed by reperfusion (R) for 7 days in an ischemic eye in a Wistar rat. The physiological effects of the retina were evaluated by electrophysiology and fluorogold retrograde labelling RGCs. The protein levels of angiopoietin, pyruvate kinase M2 (PKM2), Wnt3a and β‐catenin were assessed by Western blotting.Results: Pre‐ischemic administration of paeoniflorin dose‐dependently (less effect at 0.25 mM) and significantly (p < 0.05; 0.5 mM) alleviated OGD induced significant (p < 0.001) decrease in RGC‐5 cell viability. Furthermore, pre‐ischemic administration of paeoniflorin dose‐dependently (less effect at 0.25 mM) and significantly (p < 0.05/p < 0.001; 0.5 mM) attenuated ischemia‐induced significant (p < 0.001/ p < 0.05) reduction in ERG b‐wave amplitude/RGC cell number.Compared to eyes treated with vehicle, paeoniflorin (p < 0.05/p < 0.01/p < 0.05; 0.5 mM) seemed to protect against retinal ischemia by regulating angiopoietin, β‐catenin, WNT and PKM2 expression.Conclusions: The treatment with paeoniflorin is able to effectively reduce retinal ischemia by affecting angiopoietin, β‐catenin, WNT and PKM2 biomarkers.References
Windsor Wen‐Jin Chao, Howard Wen‐Haur Chao, Hung‐Fu Lee, Hsiao‐Ming Chao. The Effect of S‐Allyl L‐Cysteine on Retinal Ischemia: The Contributions of MCP‐1 and PKM2 in the Underlying Medicinal Properties. Int J Mol Sci. 2024 Jan 22;25(2):1349.
Chao HM, Osborne NN. Topically applied clonidine protects the rat retina from ischaemia/reperfusion by stimulating alpha(2)‐adrenoceptors and not by an action on imidazoline receptors. Brain Res. 2001 Jun 15;904(1):126‐36.
Actin‐related proteomic changes in age‐related, diabetic and post‐vitrectomy cataract
Authors: Karakosta Christina , Samiotaki Martina , Parayotou George , Papaconstantinou Dimitrios , Moschos Marilita 
Published: January 2025

Aims/Purpose: Actin has been implicated in lens opacification; however, the specific actin‐related pathways involved in cataracts remain unclear. In this study, actin‐related signaling pathways involved in the development of different types of cataract were evaluated.Methods: Two sample types were collected during routine cataract surgery; the anterior capsule (AC) and phacoemulsification cassette contents (PCC). Participants were divided into three groups. Age‐related cataract (ARC) group included 12 patients without a history of DM, and age > 75 years; Diabetic cataract (DC) group included 11 patients with diabetes mellitus (DM) and age < 65 years.; and Post‐vitrectomy cataract (PVC) group included 7 patients without a history of DM, who had vitrectomy surgery in the past 12 months. The sample preparation was based on Sp3 protocol (Single‐Pot, Solid‐Phase‐enhanced, Sample‐Preparation). Liquid chromatography online with tandem mass spectrometry was used for protein recognition and quantification. DIA‐NN software was applied for data analysis. Statistical analysis was performed on Perseus software.Results: In PCC samples, proteins with significant differential expression in ARC compared to DC and PVC were involved in pathways including actin binding, actin cytoskeleton reorganization, and small GTPase‐mediated signal transduction pathways. In AC samples, proteins with significant differential expression in ARC compared to DC and PVC were involved in actin binding and actin cytoskeleton reorganization pathways.Conclusions: Our findings suggested that actin‐binding pathway may be involved in ARC formation by causing abnormal lens fiber cell elongation and differentiation. The results of the present study revealed that small GTPase‐mediated signal transduction pathway exhibit lower expression in ARC than in the DC and PVC groups in PCC, and this may be linked to ARC formation through abnormal fiber cell organization, leading to lens opacification and cataract.
A novel artificial intelligence‐based classification of highly myopic eyes based on visual function and fundus features
Authors: Meng Jiaqi , Song Yunxiao , He Wenwen , Lu Zhong‐Lin , Chen Yuxi , Wei Ling , Zhang Keke , Qi Jiao , Du Yu , Lu Yi , Zhu Xiangjia 
Published: January 2025

Aims/Purpose: To develop a novel classification of highly myopic eyes using artificial intelligence (AI) and investigate its relationship with contrast sensitivity function (CSF) and fundus features.Methods: 616 highly myopic eyes of 616 patients were enrolled. CSF was measured using the quantitative CSF method. Myopic macular degeneration (MMD) was graded according to the International META‐PM Classification. Thickness of the macula and peripapillary retinal nerve fiber layer (p‐RNFL) were assessed by fundus photography and optical coherence tomography, respectively. Classification was performed by combining CSF and fundus features with principal component analysis and k‐means clustering.Results: With 83.35% total variance explained, highly myopic eyes were classified into 4 categories. The percentages of categories 1 to 4 were 14.9%, 37.5%, 36.2%, and 11.4%, respectively. CSF of the eyes in category 1 were the highest, followed by those in category 2 and then category 3, while the lowest was seen in category 4. Compared to those in category 1, eyes in category 2 presented higher percentage of MMD2 and thinner temporal p‐RNFL. Eyes in categories 3 and 4 presented significantly higher percentage of MMD≥3, thinner nasal macular thickness and p‐RNFL (p < 0.05). Multivariate regression showed category 4 had higher MMD grades, thinner macular and p‐RNFL thickness compared to category 3.Conclusions: We proposed an AI‐based classification of highly myopic eyes by integrating features from both visual function and fundus. It might be an important tool to comprehensively evaluate highly myopic eyes.
Regulation of the stress response of Müller cells after retinal detachment by amniotic membrane secretome in vitro
Authors: Hillenmayer Anna , Christian Wertheimer , Thomas Sterz , Azza Dammak , Armin Wolf 
Published: January 2025

Aims/Purpose: Müller cells play a key role in retinal homeostasis, structural support and immune response. They respond to retinal detachment and subsequent hypoxic conditions with increased stress response leading to structural changes. Due to the stabilizing properties of the amniotic membrane, first potential intraocular applications in vitreoretinal pathologies have been published. The aim was to investigate possible effects of amnion on Müller cells in the context of hypoxic damage after retinal detachment in vitro.Methods: Secretome was isolated from cryopreserved amniotic membranes. Immortalized Müller cells (MIO‐M1) with and without hypoxia treatment were incubated with the secretome and toxicity was excluded by a life/death assay and a cell death detection ELISA. A Wst‐1 and BrdU assay were performed for cell activity and proliferation; Western blot analysis and immunofluorescence staining were used to detect changes in protein expression of alpha‐SMA, SOX‐2 and GFAP.Results: Both hypoxia and the addition of amniotic secretome significantly reduced the metabolic activity of the cells. Incubation with secretome led to a statistically significant stagnation under both normoxic (p = 0.005) and hypoxic conditions (p > 0.01) in cell proliferation. Hypoxia led to increased expression of alpha‐SMA (p = 0.6), GFAP (p = 0.02) and SOX‐2 (p = 0.03) in Western blot analysis while secretome led to a normalization of alpha‐SMA (p = 0.03), GFAP (p = 0.1) and SOX‐2 (p = 0.001) under normoxic as well as hypoxic conditions. This observation was affirmed in immunofluorescence. Toxicity was excluded.Conclusions: In vitro simulation of hypoxic conditions in retinal detachment leads to stress responses of Müller cells. The amniotic secretome appears to regulate Müller cell behavior in vitro by supporting a stable phenotype under normoxic and hypoxic conditions. Further studies are needed to evaluate the clinical potential of the amniotic secretome after retinal detachment.
Correlation between diabetes and glaucoma risk: Insights from a population‐based glaucoma screening (NCT 05875090)
Authors: Monteiro Bernardo , Lima‐Cabrita Afonso , Lobo Vasco , Whitfield Rafael , Marques Rodrigo , Ourique Matilde , Varandas Teresa , Barão Rafael , Pazos Marta , Stalmans Ingeborg , Abegão‐Pinto Luís 
Published: January 2025

Aims/Purpose: To evaluate the association between Glaucoma referral and Diabetes in participants in a population‐based glaucoma screening using artificial intelligence (AI).Methods: Analysis of cohort characteristics at baseline contact (screening visit). Glaucoma referral was defined by intraocular pressure (IOP) ≥ 24mmHg or AI score ≥ 0.73. Diabetes information, including HbA1C, was collected from electronic medical records. Our analysis used descriptive and bivariate statistics, including chi‐square tests. Significance was p < 0.05 with 95% confidence intervals (CI).Results: Data from 837 participants were analyzed, comprising 54% males, with an average age of 62±4 years, across 11 functional units of Santa Maria Local Health Unit. A significant portion of participants had diabetes (69%), of which 8.3% were referred. AI scores were lower in diabetic patients compared to the non‐diabetic sub‐cohort (0.57 vs 0.61; p = 0,009). Intrigingly, while no correlation in the overall range of HbA1C with the AI score was detected, there was a detectable trend towards higher AI scores in decompensated diabetic patients (HbA1C > 9%; n = 10): (ρ = 0.591; CI‐0.083‐0.894; p = 0.072)Conclusions: Overall, diabetes diagnosis may influence glaucoma referral programs. AI threshold for referral may be adapted to the setting (particularly if a dual diabetic retinopathy and glaucoma screening is considered). Interestingly, AI appears to detect retinal/disc abnormalities in metabolic decompensated patients.
Recovery of the glaucoma service after the COVID‐19 pandemic; Barnsley glaucoma audit
Authors: Sharma Rohit , Awwad Mohamed , Firan Anne Marie 
Published: January 2025

Aims/Purpose: To audit the new referrals to the Glaucoma Unit at Barnsley Hospital for compliance with NICE guidelines and compare them to the 2020 audit.Methods: Between August and September 2023, we audited newly referred patients to the glaucoma service at Barnsley Hospital. We assessed the management of these patients based on the NICE guidelines, specifically in terms of recording visual acuity, Goldmann applanation tonometry (GAT), pachymetry, standard automated perimetry, gonioscopy, OCT optic disc and macula, and family history of glaucoma. We compared our findings to a previous audit conducted in October 2020.Results: We examined 30 newly referred patients. We conducted visual acuity, GAT, and OCT optic disc and ensured proper follow‐up requests for 100% of the patients. Additionally, 97% of patients underwent standard automated perimetry and pachymetry, while 87% had their family history recorded and underwent gonioscopy. We managed to discover treatable maculopathy in 40% of patients. Our compliance with NICE guidelines regarding pachymetry, gonioscopy, and family history recording was significantly higher than the 2020 audit.Conclusions: Our glaucoma unit has complied better with NICE guidelines during the recovery from the COVID‐19 pandemic. We've minimized virtual clinics and discovered silent progression in glaucoma patients.