bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between localized retinal nerve fibre layer defects and metabolic syndrome in nonglaucomatous eyes: A propensity score‐matched analysis
Authors: Jung Youn hea , Ohn Kyoung , Moon Jung Il 
Published: January 2024

Aims/Purpose: To investigate the association between metabolic syndrome and localized retinal nerve fibre layer (RNFL) defects in nonglaucomatous subjects.Methods: We examined 20 385 adults at the Health Promotion Center in Seoul St. Mary's Hospital between May 2015 and April 2016. Subjects with and without localized RNFL defects were 1:5 propensity score matched. Metabolic syndrome components, central obesity, elevated triglyceride, reduced HDL cholesterol, elevated blood pressure and elevated fasting glucose, were compared between two groups. Logistic regression was performed to investigate the association between RNFL defects and each metabolic syndrome component as well as the number of metabolic syndrome components.Results: Subjects with RNFL defects showed higher waist to hip ratio, systolic and diastolic BP, fasting blood glucose and HbA1c compared to those without RNFL defects before and after propensity score matching. The number of metabolic syndrome components was significantly greater in those with RNFL defects (1.66 ± 1.35) compared to those without (1.27 ± 1.32, p < 0.01). In multivariate logistic regression, the odds of RNFL defects were significantly increased in subjects with central obesity (OR = 1.53, 95% confidence interval [CI] = 1.11–2.13), elevated blood pressure (OR = 1.50, 95% CI = 1.09–2.05), and elevated fasting glucose (OR = 1.42, 95% CI = 1.03–1.97). Greater number of metabolic syndrome components was associated with higher odds of RNFL defects.Conclusions: The presence of localized RNFL defects in nonglaucomatous subjects is associated with metabolic syndrome components, including central obesity, elevated BP and elevated fasting glucose, suggesting that comorbid metabolic syndromes should be considered when evaluating subjects with RNFL defects.
Secondary full thickness macular holes following vitrectomy for rhegmatogenous retinal detachment: Clinical data, surgical outcome and prognosis
Authors: Schöneberger Verena , Jonas Rahul , Menghesha Leonie , Brockmann Claudia , Krohne Tim , Cursiefen Claus , Fuchsluger Thomas , Schaub Friederike 
Published: January 2024

Aims/Purpose: Formation of a full‐thickness macular hole (MH) after vitrectomy is extremely rare. Previous studies only included small numbers of cases. Aim of the present study was to describe course, functional prognosis and risk factors of secondary macular hole development following surgical treatment of a primary rhegmatogenous retinal detachment (RRD) in a large data set from two tertiary eye clinics.Methods: Formation of a full‐thickness macular hole (MH) after vitrectomy is extremely rare. Previous studies only included small numbers of cases. Aim of the present study was to describe course, functional prognosis and risk factors of secondary macular hole development following surgical treatment of a primary rhegmatogenous retinal detachment (RRD) in a large data set from two tertiary eye clinics.Results: Out of 9317 eyes following PPV 28 eyes (mean age 58.7 ± 9.6 yrs, 50% male, 60.7% right eyes) could be included. The interval between vitrectomy and MH formation was 46.9 ± 80.3 (range: 1–373) months. 15 eyes showed history of macular involving RRD, 7 macular sparing RRD. Sulphur‐hexafluoride (SF6) 20–25% was used as endotamponade in 18 cases for RRD repair, silicone oil (Sil5000® and Sil2000®) in 4 cases. Six cases were not assessable due to earlier external surgery. In secondary MH re‐PPV with SF6 20–25% endotamponade in 21 eyes (thereof with an ILM flap in 8 cases), Sil5000® in 6 eyes and Densiron® in one eye was performed. A primary closure rate of 88.2% with gas was achieved with a final best corrected visual acuity of 0.67 ± 0.99 logMAR. Degree of myopia, which correlated with functional results (p = 0.019) and earlier time of onset (p = 0.007), as well as timing of cataract surgery (p < 0.001) could be identified as risk factor for secondary MH development.Conclusions: Secondary MH after RRD repair is rare. In our study with the largest cohort studied so far, we can identify risk factors that lead to earlier MH formation. Myopia was shown to be a prognostic factor for functional outcome.
Molecular characterization of an iPSC line derived from a patient with cone‐rod dystrophy related to a mutation in the PROM1 gene
Authors: Puertas‐Neyra Kevin , Fernandez‐Bueno Ivan , Hernández‐Rodríguez Leticia , García‐Ferrer Yenisey , Gobelli Dino , Coco Rosa , de la Fuente Miguel Angel 
Published: January 2024

Aims/Purpose: The PROM1 gene encodes the protein Prominin‐1, which plays a crucial role in the morphogenesis of photoreceptor outer segments. The c.1354dupT mutation, associated with various inherited retinal diseases (IRD) phenotypes, leads to a premature stop codon. This study aimed to assess the silencing efficiency of reprogramming vectors and the expression of endogenous pluripotency genes in the iPSC line [DCB]‐FiPSC1‐Ep5F‐2.Methods: The iPSC line [DCB]‐FiPSC1‐Ep5F‐2 was generated from a patient with Cone‐rod dystrophy (CRD) linked to the c.1354dupT mutation in the PROM1 gene. iPSC colonies were stained using alkaline phosphatase (AP) blue membrane substrate. The c.1354dupT mutation was Sanger sequenced. To confirm the absence of episomal vector integration, quantitative PCR (qPCR) targeting a region common to all reprogramming vectors (within the EBNA1 gene) was conducted. Vector‐specific primer‐based quantitative reverse transcription PCR (qRT‐PCR) was used to assess the expression of reprogramming genes from the episomal vectors. Additionally, qRT‐PCR with gene‐specific primers was utilized to evaluate the expression of endogenous pluripotency genes. Untransfected fibroblasts served as the negative control, while fibroblasts transfected with the episomal vectors 72 h earlier were used as the positive control.Results: The iPSC line [DCB]‐FiPSC1‐Ep5F‐2 exhibited positive AP activity. The presence of the c.1354dupT mutation was confirmed. Furthermore, the number of copies of the EBNA1 gene was significantly lower in the generated iPSC line compared to the control. The relative mRNA expression of the reprogramming vectors was also significantly lower in the iPSC line, while the relative mRNA expression of the endogenous pluripotency genes was significantly higher than in the control.Conclusions: While further immunocytochemical characterization is necessary to fully ascertain iPSC pluripotency, the patient‐derived iPSC line [DCB]‐FiPSC1‐Ep5F‐2 shows promise as a disease model for personalized therapy development.
Human iPSC‐derived RPE cells implantation into minipig eye: Two weeks follow‐up study
Authors: Ardan Taras , Erceg Slaven , Artero‐Castro Ana , Studenovska Hana , Mueller Brigitte , Stieger Knut , Lytvynchuk Lyubomyr , Straňák Zbyněk , Ellederová Zdeňka , Juhás Štefan , Motlik Jan , Petrovski Goran 
Published: January 2024

Aims/Purpose: Retinal pigment epithelium (RPE) replacement is a very promising cell‐based therapy for retinal degenerative diseases including age‐related macular degeneration (AMD). RPE dysfunction is the main cause of secondary damage to the photoreceptors. We hereby present RPE implantation into the minipig eye with a 2‐week follow‐up.Methods: Cultured human iPSC‐derived RPEs (iRPE) on nanofibrous membranes, with properties very similar to Bruch's membrane, were characterized for expression of differentiation and polarization markers using immunohistochemistry. The implantations of iRPE‐scaffolds were carried out into the minipig eyes using 3‐port pars plana vitrectomy. Due to the xenogeneic transplantation of human cells into minipig eyes, tacrolimus immunosuppression therapy was used. At the 2‐week follow‐up from transplantation, non‐invasive OCT and fundus camera examinations of the implanted iRPE‐scaffolds were performed. Consequently, euthanasia, histological and immunohistochemical investigations of the implanted retina were performed.Results: OCT and fundus camera examinations revealed successfully implanted iRPE‐scaffolds into the subretinal space with a healthy neuroretina above the implant, and healed retinotomy, without immune cell reaction against the implant. Histological and immunohistochemical investigation of the iRPE implants and adjacent retina showed structurally healthy iRPE‐scaffold implant and neuroretinal cells above the implant.Conclusions: RPE cell therapy for replacement of diseased RPEs by ex vivo cultured Ipsc–RPEs on highly permeable nanofibrous membranes supports the survival of adjacent photoreceptors and thus positively affects the structural changes seen in retinal neurodegeneration.
Proteome changes in ferroptosis‐induced retinal pigment epithelial cell death in age‐related macular degeneration
Authors: Qu Sichang , Perumal Natarajan , Pfeiffer Norbert , Grus Franz , Manicam Caroline 
Published: January 2024

Aims/Purpose: Ferroptosis is known to be involved in the pathogenesis of age‐related macular degeneration (AMD). We elucidated the potential roles and related pathways of ferroptosis in an in vitro AMD cell culture model and the mass spectrometry (MS)‐based proteomics analysis.Methods: To mimic ferroptosis in AMD, ARPE‐19 cells were treated with erastin (ERS; 1, 2, 5 and 10 μM) or RSL3 (1, 2, 4, and 6 μM) for 24 h. Cells without treatment were used as control. Cell viability and glutathione peroxidase 4 (Gpx4) expression levels were used to determine the optimal AMD model. The MS‐based proteomics approach was employed to profile the protein expressions in ferroptotic RPE cells compared to controls. Next, bioinformatics analysis identified the significantly affected functions and pathways of the differentially expressed proteins.Results: Cell viability and Gpx4 expression levels of ARPE‐19 cells were decreased in a dose‐dependent manner after induction with ERS (1, 2, 5 and 10 μM) and RSL3 (1, 2, 4, and 6 μM). Doses corresponding to ~60% cell viability (5 μM ERS and 2 μM RSL3) were selected for the proteomics analysis. A total of 1356 proteins were identified in all groups, with 300 and 209 significantly (p < 0.05) differentially expressed proteins in the ERS and RSL3 group, respectively. The induction of ferroptosis in this optimized model with ERS (p = 6.3 × 10−3) and RSL3 (p = 1.5 × 10−4), and disruption of iron homeostasis signalling pathway (p = 1.9 × 10−4 in RSL3) were further confirmed by proteomics analysis. Iron metabolism‐related proteins ferritin light chain and heme oxygenase 1 were significantly up‐regulated in the RSL3 group. Notably, a large cluster of proteins were highly significantly implicated in the eukaryotic initiation factor 2 signalling pathway (p = 2.0 × 10−30 in ERS and 1.0 × 10−5 in RSL3), which was correlated with ferroptosis. Furthermore, the upregulation of autophagy‐related Ras‐related protein Ral‐A and involvement of mTOR signalling pathway were found in both groups (p = 3.2 × 10−6 in ERS and p = 1.9 × 10−3 in RSL3).Conclusions: In summary, this study established an optimum model for ferroptosis and demonstrated that it is involved in RPE cell death and is autophagy‐dependent. Our results also suggested that the disruption of iron uptake and intracellular storage in RPE cells are involved in AMD progression.
Be mindful of the blood glucose measurement: The relevance of blood glucose in the eye emergency department
Authors: Nazeer Shanees , Stone Amy 
Published: January 2024

Aims/Purpose: Diabetic eye disease is a leading cause of blindness worldwide and diabetes‐related eye conditions are frequent presentations in Eye Emergency Departments (EEDs). Early detection and intervention of inadequate blood glucose control in the EED could be sight‐saving.The aims of this study are to determine the:
prevalence of pre‐existing diabetes mellitus (DM) in the EED.
prevalence of suboptimal (HbA1c 53–70 mmol/mol) or poor (HbA1c >70 mmol/mol) glycaemic control in the EED.
proportion of diabetes patients with this diagnosis documented in the EED.
proportion of EED patients at risk of undiagnosed diabetes.
number of EED patients that had a capillary blood glucose measurement (BgM).

Methods: A retrospective review of 683 patients attending the EED over 10 consecutive weekdays at Manchester Royal Eye Hospital, Manchester, United Kingdom. The following parameters were assessed:
EED documentation: patient age, gender, presentation, diagnosis, management plan and whether a BgM was done.
General Practitioner records: diabetes diagnosis cross‐referenced with EED documentation.
If diabetes patients: diabetes type, duration, and glycaemic control.
Potentially undiagnosed diabetes.

Results: The prevalence of diabetes patients was 9.5%–64.6% of these patients had diabetes documented in EED and 1 had a capillary BgM. 70.7% of diabetes patients had pre‐existing suboptimal [33.8%] or poor [36.9%] glycaemic control. 8.5% of patients were considered high‐risk for undiagnosed diabetes of which 1 had a BgM.Conclusions: There is a high prevalence of diabetes patients in the EED, and most have inadequate glycaemic control. This makes the EED an important setting to detect patients at high risk of diabetes‐related ocular disease and complications. BgM testing for all suspected patients is a quick test to allow earlier detection and intervention of inadequately controlled diabetes and reduce the risk of diabetes‐related vision loss.
The impact of elevated lipoprotein a levels on retinal vein occlusion in young individual: Case report with 7 months follow‐up
Authors: Smiri Meryam , Haddoum Karim Nassim , Mansouri Abdeldjalil , El Sanharawi Mohamed 
Published: January 2024

Aims/Purpose: Branch retinal vein occlusion (BRVO) occurs when a branch of the retinal vein becomes obstructed. The aim of this study case was to provide insights into the potential role of Lipoprotein (Lp) (a) in the pathogenesis of BRVO.Methods: Case of a 47‐year‐old woman with no significant ophthalmological or general medical history, except the use of oral contraception and smoking habits. Presented to the emergency care after 5 days of experiencing a sudden vision loss in her right eye.Results: The ophthalmological examination revealed a visual acuity of 10/10 on the left (OS) and VBLM/10 on the right eye (OD). Slit lamp and Fundus examination showed on OD a relative afferent pupillary defect and the classic features of acute retinal branch vein occlusion, including tortuous veins, capillary occlusion, papillary and macular oedema and haemorrhages. While all was normal in OS. A comprehensive ophthalmic examination was conducted, including fluorescein angiography and optical coherent tomography that showed no abnormal vessel growth at this stage. Then, the indication for a dexamethasone intravitreal implant has been made along with panretinal photocoagulation (PRP) in the ischaemic areas. More, discontinuing oral contraception, the serum concentrations of specific antibodies, as anticardiolipin and antiphospholipids, as well as homocysteine and Lp (a) levels. The blood tests yielded negative results except for the abnormal plasma level of lipoprotein (a), which was measured at 900 mg/L. After 2 months of follow‐up. The visual acuity in OD was measured at 9/10. Moreover, the restoration of normal macular thickness after 4 months. However, at 6 months follow‐up, the appearance of a neovascularization adjacent to the previously laser‐treated area. As a result, a series of closely spaced PRP was performed along with an intravitreal anti‐vascular endothelial growth factor. After 1 month, a complete disappearance of the neovascularization was observed.Conclusions: Identification of independent and highly predictive risk factors for BRVO is still a big challenge. The main goals are the preservation of visual acuity and the prevention of relapses. This case report emphasizes the importance of incorporating a systematic Lp (a) testing into clinical practice, even in young individual.
Ridge‐shaped peripapila dry, fluid associated, and self‐resolved fluid associated presentations
Authors: Sancho Ainhoa Mimendia , Maeso Alicia Traveset , Bertomeu Pau Cid , Costales‐Mier Felipe 
Published: January 2024

Purpose: We aim to describe three different clinical presentations of ridge‐shaped peripapilla.Methods: A series of case reports. Fundus images, autofluorescence (AF), optical coherence tomography (OCT) Angio‐OCT, indocyanine (ICG) and fluorescein angiography (FA) was performed.Results: The first case is a 55‐year‐old woman, that was referred to the clinic due to central visual acuity loss in her left eye. RPE atrophy, and a scleral nasal protrusion (same configuration on both eyes) with a thinned overlying choroid, with subretinal fluid around the peripapillary area and the submacular area was observed on the OCT. FA and ICG with no hotspots, nor any dilated choroidal vascular pattern was observed, nor any signs of a neovascular membrane (NVM). On FA patched hypoAF was observed around the nasal retina. Posterior staphyloma was corroborated with ocular echography. Four months after initial presentation, fluid resolved spontaneously, visual acuity improved, but fundus pigmentary defects remained unchanged. The second case is a 60 year‐old woman (OS), peripapillary subretinal fluid was observed on the oct, choroidal thinning and scleral protrusion nasal to the optic disc. The third case, a 70‐year‐old male (OD), showed a temporal whitish lesion, engorged scleral protrusion was seen on oct, with overlying RPE atrophy, very thinned choroid and retina, without subretinal fluid.Conclusions: Pathologic myopia is defined as myopic refractive error greater than −6.00 diopters. Many chorioretinal findings have been described regarding this condition, one of these is a ridge shaped peripapilla, a form of scleral protrusion around the optic disc. These patients presented on the fluorescein angiography and OCT findings, signs of protrusion of the sclera that seemed to result in overlying choroidal thinning with choroidal blood flow disturbances, and consequent RPE atrophy, leading to the subretinal fluid accumulation.
Comparative analysis of the effects of limbal and adipose‐derived mesenchymal stem cell conditioned media on oxidative stress‐induced damage in retinal pigment epithelial cells
Authors: Aydemir Ayse Dilara , Canbulat Zehra , Hasanreisoğlu Murat 
Published: January 2024

Aims/Purpose: The purpose of this investigation was to evaluate the impact of adipose and limbal tissue‐derived mesenchymal stem cell‐conditioned media on survival, and inflammation in H2O2‐induced retinal pigment epithelial cells.Methods: Following national regulations and with the approval of the Koç University Ethics and Investigation Committee, human limbal (L) and adipose‐derived (Ad) mesenchymal stem cells (MSCs) were isolated from cadaveric corneaoscleral rims from donors that originated from the cornea bank of Ministry of Health in Turkey and adipose tissue from discarded human liposuction surgery specimens, respectively. Conditioned medium (CM) that obtained by culturing MSCs in absence of serum was concentrated by filtration. Following a 24‐h pre‐treatment with H2O2, retinal pigment epithelial (RPE) cells were treated with MSC‐CM. Groups were defined as follows: Control, H2O2‐treatment (OS), OS‐Basal Medium, OS‐AdMSC‐CM and OS‐LMSC‐CM. Cell viability was assessed using MTT assay. Gene expression levels of pro‐ and anti‐inflammatory cytokines were analysed by qRT‐PCR.Results: Based on MTT assay, H2O2 inhibited the growth of RPE cells with IC50 values of 150 μM at 24 h. We found that MSC‐CM attenuated H2O2‐induced loss of cell viability. In comparison to the OS group, the LMSC‐CM and AdMSC‐CM treatments demonstrated significantly decreased levels of IL‐6, IL‐8, IL‐10 and TGF‐β1 gene expression.Conclusions: MSC‐CM ameliorated H2O2‐induced retinal pigment epithelial cell damage by alleviating inflammation.
Therapeutic potential of photobiomodulation on hydrogen peroxide‐induced oxidative damage in retinal pigment epithelial cells
Authors: Aydemir Ayse Dilara , Canbulat Zehra , Hasanreisoğlu Murat 
Published: January 2024

Aims/Purpose: Photobiomodulation (PBM) is a cutting‐edge therapeutic method for restoring the functioning of injured mitochondria in experimental settings. Our goal was to find out how 780 nm PBM therapy affected the apoptosis and cell survival of hydrogen peroxide‐treated retinal pigment epithelial cells.Methods: After being treated with 150 μM hydrogen peroxide for 24 h, the retinal pigment epithelial (RPE) cells were exposed to continuous wave laser radiation with the following parameters: wavelength of 780 nm, power density of 140 mW/cm2, 65 mW/cm2 and 40 mW/cm2 and duration of 10 min and 30 min. Furthermore, light therapy was given to untreated control cells to check PBM effect on healthy group. After PBM therapy in a time‐dependent manner, cell survival and apoptosis were assessed by MTT assay and Annexin V/PI staining, respectively.Results: Based on MTT findings, PBM showed no obvious effect on cell viability in H2O2‐treated RPE cells, while after 48 h post‐PBM incubation, cell viability was dramatically improved. It was significantly increased at the power density of 140 mW/cm2 for 30 min application without unacceptable effect on control cells. RPE apoptosis was strikingly decreased in post‐PBM incubation group compared to H2O2‐treated group in a time‐dependent manner, as detected by flow cytometry.Conclusions: As a result, photobiomodulation supported its potential utility in the prevention and treatment of retinal disorders associated with oxidative stress by promoting cell survival and reducing apoptosis under oxidative stress.
Tomographic findings in the retina of unvaccinated patients with COVID pneumonia: Prospective longitudinal study
Authors: Lucas Carlos Enrique Monera , Diaz Manuel Vicente Baeza , Quesada Jose Antonio , Pineda Adriana Lopez , Martinez Cristian Fernandez , Toldos Jose Juan Martinez , Guillén Vicente Francisco Gil 
Published: January 2024

Aims/Purpose: There is no definitive evidence on the extent of SARS‐CoV‐2's effect on the retina. This study aimed to determine if the natural history of SARS‐CoV‐2 infection influences tomographic findings in the retina of patients with COVID‐19 pneumonia.Methods: Prospective cohort study of patients hospitalized with COVID‐19 pneumonia. Patients underwent ophthalmological explorations and optical coherence tomography during the acute phase of the infection and at 12 weeks' follow‐up. Primary outcomes were central retinal thickness and central choroidal thickness, which were compared longitudinally and with non‐COVID‐19 historical controls.Results: No statistically relevant differences were observed in the longitudinal analysis of the thickness of the central retina (p = 0.056), central choroid (p = 0.99), retinal nerve fibre layer (p = 0.21) or ganglion cell layer (p = 0.32). Patients with acute COVID‐19 pneumonia showed significantly greater central retinal thickness than non‐COVID controls (p = 0.006).Conclusions: In conclusion, tomographic measures of the retina and choroid are not influenced by the phase of COVID‐19 infection and remain stable during 12 weeks. Central retinal thickness may increase in the acute phase of COVID‐19 pneumonia, but more epidemiological studies using optical coherence tomography in early stages of the disease are needed.References1. Invernizzi A, Torre A, Parrulli S, Zicarelli F, Schiuma M, Colombo V, Giacomelli A, Cigada M, Milazzo L, Ridolfo A, Faggion I, Cordier L, Oldani M, Marini S, Villa P, Rizzardini G, Galli M, Antinori S, Staurenghi G, Meroni L. Retinal findings in patients with COVID‐19: Results from the SERPICO‐19 study. EClinicalMedicine 2020 Oct;27:100550. doi: 10.1016/j.eclinm.2020.1005502. Patel NS, Moon JY, Katz R, et al. Retrospective Analysis of Retinal Imaging in COVID‐19 Positive Patients at a Tertiary Eye Care Center. Clin Ophthalmol 2021 Sep 3;15:3727–3731. doi: 10.2147/OPTH.S309346