bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical, phenotypic and genetic characteristics of macula‐sparing stargardt disease
Authors: Hristova Rozaliya , Shahinyan Lilit , Kuneva Yoanna , Petkova Iva , Veleva Nevyana 
Published: January 2024

Aims/Purpose: Fundus flavimaculatus and Stargardt's disease are monogenic but heterogeneous disease entities leading to loss of central vision in adolescence, caused by more than 490 mutations in the ABCA4 gene. We herein report the clinical, phenotypic and genetic characteristics of adult onset fovea sparing Stargardt's disease.Methods: Two Caucasian males in their 40s presenting with complaints of paracentral scotomata underwent complete ophthalmic exam, visual field testing, optical coherence tomography (OCT), fundus autofluorescence (FAF), fluorescein angiography (FA), electroretinography (ERG) and genetic testing.Results: Visual acuity was 20/20 in both patients with normal IOP. Anterior segments were unremarkable. Posterior segment examination revealed pigment mottling in the macula with ring‐shaped perifoveal chorioretinal atrophy and numerous white deposits in the mid‐periphery. Visual fields confirmed the paracentral ring scotomata. OCT demonstrated concentric perifoveal loss of outer retinal layers with foveal sparing simulating oedema. Extensive hyperautofluorescence in the area of chorioretinal atrophy was revealed by FAF. Full‐field ERG confirmed incomplete loss of cone bioelectrical activity with preserved morphology of the foveal peak and normal rod function. Genetic testing discovered several pathogenic mutations in both patients with shared ABCA4 c.5603A>T, p.(Asn1868Ile), a risk factor mutation. None of the mutations of our patients were previously reported in foveal sparing Stargardt's disease.Conclusions: The variant ABCA4 c.5603A>T, p.(Asn1868Ile) might be associated with foveal sparing Stargardt's disease. Further population studies are need to confirm this association.
Crosstalk between oxidative stress, inflammation, angiogenesis and apoptosis in diabetic macular edema
Authors: Andrés‐Blasco Irene , Gallego‐Martínez Alex , Palos Sarah Karam , Lleó Antonio , Casaroli Ricardo , Di Lauro Salvatore , Millas Sara Crespo , Pinazo‐Duran Maria Dolores 
Published: January 2024

Aims/Purpose: To evaluate molecules involved in oxidative stress (OS), inflammation, angiogenesis, and apoptosis, and discern which of these are more implicated in diabetic retinopathy (DR) and diabetic macular edema (DME) by investigating the correlation between them in the plasma (PLS) and vitreous humour (VIT), and examining data obtained from ophthalmological examinations.Methods: Type 2 diabetic (T2DM) patients with DR/DME (DRG/DMEG n = 112) and non‐DM subjects as the surrogate controls (SCG n = 48) were selected. Blood samples were processed to determine the glycaemic and lipid profiles, C reactive protein, malondialdehyde (MDA), 4‐hydroxynonenal (4HNE), superoxide dismutase (SOD), catalase (CAT) levels and total antioxidant capacity (TAC). In addition, interleukin 6 (IL6), vascular endothelial growth factor (VEGF), and caspase 3 were assayed. The VIT samples were collected to measure the expression levels of all the above‐mentioned molecules.Results: Our findings support the presence of molecules involved in OS, inflammation, angiogenesis, and apoptosis in the PLS and VIT samples from T2DM. In PLS from DRG, there was a decrease in the antioxidant load and an increase in pro‐angiogenic molecules, but an increase in pro‐oxidants and a decline in antioxidants intravitreally. In PLS from DMEG, pro‐oxidants and pro‐inflammatory molecules were augmented and the antioxidant capacity diminished, but the pro‐oxidants increased, and antioxidants decreased intravitreally. Furthermore, we found a positive correlation between the PLS‐CAT and the VIT‐SOD levels in DRG, and a negative correlation between the PSD‐4HNE and the VIT‐TAC levels in DMEG.Conclusions: We conclude that hyperglycaemia induces anomalies in biochemical pathways with crosstalk between them; MDA, 4HNE, TAC, VEGF, and IL6 are promoters of the clinical manifestations of PDR and DME. The above molecules have been selected as biomarker candidates for distinguishing T2DM patients at risk of DR, DME and vision loss.
The global incidence and prevalence of Acanthamoeba keratitis
Authors: Ceccarelli Francesca , Afflitto Gabriele Gallo , Han Yuyi , Turco Maria Vittoria , Aiello Francesco , Nucci Carlo 
Published: January 2024

Aims/Purpose: To assess the global incidence and prevalence of Acanthamoeba keratitis (AK).Methods: The review protocol was prospectively registered in PROSPERO (CRD42022363243) and the Cochrane Handbook was followed in the conduction of the analysis. The study included male and female participants worldwide (>15 years old). PubMed, Scopus, Web of Science, EMBASE, and CINHAL were the sources of data. The incidence of AK was determined by calculating the number of cases per centre per year, while the prevalence was evaluated for the entire population and the entire population of patients with non‐viral infectious keratitis. Based on the population prospects of the United Nations, actual and provisional estimates of the global epidemiological burden of AK, covering a period of up to 50 years, were provided.Results: A total of 134 articles were included in the analysis. The analysis revealed a median incidence of 2.42 (95% CI: 1.67, 3.8) new cases of AK per centre per year, without any statistically significant difference among the continents (p = 0.1411). The percentage of AK cases within the total number of MK cases was found to be 1.62% (95% CI: 1.51, 1.74). Using a random effect model, the prevalence of AK in relation to the entire population was estimated to be 0.0003% (95% CI: 0.0001; 0.0006). The projected increase in the total and provisional numbers of AK cases indicates a rise of 20.4% (2003 AK cases) in 2053 and 24.8% (2076 AK cases) in 2073, compared to the baseline of 2023 (1663 AK cases).Conclusions: Although rare, AK is a significant condition that is projected to increase in prevalence by up to 24% over the next 50 years.
Transcriptional profilling to identify the inhibitor effect of trehalose as an alternative natural therapeutic agent on pterygium cells
Authors: Yılmaz Uğur , Durkal Yasin , Tokgün Onur , İnci Kubilay 
Published: January 2024

Aims/Purpose: The aim of this study to investigate transcriptome analysis of the inhibitory effects of trehalose on changing expression of regulator genes in pterygium development.Methods: Human primary pterygium cells and normal conjunctiva cells were isolated from the pterygium and conjunctiva tissues of six individuals, three of whom were men and three of which were females. The MTT test was used to investigate cell proliferation in pterygium treated with different concentrations dosage of trehalose. Differential mRNA expression in pterygium cells following indicative treatment was measured using an mRNA microarray and evaluated using GO and KEGG pathways. In addition, we employed QRT‐PCR to confirm the expression levels of genes linked to pterygium pathogenesis.Results: We have found that pterygium cells are more sensitive to trehalose treatment than conjunctival cell. In total, 419 probe were differentially expressed pterygium cells treated with trehalose compared with paired non‐treated pterygium cells. Gene‐Enrichment and Functional Annotation analysis indicated that differentially expressed RNAs were associated with cellular process including especially fibroblastic cell migration, sterol biosynthetic process (p < 0.00034), extracellular matrix recomposition (p < 0.000740288), cell proliferation (p < 0.004391252), steroid biosynthetic process (p < 0.00029971). Composed of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein–protein interaction (PPI), and gene set enrichment analysis (GSEA) analysis, bioinformatic analyses showed that four hub genes were upregulated (MSMO, RANBP3L, DHCR7, CCL2) and five were downregulated (NR4A1, TENASTN C, CXCL8, CXCL12, ADAMTS12). Additionally, QRT‐PCR is used to confirm the expression of particular genes. Consistent with these findings, the migration capability of pterygium cells decreased after treatment of trehalose for 24 h.Conclusions: We consider that this study provides a scientific basis for elucidating the effect of trehalose on the pathogenesis of pterygium and exhibited that trehalose affects cellular processes that have essential roles in the progression and development of pterygium.
Effect of melatonin‐induced exosomes on proregenerative and antifibrotic pathways involved in corneal scarring
Authors: Tasa Burcugül Altuğ , Soykan Merve Nur , Sarıboyacı Ayla Eker , Ozalp Onur , Atalay Eray 
Published: January 2024

Aims/Purpose: Melatonin is a time‐and‐concentration dependent pro and antiinflammatory agent that also regulates cell proliferation, migration, angiogenesis, fibrosis, and extracellular matrix synthesis. This study aims to assess the effect of exosomes obtained from melatonin‐treated human limbal mesenchymal stem cells (hLMSCs) on naive hLMSCs and ascertain their influence on antifibrotic and proregenerative pathways involved in corneal scarring.Methods: hLMSCs were harvested from the eye bank of Eskişehir Osmangazi University Hospital and were subsequently isolated and characterized. We then treated hLMSCs (Mel‐treated hLMSCs) with varying concentrations of melatonin followed by isolation and characterization of the procured exosomes. These exosomes were added to enrich cell culture media of naïve hLMSCs (Mel‐exo‐treated hLMSCs) to examine their antifibrotic and proregenerative effects. The expression of miR155, miR29 Transforming Growth Factor Beta 1 (TGFβ1), TGFβ3, Peroxisome Proliferator‐Activated Receptor Gamma (PPARγ), and Alpha‐Smooth Muscle Actin (α‐SMA) miRNA and genes were compared between Mel‐treated hLMSCs and Mel‐exo‐treated hLMSCs by using Real‐Time PCR.Results: TGFβ3 expression increased dramatically in response to Mel‐exo, while the increase in TGFβ1 expression was only minimal in correlation with levels of miR155 expression. Likewise, PPARγ expression was increased while an inhibition was observed in α‐SMA expression and miR29 expression in Mel‐exo‐treated hLMSCs compared to Mel‐treated hLMSCs.Conclusions: Melatonin treatment of hLMSCs resulted in expression of exosomes that could drive naïve hLMSCs in favour of antifibrotic and proregenerative effects as evidenced by higher TGFβ3 and PPARγ expressions and inhibition of α‐SMA. This approach could prove beneficial in cornea and ocular surface tissue engineering applications.The authors acknowledge the support from Eskisehir Osmangazi University, Scientific Research Projects (Grant ID: TOA‐2022‐2458).
Kruppel‐like factor 5 (KLF5) as a genetic factor associated with the etiopathogenesis of Keratoconus
Authors: Regueiro Uxía , Pastoriza Yaiza , López‐López Maite , Venema Wouter , Lema Isabel , Kuiper Jonas , Wisse Robert 
Published: January 2024

Aims: To analyse expression and genotype of Krüppel‐Like Factor 5 (KLF5) gene in the corneal epithelium of eyes with Keratoconus (KC) compared to normal eyes (controls); as well as, to determine the effect of several pro‐inflammatory cytokines on the KLF5 expression by an in vitro study.Methods: 64 corneal epithelium samples from 53 KC and 11 controls were included in this study. KC samples were collected from patients who received crosslinking epi‐off or penetrating keratoplasty for their mild to advanced KC. Control samples were collected from dead donors with healthy corneas. Molecular determinations to measure KLF5 expression and genotype on these samples were performed respectively by qPCR and TaqMan targeting the SNP of interest (rs17285550). In addition, using a cell line of healthy corneal epithelial cells, incubations with increasing concentrations of interleukin 6 (IL6), interleukin 1 beta (IL1β), and tumour necrosis factor alpha (TNFα) were performed to determine the KLF5 response to a pro‐inflammatory environment. KLF5 expression in the stimulated cell cultures was assessed by qPCR analysis.Results: KC samples evidenced significantly higher levels of KLF5 gene expression than the controls (p < 0.0001). The GG genotypes showed an upward tendency for higher expression of KLF5 in the KC group. Higher IL6, IL1β, and TNFα concentrations contribute to a significatively KLF5 overexpression in corneal epithelial cell cultures.Conclusions: Overexpression of KLF5 in the corneal epithelium of KC patients and its upregulation against a proinflammatory microenvironment, could lead to an inadequate epithelial barrier function that destabilizes the surrounding corneal layers and contributes to the KC pathology. KLF5 represents a promising target for gene therapy in KC.
Serum microRNAs as biomarkers associated with the course of diabetic macular oedema
Authors: Aragona Emanuela , Arrigo Alessandro , Aguennouz M' Hammed , Aragona Pasquale , Bandello Francesco 
Published: January 2024

Aims/Purpose: Intravitreal drugs are powerful therapies for diabetic macular edema (DME), but the clinical course and the response to treatments still remains unpredictable. MicroRNAs (miRNAs) represent a class of small molecules associated with the regulation of several metabolic pathways, including diabetes. However, their use in the clinical setting of DME is limited by lack of data regarding the correlation with clinical and imaging features. In the present study we evaluated some miRNAs profiles obtained by serum samples of newly diagnosed DME patients.Methods: Prospective study, including baseline visit (V0), a 4‐months visit (V1) and a 12‐months visit (V2). At V0 patient underwent serum sampling, imaging was repeated at every study visit. Enriched serum microRNAs were extracted and real‐time PCR was performed. OCT features were used to assess the severity and progression of the disease.Results: We collected data of a cohort of type 1 and type 2 diabetic patients. All the patients presented DME and were naïve to intravitreal treatments. The follow‐up was of 12 months. Diabetes‐related miRNAs were found up‐ or downregulated and associated with the course of DME (resolved/recurrent/persistent). Correlations were found with imaging biomarkers.Conclusions: On the basis of these findings, serum miRNAs assessment is a feasible and clinically relevant assessment to be performed in the diagnostic work‐up of diabetic patients affected by DME. MiRNAs might pave the basis for customized treatment strategies to optimize the management of DME.References1. Mastropasqua R, Toto L, Cipollone F et al. Role of microRNAs in the modulation of diabetic retinopathy. Prog Retin Eye Res. 2014.2. Arrigo A, Aragona E, Capone L et al. Foveal Eversion: A Possible Biomarker of Persistent Diabetic Macular Edema. Ophthalmol Ther 2021.3. Arrigo A, Capone L, Lattanzio R et al. Optical Coherence Tomography Biomarkers of Inflammation in Diabetic Macular Edema Treated by Fluocinolone Acetonide Intravitreal Drug‐Delivery System Implant. Ophthalmol Ther 2020.4. Arrigo A, Aragona E, Battaglia Parodi M, Bandello F. Quantitative approaches in multimodal fundus imaging: State of the art and future perspectives. Prog Retin Eye Res. 2023.
Leber hereditary optic neuropathy. The Dutch approach
Authors: Lushchyk Tanya , van Everdingen Judith 
Published: January 2024

Aims/Purpose: To share the structure of care for patients with Leber Hereditary Optic neuropathy (LHON) in the Netherlands. This includes the role of Expertise centers in coordinating rapid diagnosis and start of treatment, as well at the introduction of a specific database to track data of patients with LHON.Methods: Dutch LHON Expertise centres are organized to act as central points for patient referrals from regional hospitals with the aim to speed up the diagnostics and treatment of LHON patients. The database of Dutch LHON patients has been created and is online today, to provide demographical, epidemiological, clinical characteristics and effects of treatment with Idebenone on disease progression.Results: Three LHON Expertise centers provide fast diagnostic, coaching and treatment services in the whole of the Netherlands. Patient referral is done easily due to the small geography. A DNA test on primary and non‐primary mtDNA mutations is performed as standard, including the DNAJC30 gen. Additional parameters are obtained to monitor disease progression: Visual Acuity Score by ETDRS letters chart, HRR colour tests, OCT of ganglion cell layer and retinal neurofibral layer, Visual field by Goldmann kinetic perimetry or Humphry static perimetry. All patients have access to a social worker. They are provided with a flyer about LHON disease and contact details of the relevant patient association.Conclusion: A thoroughly organized clinical path for LHON patients provides rapid diagnostics and start of treatment. Patients referrals is done easily and treatment delay minimized. The centralization of Dutch LHON patients in three expertise centres enables us to maintain a central database with important clinical and epidemiological data. This information is relevant to optimize current therapy options with Idebenone and also for supporting future studies on novel therapy options.
Diagnosis of non‐strabismic binocular vision anomalies ‐ why are there so many different approaches?
Authors: Evans Bruce 
Published: January 2024

Aims/Purpose: To review and contrast the main approaches for diagnosing and managing non‐strabismic binocular vision anomalies (BVA), including decompensated heterophoria, binocular instability, accommodative anomalies.Methods: A literature search was undertaken to determine the main methods of diagnosing and correcting/treating BVA. Findings from leading textbooks were compared with research literature. The literature was filtered by country and by profession to investigate factors that may contribute to diversity of approaches.Results: The literature searches reveal marked variation in the methods recommended for diagnosing BVA. There is agreement concerning the interventions available (refractive correction, prisms, eye exercises, surgery). However, there are diverse opinions concerning the criteria for determining when treatment is required. For refractive correction or prisms, the evidence suggests that different methods used for determining the correction required will lead to different prescriptions. To some extent, the variation can be attributable to national differences. However, even within some countries, very diverse diagnostic criteria and prescribing philosophies are evident. A wide variation sometimes is present within as well as between the different eyecare professions.Conclusions: Research with standardized patients indicates, clinical practice is likely to be even more varied than the review indicates. The wide variation means that even within a country/profession, a patient may consult two practitioners and receive different diagnoses, or dissimilar interventions. One reason for the variation is likely to be the historical influence of prominent clinicians/teachers. Evidence‐based scrutiny should be applied to old methods as well as new. Research is required that compares different philosophies for diagnosis and prescribing.
School eye screening survey in the Gaza Strip/Palestine
Authors: Mikki Nahed 
Published: January 2024

Aim: To estimate prevalence of vision impairment and associated refractive error in basic school children in the Gaza Strip in the State of Palestine. The study will also provide an estimate of the use of corrective spectacles among children with refractive error. Associated factors like age, sex, type of school, residence, parents’ education, parents’ occupation, other indicators of socio‐economic status and vision problems in the child and the family will be studied.Methods: This is the first comprehensive study of school children vision impairment in the Gaza Strip.The method is an adaptation of WHO's Assessment of the prevalence of visual impairment attributable to refractive error or other causes in school children (RESC) methodology.Study population are students in the first and the nineth grades from public and United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) schools in the Gaza Strip.The sampling unit (cluster) was classes in the target grade levels and the strata were grade (grade 1 and grade 9), type of school (public and UNRWA) and school gender (all male, all female and co‐ed schools).Based on an expected prevalence of blindness of 20% among target population, 95% confidence level, 20% non‐response rate (refusals and absent students/total number of students), 3.4% margin of error and a design effect of 1.35 to account for clustering, a sample size 1100 students was determined. 28 classes were selected with probability proportionate to size from a list of classes of target grades along with number of children enrolled within each class in public and UNRWA schools in the Gaza Strip.Results: The actual number of students was 1094 in 15 UNRWA and 13 public schools (15 first grade classes and 13 ninth grade classes). The total non‐response rate was 12%.Data collection was completed on 18.5.2023. I did not have time to clean and analyse the data. Results will be presented at the conference.Conclusions: Conclusions will be presented at the conference.
The predictive value of parameters of optic disk in evaluating the progression of myopia
Authors: Huseva Yuliya , Zharikova Olga 
Published: January 2024

Aims/Purpose: To analyse the parameters of the optic nerve head (ONH) as markers of the progression of myopia with the usage of optical coherence tomography (OCT).Methods: 72 patients (144 eyes) aged 9–57 years with myopia were investigated. The standard OCT parameters of the ONH, the ovality index (OI), the zone of parapapillary atrophy (PPA), location of the lamina cribrosa (LC) of the sclera and the trunk of the central retinal vessels (CRV) were evaluated. Data was statistically approved.Results: A positive correlation between the axial length (AL) and the optic disc cup area, its horizontal and vertical diameters was found. Whilst the volume and the depth of the optic disc cup increased till the AL reached a certain critical value (26.3 mm) with subsequent reduction. An inverse correlation between the AL and the neuroretinal rim area, volume and rim/disc ratio was revealed. These changes in the ONH can be explained by scleral remodelling during elongation of the eye. Formation of γ‐zone PPA and an increase in the β‐zone PPA was accompanied by the tendency of thinning of the retinal nerve fibre layer (RNFL) in the inferior, nasal‐superior and superior sectors of the ONH. In 27.63% cases tilted optic discs were noted, of which 61.90% were vertically and 38.1% ‐ horizontally tilted. The direction of the tilt was determined by the location of the PPA zone with a tendency to thinning of the RNFL in the same sectors. A positive correlation between the AL of eye and the location of the LC of sclera was found. In 29.17% the superficial location of the LC was determined. In 54.17% elongation was accompanied by displacement of the trunk of the CRV on ONH in the nasal ‐ 71.79%, or in the superior‐nasal direction ‐ 28.21%.Conclusions: The revealed changes of optic disc cup, neuroretinal rim and the parapapillary zones; a superficial displacement of LC of sclera and ‘nasalization’ of the trunk of CRV; a decrease in the OI with growth in the AL; relationships of the PPA zone with a tendency to thinning of the RNFL and direction of the tilt can be useful as OCT markers in interpreting normative data in patients with myopia, predicting its progression, and also in differential diagnosis with glaucomatous optic neuropathy.