bluuebunny/crossref_metadata_2025_split huggingface dataset:
Segmentation errors in OCT‐angiography associated with epiretinal membranes
Authors: Xirou Tina , Bontzos Georgios , Garnavou‐Xirou Christina , Kontou Eugenia , Gkizis Ilias , Kabanarou Stamatina 
Published: December 2019

AbstractPurposeTo explore segmentation errors, image quality and motion associated artifacts in eyes with idiopathic epiretinal membrane (ERM).MethodsRetrospective comparative study. We included 32 eyes from 32 patients affected by ERM, as well as 32 eyes from 32 healthy, age‐matched subjects. Optical coherence tomography‐angiography (OCT‐A) was performed in the right eye of healthy controls (65.82 ± 17.43 years) and on the eye with the most advanced clinically diagnosed ERM (69.53 ± 13.12 years). The device used in this study provides a set of reference planes automatically segmented by the integrated software including the internal limiting membrane (ILM), the inner plexiform layer (IPL), and the retinal pigment epithelium (RPE) reference. Segmentation was regarded as inaccurate if either segmentation deviated from the correct plane by more than 50 μm. Presence of motion artifacts (blink lines, displacement, stretch artifacts, quilting, vessel doubling) as well as image quality were reported.ResultsMean image quality was 7.2 ± 0.9 for the ERM patients. Phakic eyes had a mean quality of 7.4 ± 0.8, and pseudo‐phakic eyes had a mean quality of 7.2 ± 0.6 (p = 0.107). Motion artifacts were 1.22 ± 0.7 in the study cohort. Segmentation was accurate in all healthy subjects (n = 32). Segmentation errors occurred in 65.6% of ERM patients. The IPL was the segmentation boundary most prone to inaccurate segmentation, followed by the ILM. Segmentation of RPE layer was accurate in 96.7% of all cases.ConclusionsOCT‐A image quality is an essential aspect in clinical practice, however, in several cases it cannot be reproduced in pathological conditions and is prone to motion artifacts and segmentation errors. Incorrect segmentation results in anatomically incorrect en‐face OCT‐A images and consequently in false quantification measures. Even though manual segmentation can be performed, it is rather laborious and suffers from interobserver errors.
Effects of type 2 diabetes mellitus on gene expression profile of meibomian glands in mice
Authors: Yildiz Erdost , Zibandeh Noushin , Özer Berna , Sahin Afsun 
Published: December 2019

AbstractPurposeDiabetes mellitus (DM) is a major health problem and its complications cause blindness. Meibomian gland dysfunction and dry eye disease are also important ocular complications related with DM. According to our hypothesis, DM can exhibit significant altered gene expression in meibomian glands. To test our hypothesis, meibomian glands of leptin deficient spontaneous diabetic and non‐diabetic mice were extracted and gene expression profiles were analyzed with microarray.MethodsNine Lepob/ob spontaneous diabetic mice and nine non‐diabetic Balb/c mice (control group) were used. Blood glucose levels, tearfilm break‐up time and fluorescein scores were measured for 12 weeks. Meibomian glands were dissected and RNAs were isolated for microarray gene expression analysis. Probes with standard deviation more than 0.1 were filtered and used 40 452 of 45 281 probes for processing. Fold change analysis were performed and identified for affected genes, and impact of genes on proteins, pathways and gene ontologies were analyzed by using various databases.ResultsWe observed 172 up‐regulated and 118 down‐regulated genes in type‐2 diabetic mice when compared to non‐diabetic mice. Interestingly, expression of collagen type‐I, integrin beta‐I binding protein‐I, pyruvate dehydrogenase kinase, TNF receptor genes up‐regulated with DM; on other hand, IL‐33, cholecystokinin, plasminogen activator, IL‐1 and serine peptidase inhibitor genes down‐regulated significantly. Also, we have seen significant decrease in WNT signaling and pentose phosphate pathways related genes.ConclusionOur data shows these changes in gene expression caused by endocrine and immune mechanisms of type‐2 DM which result disrupted homeostasis of epithelial cells of MG. Increased expressions of apoptosis and inflammation related genes and their effects on related pathways have proven that meibomian glands were negatively affected from type‐2 DM.
Necrotizing scleritis after “pterygium” excision with mitomycin C
Authors: Friesacher Anna , Alder Marco , Rüesch Rheinhard , Valmaggia Christophe , Todorova Margarita 
Published: December 2019

AbstractPurposeApplication of Miitomycin C during pterygium excision is discussed to reduce its recurrence rate. Nevertheless, potential adverse effects of Mitomycin C application should be evaluated in each individual patient.MethodWe report on minimal invasive procedures applied in a case of scleral necrosis following pterygium excision combined with intraoperative application of Mitomycin C. A 87‐year old man presented for a second opinion having suffered a severe ocular pain on the left eye for the last three weeks after pterygium surgery. At presentation, a gradual thinning of the sclera spreading to the adjoining cornea was observed. In addition, signs of chronic blepharitis with a dysfunction of the marginal eyelid glands, as well as, a negative Bell’s sign were observed on both eyes.ResultsLocal lubrication was applied, supported by broad‐spectrum local antibiotic therapy. In order to prevent perforation and strengthen the corneal stroma, doxycycline 100 mg daily, was added. The initiated systemic prednisone treatment was reduced to 20 mg daily. In addition, to support sufficient eyelids closure in the presence of negative Bell’s phenomenon, 20 units Botox was applied. Within the following days a gradual remission was achieved; with reduction of necrotic area and perilimbal ischemia, supporting thus, the corneal thickening and consequently the symptomatic pain release. Furthermore, histological results of the excised pterygium revealed conjunctival tissue with focal metaplasia of the squamous epithelium, stromal fibrosis, elastosis, and a small amount of conjunctival calcification, findings compatible with pinguecula on atypical location.ConclusionThe presented case confirms that application of mitomycin C should be used with consideration in patients featuring pre‐existing trophic anterior segment disease and/or systemic disease predisposing to wound‐healing impairment.
Upregulation of the mu‐opioid receptor in the cornea and trigeminal ganglion following corneal inflammatory pain
Authors: Guerrero Moreno Adrián , Joubert Fanny , Fakih Darine , Baudouin Christophe , Mélik Parsadaniantz Stéphane , Réaux‐Le Goazigo Annabelle 
Published: December 2019

AbstractOcular pain following corneal injury is frequently observed in clinic, but its management remains as therapeutic challenge. The innervation of the cornea is provided by sensitive neurons located in the ophthalmic branch of trigeminal ganglion (TG). We recently reported that increasing endogenous enkephalin levels reduced ocular pain in a opioid receptor‐mediated manner (Reaux‐Le Goazigo et al., 2019). As the expression of the mu opioid receptor (MOR) in the cornea and TG is not known, this work aims to study MOR distribution both in control and under inflammatory pain conditions.MethodologyAdult male mice were submitted to a corneal scraping followed by 10 μL of lipopolysaccharide (LPS) at day 1 and day 3. Mechanical corneal sensitivity was measured by Von Frey filaments and corneal integrity was evaluated with in vivo confocal microscopy (IVCM). At D5, animals were perfused with 4% PFA to study the MOR expression by immunofluorescence (IF) and in situ hybridization (RNAscope method) in the ipsilateral cornea and TG. Images were captured with a confocal microscope and staining was quantified using imageJ.ResultsA corneal scraping and LPS instillation induced a mechanical corneal hypersensitivity compared to control mice. IVCM images showed a superficial epithelium alteration and inflammatory cells. IF experiments highlight the presence of MOR in corneal nerve fibers in both groups of animals but an increase of MOR immunoreactivity was noted in scraping + LPS mice. At the level of the ophthalmic branch of TG, MOR (protein and mRNA) was detected in a large population of primary sensory neurons. Quantification of MOR mRNA signal revealed a significant (+60%) increase of the receptor following corneal pain.ConclusionThis study provides novel information about the distribution of MOR in the cornea and TG in control and under corneal pain condition. Altogether, these results suggest that MOR could constitute a new therapeutic target for inflammatory ocular pain.
Protein cages modified for oligonucleotide delivery to retinal cells
Authors: Pretto Chiara , van Hest Jan 
Published: December 2019

AbstractPurposeInvestigation on the applicability of Virus‐like particles (VLPs) based on the Cowpea Chlorotic Mottle Virus (CCMV) for the selective treatment of age‐related macular degeneration (AMD) exploiting RNAi technology.MethodsAnti‐luciferase siRNA was selected as a prototype cargo (Luciferase GL3 Duplex, Dharmacon). CCMV‐siRNA loaded nanoparticles were formulated and stabilization of the protein scaffold was achieved by crosslinking the particle surface with a disulfide containing crosslinking agent DTSSP (3,3′‐dithiobis[sulfosuccinimidylpropionate], Thermo Fisher). Particles were characterized by Transmission Electron Microscopy, Dynamic Light Scattering and Size Exclusion Chromatography. CCMV‐induced siRNA protection against enzymatic digestion with benzonase was assessed exploiting agarose gel electrophoresis. The efficacy of siRNA‐loaded nanoparticles was investigated in vitro exploiting the luciferase assay kit (Promega).ResultssiRNA‐loaded CCMV spherical nanoparticles of 28 nm in diameter were formulated. A 20:1 DTSSP: CP molar ratio was found to be optimal for particle crosslinking and stabilization in physiological conditions. Crosslinked siRNA‐loaded particles showed to be stable at 37°C for at least 12 hr. The drug delivery system showed the capability to protect encapsulated siRNA from degradation. A loading efficiency of 56% corresponding to 22 siRNA molecules per capsid was assessed. Particles incubated with Lipofectamine2000 were able to effectively knock down luciferase expression in HeLa‐Luc cells.ConclusionsCCMV nanoparticles represent an innovative platform for oligonucleotide delivery to the posterior segment of the eye due to their dynamic structure, high loading capacity as well as their cargo protective effect.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska‐Curie grant agreement No 722717.
Evaluation with angiography by optical coherence tomography of patients with multiple sclerosis
Authors: Cordón Ciordia Beatriz , Pérez Velilla Javier , José Vicente Altabas Maria , Viladés Palomar Elisa , Orduna Hospital Elvira , Pérez ‐ Del Palomar Amaya , Cegoñino Banzo Jose , Montolio Marco Alberto , Ramón Ara Callizo Jose , Jesus Rodrigo Sanjuán Maria , Satué Palacián Maria , García‐Martín Elena 
Published: December 2019

AbstractPurposeTo evaluate the microvascular changes in the superficial plexus of the retina and peripapillary plexus in patients with relapsing‐remitting multiple sclerosis (RR MS) by optical coherence tomography angiography (OCT‐A).MethodA prospective study was performed in a total of 75 patients. The control group consisted of 84 eyes of 42 subjects without any ocular disease. The study group was formed by 66 eyes of 33 patients with RR MS. Visual function was evaluated by visual acuity with Bailey‐Lovie optotype and contrast sensitivity with Pelli Robson test. The Deep Range Image (DRI) Triton, Swept Source OCT (Topcon Eye Care Company) was used to analyze vascular density of superficial plexus of the retina and the peripapillary area using (OCT‐A).ResultsThe nasal, temporal, superior and inferior parafoveal areas of RR MS patient group showed a significant decrease in vascular flow compared with the control group (p = 0.024, 0.039, 0.001 and <0.014 respectively). No significant differences were found in the peripapillary plexus between controls and patients groups.ConclusionsThere is a vascular reduction in the macular zone at the superficial plexus level in patients suffering RR MS.
Impact of OCT and visual function in multiple sclerosis patients treated with Fingolimod
Authors: Pérez‐Velilla Javier , José Vicente María , Vilades Palomar Elisa , Orduna Hospital Elvira , Cordón Ciordia Beatriz , Gil‐Arribas Laura , Ruiz De Gopegui Erika , Jesús Rodrigo María , Satué Palacian María , García‐Martín Elena 
Published: December 2019

AbstractPurposeTo evaluate the effect of Fingolimod during one year on the neuro‐retinal structures and visual function in patients with multiple sclerosis (MS).MethodsSeventy eight eyes of 78 patients with MS treated with Fingolimod were evaluated every 3 months (for a year) and compared with 32 MS patients treated with Interferon. All subjects underwent visual acuity (VA) test for high and low contrast (100%, 2.5% and 1.25%), contrast sensitivity vision (using the CSV‐1000 and Pelli‐Robson tests), color vision (using the Fansworth and L'Anthony D15 desaturated tests), the thickness of the retinal fiber layer, the ganglion cell layer and the macula by Fourier‐domain optical coherence tomography (OCT).ResultsIn MS patients treated with Fingolimod, a decrease in visual acuity was registered in 100% and 1.25% contrasts (p = 0.009 and p = 0.008respectivelly), as well as a reduction in contrast sensitivity in the Pelli‐Robson test (p < 0.001). Structurally a decrease in the ganglion cell layer (p = 0.008) and an increase in macular thickness (p = 0.006) were found. In MS patients treated with Interferon there is a significant decrease only in ganglion cell layer thickness (p = 0.006), being this decrease higher than in the Fingolimod group (P < 0.006).ConclusionsTreatment with Fingolimod causes a significant decrease in visual acuity and contrast sensitivity. It also causes an increase in average central macular thickness compared to the Interferon treatment. It's probable that the increase in central macular thickness is the cause of changes in visual function.
Rapid healing with ReGeneraTing Agent (RGTA) of a refractory post surgical corneal ulcer
Authors: Le Aurélie , Makhoul Dorine , Willermain François , Postelmans Laurence , Caspers Laure 
Published: December 2019

AbstractPurposeCorneal ulcer, especially in the context of neurotrophic keratopathy is a potentially challenging and sight threatening condition. We present a case of refractory post‐surgical ulcer with decreased corneal sensitivity, successfully treated with RGTA (Cacicol®).MethodsA 95 years‐old man underwent eyelid surgery for basocellular carcinoma. Because of a secondary eyelid malocclusion, a band keratopathy developed, leading visual acuity to 3/10. Two EDTA scratching surgeries were performed in order to improve vision. But six weeks after the last surgery, a partial loss of sensitivity associated with an epithelial defect (1.5 mm*2.5 mm) and deep stromal ulcer (with stromal edema all around and temporal neovascularization) was still present despite an intensive treatment with artificial tears, vitamine A ointment, antibiotic drops, 24‐hr bandage with a topical antibiotic cream: oxytetracyclin‐ polymyxin and hydrocortisone (Terracortril®). For this refractory corneal ulcer with neurotrophic keratitis, we then decided to stop this treatment and to replace it by RGTA 1*/48 hr and artificial tears 5*/day.ResultsWhile it did not respond to previous topical treatments for six weeks, this post‐surgical ulcer with decreased corneal sensitivity and exposed cornea, responded quickly to RGTA drops. After one week, the size of the ulcer was a fifth from its original size. It took fifteen days to completely close the ulcer.ConclusionThe healing of corneal ulcers especially when the corneal sensitivity is involved with a consequent neurotrophic keratitis is a challenge. Several steps are necessary: to stop topical toxic treatment, to find and to treat causes of the ulcer and then apply and alternative treatment. In some cases, RGTA drops can quickly help.
Anti‐glaucomatous preparations and effect on human conjunctival goblet cells
Authors: Hedengran Anne , Begun Xenia , Müllertz Olivia , Mouhammad Zaynab , Vohra Rupali , Petrovski Goran , Kolko Miriam 
Published: December 2019

AbstractPurposeTo investigate goblet cell (GC) survival after treatment with benzalkonium chloride (BAC)‐preserved anti‐glaucomatous eye drops. Conjunctival GCs produce mucin which stabilizes the tear film and protects against dry eyes. Eyedrop‐induced GC death may cause ocular surface disorders.MethodLatanoprost Teva (LT; prostaglandin analogue), Optimol® (OP; beta‐blocker), Dorzolamid Stada (DS; carbonic anhydrase inhibitor) and Brimondine tartrat Teva (BT; alfa2‐agonist) BAC‐preserved eye drops were used for treatment of ex vivo cultivated human GCs. The cell survival was evaluated by lactate dehydrogenase assay on human GCs after 30 min and 6 hr exposure to the different treatments and compared to the untreated control group. pH‐value and osmolality were also measured.ResultsAfter 30 min of treatment, the human GC survival was 69.05% for LT, 69.78% for OP, 71.12% for DS and 93.42% for BT. The survival was significantly reduced only for the treatment with LT compared to the controls (p = 0.044). After 6 hr of exposure, GC survival was 31.08% for LT, 33.81 % for OP, 51.64 % for DS and 74.49 % for BT. The survival was significantly reduced for LT, OP, and DS compared to controls (p = 0.002, p = 0.004, p = 0.022). DS had the lowest pH (5.58), while OP the highest (6.84). LT had the lowest osmolality (267.6 mOsm/kg), while BT had the highest (293.2). There was no apparent correlation between GC survival, pH and osmolality. However, there seemed to be a connection between GC survival and BAC concentration. LT caused the lowest survival with a BAC concentration of 0.02%, while OP had a concentration of 0.01%, DS of 0.0075% and BT of 0.005%.ConclusionLatanoprost Teva was the most cytotoxic, causing significant GC death after 30 min and 6 hr of treatment. OP and DS caused significant GC death only after 6 hr of exposure. BT did not affect the GC survival. The cytotoxicity appeared to correlate with the BAC concentration, but not pH and osmolality.
Visual changes in patients with early type 2 diabetes mellitus without diabetic retinopathy due to possible subclinical ischemia
Authors: Vicente María José , Vilades Elisa , Orduna Elvira , Cordón Beatriz , Pérez‐Velilla Javier , Melchor Isabel , Gil‐Arribas Laura , Rodrigo María Jesús , Satué María , García‐Martín Elena 
Published: December 2019

AbstractPurposeTo assess visual changes in patients suffering from early type 2 diabetes mellitus (DM2) with good metabolic control and without diabetic retinopathy as a possible implication of subclinical ischemia.MethodSixty patients with early DM2 with good metabolic control and without diabetic retinopathy and sixty age and sex‐matched healthy controls were recruited for the study. Only one eye per subject was randomly selected and included. Psychophysics tests were performed as visual acuity (VA) by ETDRS charts, colour vision using the Farnsworth and L’Anthony D15 desaturated colour tests, contrast sensitivity vision (CSV) using Pelli Robson chart and CSV 1000E test and visual field with the automated Easyfield perimeter. Systemic parameters such as the presence or absence of vascular complications and the HbA1c levels were recorded, as well as the disease duration.ResultsPatients with DM2 showed worse VA at low contrast level (2.5%, p = 0.002; 1.25%, p = 0.007), worse CSV at high spatial frequencies (12 cpd, p = 0.007; 18 cpd, p = 0.011) and worse colour vision (Farnsworth, p = 0.006; Lanthony, p < 0.001) recordings compared to the control group. However, visual field parameters were similar in both groups. Patients with more than 10 years of disease duration obtained lower results with the ETDRS test, and those ones with systemic vascular complications got worse results in CSV and colour vision tests (CSV 18 cpd, p = 0.024; Lanthony test, p = 0.014). There were no significant differences between patients with HbA1c levels higher versus lower than 7%.ConclusionsPatients with early DM2, with good metabolic control and no diabetic retinopathy showed visual dysfunction compatible with retinal neurodegeneration. Subclinical ischemia could contribute to neuronal damage, before than the evident vascular changes appear.
The relationship between ambient air pollution and glaucoma phenotypes in a large community cohort
Authors: Chua Sharon , Khawaja Anthony , Reisman Charles , Khaw Peng , Patel Praveen , Foster Paul 
Published: December 2019

PurposeGlaucoma is reportedly more frequent in people living in urban areas and more than 91% of the world’s population live in areas with air pollution above WHO recommended limits. However, few studies have examined the association between air pollution and risk of glaucoma.MethodsUK Biobank participants aged 40–69 years old completed a detailed baseline questionnaire and underwent ophthalmic and air pollution assessments. Ambient particulate matter with an aerodynamic diameter <2.5 µm (PM2.5) concentration was estimated. Eye measures including self‐reported glaucoma status, corneal compensated intraocular pressure (IOPcc), Goldmann‐correlated intraocular pressure (IOPg) and thickness of retinal layers were collected. Total average thickness of the retinal nerve fibre layer (mRNFL), ganglion cell‐inner plexiform layer (mGC‐IPL), ganglion cell complex (mGCC) and total macular layer were obtained from spectral‐domain optical coherence tomography (SD‐OCT). Multivariable regression models were used to evaluate associations between PM2.5 concentration with self‐reported glaucoma, IOP and retinal layer thickness.ResultsIn multivariable regression analysis, participants resident in areas with higher PM2.5 concentration were more likely to report a diagnosis of glaucoma (OR = 1.13, 95% CI 1.08 to 1.19, per interquartile range [IQR] increase). Higher PM2.5 concentration was associated with thinner mGC‐IPL (β = −0.47 µm, 95% CI −0.56 to −0.39, per IQR increase), mGCC (β = −0.21 µm, 95% CI −0.33 to −0.09, per IQR increase) and total macular thickness (β = ‐0.36 µm, 95% CI −0.56 to −0.15, per IQR increase), while a thicker mRNFL (β = 0.25 µm, 95% CI 0.18 to 0.32, per IQR increase) was observed. There was no relationship between PM2.5 concentration and IOP that was biologically relevant (IOP: β = 0.06 mmHg, 95% CI 0.03 to 0.09, per IQR increase; IOPcc (β = 0.08 mmHg, 95% CI 0.01 to 0.15, highest versus lowest quartile).ConclusionIn this large adult population, higher PM2.5 concentration was associated with a self‐reported diagnosis of glaucoma, and thinner inner retinal layers, consistent with structural changes seen in glaucoma. No biologically relevant relationship was observed for either IOPcc and IOPg. This suggest that PM2.5 concentration may be a potential modifiable risk factor for glaucoma that is independent of IOP.