bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of ocular surface disease symptoms and patient satisfaction in dry eye disease after 84 days of treatment with preservative‐free eye drops containing sodium hyaluronate and trehalose
Authors: Mateo‐Otobia Antonio , Del Prado Sanz Eduardo , Martínez Alejandro Blasco , Corta Miriam Idoipe , Sanz María Romero , Pablo Júlvez Luis E. , Farrant Sarah 
Published: January 2022

AbstractPurposeDry eye disease (DED) has a multifactorial etiology, including insufficient tear production and/or excessive tear evaporation linked to multiple conditions. A preservative‐free eye drop formulation containing sodium hyaluronate and trehalose (SH‐THL, Thealoz® Duo) capitalizes on the bioprotectant properties of trehalose. This study evaluated the improvement of ocular surface disease (OSD), dry eye signs and symptoms, treatment satisfaction in patients with DED receiving SH‐THL.MethodsMulti‐center, international, non‐interventional prospective survey lasting 84 days with up to 2 post‐baseline visits in up to 310 adult subjects with clinically confirmed DED requiring artificial tears. Clinical signs with Schirmer Test, tear Break Up Time, hyperemia, dry eye symptoms with OSDI® scale and the five‐item dry eye questionnaire (DEQ‐5) as well as patient satisfaction were assessed at baseline, visit 1 (28 days) and 2 (84 days). SH‐THL was to be instilled when needed. The number of eye drops instilled per day was determined using the Kali Care Drop Meter (n=42).ResultsData from 238 patients were analyzed. 83.2% were women, the mean age was 57.9 ± 15.1 years. At baseline, the overall OSDI was 42.2 ± 19.9 and 61.3% of patients had severe OSDI. The DEQ‐5 score was 12.4±4.1 and the patient treatment satisfaction score was 6.4 ± 2.1. The OSDI significantly improved (p < 0.001) after 84 days. The DEQ‐5 score significantly improved at visit 1, persisting until visit 2 (both p < 0.001) with a statistically significant (p = 0.002) difference between visit 1 and 2. Patient satisfaction with treatment significantly improved (p < 0.001) at visit 1 and 2 compared to baseline. All clinical signs significantly improved after 84 days of SH‐THL.ConclusionsResults confirm that continued use of eye drops containing SH‐THL reduced DED signs and symptoms, OSDI scores, and result in a very high patient satisfaction.
Neuronal sources of visually evoked potentials using selective color opponent channel stimulation
Authors: Klee Sascha , Link Dietmar 
Published: January 2022

AbstractPurposeThe retinal stages of color processing have been extensively researched in recent years. In contrast, the cortical stages, especially the spatial distribution of visual processing are less understood. It is known that many cells in the visual cortex respond to color. However, what kind of computations these cells perform on their visual input, and what are their temporal and spatial properties are still under debate. In this study, we aimed to analyze the neuronal sources of visually evoked potentials using selective color opponent channel stimulations.MethodsThe study was conducted on 10 healthy subjects (6 male, 4 female, 1 eye each, mean age 25.5±5.1 yr). All subjects were free of eye diseases. Normal color vision was checked with Ishihara and Stilling‐Velhagen plates. To modulate selective activity in the S‐cone and L/M‐cone driven channels (the related cells are: short‐wavelength absorbing: S‐cone, medium‐wavelength absorbing: M‐cone, long‐wavelength‐absorbing: L‐cone) we presented two silent substitution flash sequences (total of 200 stimuli) in a full circle with a diameter of 22°. Electroencephalography was performed using a 64‐channel amplifier system (Theraprax, neuroConn GmbH, Germany) in combination with Ag/AgCl ring electrodes (B10‐S‐200, EASYCAP GmbH, Germany). The preprocessed data were analyzed with source localization software (CURRY v4.6, Compumedics, USA). For each subject, a realistically shaped volume conductor was constructed by a boundary element model.ResultsWe found two main components (N1, P1) in all subjects, as well as a third late component in most subjects. For these components significant latency differences (mean: N1 = 33 ms, P1 = 22 ms; p < 0.05) between both color opponent channels were found. The results showed no differences in the topography and no differences in dipole localization between both color channels. Talairach coordinates of grand averages indicated activation in area 18.ConclusionsOur findings showed that neural processing occurs in the same areas of the visual cortex for stimuli with different spectral properties. The signals of S‐ and L/M‐cone driven channels are transmitted in distinct pathways to the cortex. Thus, the observed latency differences might be caused by different anatomical and functional properties of these pathways.
Evaluation of the effect of eye movements on the Sweep VEP
Authors: Dimopoulos Ioannis , Kantungane Lynca , Coupland Stuart 
Published: January 2022

AbstractPurposeTo evaluate the effect of fixation stability on the sweep visual evoked potential (sVEP) visual acuity estimate in normal subjects.MethodsTwenty eyes of 10 subjects with normal ophthalmic exam and best‐corrected Snellen chart visual acuity (BCVA) of 20/20 or better in the tested eye underwent sVEP visual acuity estimation using commercially available equipment and software (Diagnosys Espion E3 System Lowell, MA, USA). sVEP was sequentially recorded under two conditions: (i) steady fixation using a central stationary target; and (ii) simulated unsteady fixation with the subject allowed roving eye movements outside the central stationary target. Fixation was monitored using eye‐tracking technology (Tobii Eye Tracker 4C, Tobii Technology AB, Sweden). Fixation stability was classified based on the proportion of fixation points within 4° retinal diameter circle (stable fixation: >75% fixations within 4° circle; unstable fixation: <75% fixations within 4° circle). Within‐subject differences in the estimated sVEP visual acuities under the two tested conditions were assessed using Wilcoxon non‐parametric signed comparisons with significance level set at p < 0.05. Bland‐Altman plots were used to calculate 95% limits of agreement.ResultsSimulated unsteady fixation yielded significant differences in sVEP visual acuity estimation compared to steady fixation (p < 0.0001). The median difference between the two conditions was 0.19 logMAR (~2 Snellen VA lines), with 95% limits of agreement ranging from 0.05 to 0.49 logMAR. Steady fixation overestimated visual acuity compared to BCVA (p < 0.0001), contrary to simulated unsteady fixation, which yielded estimates not statistically different from the expected BCVA (p = 0.91).ConclusionsSimulated unsteady fixation affects sVEP acuity estimates in normal subjects. However, the estimated visual acuities are not significantly different from the expected normal visual acuity of 20/20. sVEP testing can therefore be used to document normal visual acuity without the requirement of steady and central fixation.
Preventive screening of open‐angle glaucoma: an innovative machine learning risk assessment tool based on health insurance claims data
Authors: Bremond‐Gignac Dominique , Dairazalia Sanchez‐Cortes , Jihyun Lee‐Engler , Maxime Coriou , Duru Gerard , Nicolas Loeillot , Ariel Beresniak 
Published: January 2022

AbstractPurposeDespite progress in management of open‐angle glaucoma, early diagnosis remains difficult due to delayed ophthalmologist consultation. Early glaucoma treatment avoids vision loss, thus developing automated detection methods is of importance for public health. We used supervised machine learning models on medical insurance claims data to identify at‐risk patient profiles that would benefit from undergoing glaucoma diagnosis, leading to early detection.MethodsUsing medical claims records from a Swiss health insurance company, we identified a “glaucoma group” composed by 2700 patients (18–65 yo) with at least 3 years of historical data in the database and at least one year of medications for lowering intraocular pressure. To complete the training dataset, we randomly selected a “non‐glaucoma control group” (N = 2700) with same age range and medical criteria. Random Forest models were then trained using patient medical consumption data (e.g. number of drugs, number of consultations, ocular tests) in order to estimate individual’s probability of having glaucoma based on medical claims records. Population was split into training set (70%) and test set (30%) to estimate the model prediction performance.ResultsThe mean age of population with glaucoma was 55.3 (SD: 11.3), and had an average of 1.96 (SD: 2.8) eye visits within the 3 years period prior to their first glaucoma prescription. t‐test showed significant association between consumption of eye products (e.g. artificial tears) during the two years prior to glaucoma medication. The Random Forest classifier accuracy computed on the test set (N = 1600) showed a positive predictive value of 78.5%, a negative predictive value of 79.2%. Sensitivity and specificity were of 79.4% and 77.2% respectively.ConclusionsTo our knowledge, this study is the first to attempt estimating glaucoma probabilities from medical consumption invoice data. Our preliminary results show that using supervised machine learning algorithms could identify high‐risk patient profiles of glaucoma with an accuracy of almost 80%. These patients may benefit from an early ocular examination. Automated screening based on medical claims data could thus allow improving open‐angle glaucoma‐related health outcomes, minimizing serious vision loss, and reducing health costs.
Multivariate normative comparison, a novel method for improved use of the retinal nerve fiber layer thickness to detect early glaucoma
Authors: Chua Jacqueline , Schwarzhans Florian , Wong Damon , Li Chi , Vass Clemens , Schmetterer Leopold 
Published: January 2022

AbstractPurposeTo assess whether compensating the RNFL thickness for multiple demographic and anatomical factors improves the detection of glaucoma.MethodsThis case‐control study enrolled 2699 healthy participants to construct and test a multivariate compensation model, which was then applied in 387 healthy controls and 387 glaucoma cases (early, n = 219; moderate, n = 97; and, advanced, n = 71). Participants underwent Cirrus spectral‐domain OCT (Carl Zeiss Meditec) imaging of the optic disc and macular cubes. Compensated RNFL thickness was generated based on ethnicity, age, refractive error, optic disc (ratio, orientation, and area), fovea (distance and angle), and retinal vessel density. RNFL thickness measurements and their corresponding areas under the receiver operating characteristic curves (AUCs) were obtained.ResultsAfter applying the Asian‐specific compensation model, the standard deviation (SD) of RNFL thickness reduced, where the effect was greatest for Chinese (16.9%), followed by Malays (13.9%) and then Indians (12.1%). Multivariate normative comparison outperformed measured RNFL for discrimination of early glaucoma (AUC = 0.90 vs 0.85; p < 0.001), moderate glaucoma (AUC = 0.94 vs 0.91; p < 0.001) and advanced glaucoma (AUC = 0.98 vs 0.96; p < 0.001).ConclusionsThe multivariate normative database of RNFL showed better glaucoma discrimination capability than measured RNFL thickness, which suggests there may be utility in accounting for demographic and anatomical variance in RNFL thickness to improve glaucoma detection.
Analysis of vitreous opacities in chronic glaucoma by vitreo‐optical coherence tomography imaging
Authors: Perié Manuel Subías , Campo Lorena Arias , Vicente Altabás María José , Fernández Álvaro Tello , Castro‐Roger Luisa , Palomar Elisa Viladés , Ciordia Beatriz Cordón , del Palomar Amaya Pérez , Cegoñino José , Montolio Alberto , Garcia‐Martin Elena , Rodrigo Maria Jesus 
Published: January 2022

AbstractPurposeTo analyze the vitreous opacities of rat eyes by optical coherence tomography (OCT) in two models of chronic glaucoma. Hyperreflective opacities at the vitreoretinal interface, their dynamics over time (changes in number, size, intensity, eccentricity, and orientation) and as a function of intraocular pressure were analyzed in two different glaucoma models and compared to healthy controls.MethodsImages of the vitreoretinal interface were obtained by OCT and exported as videos (composed of cross‐sectional images acquired by means of 61 b‐scans measuring around 3 mm in length and centred on the optic nerve). These videos were analysed using a custom program implemented in Matlab. The vitreous opacities, closely related to the immune cells, were analysed.ResultsHyperreflective opacities, extrapolated as soma areas, were classified according to their size: isolated cells (<10 μm2), non‐activated cells (10–50 μm2), activated cells (50–250 μm2) and cell complexes (>250 μm2). In glaucoma models, right eyes showed significant increase of total area compared with left non‐induced eyes, and left eyes showed significant increase compared to healthy controls. The physiological number of opacities was 10–20. Glaucoma‐induced right eyes showed a mean of 70 opacities, a specular response between activated cells and non‐activated cells, and a greater variation in intensity in the smallest cells, that showed an early change in orientation compared with physiological eyes.ConclusionsOur method of analyzing vitreous opacities by OCT could serve as a reliable neuroimaging biomarker to detect disease onset and early progression applicable to glaucoma and potentially other neurodegenerative diseases impacting the retina and optic nerve.
Posture‐dependent collapse of the optic nerve subarachnoid space: a combined MRI and modeling study
Authors: Holmlund Petter , Støverud Karen , Wåhlin Anders , Wiklund Urban , Malm Jan , Jóhannesson Gauti , Eklund Anders 
Published: January 2022

AbstractPurposeLarge trans‐lamina cribrosa pressure differences (TLCPD) have been suggested to play a role in the development of normal‐tension glaucoma. To avoid substantial increases in the TLCPD in upright postures, we hypothesize that a collapse of the optic nerve subarachnoid space (ONSAS) protects the eyes from large TLCPDs when we stand up, i.e., by preventing low cerebrospinal fluid pressures around the optic nerve. In this study, we combined magnetic resonance imaging (MRI) and mathematical modeling to investigate the suggested ONSAS collapse and its effects on the TLCPD.MethodsFirst, MRI was performed on six healthy volunteers in 6° head‐down tilt (HDT) and 13° head‐up tilt (HUT) to assess changes in ONSAS volume with changes in posture. The volume change represents optic nerve sheath distensibility. Second, we used the MRI data and mathematical modeling to simulate the ONSAS pressure and the potential ONSAS collapse in a fully upright posture (90°).ResultsThe MRI showed a decrease of 33% in the ONSAS volume when going from the HDT to the HUT position (p < 0.001). In the upright posture, the simulations predicted an ONSAS collapse in the orbital section of the optic nerve, disrupting the pressure communication between the ONSAS and the intracranial subarachnoid space. The collapse reduced the simulated postural increase in TLCPD by roughly 1 mmHg, although this reduction was highly sensitive to the optic nerve sheath distensibility, varying between 0–4.8 mmHg when varying the distensibility by ±1 SD.ConclusionsThe ONSAS volume along the optic nerve is posture dependent during acute posture changes. The simulations supported the hypothesized ONSAS collapse in the upright posture and showed that even small changes in optic nerve sheath stiffness/distensibility may substantially affect the TLCPD, and thereby bear relevance for suggested TLCPD‐related disorders such as normal‐tension glaucoma.Ref‐erenceHolmlund, P. et al. Posture‐Dependent Collapse of the Optic Nerve Subarachnoid Space: A Combined MRI and Modeling Study. IOVS 62.4 (2021).
The ubiquitin‐proteasomal pathway in glaucomatous lamina cribrosa cells
Authors: McElhinney Kealan , Irnaten Mustapha , Wallace Deborah , O'Brien Colm 
Published: January 2022

AbstractPurposePrimary open‐angle glaucoma (POAG) is an age‐related fibrotic condition and a leading cause of blindness worldwide. POAG‐related damage is initiated within the lamina cribrosa (LC) region of the optic nerve head, driven by the pathological activation of resident LC cells. LC cells bear striking similarities to proliferative, apoptotic‐resistant myofibroblasts known to be responsible for organ fibrosis. Myofibroblast dysregulation is linked to targeted proteasomal degradation of p53 by the E3 ubiquitin‐protein ligase MDM2 (mouse‐double‐minute‐2) thus negating p53’s important regulatory role in cell‐cycle/apoptosis. This project aims to evaluate the role of p53, MDM2, and the ubiquitin‐proteasomal pathway in glaucomatous LC cells.MethodsPrimary human normal LC (NLC) and glaucoma LC (GLC) cells (n = 3 donors) were cultured under standard conditions and treated for 48 hours with RG‐7112 (p53‐MDM2 interaction inhibitor, Abcam). The p53‐MDM2 ubiquitin‐proteasomal pathway was analysed by real‐time polymerase chain reaction (qRT‐PCR) for gene expression and protein levels via western blotting.ResultsMDM2 gene expression levels were significantly elevated (p = 0.006) in GLC cells (1.00 ± 0.12) versus NLC cells (0.89 ± 0.08). p53‐MDM2 inhibitor RG‐7112 treatment caused a further significant (p = 0.001) increase in MDM2 transcription levels in GLC cells (1.17 ± 0.04). p53 transcription levels were equivocal between GLC cells (0.88 ± 0.09) and NLC cells (0.87 ± 0.08), with RG‐7112 treatment leading to a significant increase (p = 0.028) in p53 transcription levels in GLC cells (0.95 ± 0.06). Western blot analysis showed significant decreased protein expression levels of p53 (0.76 ± 0.09)(p = 0.047) and increased protein expression of MDM2 (1.57 ± 0.33)(p = 0.042) in GLC cells compared to NLC. Interestingly, p53‐MDM2 inhibitor RG‐7112 treatment increased p53 (1.14 ± 0.43)(p = 0.267) and decreased MDM2 protein expression levels (0.92 ± 0.25)(p = 0.06) in GLC cells.ConclusionsOur data suggest the ubiquitin‐proteasomal pathway is significantly dysregulated in GLC cells with MDM2 led p53 protein degradation negatively impacting its key role as “guardian of the genome”. Targeting the p53 ubiquitin‐proteasomal pathway in lamina cribrosa fibrosis may lead to future novel therapeutic interventions.
Resveratrol nanoparticles reduce retinal ganglion cell loss in glaucoma
Authors: Shamsher Ehtesham , Guo Li , Davis Benjamin M. , Luong Vy , Ravindran Nivedita , Somavarapu Satyanarayana , Cordeiro M. Francesca 
Published: January 2022

AbstractPurposeResveratrol is a natural polyphenol found in red wine and dark chocolate known for its antioxidant, anti‐inflammatory and anti‐apoptotic properties. All these properties can be used to treat neurodegenerative diseases such as glaucoma. To date, resveratrol low solubility in water and bioavailability limits its clinical use. The goal of this study was to develop a novel nanoparticle formulation of resveratrol and to assess it in an ocular hypertension (OHT) rat model of glaucoma.MethodsResveratrol nanoparticles (RNs) were formulated using a thin film rehydration technique. OHT rat model was induced with the injection of 1.85 M normal saline solution in two episcleral veins of the left eye of 10 Dark Agouti rats. The right eye was used as an internal control. RNs (n = 5) or vehicle (n = 5) were given topically as an eye drop daily for 3 weeks from induction. After 3 weeks, rats were imaged with the Detection of Apoptosing Retinal Cell (DARC) technology. DARC count was defined as the number of apoptosing retinal cells counted by a masked investigator. Next, all rats were sacrificed, and their retinas immunostained with Brn3a antibody. Retinal Ganglion Cell (RGC) density ratio was defined as the ratio between the left treated and the right untreated eye (control).ResultsRNs were formulated with an encapsulation efficiency >70% and a stability >90 days. They were well‐tolerated without any sign of ocular irritation and neuroprotective in the OHT glaucoma model as evidenced by the reduction of RGC apoptosis compared to the vehicle (1.02 ± 0.05 vs 0.70 ± 0.11 RGC density ratio, p < 0.05). RNs did not reduce the Intraocular Pressure (IOP) suggesting that their effect was independent from IOP modulation. However, RNs were not able to reduce significantly DARC count compared to the vehicle (493 ± 83 vs 612 ± 84 DARC count, p > 0.05).ConclusionsThese promising results show that topical administration of RNs is neuroprotective in an OHT glaucoma rat model by reducing significantly RGC apoptosis. DARC count reduction is not significant owing to the low number of animals used. Therefore, bigger studies are needed to confirm these encouraging results.
Scleral fixation of intraocular lenses using MERSILENE suture
Authors: Fehmy Nafaa , Meriem Ouederni , Ahmed Selmi , Maamouri Rym , Elyes Jerbi , Monia Cheour 
Published: January 2022

AbstractPurposeTo report the outcomes of the scleral fixation of intraocular lens using MERSILENE suture technique in the absence of adequate capsular bag supportMethodsWe report a retrospective study carried out in the ophthalmology department of Habib Thameur hospital (Tunis, Tunisia) of patients who underwent scleral fixation of Bausch and Lomb Akreos AO60 IOL using MERSILENE suture 5‐0. All patients were evaluated for surgical indication, complete ocular examination pre and postoperatively was performed including refractive status, intraocular pressure (IOP) as well as anterior segment evaluation and fundus examinationResultsWe included 12 eyes of 10 patients operated using the mentioned surgical technique. Surgical indication was Ectopia Lentis for 5 eyes, post‐traumatic lens dislocation for 3 eyes, post‐traumatic IOL dislocation for two eyes and surgical management of postoperative aphakia in two eyes. Best corrected visual acuity increased from 1.15 logMAR preoperatively to 0.49 logMAR at 6‐months postoperatively, with an average gain of 0.66 logMAR. Mean postoperative IOP was 15.5 mmHg. Complications included post‐operative hypotony in 3 eyes resolved with medical treatment, conjunctival inflammation and erosion due to an unburied knot after one month in 2 eyes managed with topical antibiotic and steroids followed by surgical burial of the knot.ConclusionsScleral fixation of Akreos AO60 IOL with MERSILENE suture is a safe, economical and well tolerated procedure leading to improvement of visual acuity. MERSIENE suture use appears to be effective and safe without suture‐related complication on the short‐term. However, long‐term assessment and comparative studies will be necessary to extend our results.