bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA‐binding protein ELAVL1‐mediated neuroprotection of retinal ganglion cells
Authors: Pacwa Anna , Machowicz Joanna , Rodak Piotr , Liu Xiaonan , Amadio Marialaura , Lewin‐Kowalik Joanna , Smedowski Adrian 
Published: January 2024

Aims/Purpose: To evaluate the impact of ELAVL1 overexpression on survival and function of retinal ganglion cells (RGC) in rat glaucoma model.Methods: The study included ex vivo and in vivo approaches. Ex vivo, we used rat retinal explants to investigate, whether AAV‐ELAVL1 delivery affects the survival of RGC in the degeneration model induced by axotomy. In vivo approach investigated histology and function of RGC in rat glaucoma model. Rats received intravitreal injection of AAV‐ELAVL1, AAV‐ELAVL1(S202A) or AAV‐control. To induce chronic glaucoma, unilateral episcleral vein cauterization was performed. Animals underwent electroretinography tests (ERG) during the experiment. Collected retinas and optic nerves were processed for immunostainings, western blots, and stereology.Results: In ex vivo retinal explants culture, the RGC count was 162 ± 35, 148 ± 22 and 149 ± 28 for AAV‐ELAVL1, AAV‐ELAVL1(S202A) and control, respectively (p < 0.03). The IOP values were similar in all experimental groups, and on average, they were significantly higher than in healthy eyes (p < 0.001). In retinal histology, clear neuroprotective effect in the AAV‐ELAVL1 group was observed. After AAV therapy, both constructs (ELAVL1 and ELAVL1(S202A) showed a significant increase in protein expression in RGC, which was also associated with a significant increase in the expression of BDNF in the retinas, especially after AAV‐ELAVL1 treatment. In functional tests, the PhNR response was significantly reduced in AAV‐control glaucoma (p < 0.001). The application of AAV‐ELAVL1 treatment resulted in the preservation of RGC function at a level very similar to the situation before the induction of glaucoma.Conclusions: The AAV‐ELAVL1 approach showed a very strong neuroprotective effect in a rat glaucoma model. The neuroprotective effect is associated with antioxidant and anti‐inflammatory activity with the increase in BDNF expression, which intensifies the neuroprotective effect.
Combined surgery and Preserflo coating with conjunctival graft autologous in acute pseudo‐exfoliative glaucoma
Authors: Ortega Aranzazu Caro , Prades Gemma Ortega , Pérez‐Torregrosa Vicente T. , Casado Francisco Calleja , Rovira Elena Gracia , Pérez Prudencia Rochina , Duch‐Samper Antonio M. 
Published: January 2024

Aims/Purpose: To describe a case of cataract and acute pseudo‐exfoliative glaucoma in which combined surgery with a Preserflo implant was performed and required a conjunctival graft to cover the device due to the friability of the conjunctiva.Methods: A 72‐year‐old male with glaucoma in the left eye (LE) with triple hypotensive treatment, who lost follow‐up due to the pandemic, goes to the emergencies for loss of vision in the LE. A medium dilation, pseudo‐exfoliation and white hypermature cataract can be seen. The intraocular pressure (IOP) is 45 mmHg and does not revert to adequate values with topical and systemic maximum hypotensive treatment. A temporary access cataract surgery is performed without complications. The glaucoma procedure is then performed using the Preserflo implant in the upper nasal area, but the suture produced buttonholes and tears in the conjunctiva that forced us to perform an autologous graft of inferior temporal conjunctiva to cover the implant and ensure a tight closure of the flap.Results: The evolution of AV was favourable. IOP decreased to 10 mmHg and initially at biomicroscopy and Anterior segment optical coherence tomography (AS‐OCT) revealed a diffuse, functioning blister that progressively flattened. The graft was well adhered and positioned. The sclera of the donor area healed by secondary intention. At the 3‐month review, the device was vacuum packed and it was necessary to reintroduce hypotensive eye drops.Conclusions: The Preserflo implant may be less traumatic than other filtering surgeries. The time with hypotensive eye drops contributes to the friability of the conjunctiva and makes us cover the device with an autograft to complete the surgery initially successfully. Although the chronic conjunctival damage may promote fibrosis, disrupt filtration, and require new hypotensive treatment.References1. Gambini G, Carlà MM, Giannuzzi F, Caporossi T, De Vico U, Savastano A, Baldascino A, Rizzo C, Kilian R, Caporossi A, Rizzo S. PreserFlo Microshunt: An Overview of This Minimally Invasive Device for Open‐Angle Glaucoma. Vision (Basel). 2022 Feb 9;6 (1):12.
Idebenone addition in protein‐loaded PLGA/VitE microspheres as neuroprotective IODDS
Authors: Morilla‐Lomeña Cristina , Reguera‐Insausti Blanca , Andrés‐Guerrero Vanessa , de la Torre Marta Vicario , Brugnera Marco , de las Heras Beatriz , Herrero‐Vanrell Rocio , Cuadrado‐Berrocal Irene , Bravo‐Osuna Irene 
Published: January 2024

Purpose: Anti‐inflammatory and antioxidant evaluation of idebenone (IDB) in ARPE‐19 cell line and subsequent encapsulation in PLGA (polylactic‐co‐glycolic‐acid)/vitamin E microspheres (MS), together with neurotrophic factors, to confer additional neuroprotective activity and technological advantages.Methods: ARPE‐19, a human RPE cell line, were incubated for 24 with IDB (0.5‐150 μM) to determine cell viability by MTT assay. For anti‐inflammatory evaluation, cells were pre‐treated with IDB (10 μM) for 3 h and then, stimulated with LPS (10 μg/mL;24 h). Interleukin‐6 (IL‐6) and chemokine CCL2 levels were quantified by ELISA. To determine the antioxidant activity of IDB, the induction of intracellular reactive oxygen species (ROS) was investigated. Cells were 3 h pre‐treated with IDB (10 μM), posterior exposed to hydrogen peroxide (H2O2) (100 μM;6 h), and measured by a Cellular ROS Assay kit. The elaboration of the PLGA/vit E MS loaded with IDB and protein was carried out by the method of extraction‐evaporation of the solvent from an S/O/W emulsion. Microspheres were characterized by SEM, Confocal microscopy and LDS. The protein encapsulation efficiency and the % released in the first 24 h of in vitro release study was measured by fluorimetry.Results: IDB (10 μM) significantly suppressed LPS‐induced secretion of IL‐6 and CCL2 in ARPE‐19 cells. Moreover, pretreatment with the additive significantly attenuated the increased ROS levels in H2O2‐induced cells. Monodisperse spherical MSs were obtained with mean particle size suitable for intravitreal injection (29.41 ± 0.34 μm) and small superficial porous due to the presence of VitE. MSs showed a protein‐loading of 64.48 ± 1.99%. According to confocal images, protein was mainly distributed on the MS core. The initial protein release was 57.21 ± 10.89%.Conclusions: The inclusion of IDB in the PLGA/VitE MSs loaded with active proteins could increase the neuroprotective activity of the IODDS as well as improve its technological characteristics.
Late T‐Flux extrusion: A series of 5 cases
Authors: Parot Álvaro Andrés Ojeda , Fabra Yolanda Cifre , Prades Gemma Ortega , Torregrosa Vicente Tomás Pérez , Pérez Prudencia Rochina , Samper Antonio Miguel Duch 
Published: January 2024

Aims/Purpose: To Report T‐Flux® implant (Zeiss, La Rochelle, France) extrusion, as a new complication of non‐penetrating deep sclerectomy (NPDS). Analyse the risk factors that lead to it. Describe the treatment realized, and its complications.Methods: 5 eyes of 5 patients who had undergone NPDS Surgery and presented a late T‐Flux® extrusion were included in this study. We made an epidemiological description of the cases. The treatment consisted in surgical exploration, extraction of the T‐Flux® and closure of the scleral and conjunctival defect. In 1 patient reopening of the scleral flap was needed to access and extract the implant. In the postoperative, values of intraocular pressure (IOP) and complications were evaluated.Results: Of the 5 patients, 2 were man and 3 were female, the mean age was 78 years old, the mean time from the implantation until the extrusion was 11 years and 7 months. Mitomycin C was applied intraoperative during the NPDS in all cases, the concentration used was 0.02%, and the application time 1 min. 4 of the patients were operated by the same surgeon, one of the cases was re intervened later with trabeculectomy. All cases presented a partial or total dissolution of the scleral flap. There was no significant variation on the IOP prior and after surgery, The mean IOP at the diagnosis was 14 mmHg, and the mean IOP postoperative was 13.4. One patient had post surgical seidel that resolved without the need of re intervention.Conclusions: Extrusion T‐Flux® implant is a late postoperative complication of NPDS, unknown up to date, that may occur many years after the original intervention. Treatment consists in surgical extraction and repair. In our experience this complication might be related to mitomycin C use, given that all of our eyes presented a scleral flap necrosis. There is a need of more reports on this complication, to approach its real incidence and predisposing factors.
Patterns of ganglion cell complex defects and association with functional status in glaucoma patients and suspects
Authors: Amorim‐Cabral Camila , Zangarini Vinicius , Pacovska Mayara , Hilariao Ana Aurea , Kasahara Niro 
Published: January 2024

Aims/Purpose: To evaluate the frequency and patterns of ganglion cell complex (GCC) defects by spectral‐domain, high‐resolution optical coherence tomography (OCT) in POAG patients and suspects. Secondary endpoint was to analyse and compare the peripapillary retinal nerve fibre layer (RNFL) and GCC thickness as well as the visual field parameters among each GCC defect pattern.Methods: This was a cross‐sectional study and included 220 patients with POAG and suspects. The OCT printouts were analysed by two examiners who carefully searched for GCC defects and in common agreement stratified them into 10 different patterns. GCC thickness, retinal nerve fibre layer (RNFL) thickness were determined for every participant from the exams; mean deviation (MD) and pattern standard deviation (PSD) values were retrieved from automated perimetry exams for every patient. The structural and functional variables were compared among the groups.Results: The sample comprised 91 eyes of 47 patients. The most frequent GCC defect pattern was the minimal (39.1%). It affected more women than man at a rate of 1.4 and was associated with early disease (p < 0.001). The least frequent were inferior and superior confined (2.2% and 1.1% respectively); both were associated with moderate disease (MD = 10.0 dB, p < 0.001). The temporal raphe sign was observed in 5.5% of eyes and was associated with early disease (MD = −5.0 db).Conclusions: In this cohort of Brazilians patients with POAG and suspects, the minimal pattern was the most prevalent GCC defect and was noticed in eyes with early disease. Clinicians should pay special attention to this defect when evaluation eyes with suspicious looking optic disc and POAG patients with early disease.
Peripapillary and macular vessel density changes after trabeculectomy
Authors: Jašinskienė Ernesta , Kadziauskiene Aiste , Asoklis Rimvydas , Schmetterer Leopold 
Published: January 2024

Aims/Purpose: to evaluate peripapillary, optic disc and macular microvascular changes in glocomatous eyes after trabeculectomy using optical coherence tomography angiography (OCTA).Methods: 90 eyes of 52 patients with primary open angle (20%), pseudoexfoliative (71%) and angle closure glaucoma (9%), and were included. 24 eyes (Group 1) underwent trabeculectomy during the study, 34 eyes (Group 2) had previous trabeculectomy three years more ago and 37 eyes (Group 3) had no trabeculectomy trabeculectomy. The AngioVue OCTA (Optovue Inc., Fremont, CA, USA) was performed at baseline (within one week before trabeculectomy for Group 1), one week and one month following baseline examination. The main outcomes of interest were changes in the superficial and deep macular vessel density (VD) as well as whole image and inside optic disc.Results: The mean IOP at baseline was 25.3 ± 5.0 mmHg, 14.4 ± 3.7 mmHg and 14.7 ± 3.6 mmHg for the Group 1, Group 2 and Group 3 respectively. No significant differences in baseline characteristics were found between three groups, except for Group 3 group had milder glaucoma (it would be good to put the VF MD values of the groups). A reduction of IOP was observed in Group 1 one week and one month after trabeculectomy (14 ± 6.0 mmHg and 10 ± 6.2 mmHg respectively, p < 0.001). There were no significant IOP changes in Group 2 and 3. In all groups the changes in macular vessel density were nonsignificant. In Group 1 the mean inside disc small vessel density increased one week postoperatively (p = 0.04) and peripapillary vessel density increased one month postoperatively(p = 0.03) when compared with the baseline values. There was no significant difference in mean peripapillary or macular vessel densities between groups.Conclusions: IOP reduction causes mild microvascular changes of optic disc and peripapillary regions in early postoperative period, however, does not affect macula.
Glaucoma screening: How and why?
Authors: Chafter Camilia , Maamouri Rym , Aoun Hichem , Nouri Hela , Meriem Ouederni , Cheour Monia 
Published: January 2024

Purpose: To assess the results of glaucoma screening in the population over age 40.Methods: A population‐based glaucoma screening was performed at Habib Thameur Hospital, Tunis TUNISIA on March 12, 2023. Screening included intraocular pressure (IOP) measurement with Goldmann applanation tonometry, visual acuity measurement (VA) with the Snellen chart, fundus examination to detect characteristic optic disc changes, and questions regarding systemic diseases, family history of glaucoma, and current medications.Results: A total of 280 subjects were examined. Forty‐six had ocular hypertension, including 12 glaucomatous. All these patients were referred to the ophthalmology department for a complete ophthalmological examination, explorations (pachymetry, OCT of the optic nerve, visual field), treatment and regular follow‐up. Twenty‐two had unilateral or bilateral cataracts which we scheduled for surgery and fifteen had diabetic retinopathy at various stages which were referred to our specialist consultation for treatment.Conclusions: The need for effective and early detection and management of glaucoma may reduce the prevalence of glaucoma‐induced blindness.
Liposomes versus microemulsions: Two novel nanosystems achieved an increased latanoprost hypotensive effect compared to traded medication
Authors: Brugnera Marco , Casamayor Miriam González‐Cela , Cano José López , de la Torre Marta Vicario , Guerrero Vanessa Andrés , Osuna Irene Bravo , Toral Fernando Huete , Rubio María González , Carracedo Gonzalo , Martínez Irene Molina , Vanrell Rocío Herrero 
Published: January 2024

Aims/Purpose: The design of new topical ophthalmic nanosystems is linked to obtain non‐harmful carriers capable of increasing drug bioavailability and reduce the frequency of its instillations. Hypotensive actives such as latanoprost (L) are used to decrease intraocular pressure (IOP) in glaucoma patients. Two novel formulations, L‐loaded liposomes (LL) and L‐loaded microemulsions (LME), both including hyaluronic acid for its mucoadhesive properties were elaborated. The efficacy in reducing IOP of both formulations (48 h) was compared to a traded L‐ophthalmic solution (TM).Methods: LL were manufactured by the lipid film hydration method using synthetic phospholipids and cholesterol. LME were produced according to the self‐emulsification method by employing well‐tolerated oils and co‐solvents. Both LL and LME were characterized in terms of pH, osmolarity, size distribution, viscosity, and surface tension. Their hypotensive effect was evaluated up to 48 h in normotensive male albino New Zealand rabbits (n = 6, 12 eyes) using a tonometer following a single 25 μL topical administration and related to TM (n = 6). Draize test was performed before and 4 h after the instillation to establish LL, LME and TM tolerance.Results: Both LL and LME displayed proper physicochemical properties for the parameters evaluated. According to Draize test, both formulations resulted well‐tolerated without any sign of conjunctival hyperaemia, chemosis or discharge. Both LL and LME showed at least a 24‐h longer IOP reduction compared to TM, with the higher decrease at 3 h for LL and TM (24.02 ± 8.26% LL; 21.94 ± 10.14% TM) and 28 h for LME (30.40 ± 6.50%). Whilst at 24 h animals treated with TM (101.68 ± 5.27%) recuperated basal values, LL (91.08 ± 7.89%) and LME (80.14 ± 7.19%) rabbits still showed IOP decrease effect.Conclusions: Liposomes and microemulsions showed a longer hypotensive effect compared to traded medication, which makes them encouraging novel compliance‐friendly eye drops for glaucoma treatment.Acknowledgments: PID2020‐113281RB‐C21 funded by MCIN/AEI/10.13039/501100011033; 813440‐ORBITAL‐H2020‐MSCA‐ITN‐2018.
Study of the influence of care overburden on the indication for glaucoma surgery
Authors: Angulo Cristina García‐Velarde , Aroco Clara Lara , Blazquez Javier Guzmán , Martínez Teresa Pérez 
Published: January 2024

Aims/Purpose: The indication for glaucoma surgery is a long process. Includes decision, information and administrative procedures. The purpose of the work is to study the factors different than the strictly clinical ones that condition the indication for surgery.Methods: Retrospective study, consecutive sampling of glaucoma surgery indication with the variables age, sex, time of indication, number of patients attended per day and ratio indications/number of patients seen per day, type of glaucoma, type of surgery and physician who indicated it. The Shapiro–Wilk test was used to determine normality and the Kruskal‐Wallis test. The correlation between the ratio of surgeries and the total number of patients seen on the day (Sperman correlation) was measured.Results: 131 surgeries were analysed, collected in 82 days of consultation during a year. The patients reviewed were 2886, of the annual total of 5255. The surgeries were indicated by 4 specialists and by residents. The mean age was 69.24 ± 13.49 years. The mean ratio of indication to the number of patients seen that day was 4.74% and the ratio to the total number of patients seen per year was 2.49%. The mean number of patients per day was 35.20 ± 13.20. The hourly distribution of the indications was: 3.1% between 8–9 h, 26% 9–10 h, 16% 10–11 h, 19.8% 11–12 h, 17.6% 12–13 h, 10.7% 13–14 h and 6.9% between 14–15 h. There were no significant differences in the ratio of indication per hour of indication (p = 0.318) or regarding the doctor (p = 0.295). There were significant differences between specialists with respect to the number of patients treated (p = 0.02). The correlation data were moderate and presented a statistically significant inverse relationship (p = −0.455), with a tendency towards fewer indications for glaucoma surgeries the more patients there are in consultation.Conclusions: The care overload can influence the decisions when indicating glaucoma surgery.
Sigma‐1 receptor agonist ameliorates trabecular meshwork fibrosis by modulating extracellular matrix remodelling and increasing nitric oxide production
Authors: Hodrea Judit , Tran Minh , Besztercei Balazs , Medveczki Timea , Kovacs Illes , Gasull Xavier , Szabo Attila , Fekete Andrea 
Published: January 2024

Purpose: Maintenance of normal tissue homeostasis in the trabecular meshwork (TM) is crucial for unaltered intraocular pressure (IOP). Fibrotic‐like disorder of TM can be one of the main causes of increased IOP. Thus, anti‐fibrotic drugs could be novel therapeutics for glaucoma. Nitric oxide (NO) has been recognized as an important regulator of TM outflow and maintain IOP. Recently, we reported that fluvoxamine (FLU), a potent sigma‐1 receptor (S1R) agonist, decreases the levels of key elements of fibrosis in the kidney and in lung. Therefore, here we investigated the antifibrotic effectiveness of FLU in mouse and human TM cells.Methods: Fibrosis was induced with platelet‐derived growth factor (PDGF, 20 ng/mL, 24 h) in human and mouse primary TM cells (wild type: WT; and S1R knockout: KO). All cells were treated with 10 μM FLU for 24 h. Then localization of S1R, cell ‐toxicity, −proliferation and ‐migration, and levels of F‐actin, αSMA, fibronectin, and cathepsin K were determined with immunofluorescence or brightfield microscopy. NO production was measured with a fluorescent reader.Results: S1R is localized in the endoplasmic reticulum and TM cells' cytoplasm. FLU treatment is non‐toxic and reduces the PDGF‐induced cell proliferation, migration and fibrotic protein levels (fibronectin, αSMA). Furthermore, in human TM cells, FLU increases NO production and the level of the protease, cathepsin K thus moderating the cytoskeletal rearrangements. The protective role of S1R in fibrosis is confirmed by the more prominent increase of αSMA and F‐actin bundle and clumps in the KO cells.Conclusions: S1R agonist FLU reduces fibrosis‐related processes in TM cells by increasing NO production and facilitating ECM degradation. We propose in vivo investigations as a next step, since we believe that S1R activation could be a novel and efficient treatment in glaucoma or in other fibrosis related eye disease.GrantsOTKA‐ K135398, LP2021‐3/2021, TKP2021‐EGA‐24.
EyeLife: A prospective glaucoma screening study with double‐blind genetic pre‐screening conducted within the population‐based Lifelines cohort
Authors: Jansonius Nomdo , Neustaeter Anna , Nolte Ilja , Snieder Harold 
Published: January 2024

Purpose: Glaucoma screening potentially prevents blindness but is currently considered not cost effective due to insufficient screening test specificity given a low disease prevalence in the general population. Genetic pre‐screening could increase the prior probability (higher prevalence in a selected population). The aim of this study was to identify the relative risk of glaucoma in a subgroup of the general population with a high compared to one with a low genetic glaucoma risk.Methods: The study protocol has been published previously (PMID: 33413217). We invited 1600 participants from the European Lifelines cohort (n = 165 000) aged 55+. Participants belonged to either the highest or lowest 20% of a GWAS‐based genetic risk score distribution; subgroups had similar age and gender. Researchers and participants were blinded regarding subgroup allocation. All participants underwent frequency doubling perimetry (FDT), optical coherence tomography (OCT) of the peripapillary retinal nerve fibre layer, and fundus photography to assess the optic nerve head (ONH). Any abnormal test result resulted in an ophthalmic exam including gonioscopy. Participants were classified as definite (abnormal FDT and either abnormal OCT or ONH), probable (either abnormal FDT or abnormal OCT and ONH), or possible (normal FDT with either abnormal OCT or ONH) open‐angle glaucoma (OAG), or as healthy. We obtained the relative risk of combined definite and probable OAG compared to healthy, excluding possible OAG.Results: A total of 1031 participants responded (65%; 493 with high versus 538 with low risk). Of those, 31 (29 versus 2) were classified as definite and 28 (21 versus 7) as probable OAG. The prevalence of combined definite and probable OAG was 5.7%. The relative risk was 6.3 (95% CI 3.1–12.9).Conclusions: Genetic pre‐screening seems a promising way to increase the prior probability of glaucoma and thus make glaucoma screening more cost‐effective.