bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hsa‐miR‐150‐5p regulates human corneal epithelial stem cells through Wnt signaling
Authors: Kalaimani Lavanya , Devarajan Bharanidharan , Prajna Namperumalsamy Venkatesh , Veerappan Muthukkaruppan , Daniels Julie T. , Priya Chidambaranathan Gowri 
Published: December 2019

AbstractPurposeThe aim of this study was to understand the molecular regulatory function of hsa‐miR‐150‐5p in association with the maintenance of stemness in corneal epithelial stem cells (CESCs).MethodsSmall RNA sequencing identified hsa‐miR‐150‐5p to be highly expressed in enriched CESCs compared to central corneal epithelial cells (CCECs). The validation of differential expression of hsa‐miR‐150‐5p in enriched CESCs in comparison to CCECs was carried out by quantitative real time PCR (Q‐PCR) and by locked nucleic acid in‐situ hybridization (LNA‐ISH) in human corneo‐limbal cryosections. Primary cultured limbal epithelial cells were transfected with hsa‐miR‐150‐5p mimic, inhibitor and scrambled sequence (25 nM) using lipofectamine 3000. The transfected cells were analysed for (i) colony forming potential (ii) expression of stem cell markers (ABCG2, NANOG, OCT4, KLF4 and ΔNP63), differentiation marker (connexin‐43) and the hsa‐miR‐150‐5p predicted targets (JARID 2, AKT 3, INHBA and CTNNB1) by Q‐PCR and (iii) expression of ABCG2, p63, connexin‐43, JARID 2, AKT 3 and catenin by immunofluorescence staining.ResultsThe expression of hsa‐miR‐150‐5p was higher (13.86±1.5) in enriched CESCs compared to CCECs by Q‐PCR analysis. Hsa‐miR‐150‐5p had relatively higher expression in clusters of cells in limbal basal epithelium compared to other layers by LNA‐ISH. Ectopic expression of miR‐150‐5p increased the colony forming potential (8.28 ± 0.33%) with the ability to form holoclones in comparison to inhibitor treated (0.71 ± 0.10%) and control (1.8 ± 0.15%). The mimic treated cells had higher expression of stem cell markers but reduced expression of connexin‐43 and hsa‐miR‐150‐5p targets involved in Wnt signaling pathway.ConclusionA regulatory role for hsa‐miR‐150‐5p in maintenance of stemness by inhibiting Wnt signaling pathway is thus indicated.
Unexpected visual acuity loss as the first sign of a xen implant complication
Authors: Monzón Sara Marco , Sangros Isabel Lopez , Riegel Gisela Karlsruher , Rodriguez Paula Montes , Barreda Maria Dolores Diaz , Murillo Ana Boned , Morales Juana Martinez , Puyuelo Javier Ascaso 
Published: December 2019

AbstractPurposeMinimally invasive glaucoma surgery (MIGS) using diferent devices is a promising strategy for treating mild glaucoma. However, long‐term complications require further evaluation. We report a case of displacement to the anterior chamber and cornea of a previously successful XEN implant.MethodsA 85‐year‐old female treated for open angle glaucoma with Latanoprost, Timolol and Brinzolamide started presenting IOP of 24 mmHg in her right eye and a progression was also evident in visual field examination and spectral‐domain optical coherence tomography. Due to failure of medical treatment, surgery with a XEN implant was offered to the patient. The XEN implant was successfully implanted in the right eye and an adecuate control of the IOP was achieved for eight months. After that period of time, IOP raised to 22 mmHg and topical treatment with Brinzolamide and Timolol was reintroduced. Nine months later, the patient suffered a visual acuity loss and came to the emergency department. During the slit‐lamp examination intense corneal edema, Descement membrane folds and a dislocation of the XEN implant into the anterior chamber affecting the cornea were described.ResultsTaking into account the patient situation we started adding topical corticosteroid therapy to her previous treatment. Finally a surgical removal of the implant was performed. Rejecting other surgical therapies for now, the patient is at the moment treated topically.ConclusionsDespite MIGS is a safe and useful technique, long‐term complications require further evaluation. We describe the dislocation of a XEN implant into the anterior chamber or to the cornea as a new potential complication of this device to keep in mind.
Clinical validation trial of Glaucoma Easy Screener (GES) as a low‐cost and portable visual field screening tool
Authors: Nida Esmael Kedir , Vandewalle Evelien , Van Keer Karel , Vanden Abeele Vero , Geurts Luc 
Published: December 2019

AbstractPurposeThe aim of this study is to compare the performance of Glaucoma Easy Screener (GES), as a low cost and portable visual field screening tool to the glaucoma screening test (GST) from Octopus.MethodsGES is comprised of a Moto G5 smartphone, Homido v1 virtual reality headset and a gaming joystick for user input. The screening app’s design is based on the recently introduced Octopus GST perimeter. The test contains 28 points in the central 300. Test stimuli at each location are presented at an intensity level that can be detected in 95% of the time in case of a normal visual field. The app monitors false positive errors with catch trials and fixation losses using the blind spot method. Test result is presented with a plot of seen and missed points along with other parameters including test duration and reliability indices. A normative database for the GES was constructed by testing 62 eyes of 33 normal subjects (aged 22–56, 10 male/23 female) using a threshold procedure. To evaluate agreement between Octopus GST and GES, 36 eyes of 18 subjects (among the 33 normal subjects) were tested both with GES and Octopus GST.ResultsThere is a good level of agreement between Octopus GST and GES, with 31 eyes(86%) showing above 85% agreement, based on the count of seen and missed points. There was above 85% agreement for 24 points in all eyes. The remaining 4 points had an agreement between 78 and 85%. Test duration was slightly higher for GES with an average of 2 min per eye compared to 1.1 min with Octopus GST.ConclusionsResults from this clinical trial show a good level of agreement between GES and Octopus GST. GES can serve as a low‐cost and portable visual field screening kit to complement other glaucoma tests, to make referral decisions in situations where standard equipment is not available.
Progression patterns of normal‐tension glaucoma groups classified by Hierarchical cluster analysis
Authors: Song Park Hyo , Woo Kim Eun , Keum Park Cham , Choi Wungrak , Hyun Lee Kwang , Je Seong Gong , Yun Kim Chan , Yeop Lee Sang , Won Bae Hyoung 
Published: December 2019

AbstractPurposeTo investigate differences in progression patterns of normal‐tension glaucoma patients in three clusters classified by Hierarchical cluster analysis (HCA).Method200 eyes of NTG patients classified by HCA in 2015 who were followed up until now were included. We evaluated the progression rate of NTG in SD‐OCT and visual field test and compared characteristics of the progression in each group.ResultA total of 153 patients were followed up and the mean observation period was 5 years. In cluster 1, which showed early glaucomatous damage in the previous report, the mean retinal nerve fiber layer (RNFL) reduction rate was −0.83 μm/year. In cluster 2, which showed moderate glaucomatous damage, the reduction rate was −0.45 μm/year, and In cluster 3, which showed young and myopic glaucomatous damage, the rate was −0.36 μm/year. The progression pattern of cluster 3 showed a double‐peak distribution with the RNFL reduction rate being 0.11 μm/year in non‐progressive group and −1.07 μm/year in progressive group.ConclusionWhen the optic nerve head parameters were classified by HCA, the divided groups showed different patterns of NTG progression. In particular, the group of young myopia showed a mixture of two different patterns. /
In vitro evaluation of cytotoxic potential associated to antimicrobial agents commonly used in clinical ophthalmological practice
Authors: Viola Santa , De Pasquale Giuseppe , Zappulla Cristina , Cristina Curatolo Maria , Grazia Mazzone Maria , Giuliano Francesco 
Published: December 2019

AbstractPurposeTopical antibiotics may cause cytotoxic effects on eye surface, especially when the integrity of ocular epithelia is a major concern (e.g. corneal damage). Here we investigated the potential cytotoxicity of one antiseptic (povidone‐iodine) and three antibiotics commonly used in ophthalmology (netilmicin, levofloxacin and chloramphenicol).MethodsHuman Corneal Epithelial cells (HCE) were exposed to all compounds (1.5, 3 or 6 mg/ml) for different lengths of time, i.e. 0.5, 1, 3, 6 and 24h. Cell viability was then assessed by MTT assay. Cell viability cut‐off was fixed at 50% (DB‐ALM: Protocol n°17). Statistics were by two‐way ANOVA.ResultsNone of the compounds tested at 1.5 mg/ml had any significant cytotoxic effect, except for levofloxacin producing a 66% cell mortality at 24h. At 3 mg/ml, in addition to levofloxacin, chloramphenicol too produced a submaximal cytotoxic effect at 24h (76%). Netilmicin was the only to be devoid of any cytotoxic effect at 6 mg/ml while all the other compounds produced significant cytotoxic effects with varying onset times, chloramphenicol and povidone‐iodine showing the earliest onset (see figure).ConclusionsResults demonstrate that levofloxacin and chloramphenicol produce cytotoxic effects on HCE even at concentrations that are lower than those used in clinical ophthalmological practice. Conversely, povidone‐iodine only showed cytotoxic effects at 6 mg/ml, that is the concentrations of eye drops available on the market. Most importantly, netilmicin was found to be endowed with an advantageous cytocompatibility profile being devoid of any cytotoxicity even at concentration exceeding those currently used in clinical ophthalmological practice (3 mg/ml). Further studies are warranted to investigate the potential cytotoxic effects of antimicrobial agents tested in a pulsed‐treatment setup in order to mimic the human dose regimen thus accounting for potential biases due to prolonged cell exposure.
Involvement of innate immunity in the course of choroidal neovascularization in mice
Authors: Kokona Despina , Tsioti Ioanna , Schwarzer Petra , Zinkernagel Martin S. 
Published: December 2019

AbstractPurposeTo investigate the effect of retinal microglia depletion, and the effect of systemic lipopolysaccharide (LPS) exposure, in the course of laser‐induced choroidal neovascularization (CNV) in mice.MethodsFor microglia depletion, C57BL6/J mice were kept under a diet containing the colony‐stimulating factor 1 receptor (CSF‐1R) inhibitor PLX5622, for 1 week prior to CNV induction and until the end of the experiments. To evaluate the effect of systemic LPS challenge on the CNV course, LPS (1 mg/kg) was given intravenously in control‐fed mice for 1 or 4 consecutive days, immediately after CNV. Mice were imaged with optical coherence tomography (OCT) and fluorescein angiography (FA) at baseline, and at day 3, 7 and 14 after CNV. CNV lesions were measured in the FA images and flow cytometry was used to investigate the effects of PLX5622 on the innate immune cell populations in the retina and the choroid‐RPE of CNV‐subjected mice.ResultsPLX5622 led to microglia depletion in the retina, reduced numbers of dendritic cells, macrophages and leukocytes in the choroid‐RPE and a faster involution of CNV. Retinal swelling, vasodilation and accumulation of microglia/macrophages around retinal vessels were observed at day 4 after the first LPS challenge but not 1 day after a single LPS injection. Moreover, a single LPS injection led to exacerbation of the CNV lesion, while 4 consecutive LPS injections did not affect the CNV size compared to non‐injected mice.ConclusionsThe data suggest that suppression of the ocular innate immune response leads to a faster involution of CNV, while activation of innate immune cells with an acute systemic inflammatory stimulus results in increased CNV areas and slower involution. Moreover, chronic systemic LPS exposure do not affect the course of CNV. These findings highlight the importance of innate immunity in the course of experimental CNV and the different effects of acute and chronic systemic inflammation in the diseased retina.
Disease etiology‐based design of multifunctional trehalose emulsion eye drops for moderate or severe dry eye: a randomised, quadruple‐masked and active‐controlled clinical trial
Authors: Kaarniranta Kai , Järvinen Riikka , Wylegala Edward , Laihia Jarmo 
Published: December 2019

AbstractPurposeTo assess the safety and efficacy of multi‐ingredient trehalose emulsion eye drops (TEED) designed to target (1) tear film instability, (2) tear hyperosmolarity, and (3) ocular surface damage and inflammation in moderate or severe dry eye.MethodsThis randomised, quadruple‐masked, active‐controlled parallel study in 64 adult patients comprised three parts. Part 1 (n = 3): One eye was treated with TEED for one day. Part 2 (n = 9): Randomised eyes were treated with TEED and 0.2% hyaluronic acid (HA) control eye drops 3 times a day for 10 days. Part 3 (n = 26 + 26): Randomised treatment was applied on both eyes 3 times a day for 30 days. Ocular assessments were performed at baseline and after the last dose.ResultsBoth treatments were well tolerated without adverse device effects. Tear film break‐up time (p = 0.0025) and ocular protection index (p = 0.0026; change vs. HA, p = 0.047) increased significantly with TEED after 30 days. Tear osmolarity decreased more in TEED than in HA group and significantly with both eye drops in hyperosmolar subgroups. Corneal (p = 0.014) and nasal conjunctival staining (p = 0.043) were reduced with TEED in per‐protocol patients (n = 24). Conjunctival (p = 0.001) and lid redness (p = 0.012) decreased with TEED in all patients (n = 26). Symptoms decreased by about 25 OSDI units with both treatments (p < 0.0001).ConclusionsTEED proved safe and efficacious in improving each etiologic factor for dry eye. Hyperosmolar stress dominating blink cycles must be disrupted by biophysical protection of the ocular surface to facilitate resolution of cellular damage and inflammation, and relief of ocular symptoms.
Microglial analysis in whole‐mount retina of Alzheimer's disease 3xTg‐AD mouse model
Authors: Ramírez Ana I. , Salobrar‐García Elena , Rodrigues‐Neves Ana C. , de Hoz Rosa , Salazar Juan J. , Fernández‐Albarral José A. , López‐Cuenca Inés , Rojas Pilar , Ambrósio Antonio F. , Ramírez José M. 
Published: December 2019

AbstractPurposeAlzheimer’s Disease (AD) is a primary degenerative disease that is characterized by the accumulation of β‐amyloid and tau in central nervous system, even in visual brain areas and in the retina. This raises the possibility that tracking changes in the retina can be used to assess neurodegeneration in AD.MethodsWe analysed the retinas of 16‐month‐old 3xTg‐AD transgenic mice, which are used as an animal model of AD, and wild‐type (C57BL6/129S). Whole mount retinas were stained with antibodies against Iba‐1 and OX‐6. The morphology, number and soma size of microglia in the retina were analysed.ResultsRetinas from 3xTg‐AD transgenic mice showed signs of microglial activation relative to retinas from wild‐type animals: greater number of microglia, thickening of microglial soma, retraction of microglial processes and migration of microglia within and between layers. This activation was associated with alterations in the microglial plexus in the external plexiform layer and in the complex of internal layers. Retinas from 3xTg‐AD mice showed circular groups of microglia that reoriented and polarized their processes differently than in control retinas. Moreover, it was found a significant increase in both the number and cell body area of Iba‐1+ cells in 3xTg‐AD retinas in comparison with wild‐type retinas.ConclusionsRetinas from a mouse model of AD show signs of microglial activation. Reactive gliosis caused by AD‐associated protein aggregation may trigger morphological changes in the retinas of AD patients.AcknowledgmentsSanta Casa Mantero Belard Award 2015 (MB‐1049‐2015), Foundation for Science and Technology (PEst UID/NEU/04539/2013), COMPETE‐FEDER (POCI‐01‐0145‐FEDER‐007440), and Centro 2020 Regional Operational Programme (CENTRO‐01‐0145‐FEDER‐000008: BrainHealth 2020).
Study about the association between diabetic macular edema and avascular foveal area, diameter and thickness of the superficial and deep retinal plexuses
Authors: Montes Paula , Karlsruher Gisela , Boned Ana , Dolores Díaz María , Marco Sara , López Isabel , Esteban Olivia , Javier Ascaso Francisco 
Published: December 2019

AbstractPurposeOur objective is to study in diabetic patients if there is an association between the presence of macular edema (diffuse or cystic) or not and the area of the foveal avascular zone (ZAF) in the superficial and deep retinal plexuses, diameters and the macular thicknesses measured with OCT and OCT‐A.MethodsWe performed a retrospective observational study with 13 diabetic patients (26 eyes). We have extracted general data of its history, characteristics about the evolution of its disease and ocular affectation, such as sex, age, time of evolution of diabetes, presence of diabetic retinopathy or not, treatments received and visual acuity. In each patient, on two images of OCT angiography (superficial plexus and deep plexus), we measured (with the “Triton” software) the area of the ZAF, as well as the larger diameter. In the classic OCT we have determined the central macular thickness and the type of macular edema: diffuse, cystic, or with neuroepithelial detachment at the foveal level due to the presence of subretinal fluid. We correlated the macular ischemia data of OCT‐A with the classical OCT data to see if there is any relationship.ResultsIt is verified that all parameters have a higher value in patients who do have macular edema and that in one of the measured characteristics (the diameter of the superficial plexus) this difference is statistically significant. Finally, when observing the values of the effect size, it is verified that there are three parameters (FAZ Plexus superficial, Diameter of superficial plexus superficial and Diameter of deep plexus) where a higher clinical significance is obtained.ConclusionsThere is a positive association between the area and diameter of the ZAF and the presence of macular edema in diabetic patients.
Release of cytokines/myokines by retinal tissue at different times in a mouse model of glaucoma
Authors: Fernández‐Albarral José A. , Ramírez Ana I. , de Hoz Rosa , López‐Gallardo Meritxell , Moya M. , Marco E. , ElenaSalobrar‐García  , MarcelinoAvilés‐Triguero  , Villegas‐Pérez Maria P. , Salazar Juan J. , Ramírez José M. , Ramírez José M. 
Published: December 2019

AbstractDiverse cytokines released by retinal glial cells (IL‐1β, IL‐4, IL‐6, IL‐10, IL‐17, IFN‐, BDNF, VEGF and Fractalkine) were analyzed in order to determine the changes in the expression, at different times after unilateral laser‐induced ocular hypertension (OHT), both in OHT eyes and their contralateral eyes respect to naïve eyes.At each of time point after OHT induction (days 1, 3, 5, 7 and 15), 12 OHT retinas, 12 contralateral retinas and 12 naïve retinas (lasered group n = 60, naïve n = 12) from Albino Swiss mice were analyzed. The samples obtained were processed and multiarray kits (MILLIPLEX MAP Mouse Cytokine/Myokine Magnetic Bead Panel) were used to quantify the expression of cytokines.In OHT eyes, the expression of the following cytokines: BDNF (1, 3, 7 and 15 days), VEGF (1 day), IL‐4 (at all‐time points except day 15), IL‐6 (1, 3 and 5 days), IFN‐ (3, 5 and 15 days), IL‐10 (3 and 5 days), and Fractalkine (1 day) were significant higher than in naïve. In contralateral eyes, the following cytokines: IL‐6 (1, 5 and 7 days), IL‐1β (1 and 3 days), IL‐4 (7 and 15 days), IL‐10 (7 days) and IL‐17 (15 days) showed a significant increase in comparison with naïveAfter unilateral laser‐induced ocular hypertension, OHT eyes and contralateral eyes showed changes in the expression of the anti‐ and pro‐inflammatory cytokines associated with inflammatory process, mainly 3 days after OHT induction. These factors, which may be released by activated macroglia and microglia, may exert neuroprotective and neurodegenerative effects.This work was supported by Ophthalmological Network OFTARED (RD12‐0034/0002 and RD12/0034/0014. Prevención, Detección Precoz y Tratamiento de la Patología Ocular Prevalente Degenerativa y Crónica), the Institute of Health of Carlos III of the Spanish Ministry of Economy; PN I+D+i 2008‐2011; ISCIII, General Subdirection of Networks and Cooperative Research Centers; by the FEDER European program. Grants to J.A. Fernández‐Albarral are currently supported by a Predoctoral Fellowship (FPU) from the Spanish Ministry of Science, Innovation and University.
Role of interferon alpha 2b (IFN‐α2b) in the treatment of conjunctive squamous neoplasia
Authors: Diaz Maria Dolores , Boned Ana , del Buey Maria Angeles , Marco Sara , López Isabel , Karlsruher Gisela , Montes Paula , Ascaso Francisco Javier 
Published: December 2019

AbstractPurposeIFN‐α2b has been postulated as an effective treatment to treat ocular surface tumors since the mid‐1990s. It could be used as a neoadjuvant agent, adjuvant therapy if there are positive margins after resection or as a primary agent for small tumors. It causes anti‐angiogenic, anti‐proliferative, cytotoxic and immunomodulatory effects. Consequently, it reduces the number of recurrences with few and mild side effects.MethodsWe present the case of a 77‐year‐old man with history of right eye cataract surgery who was seen in our Ophthalmology Department, due to a new appearance of a conjunctival tumor in the upper and lower temporal sectors, arriving at the bulbar conjunctiva with corneal invasion in the right eye. After performing a biopsy, squamous cell carcinoma with mild dysplasia was diagnosed. Ultrasonography and MRI were requested, ruling out infiltration. Surgical excision and amniotic membrane implantation were decided. Despite starting treatment with mitomycin C (MMC) 4 times a day, he suffered from a temporary recurrence. A second excision was performed 3 months later. This time, treatment with IFN‐α2b was started 4 times a day.ResultsIFN‐α2b is consolidating as a postoperative adjuvant treatment. In our case, it has managed to avoid new recurrences. We observed an asymmetric rise of the intraocular pressure (IOP) which could be associated with IFN‐α2b and need antihypertensive ocular topic treatment.ConclusionNowadays, surgery remains the gold standard in the treatment of these tumors. Nevertheless, the high rate of recurrences and the appearance of different treatments makes search for an optimized treatment of these patients possible and necessary. IFN‐α2b stands out in terms of cost‐effectiveness and must be present among the therapeutic arsenal of any ophthalmologist who faces this carcinoma but it side effects should be studied.
Clinical Experiences in Flash Adaptometry
Authors: Krastel Hermann , Zyganow Marlene , Kaltakji Feras , May Michael , Schlichtenbrede Frank 
Published: December 2019

AbstractPurposeTo demonstrate that flash adaptometry can easily be applied in clinical routine as extension of the ISCEV Standard Ganzfeld ERG.recording protocol.MethodsThe flash adaptometer has already been presented to the EVER community (2017). To avoid ocular electrode displacement during the 20 min of dark adaptation, stable conditions of recording are now maintained by skin electrodes. The small (5 mm of diameter) active electrode is placed onto the middle of the lower eyelid margin just below the eyelashes. Standard gold cup electrodes on temple and forehead provide reference and grounding. After dark adaptation, sensory thresholds are determined for perception of the 6,7 Hz ganzfeld stimuli and for recognition of a 10° contrast grid. Simultaneously, ERG ganzfeld thresholds are recorded.ResultsRecordings are shown in cases of age‐related macular degeneration, retinitis pigmentosa of dominant inheritance, late onset retino‐choroidal degeneration, congenital stationary night blindness and congenital achromatopsia.ConclusionBy flash adaptometry, a supplementary functional parameter of sensory and retinal function can be recorded in a clinical setting at small expense in time and no additional patient encumbrance.