bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case report: persistent corneal epithelial defect after glaucoma device implantation for radiation glacoma
Authors: Shimizu Daisuke , Tawada Ayako , Yamamoto Shuichi 
Published: December 2019

AbstractPurposeWe report a case with persistent epithelial defect after Barvert glaucoma implant for radiation glaucoma.Methods and Results62‐year‐old man had a total of 70 Gray radiation exposure for 2 months for left ethmoid sinus cancer In December 2015. In February 2016, the patient visited eye clinic for left eye pain. Only SPK was found and artificial tear drop was prescribed and followed‐up in the clinic. In January 2017, left intraocular pressure was elevated and angle neovascularization was found. Photocoagulation was started on diagnosis of radiation glaucoma. Although the treatment could not be completed due to progression of cataract, intraocular pressure had been within normal range under glaucoma drops treatment. He was referred to our hospital in August 2018 for the treatment of cataract surgery in his left eye. At the first visit, his left best corrected visual acuity was 0.01 and left Intraocular pressure was 20 mmHg. Mild Superficial punctate keratitis was found in his left eye but tear fluid meniscus was normal. We planned to add PC after cataract surgery at first. But in consideration of the possibility of deterioration of Neovasucular Glaucoma after surgery, we performed not only cataract surgery but also vitrectomy with Barvert glaucoma implantation and photocoagulation in September of the same year. Postoperative inflammation was transient, the intraocular pressure was good, and small corneal erosion was found immediately after the operation. However, after surgery, there was an extreme decrease in lacrimal secretion, and corneal erosions were enlarged, resulting in persistent epithelial defects. Treatment with a punctum plug, a therapeutic soft contact lens, eye drops etc. was poorly improved, and a corneal infiltration suspected of fungal keratitis was found during the course.ConclusionsImplantation or vitreous surgery for radiation retinopathy or radiation glaucoma may cause persistent corneal epithelial defects. It is necessary to carefully check the preoperative evaluation of tears and corneal condition and to carry out minimally invasive treatment.
EYS606 for the Treatment of Non‐Infectious Uveitis
Authors: Hoogewoud Florence , Buggage Ronald , Behar‐Cohen Francine 
Published: December 2019

AbstractPurposeWhile effective for corticosteroid sparing, systemic anti‐tumor necrosis factor‐alpha (TNF) therapy is associated with potentially serious side effects. Intraocular anti‐TNF therapy offers the possibility to reduce systemic safety concerns, improve patient compliance and enhance efficacy. EYS606 is a novel non‐viral gene therapy that induces ciliary muscle cells to express a potent anti‐TNF fusion protein in the eye. Herein, we present the results from Part 1 of a first‐in‐human study investigating EYS606 in patients with NIU.MethodsThe EYS606‐CT1 study is an ongoing, 24 week, multicenter, open‐label, phase I/II study investigating the safety and tolerability EYS606 administered using a proprietary electrotransfection system. In Part 1, end stage NIU patients were assigned to treatment with one of three escalating EYS606 doses, while in Part 2, patients with less severe, active NIU will receive the maximally tolerated EYS606 dose. The primary outcome is the assessment of adverse events (AEs) after treatment administration.ResultsNine patients (3 per cohort) with refractory posterior or panuveitis were enrolled and treated in Part 1 of the study. The majority AEs occurring within 4 weeks of EYS606 treatment were mild in severity, ocular in nature and related to the treatment administration procedure. No serious adverse events related to EYS606 were reported. Despite the advanced disease stage, clinically significant improvements from baseline were observed in 3 patients including >10 ETDRS letter gain in visual acuity in one and reductions in macular edema in two treated in the highest dose cohort.ConclusionsThese results suggest that EYS606 could be a safe and effective local treatment for NIU that avoids the safety concerns and inconveniences of systemic NIU therapies. Treatment of active NIU patients in Part 2 of study will further clarify the risks and benefits of sustained TNF inhibition in the eye.
In Vivo corneal confocal microscopy study of keratoendotheliitis fugax hereditaria caused by a pathogenic variant in the NLRP3 gene
Authors: Turunen Joni , Immonen Annamari , Järvinen Reetta‐Stiina , Kawan Sabita , Repo Pauliina , Korsbäck Anna , Jaakkola Aino , Majander Anna , Vesaluoma Minna , Kivelä Tero 
Published: December 2019

AbstractPurposeTo elucidate by using in vivo corneal confocal microscopy (IVCM) the pathogenesis of keratoendotheliitis fugax hereditaria, an autosomal dominant cryopyrin‐associated periodic keratitis associated with a pathogenic variant in NLRP3, in its acute and chronic phase.MethodsCross‐sectional, hospital‐based study of 7 patients during an acute attack and 18 patients in the chronic phase. Corneal photography, IVCM and Sanger sequencing to confirm NLRP3 variant c.61C>G were performed.ResultsDuring the acute attack, the stroma was transiently infiltrated with hyperreflective small roundish bodies consistent with inflammatory cells. Other layers of the cornea were essentially normal. With multiple recurring attacks, a central corneal stromal opacity gradually develops. IVCM revealed that the opacities correspond to hyperreflective needle‐shaped structures in the extracellular matrix of the stroma.ConclusionsKeratoendotheliitis fugax hereditaria mainly involves the middle layers of the corneal stroma, and is stromal keratitis rather than a true keratoendotheliitis. IVCM shows that inflammatory cells invade only the stroma during an acute attack. With repeated attacks, needle‐shaped hyperreflective extracellular matrix elements emerge and cause a persistent opacity. The disease will be excellent in vivo human model to study the activation of the NLRP3 inflammasome and the tissue specificity in cryopyrin‐associated periodic syndromes.
Towards improved siRNA delivery to the corneal epithelium: exploring cationic amphiphilic drugs as siRNA delivery enhancers
Authors: Wels Mike , Sauvage Félix , Raemdonck Koen , De Smedt Stefaan 
Published: December 2019

AbstractPurposeCorneal blindness is one of the most important causes of preventable blindness. With a shortage of donors people end up losing their vision. Alternatives to heal the cornea are clearly needed. Small interfering RNA (siRNA) has the ability to regulate intracellular protein concentration and shows potential to modulate corneal wound healing. However, to exert its function siRNA needs to reach the cytosol. Here we investigate a strategy to avoid lysosomal siRNA degradation.MethodsDue to their capacity to permeabilize (lysosomal membranes, cationic amphiphilic drugs (CADs) can enhance the release of siRNA from lysosomes to the cytosol. By staining the lysosomes we were able to determine the effect of several CADs in primary bovine corneal epithelial cells (pBCECs) by flow cytometry and confocal microscopy. To correlate CAD‐induced lysosomal membrane permeabilization with improved siRNA delivery in pBCECs, we investigated the silencing efficiency of t siRNA when followed by a CAD treatment.ResultsUp to two‐fold increase of fluorescence signal was observed indicating swelling of existing lysosomes and/or an increase in the number of lysosomes inside pBCECs. Confocal imaging of stained pBCECs confirmed the increase in lysosomal size. Cytotoxicity tests (MTT assay) showed concentrations used to induce lysosomal swelling were not toxic (metabolic activity ≥80%).Treatment with siRNA with a subsequent treatment with CADs increased silencing efficiency suggesting an improved siRNA delivery.ConclusionsWe have shown the ability to induce lysosomal membrane permeabilization in primary bovine corneal epithelial cells with CADs. A subsequent administration of CADs after siRNA treatment increased its capacity of silencing indicating an enhanced release from the lysosomal compartment.
Substance P receptor antagonists fosaprepitant and spantide in an UVR‐B‐induced cataract mouse model
Authors: Wegener Alfred , Kronschläger Martin , Schönfeld Carl‐Ludwig , Holz Frank , Meyer Linda , Gross Janine 
Published: December 2019

AbstractPurposeTo investigate the neurokinin receptor‐1 (NKR‐1) antagonists fosaprepitant and spantide in an UVR‐B‐induced cataract mouse model. To examine their effect on the expression of pro‐inflammatory cytokines and chemokines in ocular tissues of both eyes after unilateral UVR‐B exposure.MethodsMice were injected intraperitoneally with NKR‐1 antagonists before and after unilateral UVR‐B exposure to a 5‐fold cataract threshold dose. The contralateral partner eye was completely shielded during the experiment. Control mice were similarly injected with saline only. Mice were categorized into latency period groups of 3 and 7 days following exposure. Subsequently, eyes were enucleated and ocular tissues were microsurgically dissected for NKR‐1 protein concentration by enzyme‐linked immunosorbent assay (ELISA). Cytokines and chemokines in ocular tissue samples were measured using a Multiplex Immunoassay.ResultsPretreatment with fosaprepitant decreases NKR‐1 protein levels in mouse eyes after UVR‐B exposure to only one eye. NKR‐1 protein level was reduced in the exposed cornea, lens epithelium, iris/ciliary body, aqueous humor, retina and choroid as well as in the unexposed lens epithelium when compared with the saline treated mice. Spantide I treatment showed nearly the same NKR‐1 level in comparison to the saline group. Initiated fosaprepitant injection resulted in a significant reduction of Gro‐alpha/CXCL1 in the exposed cornea. No differences were measured between the treatment groups of other tested cytokines/chemokines in the mouse eye.ConclusionThe UVR‐B induced expression of NKR‐1 in ocular tissues is decreased by fosaprepitant in the exposed as well as in the unexposed partner eye. A previously reported sympathizing NKR‐1 upregulation in the unexposed partner eye can be counteracted by fosaprepitant. Therefore, substance P and its receptor seem to be the signaling molecules involved in the contralateral reaction following unilateral UVR‐B exposure.
Ocular melanin binding of drugs: in vitro binding studies
Authors: Bahrpeyma Sina , Rimpelä Anna‐Kaisa , Hagström Marja , Urtti Arto 
Published: December 2019

AbstractCertain drugs accumulate into pigmented tissues due to their binding to melanin, a macromolecule inside pigmented cells. Melanin can affect the drug’s pharmacokinetics by acting as a drug reservoir. Binding of drugs to the ocular melanin might enable ocular drug targeting, prolonged duration of action and retinal delivery after non‐invasive drug administration (eye drops, tablet). Interestingly, chloroquine levels are maintained in the pigmented retinal and choroidal cells for months after discontinuation of dosing. The aim of the experimental part was to study melanin binding of a set of compounds in vitro with isolated melanin from the retinal pigment epithelium (RPE) and choroid of porcine eyes. The in vitro binding with melanin was studied at three different pH (i.e. 5, 6, 7.4) since melanosomal pH is unknown but expected to be acidic, so these range of pH will help us to understand the effect of pH on binding affinity and capacity. The compounds chosen for the study; papaverine, levofloxacin, terazosin, pazopanib, are small molecules with diverse physicochemical properties (octanol/water partitioning coefficient (log P), pKa, acid/base status). The binding parameters (Bmax and Kd) estimated from Sips isotherm where the actual distribution of binding energies is most likely continuous and unimodal. Binding parameters were calculated based on experimental data and terazosin is the most potent melanin binder by having K value of 13.30 (K = Bmax/Kdn ). In addition, pH has quite large effect on binding for example binding affinity and capacity of levofloxacin at pH 5 is almost as three times as pH 7.4. This study demonstrates the importance of melanosomal pH on melanin binding of drugs and a useful step toward building a bottom‐up pharmacokinetic model for ocular drug delivery.
Across‐frequency interference in visual temporal gap detection revisited
Authors: Hirose Nobuyuki , Mori Shuji 
Published: December 2019

AbstractPurposeAt EVER2017, we reported that visual detection of a temporal gap becomes difficult when spatial frequency separation is introduced between markers delimiting the gap. In that report, however, gap thresholds were measured separately, in different runs, for within‐frequency and across‐frequency gap detection. Therefore, our previous findings may be simply explained by the effect of spatial‐frequency specific adaptation on visible persistence. Here, we reassessed the across‐frequency interference in gap detection using a procedure uncontaminated by spatial‐frequency specific adaptation.MethodsGaussian‐windowed sinusoidal gratings were used for gap markers. Spatial frequencies of the leading and trailing markers were manipulated to be either 2 or 4 cpd. Gap thresholds were measured using a two‐interval, two‐alternative forced choice method with a two‐down/one‐up interleaved adaptive staircase procedure targeting 70.7% correct detection: Four staircases corresponding to the four combinations of marker frequencies were interleaved in a single run and randomly selected in each trial. Sixteen observers with normal vision completed two runs, and the mean of estimated thresholds between two runs for each condition were subject to analysis.ResultsGap thresholds for across‐frequency markers (2‐4 and 4‐2 conditions) were significantly higher than those for within‐frequency markers (2‐2 and 4‐4 conditions). For within‐frequency gap detection, gap thresholds were significantly higher for 4 cpd than for 2 cpd markers, which was consistent with the well‐known decreased temporal resolution with increasing spatial frequency.ConclusionWe confirmed our previous findings that temporal gaps bounded by different frequency markers are more difficult to detect than those bounded by identical frequency markers. We propose that perceptual discontinuity signaling the frequency separation interferes with gap representation and longer gaps are required for correct gap detection.
The role of magnetic resonance imaging in diagnosis of uveal melanoma
Authors: Serras‐Pereira Rita , Morais Teresa , Vieira Luísa , Batalha Carlos , Ramalho Joana , Duarte Ana , Magriço Ana 
Published: December 2019

AbstractPurposeTo evaluate the potential role of Magnetic Resonance Imaging (MRI) in the diagnosis of uveal melanoma.MethodsRetrospective case series involving a total of 10 patients, 9 with uveal melanoma and 1 with a suspicious melanocytic lesion, diagnosed by A‐mode and B‐mode ultrasound (US) scan. 6 of the 10 patients simultaneously performed MRI for diagnostic purposes. The results of both modalities were compared with respect to lesion dimensions, extra‐scleral extension and presence of retinal detachment (RD).ResultsIn this case series, 4 patients were diagnosed with uveal melanoma based exclusively on echographic findings and 6 patients underwent both US and MRI for diagnostic purposes. The MRI excluded the diagnosis of uveal melanoma in one patient with suspected US imaging. In the remaining 5 patients that underwent both modalities, we did not identify significant differences in lesion dimensions. Extra‐scleral extension was not identified in this subgroup by US, and MRI findings corroborated these results. With respect to RD, it was identified in 2 of these 6 subjects by US but MRI failed to identify a discrete RD in one of the subjects.ConclusionsThe present case series focused on the differences between US and MRI in the diagnosis of uveal melanoma in order to assess the potential role of MRI in such cases. We did not find any difference in diagnostic accuracy, lesion dimensions and detection of extra‐scleral extension between the two modalities, except for one patient with a suspected lesion on US that was excluded with MRI. US, however, was found to be more sensitive than MRI in the diagnosis of RD, detecting a small RD not identified by MRI. The authors identify as main limitation the small number of subjects included in the case study. Further studies involving a greater number of patients are necessary to precisely determine the role of MRI in diagnosis of uveal melanoma.
The Role of TGF‐□1 on RHO GTPase, GSK3, JNK, MMP‐2, ‐Catenin and ‐SMA expression in myofibroblast cell culture orbital soket contracture
Authors: Dewi Debby Shintiya 
Published: December 2019

AbstractPurposeTo study the role of TGF‐□1 on the expression of RHO GTPase, GSK3, JNK, MMP‐2, □‐catenin and □‐SMA in the myofibroblast cell culture of orbital socket contracture.MethodsThis research is an experimental research with invitro model of the myofibroblast cell culture of orbital socket contracture. □‐Sma expression examine with immunohistochemistry and confocal microscopy. Examination of the RHO GTPase, GSK3, JNK, MMP‐2, and □‐catenin expression using ELISA KIT, while the morphology of fibroblasts or myofibroblasts was examined by 100× magnification with an inverted Olympus IX 71 microscope and 400× magnification with CLSM FV1000ResultsIncreased dose of TGF‐□1 in passages 3 decreased the expression of a‐SMA and no morphological changes in myofibroblast cells. The morphology of myofibroblasts cells can not turn back into fibroblasts. Increased doses of TGF‐□1 increase JNK expression, slightly increase RHO GTPase expression, decrease GSK3 and a‐SMA expression, and doesn’t change MMP‐2 and □‐cathenine expression.ConclusionsTGF‐□1 increase JNK expression and slightly RHO GTPase, but decrease the expression GSK3 and a‐SMA, and has no effect on MMP‐2 and □‐cathenine expression in Myofibroblast Cell Culture Orbital Soket Contracture.
The development of inflammatory eye diseases in patients with endocrine ophthalmopathy after the removal of restrictive strabismus
Authors: Gladysheva Galina 
Published: December 2019

AbstractResearch objectiveIs to show the ways of prevention of corneal complications that patients with endocrine ophthalmopathy (EOP) may have after restrictive strabismus removal.MethodsA patient with an acute keratouveuitis, a purulent helcoma of the left eye against the background of EOP of both eyes after left eye restrictive strabismus removal was examined. The patient underwent biomicroscopic examination with staining solution of fluorescein, beta scanning, anterior segment optical coherence tomography and anti‐inflammatory, antibacterial, keratoprotective treatment was prescribed. There was done bacteriological conjunctival test. Design of the research – case series.ResultsAn important point of intraoperative case management in patients with EOP was to prevent corneal complications. It was related to the duration of surgical intervention, risk of damage to the corneal epithelium during its contact with expander as a result of significant vertical eye rotations during the surgery. We use more frequent irrigation of cornea with normal saline solution or instillation of viskoelastics as keratoprotectors. After surgery, the patient does not have the ability to close the eyelids. It also increases the risk of corneal damage. The cause may be the contact of the cornea with a sterile gauze bandage applied and its non‐moisturizing due to the lack of blinking. In addition, the preoperative hypotropia created protection of the cornea by its contact with the conjunctiva of the lower eyelid. The eye level achieved after the surgery deprives the patient of this “protection”. Therefore there wasn’t applied a gauze bandage but a perforated convex plastic occluder. The cornea is irrigated with keratoprotectors till the ability to close eyelids is reached.ConclusionsSuggested intraoperative and postoperative strategies to manage cases in patients with EOP are the most effective. As long as they allow to reduce all possible corneal complications.
Papillorenal syndrome with secondary serous retinal detachment: family history can help the diagnosis
Authors: Roulez Francoise 
Published: December 2019

AbstractIntroductionCavitary congenital optic discs anomalies include optic disc coloboma, optic disc pit, morning glory syndrome and papillorenal syndrome. Optic disc aspect and retinal complications are often very similarMethodCase report of a young boy with bilateral congenital malformation of the optic disc and secondary exsudative maculopathy.ResultsOptic disc morphology and slow spontaneous resolution of the serous retinal detachment is illustrated. Family history and father examination oriented towards the diagnosis of papillorenal syndrome.ConclusionCharacteristic optic disc features of the syndrome is described. Patients with multiple cilioretinal vessels should be evaluated to identify the sometimes serious renal abnormalities in papillorenal syndrome. Early diagnosis is important, because prophylactic systemic antihypertensive treatment can limit renal morbidity.
Oxidative stress induces mitochondrial dysfunction and autophagy in ARPE‐19 cells
Authors: Blasiak Janusz , Barszczewska Gabriela , Gralewska Patrycja , Kaarniranta Kai 
Published: December 2019

AbstractPurposeOxidative stress plays an important role in the pathogenesis of age‐related macular degeneration (AMD), but the exact mechanism of the influence of the stress is not completely clear. The stress can affect both neural retina and retinal pigment epithelium (RPE) cells The purpose of our study was to evaluate changes in some mitochondrial properties and autophagy in the response of RPE cells to oxidative stress.MethodsRetinal pigment epithelium ARPE‐19 cells were challenged with 200 mM H2O2 for 2 h. Mitochondrial ROS (mtROS) were assessed by the MitoSOX probe, mitochondrial membrane potential (MMP) with JC‐1, the activity of the complex I of the mitochondrial respiratory chain with MitoCheck. To assess autophagy cells were transfected with the pBABE‐puro mCherry‐EGFP‐LC3B plasmid and autophagic flux was evaluated with confocal fluorescent microscopy; expression of the LC3‐I and LC3‐II proteins were quantified by immunoblotting.ResultsHydrogen peroxide induced an increase in mtROS and decrease in MMP in ARPE‐19 cells as well as it inhibited the activity of the complex I. Furthermore, an increase in the LC3‐II/LC3‐I ratio and an increased number of autophagolysosomes was observed in ARPE‐19 cells challenged with hydrogen peroxide.ConclusionOxidative stress induces detrimental changes in mitochondria of RPE cells that can respond to these changes by increased autophagy, confirming that mitochondrial homeostasis and autophagy may be important in AMD pathogenesis.This work was supported by National Science Centre, Poland grant number 2017/27/B/NZ3/00872.