bluuebunny/crossref_metadata_2025_split huggingface dataset:
Individuals prevalence affected by myopia in the riverside population of Santarém, Pará, compared to the urban population of Campinas, São Paulo
Authors: Raphaelli Caramel Lais , Scremin Czezacki Alexandre , Albertini Reis Bruna , Oncala Simão Giovanna , Olavarria Gustavo de Campos , Ferreira Greco Henrique , Carinhani Bragheto Isabella , Soares Ricioli Isabella , Anibale Rodrigues Junior José , da Cunha Gobbo Luísa , Benedicto de Souza Marianne , Albuquerque Beckedorff Otto , Giffoni Braga Mont'Alvão Vanessa , José Delfraro Carmo Thiago , Abreu Minussi Luíza , Barbosa Abreu Elvira 
Published: December 2019

AbstractPurposeMensure the prevalence of myopia between 5–14 years and the use of technology between urban and rural populations.MethodsA prospective, observational, analytical, cross‐sectional, ecological study based on the review of 225 medical records and questionnaires applied in the voluntary project Barco de Saúde São Leopoldo Mandic, in Santarém and in the Penido Burnier Institute, in Campinas. The questionnaire measured the variables: age, sex, age at onset of exposure to technology, exposure time, type of technology and reason for use. Refractometric data were collected from the same autorefractive equipment in the two city to minimize divergences.ResultsOf the 225 patients analyzed, 14.66% are myopic, 27.27% from Santarém and 72.73% from Campinas. It was seen that 78.89% of patients in Pará did not use technology or only used television, in Campinas only 21.11% had this kind of contact. In Campinas there is greater use associated of cell phones, television, computer and tablets, besides the time of technology use in Pará to be between 0 to 3 hours while in Campinas it takes more than 3 hours.ConclusionThe myopia has its prevalence increasing significantly. It is a disorder with great social impact and eye health. The fast growth of its prevalence has suggested the involvement of environmental factors, such as the extensive use of near vision and poor exposure in outdoor settings. The study evidenced the relevant contribution of the environment.
Unilateral optic nerve axotomy in pigmented mice causes RGCs loss in the contralateral uninjured retina that is prevented by microglial inhibition
Authors: Ruiz Fernando Lucas , Galindo‐Romero Caridad , Rodríguez‐Ramirez Kristy Tatiana , Vidal‐Sanz Manuel , Agudo‐Barriuso Marta 
Published: December 2019

AbstractPurposeUnilateral optic nerve crush (ONC) causes in adult mice microglial activation and phagocytosis in contralateral un‐injured retinas [1]. Minocycline is a tetracycline antibiotic that penetrates the central nervous system and inhibits microglial activation. The purpose is to evaluate if an unilateral axotomy (ONC) causes RGC loss in the contralateral retina, and to study if this death is modulated by microglial inhibition with minocycline.MethodsThe left optic nerve of adult male C57Bl/6 mice was crushed at 2 mm from the optic disk. Animals were treated daily by an intraperitoneal injection of minocycline. Both retinas were analyzed 3, 9 or 90 days after the lesion. Controls were retinas from intact animals, and ONC matched groups treated with vehicle. mRNA levels of Casp3, Pou4f1, Rbpms, Sncg were assessed by qPCR. For anatomical analyses retinas were dissected and immunolabelled for Brn3a and Iba1. The total number of RGCs was automatically quantified and their topography assessed by neighbour maps.ResultsIn the injured retinas, the loss of RGCs is first significant at day 3, and proceeds up to 90 days when only 1.5% of the original population survives. In the contralateral retinas, there is a significant loss of 15% of the RGCs at day 9 post‐lesion that does not proceed further, at least up to 90 days. Casp3 mRNA is up‐regulated at 3 and 9 days post‐ONC in the injured retinas, and at 3 days in their contralateral ones. The expression of RGC markers decreases over time in the injured retinas, while in their contralateral ones is transiently down‐regulated at 3 days. Minocycline treatment does not rescue RGCs in the injured retinas, but prevents RGC death in their contralateral ones.ConclusionsIn adult pigmented mice, ONC induces RGC loss in the contralateral uninjured retina that may be prevented with systemic minocycline treatment.Reference

Galindo‐Romero et al., 2013.
Retinal vessel diameters and systemic antioxidant capacity during hypoxia in patients with normal‐tension glaucoma and individuals with ocular hypertension
Authors: Langbøl Mia , Baskaran Thisayini , Tiedemann Daniel , Saruhanian Sarkis , Katrine Toft‐Kehler Anne , Koch Jensen Peter , Skov Jensen Peter , Vidiendal Olsen Niels , Vohra Rupali , Kolko Miriam 
Published: December 2019

AbstractPurposeAutoregulation is essential for a constant circulation of O2. The apparent dissimilarity of vulnerability towards increased intraocular pressure in patients with normal‐tension glaucoma (NTGs) and individuals with ocular hypertension (OHTs) has been linked to disturbed autoregulation. The retina is particularly O2‐dependent and susceptible towards oxidative stress. The purpose was to evaluate the impact of a fluctuating O2 level on retinal vessel diameters and plasma levels of vasoregulators, nitric oxide (NO) and endothelin‐1 (ET‐1), and total antioxidant capacity (TAC) in strictly characterized NTGs, OHTs and age‐matched controls.MethodsNTGs (n = 10–16), OHTs (n = 9–10) and controls (n = 9–14) were exposed to 2 h of hypoxia followed by 30 min of normoxia. Fundus pictures and blood samples were taken before hypoxia (“baseline”), during hypoxia (“hypoxia”) and after hypoxia (“recovery”). NO, ET‐1 and TAC was measured in plasma. Retinal arterial and vein diameters were measured with MATLAB.ResultsRetinal arteries dilated in NTGs and OHTs during hypoxia, while controls constricted. No significant changes were seen in retinal veins. During hypoxia controls and NTGs increased plasma levels of ET‐1 and NTGs sustained a high level in recovery. OHTs did not regulate ET‐1 but maintained a lower level compared to NTGs during hypoxia and recovery. No significant differences were seen in NO. OHTs had a higher TAC compared to NTGs and controls throughout the experiment.ConclusionsThe present study suggests a link between NTG and dysfunctional autoregulation. ET‐1 increase in controls and NTGs during hypoxia. As a vasoconstrictor, a vascular constriction is expected as evident in controls. The observed dilation in NTGs therefore might indicate that molecular mechanisms for vasoregulation are abolished. Surprisingly, OHTs present a similar pattern of autoregulation to NTGs but there is a prominent difference in the TAC. The higher level of TAC in OHTs compared to NTGs and controls indicates that the antioxidant defence might be important in providing resistance towards glaucomatous neurodegeneration.
Characterization and tissue localization of ocular carboxylesterases in multiple species
Authors: Hammid Anam , Vellonen Kati‐Sisko , Ruponen Marika , Urtti Arto , Honkakoski Paavo 
Published: December 2019

AbstractIntroductionOcular ADME (absorption, distribution, metabolism & elimination) is gaining interest due to rapidly growing incidence of eye diseases and the need of new therapeutic applications. The information regarding drug‐metabolising enzymes (DME) in different ocular tissues is scattered. In addition, animal models may not be predictive of the human situation due to species differences.Aimof the studyWe sought to obtain quantitative and functional data of ocular carboxylesterases in multiple species to help comparisons between preclinical animal models and humans.Methods

Esterase activity assays were optimized using established human‐specific substrates.

Quantitative proteomics was done using specific marker peptides to quantify the selected esterases in ocular tissues of different species (porcine, rabbit and human).

Finally, the functional and quantification data was compared between tissues and species.

Main findingsThe rabbit ocular tissues had about 3‐fold higher hydrolysis rates for the generic esterase substrate, p‐nitrophenyl acetate, than the pig tissues. Carboxylesterase 1‐mediated activity (D‐luciferin methyl ester as substrate) in pig ocular tissues were low as compared to rabbit. Moreover, carboxylesterase 2‐mediated activities (fluorescein diacetate as substrate) varied over a 5‐ to 20‐fold range among seven ocular tissues (conjunctiva, cornea, aqueous humor, vitreous, retina, RPE and choroid) in the pig and rabbit, respectively. On average, corneal and choroidal tissues showed high expression and functional activity of carboxylesterase isoforms while retinal pigment epithelium and aqueous humor showed the least activity. More detailed enzymatic and proteomic data will be presented at the poster.ConclusionThis study provides new insight in ocular esterase expression and esterase‐mediated drug metabolism in multiple species.
Protective effect of lipidure on ocular surface and soft contact lens against desiccation damage
Authors: Cristaldi Martina , Rusciano Dario , Olivieri Melania , Pezzino Salvatore , Lupo Gabriella , Daniela Anfuso Carmelina 
Published: December 2019

AbstractPurposeThe insertion of a contact lens (CL) disturbs the homeostasis of the tear film, favouring its evaporation and producing friction between the lens and the eyelids and the lens and the ocular surface. These events may induce or aggravate a pre‐existing condition of eye dryness. Lipidure is a biocompatible polymer of 2‐methacryloyloxi‐ethyl‐phosphorylcholine, showing a structure similar to the phosphatidylcholine polar bases; it is endowed with excellent antifouling and moisture retaining abilities. Aim of this study has been to address the protective effects of lipidure, with or without either hyaluronic acid (HA) or hydroxyl‐propyl‐methyl‐cellulose (HPMC), on desiccation of Statens Seruminstitut Rabbit Cornea (SIRC) cells and explanted porcine corneas. Moreover, the ability of lipidure to protect soft CL from desiccation damage and loss of transparency has also been evaluated.MethodsThe protective effect of lipidure was evaluated measuring viability on SIRC cells and explanted porcine corneas leaving them dried at 37°C, 5%CO2 and 95% humidity for 1 h. The ability of lipidure to protect soft CL from desiccation damage and loss of transparency has also been evaluated leaving them air‐dried at 26°C and 46% humidity.ResultsThe protective effect of 0.1% lipidure±HA (0.15%) or HPMC (0.3%), was compared to trehalose (3%), a sugar known in nature to protect cells from dessiccation damage. Results obtained indicate that lipidure either alone or in association with HA or HPMC is able to improve corneal epithelial cells survival under desiccation conditions, both in vitro and ex vivo, similar or even better than threalose alone. Moreover, lipidure in association with HPMC can better preserve morphology and transparency of CL from dehydration.ConclusionsIn conclusion, these studies support the use of lipidure both in artificial eye drops to protect the ocular surface form dryness, and as wetting agents for CL improve their tolerance over the eye surface.
Familial aniridia spectrum in four families of Czech origin with PAX6 mutations
Authors: Moravikova Jana , Dudakova Lubica , Kozmik Zbynek , Skalicka Pavlina , Liskova Petra 
Published: December 2019

AbstractPurposeTo identify disease‐causing mutations in four families with aniridia spectrum of Czech origin, to describe the associated phenotypes and to perform functional assessment of mutations located in canonical splice sites.MethodsAfter complex ophthalmic examination of all available family members, DNA extraction from blood or saliva samples was performed. All coding regions of PAX6 gene were Sanger sequenced. In two cases of mutations which could potentially affect splicing of pre‐mRNA functional reassessment was accomplished using Exontrap vector. In one family paternity testing using a standard set of markers was performed.ResultsIn total 13 affected individuals were examined. Except for common finding in aniridia, one individual had partial aniridia in the right eye and iris hypoplasia in the left eye, had bilateral ptosis, keratopathy with marked fibrovascular pannus, anterior polar cataracts, foveal hypoplasia, hepatopathy and trombocytopenia of unclear etiology. His affected daughter showed classical aniridia with total absence of iris and foveal hypoplasia in both eyes. Another individual had mild unilateral ptosis and anterior and posterior subcapsular cataracts. Bilateral microcornea, partial aniridia, surgically removed congenital cataracts and large posterior segment coloboma were present in another patient. In four probands, four different PAX6 mutations were identified, one mutation was novel (c.1183+1G>T). Two of detected variants were proven to affect pre‐mRNA splicing by skipping of adjutant exon sequences from mature mRNA.ConclusionLoss of visual functions in anterior segment dysgenesis disorders is often very severe, therefore establishing molecular diagnosis highly impacts patient management, enabling prenatal and preimplantation diagnostics. Our study enlarges the spectrum of known PAX6 mutations and confirms that anirida spectrum may also encompass combination of congenital ptosis, severe keratopathy and anterior polar cataracts. Vector Exontrap has been shown as an effective system for the evaluation of variants in canonical splicing sites.FundingSupported by SVV 260367/2017 and GAUK 82318‐2018.
In situ forming hydrogel for sustained intraocular drug delivery
Authors: Ilochonwu Blessing C. , Mihajlovic Marko , Tang Miao , Chen Mei , Hennink Wim E. , Vermonden Tina 
Published: December 2019

AbstractPurposeDelivery of therapeutic proteins to the posterior segment of the eye faces significant challenges because of frequent intraocular injections, related adverse effects and high treatment costs. This research project aims to design in situ forming hydrogels, which can be easily injected in the vitreous cavity using a small needle. After injection, the polymeric solution undergoes a phase transition to form a cross‐linked hydrogel at the site of administration, entrapping bioactives, which will be released over a prolonged period. In this study, Hyaluronic acid‐modified with furan moieties (HAFU) was successfully crosslinked with four arm‐PEG10K‐maleimide (4APM) yielding stable hydrogels. The potential use of this system for ocular applications was shown by testing the injectability, sustained release of a therapeutic protein and cytocompatibility to retinal cells.Methods & ResultsHAFU‐4APM hydrogels were prepared by mixing an aqueous solution of HAFU and 4APM at physiological conditions to obtain transparent hydrogels. Rheological analysis showed rapid hydrogel network formation at 37°C. The gelation time and final hydrogel stiffness are strongly dependent on polymer concentration. Hydrogel solutions could be injected to the vitreous body of a porcine eye through a 29G needle. Swelling and degradation analysis showed that the hydrogel system is degradable at physiological conditions. The hydrogels showed no toxicity to retinal cells at the used concentrations. HAFU‐4APM hydrogels could sustain the delivery of bevacizumab for 71 days.ConclusionInjectable in situ forming hydrogels have been prepared for the sustained retinal delivery of bevacizumab. The formulation has potential for the treatment of age‐related macular degeneration and diabetic retinopathy.AcknowledgementsThis project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska‐Curie grant agreement No 722717.
Detecting Hydroxychloroquine Retinal Toxicity using a Novel Multifocal Electroretinography Stimulus
Authors: Coupland Stuart , Tsang Adrian , Gottlieb Chloe , Gostimir Miso , Dollin Michael , Nithianandan Harrish 
Published: December 2019

AbstractPurposeTo evaluate a novel 5‐ring multifocal electroretinogram (mfERG) stimulus as a screening test for detecting hydroxychloroquine (HCQ) retinopathy.Study DesignA stratified case‐control study conducted in accordance to the Standards for Reporting of Diagnostic Accuracy Studies (STARD).MethodsConsecutive patients referred to the University of Ottawa for HCQ retinopathy screening from July 2018 to September 2018 underwent testing using a novel 5‐ring mfERG stimulus and the standard 61‐hexagon mfERG stimulus. Patients with amblyopia, high myopia or hyperopia, coexisting retinal disease, and prior retinal surgery were excluded. mfERG parameters were compared between protocols and against cumulative dose (CD), dose by real body weight (RBW), and duration of HCQ therapy. Ring amplitudes (R1‐R5) and ring ratios (R1‐R4/R5) were collected for each stimulus protocol. mfERG data was collected from an additional group of controls with no previous exposure to HCQ. Stata 15.1 software was used to perform the regression analyses, and to compute Spearman correlation coefficients between variables.Results24 eyes (10 patients, 2 controls) were included in the final analysis. The novel R2 and R3 P1 amplitudes and R2/R5 were moderately correlated with the respective R2 (r = 0.434, p = 0.034) and R3 (r = 0.429, p = 0.036) P1 amplitudes and R2/R5 (r = 0.422, p = 0.040) of the 61‐hexagon stimulus. The novel R2 P1 amplitude was highly correlated with CD (r = −0.687, p < 0.001), treatment duration (r = −0.687, p < 0.001), and dose by RBW (r = −0.763, p < 0.001). Similarly, novel R2/R5 was highly correlated with CD (r = −0.743, p < 0.001), treatment duration (r = −0.743, p < 0.001), and dose by RBW (r = −0.567, p = 0.004). The correlations between the 61‐hexagon stimulus R2/R5 and HCQ risk factors also reached significance but were not as robust. Linear regression analysis showed that CD may account for almost half of the variance in the novel R2/R5. (r2 = 0.486, R2/R5 = 9.68063 + cumulative dose ‐0.00286)ConclusionsThe 2016 AAO guidelines focused primarily on the use of subjective functional testing and objective structural testing and relegated mfERG based on a lack of accessibility. This pilot study describes a new 5‐ring mfERG protocol specific for HCQ retinopathy screening and suggests equivalence to the 61‐hexagon protocol at characterizing parafoveal function. This novel 5‐ring stimulus has a significantly shorter acquisition period and the ring design may be more sensitive to HCQ induced electrophysiologic change in the parafoveal region. R2 P1 amplitude and R2/R5 ring ratios acquired using this novel mfERG stimulus are strongly correlated to treatment duration and HCQ dosing. Additional prospective cohort studies are needed to validate this novel stimulus which may decrease the resource burden associated with objective functional testing.
Activating mutations in discoidin domain receptor 2 cause Warburg‐Cinotti syndrome
Authors: Zi Yan Xu Linda , Jensen Hanne , Johnston Jennifer J. , Di Maria Emilio , Kloth Katja , Cristea Ileana , Sapp Julie C. , Darling Thomas N. , Huryn Laryssa A. , Tranebjærg Lisbeth , Cinotti Elisa , Kubisch Christian , Rødahl Eyvind , Bruland Ove , Biesecker Leslie G. , Houge Gunnar , Bredrup Cecilie 
Published: December 2019

AbstractPurposeIn 2006 Warburg et al. described a patient with blepharophimosis, corneal vascularization, retinal degeneration, deafness, loss of subcutanous tissue, flexion contractures of the fingers and acro‐osteolysis. Some years later Cinotti et al. reported a similar patient. In addition, we identified tree individuals from two different families with a similar clinical picture. In total, all six individuals from four different families were examined to identify the gene mutation associated with this diseaseMethodsExome sequencing was performed on affected individuals. Patient skin fibroblasts was obtained and examined using Elisa and Western blot analysis to determine levels of phosphorylated DDR2 and downstream effector proteins. Patient fibroblasts were also treated with Dasatabib, a protein kinase inhibitor affecting DDR2.ResultsWe found two recurrent de novo mutations in DDR2, p.Leu610Pro or p.Tyr740Cys, to be associated with the condition. Increased phosphorylation of DDR2 was found suggesting reduced receptor autoinhibition and ligand‐independent activation of the kinase. Dasatinib prevented DDR2 autophosphorylation. No effect of the mutations were found on the examined downstream effector proteins of DRR2.ConclusionWe found two recurrent, activating mutations in DDR2, p.Leu610Pro and p.Tyr740Cys, to be associated with this progressive fibrotic condition that we suggest to be called Warburgh‐Cinotti syndrome. In vitro dasatinib prevented autophosphorylation of DDR2 suggesting an approach to patient treatment.Reference
et al. (2018): . The American Journal of Human Genetics. https://doi.org/10.1016/j.ajhg.2018.20.013.
Digital carcinoma of a sweat gland metastasizing to the lacrimal gland: report of a rare case
Authors: Philips Simon , Jadnanansing Jayant , Fordel Nerea , Vanclooster Andreas , Geldhof Kurt , De Schryver Ilse 
Published: December 2019

AbstractPurposeTo report a rare case of a digital carcinoma of the sweat gland with lacrimal gland metastasis.MethodsObservational case reportResultsA 62‐year‐old woman presented with right proptosis and diplopia. General examination showed unilateral lymphedema of the left upper limb, initially restricted to the forearm and progressively involving the upperarm with an axillary lymphadenopathy. Work‐up included a whole‐body 18F‐FDG‐PET/CT showing high uptake in the right lacrimal gland, the cervical and axillary glands. Screening for breast carcinoma was negative. A biopsy of the axillary lymph nodes was performed. Immunohistochemical analysis was positive for CK7 and negative for GATA3, ER, PR, TTF1 and SOX10. The diagnosis of a metastatic process of a CK7 positive undifferentiated tumor of unknown primary origin was withheld. Physical examination of the left upper limb showed a small scar at the level of the thumb. Retrograde investigation revealed resection of a lesion in 2016 with the histopathological diagnosis of an eccrine ductal carcinoma of a sweat gland. Immunohistochemical analysis showed concordance between primary and metastatic lesions.ConclusionAlthough the clinical presentation and the general work‐up are highly suggestive for a metastatic process in the lacrimal gland, the final diagnosis relies on the histopathology or cytology. To the best of our knowledge, metastasis of a primary cutaneous sweat gland carcinoma to the lacrimal gland has not been reported in the literature.