bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nation‐wide survival outcomes of metastatic uveal melanoma with best supportive care
Authors: Rantala Elina , Hernberg Micaela , Kivelä Tero 
Published: December 2019

AbstractPurposeTo report overall survival (OS) of patients with metastatic uveal melanoma who received best supportive care (BSC).MethodsRetrospective cohort study of patients with primary uveal melanoma treated between January 1999 and December 2016 at a national referral center and diagnosed with metastasis before December 2016. The patients who received BSC as the only treatment were enrolled. Complete data for all patients was requested from all hospitals that had participated in management. Age, gender, time from primary tumour to metastasis, presence of symptoms, locations of metastases, largest metastasis diameter, WHO performance index, and liver function tests were collected. Predicted median survival time calculated according to the Ophthalmic Oncology Group (OOG)‐validated Helsinki University Hospital Working Formulation (HUCH‐WF) was used to assign patients to stages IVa, IVb, and IVc, which correspond to predicted survival times of >12, <12–6, and <6 months, respectively. Primary endpoint was OS estimated with Kaplan–Meier analysis.ResultsThe median OS was 1.6 months (range 0–65.8, 95% CI 1.0–3.4) from the beginning of treatment in 84 patients. According to the HUCH‐WF, 20 (23%) patients with known survival time were assigned to stage IVa, 16 (19%) to IVb, 41 (49%) to IVc, and 7 (8%) were missing data. OS according to the HUCH‐WF was 11.1 months (95% CI 8.3–22.0) in stage IVa, 3.4 months (95% CI 1.0–10.0) in IVb, and 0.7 months (95% CI 0.4–0.9) in IVc.ConclusionsHUCH‐WF can differentiate by OS patients who receive BSC. The OS for stage IVa disease was similar to the median OS of 12.8 months reported in a meta‐analysis for all patients who receive active treatment. However, divided by HUCH‐WF, comparison with our data suggest that patients who receive active treatment for stage IVa and IVb disease might live on average 7 months longer (OS 18.6, 10.7, and 4.6 months for stage IVa, IVb, and IVc, respectively, in the OOG validation study).
Intravitreal kinetics of macromolecules in rats and rabbits: evaluation with ocular fluorophotometry
Authors: Sadeghi Amir , Toropainen Elisa , Valtari Annika , Puranen Jooseppi , Ruponen Marika , Ranta Veli‐Pekka , Urtti Arto 
Published: December 2019

AbstractPurposeRats and rabbits are widely used in preclinical ocular pharmacodynamics and pharmacokinetics. Despite the wide application in the evaluation of intravitreally injected drugs, there is no information about scaling of vitreal kinetics between rats and rabbits. In this study, the vitreal kinetics of macromolecules in rats and rabbits were evaluated using in vivo fluorophotometry.MethodsIn order to elucidate the pharmacokinetics of macromolecules and drug delivery systems we used ocular fluorophotometry that is a noninvasive technique for non‐invasive and quantitative measurement of fluorescence signals from the eye. Molecules with different molecular weights (peptide 4.5 kD, FITC‐hyaluronic acid 770 kD, FITC‐dextran 500 kD and fluorescein 330 D, FITC‐dextran 10 kD and FITC‐dextran 150 kD) were injected to the vitreous of rabbits and rats. The concentrations of these molecules were quantified in the vitreous at various time.Results and DiscussionThe data were used to calculate kinetic parameter, such as vitreal elimination half‐life and clearance. For example, the vitreal elimination half‐lives of FITC‐hyaluronic acid 770 kD in rabbits and rats were about 280 hr and 9 hr, respectively. Overall the vitreal elimination half‐lives of the compounds in the rats were much faster than in the rabbits. Since rats are widely used in the retinal pharmacodynamics studies, the fast elimination of macromolecules from the rat vitreous should be taken into account when scaling the doses from rats to rabbits and man.
Inhibition of adaptor proteins MAVS and TXNIP reduces inflammasome activation in RPE cells
Authors: Ranta‐aho Sofia , Bhattarai Niina , Korhonen Eveliina , Piippo Niina , Hytti Maria , Kaarniranta Kai , Kauppinen Anu 
Published: December 2019

AbstractNLRP3 inflammasome is one of the inflammatory factors linked to the development of age‐related macular degeneration (AMD). For its activation, several regulatory proteins are needed. Mitochondrial antiviral‐signaling protein (MAVS) recruits NLRP3 inflammasome to the surface of mitochondria, where it is activated. Another adaptor protein, thioredoxin (TRX)‐interacting protein (TXNIP) binds to NLRP3 promoting its activation. It has been shown that the silencing of MAVS or TXNIP leads to the reduced secretion of IL‐1β, which is a marker of NLRP3 activation. Here, we tested whether the silencing of MAVS or TXNIP reduces the activation of NLRP3 also on human retinal pigment epithelial cells (RPE). ARPE‐19 cells we tranfected with three different commercial MAVS and TXNIP siRNAs. The NLRP3 was primed with IL‐1α and activated by blocking proteasomal and autophagosomal clearance with MG‐132 and Bafilomycin A (BafA), respectively. Thereafter, the levels of IL‐1β and NLRP3 were detected using the ELISA method and cytotoxicity was measured by the lactate dehydrogenase (LDH) assay. Specific siRNAs to MAVS and TXNIP significantly reduced the secretion of IL‐1β from human RPE cells upon inflammasome activation by the blockade of intracellular clearance. Additionally, silencing of TXNIP protected from cell membrane rupturing and reduced the amount of extracellular NLRP3, which indicates attenuated inflammasome activity. In RPE cells, regulatory proteins TXNIP and MAVS are involved in the activation of NLRP3 inflammasome.
Complete blood cell count indexes in non‐arteritic anterior ischemic optic neuropathy
Authors: Pinna Antonio , Porcu Tiziana , Marzano Jacopo , Boscia Francesco , Paliogiannis Panagiotis , Carru Ciriaco , Zinellu Angelo 
Published: December 2019

AbstractPurposeTo investigate the role of some blood count‐derived inflammation biomarkers in non‐arteritic anterior ischemic optic neuropathy (NAION).Methods37 newly diagnosed NAION patients and 37 sex‐ and age‐matched subjects without NAION were recruited between January 2017 and December 2018. A blood sample was taken and complete blood cell count was performed. The following blood cell count‐derived indexes were evaluated: neutrophil/lymphocyte ratio (NLR), derived NLR [dNLR = neutrophils/(white blood cells‐neutrophils)], platelet/lymphocyte ratio (PLR).ResultsNAION patients had significantly higher median values of mean platelet volume (MPV; p = 0.01), red cell distribution width (RDW; p = 0.015), NLR (p = 0.03), and dNLR (p = 0.01). There were no significant differences in white blood cells, lymphocytes, neutrophils, and PLR.ConclusionResults suggest that MPV, RDW, NLR and dNLR may be disease biomarkers in NAION. Larger scale studies are necessary to confirm these findings.
Positive correlation of blood reflux in Schlemm’s canal and reduction of intraocular pressure after ab interno 360‐degree viscocanalostomy in primary open‐angle glaucoma
Authors: Grieshaber Matthias , Pienaar Ané , Stegmann Robert 
Published: December 2019

AbstractPurposeThe aim was to investigate the association between blood reflux in Schlemm’s canal (SC) and the reduction of intraocular pressure (IOP) after ab interno viscocanalostomy in primary open‐angle glaucoma (POAG).MethodsNon‐comparative study of consecutive patients with early to moderate POAG underwent ab interno viscocanalostomy with a follow‐up time of at least 12 months. Indications for glaucoma surgery were inadequate IOP and /or intolerance to eye drops. Through clear cornea incision, the IOP was lowered below episcleral venous pressure by aspiration of aqueous from the anterior chamber to provoke blood reflux into the SC. After a 1‐min waiting period, a goniolens was placed on the globe, and blood reflux was observed and classified into three filling patterns: no filling, partly filling and complete filling. Then, the anterior chamber was filled with viscoelastic material and ab interno viscocanalostomy was performed with a microcatheter system (Visco360).ResultsIn provocative gonioscopy, 12 eyes had no blood reflux (group 1), 19 had patchy blood reflux (group 2), and 14 had complete blood reflux (group 3). For the different reflux patterns, the preoperative IOP was 17.0 mmHg (SD ± 2.8) mmHg for group 1, 18.4 mmHg (SD ± 2.0) for group 2, and 22.2 mmHg (SD ± 2.8) for group 3. The IOP difference between preoperative and 6 months postoperative was 1.8 mmHg (SD ± 1.2) group 1, 4.9 mmHg (SD ± 0.9) for group 2, and 9.9 mmHg (SD ± 2.5) for group 3 (p < 0.001). In a linear regression model, there were highly significant differences between the groups even after adjustment for preoperative IOP (p < 0.001).ConclusionsBlood reflux in SC seems to be a significant positive prognostic indicator in uneventful ab interno viscocanalostomy concerning IOP reduction, possibly representing the patency of the physiologic aqueous outflow system.
Improvements of retinal sensitivity, visual acuity, and central retinal thickness after intravitreal injection of aflibercept in patients with wet age‐related macular degeneration
Authors: Nizawa Tomohiro , Kitahashi Masayasu , Baba Takayuki , Iwase Takehito , Kubota Mariko , Hattori Yoko , Kawasaki Yohei , Iwase Takayuki , Sato Takatoshi , Ogawa Shoko , Sugawara Takeshi , Yamamoto Shuichi 
Published: December 2019

AbstractPurposeTo determine the retinal sensitivity, best‐corrected visual acuity (BCVA), and central retinal thickness (CRT) in patients with wet age‐related macular degeneration (wAMD) after intravitreal aflibercept (IVA).MethodsAn observational study conducted at the Chiba University Hospital between October 2016 and March 2019. All patients were treatment‐naïve with wet AMD and received three monthly (induction phase) and bimonthly (maintenance phase) of IVA for 12 months. Each patient underwent spectral‐domain OCT, fundus autofluorescence, indocyanine green angiography, and microperimetry. The primary outcome was the change in the retinal sensitivity from the baseline at 6 months (6 M). The retinal sensitivity was determined by the average of 13 points within the central 2 degrees and measured by Macular Integrity Assessment (MAIA, CenterVue, Italy). The secondary outcomes were the changes in the BCVA, CRT, presence of subretinal exudations, and greatest linear dimension (GLD) at 12 M relative to the baseline.ResultsThirty‐seven eyes of 37 patients were studied. The mean age was 72.8 ± 7.4 years (mean ± SD), and there were 26 men (72.2%). There were 18 eyes (49%) with typical wAMD and 19 eyes with PCV (51%). The mean retinal sensitivity was significantly improved from 15.4 ± 4.2 dB at the baseline to 19.9 ± 5.0 dB at 3M, 20.3 ± 4.5 dB at 6M, and 20.9 ± 4.6 dB at 12M (all p < 0.0001 relative to baseline). The mean BCVA at the baseline was 0.35 ± 0.23 logMAR units which improved to 0.22 ± 0.28 logMAR units at 12 months (p = 0.001). The BCVA was improved or maintained at 12M in 71% of the patients. The mean CRT and GLD were significantly reduced at 12M (p < 0.001). Twenty‐two eyes (71%) had a dry macula at 12M.ConclusionsThese results indicate that IVA applied with this protocol will improve not only the morphology (CRT) but also the physiology (BCVA, retinal sensitivity) of the retina at 12M.
Quantification of Bruch’s Membrane calcification in Pseudoxanthoma Elasticum: a proof‐of‐concept study using SD‐OCT
Authors: Risseeuw Sara , Bennink Edwin , Poirot Maarten , Imhof Saskia , van Leeuwen Redmer , Ossewaarde ‐ van Norel Jeanette 
Published: December 2019

AbstractPurposeProgressive calcification of Bruch’s membrane (BM) causes considerable visual morbidity in patients with pseudoxanthoma elasticum (PXE). Since calcification is hyperreflective in SD‐OCT imaging, our aim was to quantify BM calcification using SD‐OCT.MethodsWe performed a ‘proof of concept’ study with 45 PXE patients under 40 years and 25 age‐matched controls. Spectralis HRA‐OCT imaging was performed, consisting of 7 macular B‐scans with 250 µm distance in between. Retinal segmentation was performed using OCT Explorer (and visually verified per B‐scan on correct segmentation and an intact outer retinal layer). Matlab was used to extract and average z‐axis intensity profiles for each set of B‐scans. Mean layer intensities normalized to the GCL‐IPL layer were used for descriptive analysis. Intensity ratios, defined as the retinal pigment epithelium (RPE)‐BM peak intensity relative to another layer, were calculated to quantify RPE‐BM intensity. These ratios were compared with the control group to find a discriminative value using ROC analysis.ResultsThe age of the groups were comparable, with a mean age of 27.0 years in PXE patients and 26.9 years in the control group. The median normalized intensity of the RPE‐BM was 34.0 (IQR 24.7–42.3) in patients with PXE, compared to 20.4 (IQR 17.2–24.4) in normal controls (p < 0.001). The RPE‐BM/ ellipsoid zone (EZ) ratio was the most discriminative with an AUC of 0.97 (95% CI 0.92–1). In PXE patients, the median ratio was 1.79 (IQR 1.33; 2.63) compared to 0.75 in controls (IQR 0.61; 0.97). The RPE‐BM/EZ ratio increased with age in PXE patients: 1.14 (IQR 1.01–1.32) in patients under 20 (n = 7), 1.81 (IQR 1.35–2.19) in patients aged 20–30 years (n = 22) and 2.35 (IQR 1.68–3.08) in patients aged 30–40 (n = 16) (p = 0.010).ConclusionsWe demonstrated that BM calcification is quantifiable as hyperreflectivity in young PXE patients, that the RPE‐BM/EZ intensity ratio can discriminate between PXE and normal controls, and that this intensity ratio increases with age.
Etiologies and treatment of manifest vertical deviations: series of 95 patients
Authors: Boucenna William , Taright Nabil , Rahmania Nesrine , Morfeq Hussein , Jany Benjamin , Promelle Veronique , Bremond Gignac Dominique , Milazzo Solange 
Published: December 2019

AbstractPurposeManifest vertical deviations (MVD) are permanent vertical misalignment of one or both eyes. A hypertropia is a form of vertical strabismus where one eye is deviated upwards in comparison to the fellow eye, as opposed to hypotropia, where one eye is deviated downwards. The aim of this study is to analyze the different etiologies associated with MVD and their management.MethodsA retrospective analysis of patients referred to our center with MVD between September 2013 and February 2016 was done. A total of 95 patients were included. Each patient received an orthoptic and complete ophthalmological assessment. The outcomes studied were the age, sex of the patient, etiologies associated with MVD, angle of deviation in primary position at near and distance fixation as well as the proposed treatment.ResultsFifty men (53%) and 45 women (47%) were included with a mean age of 33 years (range 2‐86 years), without statistically significant difference of affected eye or to gender. The mean deviation angle, at far and near distances, was 10 diopters. The majority of MVD were acquired (46%), congenital (35%), residual (13%) and consecutive (6%). The most common etiology was cranial nerves IV paralysis (29% n = 26). The other etiologies were cranial nerves III paralysis (20% n = 19), residual MVD (12% n = 10), strabismus (6% n = 5), consecutive MVD (5% n = 4),cranial nerves VI paralysis (3% n = 3), Graves’ disease (3% n = 3), orbital floor fracture (1% n = 1), other etiologies (21% n = 24). Treatment was surgical for 52% of patients, prism correction (25%), eye occlusion (4%), optical correction alone (5%). Eleven per cent are regressed spontaneously and treatment was not specified for the remaining 3%.ConclusionsMVD are the most common finding in acquired oculomotor palsy. The variability of the clinical forms and etiologies makes their proper diagnosis and testing challenging. Indications of the treatment are guided by functional repercussion.
Diabetes exacerbates the early RGCs loss of function in the DBA/2J inherited mouse model of Glaucoma
Authors: Amato Rosario , Lazzara Francesca , Chou Tsung Han , Porciatti Vittorio , Dal Monte Massimo , Casini Giovanni 
Published: December 2019

AbstractPurposeGlaucoma is a multifactorial disease that progressively determines the dysfunction and the subsequent death of retinal ganglion cells (RGCs), depending or not by the intraocular pressure (IOP) elevation. The possible influence of diabetes as a risk and/or exacerbating factor for glaucoma has been postulated, but the relationship between diabetes and glaucoma remains controversial. The purpose of this study is to clarify the effect of diabetes in the early progression of glaucoma during the RGCs dysfunction stage preceding the IOP elevation and the cell death.MethodsDBA/2J glaucomatous mice were injected with streptozotocin (STZ) to obtain a combined model of diabetes and glaucoma. In addition, non‐treated DBA/2J mice and STZ‐injected C57BL/6J were analyzed respectively as glaucomatous and diabetic only controls. RGCs and outer retina activities were evaluated performing respectively pattern electroretinogram (PERG) and flash electroretinogram (FERG) from 4 to 6 month of age. Additionally, IOP and glycaemia were followed up to monitor the progression of the disease.ResultsAs expected, non‐treated DBA/2J mice didn’t show any elevation of IOP nor alteration of FERG response during this time window. However, this group showed an age‐dependent worsening of the amplitude and the latency related to the PERG response. C57BL/6J mice treated with STZ showed an IOP‐independent decrease in PERG response preceding alterations of FERG. Interestingly, hyperglycemia determined the exacerbation of the PERG response in STZ‐treated DBA/2J compared to both diabetic and glaucomatous only groups starting from the very beginning of the diabetic condition independently from both IOP and FERG changings.ConclusionOur results show that diabetes act as an exacerbating factor for the progression of glaucoma. Indeed, hyperglycemic condition act as a further stressor which leads to a quicker loss of RGCs function and cell death.
The effect of stimulus contrast on the harmonic components of steady state visual evoked potentials
Authors: Solf Benjamin , Klee Sascha 
Published: December 2019

AbstractPurposeSteady state visual evoked potentials (ssVEP) are widely used for objective functional diagnostics. Due to stimulation with intermittent stimuli, the evoked response contains frequency components related to the stimulation frequency and its harmonics. In general, the evoked amplitude at stimulation frequency is used for functional diagnostics. However, clinicals trails also reported main components at harmonic frequencies. The origin of the harmonic frequency components is not fully understood. This work aims to analyze the influence of the stimulation contrast on harmonic components of ssVEP.MethodsWe studied 10 healthy subjects (mean age 27.2 ± 5.8 years) using checkerboard stimuli (d = 7.2°) with a check size of 0.35°. Stimuli were presented in pattern‐reversal mode (7.5 changes per second) for 5 contrast levels (98%, 50%, 25%, 12.5%, 10%) at mean luminance of 50 cd/m2 and 20 cd/m2 in a random order. The active electrode was placed at Oz, reference electrode at FCz and ground electrode at FPz. The stimulations were performed monocularly in a dimmed room. The recorded ssVEP were transformed using Fourier Analysis. The normalized ratio of the amplitudes at stimulation frequency (7.5 Hz) and first harmonic (15 Hz) were calculated. For statistical analysis Wilcoxon test for paired samples were used.ResultsIn our investigation, all 10 subjects exhibited the main component at stimulation frequency (7.5 Hz). The normalized ratio of the amplitudes showed no significant differences between the 5 contrast levels for the mean luminance of 50 cd/m2 and 20 cd/m2.ConclusionThe presented work revealed, that main components at harmonic frequencies are not dependent on the stimulation contrast. The stimulation contrast has no significant effect on the harmonic responses of ssVEP.
Retrospective descriptive study on diagnosed patients of choroidal metastases
Authors: Montes Paula , Karlsruher Gisela , Boned Ana , Díaz María Dolores , Marco Sara , López Isabel , Pérez Diana , Ascaso Francisco Javier 
Published: December 2019

AbstractPurposeThe most frequent intraocular tumour are metastatic carcinomas. Although it is a rare entity, choroidal involvement is considered the most frequent intraocular malignancy due in part to its abundant vascularization. Although they are often the first manifestation of the tumour, they usually appear late in the course of a tumour disease and are associated with poor prognosis. The most frequent primary origin in the case of women is the breast and in the male the lung. Blurred vision or visual loss is the most common form of presentation. The therapeutic options include systemic treatments and local therapies such as radiotherapy or surgery among others.MethodsRetrospective descriptive study conducted in our centre from May 2009 to May 2019 on patients diagnosed with choroidal metastases. We analysed the primary tumour origin, clinic at the beginning, initial presentation of neoplastic disease, therapeutic attitude and median survival.ResultsOf the 10 patients studied there were four males (40%) and six females (60%). The average age was 63.6 years. The initial presentation clinic was headache in four patients (40%), exophthalmos in two (20%), visual field reduction in one (1%), blurred vision in one (10%), retinal detachment in one (10%) and seizure in one (10%). As a primary source, pulmonary neoplasia was identified in four patients (40%) (two adenocarcinomas, one squamous and one small cell carcinoma), breast cancer in three patients (30%), adenocarcinoma of the pancreas in one patient (10%), papillary carcinoma of thyroid in one (10%) and high‐grade undifferentiated carcinoma in one (10%). Regarding the treatment received, six patients were candidates for palliative chemotherapy, one for radioactive iodine, one patient could not receive any type of treatment for death and two were candidates for local therapy by exantheration.ConclusionsThe results obtained in our sample are concordant with those found in the literature, obtaining a median survival of 10 months after the diagnosis of choroidal metastases. Choroidal metastases are a rare entity and generally associated with poor survival. The most commonly identified primary origins are carcinomas of the lung and breast. In a significant percentage of cases, choroidal metastases are the initial presentation of an unknown systemic neoplasm.