bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aflibercept in neovascular age related macular degeneration previously refractory to standard intravitreal therapy: An Irish perspective to compare against international trends
Authors: Mccloskey C. , Mongan A.M. , Chetty S. , McAteer D. , Quinn S. 
Published: September 2017

PurposeTo determine visual and anatomical outcomes of Age‐Related Macular Degeneration (ARMD) patients, in a tertiary centre, following conversion to Aflibercept having been refractory to previous treatment with Bevacizumab and/or Ranibizumab and to make international comparisons.MethodsA retrospective chart review of patients with a diagnosis of neovascular AMD (nvAMD) undergoing Aflibercept intravitreal therapy for at least six months who had previous treatment with three consecutive Bevacizumab ± Ranibizumab injections prior to switch. Exclusion criteria included any other procedures affecting visual outcome performed within the treatment period. Outcomes measured included visual acuity (VA), central macular thickness (CMT) and injection frequency.ResultsSixty eyes of 52 patients were included, 25 of which were male. Mean BCVA pre‐switch was 55 ± 15 letters and CMT was 285 μm ± 77. Eyes received a mean of 14 ± 8 prior Bevacizumab/Ranibizumab. The mean follow up post switch was 13.2 months (SD = 5.5). Mean BCVA improved by two letters at six months (SD = 6.6, p < 0.05), by four letters at 12 months (SD = 6, p < 0.01). The mean VA at 18 and 24 months was unchanged from baseline VA. The mean CMT decreased by 44 μm at six months (SD = 73.5, p < 0.0001), 48.4 μm at 12 months (SD = 88.1, p < 0.01), 48 μm at 18 months (SD = 22.39, p < 0.001). The mean number of injections in the six months pre‐switch was 2.8 (SD = 0.8), this increased to a mean of 4 injections (SD = 0.94) in first six months post switch then decreased to 2 injections (SD = 1) in each six month period thereafter (p = 0.002).There were no significant systemic or ocular adverse events.ConclusionsSwitching to Aflibercept in patients with treatment resistant AMD produces statistically significant improvements in visual and anatomical outcomes with eventual maintenance of visual acuity levels at one year post switch.
Automated gonioscopy photography for iridocorneal angle grading
Authors: Teixeira F. , Sousa D. , Leal I. , Marques‐Neves C. , Abegão‐Pinto L. 
Published: September 2017

PurposeThis study aims to assess inter‐device and inter‐observer agreement of iridocorneal angle grading using automatic gonio‐photography and dynamic gonioscopy.MethodsCross sectional single‐center observational study. Consecutive patients from Glaucoma Clinic were recruited to perform two types of gonioscopy. Manual gonioscopy (MG) was performed using a dynamic gonio lens, while the automatic Gonio‐Photography (AG) was done using a contact‐gonioscope prototype (from NIDEK). AG images were graded by two masked observers (glaucoma specialist and resident). Criteria for classification was similar in both methods. An eye was classified with angle closure when the posterior trabecular meshwork couldn't be seen in two or more quadrants. Inter‐device agreement (AG vs MG) was ascertained by κ statistic and comparison of area under receiver operating characteristic curves (AUC). Agreement among raters was ascertained by Fleiss’ κ statistic and intraclass correlation coefficient (ICC).ResultsForty‐eight eyes were analyzed. Mean age was 63 ± 16 years. Angle closure was detected in 11 eyes (23.4%) with MG in comparison with 2 eyes (4.3%) using AG images grading. The agreement for angle closure diagnosis between MG and AG was poor (κ=0.09 ± 0.10; p = 0.18). The AUC for detecting eyes with gonioscopic angle closure showed poor accuracy between automated and manual methods (AUC=0.53 ± 0.05, confidence interval (CI) 95%: 0.44‐0.62). The ICC for iridocorneal angle grading between the two raters was 0.34 [CI 95%: 0.10‐0.51] and Fleiss’ kappa coefficient for opening status was 0.13 [CI 95%: 0.04‐0.30].ConclusionsOnly slight agreement was found when comparing automated with manual dynamic gonioscopy and also when comparing two raters. Manual dynamic gonioscopy is the gold standard and further technological development is desired for promising automated gonioscopy.
Interest of analysis of circumpapillary retinal nerve fibers layer thickness at different measurement diameters
Authors: El Chehab H. , Agard E. , Loria O. , Théo L. , Dot C. 
Published: September 2017

PurposeThe analysis of the circumpapillary retinal nerve fiber layer (RNFL) is a major data in structural analysis in glaucoma. Since OCT development, analysis is on a circle of 3.4 mm diameter. This study evaluates the diagnostic capability of an RNFL analysis with different diameter measurements.Methods60 glaucomatous and 58 control patients had a complete ophthalmological exam to exclude patients with papillary morphological abnormalities (coloboma, dysversion …). Others had an OCT Spectralis (Heidelberg Engineering, Germany) of RNFL on 4 circles of different diameters: 3.4, 3.5, 4.1 and 4.7 mm. Only one eye per patient was randomly included. The diagnostic capabability of each of these circles was analyzed for global mean thickness and for each sector (temporal, temporal‐superior, nasal‐superior, nasal, nasal‐inferior and temporal‐inferior) by calculating areas under ROC curve (AUROC).ResultsPatients were comparable for clinical characteristics. In glaucomatous patient group, 58.9% of the patients were early glaucoma (MD> ‐6 dB) and 21.4% of the patients were severe (MD <‐12 dB). For conventional RNFL measurement (3.4 mm), the temporal‐inferior sector had the highest diagnostic capability with an AUROC of 0.916. For the 3.5 mm measurement, the global mean thickness of the RNFL had the highest diagnostic capability (AUROC = 0.909). For the 4.1 mm measurement, the global mean thickness of the RNFL had the highest diagnostic capability (AUROC = 0.915). For the 4.7 mm measurement, the average thickness of the temporal‐inferior sector had the highest diagnostic capability (AUROC = 0.909). There was no statistically significant difference between these 4 AUROC.ConclusionsRegardless of the diameter of RNFL analysis, the diagnostic capability remains very good with no significant difference in patients with normal papillary morphology.
Screening for glaucoma progression by using non‐parametric tests
Authors: Pantalon A. , Chiselita D. , Feraru C. 
Published: September 2017

PurposeAutomated perimetry still represents the gold standard in long term glaucoma monitoring.Early detection of progression tendency in glaucoma patients is crucial. Purpose of this study was to assess an alternative fast and convenient method compared to GPA (Humphrey Perimeter, Carl Zeiss®) for detecting glaucoma progression shortly after diagnosis‐24 months.MethodsWe studied in a longitudinal manner 41 eyes from 41 patients with early open angle glaucoma forms, followed in the first 24 months after diagnosis. Glaucoma was defined according to EGS criteria and a minimum of 5 valid visual fields were required form each patient. All specific glaucoma clinical data were recorded and progression was verified by two distinctive methods: Glaucoma Progression Analysis (GPA) software from Hymphrey Visual Field Analyzer and a non parametric analysis (NPA) according to Wesselink protocol.ResultsIn GPA analysis, a positive „event” (progression) was detected in 11/ 41 eyes, 26.82%. NPA confirmed progression in all GPA cases, but additionally detected 8 moreprogression cases (46.34% eyes). The concordance between tests was good (k = 0.596, p = 0.000), with positive correlation (Mc Nemar test r = 0.652, p = 0.008). In the first 2 years after diagnosis, GPA sensitivity was 26.82% and a specificity of 73.33%, whereas NPA sensitivity was 46.34% and comparable specificity 72.41% to GPA. Likelihood ratio for progression (LR) in GPA was 1.00 vs 1.51 for NPA analysis.ConclusionsNPA tends to overestimate progressor number in a cohort, but its purpose is to allert and orient the clinician on the progression profile of the followed patients. In the first years, the GPA analysis can be highly inaccurate, therefore combining two methods with similar specificity might aid this purpose and ease the glaucoma care management.
Signs and symptoms of uveitis
Authors: Neri P. , Calamita R. , Pelliccioni P. , Gorgoni F. , Lassandro N. , Pirani V. 
Published: September 2017

SummaryUveitis can be a sight‐threatening disease. In ammation of uveal tract can be divided into: anterior, intermediate, posterior, and panuveitis. Blurred vision, ocular pain, photophobia and oaters are some of the symptoms complained by those who are a ected by uveitis. e onset of uveitis can be either acute or insidious, bilateral rather than unilateral. Posterior uveitis is usually associated with vitritis. Anterior chamber cells and are should be graded according to standardized uveitis nomenclature (SUN) working group. Binocular indirect ophthalmoscopy (BIO) score is used to evaluate the severity of vitritis. Vitreous changes may comprehend: vitreous hemorrhage, vitreous strands, and vitreous traction. A further classi cation of posterior uveitis depends on the primary site of in ammation, which can identify: retinitis, choroiditis, retinochoroiditis, and chorioretinitis. Posterior pole uveal involvement can be: focal, multifocal, and placoid. Retinal vasculitis can be present. Uveitis might be complicated by anterior and posterior synechiae, which can lead to uveitic glaucoma, cystoid macular oedema, retinal and choroidal neovascularizations, and retinal ischemia.
Bioinformatic analysis of experimental and clinical proteomic data
Authors: Nättinen J. 
Published: September 2017

SummaryProteomics, along with other omics, can be utilized as a tool of personalized medicine in order to understand the individual needs of patients better based on their expression levels of proteins. This type of personalized approaches are likely to be much more common in the future, since new diagnostic and therapeutic methods are constantly being developed and there is already currently a great need to select the most cost‐effective ones for each patient. For these reasons, a lot of effort is currently going into finding potential biomarkers through discovery studies. In addition to sample processing and advanced equipment, proteomic research also requires the work of statisticians and bioinformaticians as the research methods produce a growing amount of statistical data. Hence, methods of analyzing big data are also increasingly important and therefore researchers in bioinformatics field are both developing new methods and utilizing old ones in order to tackle the growing data. This course will focus on some of the most basic aspects of bioinformatics analysis of proteomic data and is aimed to provide clinicians and other researchers alike better understanding of the aspects important to the analysis.
Do we need to treat?
Authors: Meier‐Gibbons F. 
Published: September 2017

SummaryThe gold standard for treating glaucoma patients has always been a reduction of the intraocular pressure with medical therapy, laser or surgery. But despite reaching a defined target intraocular pressure, many glaucoma patients still progress and show a deterioration of their optic nerve or their visual field. Using examples of glaucoma patients, we will discuss if we should treat patients with other therapeutic options besides intraocular pressure control.
B27‐associated uveitis, Fuchs uveitis
Authors: Xxxx Xxxx 
Published: September 2017

SummaryB27‐associated uveitis is a very frequent form of non infectious intraocular inflammation which account for approximately 50% of acute anterior uveitis. Its main clinical features, natural history and association with seronegative arthritis are well known. Fuchs uveitis is another frequent cause of anterior and intermediate uveitis. Its natural history is well characterised as well as its association with intraocular production of anti‐rubella antibodies. Both diseases are thus often considered as easy diagnosis. However, several aspects of those diseases remain challenging and debated. In this interactive course, based on clinical cases, we will insist on those difficult aspects as well as on the more recent issues discussed in the literature.
Behçet's disease, VKH, sarcoidosis
Authors: khairallah M. , Ksiaa I. , Jelliti B. 
Published: September 2017

SummaryOcular involvement associated with Behçet disease is characterized by a relapsing remitting panuveitis with diffuse vitritis, retinal infiltrates, and occlusive vasculitis. Proper management relies on the early use of immunosuppressive drugs in combination with corticosteroids and administration of biologic agents in resistant and severe posterior segment involvement. VKH disease is a bilateral panuveitis that may be associated with extraocular manifestations. Exudative retinal detachment, associated with typical imaging findings, is the most specific feature to acute VKH disease. Sunset glow fundus is typical to chronic VKH disease. Complications are more likely to occur in the chronic recurrent phase. Treatment for acute VKH disease relies on systemic corticosteroids for at least 6 months. Immunosuppressive therapy is mainly used in chronic recurrent disease. Main ocular features of sarcoidosis include bilateral granulomatous anterior uveitis, vitritis with snowballs, multifocal chorioretinitis, and segmental periphlebitis. Diagnosis is challenging in the absence of apparent systemic involvement. Treatment of sarcoidosis relies on corticosteroids and immunosuppressive agents, in severe cases.
Choroiditis (non‐infectious)
Authors: Herbort C.P. 
Published: September 2017

SummaryChoroiditis (non‐infectious) Non‐infectious choroiditis is classically subdivided into at least two main categories, including choriocapillaritis and stromal choroiditis. In the latter, the site of inflammation is situated in the choroidal stroma. When inflammation exclusively originates from the choroidal stroma which is the target of an immune reaction such as in Vogt‐Koyanag‐Harada disease (VKH), sympathetic Ophthalmia (SO) or birdshot retinochoroiditis (BRC), the term of primary stromal choroiditis is used. When the choroidal stroma is a chance and random location of a systemic disease such as sarcoidosis, the term of secondary stromal choroiditis is used. In the choriocapillaritis group the lesion process is an inflammatory non perfusion of the choriocapillaris, a mechanism occurring or suspected to occur in diseases such as multiple evanescent white dots syndrome (MEWDS), (idiopathic) multifocal choroiditis, acute posterior multifocal placoid pigment epitheliopathy (APMPPE). The difference of these two mechanism will be further presented with the help of practical examples presented in the same fashion as the “viva voce” EBO examination.
Loss of Nrf‐2 and PGC1‐alpha genes changes macromorphology of the eye and evokes microstructural and pigmentation pattern changes of the retinal pigmented epithelium
Authors: Felszeghy S. , Viiri J. , Koskela A. , Paterno J. , Kettunen M. , Jokivarsi K. , Kaarniranta K. 
Published: September 2017

PurposeNrf2 (NF‐E2‐related factor 2) and PGC1‐ α (peroxisome proliferator‐activated receptor‐gamma coactivator 1‐alpha) regulate oxidative stress response in cells. Nrf‐2 and PGC1‐alpha double‐knock‐out (dKO) mice were used to monitor macro and morphological changes of eye, retina and retinal pigmented epithelium (RPE), respectively.MethodsThe mMRI and mCT imaging were carried out for mice aged at 6 weeks (mCT), 12 weeks and 12 months (mMRI). The retinal and RPE microanatomy and pigmentation were studied from HE‐stained thin wax and toluidine blue‐stained epoxy sections. Finally, cellular proliferation and pigmentation patterns were studied in the primary cell cultures.ResultsThe dKO samples showed smaller body parameters and weight. mMRI, mCT assays indicated size differences and dysmorphic body features in the dKO mice. Moreover, dKOs exhibited reduced retinal full tickness joined with retained RPE morphology. The melanosomes of dKO RPEs were heterogeneous in shape morphology, but comparable in size to aged matched wild type melanosomes, respectively. However, there was a striking trend of increase in the density of melanosomes in RPE of dKOs that was convinced by the primary RPE cultures.ConclusionsNrf‐2/PGC‐1α knockout mice provide a novel model to study degenerative changes in retina and RPE.
Effects of HSP90 inhibitor TAS‐116 on the inflammasome activation in ARPE‐19 cells
Authors: RANTA‐AHO S. , Piippo N. , Korhonen E. , Hytti M. , Kinnunen K. , Kaarniranta K. , Kauppinen A. 
Published: September 2017

PurposeChronic inflammation is one of the key characters of Age‐Related Macular Degeneration (AMD), the leading cause of blindness in the Western countries. The NLRP3 inflammasome contributes to the induction of inflammation. The heat shock protein, Hsp90 protects NLRP3 prior to its activation, and its removal releases the receptor protein for degradation. In this study, we tested the effect of the Hsp90 inhibition on the regulation of NLRP3 inflammasome in human ARPE‐19 cells.MethodsThe experiments were carried out using IL‐1α‐primed ARPE‐19 cells. Proteasomal degradation and autophagy were blocked with MG‐132 and Bafilomycin A, respectively. TAS‐116 was used as an Hsp90 inhibitor. The cytokine levels of IL‐1β, IL‐6, IL‐8, and MCP‐1 were measured from cell culture medium using the ELISA method. In addition, the activity of caspase‐1 was measured by a commercial assay, and the levels of Hsp70 and Hsp90 were determined by the western blot technique from cell lysates. The toxicity of TAS‐116 was assessed by measuring lactate dehydrogenase (LDH) levels from cell culture medium and using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay.ResultsAccording to our data, TAS‐116 showed no toxic effects on ARPE‐19 cells. TAS‐116 decreased the secretion of IL‐1β and IL‐8 from IL‐1a‐primed RPE cells with dysfunctional intracellular clearance. The caspase 1 activity decreased along with the IL‐1β levels. No changes were seen in the levels of IL‐6 and MCP‐1.ConclusionsOur results suggest that TAS‐116 is capable of reducing the NLRP3 inflammasome activation and the subsequent release of IL‐1β and IL‐8 in human RPE cells.
Deep learning to screen for referable diabetic retinopathy
Authors: De Boever P. , Malik R. , Afifi N. , Elen B. 
Published: September 2017

PurposeDiabetes patients worldwide are at risk for diabetic retinopathy (DR). High performance informatics technologies, such as deep learning, are envisioned to achieve acceptable sensitivity for detecting referable retinopathy and appear to be cost‐effective alternatives to manual scoring, allowing for large‐scale, cost‐effective DR screening. The purpose of this work was to develop a deep learning computer model and evaluate its performance.MethodsAn ensemble of two deep convolutional neural networks (resp. 25 and 26 layers; high resolution (512 × 512 pixels); different filter sizes) was trained to detect the presence of signs of DR using labeled fundus images from the Kaggle dataset. The computer model has been evaluated with the public Messidor‐2 dataset for referable DR. Next, the model has been evaluated “in the field” in the context of the Qatar Biobank initiative. Study participants undergo fundus imaging. These images have been graded by retinal specialists in the context of this study.ResultsAll 190 patients in the Messidor‐2 database with referable DR (moderate non‐proliferative DR or worse) have been detected by the trained computer model (sensitivity 100%, 95% CI: 98,1%‐100%). The software labeled 444 of the 684 diabetes patients without referable DR accordingly (specificity 64.9%, 95% CI: 61.2–68.5%). A total of 385 participants of the Qatar Biobank were examined, with 23 individuals having referable DR. The model identified them with 100% sensitivity (90% CI: 85.2–100%) and 88% specificity (95% CI: 84.3–91.3%).ConclusionsThe deep learning network obtains high sensitivity combined with a good specificity. The model is conservative while screening for the presence of referable DR, allowing users to focus their attention on patients in which signs of referable DR are detected by the automated screening.
Cross‐sectional static retinal vessel analysis in routine optometric practice
Authors: French C. , Heitmar R. 
Published: September 2017

PurposeDo retinal vessel calibres provide the same conclusions regardless of which eye was assessed?MethodsA cross‐sectional sample of patients seen in routine optometric practice [n=225] underwent a standard eye examination including subjective refraction and slit‐lamp biomicroscopy. Undilated optic nerve‐centred fundus photographs were obtained (camera angle: 50 degrees). Red‐free photographs were analysed using iFlexis software (Vito, Belgium) to give objective retinal vessel calibre measurements (central retinal artery/vein equivalents; CRAE/CRVE), as described by Knudtson et al.ResultsThe mean age of the cohort was 59 years (range: 16‐90 years ±15) and comprised of 137 women and 88 men. BMI ranged between 17.6 – 37.3 kg/m2. Average systolic blood pressure (BP) was 131mmHg ±20 and diastolic BP was 82mmHg ±12. Refractive error (MSE) ranged from ‐10.00 to +7.00D. CRAE was found to be 142AU ±16 (RE) and 143AU ±18 (LE). CRVE was 210AU ±23 (RE) and 209AU ±22 (LE). Paired t‐test showed no difference between RE and LE calibres. There was good agreement of both vessel calibres in both eyes, as shown by Bland‐Altman plots. (CRAE: bias: ‐0.88; upper/lower limits: 27.81/‐29.57; CRVE: bias: 0.08; upper/lower limits: 33.43/‐33.26). Stepwise forward multiple regression analysis found a significant (all p<0.001) decrease in both CRAE and CRVE with increasing myopia and age; CRVE also increased with increasing BMI. Analysis was run on all RE, all LE and randomly selected eyes to test if the same conclusion could be drawn regardless of eye selected.ConclusionsEstablished associations between age, refractive error and BMI with retinal calibres were in agreement with the sample used. The impact of refractive error on retinal vessel calibre measurements highlights its importance as a co‐variate in larger studies, especially when assessing systemic vascular disease.
Estimating basal rear osmolarity in normal and dry eye subjects
Authors: Willshire C. , Buckley R. , Bron A. 
Published: September 2017

PurposeTear osmolarity (tOsm) is used as a measure of severity in dry eye disease (DED) and has also been proposed as an index of body hydration. Currently in DED the level of tear hyperosmolarity is compared with that of a normal population. We propose that a more valid reference point for both DED and body hydration could be acquired by measuring tOsm after a period of evaporative suppression.MethodsEight normal (N) and eight DED subjects were recruited and their tOsm measured with a TearLab® osmometer in uncontrolled environmental conditions. They then entered a controlled environment chamber (CEC) set to 23°C and 0.08 m/s airflow and, either: (1) had tOsm measured after 45 min of eye closure and then at 15 min intervals for a further 45 min at 45% relative humidity (RH), or (2) had tOsm measured every 15 min for 45 min, at 70% RH, to suppress evaporation.ResultsTear osmolality was significantly reduced after eye closure in both N and DED subjects, to levels in the range of plasma osmolarity, between 285 and 295 mOsm/L (N p = 0.03; DED p = 0.006). The tOsm rose towards the start value on eye opening. In subjects exposed to 70% RH, which was not expected to suppress evaporation completely, a fall in tOsm also occurred, but to a lesser extent than achieved with eye closure. This was significant in DED patients (p = 0.026) but not in N subjects (p = 0.12).ConclusionsAs predicted, total suppression of tear evaporation resulted in a fall in tOsm. We hypothesise that complete suppression of evaporation, for a sufficient period, drives down tOsm to a basal tear osmolarity value that will be a better measure of body hydration than tOsm measured in open eye conditions. It will also provide a personal baseline against which to gauge the severity of tear hyperosmolarity in DED patients.