bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural crest FGF signaling controls lacrimal gland development
Authors: Garg A. , Zhang X. 
Published: September 2017

SummaryNeural crests are multipotent progenitors that migrate from the neural tube to populate the entire body, differentiating into diverse cell types in many organs. FGF signaling is one of the key regulators of neural crest development, but the downstream signaling mechanism is not well understood. Here we show that conditional knockout of Shp2 disrupted migration, survival and differentiation of neural crests, culminating in the loss of Fgf10 into the periocular mesenchyme. This results in abrogation of lacrimal gland development. These phenotypes are reproduced by genetic ablation of Fgfr, adaptor protein Frs2 and downstream kinases Mek and Erks in the neural crest, and rescued by constitutive activation of Kras, establishing a FGFR‐Frs2‐Shp2‐Ras‐MEK‐ERK cascade. By RNAseq analysis, we showed that Shp2 deficiency causes significant changes in the neural crest transcriptome and identified critical regulator of Fgf10 expression in the periocular mesenchyme. These results demonstrate that neural crest FGF signaling is essential for lacrimal gland induction.
Optical coherence tomography – basic optical principles
Authors: Irsch K. 
Published: September 2017

SummaryOptical Coherence Tomography (OCT) is an optical analogue to ultrasound imaging. The much higher speed of light compared with sound allows for finer cross‐sectional views of the retina and anterior segment. Since it is extremely difficult to directly detect the shorter “echo” times it takes light to travel from different structures at axial distances within the eye, interferometry is used. Incident light is thus split into two beams, and the beam backscattered from the ocular tissue is then compared (“interfered”) with the beam that has traveled a known time from the reference mirror. Broadband (i.e., low “coherence”) light sources are used, because they produce a wider band of wavelengths, and thereby enable greater sensitivity in comparing the travel time differences of the two beams. In time‐domain OCT, the reference mirror position is altered, so that interference patterns are generated whenever the two beams have traveled almost the same amount of time. In spectral‐domain OCT, the reference mirror position is fixed and the mixed interference patterns are separated via spectral wavelength analysis. This lecture will explain underlying concepts of OCT with a discussion of cutting‐edge technological developments.
Optical coherence tomography – machine learning
Authors: Bernardes R. , Castelo‐Branco M. 
Published: September 2017

SummaryMachine learning is a method of data analysis. It gives computers the ability to learn from data and to build models from which predictions can be made. Even though OCT is mainly used to visualize retinal structures and compute thickness maps, it conveys information on subtle changes within the retina before structural ones can be identified. Exposing the machine learning model to a set of examples allows it to build a model from which predictions can be made on new data and explain differences between groups. This lecture will explain the underlying principles of machine learning and discuss potential applications in ophthalmology and CNS disorders through the imaging of the retina.
27‐Gauge vitrectomy – the smaller the better?
Authors: Falkner‐Radler C. , Bukaty E. , Krebs I. 
Published: September 2017

PurposeTo evaluate anatomic, functional and refractive outcomes after 27‐gauge vitrectomy in a prospective study.MethodsThe study was designed to include patients presenting with vitreoretinal disorders (epiretinal membrane [ERM], macular holes, asteroid hyalosis and vitreomacular traction [VMT]) with or without coexisting significant cataract. Exclusion criteria were (a) patients with rhegmatogenous or tractional detachment, (b) previous vitreoretinal surgery, and (c) the need for silicone oil tamponade. Surgical conditions using a scaled questionnaire, complication rates, IOP, functional and refractive outcomes were evaluated. All surgeries were performed by one surgeon (F‐R CI).ResultsUp to now, 60 patients, 41 females and 19 males with a mean age of 72 years, have completed the 3 months follow‐up. The vitreoretinal diagnosis was ERM in 36 eyes, macular holes in 9 eyes, VMT in 2 eyes, and asteroid hyalosis in 13 eyes. In 47 eyes cataract surgery was combined with vitrectomy. Intraoperative conditions were graded good to excellent. However, a slightly increased time needed for core vitrectomy was noted and particularly in hyperopic and left eyes the 27 gauge instruments were graded to be more flexible. No wound leakage was found and the IOP was stable in all eyes. Complication rates included a mild postoperative vitreous hemorrhage in one patient which spontaneously resolved during follow‐up. Visual acuity improved in all patients and the refractive results in the combined cases were excellent.ConclusionsThese results suggest that 27 gauge vitrectomy with or without combined cataract surgery results in excellent wound architecture and offers promising functional and refractive results.
Bidirectional cross talk between uveal melanoma cells and hepatic myofibroblasts promotes inflammation‐induced chemokines expression
Authors: Babchia N. , Landreville S. , Clement B. , Coulouarn C. , Mouriaux F. 
Published: September 2017

PurposeUveal melanoma (UM) is the most common primary ocular neoplasm in adults. Its cause is largely unknown, and no risk factors have yet been identified. The metastatic disease develops in up to 50% of patients, usually involving the liver. Treatment only rarely prolongs survival, because metastases are highly resistant to most chemotherapeutic agents. Tumor cells may modulate the functions of surrounding cells to facilitate their own growth, survival, invasion, and metastasis. This study was conducted to investigate the role of hepatic microenvironment on UM cells (UMC).MethodsHere, we utilized metastatic (Omm2.3) and non‐metastatic (Mel270) UMC in coculture with hepatocyte‐stellate cells (HSC) LX2. The transcriptomic study was performed by microarray assay. Expression of relevant genes was measured by qPCR. Cytokines were quantified by Elisa test. Cell proliferation was assessed by MTT staining. Extracellular matrix components were evaluated by quantitative cell adhesion assay.ResultsHepatic microenvironment increased the expression of numerous genes. However, the number of genes overexpressed in metastatic co‐cultures is three‐times higher than in non‐metastatic cocultures, demonstrating that hepatic microenvironment has more impact on metastatic UMC. Over‐expressed genes in coculture were linked to inflammation and included several interleukins. In addition, UMC‐HSC crosstalk generated expression of cell adhesion receptors, particularly by increasing fibronectin. In contrast, hepatic microenvironment had no effect on cell proliferation.ConclusionsOur results provide evidence for an important role of inflammation in the progression of metastatic UM. Therefore, the inflammatory characteristics of the tumor microenvironment might offer therapeutic opportunities.
Principles and techniques; pearls and pitfalls
Authors: Lupidi M. , Coscas G. , Coscas F. 
Published: September 2017

SummaryThe contrast generated between static and non‐static tissue results in a vascular signal. This principle stands at the base of OCT‐Angiography (OCT‐A), a novel imaging technique that allows to visualize the retinal and choroidal perfusion in a depth‐resolved approach. Clinical investigations of OCT‐A have demonstrated its potential in a wide variety of retinal and macular diseases. Dye angiographies maintain several advantages mainly related to the larger imaging field. Moreover OCT‐Angiography needs some learning time to interpret the images, in order to distinguish new imaging features of a well know clinical entity from artifacts. Motion errors, improper software correction or shadowgraphic flow projection can lead to severe artifacts, which influence and sometime interfere with the imaging assessment.Purpose of this lecture is to highlight the role of OCT‐A in clinical practice: describing its principles, pearls and pitfalls may help the clinician to integrate this innovative approach in common patient care.
OCT‐A and VRO
Authors: COSCAS F. , Coscas G. , Souied E.H. 
Published: September 2017

SummaryCorrelations in retinal vein occlusion (RVO) patients between macular vascular densities in the superficial and deep capillary plexuses obtained using OCT‐Angiography (OCTA) and the data from conventional examination (visual acuity and peripheral retinal non perfusion on fluorescein angiography) might reveal new insights in the pathogenesis of vascular damage. Through a retrospective, observational study of RVO patients with who underwent a comprehensive ophthalmic examination including FA and OCTA a significant correlation between automatically quantified macular vascular density on OCTA and peripheral non‐perfusion on FA was demonstrated; OCTA could help in identifying high‐risk RVO patients who may benefit from further evaluation using FA.
OCT‐A A in CSC and in MacTel type 2
Authors: Mauget‐Faysse M. , Wolff B. , Vasseur V. , De Bats F. 
Published: September 2017

SummaryOCT‐A with OCT « en face » allow a good imaging and location of vessel abnormalities in MacTel2. OCT‐A reflects the progressive transformation of the perifoveolar capillaries and detects the presence of CNVs. There are still difficulties to analyse the link between the different layers of the retina & the choroid due to the frontal section of OCT‐A. There is a need for 3D imaging. A new symptomatology is described on OCT A in CSC as abnormal dark and white lesions. OCT B, C and multimodal imaging are mandatory in addition to OCT A to diagnose non neovascular retinal and choroidal CSC lesions. However, OCT A is very helpfull in the detection of abnormal choroidal neovascular membrane in CSC patients. In CSC, signs on OCT‐A must be interprete with caution and compare with multimodal imaging OCT « En‐Face ». The main contribution in CSC of OCT‐A is for CNV detection.
OCT‐A in ocular oncology
Authors: Zografos L. 
Published: September 2017

SummaryOCT‐A allows the visualization of various capillary plexusses located in front of the retinal pigmented epithelium. In case of partial depigmentation or metabolic modifications of the retinal pigmented epithelium, vascular networks located in the choroid can also be observed. This new imaging technique is currently used mainly in the diagnosis, the follow‐up and the prognostication of irradiation induced maculopathy. The presence of a vascular network in pigmented and unpigmented small choroidal tumors visible in selected cases on OCT‐Angiography offers new diagnostic perspectives which are currently under investigation.
Mouse case
Authors: Roux M. , Amiot C. , Maréchal D. , Hérault Y. 
Published: September 2017

SummaryThe retina of Down syndrome (DS) patients is thicker than the one from controls, an anomaly reproduced in two murine models of the disease, Ts65Dn and Tg(Dyrk1a) and attributed to the increased dosage of Dyrk1a (Laguna et al. 2013), considered as one of the key genes in the apparition of DS symptoms. As HSA21 genes not triplicated in Ts65Dn may affect the expression/function of DYRK1A, we have analyzed by optical coherence tomography (OCT) the retina of Ts65Dn and Tg(Dyrk1a) mice, and compared the results to those obtained on various additional models, notably Dp(16)1 Yeh mice, which have a triplicated segment of MMU16 longer than Ts65Dn, and crosses between Tg(Dyrk1a) and Dp1 Yah, which carries a triplication of the MMU17 genes orthologue to HSA21. In parallel, we have started to analyze by immunohistochemistry the retinal neuron populations in Tg(Dyrk1a) mice, showing an increase in dopaminergic amacrine cells when Dyrk1a is triplicated. Mirror results were obtained on the retina of Dyrk1a+/‐, a model of Mental Retardation 7.Laguna et al. (2013 ): Triplication of DYRK1A causes retinal structural and functional alterations in Down syndrome. Hum Mol Genet 15;22(14):2775‐84.
Inflammation in relation to retinal diseases
Authors: Dick A. 
Published: September 2017

SummaryMaintaining tissue and cellular health to preserve vision requires active immune responses to prevent damage and respond to danger. Macrophage polarisation may determine the result of the immune response and subsequent tissue health and TNF–alpha is a central regulator. With respect to an insidious degeneration in atrophic AMD or in neovasular AMD, the ability to attenuate pathogenic immune responses is observed despite known inflammasome activation. The result of immune cell activation is environmentally dependent, for example on retinal cell bioenergetics status, autophagy and oxidative stress, alterations in which skew interaction between macrophages and retinal pigment epithelium (RPE). For example, dead RPE eliciting macrophage VEGF secretion but exogenous IL‐4 liberates an anti‐angiogenic macrophage sFLT‐1 response. Impaired autophagy or oxidative stress drives inflammasome activation, increases cytotoxicity and accentuation of neovascular responses, yet exogenous inflammasome derived cytokines such as IL‐18 and IL‐33 attenuate responses.
Elevation of intraocular pressure in relation to retinal diseases
Authors: Vidal‐Sanz M. , Valiente‐Soriano F.J. , Rovere G. , Nadal‐Nicolás F.M. , Salinas‐Navarro M. , Agudo‐Barriuso M. , Villegas‐Pérez M.P. 
Published: September 2017

SummaryIntraocular pressure remains the only modifiable risk factor in glaucoma, a disease characterized by progressive loss or retinal ganglion cells (RGCs) and visual field deficits leading to blindness. Using two rat models of chronic (COH) or acute (AOH) ocular hypertension we study the response of the general population of RGCs responsible for image‐forming visual information and the intrinsically photosensitive population of RGCs responsible for nonimage‐forming visual information, identified with Brn3a and melanopsin antibodies, respectively. For AOH the anterior chamber of the left eye was cannulated and connected to saline elevated 1½ meters for 75 minutes. COH was induced by laser‐photocoagulation of limbar tissues. In both models prior to OH a single intravitreal injection of brain derived neurotrophic factor (5 μg BDNF in 1% albumin PBS) or vehicle was administered. Re retinas were examined at 12 or 15 days after COH or 3, 7, 14, or 45 days after AOH to identify surviving Brn3a+RGCs and m+RGCs. COH induced comparable loss of RGCs but only Brn3a+RGCs responded to BDNF. After AOH, Brn3a+RGCs died progressively while m+RGCs did not, and BDNF induced a permanent protection up to 45 days after AOH in both types of RGCs.
Mitochondrial impairment regulates inflammasome activation in human retinal pigment epithelial cells
Authors: Korhonen E. , Piippo N. , Hytti M. , Kaarniranta K. , Kauppinen A. 
Published: September 2017

PurposeDysfunctional mitochondria and excessive inflammasome activation have been shown to play a role in age‐related macular degeneration. The aim of the present study was to investigate whether release of mitochondrial reactive oxygen species (ROS) by impaired mitochondria leads to inflammasome activation and further secretion of IL‐1β in human retinal pigment epithelial cells.MethodsARPE‐19 cells were primed with IL‐1α and exposed to mitochondrial electron transport chain III inhibitor, Antimycin A, after pretreatment with caspase‐1 inhibitor, Ac‐YVAD‐CMK or mitochondrion‐specific ROS scavenger, mito‐TEMPO. Pro and mature forms of IL‐1β were measured from cell lysates and cell culture supernatants by enzyme linked immunosorbent assay (ELISA) method. Cytotoxicity was determined by commercial lactate dehydrogenase (LDH) assay.ResultsAntimycin A induced secretion of mature form of IL‐1β in IL‐1α primed ARPE‐19 cells. However, secretion of IL‐1β was significantly declined by Ac‐YVAD‐CMK and further by pretreating cells with mito‐TEMPO. AC‐YVAD‐CMK or mito‐TEMPO had no impact to the cell viability.ConclusionsIn conclusion, the present study reveals that impaired mitochondria increases release of bioactive IL‐1β through the inflammasome activation in human retinal pigment epithelial cells.
Inner retina changes in hydroxychloroquine patients
Authors: Barata A. , Leal I. , Sousa F. , Teixeira F. , Pinto F. 
Published: September 2017

PurposeTo study if hydroxychloroquine (HCQ) patients with apparent no retinal toxicity will show lower retinal thickness in inner layers as compared to healthy controls.MethodsRetrospective study of 43 patients (86 eyes) evaluated for HCQ macular toxicity with spectral‐domain OCT (SD‐OCT) and with no OCT signs of maculopathy were subdivided into two groups: (1) no blunting of the foveal contour (foveal splaying), (2) with foveal splaying. Age and sex‐matched controls were used for comparison. Automated retinal layer segmentation at the center of fovea and at a radius of 3 (parafoveal) to 6mm (perifoveal) from the superior, inferior, temporal and nasal sectors was performed. Statistical analysis using two sample t‐test was made to calculate significant results between groups.ResultsCenter macular and internal retinal layers thickness in all parafoveal sectors, particularly in the retinal nerve fibre (RNFL) and ganglion cell layer (GCL), was statistically reduced when compared to control group (p < 0.05) and differed between group 1 and 2. RNFL thickness was also reduced in all perifoveal sectors but temporal sector (p < 0.05) and inner plexiform layer and inner nuclear layer thickness showed only significant reduction in foveal and nasal parafoveal sector (p < 0.05) in HCQ eyes. No significant differences in outer layers was observed between groups.ConclusionsSmall changes in inner retinal layers thickness have been described with HCQ use and conflicting correlation with HCQ toxicity is present in the literature. This study supports that inner retina at the fovea and parafovea is thinner in patients with no outer retinal OCT signs of HCQ toxicity. Further investigation is needed to assess if an inner retinal thickness reduction threshold could serve as valuable tool for identifying patients with increased risk of HCQ maculopathy.
Idiopathic retinal vasculitis, arteriolar macroaneurysms and neuroretinitis (IRVAN): case series of three patients with multimodal imaging
Authors: Yu Jeat C. , Logeswaran A. , Damato E. 
Published: September 2017

PurposeTo describe the clinical presentation, disease progression, treatment and complications of IRVAN.MethodsRetrospective review of three patients with a diagnosis of IRVAN seen at the Birmingham and Midland Eye Centre between 2010 and 2017. Multimodal imaging investigations included wide‐field fluorescein angiography, optical coherence tomography, and indocyanine green angiography.ResultsA total of 6 eyes from 3 patients with bilateral disease were included. All six eyes were treated with panretinal photocoagulation (PRP). One eye received a dexamethasone implant for refractory macular oedema and exudation. One eye was treated with Avastin injections for persistent optic disc neovascularization. All 3 patients were treated with oral steroids at some point in the course of their disease and one was subsequently immunosuppressed with mycophenolate mofetil. Visual outcomes varied. One patient maintained excellent visual acuity of 6/6 in both eyes at 72‐months follow‐up. The second patient experienced progressive visual loss from 6/9 right eye, 6/6 left eye at presentation; to 6/18 right eye, 6/60 left eye at 12 months follow‐up due to macular exudation despite aggressive PRP and intravitreal Ozurdex. The third patient deteriorated from 6/5 right eye, 6/4 left eye at presentation to 6/60 right eye at 6 months, despite aggressive PRP. He had recurrent vitreous haemorrhages in the right eye secondary to NVD despite further interventions with Avastin injections; seven years after presentation, vision remained at 6/60 right eye and 6/18 left eye.ConclusionsThe cadence of progression of IRVAN can vary greatly, despite aggressive treatment with PRP, intravitreal steroids, and anti‐VEGF agents. We observed variation in disease progression both among patients as well as within the same individual, supporting an individualized approach to therapy.
Sicca syndrome ‐ disease continnum. Anatomical, functional and systemic assessment
Authors: CARDIGOS J. , Crisostomo S. , Costa L. , Vaz Patto J. , Maduro V. , Barcelos F. , Alves N. 
Published: September 2017

PurposeTo evaluate objective findings in the ophthalmologic examination and search for patterns of association with the clinical and laboratory characteristics in patients with Sicca Syndrome (SiS).MethodsCross‐sectional study of 80 eyes of 80 patients with SiS divided into four groups. 20 patients with pSS for more than 10 years (group1), 20 patients with pSS for less than 2 years (group 2), 20 patients with SiS associated to undifferentiated connective tissue disease (UCTD) (group 3) and 20 patients with SiS without UCTD (group 4). Demographic, clinical and immunologic data were recorded. Ophthalmologic examinations included Schirmer test, break up time (BUT), Corneal Staining Score (CSS), tear meniscus evaluation in Anterior Segment – Optical Coherence Tomography (AS‐OCT) and corneal sub‐basal nerve plexus (CSNP) measurements with in vivo Confocal Microscopy (IVCM).ResultsGroup 1 had an early diagnosis when compared with group 2. Group 1 presented a higher frequency of positivity for anti‐SSA, anti‐SSB, Rheumatoid Factor and ANA titers compared to groups 2‐4 (p<0.05). Patients in group 1 presented more frequently systemic manifestations compared to groups 2‐4 (p<0.05). Sjogren Syndrome Activity Index (SSDAI) correlated positively with positive anti‐SSA (r=0.470, p<0.0005). Group 1 showed a higher CSS and a lower BUT, tear meniscus height and area compared to group 2 and 3 (p<0.005). CSNP's length and density were significantly smaller in group 1 compared to group 2 and 3 (p<0.05).ConclusionsCSNP's density and length, as well as tear meniscus area and height are smaller in advanced pSS compared to pSS with recent diagnostic and SiS‐UCTD. AS‐OCT and IVCM may be useful for risk stratification in SiS.