bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinicopathologic features and outcome of mycophenolate‐induced colitis in renal transplant recipients
Authors: de Andrade Luis Gustavo M. , Rodrigues Maria Aparecida M. , Romeiro Fernando G. , Garcia Paula D. , Contti Mariana M. , de Carvalho Maria Fernanda C.
Published: August 2014

Reports on the clinical course of mycophenolic acid (MPA)‐related colitis in kidney transplant recipients are scarce. This study aimed at assessing MPA‐related colitis incidence, risk factors, and progression after kidney transplantation. All kidney transplant patients taking MPA who had colonic biopsies for persistent chronic diarrhea, between 2000 and 2012, at the Kidney Transplantation Unit of Botucatu Medical School Hospital, Brazil, were included. Cytomegalovirus (CMV) immunohistochemistry was performed in all biopsy specimens. Data on presenting symptoms, medications, immunosuppressive drugs, colonoscopic findings, and follow‐up were obtained. Of 580 kidney transplant patients on MPA, 34 underwent colonoscopy. Colonoscopic findings were associated with MPA usage in 16 patients. The most frequent histologic patterns were non‐specific colitis (31.3%), inflammatory bowel disease (IBD)‐like colitis (25%), normal/near normal (18.8%), graft‐versus‐host disease‐like (18.8%), and ischemia‐like colitis (12.5%). All patients had persistent acute diarrhea and weight loss. Six of the 16 MPA‐related diarrhea patients (37.5%) showed acute dehydration requiring hospitalization. Diarrhea resolved when MPA was switched to sirolimus (50%), discontinued (18.75%), switched to azathioprine (12.5%), or reduced by 50% (18.75%). No graft loss occurred. Four patients died during the study period. Late‐onset MPA was more frequent, and no correlation with MPA dose or formulation was found.
Borrower Targeting under Microfinance Competition with Motivated Microfinance Institutions and Strategic Complementarity
Authors: Guha Brishti , Chowdhury Prabal Roy
Published: August 2014

We examine how increased competition among motivated microfinance institutions (MFIs) impacts the poorest borrowers' access to microfinance. We find that competition depends on inequality, technology, and the possibility of double‐dipping (borrowing from several sources). Without competition, even a motivated MFI may lend to the not‐so‐poor in preference to poor borrowers. If double‐dipping is feasible, competition may encourage lending to the poor. The presence of double‐dipping is critical for MFI competition to have a positive effect. When double‐dipping is feasible, MFI coordination may worsen borrower targeting whenever inequality is intermediate. We discuss policy implications dealing with double‐dipping, MFI coordination, and competition.
Do Export Promotion Agencies Increase Exports?
Authors: Hayakawa Kazunobu , Lee Hyun‐Hoon , Park Donghyun
Published: August 2014

In this paper, we examine the role of export promotion agencies (EPAs) in promoting exports from Japan and Korea. Looking at two home countries enables us to tackle endogeneity issues by controlling for both country‐pair time‐invariant characteristics and importing‐country time‐varying characteristics. Our empirical results indicate that EPA has a positive and significant effect on exports even when we control for endogeneity. However, the size of the effect becomes substantially smaller, implying the importance of addressing endogeneity in accurately measuring the impact of EPA on exports. In addition, we find that EPA's (marginal) effects are larger in exporting to low‐income trade partners than in exporting to high‐income trade partners.
Evidence of Earnings Inequality Based on Caste in Nepal
Authors: Karki Menuka , Bohara Alok K.
Published: August 2014

In this article, the monthly earnings gap between Dalit and non‐Dalit caste members in Nepal is estimated using two methods: Blinder‐Oaxaca decomposition method and the matching‐based nonparametric decomposition method. The nonparametric decomposition method estimates the monthly earnings gap based on a one‐to‐many matching of the given income‐generating characteristics, taking into account the differences in the support of the distribution of those characteristics for Dalits and non‐Dalits. According to the results, the majority of the earnings gap between Dalits and non‐Dalits is attributed to the endowment effect. Dalits earn less than non‐Dalits because Dalits have some characteristics that non‐Dalits do not, that are unfavorable in the labor market. That this endowment effect works against Dalits could be a reflection of the social exclusion and job segregation faced by Dalits in the past.
Spider cues stimulate feeding, weight gain and survival of crickets
Authors: BUCHER ROMAN , BINZ HELLENA , MENZEL FLORIAN , ENTLING MARTIN H.
Published: August 2014

1. To avoid predation, prey often change their behaviour upon encountering cues of predator presence. Such behavioural changes should enhance individual survival, but are likely to be energy‐demanding. This should deplete energy reserves of the prey, unless it increases food intake.

2. These hypotheses were studied by conducting two microcosm experiments. In the first, crickets were kept on plants previously occupied by a spider or on control plants. After 3 days leaf consumption and weight gain of the crickets were quantified. In the second experiment, crickets were kept in the presence or absence of spider cues for 3 days. Spiders were then added and predation of the crickets was recorded during 24 h.

3. Crickets that had previously experienced spider cues were more successful in avoiding predation. Moreover, crickets under predation risk tended to increase foraging in the first microcosm experiment and gained more weight in the second microcosm experiment.

4. The results demonstrate that previous experience of predator cues decreases predation rate. Furthermore, they suggest that crickets are able to compensate for increased energy demands caused by antipredator behaviour. In more natural situations, moving to cue‐free plants may play an addition role.
Non‐neuronal acetylcholine as an endogenous regulator of proliferation and differentiation of Lgr5‐positive stem cells in mice
Authors: Takahashi Toshio , Ohnishi Hiroe , Sugiura Yuki , Honda Kurara , Suematsu Makoto , Kawasaki Takashi , Deguchi Tomonori , Fujii Takeshi , Orihashi Kaoru , Hippo Yoshitaka , Watanabe Takehiro , Yamagaki Tohru , Yuba Shunsuke
Published: August 2014

Non‐neuronal acetylcholine (ACh) is predicted to function as a local cell signaling molecule. However, the physiological significance of the synthesis of non‐neuronal ACh in the intestine remains unclear. Here, experiments using crypt–villus organoids that lack nerve and immune cells in culture led us to suggest that endogenous ACh is synthesized in the intestinal epithelium to evoke growth and differentiation of the organoids through activation of muscarinic ACh receptors (mAChRs). The extracts of the cultured organoids showed a noticeable capacity for ACh synthesis that was sensitive to a potent inhibitor of choline acetyltransferase. Imaging MS revealed endogenous ACh localized in the epithelial layer in mouse small intestinal epithelium in vivo, suggesting that there are non‐neuronal resources of ACh. Treatment of organoids with carbachol downregulated the growth of organoids and the expression of marker genes for epithelial cells. On the other hand, antagonists for mAChRs enhanced the growth and differentiation of organoids, indicating the involvement of mAChRs in regulating the proliferation and differentiation of Lgr5‐positive stem cells. Collectively, our data provide evidence that endogenous ACh released from intestinal epithelium maintains homeostasis of intestinal epithelial cell growth and differentiation via mAChRs in mice.
Can current velocity mediate trophic cascades in a mountain stream?
Authors: Wellnitz Todd
Published: August 2014

Trophic cascades can be context‐dependent in that they occur under some conditions but not others. An important context for stream benthic communities is near‐bed current velocity, which varies at the spatial scale at which benthic species interactions occur.

To investigate how centimetre‐scale variation in near‐bed current velocity influenced the occurrence of benthic cascades, I studied a stonefly/mayfly/algal system in a high‐gradient Rocky Mountain stream and examined the effect of 10 and 25 cm s−1 current (i.e. ‘slow’ and ‘fast’, respectively) on stonefly predation and its top‐down effects.

There were two experiments using stream‐side mesocosms and a third using in‐stream troughs. The two mesocosm experiments had known numbers of stoneflies and mayflies and examined how near‐bed current influenced (i) top‐down cascades driven by non‐trophic, behaviourally mediated predator effects (stonefly mouthparts were glued shut) and (ii) direct predation. The in‐stream experiment allowed mayfly grazers to arrive and depart freely and examined how near‐bed current and stoneflies influenced algal accumulation and community structure.

Results from these experiments showed that top‐down cascades occurred in slow, but not fast current, and that these cascades are driven largely by the non‐trophic effects of predation. The mesocosm experiment showed that mayflies removed less algae in slow current when stoneflies with glued mouthparts were present. There was 33% greater algal biomass in slow compared with fast current, and algal biomass in the slow current did not differ from that in the grazer‐free controls. The predation experiment showed that stoneflies captured approximately twice as many mayflies in slow as compared to fast current.

The in‐stream experiment found that algal biomass increased when stoneflies were present, but grazer densities did not differ from stonefly‐free controls, supporting the hypothesis that effects mediated by behaviour drove the cascade.

This study suggests that near‐bed current can turn stonefly/mayfly/algae cascades ‘on’ and ‘off’ at small spatial scales and provides a new perspective for understanding algal heterogeneity on natural streambeds.
Efficient Calibration/Uncertainty Analysis Using Paired Complex/Surrogate Models
Authors: Burrows Wesley , Doherty John
Published: August 2014

The use of detailed groundwater models to simulate complex environmental processes can be hampered by (1) long run‐times and (2) a penchant for solution convergence problems. Collectively, these can undermine the ability of a modeler to reduce and quantify predictive uncertainty, and therefore limit the use of such detailed models in the decision‐making context. We explain and demonstrate a novel approach to calibration and the exploration of posterior predictive uncertainty, of a complex model, that can overcome these problems in many modelling contexts. The methodology relies on conjunctive use of a simplified surrogate version of the complex model in combination with the complex model itself. The methodology employs gradient‐based subspace analysis and is thus readily adapted for use in highly parameterized contexts. In its most basic form, one or more surrogate models are used for calculation of the partial derivatives that collectively comprise the Jacobian matrix. Meanwhile, testing of parameter upgrades and the making of predictions is done by the original complex model. The methodology is demonstrated using a density‐dependent seawater intrusion model in which the model domain is characterized by a heterogeneous distribution of hydraulic conductivity.
Niche shift in four non‐native estrildid finches and implications for species distribution models
Authors: Stiels Darius , Gaißer Bianca , Schidelko Kathrin , Engler Jan O. , Rödder Dennis
Published: August 2014

Non‐native species can have severe impacts on ecosystems. Therefore, predictions of potentially suitable areas that are at risk of the establishment of non‐native populations are desirable. In recent years, species distribution models (SDMs) have been widely applied for this purpose. However, the appropriate selection of species records, whether from the native area alone or also from the introduced range, is still a matter of debate. We combined analyses of native and non‐native realized climate niches to understand differences between models based on all locations, as well as on locations from the native range only. Our approach was applied to four estrildid finch species that have been introduced to many regions around the world. Our results showed thatSDMs based on location data from native areas alone may underestimate the potential distribution of a given species. The climatic niches of species in their native ranges differed from those of their non‐native ranges. Niche comparisons resulted in low overlap values, indicating considerable niche shifts, at least in the realized niches of these species. All four species have high potential to spread over many tropical and subtropical areas. However, transferring these results to temperate areas has a high degree of uncertainty, and we urge caution when assessing the potential spread of tropical species that have been introduced to higher latitudes.
OCT elastography
Authors: LEITGEB R
Published: August 2014

Functional extensions of optical coherence tomography (OCT) are today extensively studied as they have the potential to further enhance the diagnostic capabilities of OCT. Modern Doppler OCT, as the most prominent functional extension, yields outstanding contrast for the vascular plexus down to even smallest capillaries. Optical or OCT elastography is a very young functional OCT approach that gained from the developments of high speed OCT technology. It is capable to sense smallest structural tissue deformation during mechanical stress. The achieved deformation sensitivity is on the nanometer scale even in living retinal tissue. Due to the high sensitivity, OCT elastography is capable to observe tissue derformation caused by the natural pulse of the perfusion bed. This avoids external mechanical stress applied to the eye bulb and allows studying the biomechanical properties of tissue in its natural environment. Of particular interest is the motion of the fundus and of the lamina cribrosa (LC). First results indicate differential motion within the retina and LC of a few micrometer/second. This might be the basis for using the biomechanical status of the LC as new diagnostic biomarker of disease for example for glaucoma.
Choroidal thickness
Authors: SOUBRANE G
Published: August 2014

The role of the choroid has been established in a number of chorioretinal diseases. The choroid is qualitatively assessed with Fluorescein Angiography and even better with ICG angiography that explores the choroidal vasculature and the different originating pathologies. The quantitative assessment is yet clinically performed with OCT.The normal choroidal thickness ranges from 287 ± 74.2 to 345 ± 111µ depending on the instrument, the OCT technic, of the delineation of the choroidal limit. Factors affect choroidal thickness:age (and weight), axial length, possibly gender. Diurnal variations have been noted as well as a relation with water drinking. A number of chorioretinal diseases are associated with changes in the choroidal thickness. Central Serous Chorioretinopathy (CSC) exhibiting a choroidal hyperpermeabilityon ICG is associated with an increased choroidal thickness that elevates globally the retina from the RPE‐choriocapillaris band. The choroid may be so thickened as to lose signal penetration and intensity at increasing depth. The implication in CSC of the choroid is further supported by the aspect of the fellow eye. Polypoidal Choroidal Vasculopathy (PCV) a vascular choroidal abnormality has a thick subfoveal choroid. Decreased choroidal thickness is found in Age related Macular Degeneration. In dry AMD, it is possible to visualize the hyperreflective choroid in the area of RPE atrophy.Similarly in exudative AMD, the choroid can be visualized beneath choroidal neovascularization. The choroid is very thin in degenerative myopiaand related to the axial lenght. The comparison of the choroidal thickness among eyes with neovascular AMD, PCV, CSC and normal eyes demonstrated that the choroid was thicker in PCV and CSC. The thicker choroid could be partially attributed to the dilation of middle and large choroidal vessels or an increase in the choroidal vascular permeability. Choroidal thickness may thus be very helpfull to differentiate border line cases with different treatment approaches. Post treatment analysis demonstates choroidal thinning, following PDT for CSC, anti‐VEGF therapy for wet/exudative AMD, and PDT + antiVEGF for PCV. Choroidal thickness can be an aadditional parameter to assist diagnosis and may indicate the activity of the disease and the response to treatment.
Neoplastic causes of acute visual loss
Authors: BOSCHI A
Published: August 2014

Visual loss in relation with cancer has greatly increased in adult as in child. Not only because improvement of diagnostic techniques, but because survival rate has dramatically improved. Acute visual loss may be associated to direct or metastatic involvement of the eye or may be a consequence of cancer therapy including chemotherapy, radiation as newer modality like intra‐arterial injections. Considering the possible immunodysfunction in these patients infection as autoimmune disorders should be considered in the differential diagnosis of acute uni or bilateral visual loss. Clinical features and therapeutic options will be discussed through clinical cases.
Macular response to a carotenoid supplement in healthy eyes
Authors: MARQUINA I , BRAUTASET R , NILSSON M
Published: August 2014

Purpose Reduced macular pigment (MP) density is related to an increased risk of developing age‐related macular degeneration (AMD). The aim of this study was to measure the macular response to a MP supplement by measuring macular pigment optical density (MPOD) before and after consumption.

Methods Fifty‐one healthy subjects (age 18‐62 years) participated in the study and were divided in two groups, one control group and one supplementary group. MPOD values were measured using heterochromatic flicker photometry (HFP) at baseline and after 90 days of supplementation with the dietary supplement MacuShield® (10 mg lutein, 10 mg meso‐zeaxanthin and 2 mg zeaxanthin).

Results Mean MPOD values did not change significantly in any of the groups. A correlation between low MPOD values at baseline and a larger increase of MPOD values after supplementation was found in the supplementary group (r = ‐0.52, p = 0.008). Increased MPOD values also correlated with increasing age (r = 0.40, p = 0.0454).

Conclusion The results of the present study indicate that older subjects with low MPOD values increase their MPOD values after supplementation. As increased age and low MPOD values increase the risk of developing AMD, it might be beneficial for these individuals to consume macular pigments to reduce the risk of developing AMD.
The best corrected visual acuity and retinal thickness are associated with improved cortical visual processing in treated wet‐AMD patients
Authors: VOTTONEN P , KAARNIRANTA K , TARKKA I , PÄÄKKÖNEN A
Published: August 2014

Purpose Age‐related macular degeneration is the most common cause of blindness in the western world among elderly people. In response to anti‐VEGF treatment for wet‐AMD retinal anatomy and visual acuity is often remedied. In our previous study, we showed that also visual evoked potentials (VEP) improve following successful anti‐VEGF treatment. The aim of the present study was to investigate, if visual acuity and retinal thickness changes are associated with VEP parameters.

Methods Fifteen patients enrolled this study. Patients received three bevacizumab intravitreal injections. At the beginning of the study and 4‐6 weeks after the last injection, the best corrected visual acuity (BCVA) test, full biomicroscope examination, OCT analysis and VEP were performed.

Results In treated eyes, logMAR visual acuity decreased on average 0.2±0.3 units, OCT retinal thickness decreased 170±200 micrometers and VEP amplitude increased 1.0±1.4 microvolts. All changes were significant at p<0.05. The relative changes of VEP amplitude and retinal thickness correlated significantly r=‐0.630 (p<0.05), as well visual acuity (logMAR) and retinal thickness r=0.576 (p<0.05). VEP latency did not correlate with retinal thickness or visual acuity.

Conclusion We showed that both the increase in VEP amplitude and the improvement in visual acuity are correlated with the decrease in retinal thickness in treated wet‐AMD patients indicating that successful intravitreal anti‐VEGF treatment initiates significant changes in upstream visual processing in the brain.
CRVO treatments in 2014
Authors: GLACET‐BERNARD A
Published: August 2014

Although central retinal vein occlusion (CRVO) accounts for a minority of retinal vein occlusions, it is associated with more severe vision loss and with the vision‐threatening risk of neovascular glaucoma. The newly available treatments for macular edema have considerably improved visual outcome of many CRVO patients. Nevertheless, the evaluation of the ischemic component remains essential. The presentation will include when to perform laboratory workup for systemic disease and how macular edema treatment could be combined with classical treatment (etiologic treatment such as hemodilution, treatment of non‐perfusion area with laser photocoagulation).

Commercial interest
RVO related macular edema: Rules for the patients follow up; how to choose the applied treatment?
Authors: LOEWENSTEIN A
Published: August 2014

The treatment of RVO has dramatically evolved during the last few years. The main evidence base therapies are antiVEGF agents (Ranibizumab, Aflibercept, and level 2 evidence for bevacizumab) and steroids (Ozurdex). Each approach has advantages and limitations, while both have good efficacy results. In the decision making of the needed treatment inflammatory as well as VEGF pathways need to be taken into consideration. The treatment is to be tailored to the individual patient taking into consideration both ocular (existence of glaucoma, if it is controlled, existence of cataract, pseudophakia, ischemia), systemic (existence of cardiovascular risk factors) and social (ability to come monthly and availability of the health care system). Results of head to head trials are awaited.
Corneal decellularisation: recycling tissue for transplantation
Authors: WILSON SL
Published: August 2014

Purpose There is a clinical need for reliable, reproducible biomimetic corneas. Decellularised tissues are advantageous compared to synthetic/semi‐synthetic tissues in that the native matrix ultrastructure and intrinsic cues including growth factors, cytokines and glycosaminoglycans (GAGs) may be retained. However, there is currently no reliable, standardised human corneal decellularisation method. Here, we provide a systematic study of commonly used decellularisation methods and assess their appropriateness for corneal applications.

Methods Eye‐bank tissue unsuitable for transplantation was used to test decellularisation methods: Dispase removal of the epi‐ and endothelium; Mechanical agitation; Hypertonic NaCl; Ionic detergent (SDS); Non‐ionic detergent (Triton‐X100); all followed by nuclease treatment. Removal of cellular material, preservation of transparency, retention of corneal architecture and GAGs was assessed via histological, immunofluorescence and quantitative analysis. Potential cytotoxicity in vitro of the treated tissue was also assessed.

Results No decellularisation technique investigated successfully removed 100% of cellular components. The techniques which had the least residual DNA, SDS and Triton‐X100, were most structurally compromised with reduced GAG content. Dispase treated, NaCl and mechanically agitated corneas had better preservation of structure, transparency and GAGs, but had higher residual DNA.

Conclusion The ability to reprocess and regenerate tissues deemed “unsuitable” for transplantation allows us to salvage valuable tissue. However, in order to progress, we may need to take a step back to establish a “decellularisation” criterion; which should balance effective removal of immune reactive material with maintenance of tissue functionality.
Behçet’s disease, VKH, sarcoidosis
Authors: KHAIRALLAH M , KAHLOUN R , BEN YAHIA S
Published: August 2014

Ocular 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 agent 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. The mainstay of treatment for acute VKH disease relies on systemic corticosteroid therapy 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 may be challenging in the absence of apparent systemic involvement. Treatment of sarcoidosis is based on corticosteroids and immunosuppressive agents, in severe cases.
Photoreceptor toxicity of subretinal Mononuclear Phagocytes
Authors: GUILLONNEAU X , HU S , CALIPPE B , LAVALETTE S , SENNLAUB F
Published: August 2014

Growing evidences indicates that inflammation play an important role in AMD. In particular, subretinal mononuclear phagocytes (MPs) accumulate in the vicinity of the atrophic lesion of GA patients and are thought to contribute to photoreceptor degeneration. The mechanism by which MP participates to neuronal cell loss is currently unknown and no treatment is available to date to delay degeneration. We have recently shown that subretinal MPs that originate from the blood circulation and accumulate in the subretinal space are particularly detrimental in animal models of subretinal inflammation. Defects in the CX3CR1/CX3CL1 axis have been associated in animals with cardinal features of AMD including photoreceptor loss. We here show that CX3CR1 deficiency resulted in an exacerbated neurotoxicity of subretinal MPs. we present evidences that CX3CR1‐/‐ deficiency lead to the differentiation of subretinal MPs into an exacerbated pro‐inflammatory profile. Inhibiting neurotoxic mediators produced by subretinaly differentiated monocytes efficiently reduces photoreceptor loss in vitro and in animal models where MP accumulates. Our result provides new rationales to protect retina from damaging age‐dependent subretinal inflammation.
Use of antibiotic‐resistance‐free plasmids for non‐viral transfection of pigment epithelium‐derived factor in rat primary cells
Authors: GARCIA GARCIA L , RECALDE S , FERNÁNDEZ‐ROBREDO P , HERNÁNDEZ M , RODRIGUEZ JR , BEZUNARTEA J , MARIE C , SCHERMAN D , IZSVÁK Z , JOHNEN S , THUMANN G , GARCIA‐LAYANA A
Published: August 2014

Purpose We aim to assess the pigment epithelium‐derived factor (PEDF) production in cells after transfection with plasmids free of antibiotic resistance markers (pFAR4) in a non‐viral Sleeping Beauty transposon system (SB100X).

Methods ARPE‐19 cell line and primary rat iris and retinal pigment epithelial (IPE and RPE) cells were transfected with SB100X transposase and PEDF transposon encoding pFAR4 plasmids (1:16 ratio). Control cells were transfected with SB100X and pFAR4‐Venus plasmids. Supernatants were taken every 24 hours for kinetics. The effect of transfecting different amount of cells was also analyzed. PEDF production was tested by Western blot and ELISA.

Results A cumulative PEDF secretion over time in ARPE‐19 and primary cells was shown, reaching almost 3‐fold higher PEDF production in ARPE‐19 cells. Control cells did not express recombinant PEDF, but showed fluorescence. The transfection of 10,000 cells clearly showed higher PEDF expression than cells that were transfected as a group of 70,000 and subsequently divided.

Conclusion Rat primary cells are efficiently transfected and produced PEDF as it happens in ARPE‐19 cell line. Merging of the SB100X and pFAR4 technologies led to increased PEDF expression and improved safety by avoiding the transfer and potential integration of antibiotic resistance genes. This study demonstrates the feasibility of our approach based on ex vivo transfection of a low number of primary autologous pigment epithelial cells.
Contribution of "en face" SD‐OCT in inflammatory diseases
Authors: WOLFF B , VASSEUR V , BASDEKIDOU C , DE BATS F , SAHEL J , MAUGET‐FAYSSE M
Published: August 2014

To evaluate the retinal and choroidal changes in White Dot syndromes (WDS) using ‘’en face’’ and B‐scan OCT images. All the study patients underwent a comprehensive ophthalmologic examination including biomicroscopic fundus examination, color photography, fundus autofluorescence, fluorescein angiography, indocyanin green angiography and B scan and "en face" SD‐OCT. A total of 10 patients with Multiple evanescent white dot syndrome (MEWDS), 4 cases diagnosed with acute posterior multifocal placoid pigment epitheliopathy (AMPPE), 1 case of serpiginous choroidopathy, 4 cases of multifocal choroiditis, 3 cases of punctuate inner choroidopathy (PIC) and 3 cases diagnosed with Birdshot disease were analysed and included in the study. The B‐scan findings were correlated with the angiography findings as well as with the ‘’en face’’ OCT scans. In all the cases the ‘’en face’’ OCT, providing a layer‐by‐layer view of the involved retina, enabled depicting in detail the IS/OS envolvement and the extent of the outer retinal damage. The patho‐physiologic mechanism of the WDS remains poorly understood. All these entities probably share a common pathway leading to external retinal involvem
Contribution of "en face" SD‐OCT in MacTel type 2
Authors: BASDEKIDOU C
Published: August 2014

Purpose:To comprehensively evaluate the retinal and choroidal changes in eyes with type 2 idiopathic macular telangiectasia (MacTel) using "en face" and B‐scan SD‐OCT. Methods:Eyes with a diagnosis of proliferative or nonproliferative type 2 MacTel were prospectively studied. All the study patients underwent a comprehensive ophthalmologic examination including biomicroscopic fundus examination, color photography, fundus autofluorescence, fluorescein angiography, and B scan and "en face" SD‐OCT. Results: 20 eyes of 10 patients were included in this study. "En face" OCT C‐scans and conventional B‐scans were both able to show inner crystalline deposits (15%), retinal capillary anomalies (100%), intraretinal cysts (80%), hyperreflective spots in the outer nuclear layer (100%) and external limiting membrane (80%), hyperplastic pigment plaques (30%), intraretinal neovascularization (20%), photoreceptor loss (100%) and choroidal cavitations (30%). "En face" OCT C‐scans provided more information than B‐scans on intraretinal neovascularization, photoreceptor loss and Choroidal cavitations. “En face” OCT is a non‐invasive, and reproducible technique that helps to better assess and follow up retinal and choroidal processes in type 2 MacTel
Contribution of "en face" SD‐OCT in retinal toxicity
Authors: CAHUZAC A , VASSEUR V , PAQUES M , WOLFF B , MAUGET‐FAYSSE M
Published: August 2014

PURPOSE: To assess retinal and choroidal changes in drug‐induced retinal toxicity using "en‐face" and BScan OCT images. METHODS: All patients underwent complete ophthalmologic examination, including fundus examination and autofluorescence, color photography, fluorescein and indocyanin green angiography. Type, amount and time of drug intake was precisely assessed. RESULTS: 8 patients were analysed and included retrospectively. Retinal toxicity was induced by tamoxifen in 2 cases, by synthetic antimalarial (SAM) drug in 3 cases and by inhaled amyl nitrite ("poppers") in 3 cases. The angiographic features, B‐Scan and "en‐face" OCT scans findings were correlated. In all cases, "en‐face" OCT provided precise anatomic location of the retinal layers involved, the extend of retinal damage, as well as follow‐up of these changes. CONCLUSION: "En‐face" OCT allows full imaging and better understanding of retinal toxicity induced by tamoxifen, SAM drugs and amyl nitrite.
Retinal astrocytes ‐characteristics and role in retinal blood vessel development
Authors: FRUTTIGER M
Published: August 2014

During development retinal astrocytes emerge from the optic nerve as a proliferating and migrating cell population that spreads across the inner surface of the retina. This process is driven by retinal ganglion cells secreting platelet derived growth factor (PDGFA). The resulting retinal astrocyte network is essential for the developing retinal vasculature. The retinal astrocytes provide a critical substrate and trophic support via the secretion of vascular endothelial growth factor (VEGF) for the growing blood vessels.

Commercial interest
Antibodies, MRI and unusual clinical features of NMO
Authors: DE SEZE J
Published: August 2014

Neuromyelitis optica (NMO) is a rare disease including both optic neuritis and myelitis together or successively. Recently, a specific antibody named anti‐NMO has been discovered allowing a more precise diagnosis. This antibody is directed againbst abti‐AQP4 protein, a watter chanel protein. This discovery enlarged the spectrum of NMO to patients with recurrent optic neuritis and positive antibodies, now include in the NMO spectrum disorder (NMOSD). MRI frequently shows intense hypersignal of optic nerve and spinal cord with normal or atypical brain MRI for MS. NMO is frequently associated with other auto‐immune diseases such as Sjogren syndrome ou lupus. The outcome of the disease may be severe with blindness and para/tetraplegia implying that an intensive treatment should be propose as soon as the diagnosis has been made.
Tale of lysosome in RPE cells and in the pathogenesis of AMD
Authors: SINHA D
Published: August 2014

In RPE cells, the lysosomal system is a crucial regulator of both phagocytosis and autophagy. We have recently shown in the Nuc1 rat (a spontaneous mutation in the Cryba1 gene encoding for betaA3/A1‐crystallin) and in mice lacking betaA3/A1‐crystallin specifically in the RPE, that impaired lysosomal clearance decreases both autophagy and phagocytosis. This leads to the accumulation of lipofuscin within RPE cells, subretinal lesions in the posterior pole, and deposits between the RPE and Bruch’s membrane. It is likely that disturbances in the homeostasis of RPE cells, due to accumulation of undegraded intracellular material in the mice lacking betaA3/A1‐crystallin, trigger a para‐inflammatory response in an attempt to restore normal RPE function. Severe or prolonged impairment of lysosomal‐mediated clearance may also convert para‐inflammation to chronic inflammation, leading to retinal degeneration. Several studies support the hypothesis that the immune system is involved in the pathogenesis of AMD, in concert with, or in addition to, other factors. We have generated a genetically engineered mouse model that exhibits a slowly progressing form of AMD‐like pathology associated with inefficient lysosomal clearance.
Therapeutic approaches‐ aflibercept first french results of intravitreous aflibercept for active naïve polypoidal choroidal vasculopathy‐6 months follow up
Authors: DIRANI A , COSCAS F , COSCAS G , SEMOUN O , SOUIED E
Published: August 2014

To evaluate the anatomical and functional effect of intravitreous aflibercept (IAI) for the treatment of polypoidal choroidal vasculopathy (PCV) associated with exudative AMD, with a follow up of 3 months.This is a case series study that included 22 eyes with active PCV. All eyes were naive to treatment before inclusion in the study. The treatment protocol consisted of an induction phase of 3 IAI, then the injections were done every 2 months. A complete ophthalmologic workup was done for every patient and included: best corrected visual acuity (ETDRS scale), Fluorescein and Indocyanine Green Angiography, EDI‐OCT (Spectralis HRA+OCT®, Heidelberg engineering). All results were analyzed at inclusion and at 3 months.The mean age was 76.3 +/‐ 11.3. Male to female ratio was 1. The BCVA improved at 3 months (0.58 +/‐ 0.39logMAR vs 0.20±0.27 log MAR; p= 0.01). The patients gained a mean of 15 letters in the BCVA. No loss of BCVA was noted in any patient. The central macular thickness improved significantly from 376.77+/‐99.54 to 279.80±82.53 at 3 months (p= 0.043).The polyp’s regression started at one month after the first injection and was almost complete at 3 months. A significant improvement of retinal pigment epithelium detachment
Modulators for autophagy: implications for ageing and neurodegeneration
Authors: BEHL C
Published: August 2014

Autophagy is a key player in the cellular proteostasis and a degradative pathway that sequesters and transports cytosolic cargo in autophagosomes to lysosomes. This process is dependent on complex membrane dynamics and its deregulation leads to a disturbance in proteostasis contributing to several diseases, including neurodegeneration. In addition to selective macroautophagy pathways such as the "Bag3‐mediated selective macroautophagy" different key regulator proteins control the canonical autophagy process. In an RNAi screen in C. elegans designed to identify novel modifiers of proteostasis, we isolated RBG1, the homolog of mammalian RAB3GAP1 and found that the RAB3GAP complex previously known to be involved in cellular endocytosis is required for basal and rapamycin‐induced autophagy. The analysis of such distinct key modulators of macroautophagy will help to understand the involvement of the degradation pathways in ageing and disease.
Autophagy in retina and axonal degeneration
Authors: BOYA P
Published: August 2014

Autophagy is a catabolic pathway that degrades and recycles intracellular components inside lysosomes to maintain cell homeostasis. This pathway is essential to keep postmitic cells such are neurons free of garbaje and damaged cell components. There are several types of autophagy. During macroautophagy, simply called autophagy, parts of the cytosol and even entire organelles are engulfed in an autophagosome that will finally fuse with a lysosome where degradation will take place. In chaperone mediated autophagy (CMA) proteins harbouring a specific aminoacid sequence will be recognized by a chaperone Hsc70 and delivered inside lysosomes thanks to the lysosomal receptor LAMP‐2A. The role of autophagy in the physiology and pathology of the retina is just starting to be investigated. We have demonstrated the cytoprotective role of autophagy in a model of optic nerve axotomy in mice. We show that autophagy‐deficient animals have reduced number of surviving RGCs after ONT and that pharmacological induction of autophagy delays neuronal cell death. We have also observed a reduction in the levels of autophagy during retinal aging and Atg5 deficient animals in the retina show increased photoreceptor death and reduced scotopic vision. Unexpectedly CMA seems to increase in these conditions and we postulate that this is a compensatory response to sustain cell survival. Thus balance in autophagic pathways plays important roles to maintain retinal homestasis.
Autoimmunity and neuroprotection in glaucoma
Authors: GRUS F
Published: August 2014

Immunoproteomics could play a significant role in glaucoma. There are many hints for an involvement of autoantibodies in the pathogenesis of the disease. This paper will address the changes in immunoreactivities in glaucoma pateints. If will further demonstrate the findings about immunological changes in human glaucomatous retinae and the possible involvement of cellular components. Furthermore, the paper will address the clinical use for diagnosis and new approaches to neuroprotection in future.
Electron microscopic evaluation of the surfaces of variable depth lenticules in SMILE cases
Authors: OSMAN I
Published: August 2014

Purpose Evaluating lenticule surfaces using electron microscopy in deeper corneal layers and comparing them to the superficial ones. This aims at determining the possibility of preserving the stronger superficial layers in the cornea by removing deeper lenticules in SMILE cases while attaining the same visual results and with the same ease.

Methods 40 eyes underwent SMILE refractive procedure using femtosecond laser by VisuMax ( Zeiss Meditech). 2 groups were used, one with lenticules at 100 µm and the other with lenticules at 160 µm. Lenticules were immediately processed (fixed, dehydrated, dried and mounted with gold coating). JSM‐5300 scanning electron microscope was used for observations.

Results Deeper lenticules had more irregular surfaces and were more difficult to dissect. Comparing the central and peripheral thickness of lenticules to the intended thickness was significantly more accurate in the superficial group. The visual results of the two groups were comparable. Surface irregularities were resulting from the break of bridges between the femtosecond cavities.

Conclusion Energy settings still needs further adjustment to be able to create deeper predictable lenticules in SMILE cases
New concepts concerning the neural mechanisms of infantile strabismus and amblyopia
Authors: TEN TUSSCHER M
Published: August 2014

Infantile strabismus results in a loss of binocularity in the primary visual cortex. Beyond the primary visual cortex, the contralateral eye dominates while the temporal retinal signal appears to lose influence. This may either be caused by inadequate retinotopic matching between the nasal and temporal retinal signals (e.g. albinism or agenesis of the corpus callosum), or the result of a lack of normal sensory input. Dominance of the crossing retinal signal might also explain the motor characteristics of infantile esotropia (asymmetric OKN, latent nystagmus, DVD). Only a normal binocular cortical signal will predominate over the evolutionary older, originally non‐binocular, retinal projections to the superior colliculi (CS) and the accessory optic system (AOS). Amblyopia seems to be the result of active suppression by the crossing ganglion cells of the non‐amblyopic eye. Early‐onset monocular deprivation is thought to produce competitive imbalance for synaptic sites, which in turn results in a reduced proportion of functionally binocular neurons.Amblyopia treatment may aim at an optimal binocular balance and pharmacological treatment after the critical period.
Amblyopia treatment trials
Authors: HOLMES JM
Published: August 2014

Recent randomized clinical trials and observational studies conducted by the Pediatric Eye Disease Investigator Group, and other research teams, have led to an evidence‐based approach for treating anisometropic and strabismic amblyopia. Starting spectacle correction first, as optical treatment alone, results in resolution of amblyopia in at least a quarter of children. Starting low intensity treatment is the next reasonable step, offering parents a choice between 2 hours a day of patching the fellow eye or atropine drops to the fellow eye at the weekend. If amblyopia does not completely respond to these low‐intensity approaches, then more intense patching is warranted, such as patching 6 to 8 hours a day or changing the spectacle lens to plano while using atropine to increase penalization. We also have evidence that treating older children (13‐17 years old) has merit, particularly if not previously offered treatment. But despite these advances in treatment of amblyopia, one of our ongoing challenges is that a proportion of children are still left with residual amblyopia, so we continue to investigate alternative approaches such as oral levodopa as an adjunct to patching and a new treatment approach based on binocularity.
Genome‐wide association studies for the identification of keratoconus susceptibility regions
Authors: HYSI P
Published: August 2014

Consensus seems to be building that most diseases are of complex nature and the result of interaction of a polygenic architecture with the environment. A great deal on the genetic architecture of the disease can be learned from population‐based and family studies. This presentation will explore the influence of heritable factors over keratoconus as well as shared genetic elements that influence both abnormal cornea and other phenotypic anomalies of the eye.
Coming back to the basics – overview on therapeutic contact lenses and scleral lenses
Authors: MELY R
Published: August 2014

Scleral lenses were introduced at the end of the 19th century but these first glass blown shells had a very limited success related to the corneal hypoxia they induced after a short wearing time. Therapeutic contact lenses (TCL) did not become widespread until the introduction of hydrogel lenses in the 1960s. The availability of high gas permeable silicone hydrogel materials (1999) was a major breakthrough and these lenses are now the most popular TCL used in everyday practice. Thanks to a better understanding of the scleral shape and the availability of high gas permeable materials, scleral lenses have made a significant comeback in recent years. These lenses rest on the sclera and are designed not to touch the cornea, creating a reservoir filled with fluid that prevents any desiccation and mechanical irritation of the cornea. Sclerals are often the only effective non‐surgical treatment option in a wide range of severe ocular conditions, including graft‐versus‐host disease, pellucid marginal degeneration, Stevens‐Johnson syndrome, ocular cicatricial pemphigoïd, severe dry eye, non‐healing epithelial defects.Scleral lenses dramatically improve the visual acuity and the quality of life of these patients.
Macular edema
Authors: LOEWENSTEIN A
Published: August 2014

Diabetic macular edema (ME) is a severe complication of diabetic retinopathy (DR). The increasing worldwide prevalence of DR is fueling sustained efforts in devising new ways to prevent as well as to diagnose diabetic ME at an early stage in order to allow effective management to preserve or restore patient’s visual acuity. The extant knowledge of the pathophysiology underlying ME points to an interplay among systemic factors, retinal vascular dysfunction, chronic inflammation, angiogenic hyperactivity that promotes permeability and other pathological changes at cellular level, all of which may contribute to the breakdown of the blood‐retina barrier and accumulation of extracellular fluid, with subsequent leakage and ME formation. We overview the signs and symptoms which may help diagnose the pathology at different stages (reduced visual acuity, leakage from microaneurysms and nonperfusion) by assessing the role of imaging modalities such as FA and OCT in detecting these pathological changes.
Steroids
Authors: KODJIKIAN L
Published: August 2014

Diabetic macular edema (DME) is the most common cause of moderate vision loss in working‐age individuals in developed countries. Corticosteroids reduce expression of VEGF and other permeability, providing good rationale for their use in DME. The first steroid used was the triamcinolone by intravitreal injection. Efficacy was good but the adverse events were rather important (elevated intraocular pressure being the most common). Different steroids implant with sustained ocular delivery are available. The Fluocinolone Acetonide for Macular Edema (FAME) studies permitted to the ILUVIEN® implant (190 µg) has received its marketing authorization approval in different European countries. It is indicated for the treatment of vision impairment associated with chronic DME, considered insufficiently responsive to available therapies. Dexamethasone Intravitreal Implant (OZURDEX®) provided long‐term vision improvement, with a mean of 4.1 injections over 3 years (phase III MEAD study). Its label is not yet obtained (March 2014). It safety profile was better or equivalent than that of steroids currently used in clinical practice. In summary, two platforms for sustained steroids drug delivery are available in DME.