bluuebunny/crossref_metadata_2025 huggingface dataset:
Human induced pluripotent stem cells (hiPSC)‐derived endothelial cells: new opportunity for corneal bioengineering
Authors: THURET G , HE Z , SUFFEE N , FOREST F , BERNARD A , PISELLI S , PERRACHE C , DUMOLLARD JM , PEOC'H M , GAIN P
Published: August 2014

Purpose hiPSCs can self‐renew indefinitely, while maintaining the capacity to differentiate into somatic cells. As such, they represent an essentially inexhaustible source of committed corneal endothelial cells (CECs) of potential use in cell‐based corneal therapies. We present a method of differentiation of hiPSCs into CE‐like cells.

Methods hiPSCs reprogrammed from adipocytes by retrovirus (SBI) were expanded in mTSR1 medium. Differentiation was induced by sequential treatment mimicking the normal embryonic endothelial development, using co‐cultures during 3 weeks (not detailed because of ongoing patent application). Cells were sorted using magnetic beads with negative selection with anti‐K3/K12. Sorted cells were subsequently cultivated in maintenance medium for 3‐4 weeks. Differentiation was assessed by immunolabeling of ZO‐1, Glypican‐4, CD200R, Na/K/ATPase, CLCN3, MiTF, K3/K12. Stemcellness was assessed using anti‐OCT‐4.

Results hiPSCs were successfully and stably differentiated into a monolayer of tightly packed cells expression typical ECs makers and neither keratocytes nor epithelial markers. We observed the consecutive formation of embryoïd bodies after 4 days (D), neural crest cells after 7D, mesenchymal cells after 10D and cells with CEC phenotype after 15D. They lost expression of OCT‐4.

Conclusion hiPSCs are a promising source of CECs. In addition to the short‐circuit current measurement using a Ussing chamber, their ability to deswell corneas is being studied using our innovative bioreactor. Safe sources of cornea‐derived hiPSCs are also under study to facilitate clinical translation. Grants: ABM2013, IUF2012‐17, UJM2013
Influence of pressure on in vitro human corneal endothelial cells derived from human induced pluripotent stem cell (hIPSC)
Authors: JUMELLE C , SUFFEE N , FOREST F , HE Z , BERNARD A , NANGOUM‐FOSSO T , NAIGEON N , PERRACHE C , PEOC'H M , GAIN P , THURET G
Published: August 2014

Purpose Human induced pluripotent stem cells (hIPSC) have infinite self‐renewal capacity and can differentiate into somatic cells. We obtained hIPSC‐derived corneal endothelial‐like cells (CE‐likeC) using a sequential supply of growth factors. As, in vivo, the functionality of CEC may depend on various environmental factors, including intraocular pressure, we investigated whether pressure could influence the hIPSC differentiation into EC

Methods We developed a specific device for pressurizing cell cultures placed in a CO2 incubator. The device consists of a pump injecting the gas mixture from the incubator into a sealed container equipped with a pressure sensor and an electronic control system. hIPSC‐derived CEC were cultured in the differentiation medium for 1 week either in a standard incubator at atmospheric pressure or under a pressure of 20 mmHg. The medium was changed every 2 days. Differentiation was determined by cell morphology analysis and ionic pumps immunostaining (CLCN3, VDAC3, SLC4A and Na+/K+/ATPase) and tight junctions (ZO‐1).

Results At D8, the 2 cultures showed similar endothelial morphology, ZO‐1 and SLC4A, but expression of ionic pumps CLCN3, VDAC3, and Na+/K+/ATPase were increased under pressure.

Conclusion The device developed is fully functional. Our results show that, in vivo, a pressure of 20 mmHg did not modify the cell morphology. However, it tends to modulate the expression of some ionic pumps. Pressure level seems to be an important parameter in the differentiation into EC. Considering this, it could improve the EC functionality, i.e. deswelling capacity Grants: ABM2013, IUF2012‐2017 and postdoc UJM 2013
Positive cultures in corneas stored with cold storage technique to be used for corneal grafting
Authors: JULIAN HO , LINDEGAARD J , HØJGAARD‐OLSEN K , HEEGAARD S
Published: August 2014

Purpose Tissue for cornea grafting processed in the US is stored using cold storage method whereas corneas processed in the EU is stored in organ culture. The two preservation techniques differ in technical aspects, evaluation techniques, storage time and microbiological safety. Both techniques are considered to result in similar graft survival. Due to low availability of Danish donor tissue, we have used US donor tissue for more than seven years in Denmark.

Methods Routine microbiological culturing of the cornea‐scleral ring was performed at the time of DSAEK surgery.

Results From April 2013 to March 2014 a total of 11 donor rims tested after grafting were positive for bacteria or fungi with the cold storage technique. Microbiological testing of donor rims stored with organ culture were all negative. Total number of grafts, n = 210. Six candida, one MRSA, two E. Faecium and two E.coli were cultured. Two eyes had severe and vision threatening infection (fungi). Four eyes showed primary graft failure. Five eyes showed no signs of infection.

Conclusion Corneas prepared with the cold storage technique were more prone to microbiological contamination, some with vision‐threatning fungal infection. Anti‐mycotics are now added to the current hypothermic storage solution.
Rho Kinase Inhibitor AMA0526 improves surgical outcome in a rabbit model of glaucoma filtration surgery
Authors: VAN DE VELDE S , VAN BERGEN T , VANDEWALLE E , STALMANS I
Published: August 2014

Purpose To elucidate the effect of the ROCK inhibitor AMA0526 on the wound healing process and surgical outcome of glaucoma filtration surgery.

Methods The in vitro effect of ROCK inhibitor AMA0526 on human brain microvascular endothelial cells (HBMEC) and human Tenon fibroblasts (HTF) was determined using a proliferation assay. Secondly the in vivo effect of topical AMA0526 0.3% TID was investigated in a rabbit model of glaucoma filtration surgery (n=5/time point). Treatment outcome was studied by clinical investigation of the bleb area as well as immunohistological analyses for inflammation (CD45), angiogenesis (CD31) and collagen deposition at day 8, 14 and 30 after surgery. Contralateral eyes were used as control and were treated with vehicle.

Results A dose‐dependent reduction of HBMEC and HTF proliferation was measured after incubation with AMA0526. Incubation with the highest concentration of AMA0526 reduced proliferation of HBMEC and HTF to 22 and 35%. In the surgery model, AMA0526 significantly improved bleb area and survival compared to vehicle treated eyes. Immunohistological analyses showed significant reduction of inflammation, angiogenesis and collagen deposition after treatment with the ROCK inhibitor. Compared to vehicle, inflammation was decreased by 33% at 8 days and angiogenesis by 52% on day 8 and by 29% at 14 days. Collagen deposition was significantly reduced by 11 and 42% on day 14 and 30.

Conclusion This study shows that AMA0526 is able to inhibit proliferation of microvascular endothelial cells and Tenon fibroblasts in vitro, and to improve glaucoma surgery outcome in rabbits. In addition to improved bleb area, AMA0526 led to decreased inflammation, angiogenesis and fibrosis.
Selective laser trabeculoplasty in pseudophakic eyes with glaucoma
Authors: MAGOURITSAS G , PORTALIOU DM , MOSCHONAS K , GEORGOPOULOS V
Published: August 2014

Purpose To evaluate the efficacy and safety of selective laser trabeculoplasty(SLT) in patients with open angle glaucoma, which had previously undergone uneventful phacoemulsification with intraocular lens implantation. We also studied the intraocular pressure(IOP) lowering effect in association with the stage of glaucoma and the customized for each patient target‐IOP.

Methods In this prospective study we enrolled 30 consecutive pseudophakic patients (30 eyes) with uncontrolled glaucoma under maximum tolerated medical treatment and without any previous filtering surgery. We performed a 360° treatment using the Ellex Solo laser system. Mean IOP measurements were carried out month 1, month 6 and month 12 post‐laser treatment. Glaucoma stage was classified according to visual field loss as early, moderate or advanced. A range of target IOP was determined for each glaucomatous eye and used as an absolute success criterion. An IOP <21 mmHg was defined as a relative success.

Results During the mean follow up of 15±2 months 12(40%) eyes required either acetazolamide per os or surgical intervention. Clinically significant complications did not occur. At the last visit, the mean post‐laser IOP reduction of the remaining 18 eyes was 4.4±0,7(20%)mmHg. An IOP‐ reduction of <21 mmHg was found in 73% (month6) and in 57% (month12) of the eyes, whereas the overall absolute success was 50% and 37% respectively. SLT was significantly successful in eyes with early glaucoma.

Conclusion SLT is useful and safe for pseudophakic eyes with early to moderate glaucoma, which cannot be controlled under maximum tolerated medical treatment.
Pediatric uveitis
Authors: BODAGHI B
Published: August 2014

The etiology and treatment of uveitis in children remains different from adults. Infectious and auto‐immune conditions must be identified. Juvenile idiopathic arthritis‐associated uveitis is the main etiology of chronic anterior uveitis. Pars planitis is another frequent etiology of bilateral auto‐immune uveitis. On the other hand, toxoplasmic retinochoroiditis, ocular toxocariasis and cat scratch disease should be excluded in children with unilateral posterior uveitis. Case reports will be presented in order to illustrate the management of different pediatric uveitis entities.
The aging phenotype of microglia in the retina and its relationship to AMD
Authors: WONG W
Published: August 2014

The association between age‐related retinal diseases and chronic inflammatory change in the retina raises the hypothesis that microglia, the resident immune cell in the retina, may undergo aging related changes that drive pathological change. In live imaging experiments, we discovered that “resting” microglia in the inner retina undergo aging changes in the forms of decreased ramification and slowed dynamic behavior. Also, dynamic responses to injury in aged microglia were slowed in the acute phase, but more prolonged in the chronic phase. These changes indicated that aged microglia may be less able to carry constitutive functions and have abnormal and more chronic responses to injury. Also, the age‐associated translocation of microglia into the subretinal space has been associated with intracellular lipofuscin accumulation. We found that microglial uptake of A2E, a key bisretinoid component of lipofuscin, increases activation, decreases chemotaxis, and dysregulates complement activation. Taken together, aging‐related changes in retinal microglia may result in increased neuronal vulnerability, dysregulated injury responses, and altered complement regulation in the outer retina that together contribute to AMD pathogenesis.
Analysis of Keratoconus genetic factors within Keratoconus Loci and mtDNA
Authors: NOWAK DM , KAROLAK JA , KUBICKA M , KULINSKA K , POLAKOWSKI P , SZAFLIK JP , GAJECKA M
Published: August 2014

Purpose Keratoconus (KTCN) is a multifactorial disorder in which both environmental and genetic factors are involved. Genetic studies have led to the identification of several loci on different chromosomes, linked to KTCN. However, only few reports indicated causative genes in these loci. The aim of this project was to analyze the DNA sequence information available in the databases of SNVs located within known KTCN loci. We extended the analyzes to include miRNA genes located. Additionally, sequencing of mitochondrial genome in KTCN patients from Polish population was performed.

Methods The list of SNVs, which are located in KTCN loci were obtained on the basis of Ensemble. For analyzed SNVs allele frequencies were obtained from 1,000 Genomes Project. The list of miRNA genes was obtained from the miRBase. The potential impact of nonsynonymous amino acid substitutions on protein structure and function was assessed with PolyPhen and SIFT. Additionally, mtDNA was analyzed in samples from 93 people with the Polish population (42 ‐ KTCN, 51 – controls).

Results In this study 94 miRNA‐encoding genes and over 2 million SNVs were identified within known KTCN loci. From these SNVs, over 4,500 were located within exons and almost 600 SNVs were indicated as deleterious. Sequencing analysis of fragments of the mitochondrial genome revealed a number of changes, including several new polymorphisms.

Conclusion The KTCN development does not depend on a single change in the gene, but on the accumulation of numerous sequence variants. The complexity of KTCN etiology causes the need to find appropriate approach to investigate this disease. Support: National Science Centre, Poland, grant no. 2011/03/N/NZ5/01470
The role of ocular perfusion pressure in glaucoma
Authors: TOPOUZIS F
Published: August 2014

In hemodynamics, perfusion pressure (PP) is the driving force for blood flow, determining the nutritive delivery of arterial blood to capillary beds. When describing blood flow for an organ, PP is generally expressed as the difference between the arterial and the venous pressure. In the eye, OPP is calculated as systemic blood pressure, which is a surrogate for ocular arterial pressure, minus IOP, which conventionally equals ocular venous pressure. There is increasing evidence on an association between low Ocular Perfusion Pressure (OPP) and glaucoma. Population‐based studies conducted in different geographical locations and in populations of different ethnic and socioeconomic backgrounds have consistently reported that low diastolic OPP is associated with the prevalence of OAG. In addition, low OPP at baseline presented with increased risk of developing glaucoma in incidence studies. The presentation will discuss whether the existing evidence could be translated in clinical practice and how further research could better define the role of OPP in glaucoma pathogenesis, risk factors assessment and management.
An update on corneal bacterial infections
Authors: GICQUEL J
Published: August 2014

Because of their potential to permanently impair vision or perforate the eye, bacterial corneal ulcers are an ophthalmologic emergency. They usually follow an insult (sometimes minor) in the corneal epithelium that provides an entry for bacteria. The increased use of soft contact lenses in recent years has led to an important rise in the occurrence of bacterial ulcers (especially aggressive Gram‐ bacteria). The goal of this presentation is to propose a practical, systematic approach of the management of bacterial corneal ulcers, as well as an update on new concepts in the diagnosis and treatment of those conditions.
Using OCT to distinguish NMO and other types of optic neuropathy
Authors: KARDON R
Published: August 2014

Acute and chronic vision loss due to neuromyelitis optica (NMO) can be difficult to distinguish from optic neuritis associated with multiple sclerosis (MS) and other causes of visual loss. This is especially true in cases where classic findings of multiple spinal cord level involvement with transverse myelitis is not present and in cases where an IgG1 autoantibody (NMO‐IgG) that binds aquaporin 4 (AQP4) is not present at the time of visual loss. A number of studies have compared features of the inner retina defined by optical coherence tomography (OCT) in NMO and in MS and have found that patients with NMO have much greater axonal loss when matched for final visual acuity at the chronic phase. During acute visual loss, scanning laser polarimetry (SLP‐GDx) is abnormal before changes in OCT features are apparent. This is due to an acute disorganization of axon microfilaments and microtubules that appears to predict final outcome. At the sub‐acute phase (2‐4 weeks), the retinal ganglion cell layer thickness shows thinning before the retinal nerve fiber layer becomes thin. The literature will be reviewed on structural features in the acute, sub‐acute and chronic phases of vision loss in optic neuropathy.

Commercial interest
From protein aggregation to inflammasome activation in RPE cells
Authors: KAUPPINEN A
Published: August 2014

Retinal pigment epithelium (RPE) cells play the principal role in maintaining the functionality of overlying photoreceptors, and their degeneration is the primary event resulting in the deterioration of central vision in age‐related macular degeneration (AMD). Multifunctional RPE cells also take care of immune defence in macula. Due to high metabolic rate, lipid peroxidation products accumulating from ingested photoreceptor outer segments (POS), and almost continuous exposure to light, RPE cells are exposed to constant oxidative stress. Intralysosomal lipofuscin further promotes the production of reactive oxygen species (ROS), and chronic oxidative stress contributes to the age‐related decline of intracellular degradation systems, such as proteosomal clearance and autophagy. Dysfunctional degradation results in the intracellular accumulation of protein aggregates and ROS‐producing mitochondria, which can serve as danger signals and result in the inflammasome activation.
Classification, clinical pattern, multimodal imaging
Authors: COSCAS G
Published: August 2014

To suggest a clinical distinction between idiopathic typical polypoidal choroidal vasculopathy (PCV) and secondary polyps associated with late AMD and its therapeutic application.Retrospective case series of 30 eyes of 30 consecutive patients (xx females and xx males) with PCV. Initial diagnosis was based on SLO‐ICGA, associated with FA and EDI SD‐OCT, which allowed a clinical distinction between two subtypes of polyps. This multimodal imaging and visual acuity testing were repeated then at regular follow‐up visits. The central macular and choroidal thickness, presence and number of hyper‐reflective dots in retina and in choroid were also evaluated.The two groups were clinically different, based on demographic and ethnical characteristics, imaging findings and topography of lesions, presence of drusen, of true CNV, and changes in choroidal thickness. Therapeutic response was different in the two groups. After treatment, hyper‐reflective dots decreased significantly but choroidal morphology did not change significantly. Functional and anatomical changes after treatment are analyzed and discussed.The clinical distinction between idiopathic typical PCV and secondary polyps associated with late AMD and results of treatment, sugges
Therapeutic approaches 3: PDT , Laser and combined treatments
Authors: UZZAN J , COSCAS G
Published: August 2014

Laser photocoagulation was initially, the first and unique modality of treatment available for PCV, with useful results but risk of hemorrhage and recurrences. Verteporphin‐PDT rapidly became the first line of the treatment, mainly for sub foveal lesions with some good results. Intravitreous injections of antiVEGF (ranibizumab and bevacizumab) agents showed immediate good results and achieved regression of fluid accumulation and improvement in vision and became the only treatment of neovascular AMD. But, it has shown less efficiency on polypoidal lesions themselves . Combination therapy with PDT and anti‐VEGF became the first line treatment of many authors, beside the lack of comparative randomized study. Laser photocoagulation remains a second line option after that combination of PDT and anti‐VEGF, to lower the number of PDT in case of extra‐foveal recurrent lesions. The recent disponibility of Aflibercept with probably, a better efficiency on polypoidal lesions, may become the first line therapeutic options where Laser and PDT combinations will need to be specially evaluated.

Commercial interest
Reproducibility of keratometric measurements obtained with OCULUS® Pentacam® HR in the evaluation of keratoconus progression
Authors: SILVA N , VIEIRA L , ANJOS R , ALVES N , MADURO V , FEIJAO J , CANDELARIA P
Published: August 2014

Purpose To determine the reproducibility of keratometric parameters obtained by OCULUS® Pentacam® HR in the evaluation of keratoconus progression.

Methods Thirty nine eyes of 25 patients from the Cornea Department of the Centro Hospitalar de Lisboa Central were included in the study. Fourteen eyes presented with clinical and topographic diagnosis of keratoconus (stage 1‐3) and were defined as the “keratoconus without ring” group; 9 eyes had already an intrastromal ring implanted and were defined as the “keratoconus with ring”; the remaining 16 eyes, without clinical or topographic evidence of disease, were used as controls. Every eye was submitted to identical methodology: 5 consecutive keratometric measurements obtained with OCULUS® Pentacam® HR; central keratometry, SKmax, minimal pachymetry and anterior chamber depth were used to determine the existence of statistically significant reproducibility.

Results Overall significant measurement variability was obtained in the “keratoconus without ring” group (Km 0.129 D vs 0.0375 D, SKmax 0.507 D vs 0.0625 D, Minpach 5.429 μm vs 2.5625 μm, ACD 0.024 mm vs 0.0194 mm), with highest variability in the subgroup of patients with more advanced disease. In the “keratoconus with ring” group statistically significant variability was found for all parameters except for anterior chamber depth (Km 0.289 D vs 0.0375 D, SKmax 0.444 D vs 0.0625 D, Minpach 4.333 μm vs 2.5625 μm, ACD 0.024 mm vs 0.0194 mm).

Conclusion Keratometric measurements obtained with OCULUS® Pentacam® HR should be assessed cautiously in the evaluation of keratoconus progression, with or without intrastromal ring; the use of single measurements is unadvised.
Investigation of anterior chamber flare and corneal Langerhans cells in rheumatoid arthritis and in dry eye
Authors: MARSOVSZKY L , BAUSZ M , NÉMETH J , RESCH M
Published: August 2014

Purpose To examine the anterior chamber flare and corneal Langerhans cells (LC)in rheumatoid arthritis (RA) and compare the results to those found in patients with dry eye disease (DED) and in age matched control (C).

Methods 15 patients with RA (11 women, és 4 men, mean age: 67.3±8.6 years), 20 DED patients (11 women, 9 men, mean age: 57.2±14.4 years) and 15 control subjects (8 women, 7 men, mean age: 49.6±19.1 years) were enrolled in this study. Anterior chamber flare was evaluated using Kowa FC‐600 laser flare meter and corneal LC densities were investigated at the corneal centre with confocal microscopy (Heidelberg Retina Tomograph with Rostock Cornea Modul (HRT II RCM)) in all groups.

Results There was a significant difference in the flare values between RA and DED patients (6,65 f/ms in RA and 4,75 f/ms in DED (p<0.01). Central LC density was: 57.6±34.4/mm2 in RA and 52.3±31.3/mm2 in DED respectively. Both values were significantly lower than that of in control (24.6±18.6/mm2, p<0.05)

Conclusion The blood aqueous barrier might be altered in RA even without signs of clinically significant ocular inflammation. This alteration in the blood aqueous barrier might contribute to the accumulation of LCs at the corneal centre. The greater LC density and flare values found in RA might represent novel players in the pathogenesis of dry eye.
Possible future strategies in Neuroprotection
Authors: PICAUD S , FROGER N , MATONTI F , FORSTER V , IVKOVIC I , BRUNEL N , SAHEL J
Published: August 2014

Retinal ganglion cell (RGC) degeneration is causing blindness in retinal diseases like glaucoma. However, all therapeutic strategies in glaucoma are targeting the IOP increase but they do not aim at retinal ganglion cell neuroprotection. Using purified retinal ganglion cells, we are screening for neuroprotective molecules. Two natural protective molecules were thus identified. This investigation started when finding retinal ganglion cell degeneration in taurine‐deprived animals, we wanted to define if this taurine was acting directly on retinal ganglion cells. Taurine not only increased RGC survival in a pure culture but also in retinal explants exposed to NMDA. Taurine was also found to increase RGC survival in animal models of glaucoma and retinitis pigmentosa. In addition, we had observed that media used to culture mixed retinal cells can promote RGC survival. Using the luminex technology, we have found the presence of VEGF in such media. In fact, recombinant VEGF was able to stimulate RGC survival. RGCs were found to express VEGF receptors in vivo suggesting that this mechanism could have a role in control and pathological conditions. We therefore demonstrated that both taurine and VEGF can provide direct neuroprotective effects on RGCs. If the administration of VEGF is unlikely to become a treatment for glaucoma, these results raise questions on the generalized use of anti‐VEGF strategies for retinal diseases such as age‐related macular degeneration.
FGFβ and TGFβ contribute to tissue remodeling, fibrosis and inflammation in the orbital tissue of severe Grav
Authors: PAWLOWSKI P , RESZEC J , ECKSTEIN A , JOHNSON K , GRZYBOWSKI A , CHYCZEWSKI L , MYSLIWIEC J
Published: August 2014

Purpose To assess FGF‐β, TGF‐β, COX2 expression and immunocompetent cells in the orbital fat/connective tissue of patients with severe and mild Graves’ orbitopathy as possible prognosting factors of the course of disease.

Methods Orbital tissue from 27 patients with GO undergoing orbital decompression (26 females and 1 male): 1) patients with severe GO (n = 18), the mean clinical activity score (CAS) was 8,5 (SD 2.5); 2) Patients with mild GO (n= 9), CAS was 2.2 (SD 0.8). 10 individuals undergoing blepharoplasty with no history of orbital inflammation served as controls. We evaluated the expression of CD4+, CD8+. CD20+, CD68 and FGF‐β, TGF‐β, COX2 in the orbital tissue by immunohistochemical staining

Results The robust intraorbital CD4 + T cells infiltration in severe GO more than with mild GO with absence of CD20+ B lymphocytes and less CD8 infiltration were seen. CD68 expression (fibroblasts and macrophages staining) observed in the fibrous connective area of the adipose tissue of the mild GO and robust in severe GO. Increased FGFβ expression was observed in the fibroblasts and adipocytes in the connective tissue of the severe GO. The prominent TGFβ expression was observed in the fibrous connective tissue of the severe and mild GO. No expression of COX2 in the orbital tissue specimen was found in patients with GO.

Conclusion Macrophages and CD4 T lymphocytes are both engaged in the active/severe and long stage of inflammation in the orbital tissue. FGFβ and TGFβ expression may contribute to tissue remodeling, fibrosis and perpetuation of inflammation in the orbital tissue of GO especially in severe GO. Their high expression may suggest lack of effect of anti‐inflammatory treatment.
Individual physical therapy of MGD in private setting by a moist heat device
Authors: PURSLOW C
Published: August 2014

There is a frequent observation from patients that dry eye symptoms improve after time spent in a steam room or sauna. This presentation will outline the challenges in delivering heat to the meibomian glands and why moist heat is the gold standard in heat therapy in meibomian gland dysfunction (MGD). This understanding led to the invention of a medical device by a British ophthalmologist that was commercially developed to deliver a controlled amount of latent, moist heat (Blephasteam, Laboratoires Thea, France). Its use in patients will be presented: patient satisfaction and compliance are increased compared to conventional methods, whilst clinical signs are also improved.
Clinical experiences with short‐term delivery of azithromycin in conjunctival inflammation and MGD
Authors: DOAN S
Published: August 2014

Azithromycin is an azalide antibiotic, derived from the macrolides family. This is a good candidate for treating meibomian gland dysfunction and MGD‐related ocular surface inflammation for several reasons : (1) its bacterial spectrum is mainly oriented against gram positive cocci ;(2)it has a long tissular and lachrymal half life, because it accumulates in the intracellular compartment ; (3) it has anti‐inflammatory, anti‐MMP and lipase inhibiting properties. We tested azithromycin 1.5% eyedrops in blepharitis patients in two clinical studies. ‐ The first study was a multicenter randomized placebo controlled study, involving chronic moderate‐to‐severe blepharitis patients. ‐The second study was a single center non controlled prospective study in children suffering from ocular rosacea with chronic phlyctenular keratoconjunctivitis. In both studies, topical azithromycin was effective in reducing signs and symptoms. We will discuss the results of these studies in detail, and provide practical clinical schemes for the use of this innovative treatment.

Commercial interest
Progressive myopia and their associated pathologies (definitions and therapies)
Authors: MAIER M
Published: August 2014

Pathological myopia (PM) is a usually progressive eye disease causing significant visual loss. PM predominantly affects younger active employed patients therefore its complications have major individual and sozioeconomic consequences. Common and special myopia associated pathologies will be reviewed and their treatments will be discussed. Progressive chorioretinal distension results in pathognonomic changes at the fundus called “myopic retinopathy”. Myopic conus, posterior staphyloma, rupture of Bruch`s membrane (lacquer cracks), myopic choroidal neovascularization (mCNV), chorioret‐inal atrophy, myopic vitreopathy, myopic traction maculopathy and Fuchs spot repre‐senting the scar stage of myopic CNV can be found. Myopic choroidal neovasculari‐zation (mCNV) is the major cause of visual impairment in myopic patients. In the past, photodynamic therapy (PDT) as treatment of mCNV was only able to stabilize visual acuity. A randomiced, multicenter prospective Phase 3 study (RADIANCE) compared photodynamic therapy (PDT) and ranibizumab treatment and showed that immediate treatment of mCNV with a VEGF‐inhibitor (ranibizumab) significantly im‐prove visual acuity. There are suitable treatments of myopia associated pathologies and further studies using other VEGF‐inhibitor agents (Bevacizumab, Aflibercept) are underway.
Amniotic membrane applications in children
Authors: BREMOND‐GIGNAC D
Published: August 2014

Amniotic membrane is the innermost, multilayered part of the placenta. Its properties, stemming from its biological composition, make it a useful tissue for ophthalmic surgery. It promotes epithelization, has antimicrobial effects, decreases inflammation, fibrosis and neovascularization. Reconstruction of conjunctival and corneal defects, treatment of corneal ulcers demonstrated the beneficial effect of amniotic membrane for different ophthalmological indications. The various properties and its current clinical use in ophthalmology are studied in children. Stem cell characteristics have a potential contribution to cell‐based treatment of ocular surface disease such as ocular burns and limbal deficiency. Some specific clinical cases are exposed and show the interest of the application of amniotic membranes in children.
Introduction – Descriptions of the techniques
Authors: ZOGRAFOS L
Published: August 2014

Abstract not provided
Radiotherapy in pediatric oncology
Authors: MUNIER F
Published: August 2014

Abstract not provided
Innate immunity and retinal angiogenesis
Authors: XU H
Published: August 2014

The innate immune system plays an important role in tissue homeostasis under chronic insult conditions such as ageing and diabetes. Uncontrolled or dysregulated innate immune response to retinal insults in the elderly or diabetes may result in retinal pathologies such as age‐related macular degeneration (AMD) or diabetic retinopathy (DR). Patients suffering from AMD or DR may lose visual function due to the abnormal growth of new blood vessels. Growing evidence suggests that innate immune cells are critically involved in retinal angiogenesis. The role of monocytes/macrophages and neutrophils in retinal angiogenesis will be discussed.
Inflammation and angiogenesis in age‐related macular degeneration
Authors: SENNLAUB F
Published: August 2014

It is becoming increasingly clear that an altered immune response, which leads to low‐grade persistent inflammation, plays an important role in AMD pathogenesis in general and in choroidal neovascularization (CNV) in particular. Markers of inflammation, such as plasma levels of complement components and activation‐fragments, inflammatory cytokines and inflammatory monocytes are increased in AMD patients. Locally, mononuclear phagocytes (MPs, a family of cells that include microglial cells, monocytes, and macrophages) accumulate subretinally and possibly promote CNV. Data from different laboratories including our own indicate that the recruitment of inflammatory MPs, factors that promote their subretinal survival and the lack of tonic inhibitory signalling on MPs promotes CNV development. We will here present a summary of the current state of knowledge and its impact on the development of future therapies.
The burden of dry eye
Authors: PURSLOW C
Published: August 2014

Abstract not provided
VEGF family members (alternatively, molecular identities of anti‐VEGF agents)
Authors: SENNLAUB F
Published: August 2014

The vascular endothelial growth factors (VEGFs), comprise a family of growth factors that include VEGF‐A, VEGF‐B and Placental growth factor (PlGF) and promote angiogenesis and neovascularization. The important role of VEGF‐A in the development of choroidal neovascularization (CNV) and retinal edema has been demonstrated by the clinical success of VEGF‐inhibiting agents in wet AMD. An aptamer, an antibody, an antibody‐fragment and a soluble receptor have been developed for ophthalmological use to inhibit CNV in AMD. These therapeutic molecules differ in their spectrum of VEGF family members they inhibit, and in the structure of the molecules. We will here provide an overview of VEGF family members and their involvement in CNV and discuss the differences in the therapeutic molecules to bind VEGFs, inhibit CNV and to produce off target effects.
The role of ER stress in regulation of retinal angiogenesis and VEGF signaling
Authors: ZHANG S
Published: August 2014

The endoplasmic reticulum (ER) is the central hub for lipid and protein biosynthesis, protein folding and intracellular calcium storage in eukaryotic cells. Apart from these important and traditional roles, emerging evidence suggests that the ER functions as a principal stress sensor and signal transducer in the cell and this novel function is fulfilled primarily by the unfolded protein response (UPR). The UPR is an intricate set of adaptive signaling pathways activated upon aberrant accumulation of unfolded and/or misfolded proteins in the ER, or ER stress. Increased ER stress has been implicated in the pathogenesis of many human diseases such as neurodegenerative diseases, cancer and diabetes. The dynamic activation and differential regulation of the UPR signaling pathways plays a central role in coordinating the cellular responses to various metabolic changes and regulates a broad range of physiological and pathophysiological processes such as cell differentiation, proliferation, migration, apoptosis, inflammation, and angiogenesis. This presentation will summarize the role of ER stress in retinal angiogenesis and discuss the novel mechanisms of regulation of VEGF signaling by UPR pathways in relation to diabetic retinopathy.
European Board of Ophthalmology new subspecialty diploma; example: glaucoma surgery
Authors: SUNARIC MEGEVAND G
Published: August 2014

The main goal of the European Board of Ophthalmology is promoting education in Ophthalmology and harmonizing medical care in the field of Ophthalmology in European countries. The current EBO diploma ensures a minimum standard of knowledge in general Ophthalmology and is actually attended by a growing number of candidates, reaching in 2014 more than 500 from 28 countries. As there is a growing interest and real need for subspecialty training in different fields, the EBO is currently creating, with the help of European specialist societies , a sub‐specialty exam in order to award Ophthalmologists who complete sub‐specialty training and pass the exam with a formal recognition of their expertise by a Diploma. The aim is also to protect Sub‐Specialists and for the benefit of our patients in general, by inviting interested colleagues to obtain a distinction as a proof of excellence. During this course the example of the EBO‐Glaucoma Subspecialty exam with particular emphasis on surgical training, will be discussed.
Regulating the body clock – The unrecognised role of the eye
Authors: FOSTER R
Published: August 2014

Little more than a decade ago discussion that the eye might contain another photoreceptor, different from the rods and cones, generated either polite amusement or a hostile rebuttal. The dogma was that all light detection took place by these photoreceptors whilst the other cells of the retina act only to process visual signals. However, several lines of research led to the discovery that the vertebrate eye, including humans, contains another class of photoreceptor based upon a small number of photosensitive retinal ganglion cells (pRGCs). These specialised neurons detect environmental irradiance and regulate a wide range of physiology and behaviour including the regulation of 24h body clocks, sleep, alertness, mood and even pupil size. Furthermore, the pRGCs have been shown to utilize a novel light signalling pathway based upon the photopigment melanopsin. Collectively these findings have transformed our understanding of how the eye detects light and are redefining our assessment, treatment and care of individuals with eye disease. The discovery and current understanding of this “third” class of ocular photoreceptor will be reviewed in this presentation.
IOP measurement from corneal vibration parameters analysis: first clinical trial partial results
Authors: BITOUN P , BENZACKEN L , BOUAFIA K , HAOUCHINE B , CHAPELLE P , CHAMBARD JP , JOUROT P , PEAN V
Published: August 2014

Purpose A novel non‐contact, non‐invasive Vibration Tonometry technology with excitation of corneal vibration and their correlation to GAT IOP was tested in a large clinical trial reported

Methods 413 eyes from 207 volunteers from various origins at a suburban Paris hospital eye clinic were enrolled. History, vibration tonometry measurements in triplicate GAT, NIDEK air puff IOP, refractometry, keratometry and Tomey pachymetry. Algorithm discovery was performed by random draw splitting runs into a discovery sample and a separate validation sample performed 10 times separately on males and females.

Results 40/207 19.3% patients had glaucoma,50% were females.993 measurement runs were performed of which 83.5% were in correct position. Population aged 23‐92 yo with 42% females with mean 59.7(+/‐15.7) in females and 60.4 (+/‐13.8)in males. GAT IOP mean was 16.0 mm Hg (+/‐3.46) in females and 15.8 (+/‐3.95) in males. CCT mean was 530.2µ (+/‐35.1) in females and 526.3µ (+/‐42.4) in males, AL mean was 23.29 mm (+/‐1.68) in females and 23.73 mm (+/‐1.68) in males. None of these differences were significant. 46 eyes had GAT IOP greater >/= 20 mm Hg. No adverse events were reported during or post trial. Algorithm for women yielded 95,4% of IOP mean within 5 mm Hg of mean GAT IOP. For men 91% of IOP mean was within 5 mm Hg of mean GAT IOP

Conclusion Current algorithm seems to show no evidence of effect of CCT on measurement precision. Vibration tonometry is a valuable method for non‐invasive measurement of IOP without contact with reasonable precision and good reproducibility and independently of CCT. It may thus prove to be a valuable tool for IOP measurement in thin and surgical corneas

Commercial interest
Diagnostic and prognostic value of cerebrospinal fluid analysis in Vogt‐Koyanagi‐Harada syndrome
Authors: MOUALLEM A , TOUITOU V , BODAGHI B , CHAMPION E , DARUGAR A , FARDEAU C , CASSOUX N , LE HOANG P
Published: August 2014

Purpose To evaluate the diagnostic and prognostic values of lumbar puncture in Vogt‐Koyanagi‐Harada (VKH) syndrome.

Methods Medical records of patients seen in a single tertiary center between 1995 and 2013, with confirmed VKH syndrome according to the Revised Diagnostic Criterias, were retrospectively reviewed. Clinical stage of the disease, cerebrospinal fluid (CSF) analysis, therapeutic strategy, and prognosis were compared.

Results 68 patients with a confirmed diagnosis of VKH disease were initially reviewed. Among them, 29 patients (42%) had undergone a lumbar puncture (LP). 21 LP (72.4%) were performed at the early stage of the disease, and 11 were performed at the chronic stage of the disease (37.6%). 16 patients (55%) had a pleiocytosis. LP was abnormal in 66,7% at the acute phase and 27% at the chronic phase. An average of 62.3 lymphocytes /mm3 was observed when LP was performed during the acute phase and an average of 9.5 lymphocytes / mm3 was observed during the chronic phase ( p = 0,03). For two cases, the patient met the diagnostic criteria because of the LP findings. Patients dependant on low doses of steroids (<5mg/d) had more lymphocytes (93,8 lymphocytesmm3) into the initial CSF analysis compared to the patients dependant on high doses of steroids (>5mg/d) ( 29,3 lymphocytesmm3) (p=0.03) when LP was performed at the acute phase of the disease.

Conclusion The number of lymphocytes in the CSF at the diagnostic phase seems to be one of the prognostic factors for the outcome of VKH. Patients with a low pleiocytosis in the initial lumbar puncture should be closely monitored and may require a more aggressive treatment. Those conclusions must be confirmed with a prospective study.
Cataract surgery in children with syndromes or mental retardation
Authors: BREMOND‐GIGNAC D
Published: August 2014

Specific complications of cataract surgery in children are well known. Refractive errors, strabismus, amblyopia, glaucoma, posterior capsule opacification, inflammation, retinal complication. Young patients with syndromes or mental retardation can present some particular features that need to be evaluated and anticipated. Essentially they come from two directions. One is linked to ocular conditions that can be associated with the syndrome, such as microphthalmia, nanophthalmos, anterior segment dysgenesia, aniridia, frequency of capsular opacification, IO L calculation and complications, persistent fetal vasculature needs complex ultrasound examination to evaluate the surgical options, ocular misalignement, glaucoma, coloboma, retinal anomalies. The other condition is linked to mental retardation and the post‐operative capacity of the child. The different surgical procedures with each step and aphakia correction are discussed following specific ocular conditions and should be adjusted with the level of mental retardation.
Pulsatile versus non‐pulsatile choroidal blood flow in Primary Open‐Angle Glaucoma (POAG)
Authors: RIVA C , ABOU SAMRA W , POURNARAS C
Published: August 2014

Purpose After demonstrating altered subfoveal choroidal blood flow(F)in POAG (AbouSamra et al,Acta Ophthal 2012,we now studied the waveform of the pulsatile component of F(FP) in normal subjects and POAG patients. Methods Using laser Doppler Flowmetry (LDF,F and FP were measured in 17 healthy controls and 19 age‐ and sex‐matched POAG patients. We determined the waveform amplitude A(=1‐FPdiast/FPsyst) during the heart beat and the times T(d‐s) and T(s‐d) to increase from the diastolic to the systolic and to decrease from the systolic to the diastolic values of FP, respectively. Results Both mean F and mean FP were significantly (p < 0.001 and p = 0.02, respectively) reduced in the POAG compared to the control group. However mean FP/mean F was not significantly different between groups. Relative to the brachial artery value, the A‐value at the subfovea was significantly increased in POAG compared to controls. The mean vascular resistance (R = mean perfusion pressure /mean F) was markedly increased(p < 0.0001 in the POAG group. There was no significant differences in T(d‐s) and T(s‐d) between the groups. Conclusion These LDF‐based findings further support the presence of hemodynamic alterations in the subfoveal choroid in POAG.
Effect of acute hypoxia or hyperoxia on the optic nerve head and choroidal blood flow in healthy humans
Authors: CHIQUET C , ZHOU T , GALLICE M , APTEL F , TRUFFER F , GEISER M
Published: August 2014

This presentation deals with the ocular vasoreactivity to acute hypoxia and hyperoxia in young healthy subjects (n=16). The protocol consisted in a 15‐min inhalation of 100% O2 (hyperoxia) or 10.5% O2 + N2 (for a stable SpO2 of 85%, hypoxia) in normocapnic conditions. Blood flow was measured using laser Doppler flowmetry in the subfoveal choroid or at the temporal site of the optic nerve head (ONH). Hypoxia induced a significant 30±10% increase in ONH blood flow (due to simultaneous VEL and VOL rise). Hyperoxia significantly decreased ONH blood flow by 12±7% (due to both VEL and VOL decrease). Choroidal blood flow was not affected by hypoxia or hyperoxia. We will discuss the mechanisms associated with the effect of gas and the difference of response between choroid and ONH.
New insights into genetics of Fuchs dystrophy
Authors: BARATZ K
Published: August 2014

Fuchs endothelial corneal dystrophy (FECD) is a common, familial trait. Several genes have been associated with the disease, including LOXHD1, SLC4A11, TCF4, ZEB‐1 and COL8A2 which has been identified as a cause of an early‐onset Fuchs‐like disease. The evidence for these genetic associations will be reviewed and new data will be shared. To date, the most sensitive biomarker for FECD is an intronic TGC trinucleotide expansion in the TCF4 gene which is present in the majority of FECD cases and in a small proportion of normal control subjects. Within families, this tricnucleotide expansion tends to segregate with the disease phenotype. The biology of trinucleotide expansion diseases and possible mechanisms by which TGC expansion may conribute to FECD will be presented. A brief discussion of recent advances in our understanding of the pathophysiology of FECD, such as the unfolded protein response and oxidative stress, will also be presented in order to highlight the challenges in linking the implicated causative genes with the biochemical pathways involved in the disease.
Confocal microscopy and optical coherence tomography imaging of corneal dystrophies
Authors: WYLEGALA E
Published: August 2014

Corneal dystrophies are the group of hereditary, slowly progressive disorders affecting all corneal layers. In the past, histological examination was crucial in proper diagnosis of corneal dystrophies. In recent years, non invasive optical imaging systems such as optical coherence tomography (OCT) and confocal microscopy (CM) along with genetic testing have become a new standard procedures in the diagnostic process. Advances in diagnosis and treatment of corneal dystrophies including genetic analysis and confocal microscopy findings were included in the IC3D classification in 2008. The lecture summarizes the basic principles of the confocal microscopy and optical coherence tomography. It describes the pathological corneal changes revealed by slit lamp and histological examination in relation to non contact imaging techniques. The structural changes observed with the histological methods give an account and provide an explanation for pathological changes demonstrated by the OCT and CM. This may allow for a better understanding of the pathological process involved in the corneal dystrophies progression.