bluuebunny/crossref_metadata_2025 huggingface dataset:
TRPM1 and MITF expression in conjunctival melanocytic proliferations
Authors: MOULIN AP , ZOGRAFOS L
Published: December 2011

Purpose Downregulation of TRPM1, a transient receptor potential cation channel, has been correlated with a higher metastatic risk in skin melanoma. The promoter of TRPM1 contains MITF binding sites and MITF regulates in vitro the transcription of TRPM1. We have showed a partial loss of TRPM1 mRNA expression in a limited number of conjunctival melanoma. The aim of this study was to further investigate TRPM1 and MITF expression in a broader panel of conjunctival melanocytic proliferations

Methods Expression of MITF and TRPM1 was assessed by immunohistochemistry in 17 conjunctival naevi, 8 PAM (6 PAM with atypia) and 16 conjunctival melanoma. Statistical analysis was performed with JUMP 8,0 software.

Results A complete preservation of both MITF and TRPM1 expression was identified in all the naevi and the PAM. A partial loss of TRPM1 expression was found in 44% of the conjunctival melanoma (2 cases with a scattered loss of expression and 5 cases with a regional loss of expression). There was a significant partial loss of TRPM1 expression in the melanoma group compared with the naevi group (p=0,0027) or with the PAM group (p=0,0331). A partial loss of MITF was identified in 50% of the melanoma with significant reduction compared with the naevi group (p=0,0005) or with the PAM group (p=0,0262). There was a significant correlation between partial loss of TRPM1 expression and partial loss of MITF expression (p<0,001).

Conclusion We demonstrate a reduction of both MITF and TRPM1 expression in conjunctival melanoma compared with benign melanocytic lesions, suggesting that the loss of these proteins might be correlated with tumor progression. The concomitant partial reduction of expression of both genes is in concordance with the regulatory role of MITF on TRPM1 transcription.
Autophagic activity in uveal melanomas
Authors: BECHRAKIS NE , GIATROMANOLAKI A , SIVRIDIS E , CHARITOUDIS G
Published: December 2011

Purpose Autophagy is a self‐degradation mechanism by which cells recycle their own cytoplasmic constituents and organelles. Experimental data suggest that autophagy is up‐regulated by hypoxia in human neoplasia.

Methods The autophagic activity was investigated in a series of 73 uveal melanomas after immunohistochemical staining for the autophagy‐associated proteins LC3A and Beclin1. This was assessed in parallel with the hypoxia inducible factor 1α (HIF1α) and its downstream protein lactate degydrogenase 5 (LDH5).

Results Two patterns of LC3A expression were readily made out – diffuse cytoplasmic and cytoplasmic/juxta‐nuclear. The former was detected in 37/73 (50.7%) melanomas; the latter in 22/73 (30.1%) tumors. Beclin1 expression was invariably diffuse cytoplasmic and occurred in 37/73 (50.7%) uveal melanomas. LC3A and Beclin1, when highly expressed, were associated with intense pigmentation of the lesion, but only Beclin1 was associated with tumor necrosis (p<0.05) and a larger tumor size (p<0.05). It is of interest that Beclin1 and perinuclear LC3A expression were significantly related (p<0.02). In linear regression analysis, the LC3A juxta‐nuclear/perinuclear pattern and the Beclin1 expression were connected with the hypoxia‐related proteins HIF1α (p<0.02) and LDH5 (p<0.0001).

Conclusion Autophagy is commonly up‐regulated in uveal melanomas, and may be associated with necrosis and large tumor size. There is a connection between Beclin1 and LC3A juxta‐nuclear/perinuclear pattern, and a strong link between autophagy and hypoxia as this is inferred by the intimate relationship of LC3A and Beclin1 with HIF1α and LDH5, the major LDH isoenzyme involved in anaerobic metabolism.
An update on patient selection for OOKP surgery; Psychosocial Assessment
Authors: BUSUTTIL A , TURTON E , HEROLD J , LIU C
Published: December 2011

Purpose This presentation will provide an update on the contribution of Psycho‐social factors in the assessment and selection of patients for OOKP surgery. Assessment aims to identify Psychiatric, Psychological and Social issues which may positively or negatively affect physical and psychological outcome. Identification of such factors may not be a barrier to selection and successful outcome, as appropriate measures may be put in place to address factors which may impede physical or psychological recovery.

Methods Drawing on the existing psychological literature on patient assessment for complex surgery and studies carried out with OOKP patients in Brighton, Psychological factors associated with positive and negative biological and psychological outcome are described and the assessment protocol detailed.

Results A model which seeks to assess the contribution of psycho‐social factors in the prediction of complicated recovery is being developed and will be described. This is currently being incorporated into a prospective study to test the validity and utility of the model.

Conclusion Attention to Psycho‐social factors in selection of patients for OOKP surgery facilitates good bio‐psychosocial outcome by encouraging active patient participation in informed decision making about the surgery, good psychological preparation for the procedure and patient and family commitment to after‐care and follow‐up. For those where surgery is not appropriate or a decision needs to be postponed the selection process can also be of value for both patients and staff.
An update on glaucoma in OOKP eyes
Authors: LAM FC , HEROLD J , LIU C
Published: December 2011

Abstract not provided
An update on imaging and strengthening of the OOKP lamina
Authors: QASHOU A , FRANCIS I , HEROLD J , LIU C
Published: December 2011

Abstract not provided
An update on the Boston Type 1 KPro
Authors: CORTINA S
Published: December 2011

Abstract not provided
Meganuclease‐mediated inhibition of HSV1 infection
Authors: LABETOULLE M , HUOT N , SMITH J , GROSSE S , BARRADEAU S , ARNOULD S , MAHIET C , DESSEAUX C , CEDRONE F , PAQUES F , CHAPELLIER BC , GABISON EE , ERGANI A
Published: December 2011

Purpose Current anti‐viral treatments of Herpes simplex virus type 1 (HSV1) inhibit the viral replication but impair neither the viral cycle at its early stages nor the latent form of the virus. Latent HSV1 virus could be addressed by rare cutting endonucleases, such as specific meganucleases.

Methods Co‐transfections with plasmid expressing I‐CreI variants cleaving target sequences and GFP were performed using Lipofectamine on BSR cells for 48 hours. After infection for 8h with SC‐16 at different MOIs (Multiplicity Of Infection) ranging from 0.1 to 8, cells were incubated with i) HSV1 rabbit antibodies and ii) with phycoerytrine (PE) conjugated goat anti‐rabbit IGg secondary antibodies. Fluorescence‐activated cell sorting (FACS) analysis was performed. The ratio of infected cells among transfected (GFP+) and non transfected (GFP‐) cells were counted and an antiviral index was calculated.

Results GFP+ and GFP‐ cells were both well represented in all experiments, with an average GFP+ cell frequency of 0.63 over 90 transfections (standard deviation: 0.20). A strong inhibitory effect was observed at MOIs of 0.1 and 0.5, with 4 to 7 times less infection among GFP+ cells than among GFP‐ ones. This effect was however not detected by a MOI of 2.

Conclusion Meganuclease proteins in BSR cells inhibits the replication of HSV1, at moderate MOIs, inducing a significant reduction of the viral particules. This qualifies meganucleases as a new class of antiviral agent, with the potential to address replicative as well as latent DNA viral forms. Specific meganucleases may thus be used in the future with the aim of controlling recurrent herpetic keratitis.

Commercial interest
Loiasis. approach to a form of ocular parasitosis
Authors: CABEZON L , CASAS P , RAMIRO P , JIMENEZ B , MINGUEZ E , IBANEZ J , PEIRO C , CRISTOBAL JA
Published: December 2011

Purpose We report the case of a 37 year old male from Guinea referring foreign body sensation in his right eye intermittently for 5 years. The slit lamp examination revealed a creeping worm under the conjunctiva. The microbiological analysis after surgical removal confirmed that it was an adult form of Loa‐Loa.

Methods The anterior segment examination demonstrates the existence of a structure cordoned mobile moves creeping under the superior bulbar conjunctiva of his right eye. Given the findings are applicable to the surgical removal under local anesthesia of a worm 6 cm in length.

Results Microbiological study confirms the diagnosis of Loa Loa in their adult form (female).

Conclusion : Loiasis is a parasitic disease endemic in Africa. Recognition of the condition must be due to increased African migration to Spain. Surgical removal of adult Loa loa worms from the subconjunctival space only the ocular Improves Symptoms. An interdisciplinary approach (ophthalmology, infectious disease and parasitology) for a systemic work‐up and treatment is usually required.
Diabetic retinopathy
Authors: BANDELLO F
Published: December 2011

Diabetic macular edema (DME), defined as a retinal thickening involving or approaching the centre of the macula, represents the most common cause of vision loss in patients affected by diabetes mellitus. The pathogenesis and the course of the DME requires a complex approach with multidisciplinary intervention both at systemic and local level. In the last few years many diagnostic tools have been proved useful in the detection and the monitoring of the features characterizing DME. At the same time, several therapeutic approaches can now be proposed on the basis of the DME specific characteristics. Aim of the present chapter is to thoroughly outline the clinical and morpho‐functional characteristics of DME and its current treatment perspectives. More specifically, each DME subtype can be successfully managed making the most of the current treatment paradigm, including laser treatment, intravitreal steroids and anti‐VEGF, and macular surgery.
Spatio‐temporal responses in the visual cortex evoked from first‐ and higher order thalamic nuclei in tree shrews: a voltage sensitive dyes study
Authors: CASANOVA C , ABBAS FR , VANNI M
Published: December 2011

Purpose The primary visual cortex (V1) received its main thalamic drive from the lateral geniculate nucleus (LGN) through layer IV. In contrast, projections from the pulvinar end in layer I, suggesting that pulvinar exerts a diffuse modulatory influence on V1 activity. However, pulvinar projections to extrastriate areas (XC) mostly terminate in layer IV, suggesting that they provide a driver input to XC areas. Thus, one would expect the spatio‐temporal responses evoked by pulvinar activation to be different in striate and XC areas, reflecting the different connectivity pattern (driver vs modulator). We thus measured the spatiotemporal dynamics of voltage sensitive dyes activation in the visual cortex following thalamic electrical stimulation.

Methods Tree shrews were anesthetised and bilateral craniotomies were made on the visual cortex. RH1691 was used to stain the cortex. Stimulating electrodes were placed in LGN and pulvinar.

Results Stimulation of LGN induced fast and local responses in V1, which propagated to XC and contralateral cortex. The temporal profile of the responses was transient and monophasic in V1, and generally bimodal or tonic in XC. Stimulation of pulvinar induced fast and local responses in XC, followed by activation in V1 and contralateral cortex. The propagated waves in V1 were weak in amplitude and diffuse. Co‐stimulating pulvinar and LGN produced responses that were weaker than the sum of the responses evoked by the independent stimulation of LGN and pulvinar, even when pulvinar stimulation did not produce any responses in V1.

Conclusion The pulvinar can exert a modulator influence in cortical processing of LGN inputs while it mainly provides driver inputs to XC.
Windows‐based software for recording clinical electroretinograms
Authors: SANDBERG M
Published: December 2011

Purpose To develop user‐friendly Windows‐based software for recording submicrovolt clinical full‐field electroretinograms (ERGs).

Methods LabVIEW (National Instruments) — a parallel, graphical language based on structured dataflow diagramming created for data acquisition and instrument control — was used to write ERG software that runs on Windows XP. Data acquisition and instrument control are enabled with a National Instruments 16‐bit PCI Multifunction DAQ card.

Results This software simulates a signal‐averaging storage oscilloscope and has been used in our clinic since 2007 to record responses to 1/minute, 0.5 Hz, and 30 Hz flashes. The front panel includes virtual controls for a digital notch filter, a digital low‐pass filter, a digital band‐pass filter centered at 30 Hz, and an artifact reject buffer. Responses are saved to a sequential file readable by a spreadsheet program. A key feature when averaging cone ERGs to 30 Hz flashes is that ocular noise is removed independent of signal size, so that a low reject threshold can be used for every patient without attenuating the signal. The program can resolve cone ERGs as small as 0.05 µV to quantify retinal function in nearly all patients with retinitis pigmentosa.

Conclusion Programming in LabVIEW allows the creation of Windows‐based software that is user‐friendly and state‐of‐the‐art for resolving submicrovolt responses to 30 Hz flashes.
Assessing the wavelength dependence of intraocular scattering by a new optical approach
Authors: PEREZ G , GINIS H , BUENO J , ARTAL P
Published: December 2011

Purpose The wavelength dependence of the light scattering is related with the characteristics of the inhomogeneities in the ocular media, and therefore, an objective assessment could be used to the early detection of underlying ocular pathologies. We developed a new optical instrument for measuring light scattered in the human eye at different wavelengths.

Methods Using a double‐pass configuration, series of disks of uniform radiance with an increasing angular dimension are sequentially projected on to the retina. As a light source, a white light halogen lamp is spectrally filtered by using a liquid crystal tunable filter, selecting three different wavelengths: 550, 600 and 650 nm (FWHM = ± 50 nm). The disk’s retinal images are recorded by a cooled electron‐multiplied CCD camera. The derivative of intensity at the center of each disk’s retinal image with respect to its radius provides the eye’s wide‐angle double‐pass point‐spread function (PSF). The method was applied in an artificial eye with different levels of induced scattering, and in a group of normal subjects.

Results In the artificial eye, the increasing scattering induced is successfully discriminated at the more eccentric angular domain of the wide‐angle PSFs. In the group of subjects, the estimated wide‐angle PSFs differ from the lower to the larger wavelengths. The PSF at 550 nm is characterized by more intense light scatter in the angular range between 5 and 10 degrees, while the PSF at the 650nm showed a relatively increased scattered light between 0 and 2 degrees. This would be related to the deeper interaction of th

Conclusion An optical objective method is sensitive enough to detect consistently differences in light scatter for different wavelengths.
Lens refilling (Phaco‐Ersatz)
Authors: PAREL JM , HOLDEN BA
Published: December 2011

Purpose To demonstrate that the content of the crystalline lens can be replaced in vivo by a polymer designed to mimic the properties of the young lens to restore accommodation while maintaining ametropia, that polymer exchange can be performed anytime during follow‐up and that Phaco‐Ersatz also allows reversibility to IOL implantation in the bag.

Methods A safe endolenticular surgical technique was developed to remove relatively hard nucleus via a small capsulorhexis (~1.2mm) by US phacoemulsification (0.7mm titanium tip). The rhexis is closed by a mini‐capsulorhexis valve (~2mm), the polymer injected and then cured by low intensity light delivered by a custom made handprobe. Three families of polymers were developed allowing independent adjustment of the elastic modulus and index of refraction. These polymers were tested in 2 ex‐vivo accommodation simulators (EVASI and II) on human and primate eyes and their biocompatibility assessed in monkeys and rabbits for periods up to 8 months.

Results A safe endolenticular surgical technique was developed to remove relatively hard nucleus via a small capsulorhexis (~1.2mm) by US phacoemulsification (0.7mm titanium tip). The rhexis is closed by a mini‐capsulorhexis valve (~2mm), the polymer injected and then cured by low intensity light delivered by a custom made handprobe. Three families of polymers were developed allowing independent adjustment of the elastic modulus and index of refraction. These polymers were tested in 2 ex‐vivo accommodation simulators (EVASI and II) on human and primate eyes and their biocompatibility assessed in monkeys and rabbits for periods up to 8 months.

Conclusion Phaco‐Ersatz can be performed safely and is an effective method to restore accommodation.

Commercial interest
The use of electro optical materials to restore accommodation
Authors: MICHAEL R , BARRAQUER RI
Published: December 2011

Purpose We present a review of current developments to restore accommodation by means of electro optical materials embedded in glasses, contact lenses or intraocular lenses.

Methods Considered electro optical effects include electro active polymers, electro refractive polymers and the electrowetting principle. Possible solutions about how to measure the accommodation demand and to supply electrical energy inside the eye are also discussed.

Results Electrowetting uses the ability of a liquid to maintain contact with a surface and having a certain curved shape which can be altered by an electric field. Electro active polymers can change the size and shape under a changing electric field. Electro refractive polymers change the refractive index under an electric field. The electro active and electro refractive polymers can be put into pixelate optics were each pixel can be adjusted independently. Optical properties, energy consumption and dynamic properties of electro optical applications are compared with other accommodation restoration techniques.

Conclusion Commercial application of electro optical materials in glasses already exist, the use in contact lenses and intraocular lenses is under development.
Anti‐inflammatory mechanisms of mapracorat, a novel selective glucocorticoid receptor agonist, in human conjunctival fibroblasts
Authors: ZHANG JZ , VOLHEJN SM , WARD KW
Published: December 2011

Purpose Mapracorat (BOL‐303242‐X; ZK 245186) is a selective glucocorticoid receptor agonist (SEGRA), under clinical evaluation for the treatment of inflammatory eye and skin diseases. It is structurally distinct from glucocorticoids and NSAIDs. Data suggest an improved side effect profile of this compound compared to traditional glucocorticoids. This study was to determine its anti‐inflammatory mechanisms.

Methods Primary human conjunctival fibroblasts (HConF)were challenged with IL‐1ß and Luminex technology or ELISA was used to determine the effect of mapracorat on IL‐1ß‐induced cytokine, prostaglandin E2 (PGE2) and matrix metalloproteinase (MMP) release in the presence or absence of mifepristone (RU‐486), a glucocorticoid receptor antagonist. The effect of mapracorat on IL‐1ß‐induced cyclooxygenase‐2 (COX‐2) expression was assessed by Western blotting. Dexamethasone was used as the control.

Results IL‐1ß induced release of multiple cytokines, including IL‐6, IL‐8 and monocyte chemotactic protein‐1 (MCP‐1), and of PGE2 and MMPs (MMP‐1 and MMP‐3), as well as the expression of COX‐2. Mapracorat inhibited cytokine, PGE2 and MMP release as well as COX‐2 expression in a dose‐dependent manner with comparable effectiveness as dexamethasone. The inhibition of cytokine and PGE2 release was fully or partially reversed by mifepristone.

Conclusion Mapracorat acts as a potent anti‐inflammatory agent in HConF by inhibiting multiple intracellular mediators. The fact that mapracorat is effective on inhibiting PGE2 pathway suggests that it may reduce post‐surgery pain. Clinical significance of these findings needs further investigation.

Commercial interest
Skin tattoos and the development of uveitis
Authors: VAN CALSTER J , VANDER HULST K , GOOSSENS A , VAN DEN OORD J , JACOB J , VAN GINDERDEUREN R
Published: December 2011

Purpose To report a case of recurrent non‐granulomatous anterior uveitis associated with tattoo inflammation.

Methods A 28‐year‐old female presented to our ophthalmology department with a sharp shooting pain, photophobia and redness in both eyes but more pronounced in the right eye. A bilateral anterior uveitis was noticed. Simultaneously she experienced a rash at the site of her skin tattoos. The patient had her skin tattooed quite extensively at the chest, the back and around the umbilicus, between 13 years and one year ago.

Results Investigations for causes of anterior uveitis, including general and infectious serologic testing, ACE, HLA‐B27 and chest X‐ray were normal. Clinical pneumological examination, thoracic CT and abdominal ultrasound showed no arguments for sarcoidosis. A tattoo biopsy showed a granulomatous response of lymphocytes and histiocytes around tattoo pigment, there was no histological evidence for sarcoidosis.

Conclusion Tattoo granulomas can be a manifestation of sarcoidosis but may also be a delayed hypersensitivity reaction to pigment containing metallic tattoo compounds. The association of recurrent anterior uveitis with swelling of skin tattoos is an unusual occurrence. Similar cases of uveitis associated with tattoo inflammation have been reported in the literature.
Acute retinal necrosis. 3 case reports
Authors: CIMBALAS A , KOVALIUNAS E , KARALIUTE Z , LIVEIKIENE A , ASOKLIS R
Published: December 2011

Purpose To present three case reports of acute retinal necrosis (ARN) syndrome and discuss the aspects of diagnosis, treatment and prognosis.

Methods Retrospective analysis of clinical, laboratory, photographic and angiographic records of three immunocompetent patients with acute retinal necrosis syndrome.

Results Two male 22 and 36 years old and one female 25 years old patients had typical clinical symptoms of ARN syndrome: sudden decrease of vision acuity, eye pain, multiple areas of peripheral retinal necrosis, occlusive vasculitis, opticopathia, anterior uveitis and vitritis. Serum Ig G antiviral (VZV, HSV, CMV) titers were the basis for the etiological diagnosis. After applying systemic antiviral and steroid therapy, a rapid improvement of symptoms with the development of pigmentation in the areas of retinal whitening was observed in all patients. Retinal detachment occurred in 2 male patients and was successfully treated.

Conclusion Acute retinal necrosis syndrome is one of the vision threatening diseases for immunocompetent patients with poor prognosis. Early diagnosis and urgent antiviral therapy is therefore of vital importance for visual outcomes. Long term follow‐up is necessary due to high risk of retinal detachment.
Anterior segment optical coherence tomography study of the surgical outcome of the filtrating surgery in glaucoma
Authors: YANI A , MERCIE M , DJABAROUTI M , BADAT I , BOISSONNOT M , DIGHIERO P , GICQUEL JJ
Published: December 2011

Purpose To study the outcome of various filtrating surgery techniques in patients with glaucoma witthe Visante Anterior Segment Optical Coherence Tomograph (AS‐OCT)

Methods Fourty seven patients (47 eyes) (age 55 to 87) were enrolled after they had undergone filtrating surgery for glaucoma (Sclerectomy, Trabeculectomy, and combined surgery associating phacoemulsification and Sclerectomy or Trabeculectomy). Antimetabolites were used in all patients (mitomycin C or 5‐Fluoro Uracile). Intraocular pressure was recorded 6 months, 3 months and 1 month before surgery as well as 3 months, 6 months, 1 year and 2 years postoperatively. Each time the patients underwent full ophtalmological examination with subjective slit lamp evaluation of the bleb. Morphological evaluation of the bleb was performed with the Visante AS‐OCT in all patients after a minimum period of one year after surgery. The trabeculectomy / sclerectomy site as well as the morphology of the scleral flap, the conjunctival flap, the iris, and the relationship between these structures were analyzed

Results In most cases, a good correlation was observed between the AS‐OCT evaluation of the bleb and the measured IOP. AS‐OCT was helpful in determining the functional properties of filtration blebs in cases in which the target IOP was no reached.

Conclusion AS‐ OCT is a valuable tool for an accurate functional evaluation of the outcome of filtrating surgery in patients with glaucoma.
Is choroidal thickness different between glaucoma patients and healthy subjects?
Authors: BRON AM , FRANCOZ A , BEYNAT J , NICOT F , CATTANEO A , CREUZOT C
Published: December 2011

Purpose The aim of our study was to evaluate and compare choroidal thickness (CT) of healthy subjects and primary open‐angle glaucoma patients with spectral domain optical coherence tomography (SD‐OCT) and to seek a correlation between CT and glaucoma severity.

Methods Sixty‐five healthy eyes, 27 eyes with early glaucoma , 21 eyes with moderate glaucoma and 30 eyes with advanced glaucoma were included in this cross‐sectional study (one eye per patient). Retro‐foveolar CT, foveolar retinal thickness and average retinal nerve fiber layer thickness (RNFL) were measured by SD‐OCT. Humphrey 24‐2 visual field was also performed and mean defect (MD)recorded. Spherical equivalent (SE) was measured with automatic refractometer.

Results Average retro‐foveolar CT was statistically lower in glaucoma patients than in healthy subjects p=0.0023. The CT was not different according to glaucoma stage (p=0.078). We found a statistically significant correlation between CT and MD (p = 0.040), but not with CT and age (p=0.053), CT and retinal foveolar thickness (p=0,789), CT and RNFL thickness (p=0.732) and CT and SE (p=0.202).

Conclusion This preliminary study showed that retro‐foveolar CT measured by SD‐OCT was significantly thinner in glaucomatous patients than in healthy subjects.
Adjuvant intravenous therapy by fotemustine in uveal melanoma : a randomised study
Authors: DESJARDINS L , LEVY C , LUMBROSO LE ROUIC L , CASSOUX N , PIPERNO‐NEUMANN S , MARIANI P , SERVOIS V , DENDALE R , PLANCHER C , ASSELAIN B
Published: December 2011

Purpose to describe the protocol of adjuvant therapy by intravenous fotemustine in uveal melanoma

Methods Patient with uveal melanoma are included in a randomised protocol if their tumor has the inclusion criteria of high metastatic risk ‐ Clinical : largest tumor diameter ≥ 15 mm with extrascleral extension or retinal detachment , or largest tumor diametre > 18mm Or Genomic : tumor with at least complete or partial monosomy 3 associated to a gain of 8q , by BACs/CGH‐array performed on fine needle aspiration biopsy or on enucleation specimen. The calculation of the number of patients to be included uses the method of Freedman

Results 178 patients were screened.131 patients were not included because of refusal of the biopsy( 11), technical problems with the biopsy( 32), no genomic high risk ( 24), refusal of the chemotherapy protocol , general health problem( cardiovascular , age , co morbidity, other cancer) or delay before the patient was by the oncologist.

Conclusion Inclusion of patients in adjuvant therapy trials is difficult. More multicentric studies are necessary.
Development of new models of orthotopic primary human retinoblastoma xenografts
Authors: CASSOUX N , ASSAYAG F , NEMATI F , FONTAINE JJ , AERTS I
Published: December 2011

Purpose To develop preclinical orthotopic models of primary human retinoblastoma

Methods Orthotopic models of human retinoblastoma have been developed from three subcutaneous xenografted models that have previously been established and characterized in our laboratory, i.e. RB102‐FER, RB111‐MIL, and RB200‐GS that have been maintained in nude mice. Mice bearing xenografts were sacrificed and tumors were dissected to obtain a suspension of fresh tumor cells at a concentration of 8000 cells/l in DMEM serum‐free medium. Under intraperitoneal anesthesia, 2l of cell suspension was injected into the subretinal space of the right eye for 3 groups of mice using a 32G needle via a Hamilton syringe. Each group was constituted by 2 female SQUID mice and 3 male nude mice. After subretinal injection, ophthalmic examination of the mice was done every 15 days with binocular microscope. When tumor cells invaded vitreal cavity and anterior chamber, the mice were sacrificed for ophthalomological pathological analyses.

Results Tumor cells developed in all injected eyes, whatever the mouse categories used, 4 weeks after orthotopic transplantation for RB102‐FER and 6 weeks after for RB200‐GS. In contrast, no tumor growth was observed in injected eyes of the RB111‐MIL model. In the 2 first xenografts, the proliferation started with a white hemorrhagic retinal mass; three weeks later, the vitreous was invaded by tumor cells that extended to the anterior chamber. Pathological examination of the injected eyes confirmed the presence of a massive infiltration of the retina, vitreous and anterior chamber by retinoblastoma cells.

Conclusion We have then developed two new models of orthotopic primary human retinoblastoma that well reproduce the patient’s tumors.
Documentation of distribution of normal conjunctival vessels and their changes by mild irritation of photography using automated algorithm
Authors: BANAEE T , POURREZA HR , KHAJEH DALOUEE M , DANESHVAR KAKHKI R , BASIRI M , ABRISHAMI M
Published: December 2011

Purpose To quantify distribution of conjunctival vessels in normal eyes and the changes induced by the irritation of photography.

Methods Digital slit lamp photography of the upper and lower conjunctiva of 728 healthy eyes was done in 4 groups with different orders of succession of the photography in each person. A radon transform based algorithm was used to segment vessels and compute area occupied by vessels (AOV) of different sizes in each image. AOV of small, medium and large vessels were compared in the first photos of cases, and in the successive photos of each person using ANOVA (post hoc: Tukey) and paired sample T tests.

Results AOV of the 3 sizes of vessels had normal distribution in all images. In the first images of photography (un‐irritated eyes); AOV of medium sized vessels was the largest and was less in both fields of the left eye than the upper field of the right eye. Irritation of photography, caused an increase in AOV of the large vessels first, followed by increase in AOV of medium sized vessels accompanied by a decrease in AOV of small vessels, and finally a small increase in AOV of small vessels.

Conclusion Medium sized vessels are the most abundant in un‐irritated eye. During mild irritation, changes in large conjunctival vessels are documented first. Medium and small sized vessels seem to respond later.
Epiretinal membranes following retinal detachment surgery
Authors: KOURENTIS C
Published: December 2011

Purpose To study the factors that influence the development of secondary epiretinal membrane (ERM)formation after retinal detachment repair and to report anatomic and functional results.

Methods The patients had received either pars plana vitrectomy or scleral buckling for their retinal detachment repair. The patients underwent pars plana vitrectomy with ERM removal in the second surgical procedure.

Results Foveal morphological changes influence best corrected visual acuity outcome in patients with secondary ERM after retinal detachment repair.

Conclusion ERM development is a known complication of retinal detachment repair. The anatomic and functional results can be improved in these patients by removal of the ERM.
ElVisML: A little less conversation. Experiences with the Electrophysiology of Vision Markup Language in clinical routine and in a multi‐center trial
Authors: STRASSER T , PETERS T , ZRENNER E
Published: December 2011

Purpose The International Society for Electrophysiology of Vision (ISCEV) started a process of standardization in electrophysiology of vision to increase comparability of recordings. Standardization is important, especially in clinical trials. However, there is no standard for encoding electrophysiological data of vision. Recently, we proposed such a standard, called Electrophysiology of Vision Markup Language (ElVisML). Here we give an overview of our experiences in the application of ElVisML in clinical routine and in a multi‐center clinical trial.

Methods The University Eye Hospital Tuebingen runs three Espion (Diagnosys Ltd) systems, all connected to a central database, which is integrated into a hospital information system (HIS). ERG recordings are added to patients electronic health records (EHR) as ElVisML file. The software system of the STZ eyetrial ERG reading center uses ElVisML as a native format for the electronic exchange of ERG recordings between stakeholders of the reading process.

Results Integrated into a HIS, ElVisML allows for a network‐wide access to ERG recordings and long‐term archiving. Compliance to regulatory requirements of the reading center are successfully implemented in a multi‐center study (2 sites, 20 patients, 4 examinations) using ElVisML: An audit trail is realized by revisions of ElVisML files, conformance checks are automatically enforced during each step of the workflow using data included in ElVisML.

Conclusion Open standards like ElVisML help to ensure quality, validity, and integrity of ERG recordings, provide manufacturer independent access, and long‐term archiving in a future‐proof format in clinical routing as well as in reading centers.

Commercial interest
Electroretinogram and patterned Visual Evoked Potentials as detectors of retinal dystrophy in children affected by Joubert syndrome: a longitudinal survey
Authors: RUBERTO G , SUZANI M , SIGNORINI S , FAZZI E , ANTONINI M , BERTONE C , GUAGLIANO R , TINELLI C , BIANCHI PE
Published: December 2011

Purpose Joubert syndrome (JS) is a rare autosomal recessive congenital malformation of the brainstem and cerebellar vermis. The pathology can be associated with retinal dystrophy (RD). In a previous study we presented the data of retinal involvement and their relationship with electrophysiology in 26 JS patients. The longitudinal data are shown in a part of this sample.

Methods All the children had repeated clinical examinations. The electroretinogram (ERG) was performed without sedation. One recording skin electrode was placed on the bridge of the nose. The stimulation included the maximal combined response and a 30 Hz response after a brief adaptation. For the patterned visual evoked potentials (PVEP) a sequence of checks of 15, 30, 60, 120 and 300 minutes of arc was presented. All the JS children had both ERG and PVEP repeated from 2 to 4 times. A total of 13 JS affected children for the ERG and 12 for the PVEP were analyzed. Comparisons between percentage of reliable responses were performed by Fisher exact test.

Results A significant difference between JS children with and without RD in 30 hz ERG (p=0.050) and 120, 60, 30, and 15 minutes of arc (p=0.006,0.002,<0.001,<0.001 respectively) was found.

Conclusion ERG and PVEP repeated measures are valuable means for the diagnosis and follow‐up of RD in JS (patients).
AZOOR Defined (Acute Zonal Occult Outer Retinopathy)
Authors: HECKENLIVELY JR , WANG A
Published: December 2011

Purpose To identify common diagnostic findings in 25 patients with AZOOR, first described by Gass in 1993 as a syndrome with rapid loss of one or more large zones of outer retinal function. We were interested in better defining recog‐nizable diagnostic features and the natural history.

Methods Patients were identified by sudden onset of zonal functional loss (scotomata) on kinetic visual fields, and abnormal electroretinograhy. All patients had full clinical examinations, family histories for autoiommune disease and retinal degeneration, kinetic visual fields, autofluoresence imaging, electroretinography, Western blots for anti‐retinal antibodies (ARAs).

Results There were unifying patterns among patients; all but 4 patients were women, over half had family members with other autoimmune disorders, the disease had asymmetric presentation in 35% of patients. The ERG was always abnormal in eyes with the scotomata, and in most the photopic b‐wave amplitudes were markedly decreased in eyes with large scotomata. Enlarged blind spots extending into equatorial regions were a strong and common feature of the scotomata, which could be seen on autofluorescence. Pigment deposits were very uncommon. Western blots were very positive with an average of 6.5 immunoreactive anti‐retinal antibody bands (normal <1.2). Negative waveforms, occurred in 3/25 patients, and 30Hz flicker amplitudes abnormal in 19/25 with only 12/25 with delayed ITs. Patients with recent onset had a better response to immuno‐suppressant therapy.

Conclusion AZOOR is another atypical retinopathy that has anti‐retinal antibodies as a common feature. The ERG suggests that pathologic anti‐cone antibodies play a key role, and given the pattern of scotomata, the ARAs access the retina via the optic canal or peripapillary region.
Varicella zoster Virus
Authors: ANDROUDI S
Published: December 2011

Purpose Patients with herpes zoster ophthalmicus (HZO) are referred to ophthalmologists for prevention or treatment of its potential complications. Without prompt detection and treatment, HZO can lead to substantial visual disability. The purpose of this presentation is to summarize the typical signs and symptoms of anterior uveitis associated with varicella zoster virus (VZV).

Methods Presentation of typical signs and symptoms of anterior uveitis associated with varicella zoster virus (VZV).

Results Varicella zoster virus is often associated with corneal complications such as epithelial, stromal, and disciform keratitis; anterior uveitis; necrotizing retinitis; and cranial nerve palsies in relation to the eye. Postherpetic complications, especially postherpetic neuralgia (PHN), are frequently observed. Cranial nerve palsies are common and most often involve the facial nerve, although palsy of the oculomotor, trochlear, and abducens nerves may occur in isolation or (rarely) simultaneously. Complete ophthalmoplegia can also been seen. Vasculitis within the orbital apex (orbital apex syndrome) or brainstem dysfunction is postulated to be the cause of cranial nerve palsies.

Conclusion The management of VZV ophthalmic involvement, includes a multidisciplinary approach aiming to reduce complications and morbidity
Diagnostics of virus‐induced anterior uveitis
Authors: GARWEG JG
Published: December 2011

Purpose Virally induced anterior uveitis, accounting for more than 10 % of cases, is the most common form of infectious anterior uveitis. A distinction between the various possible infectious agents is important for therapy and prognosis, but frequently not possible basing only on history and clinical grounds only. In these cases, a laboratory confirmation of the clinically presumed diagnosis is of interest.

Methods A Medline search was conducted using the search terms “anterior uveitis”, “virus” and “diagnostic”. After exclusion of reviews and studies including less than ten samples, the remaining were assessed for their diagnostic yield with focus on the viruses of the herpes family (HSV‐1, HSV‐2, VZV, CMV, EBV, HHV6‐8), Rubella and Parechovirus including ELISA, PCR and immunoblot testing from paired samples of aqueous humour and serum.

Results Based on intraocular antibody synthesis and PCR, herpes vriuses represent the majority of viral anterior uveitis instances. Cytomagalovirus‐ and Rubella‐associated anterior uveitis have obviously been underestimated in their role, whereas the clinical relevance of Parechovirus and other forms of more recently described viral anterior uveitis cases has as yet to be determined.

Conclusion Basing on published evidence, a systematic diagnosis of infectious agents in presumed viral anterior uveitis has to be postulated for all cases without a clear clinical diagnosis or a poor response to therapy. If access to a qualified laboratory is lacking, a parallel sample of serum and aqueous humour should be collected and be referred to one of the international referrence laboratories if the clinical situation is developing unfavourably.
Rete mirabile in mouse retina?
Authors: RUBERTE J , MENDES‐JORGE L , RAMOS D , LOPEZ‐LUPPO M , NACHER V , NAVARRO M , CARRETERO A
Published: December 2011

Purpose One possible definition for rete mirabile, the “wonderful net”, is a capillary network interrupting one arteriole, as happens in kidney. In a glomerulus, the afferent and efferent arterioles are communicated by a capillary tuft. It is generally accepted that in mouse retina, capillaries communicate directly arterioles with venules. However, this must be difficult in a tissue where normally there is not concordance between the number of arterioles and veins. In the current study, we explored the presence of retia mirabilia in mouse retina which could explain the mismatch between retinal arterioles and venules.

Methods Retinas from C57BL6 and CD1 mice were used. After partially clamping of the common carotid arteries, hypoxia was detected using the Hypoxiprobe‐1 Kit (Chemicon). Mice were intravenously injected with 60 mg pimonidazole/kg body weight in phosphate‐buffered saline. Pimonidazole specifically binds to proteins in hypoxic cells at an oxygen pressure equal to or lower than 10 mmHg. Thirty minutes after injection animals were euthanized and pimonidazole binding proteins were detected in the retina by immunohistochemistry.

Results Direct capillary connections between retinal arterioles were found in C57BL6 and CD1 mice, indicating the presence of retia mirabilia. No venules were found between arterioles in the rete mirabile areas. In order to know if these retia mirabilia have some function in retinal oxygenation, partially clamping of common carotid arteries was performed and hypoxia was detected in the retina using the Hyposiprobe‐1 Kit. Interestingly, rete mirabile areas were less hypoxic than conventional capillary areas.

Conclusion There are retia mirabilia in mouse retina and these vascular structures could be important in retinal oxygenation.
Tear Film Topography
Authors: NOCHEZ Y , HABAY T , PISELLA PJ
Published: December 2011

Purpose Patient complaints such as blurry vision are a very common symptom of dry eye syndrome. We will summarize technologies to measure the optical effects of tear film instability.

Methods There are several noninvasive techniques for assessing the kinetics of tear film : high‐speed videokeratoscopy, dynamic wavefront sensing and lateral shearing interferometry. Interferometry or break up time are sensitive techniques for recording tear film surface irregularities in a noninvasive manner.

Results However, in order to understand the visual complaints associated with tear film instability, we need some dynamic visualization of the corneal tear film quality. Shack‐Hartmann wavefront sensor and wavefront aberration could realize an objective evaluation of optical quality of the eye between blinks. We will discuss the use of higher‐order aberrations fluctuations during 10 seconds. At last, we will try to quantify the visual impact of dry eye using objective scattering index.

Conclusion Dynamic aberration maps may be used for diagnosis of dry eye and for monitoring drops efficiency.
Measurements of the dynamic aberrations induced by the tear film
Authors: GICQUEL JJ
Published: December 2011

The static higher‐order aberrations of the eye are easily measured with most commercially available wavefront aberrometers.However it has been only recently that the dynamic wavefront aberrations induced by the tear film (which plays a crucial role in the quality of vision)have been measured.In this presentation we will focus on the use of double pass wavefront aberrometry OQAS™ (Optical Quality Analysis System)for measuring vision quality disturbances caused by anabnormal tear film, in various clinical situations.
Straylight as measure for quality of vision and the tear film
Authors: VAN DEN BERG TJTP
Published: December 2011

Purpose In this presentation an overview will be given on the basic optical effects connected with the tear film. A prominent role of the tear film is to create a smooth surface for the most powerful refractive interface of the eye, i.e. the air‐cornea interface. On the other hand, the tear film itself can disturb proper imaging if light is scattered in it, or if its surface is not perfectly smooth.

Methods Surface effects on optical image formation can be described with aberrometry. Only, in the case of the epithelial surface, present aberrometers do not have sufficient resolution to describe the fine irregularities. The group of Thibos designed a way to address this problem using the shape of the spot images of the Shack‐Hartmann aberrometer. Effects of light scattering can be assessed using straylight measurement (implemented in the C‐Quant from Oculus).

Results Both aberrometric and straylight outcomes combine to form the ocular point‐spread‐function defining the functional problem originating from optical defects in the tear film. The aberrometric errors dominate the central part of the PSF, and thus visual acuity. Straylight corresponds to the peripheral part of the PSF, and dominates in complaints like glare and hazy vision. Literature models for both aspects of the optical problems in the eye media were used to delineate their effects on the PSF.

Conclusion Two domains must be differentiated: the aberration domain and the small particle scatter domain, with corresponding parts (small angle vs large angle) to the PSF. Straylight typically originates ffrom small particles, as opposed to aberrations originating from refractile humps and bumps extending over large distances (tear film surface) or small small distances (epithelial surface).

Commercial interest
The implications of the mebomian glands dysfunction in the quality of vision
Authors: DIGHIERO P
Published: December 2011

Abstract not provided
Cyclosporine A‐loaded and limbal stem cell‐seeded nanofibers for the local suppression of inflammatory and transplantation reactions
Authors: HOLAN V , ZAJICOVA A , CHUDICKOVA M , LENCOVA A , TROSAN P , SVOBODOVA E , KRULOVA M
Published: December 2011

Purpose Purpose. To prepare nanofibers containing the immunosuppressive drug cyclosporine A (CsA) and to assess the potential of these nanofibers to inhibit allotransplantation and inflammatory reactions in vitro and in vivo.

Methods Methods. Nanofibers containing 10 weight percent of CsA were prepared from biocompatible polymer poly(L‐lactid) by electrospinning procedure. The kinetics of drug release was characterized in aqueous solutions in vitro and in vivo. The growth of mouse limbal stem cells (LSC) on CsA‐loaded nanofibers was evaluated. The ability of CsA‐loaded nanofibers to inhibit allotransplantion reactions in vitro and inflammatory reactions in vivo was characterized.

Results Results. The incorporation of CsA into PLA polymer did not influence the pharmacological activity of CsA nor affected the diameter, shape or architecture of nanofibers. The addition of CsA‐containing nanofibers into mixed lymphocyte culture significantly inhibited in a dose‐dependent manner cell proliferation and production of proinflammatory cytokines IL‐2, IL‐17 and IFN‐ Mouse LSC grew on CsA‐loaded nanofibers comparably as on CsA‐free nanofibers. The covering of inflammatory sites with CsA‐loaded nanofibers significantly attenuated the local inflammatory reaction.

Conclusion Conclusion. The CsA‐loaded and LSC‐seeded electrospun nanofibers can be used as scaffolds for LSC transfer and simultaneously as drug carriers for the local suppression of transplantation and inflammatory reactions.