bluuebunny/crossref_metadata_2025 huggingface dataset:
RUNX2 expression in conjunctival melanocytic proliferations
Authors: MOULIN A , NICOLAS M , HAMEDANI M , SCHALENBOURG A , ZOGRAFOS L
Published: August 2012

Purpose Amplification of RUNX2 (6p21.2), a transcription factor involved in bone formation and in tumor progression of prostate and breast cancer, has previously been identified in 76% (16/21) of primary conjunctival melanoma and in 100% (4/4) of metastatic conjunctival melanoma. The aim of this study was to investigate RUNX2 expression at the protein level in a panel of conjunctival melanocytic proliferations

Methods Expression of RUNX2 was assessed by immunohistochemistry in 26 conjunctival naevi (14 compound naevi, 11 subepithelial naevi and 1 cellular blue naevus), 13 PAM (9 PAM with atypia) and 25 conjunctival melanoma. Statistical analysis was performed with JUMP 8,0 software. Expression was regarded as negative if less than 10% of the tumor cells expressed RUNX2. Examination was independently assessed by two observers.

Results RUNX2 was found in 3 naevi (11,5 %), in one PAM with atypia (7,6%) and in 5 melanoma (20 %) without significant variation between the 3 groups. In the melanoma group, there was no correlation between RUNX2 expression and TNM category, depth of invasion, proliferation index (Ki67), local lymphatic invasion and the presence of metastasis. There was however a significant correlation between RUNX2 expression and death (p=0,0191).

Conclusion RUNX2 is expressed in a limited number of conjunctival melanocytic proliferations without significant differential expression between benign and malignant lesions. The biological significance of RUNX2 in conjunctival melanoma tumor progression requires further functional investigations.
Idiopathic orbital inflammation: a report of 18 cases
Authors: COFFIN‐PICHONNET S , LANGLOIS B , JACOMET PV , PUTTERMAN M , BADELON I , MORAX S , GALATOIRE O
Published: August 2012

Purpose Idiopathic orbital inflammation is a rare clinical entity which has protean clinical manifestations. It’s a diagnosis of exclusion which imposes a biopsy, and which can be made only after a screening to rule out a systemic etiology of inflammation.

Methods Retrospective series of 18 histologically‐proven orbital inflammation cases seen in our service between 2006 and 2011.

Results The study encompassed 7 men and 11 women, with a mean age of 47 years old (4‐83). Patients complained of a pain (44%), a diplopia (33%), a decreased visual acuity (17%). A swollen eyelid or a palpable mass were presents in 78% of the cases. Less often, we noted proptosis, or a diminished ocular motility. The radiologic analysis (CT‐scan, NMR, doppler ultrasound examination) found an inflammation localized to the orbital fat, to the lacrymal gland, and to one or several oculomotor muscle(s) in respectively 89%, 67%, and 39% of the cases. Excisional biopsy was curative for 33% of the cases. 61% of the patients received a corticotherapy, with a relapse or a recurrence in 60% of the cases, making necessary to have recourse to immunosuppressive agents (methotrexate), with a good control rate on the inflammation (75%). Finally, 76% of the patients obtained a complete resolution of their symptoms at the end of the follow‐up (mean : 20 months).

Conclusion Treatment lies on surgical exeresis if it is safely. Corticotherapy is frequently not sufficient. Methotrexate seems to be an interesting alternative. Recent works concentrate on Systemic IgG4 Disease, who could be a frequent cause of orbital inflammation, calling the term "idiopathic" into question, and letting us think about targeting treatments.
Priorities of Ophthalmic Research
Authors: SPAETH G
Published: August 2012

Purpose The purpose of this presentation is to examine critically several of the fundamental considerations regarding research, focusing on ophthalmic research. Time and resources are limited. Paradoxically, they appear to be increasingly so. In such an environment it would seem to be important to perform research that is “ useful.” Who is best suited to decide what is “useful?” Does limiting the freedom of investigators to study what they wish result in dampening creativity? Who should determine – if anybody – priorities of research?

Methods Historical and literature review, with personal opinions informing (or biasing) the conclusions.

Results The concept of “academic freedom” has long been protected by academic communities, more vigorously in some cultures than others. On the other hand, limits at least since the time of Socrates have been placed on research and commentary; these limits have been imposed by cultural mores, and by communities such as various religious groups, by economically powerful people and industries, and governments. The medical and scientific communities also have imposed limits. Who should set these? How responsible has the medical community been?

Conclusion Freedom is most likely to be allowed when that freedom leads to outcomes the community considers in their best interest. Critical reappraisal of the appropriateness of deciding priorities of research is needed. Is the concept of the “clinical an/scientist” viable? Suggestions will be given as to how to preserve or increase the creativity of research and yet promote the study of issues that are useful, relevant and likely to lead to a “better world.”
Role of vitrectomy
Authors: WOLFENSBERGER T
Published: August 2012

Abstract not provided
Case presentation
Authors: MASSIN P
Published: August 2012

Abstract not provided
Outcomes of macular hole surgery in highly myopic eyes : a case‐control study
Authors: CONART JB , HUBERT I , BERROD JP
Published: August 2012

Purpose To evaluate the outcomes of macular hole (MH) surgery in highly myopic eyes and to compare these results with controls.

Methods The study design was a matched, case‐control, retrospective chart review. Ninety‐four eyes who underwent vitrectomy with internal limiting membrane removal for a MH without retinal detachment were included. Group 1 included 47 consecutive eyes with high myopia and group 2 included 47 control eyes operated on the same period and matched for MH size. The main outcomes were preoperative and postoperative best‐corrected visual acuity (BCVA), MH closure rates and complications.

Results The mean axial length was 28,5 mm in high myopic eyes and 23,3 mm in the controls (p<0,001). There was no significant difference in the mean duration of symptoms, size of the MH and preoperative BCVA between the two groups. Closure of the MH was achieved in only 39/47 eyes (83%) with high myopia versus to 45/47 eyes (96%) in the controls (p=0,04). Mean BCVA improved in both groups (0,41 versus 0,68 logMAR) but was significantly lower in myopic eyes (p<0,001). Anatomical outcomes tended to decrease when axial length increased (p=0,06).

Conclusion MH surgery in high myopic eyes results in satisfactory anatomical and visual improvement but not as good as in the controls. Longer axial length may increase the risk of anatomic failure.
Cytopathological findings in the vitreous of patients with retinal detachment
Authors: ARNDT C , BONNAY G , RAMONT L , DIEBOLD MD , DUCASSE A , BOULAGNON C
Published: August 2012

Purpose Proliferative vitreoretinopathy (PVR) is the leading cause of failure in retinal detachment surgery. The migration of retinal pigment epithelial cells and the occurrence of extracellular matrix changes have been associated with PVR. The purpose of this prospective study was to analyze the cellular contents of the vitreous in patients with retinal detachment.

Methods The vitreous samples of patients with epiretinal membrane and rhegmatogenous retinal detachment were obtained at the initial phase of surgery without previous intraocular infusion. A cytopathological analysis and staining of the vitreous was performed in all cases. The vitreous of 40 patients with retinal detachment and 49 patients undergoing epiretinal membrane peeling (control group) were included.

Results The preparations displayed a variable cellularity. A higher amount of epithelial cell clumping was observed in retinal detachment specimens compared with controls. Furthermore, in the retinal detachment group, more free pigments were encountered and a higher degree of reticulation of the extracellular matrix was noted. In the vitreous of patients with retinal detachment, there is some cytopathological evidence for a higher concentration and an increased activity of retinal pigment epithelial cells compared with controls.

Conclusion The predictive value of cytopathological changes for the occurrence of postoperative proliferative vitreoretinopathy in patients undergoing retinal detachment surgery remains to be demonstrated.
Post‐surgical intra‐ocular inflammation in a mouse model and high mobility group box protein 1
Authors: BEUERMAN R , YUAN ZH
Published: August 2012

Purpose Postsurgical intraocular inflammation is an expected consequence of surgery or trauma. The purpose of this study was to examine new methods for preventing postsurgical inflammation that might avert the problems associated with the use of steroids. An important step was to identify a new molecule that has a leading role in the promotion of inflammation, high mobility group box protein 1, HMGB1.

Methods Surgery was carried on one eye of C57/BL6 mice and the other eye served as control. A scleral incision was created approximately 0.4 mm from the limbus with a 1mm DBL edge sapphire blade inserted at a 3 o’clock position. The incision was closed by 2 interrupted 10‐0 nylon monofilament nonabsorbable sutures. In vivo confocal imaging was performed in a preplanned fashion to analyze cell infiltration into the cornea, anterior chamber and iris at PO days 1, 3, 5 and 7. Tissues were collected on the same schedule. Immunofluorescent staining was conducted to examine S100A8, S100A9 and high‐mobility‐group box‐1 (HMGB1) expression, which was confirmed by quantitative real‐time polymerase chain reaction (RT‐PCR).

Results mRNA levels of S100A8/9 in the cornea, HMGB1 in the cornea and iris increased significantly (p<0.05) at PO day 1 and decreased over time. Immunostaining for S100A8/9 and HMGB1 corroborated the RT‐PCR results. There was no detectable S100A8/9 or HMGB1 in the unwounded iris. The expression of S100A8/9 and HMGB1 was stimulated in the cornea stroma and iris, with a peak at PO day 3, and decreasing over time. Staining of S100A8/9 and HMGB1 in the cornea epithelium was present at low levels and did not appear to increase after surgery.

Conclusion HMGB1 is a critical early phase regulator of inflammatory events after surgery. The release of HMGB1 can not be avoided as it is released from the nuclei of damagend cells and is therefore always a part of surgical outcomes.
Killer cases due to occult choroidal inflammation : how to prevent them
Authors: PAPADIA M , HERBORT CP
Published: August 2012

Purpose Inflammation of the choroid evolves mostly unnoticed when only clinical examination and/or only classical investigational methods are used. In some cases such occult inflammation, when it is finally noted has already caused irremediable damage.

Methods Inflammatory cases are presented that showed minimal or no signs on clinical examination/investigational tests, where significant occult choroïdal inflammation was detected by ICGA and that responded to therapy initiated on the base of ICGA findings. In parallel, patients that were treated with delay or received no therapy and suffered irremediable damage will be presented.

Results Primary inflammatory choriocapillaropathies PICCPs (MEWDS, APMPPE, multifocal choroiditis) known to be caused by inflammatory choriocapillaris non perfusion can only be meaningfully investigated for activity by ICGA as non‐perfused areas are not seen otherwise. If active disease (non‐perfusion) is suspected, PICCPs have to be evaluated and followed by ICGA and in case of persistence of non‐perfusion and worsening of function, therapy has to be introduced to avoid irremediable damage. For stromal choroiditis such as Vogt‐Koyanagi‐Harada (VKH) disease, persisting choroiditis after alleged clinical recovery needing continued therapy can only be shown by ICGA, so avoiding complications due to smouldering occult disease.

Conclusion ICGA in the work‐up of posterior uveitis should be part of a routine investigation for those case where angiographic work‐up is deemed necessary.
Interesting case‐reports
Authors: POURJAVAN S
Published: August 2012

Purpose The aim of this lecture is to explore and gather all the topics explained in this SIS in some real case‐reports.

Methods The diagnosis of glaucoma in high myopic patients can be very bothersome because of the variability of optic disc morphology and the difficulty in visual fields’ interpretation caused by the large peripapillary atrophy and the progressive retinal myopic changes. The management, treatment and the follow‐up of glaucoma in these patients needs more elaboration than the average, not‐myopic POAG patients. The intraocular pressure measurements in patients with a previous refractive surgery demands an especial attention not only inasmuch of the reduced corneal thickness but also because of the postoperative changes in the corneal biomechanical properties. The choice of a target pressure and a target pressure range is highly related with the degree of the myopia.
Anatomic and physiologic considerations of the intrinsically‐photosensitive retinal ganglion cells
Authors: LUCAS R
Published: August 2012

I will provide an overview of the physiology and function of intrinsically photosensitive, melanopsin‐expressing, retinal ganglion cells. Originally discovered during the search for photoreceptors regulating the circadian clock, it is now established that these receptors influence a wide array of accessory visual responses. Most recent data indicates that they also can contribute to perceptual vision.
Rod, cone and melanopsin contributions to the pupil light reflex
Authors: KARDON RANDY
Published: August 2012

Purpose To define the relative contributions of rod, cone, and melanopsin to the human pupillary light reflex (PLR) and to determine the optimal conditions for assessing their status in patients with retinal and optic nerve disorders.

Methods The pupil light reflex was measured with an eye tracker, and stimuli were precisely controlled with a Ganzfeld ERG computerized system. For rod mediated transient pupil responses, a low intensity 1‐second duration blue light was given under dark adaptation. For cone mediated transient pupil responses, a red, high intensity 1‐second duration light was given on a blue background to suppress rod contributions. For melanopsin mediated sustained pupil responses, a bright 1‐second bright blue light was given without background.

Results Rod mediated transient pupil responses were present in normal eyes but not in patients with moderate to advanced retinitis pigmentosa. A blue background suppressed rod and melanopsin responses, enabling assessment of cone contributions with a red flash. Robust melanopsin sustained pupil responses could be seen in patients with lack of contributions from the rods and cones.

Conclusion The rod, cone, and melanopsin contributions to the PLR can be assessed with a simple clinical protocol with blue flashes at two or three intensity levels in the dark and one red flash on a blue background, allowing for diagnosis and differentiation of retinal and optic nerve diseases.
Chromatic pupillometry as a novel means to assess outer retinal function in health and disease states
Authors: KAWASAKI A
Published: August 2012

Quantified pupil responses to colored light stimuli is a non‐invasive means to monitor melanopsin function as well as rod and cone activity. Understanding the trivariate contributions to the pupil light reflex has led to renewed interest in using the pupil response to monitor a variety of diseases. The characteristic pupillographic feature of intrinsic, melanopsin‐mediated ganglion cell activity is persistent contraction after light offset. This post‐illumination response is abnormal in patients with glaucoma. In patients with retinal degenerative disease, the retinal sensitivity to blue light as measured by pupillometry is reduced. This correlates with loss of rod function but also hints at reduced melanopsin activity. Clinical examples showing pupil response to red and blue light in patients with neuroretinal visual loss will be discussed.

Commercial interest
Melanopsin and its role in photophobia
Authors: KARDON RANDY
Published: August 2012

Purpose Photosensitivity is common in patients known to have migraine headaches, in patients following traumatic brain injury, in patients with certain CNS pathology and in inflammatory disorders of the eye. However, it is a subjective complaint and difficult to substantiate and treat. Recently, we have taken advantage of a primitive reflex, the photic blink reflex, to objectively quantify the eye’s sensitivity to light.

Methods Patients with light sensitivity and normal subjects were tested using red (640nm) and blue (485nm) Ganzfeld, full field light, one second in duration, over a 6 log unit range of intensity (0.5 log unit steps). Time‐stamped, computerized recording of the orbicularis and procerus/corrugator muscle EMG were quantified using the maximum root mean squared (RMS).

Results The photic blink reflex appeared to show similar response characteristics as the pupil light reflex, having both a transient response to photopic red and blue light and a sustained response to high intensity blue light. Patients with light sensitivity showed an exaggerated EMG response to light compared to normals.

Conclusion The sustained EMG response to bright blue light provides evidence for a melanopsin mediated photic blink reflex. The photic blink reflex, as measured by the electromyogram, appears useful for quantifying light sensitivity and its response to treatment.
Study of stromal femtosecond laser ablation for deep corneal cut optimization
Authors: BERNARD A , AUDOUARD E , THURET G , PEOC'H M , DUMOLLARD JM , GRANIER J , SODER H , MOINE B , GAIN P
Published: August 2012

Purpose Anterior and posterior stroma of human cornea present different biophysical characteristics, the later being more hydrated and collagen fibers less tightly packed. Our aim was to investigate interactions between femtosecond laser (FL) and stroma according to the depth of cut in order to optimize FL endothelial graft preparation

Methods organ cultured human corneas were prepared with a mechanical microkeratome (Moria, France) by a lamellar cut from anterior side at two different depths: 50µm for the study of anterior stroma and 350µm for the study of posterior stroma. Grooves were then performed in the remaining anterior or posterior stroma with a 800nm, 150fs FL (Thales, France) with different processing configurations (Speed: 1900 to 10000µm/s; Power: 0.8 to 6mW). After treatment, corneas were observed by light and second harmonic generation (SHG) microscopy to compare ablation rates (AR) (in µm/pulse) and cut quality in anterior and posterior stroma

Results Preliminary results (n=4 corneas) showed no significant differences between posterior stroma AR (1.97±0.91µm/pulse) and anterior stroma AR (1.73±0.50µm/pulse). Using SHG microscopy, two different cutting types (with or without disruption) occurred, depending on processing configurations and independently of depth in the stroma

Conclusion These results suggest that there is no significant difference of AR between anterior and posterior stroma. Consequently, difficulties usually encountered to cut endothelial grafts with FL may not directly depend on a particular ablation rate of the posterior human corneal stroma, but rather on the optical scattering when FL passes through the stromal layers, already identify as a limiting factor
New improvements in Boston Keratoprosthesis (KPro): titanium surface modifications
Authors: SALVADOR CULLA B , JEONG KJ , PASCHALIS EI , CHIANG HH , GIPSON IK , DOHLMAN CH , KOHANE DS
Published: August 2012

Purpose Improve biointegration and esthetics of Boston KPro through Ti coating.

Methods Polydopamine (PDA) was used to form a Ti oxide (TiO2) film on polymethylmethacrylate (PMMA) rods through liquid phase deposition. The rods were inserted in porcine corneas and kept in culture for two weeks. Biointegration was assessed by measuring the force required to pull the rods out of the corneas with an Instron 5542 tensiometer, followed by SEM examination of their surface. Color modification (blue or brown) of Ti backplates of the Boston KPro was achieved using oxide formation in an anodization setup, and biocompatibility was studied using human corneal limbal epithelial cells.

Results Mechanical pull‐out showed that TiO2 significantly increased the force required to separate the rods from the corneas (0.354 N), compared to bare PMMA (0.039 N) and PDA (0.098 N). SEM images showed residual cellular and extracellular materials only on TiO2‐coated rods. Ti oxidation produced blue or brown‐coated backplates. No difference was observed in proliferation, migration or cytotoxicity between coated and uncoated groups in cell culture (p>0.745).

Conclusion TiO2 coating enhanced corneal tissue integration with PMMA rods. Oxidation also improved the esthetics of the Ti backplates of the Boston KPro, without compromising its safety or biocompatibility.
Stromal alteration in post‐lasik ectasia cornea
Authors: AKHTAR S , KIRAT O , ALKATAN H , ALMUBRAD T
Published: August 2012

Purpose Post‐LASIK corneal ectasia is a serious late postoperative complication. After LASIK, the corneal stroma is structurally weakened. Patients with this complication present with an increase in myopia and astigmatism. Here we report the stromal alteration in the post‐LASIK cornea.

Methods Two Saudi male patients were diagnosed post‐LASIK ectasia. Patient 1, had ectasia six years after LASIK in both eyes. Patient 2, had ectasia four years after LASIK in right eye. Both patients had undergone penetrating keratoplasty in the right eye. The corneas were processed for light (LM) and electron microscopy (EM).

Results The LASIK flap was detached from the residual stromal bed. The posterior end of the flap which had separated from the stromal bed lacked collagen fibrils and instead contained numerous very fine microfilaments. The proteoglycans were absent. There were large keratocytes containing a large nucleus in the stroma. The stromal lamellae were thin and disorganized. The collagen fibrils were running randomly and their distribution was not uniform. There were aggregates of micro‐filaments, which replaced some parts of the Bowman’s layer and stroma.

Conclusion The present study showed the disorganisation of the lamellae collagen fibrils. A large number of microfilaments were present at the detachment end of the flap and the residual stroma. Numerous aggregates of micro‐fibrils replaced some parts of the Bowman’s layer and stroma. Acknowledgement: Supported by National Plan for Science and Technology, KSU, Riyadh.
Surgical approach in corneal perforations and deep ulcers
Authors: DOBROWOLSKI D , JANISZEWSKA D , TARNAWSKA D , KRYSIK K , WYLEGALA E
Published: August 2012

Purpose Outcomes of patch grafts in corneal perforations and deep ulcers.

Methods For the study 184 patients (follow‐up at least 6 months) were qualified: 57men and 127 women, mean age 61,7,±19,1 years. 198 procedures (112 in corneal perforations and 86 in deep ulcers) were performed. We applied grafts with diameter from 2,5 to 5 mm with oversize of 0,5 – 1 mm. Visual outcomes and corneal surface stability were analysed

Results In 175 eyes we achieved stabile corneal surface, 23 grafts were failed due to graft melting. Among 175 eyes improvement of VA was achieved in 89 eyes, 58 required further procedures of penetrating keratoplasty or cataract surgery. The best visual outcomes were achieved in peripheral ulcers or perforations, central changes usually required further management or were connected with poor prognosis for good vision. 28 eyes due to dry eye, no light localization or retinal detachment (3 eyes) were disqualified to other procedures

Conclusion Patch grafts are useful to restore vision and maintain corneal integrity.
Deutsche Uveitis Arbeitsgemeinschaft (DUAG) ‐ How patients can support research
Authors: ZIERHUT M
Published: August 2012

This presentation will summarize how the DUAG (Deutsche Uveitis Arbeitsgemienschaft) was founded and developed. The reasons for the group, having an umbrella position over the local patient groups, will become explained, and how this concept may become adapted to other ocular diseases.
Initiating a glaucoma interest group in Belgium
Authors: STALMANS I
Published: August 2012

The Belgian Association for Glaucoma Patients was founded in 2010. Its goals are to inform about glaucoma, to improve early detection and follow‐up of glaucoma, to promote interaction between the members and others, to promote the interests of the Belgian glaucoma patients and to enforce their position in the Belgian society. During this lecture, the experiences and activities during the start‐up phase will be shared with the audience, followed by an open discussion with the participants.
Reccurence of vasculitis
Authors: BODAGHI B
Published: August 2012

Retinal vasculitis (RV) is a sight‐threatening disease associated with different infectious or auto‐immune conditions. RV may be isolated or revealing a systemic disease such as Behçet's disease, sarcoidosis, SLE or multiple sclerosis. Recurrence rate depends on multiple factors such as demographics, etiology, type and extension of vasculitis and most importantly, the therapeutic strategy. The Optimal use of immunosuppressive and biologic agents block recurrences in mots of the cases and decrease the rate of complications. Long‐term remission may be achieved in specific entities, after treatment discontinuation.
Targeted delivery
Authors: BEHAR‐COHEN F
Published: August 2012

Abstract not provided
Clinical study results with new wireless electronic subretinal implant alpha‐ims
Authors: ZRENNER E , BARTZ‐SCHMIDT KU , GEKELER F , GREPPMAIER U , HEKMAT A , HOERTDOERFER G , KERNSTOCK C , KITIRATSCHKY V , SACHS H , STINGL K , WILHELM B
Published: August 2012

Purpose Restitution of vision in blind Retinitis Pigmentosa patients by the new wireless implant Alpha‐IMS (Retina Implant AG, Tübingen, Germany).

Methods Each of the 1500 subfoveal photodiodes within an 11 by 11 deg field controls an amplifier that ejects light evoked currents onto bipolar cells via TiN electrodes (Zrenner et al. Proc. R. Soc. B 2011, 278: 1489ff). Power and control signals are transmitted transdermally via retroauricular inductive coils connected to a subdermal cable to the eye.

Results Ten patients received implants since 2010 (average age 46±84). In 8 patients the chip was at the desired subfoveal position; in 2 patients slightly parafoveal. All patients were able to perform the function tests except one due to loss of inner retina function after surgery. Results in all other patients were: light perception 9/9; light localization 8/9; motion recognition 5/9; grating resolution 8/9 (up to 3,3 cycle/degree); Landolt C rings 3/9 (up to 0,036); recognition of geometric objects 8/9; recognition of objects in table setup 8/9; letter reading 4/9; clock hands reading 3/9; grey scale differentiation 6/9; improved outdoor mobility 5/9. Patients` experiences: recognition of unknown objects, facial or clothes’ characteristics, moving objects in nature and traffic, small objects (glasses, telephone, doors, door handles, washing basin, dices).

Conclusion The wireless Alpha‐IMS implant can restore useful visual abilities in blind RP‐patients. Subretinal surgery for positioning chips subfoveally is safe and the multicenter part of the study has been started in Oxford, London and Hongkong.

Commercial interest
ARHGEF26/SGEF controls fovea formation, immunity, neurodevelopment and arteriosclerosis
Authors: BITOUN P , PIPIRAS E , BENZACKEN B , DELAHAYE A
Published: August 2012

Purpose Identify cause of congenital syndrome with macular dystrophy, absent fovea in consanguineous family 6 yo girl with congenital nystagmus,low vision after informed consent.

Methods Family had complete ophthalmologic, neurologic examination, brain MRI, genetic tests, array CGH, lipid profiles, vascular Doppler US.Mouse,human fetal ISH

Results Proband had congenital nystagmus and corpus callosum agenesis.Vision was 20/200 w/o photophobia,night blindness. Fundus showed macular atrophy, normal vessels w/o pigment, small papilla. ERG, OP were normal, absent pattern VEP points to macular bundle defect.OCT showed absent fovea, thin retina (102 µm OD and 92 OS) interruption of the photoreceptor layer. MRI showed hippocampi hypoplasia. ABCA4 testing was negative as 18 ARRP genes. Parents have normal vision,ERG,VEP,OCT, angio and brain MRI. Array CGH showed 114kb homozygous 3q23 deletion up to 6th intron of SGEF gene in 3 sibs. Sister had absent fovea on OCT, low vision and macular dystrophy, brother had decreased foveal function on multifocal ERG with normal vision. Girls have repeated infections: EBV hepatitis,dental abcesses..Well parents harbor same heterozygous deletion. Mouse antibody In situ hybridisatio mapped to retina.Human Fetal brain cortex ISH wss positive. SGEF controls leukocyte trans‐endothelial migration,1st phase of atherosclerosis. Mother with high cholesterol 212mg/dl and hyper‐triglyceridemia had normal cervical arteries doppler US normal examination w/o atherosclerosis at 42yo

Conclusion Data suggests ARHGEF26/SGEF gene controls arteriosclerosis, macular cone development, immune function, axon midline crossing with recessive inheritance. Deletion possibly has protective effect against arteriosclerosis
Efficacy and safety of gene therapy with AAV4 in childhood blindness due to rpe65 mutations
Authors: LE MEUR G , LEBRANCHU P , PEREON Y , BILLAUD F , IVAN C , CHAUVEAU C , ROLLING F , WEBER M
Published: August 2012

Purpose To assess the safety and efficiency of an subretinal injection of an AAV2/4.rpe65.hrpe65 in subjects with LCA due to mutations rpe65 genes.

Methods A phase I/II clinical trial assessed the safety and the efficiency of one subretinal injection with AAV2/4.rpe65.hrep65 vector in the worse eye of patient with rpe65‐/‐ retinal dystrophy. Patients of the first cohort received up to 400 µL and patients of the second cohort up to 800 µL of a vector solution at 6.1010 vector genome/mL. The primary safety endpoints are evaluated by biomicroscopy, laser flare meter, fundus photography, fluorescein angiography, OCT and a tolerance questionnaire. Secondary efficacy endpoints are evaluated by global ERG, multifocal ERG, visual field, near and far visual acuity, color vision test, pupillometry, microperimetry, visual mobility, functional MRI and fundus autofluorescence.

Results We will present results of the first six patients included in an ongoing study. Patients are 21 to 42 years old. The three first patients were included in the first cohort and three other were included in the second cohort. No adverse effects or ocular inflammation are noticed one year to 2 months after subretinal injection. Visual acuity is limited to light perception to 1/12 and remained stable after subretinal injection. Visual field modifications in the subretinal treated area are noticed in all patients.

Conclusion subretinal injection of a serotype 4 AAV vector for gene therapy treatment of rpe65‐/‐ retinal degeneration is safe. Visual field improvement found in our adult patients want us to treat 3 childrens scheduled in the third cohort.
Genetics of keratoconus
Authors: SOLER V , CASSAGNE M , FOURNIE P , MALECAZE F
Published: August 2012

Keratoconus (KC) is a vision‐threatening condition characterized by thinning and deformation of the cornea. It is one of the most common indications for corneal grafting in industrialized countries. The disease prevalence is approximately 1 in 2000. Familial aggregation, together with increased familial risk, suggests important genetic influences on its pathogenesis. To date, it has been shown that several genomic regions are linked to KC rare familial forms but no genes have been identified as responsible for common KC. Aside from genetic determinants, environmental stresses such as eye rubbing or atopy have been suggested as possible causes or aggravating factors in KC. The interaction of genetics and environmental factors in diseases occurrence contributes to the development of complex and multifactorial trait, such as KC. And, despite the many attempts to reveal KC pathophysiology, the mechanisms leading to its corneal characteristics and vision impairment are still poorly understood. In this presentation, we will discuss all works that have been achieved on keratoconus pathophysiology and we will consider future directions on this topic.
Apoplexy in pituitary tumors, clinical and MRI analyses
Authors: DE KEIZER RJW , SCHUTTE P
Published: August 2012

Purpose The aim of the study is to evaluate the different types and incidence of pituitary tumors with apoplexy between 1988‐2009.

Methods Retrospective data analysis from the notes of the neuro‐endocrine multidiciplinary workgroup and medical records of these patients treated by neurosurgeon or conservatively.

Results complete notes were found from 5 years. Different ways of detection were found: the classic tumor pituitary apoplexy, accidental during MRI analyses and during surgery for an pituitary adenoma. Of the 82 macroadenomas, found in the notes over 5 years, in 17 cases an apoplexy was found, which is a higher incidency than described in the literature. From the in total 27 cases found during the 20 years period analysis, 15 cases had the classic pattern, with‐ at most‐ eyemovements disorders ; 10 cases had a subclinical pattern and were diagnosed by MRI, and or histopathological or biochemical; in 2 patients the mass was without tumor, and only hemorrhage.

Conclusion Headache, eye motility disturbances and +/‐ chiasmal syndrome may pronounce in 20 % of the pituirary masses to an apoplexy. Because a pituirary mass frequently is managed with surgery, but conservative treatment is possible without complications, this differential diagnosis is important in neuro‐ophthalmological clinical practice. The different MRI patterns will demonstrated during the presentation.
Four‐year‐ old child with optic nerve glioma revealed by a proptosis
Authors: BENNAI D , CRETU I , FICHTEN A , SEVESTRE H , COPIN H , BREMOND‐GIGNAC D
Published: August 2012

Purpose Optic pathway gliomas are rare tumors accounting for 3‐5% of brain tumors in children. Our case aims to understand surgical options.

Methods We report the case of a 4‐year‐old child with a single optic pathway glioma revealed by a non esthetical proptosis and blindness. Association with NF1 was not found. The MRI showed a tortuous enlargement of the left optic nerve, the glioma extended into the optic canal with a scleral invasion. Considering those results, a treatment consisting of a double team surgery, ophthalmologists and neurosurgeons was performed with enucleation and complete section of the nerve at its optic chiasm root.

Results Histology confirmed the diagnosis of glioma, as a pilocytic astrocytoma, with safety margins. Cytogenetic analysis showed an unspecific chromosome 8 deletion. Chemotherapy was avoided because of systemic toxicity and tumor localization.

Conclusion Association with NF1 is classical and the incidence of optic nerve glioma is estimated at 15%. In young children the glioma can be the first manifestation of NF1 and the disease should be kept in mind. Cytogenetic mutation must be searched with surgical sample in culture. In children, surgical treatment can be preferred to chemotherapy when excision of the total tumor removal can be performed.
Strabismus and visual acuity in children with ocular coloboma
Authors: ARNAUD M , NADEAU S , AZIZ A , HAMDAN J , DENIS D
Published: August 2012

Purpose to report visual acuity and strabismus frequency in children with ocular coloboma.

Methods We retrospectively analysed 43 children diagnosed as having ocular coloboma (18 boys and 25 girls). Median patient age at diagnosis was 30 months. We studied: visual acuity, binocular status, and refractive errors. We ranked different coloboma as anterior, posterior and antero‐posterior with a whole ophthalmological examination and were divided in two groups: with (I) or without (II) strabismus.

Results 43 children were included, 25 (58.1 %) had strabismus, 18 with esotropia (72 %) and 7 with exotropia (28 %). Groups I and II were similar on social issues. 23 children had bilateral coloboma and 20 unilateral coloboma. A total of 66 eyes were studied: we found 5 anterior coloboma, 33 posterior and 28 antero‐posterior. 13 were associated with microphtalmia. There was no significant difference between children in group I and II. 29 Colobomatous anomalies were found in group I and 37 in group II. Children in group I had a worse visual acuity than in group II (p< 0.001). Severe coloboma frequency (posterior or antero‐posterior with macular involution) was higher in group I than in group II.

Conclusion These results are comparable to those found in literature. There is a worse visual acuity for strabismus‐associated coloboma.Strabismus more often occurs in coloboma‐diagnosed children than in general population and is often associated with amblyopia.
Combined approach, the yield of microincisions for cataract surgery
Authors: BRON A
Published: August 2012

Cataract extraction combined with glaucoma surgery remains a matter of debate. Some authors advocate consecutive surgeries arguing that the expected lower inflammation will allow a better outcome of the filtering surgery. However cataract extraction after a filter may impair the long term efficacy of glaucoma surgery. Conversely the combined approach is more convenient for the patient with one operation and generally a better visual result. However it is generally considered that the IOP‐lowering effect is less effective in combined procedures. Rather than opposing these two approaches, it is probable than according to the characteristics of the patient and the type and the stage of glaucoma, a consecutive or a combined surgery is more appropriate. Therefore the surgeon must be prepared to perform the two types of surgery. Micro incisions for cataract surgery (MICS) offer some substantial advantages vs conventional corneal incisions; a better tightness of the surgical wound allows a better control of IOP during the surgery. Therefore glaucoma surgeries (penetrating or not) are much easier to perform without changing your technique. In this presentation some surgical tips will be given in order to facilitate your combined procedures.
Drug delivery by ionic hydrogel contact lenses in preoperative prophylaxis of intraocular infections
Authors: FOKINA DV , BOIKO EV , REITUZOV VA
Published: August 2012

Purpose To evaluate the efficiency of ophthalmic drug delivery through ionic hydrogel soft contact lenses (SCL) in comparison with eye drops in preoperative prophylaxis of intraocular infections.

Methods The efficiency of moxifloxacin and levofloxacin delivered via SCL was compared to eye drops in patients having cataract surgery. Investigations were conducted with 1‐DAY ACUVUE® TruEye® hydrogel SCL, saturated with moxifloxacin solution 0.16 % (Avelox) and levofloxacin solution 0.5% (Tavanic), which were put on the cornea (Group 1). Another group of patients were given five times the dosage of these drugs (Group 2). These manipulations were made one hour before phacoemulsification in both groups. Aqueous samples (0.1 mL) were collected at the beginning of the surgery. The antibiotic concentration in aqueous aliquots was determined using spectrofluorimetry and liquid chromatography.

Results Maximum therapeutic concentrations (TC) of moxifloxacin and levofloxacin in the aqueous humor were achieved after 4 hours 18.0 ± 2.0 and 9.0 ± 1.2 μg/mL (Group 1), followed by gradual decrease of them (p<0.05). TC lasted no less than 6 hours. The minimum inhibitory concentrations were only achieved by eye drops of the same drugs (Group 2). Moxifloxacin and levofloxacin delivered via SCL in 10 and 5 times respectively increased the relative bioavailability in comparison with the eye drops of these antibiotics.

Conclusion 1. The application of ionic hydrogel soft contact lenses is an effective drug delivery method. 2. Ionic hydrogel soft contact lenses, saturated with moxifloxacin and levofloxacin, provide a therapeutic antibiotic concentration in the aqueous humor. 3. Ophthalmic drug delivery through contact lenses increases bioavailability.
Oxidative stress in retinal pigment epithelial cells: protective effect of wood‐derived phenolic compounds
Authors: REINISALO M , PAIMELA T , RYHäNEN T , KAUPPINEN A , KOSKELA A , SOININEN T , KAARNIRANTA K , KARJALAINEN RO
Published: August 2012

Purpose Oxidative stress is related to chronic diseases including age‐related macular degeneration (AMD), which is the leading cause of blindness in the elderly worldwide. Functional roles of wood‐derived phenolic compounds such as flavonoids, phenolic acids, tannins and stilbenes are not well known, but some of them are effective antioxidants capable of providing defence against oxidative stress. Besides reducing ROS production by their antioxidant activity, phenolics can also activate the expression of phase II genes via the activation of transcription factors, such as Nfr2.

Methods In this work, the protective effect of wood phenolics against oxidative stress were determined by pre‐incubating ARPE‐19 cells in medium containing wood compounds (pinosylvin, piceatannol, trans‐resveratrol or pinosylvin monomethyl ether) at different concentrations. After pre‐incubation with phenolics, cells were treated with oxidative stress causing agent, hydroquinone, for 24 hours. The viability of cells was determined by using MTT assay. To elucidate the mechanisms behind the phenolics‐mediated protection against oxidative stress and inflammation, the activity of genes such as Nrf2, IL‐6 and p62 was determined.

Results Wood‐derived phenols were well tolerated by the cells and some of the compounds such as pinosylvin were able to increase the viability of cells in response to induced oxidative stress.

Conclusion These results suggest that wood‐derived phenolic compounds can provide additional protection against oxidative stress in retinal cells.
Anatomy, physiology and pathophysiology of the meibomian gland
Authors: KNOP E , KNOP N , SULLIVAN DA
Published: August 2012

Purpose The sebaceous meibomian glands (MG) in the eyelids, that secrete lipids for the superficial tear film layer, are of increased scientific and clinical interest. The recent MGD report of the non‐profit organization Tear Film and Ocular Surface Society (TFOS, www.tearfilm.org) revealed that MG Dysfunction (MGD) with lack of tear film lipids and the resultant evaporative type of dry eye is the main underlying reason for the wide‐spread dry eye disease that affects millions of patients world wide

Methods A literature review based on the TFOS MGD Report together with own findings is discussed in order to explain the anatomy, physiology, pathophysiology and clinics of MGD.

Results MGD is a multifactorial disease based on endogeneous and exogeneous factors that interact in self propagating vicious circles. Advancing age, female sex, environmental factors such as topical medication, bacterial influences and probably subclinical inflammatory pathways as well as contact lens wear are some main factors lead to the onset and propagation of MGD. These result in hyperkeratinization of the gland epithelium as well as increased viscosity of the secretum. Together this results in the obstructive type of MGD. Two effector arms of obstruction lead to a primary lack of oil on the tear film with downstream evaporative dry eye but also to a secondary hidden degeneration of the glandular tissue inside the lids that results in gland atrophy.

Conclusion Obstructive MGD with downstream lipid deficiency is now recognized as the main cause for dry eye disease and this achievement of the TFOS MGD Workshop has already changed/revolutionized our view on dry eye disease as well as lead to several new developments for diagnosis and treatment that specifically address MGD. Support DFG KN 317‐11
Identification of MGD in dry eye patients and its treatment in the practical clinical setting & The Austrian perspective on MGD
Authors: HORWATH‐WINTER J , RABENSTEINER DF , BOLDIN I
Published: August 2012

MGD can be found in about 70% of patients with ocular discomfort as evaluated in a large clinic‐based population of Austria. It is characterized by a continuum of clinical severity. Especially discrete cases are often underestimated und receive not enough attention. In patients with ocular discomfort it is important to investigate the blinking action, the lid margins (crusts, vascularisation, Marx line, meibomian orifices) and also to perform the expression of the meibomian glands. Tear deficiency is often accompanied with MGD therefore the function of the lacrimal glands should be tested. To evaluate the damage of the ocular surface, staining with fluorescein and lissamine green are recommended. Further important diagnostic measures are the evaluation of the lipid layer and the examination of the meibomian glands with meibography. Although there is an overlap between different subtypes of dry eye, proper diagnostic evaluation is important to identify adequate therapeutic treatments that would best target the underlying dysfunctions. The most commonly recommended treatment option for every stage of MGD remains eyelid hygiene that should be performed on a regular basis. Eyelid warming to melt the meibum and eyelid massage to express secretion shall prevent obstruction of the terminal ducts. To improve compliance special devices that are more convenient for the patients can be used. Instillation of artificial lubricants, especially with lipid containing components may stabilize the tear film. Essential fatty acids, topical and systemic antibiotics and other anti‐inflammatory medication are further important therapeutic options.
Characterization of human corneal grafts’ transparency by optical coherence tomography and scattering measurements
Authors: HOFFART L , CASADESSUS O , GEORGES G , SIOZADE L , DEUMIé C
Published: August 2012

Purpose In clinical and graft sorting applications, cornea’s transparency is only subjectively qualified. The aim of this study is to bring tools to achieve transparency quantification regarding the evolution of edema within the tissue.

Methods The samples are human corneal grafts rejected from bank of tissue due to physiologic issues, which are submitted to swelling protocol to study their properties with edema. A multiscale analysis of the microstructure imaged by 1 µm resolved Optical Coherence Tomography (OCT) combined with a detailed characterization of backscattering properties is performed. Electromagnetical modelization is used to numerically link scattering measurements with structural defects observed with OCT.

Results Backscattered intensity measurements enable corneal grafts’ transparency evaluation (backscattering level increases with swelling). Moreover, microstructural tissue modifications occurring during swelling (microstructure disorganization and heterogeneities) are highlighted by OCT imagery. We show that the observed heterogeneities imply higher scattering levels and explain the experimental results.

Conclusion Combining both techniques allows linking the scattering behavior with the evolution of microstructures within the tissue and permits to quantify corneal grafts transparency. This study has to be extended to tissues eligible for graft but this characterization in the backscattered space could directly be applied to future study of tissues before removal or to in vivo diagnosis.