bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaging and the ageing retina
Authors: KEANE PA
Published: August 2012

Until recently, assessment of ageing in the living human retina has principally depended on fundus photography and related techniques (e.g., fluorescein/indocyanine green angiography and fundus autofluorescence). Since the 1990s, however, the discovery of a wholly new imaging modality ‐ optical coherence tomography (OCT) ‐ has revolutionised the diagnosis and management of retinal diseases by providing high resolution cross‐sectional images of the retina in a non‐invasive manner. In this presentation, I will review existing methods in use for imaging of the ageing human retina, with a particular focus on the latest advances in OCT imaging. I will also describe the attempts that are underway to address the shortcomings of current retinal imaging modalities; for example, the use of adaptive optics to provide cellular level image resolution, the use of Doppler and spectral imaging techniques for the assessment of retinal blood flow and oxygenation, and a number of new technologies with the potential for assessment of novel functional parameters, such as photoacoustic and magnetic resonance imaging.
Macrophages and the ageing and diseased retina
Authors: LUHMANN U
Published: August 2012

Purpose Recruitment and activation of microglia and macrophages are controlled by local cytokine and chemokine signals that also determine neurotoxic or protective responses of these cells. I will review our current understanding of how the behaviour of macrophages and microglia in the retina is controlled by Ccl2‐Ccr2 and Cx3cl1‐Cx3cr1 chemokine signalling during ageing, in retinal degenerations and choroidal neovascularisation (CNV).

Methods We investigated recruitment and activation of myeloid cells in wildtype and chemokine single‐(Ccl2, Cx3cr1) and double‐knockout (Ccl2/Cx3cr1) mice in vivo (by AF‐SLO, OCT, fluorescein angiography) and ex vivo (by FACS, immunohistochemistry, morphometric semithin histology and 3D serial block‐face scanning electron microscopy). We studied these mice during ageing, in combination with a monogenetic inherited retinal degeneration (RD8) and in the laser‐induced CNV model.

Results Ageing is associated with alterations in myeloid cell populations in the retina and the choroid that are specifically altered by chemokine signalling dysfunctions. Ccl2 deficiency leads to an age‐related accumulation of subretinal macrophages and an attenuated CNV response with reduced infiltration of neutrophils, but no significant effect on degenerative processes in inherited (RD8) or age‐related retinal degenerations. In contrast, and despite an apparently similar accumulation of subretinal macrophages, Cx3cr1 deficiency leads to a more pronounced degenerative phenotype caused by the RD8 mutation, which was similar in Ccl2/Cx3cr1 knockout mice.

Conclusion Myeloid cell behaviour, controlled by Ccl2‐Ccr2 and Cx3cl1‐Cx3cr1 chemokine signalling, differentially modulate the manifestation of inherited and age‐related retinal degenerations and contribute to the increase of CNV lesions with age.
Correction of peripheral refractive errors and its impact on visual performance
Authors: ATCHISON DA
Published: August 2012

Purpose There has been considerable recent interest in modifying peripheral refraction for the purpose of treating myopia. Correcting peripheral refraction can affect peripheral visual performance. The purpose of this study was to consider the extent of such improvement and the feasibility of making spectacle lenses for this purpose.

Methods Peripheral refraction was used as a basis for designing lenses to correct refraction out to 30 degrees along the horizontal meridian. Visual performance tests were conducted at 20 degrees nasal, 30 degrees nasal and 25 degrees temporal visual field. Tests were detection acuity for high contrast sinusoidal gratings and contrast thresholds for 1 min arc diameter spots.

Results Correcting peripheral vision has limited influence on visual acuity as this and other resolution‐like tasks are limited more by retinal sampling than by image quality. However, Lewis et al (ARVO abstract 2012) found that correcting vision at 20 degrees nasal visual field could improve low contrast resolution acuity by an average of 0.06 log unit and up to 0.16 log unit for people with large off‐axis astigmatism. Detection tasks, such as deciding in which of two presentations a grating appears without necessarily being resolvable, give up to 0.7 log unit (5 times) better acuity than resolution tasks at 20 deg N, but are sensitive to defocus such that performance reduces close to those of resolution tasks with about 2 D defocus (Wang et al, IOVS 1997). Results like the above indicate the potential value of peripheral correction for people with macular lesions. Our own results with specially designed lenses will be presented.

Conclusion The lenses were partially successful in improving peripheral vision. Difficulties included variability in peripheral refraction measurements and lack of sensitivity of some subjects to peripheral correction. Whether or not correcting peripheral refractive errors will influence myopia progression is not yet known.
Is there a rational for the use of topical antibiotics before and after intravitreal injections
Authors: LABETOULLE M
Published: August 2012

Among the possible complications of intravitreal injections (IVI), postoperative endophthalmitis is the most severe. On the first series, the incidence was between 0.7 and 1.6%. Through improved practices, it was quickly reduced to around 0.09% to 0.03%, according to two recent retrospective series. The guidelines for IVI generally recommend performing the surgery under conditions close to those of the anterior segment surgeries, i.e. in compliance with aseptic conditions. The instillation of antibiotic eye drops was initially recommended, three days before and three days after IVT. Several publications have evolved strategies. Recent studies showed low rates of endophthalmitis despite the lack of preoperative antibiotics and a retrospective study found no significant difference whether or not topical antibiotic therapy was used pre‐and postoperatively. One study showed that instillation of antibiotics before surgery does not contribute to the sterility of the conjunctiva immediately before injection, from the moment the surgical site has been prepared with povidone iodine. It therefore appears that antibiotic treatment in IVIs is essentially aimed at reducing the contamination of the conjunctiva from the immediate post‐op period to the time the site of injection is considered healed. In this respect, the ideal antibiotic should combine several of the following properties: rapid efficiency on bacteria potentially responsible for endophthalmitis, broad spectrum, no lasting change in the conjunctival flora, no selection of resistance to this antibiotic or other antibiotics by crossover mechanism, reusability without additives adverse reactions with repeated cures.
EVICR.net Reading Centre Network
Authors: PETO T , EVICR.NET READING CENTER EXPERT COMMITTEE
Published: August 2012

Purpose To promote understanding of the work of Reading Centres in Europe in order to allow for greater collaboration both between existing reading centres and reading centres and clinical investigators.

Methods During the 90 minutes session, the members of the European Reading Centre Network will introduce their work. Detailed discussion will take place on how reading centres currently contribute to different studies. These will cover anterior and posterior segment images and their grading protocols in general and then will continue with detailed analysis plan of these.

Results The results of this session will be that better and more detailed understanding of the needs of the studies and what the Reading Centres can and cannot provide. These will lead to better communication from the start of the study in order to satisfy grading and reporting criteria of the studies.

Conclusion In conclusion, the Reading Centre network will present its work and will invite collaboration from the attendees of the session with the view of developing this unique collaboration further.
Inhibition of Apaf‐1 as a potential therapeutic strategy to improve corneal quality
Authors: HERRERO C , MARCHAN S , TRAVER E , MONTAVA R , ORZAEZ M , SANCHO M , GUIMERÀ A , VILLA R , PEREZ‐PAYÀ E , LAGUNAS C
Published: August 2012

Purpose About 12 million people in the world live with visual impairment due to corneal diseases while there’s a shortage of corneal tissue suitable for transplantation. One of the major causes of inappropriateness of corneas to be transplanted is to have a low endothelial cell density being apoptosis a key mechanism mediating cell loss. The protein Apaf‐1 is a key regulator of the mitochondrial apoptotic pathway. We have developed a family of Apaf‐1 inhibitors that have shown to be active in other apoptosis based‐pathologies.

Methods We have established a corneal storage model.Corneas were preserved at 4°C for 7 days followed by a rewarming period that resembles the implant. At 4°C the endothelium was intact but not the tight junction (TJ) integrity. Throughout the rewarming, apoptosis was induced as indicated by caspase 3 activation, resulting in cell loss.

Results The addition of Apaf‐1 inhibitors in the storage media reduces apoptosis activation. Caspase 3 activity was diminished; anti‐apoptotic genes were up‐regulated and pro‐apoptotic down‐regulated resulting in a reduced endothelium loss. Apaf‐1 inhibitors not only probed to be active during the rewarming period but also at 4°C: surprisingly, their presence inhibited the TJ breakdown. Integrity of TJ is known to be crucial to maintain cellular morphology and corneal transparency.

Conclusion The results hereby presented demonstrate a dual role of Apaf‐1 inhibitors in preserving the cornea integrity by keeping TJ integrity and inhibiting apoptosis. The use of these inhibitors in the clinical setting could increase the availability and quality of tissue to be transplanted.

Commercial interest
Rabbit, rat and pig corneas: main characteristics and storage in organ culture
Authors: HE Z , CROUZET E , PISELLI S , CAMPOLMI C , FOREST F , PEOC'H M , DUMOLLARD JM , GAIN P , THURET G
Published: August 2012

Purpose Except for primates, animal models of corneal are far from human. Animal models of corneal storage are virtually non‐existent. Aim: to update the main characteristics (especially for endothelial cells (EC)) of the cornea of 3 easily available animals, as well as their ability to be stored in organ culture (OC)

Methods 30 corneas of 6 month‐old Large White pig, 20 of 10 week‐old California rabbits and 10 of 8 week‐old Lewis rats were investigated. Macroscopic data: 1/horizontal and vertical diameters (digital calliper), 2/transparency (analysis of modulation and contrast transfer functions), 3/ corneal thickness (CT) (ultrasound pachymetry). Microscopic data: 1/ histology on Hematein‐Eosin‐Safran stained cross sections and ultrastructure, 2/ EC density (ECD) and morphometry, 3/ EC proliferative status (Ki67 and 5‐Ethynyl‐2’‐Deoxyuridine incorporation (Clik‐it EdU)), differentiation status (Na+/K+ ATPase, ZO‐1, JAM‐1), and existence of stem cells (Nestin, ABCG2, Telomerase). Fresh corneas were organ cultured in 2 commercially available media. CT was measured every 2h during 6h, then every 12h. Transparency and EC survival was determined after 2, 3 and 4 days of OC

Results We constituted a complete database of ex vivo corneal characteristics of the 3 species. ECD, polymorphism and polymegathism were higher than in human. CT increased rapidly (up to 3 times) in both OC media, resulting in biconvex tissues with almost complete loss of transparency and significant endothelial folding. EC survival decreased especially in folds

Conclusion Corneas of the 3 animals cannot be stored more than 2 to 3 days in OC media designed for human. Specific media should be developed to obtain reliable models of animal corneal OC
Is there an anti‐adenoviral drug on the horizon?
Authors: ROMANOWSKI E
Published: August 2012

Adenovirus ocular infections (epidemic keratoconjunctivitis [EKC], follicular conjunctivitis, and pharyngeal conjunctival fever) are the most common ocular viral infections worldwide, including more than 1,000,000 cases annually in Japan. To date, there is no US FDA or European Medicines Agency approved antiviral therapy for these infections. Little progress on anti‐adenoviral development was made until our group developed the first reliable animal model for ocular anti‐adenoviral testing 20 years ago. Using that animal model, our group was instrumental in the preclinical development of the first topical antiviral drug for the treatment of adenoviral conjunctivitis tested in clinical trials, the nucleoside analog cidofovir. However, toxicity concerns, not efficacy, caused the sponsor to discontinue development. Since then, there has been considerable progress made regarding the discovery and development of antivirals by both academia and the pharmaceutical industry. Preclinical in vitro and in vivo studies have identified several new antiviral candidates such as 2,3‐dideoxycytidine (ddC), cyclopentenylcytosine (CPE‐C), intravenous immune globulin (IVIG), NVC‐422, and FST‐100. These preclinical studies have led to industry sponsored clinical trials which have been initiated with several agents NVC‐422 (NovaBay), Zirgan (0.15% Ganciclovir gel, Bausch + Lomb), and FST‐100 (0.4% povidone‐iodine/0.1% dexamethasone, Foresight Biotherapeutics). The first antiviral to treat adenovirus ocular infections will hopefully be available in the not too distant future.

Commercial interest
Management of inflammation in RVO
Authors: LOEWENSTEIN A
Published: August 2012

Macular edema (ME) is a leading cause of vision loss in retinal disease including retinal vein occlusion. The development of macular edema is mediated by angiogenic as well as Inflammatory processes. There is increasing evidence that management of the inflammatory part is important in the treatment of the edema. Therefore, theoretically steroid therapy has a good potential in the treatment of macular edema. Regarding retinal vein occlusion specifically treatment by Ozurdex implant, containing dexamethasoe provides visual recovery with excellent safety outcomes.
Recombinant NFG for treatment of ocular surface diseases
Authors: BONINI S
Published: August 2012

Abstract not provided
Metabolism in glaucoma using retinal oximetry
Authors: STALMANS I
Published: August 2012

Collaborative studies between the Ophthalmology departments in Leuven and Reykjavik have shown that in glaucoma patients, venous oxygen saturation increases with increasing severity of disease (i.e. with worsening visual field). Patients with considerable visual field loss show higher venous oxygen saturation than healthy individuals, while glaucoma patients with mild visual field loss have saturation similar to normal. Moreover, severe glaucomatous damage was associated with increased oxygen saturation in the retinal venules and decreased AV‐difference in retinal oxygen saturation. Finally, a positive correlation between the changes in AV difference and structural changes at the level of the optic disc and nerve fiber layer was found using HRT parameters (rim area, retinal nerve fiber layer thickness). The increase in venous saturation with increased visual field damage may be a consequence of tissue atrophy and less oxygen consumption. Longitudinal studies of glaucoma patients are needed to determine how retinal venous oxygen saturation is related to progression.
A randomized observer and subject masked trial comparing the visual outcome after treatment with ranibizumab or bevacizumab in patients with neovascular age‐related macular degeneration
Authors: TOLD R , BINDER S , KREBS I , BOLTZ A , SCHMETTERER L
Published: August 2012

Purpose The western world health care systems are confronted with an increasing burden of patients suffering from age‐related macular degeneration (AMD). Anti‐VEGF therapy revolutionized the treatment of exudative AMD, but is associated with high costs. This study seeks to compare the treatment effects of ranibizumab and bevacizumab on best corrected distance visual acuity (BCVA) in Austrian patients with neovascular AMD.

Methods This was a prospective, randomized, double blind, multicenter study. Ten clinical trial centers in Austria participated in this one year lasting study and included 321 treatment naïve patients suffering from neovascular AMD. Patients were randomized for treatment with bevacizumab or ranibizumab receiving a loading dose of three consecutive monthly intravitreal injections, followed by monthly treatment as needed.

Results No significant differences were seen in BCVA between ranibizumab (n = 167) and bevacizumab (n = 154) groups. At one year bevacizumab was equivalent to ranibizumab (p=0.78 between groups). This was also not significant when adjusted for age or baseline BCVA. Also the gain and loss of 5 or 15 letters in BCVA showed no significant difference between treatment groups. Finally the analysis of serious adverse events (SAE) revealed no significant difference between the two groups, although SAEs were slightly more in the bevacizumab group.

Conclusion The findings of this study showed no significant difference at one year between the two drugs used in an as needed manner, which displays todays most widely spread treatment regimen. The drugs showed similar efficacy and safety in the Austrian population.
Valproic acid (VPA), a class I and II histone deacetylase (HDAC) inhibitor and conjunctival melanoma
Authors: MADIGAN MC , MUNOZ‐ERAZO L , CONWAY RM
Published: August 2012

Purpose To investigate the expression of histone deacetylases (HDACs) in human conjunctival melanoma (CM) cell lines and primary melanocytes, and assess the effects of VPA, a broad Class I and II HDAC inhibitor, on cell viability and growth.

Methods CM cell lines (CRMM1 & 2; CM2005.1) and primary melanocytes were immunolabelled with antibodies to HDACs: Class I (HDAC1, 2 and 3), Class IIA and IIB (HDAC4 and HDAC6), and Class III (SIRT2). Antibody localisation was visualised with immunofluorescence and confocal microscopy. Dose‐response and proliferative potential following treatment with VPA was assessed for up to 72hrs using MTT and colony assays, respectively Cell cycle dynamics were also assessed.

Results Differential HDAC expression was observed in CM cells and melanocytes, for both immunolocalisation (nuclear vs cytoplasmic) and cell type. CM2005.1 cells displayed lower level expression of HDACs compared to CRMM1 and 2 cells. VPA IC50 (72hrs) was 3.75mM, 5.42mM and 8.33mM for CRMM1, 2 and CM2005.1 cells, respectively. Colony assays showed similar patterns of response, with surviving fractions 0.2 and 0.5 for CRMM1 (VPA 0.3125mM) and CRMM2 (VPA 2.5mM) respectively. Cell cycle analysis showed dose‐related G1 block for CRMM1 and G2 block for CRMM2 cells at 24hrs (0mM to 1.25mM VPA).

Conclusion Overall, CM2005.1 cells are more resistant to VPA compared to CRMM1 and 2 cells. VPA inhibition of CM cell growth and proliferation may be related to the observed differential expression of HDACs between cell lines. Combination therapies using VPA and other HDAC inhibitors may be potentially useful in managing the growth of primary CM. Supported by Sydney Foundation for Medical Research.
Macrophage markers and C3d in the central & peripheral choroid of young, aged and amd eyes
Authors: MADIGAN MC , VAN DEN BERG C , MORELAND A , LIANG J , LORD S , DEMIR A , JAISWAL S , JAGER MJ
Published: August 2012

Purpose To investigate the distribution and expression of macrophage phenotypes and the complement activation protein, C3d, in human choroid/retina in young, aged and AMD eyes.

Methods Paraffin sections of central and peripheral choroid/retina from young (<40 years, n=6), aged (>70 years, n=4) and AMD (>70 years, n=8) human post‐mortem eyes were co‐immunolabelled with antibodies to leukocyte and macrophage markers (CD68, CD163, Iba1 & CD45) and complement activation component, C3d. Localisation and distribution of antibodies was assessed using confocal microscopy. Counts of macrophage sub‐populations were compared in central and peripheral choroid for each group.

Results Heterogeneous populations of macrophages were found in the choroid/retina of all groups. Iba1+ and CD45+ retinal microglia and macrophages, and choroidal macrophages were observed in all eyes. In AMD eyes, Iba1+ and CD45+ cells were seen in the subretinal space amongst photoreceptors, as well as in inner retina. Compared to young eyes, aged and AMD specimens showed increased numbers of CD163+ macrophages (M2, proangiogenic) in choroid, and in central vs peripheral retina. Fewer CD68+ cells were seen in all specimens, regardless of age or location. C3d was expressed in young, aged and AMD eyes, localised to Bruch’s membrane and choriocapillaris, with more extensive immunostaining in aged and AMD eyes. C3d was also seen in drusen in aged and AMD eyes, and more peripherally, compared to young eyes.

Conclusion Age‐related changes in macrophage phenotypes and in complement pathway activation at the choroidal/retinal interface may play a role in development and progression of AMD. Supported by Sydney Foundation for Medical Research.
Ophthalmological manifestations of IgG4‐related disease
Authors: PHILIPPAKIS E , TOUITOU V , CHARLOTTE F , RIGOLET A , LEHOANG P , BLOCH‐QUEYRAT C , BODAGHI B
Published: August 2012

Purpose Ig4‐related disease is a recently defined entity characterized by a mono or multi organ lymphoplasmocytic infiltrate with IgG4+staining (IgG4+/IgG+ cell ratio>40%), associated with fibrosis or sclerosis and elevated IgG4 serum rate over 135mg/dL. Purpose is to determine the ophthalmological and histological features of IgG4‐RD, and to analyse the outcome under treatment.

Methods Patients with biopsy‐proven IgG4‐RD, seen between 2009 and 2011 in a single tertiary center, were retrospectively reviewed. Clinical manifestations, biological and radiological results, histological features and outcome under treatment were analyzed.

Results Three caucasian women were included. Mean age was 58 years (range :50‐63). One patient presented with unilateral painful propotosis, associated with third and fifth cranial nerve palsy. One patient had recurrent anterior scleritis, and one patient presented with chronic conjonctival inflitration. None of them had extra‐ocular involvement (FDG‐PET‐scan). Other inflammatory conditions were ruled out. Histopathology demonstrated lymphoplasmocytosic proliferation with expression of IgG4+ plasma cells over 40%. IgG4 serum rate was elevated in one case. All patients primary responded to corticosteroids but 2 of them required the adjunction of an immusuppressive drug(fibrosis or relapse).third one presented with epithelial carcinoma.

Conclusion IgG4‐RD is a new and rare entity, challenging to diagnose in case of isolated orbital involvement or in atypical features, such as conjonctivitis and scleritis Histopathology is the gold‐standard for diagnosis if appropriate staining is performed. Treatment is controvertial : corticosteroids are the mainstay, but many cases require associated immunosuppressors.
A patient with eyelid and anterior orbital myeloproliferative hypereosinophilic syndrome
Authors: DE KEIZER RJW , AL SABAI N , BAL TA , DE GROOT V
Published: August 2012

Purpose the aim of the study is to evaluate the clinical‐ and histopathological discrepancy of the inflamed eyelid/anterior orbital mass features

Methods case report and literature review

Results the clinical picture revealed an erythemaous eyelid‐skin inflamed mass without effect on local and general antibiotic treatments . The histopathological “diagnoses was made as “chalazion material”. However the mass was superior located from the tarsus pre‐ and intraseptal with a lot of eosinophilic cell in the pathological material; where the patient already was known with a pulmonal myoblastic hypereosinophilic disease and treated with hydrea with the extra feature of a red face

Conclusion knowledge of the systemic disease of a patient and the precise location of a pathologic ophthalmic process is important to made the definitive diagnosis. In difficult processes it is always necessary that pathologist and ophthalmologist consulted each other and made together the end conclusion
Role of corticosteroids
Authors: BANDELLO F
Published: August 2012

Purpose Diabetic Macular Edema (DME) management has been revolutionized by the advent of intravitreal approach. Ain of the presentation is to describe the results of the most important studies about intravitreal corticosteroid therapy for DME.

Methods Critical analysis of the most recent trials on the use of intravitreal corticosteroids for the treatment of DME.

Results Most promising findings can be obtained from trials employng dexamethasone and fluocinolone acetonide. Nevertheless, complication rates, (especially bearing in mind intraocular pressure rise, and cataract) may limit the practical spread of this approach.

Conclusion Long‐term trial will help define the best treatment algorithm for each form of DME.

Commercial interest
Role of anti‐VEGF
Authors: POURNARAS JA
Published: August 2012

Purpose To assess safety and efficacy of intraocular injections of anti‐VEGF in patients with diabetic macular edema (DME)

Methods The gold standard for treatment has been laser coagulation. Limitations of this therapy are refractive DME, ischemic diabetic maculopathy and complications after laser application. The need for a non‐destructive and effective strategy has led to investigations regarding VEGF inhibitors for reduction of vessel leakage and edema formation. Critical analysis of the most recent trials on the use of intravitreal anti‐VEGF will be discussed for the treatment of DME.

Results For DME, intravitreal pegaptanib and bevacizumab have shown beneficial short‐term effects on both visual acuity and retinal thickness. Most recent datas concern the use of ranibizumab and will be detailled. Incidence of ocular adverse events are consistent with prior clinical trials of ranibizumab across multiple retinal diseases. VEGF‐trap study will be reported.

Conclusion New therapeutic approaches based on intravitreal injections of anti‐VEGF molecules offer new hope for the management of diabetic macular edema. However, randomized studies are needed in order to attest longterm safety and efficacy profiles.
Retinal neuroprotection: the path from cell‐based high content screening, to animal models, and hopefully to the clinic
Authors: ZACK DJ
Published: August 2012

Purpose Vision loss in glaucoma is due to the loss of retinal ganglion cells. Current therapies all act by lowering IOP. However, IOP reduction can be difficult to achieve, and even with significant lowering, RGC loss can continue. Efforts have therefore been made to develop “neuroprotective” agents that would complement IOP‐lowering by directly interfering with the RGC cell death process.

Results Using a novel primary RGC‐based, high‐content phenotypic screen, in which we have tested over 10,000 compounds, we found that the FDA‐approved drug sunitinib, a broad‐spectrum receptor tyrosine kinase inhibitor, strongly promotes RGC survival. In rodent models of optic neuropathy, including a rat laser glaucoma model, an intravitreally administered slow‐release microparticle formulation of sunitinib protects RGCs from cell death. Unfortunately, at its neuroprotective concentration, sunitinib is reported to inhibit nearly 200 kinases, making it a challenge to determine the kinase(s) whose inhibition promotes survival. In order identify the biologically relevant kinase(s) whose inhibition by sunitinib promotes RGC survival, we developed a magnetic nanoparticle‐based high throughput siRNA‐based assay capable of knocking‐down individual genes in cultures of primary murine RGCs. We screened a library of 1869 siRNAs against 623 kinases for siRNAs that increased RGC survival. The top hits were dual‐leucine zipper kinase (DLK) and its substrate, mitogen activated protein kinase kinase 7 (MKK7).

Conclusion Our results suggest that a major part of sunitinib’s neuroprotective activity is mediated through inhibition of DLK. As a next step, the challenges of bringing a neuroprotective molecule such as sunitinib to clinic will be discussed.

Commercial interest
Primum non nocere et non occidere
Authors: HERBORT CP
Published: August 2012

Purpose "Primum non nocere, "first do no harm", is one of the essential princoples taught to medical students and should accompany us throughout our medical practice.

Methods Case presentations

Results Illustrative example of some "killer cases induced by inappropriate therapeutic interventions will show how important it is to diagnose appropriately our uveitis cases before resorting to a treatment. In particular infectious causes should be excluded before reaching out to immunosuppressive therapies and once powerful potentially dangerous are going to be used, their side‐effects should be considered and explained to the patient.

Conclusion A meticulous work‐up is necessary before potentially harmful treatments are going to be used but on the other hand exaggerated fear should not prevent us from using necessary corticosteroid and/or immunosuppressive therapeutic intervention as long as the appraisal of the patient has allowed to rule out infectious causes and as far as proper monitoring of side‐effects is taken care of.
Spectral domain OCT‐assisted “big bubble” deep anterior lamellar keratoplasty in keratoconus patients
Authors: WYLEGALA E , TARNAWSKA D , WROBLEWSKA CZAJKA E , JANISZEWSKA D , WOWRO B , DOBROWOLSKI D
Published: August 2012

Purpose To visualize intraoperative changes of corneal thickness and bubble creation process using spectral domain OCT.

Methods 15 patients underwent DALK performed using “big bubble” technique. Surgeries were assisted with intraoperative spectral domain OCT imaging (The iVue from Optovue Fremont Calfornia USA). Corneal thickness was measured preoperatively, after manual pre‐cutting and after the big‐bubble creation.

Results Manual pre‐cutting of corneal stroma revealed residual bed thickness of 240‐270 µm (mean 256 µm). When residual corneal bad was thicker than 250 µm, the 27G needle was used for big‐bubble creation, when it was thinner than 250 µm, 30G needle was used. After injection of an air bubble, in 11 eyes Descemet’s membrane was completely separated from stroma, that was shown on OCT scans. In 4 eyes the separation was incomplete that was also clearly visible on OCT images. In one eye OCT imaging showed completely unseparated Descemet’s membrane and the additional injection of air bubble was necessary to effectively create the air space between the corneal layers.

Conclusion Intraoperative imaging with Spectral domain OCT provides high‐resolution imaging of cornea bed thickness including visualization of the air‐bubble formation. This technique could provide enhanced information for the corneal surgeon during lamellar procedures such a DALK.
Genetic retinal diseases
Authors: LEROY BP
Published: August 2012

Purpose To describe the current status of treatment for inherited retinal disease, and illustrate the challenges that lie ahead.

Methods An overview of current treatment trials for inherited retinal disease in humans and animals will be used to illustrate where success has been achieved, but also where challenges remain. These include gene therapy trials in RPE65‐related Leber congenital amaurosis, Stargardt macular dystrophy and choroideraemia.

Results Albeit that encouraging breakthroughs have been made with regard to treating inherited retinal diseases, such as in the gene therapy trials in RPE65‐related Leber congenital amaurosis, challenges lie ahead, such as gene‐specificity of gene therapy, intravitreal as opposed to subretinal injections, stem cell control, and cost.

Conclusion Despite initial success of trials in inherited retinal diseases, quite a number of obstacles remain.
Circadien cycle and chronic central serous chorioretinopathy
Authors: HUBAULT B , SETROUK E , ZAMBROWSKI O , DUCASSE A , ARNDT C
Published: August 2012

Purpose Chronic central serous chorioretinopathy (CSCR) is a multifactorial disease. The present study was designed to evaluate the prevalence of circadian disturbance and corticosteroid treatment in patients treated with chronic CSCR.

Methods Patients presenting with chronic CSCR between 01/01/2009 and 30/11/2011 were prospectively enrolled. A history of corticosteroid treatment, sleep disturbances and irregular working hours was noted. Two questionnaires (PSQI and Epworth) regarding sleeping distrurbancies were applied. After a follow up of 3 months, the patients with persisting fluid and visual acuity below 20/40 were treated with photodynamic therapy (PDT).

Results During the period of inclusion, among 26 included patients, 19 were treated with PDT (73%). A history of corticosteroid tretment was found in 12 patients (19%), 4 currently used psychopharmacologic drugs (15%) and 8 had irregular working hours (30%). The analysis of the Epworth questionnaire enabled to record moderate sleeping disturbances in 11 patients (42%), none of the patients were classified as having severe sleeping disturbances.

Conclusion It is likely that general factors such as the existence of a corticosteroid treatment or a disruption of the circadian cycle are involved in the occurrence of patients with CSCR.
Comparative study of post‐natal retinal vascular development in mice models of iPLA2 inhibition and plasmalogen deficiency
Authors: SAAB S , BUTEAU B , LECLERE L , CREUZOT‐GARCHER C , BRON A , BRETILLON L , ACAR N
Published: August 2012

Purpose Plasmalogens are particular phospholipids characterized by the presence of a polyunsaturated fatty acid (PUFA) at sn‐2 position of glycerol. Plasmalogen deficiency in mouse leads to developmental abnormalities in retinal vasculature. We propose that liberation of PUFA by the specific calcium‐independent phospholipase A2 (iPLA2), is involved in the mechanism by which plasmalogens control retinal vascular development. To confirm this hypothesis, we performed a comparative study of retinal vascular development in a mouse model of retinal iPLA2 inhibition and a model of plasmalogen deficiency.

Methods Vessel and astrocyte networks were visualized on flat‐mounted retinas through immunostaining methods.

Results Similar abnormalities were observed in retina of both mouse models. They consisted in an increased number of vessel ramifications at PN14, and in an abnormal glial cells migration from the optic nerve, at PN14 and at PN21. An activation of microglial cells was also observed at adult age.

Conclusion These results confirm the implication of plasmalogen in the control of retinal vessel development through PUFA release from their sn‐2 position.
Biomechanics in keratoconus
Authors: TOUBOUL D
Published: August 2012

Abstract not provided
Chromatic pupillometry as highly sensitive testing method of photoreceptor function in retinal dystrophies
Authors: LORENZ B
Published: August 2012

Purpose Objective methods for the characterization of photosensitive cells are highly needed in patients with retinal dystrophies. The pupil light reflex is driven by rod, cone, and intrinsic photosensitive retinal ganglion cell (ipRGC) input. The aim of this study is to analyze two protocols of chromatic pupillometry with differing stimulus paradigms to gather isolated functional information of the three cell populations in patients with different forms of retinal dystrophies.

Methods The study group comprised 60 patients with different forms of retinal dystrophies, and 32 healthy probands. Patients were grouped according to their electroretinography (ERG) data. A custom made binocular chromatic pupillometer (Bino I, AMTech) connected to the Colordome Ganzfeld stimulator (Diagnosys LLC) was used to assess changes in pupil diameter in response to red (640nm) and blue (462nm) light stimuli.

Results Patients who had no measurable scotopic ERG also had the most reduced yet often still measurable rod‐weighted pupil responses (PR), while patients with abnormal or normal scotopic ERG had reduced or normal rod‐weighted PR. Similarly, patients with no measurable photopic ERG had reduced but still measurable cone‐weighted PR, while patients with abnormal of normal photopic ERG had mostly normal cone‐weighted PR. Reduced ipRGC‐weighted PR could not be correlated with the ERG classification.

Conclusion In the absence of a measurable ERG, chromatic pupillometry generates important functional and quantifiable data on residual rod and cone activity. These data show that this technique should be added to the panel of examination tools for the characterisation of retinal dystrophies and for quantifying the clinical benefit of experimental treatment protocols.
Physical therapy in MGD as a cornerstone for improvement of signs and symptoms & The British perspective on MGD
Authors: PURSLOW C
Published: August 2012

Purpose This talk will present the typical management of meibomian gland dysfunction (MGD) that is currently implemented in British primary eye care, and where the current focus lies in newer diagnostic techniques and therapies.

Methods Recent focus on MGD has highlighted this condition as one that is under‐estimated and under‐managed, particularly amongst contact lens wearers. This renewed appreciation for the major cause of dry eye has resulted in parallel interest amongst eye care practitioners for an evidence‐based approach to management. The most common approaches are reviewed, alongside some emerging popular choices.

Results There is robust evidence to support modern approaches, and to discourage some of the old‐fashioned management strategies.

Conclusion Whilst there is still a lot to understand about MGD, there is no doubt that eye care practitioners can do more to help patients manage this highly prevalent problem.
Special features of MGD in children: how to diagnose how to treat and the French perspective on MGD
Authors: BREMOND‐GIGNAC D , CHIAMBARETTA F
Published: August 2012

Purpose MGD in children is a common pathology. Many clinical forms need to be recognized, from mild to severe, with classical features of chalazia and blepharitis or more unusual the sight‐threatening ocular rosacea.

Methods Ocular rosacea in children, secondary to severe MGD, is probably underdiagnosed meanwhile it induces major ocular discomfort. The treatment aims to eyelid hygiene, anti‐inflammatory treatment and topical steroid sparing.

Results Place of heat therapy with innovative steamed goggles, topical azithromycin and topical cyclosporine with analyze of literature and clinical cases, is discussed. The French prospective clinical study performed was useful to evaluate the interest of each treatment.

Conclusion Further studies with more patients are needed to a better understanding of the severe MGD. Ocular rosacea in children should be recognized early and to avoid steroid dependence and complications. Eyelid hygiene, topical anti‐inflammatory and topical cyclosporin are essential in MGD treatment for a better quality of life of the children and their parents.

Commercial interest
Can scattered light improve visual performance?
Authors: PATTERSON EJ , BARGARY G , BARBUR JL
Published: August 2012

Purpose Light scattered by the media within the eye reduces object contrast and can also cause visual discomfort, in the presence of bright light sources. The addition of uniform veiling light over the retina can, however, change retinal sensitivity by increasing retinal illuminance. The extent to which reduction of target contrast and changes in retinal sensitivity caused by the presence of a glare source affect contrast acuity (CA) thresholds remains to be established. We investigate how CA is affected by glare source intensity, surround luminance and test target location on the retina. The aim is to determine the range of glare source intensity and background adaptation level that can improve visual performance.

Methods 45 subjects with normal vision were investigated. A psychophysical flicker‐cancellation test (Ophthalmic & Physiological Optics, 17, 171, 1997) was used to measure the amount and angular distribution of scattered light in the eye. CA thresholds were measured using the Contrast Acuity Assessment test (ASEM, 74, 551‐559, 2003). Three glare source intensities (i.e., 0, 1.35 and 19.21 lm/m^2 in the pupil plane), three eccentricities (5, 10 and 15 degrees), and three background luminances (1, 2.6 and 26 cd/m^2) were investigated.

Results CA thresholds were measured for the test target / glare source parameters listed above. In addition, the scatter function of the eye was assessed for each subject and the measured parameters were used to predict the effect of veiling glare on CA thresholds.

Conclusion Low intensity glare can improve CA in the high mesopic range. High intensity glare yields increased thresholds, but this loss of contrast sensitivity is, in general, smaller than predictions based on veiling glare luminance caused by forward light scatter in the eye.
Treatment of macular oedema due to branch retinal vein occlusion with laser induced arterial constriction. Twenty years results of retrospective interventional study
Authors: REHAK J
Published: August 2012

Purpose To evaluate the final visual acuity (VA) in patients with Branch Retinal Vein Occlusion (BRVO) treated with either laser arteriolar constriction (ACo) or grid laser photocoagulation (GLP).

Methods 265 BRVOs were treated with 3 different approaches: early ACo performed ≤ 9 weeks after onset of BRVO, late ACo performed > 9 weeks after onset and GLP. The groups were divided into 3 subgroups according to initial VA: ≤ 0.1; 0.16‐0.3; and ≥ 0.4. The data were analyzed using univariate and multivariate logistic regression and, Receiver Operating Characteristics analysis. Factors which could have influenced final VA such as age, sex, localization of occlusion (major temporal or macular BRVO) and the presence of retinal ischemia were taken into account. In the group of early and late ACo, patients with VA ≤ 0.5 and a ME persisting over three months, underwent additional macular GLP.

Results Based on the proportion of 1 year VA ≤ 0.1 as a risk category, the results of early ACo (3.8%) were significantly better than either GLP (29.6%, p < 0.001) or late ACo (16.1%, p=0.006). In the subgroup of intermediate initial VA 0.16‐0.3, a significant difference was only found between the early ACo group and GLP (p=0.004). The effect of the treatments on the prevalence of final VA ≤ 0.1 was not significantly different for patients with an initial VA ≥ 0.4. In patients treated by ACo, residual chronic ME requiring additional GLP was present in 35% of early and 44% of late ACo cases.

Conclusion ACo performed in the first 9 weeks after onset of BRVO significantly reduces the prevalence of a final VA ≤ 0.1 in patients with an initial VA < 0.3.
Comparison of the anti‐inflammatory effects of artificial tears in a rat model of corneal scraping
Authors: DAULL P , FERAILLE L , ELENA P , BAUDOUIN C , GARRIGUE JS
Published: August 2012

Purpose The aim of the present study was to evaluate the safety and tolerance of cationic oil‐in‐water emulsion on debrided cornea, and to characterize its benefits on the corneal epithelium healing process.

Methods A rat model of corneal scraping was used to characterize the effects of four commercially available artificial tears (Cationorm®, Vismed®, Optive® and Systane Balance®) on the recovery process of the debrided corneas. The upper part of the corneal epithelium was scraped mechanically prior to a 5‐day treatment with different artificial tears. At the end of the treatment, the ocular surface was evaluated clinically (corneal fluorescein staining, CFS) and by in vivo confocal microscopy (IVCM). Conjunctival function was assessed by goblet cell count and MUC5AC immunostaining.

Results The four artificial tears were all well tolerated by the debrided cornea. By restoring an adequately hydrated ocular surface environment they promote corneal healing, as evidenced by CFS measurements of the scraped area. In contrast 0.02% BAK solution inhibits the healing process. IVCM analysis of the different layers of the cornea confirmed the benefits of the cationic emulsion (Cationorm®). Interestingly inflammatory cells infiltration in the stroma was at its lower following Cationorm® treatment, while 0.02% BAK treatment resulted in marked inflammation. The different treatments were all able to protect goblet cells function and MUC5AC expression.

Conclusion BAK‐free cationic emulsion (Cationorm®) is well tolerated by debrided cornea and allow for a safe healing of the cornea. The findings suggest that Cationorm® have the potential to benefit patients with corneal epithelium disorder.

Commercial interest
Pediatric uveal melanoma
Authors: CASSOUX N , COUTURIER J , PLANCHER C , LUMBROSO‐LE ROUIC L , LEVY C , ASSELAIN B , DENDALE R , AERTS I , DESJARDINS L
Published: August 2012

Purpose To study the clinical characteristics, outcome and prognosis of very young patients treated for choroidal melanoma at l’ Institut Curie.

Methods Retrospective case‐control series. Patients aged ≤16 years were extracted from the database. Patients were treated by enucleation or irradiation depending on tumor size and site. Histology and genomics of the enucleated globes were reviewed. Metastasis and survival were evaluated using the Kaplan‐Meier method.

Results From August 1990 to January 2011, 4,857 patients treated for uveal melanoma were prospectively recorded in the database. Fourteen patients (0.3%), 10 girls, 4 boys, mean age 12 years, (median: 14; [range: 2‐16 years]) at onset were extracted. Mean basal tumor diameter was 14 mm (median: 14.5; [range: 6 to 22 mm]). Mean tumor thickness was 7.3 mm (median: 6.4 [range: 2.4 to 16 mm]). One half of patients were enucleated, while the other half was treated conservatively by proton beam or iodine plaque radiotherapy. Histopathology of enucleated globes showed epithelioid cellularity in all patients. Genomic analysis by CGH‐array was available for 4 patients and showed monosomy 3 for 2 patients and 8q gain for 3 patients. Median follow‐up was 91 months [range: 1 to 243 months]. At the end of follow‐up, 13 patients (93%) were alive, one presented metastatic disease and one had died. The eye was retained in all patients treated conservatively.

Conclusion Most children had an excellent outcome in terms of survival. An excellent eye retention rate was observed in conservatively treated patients.
Correlation between function and structure of retinal nerve fiber layer in Parkinson disease
Authors: SATUE M , BAMBO M , GARCIA‐MARTIN E , FERRANDEZ B , GIL‐ARRIBAS LM , ARA M
Published: August 2012

Purpose To determine the capacity of the axonal application for Optical Coherence Tomography (OCT) to detect axonal loss in the retinal nerve fiber layer (RNFL) in Parkinson’s disease (PD) and to evaluate the structure/function relationship between OCT measurements and visual function tests.

Methods One hundred patients and 100 controls were included in the study and underwent a complete neuro‐ophthalmologic examination consisting in best corrected visual acuity (BCVA), color vision test with Ishihara’s pseudoisochromatic charts, automatic perimetry with Strategy SITA standard 30.2 of Humphrey and Spectralis OCT using the new axonal application. Mean and standard deviation of all parameters were calculated and correlation between RNFL, BCVA, Ishihara test’s score and the mean and mean standard deviation of the automatic perimetry.

Results Significant differences between controls and patients were found in inferior and temporoinferior RNFL thicknesses (133.18 in controls vs 125.03 µm in PD, p=0.006; 149.53 vs 141.32 µm, p=0.020 respectively) and sector number 8 in papillomacular bundle (306.13 vs 271.19 µm, p= 0.006). Significant differences were also observed in automatic perimetry and Ishihara’s score (p<0.001). The RNFL thickness of the papillomacular bundle showed strong correlation (correlation index >0.700) with perimetry values and mild association with Ishihara’s score.

Conclusion RNFL loss is detectable by the axonal application of Spectralis OCT in Parkinson disease. Functional parameters obtained by automatic perimetry present strong association with papillomacular bundle measurements.