bluuebunny/crossref_metadata_2025 huggingface dataset:
Atrophic areas and/with neovascular AMD. Characteristics, evolution of atrophic lesions associated to neovascular AMD treated by series of 3 Ranibizumab IVT protocol, 4 years follow‐up
Authors: GONZALEZ C
Published: August 2012

Purpose To evaluate atrophic areas characteristics, at the first time, their change, evolution and correlation or no with and during the follow‐up of neovascular AMD treatment by series of 3 Ranibizumab IVT

Methods 102 eyes of 91 patients, 28 men, 63 women, with retrofoveolar neovascularisation complicating AMD. Atrophic areas were evaluated by autofluorescence imaging Spectralis (in particular with region finder software), OCT (notably choriocapillary depth), FA, ICG. We evaluate the size, characteristics, topography of the lesions, their growth way. The areas themselves, their edge and rim were considered and evaluated. Each element was studied, compared cut to cut and time to time to itself and to each other data, every 2 months. The impact of AMD and /or this treatment protocol on the evolution of atrophic areas is also valuate.

Results VA improved in 85% cases, stabilized in 15%. AF imaging and their region finder analyze were the main elements of the atrophic lesions’ study. The surface of the atrophic area grows by 17%, the edge changes in 20%. Speed growth was in average 1,15mm2/year. At OCT, thickness of photoreceptor, pigment epithelium layer diminished about 25% and 35% at the area’s edge. Choriocapillary depth values, FA and ICG data were mainly significative in the large atrophic areas and less than AF indications. This protocol has a little impact on the evolution of atrophic areas, apparently less than monthly IVT, and the same as AMD by itself.

Conclusion The study of atrophic process and its progression is a main question in the AMD follow –up, the evaluation of the protocol treatments and their safety too.
Trends in anterior segment surgery: what is coming?
Authors: ALIO SANZ J
Published: August 2012

Anterior segment surgery has experienced a huge development in the last 25 years. Presently, in spite of this accelerated development, new technologies have emerged that have impacted considerably the surgery of the crystalline lens, the cornea and its pathologies. Corneal blindness, corneal debilitating diseases (corneal ectatic disease), corneal opacities, post infectious or traumatic problems and complication of cataract surgery has increased the rate of performance of corneal surgery, with corneal blindness still being a worldwide problem. Concerning the crystalline lens, cataract surgery is the most widely performed surgical procedure in the human being, and every step forward in this surgery affects millions of people around the world every year. Corneal surgery has been opened to a new stage of development thanks to the introduction of femtosecond laser technology, corneal crosslinking procedures, better knowledge of corneal biomechanics, improvements in corneal transplantation, development of corneal regenerating techniques, new antiinflammatory and immunological medication and a better knowledge about the ocular surface biological behaviour. Crystalline lens and cataract surgery have experienced a major recent impact with the introduction of femtosecond lasers for cataract surgery, and the so‐called premium IOLs. Jointly, they represent a large step forward in the outcomes that are expected for cataract surgery, in which not only vision research is expected but also the spectacle independent condition for far and for near. Different models of accommodative lenses, multifocal lenses and other technologies have approached this refractive purpose. In this presentation the actual trends based on evidence based knowledge about the immediate evolution of corneal and crystalline lens surgery, the recent developments in the knowledge of the corneal diopter in normal and diseased conditions and the implementation that cataract surgery and IOL technology is undergoing today will be explained. The concept of eye modelling with modern customization of all these procedures through a global modern eye based on recent knowledge will be also outlined.
Perspectives for new treatments at Alcon ‐ part 1
Authors: RICH C
Published: August 2012

This presentation will give the audience an overview of how we identify a wide variety of potential products to develop and how we condense this list down to the final candidates that will establish our pipeline strategy for each year. This process is conducted across the 3 main franchises of Alcon: Pharmaceuticals, Surgical and Vision Care. This presentation will review products in development in the areas of Glaucoma, Anterior Segment and the Ocular Surface. In the area of Glaucoma we currently have several products that will be reviewed. This includes potential new chemical entities with novel mechanisms of action and combination products that have the IOP lowering power greater than a beta‐blocker without the risk of a beta‐blocker. In the area of anterior segment we have several exciting programs in development to meet the unmet medical need around cataract surgery healing and post‐operative infection. In the area of the ocular surface we have several projects in development for improved treatment in allergy (both nasal and ocular) and dry eye. In addition, as an extension of this area, we have projects for the treatment of acute otitis externa and antibacterial use during the peri‐operative placement of tympanostomy tubes.
Gullstrand (ECR‐CCRS‐2010‐01)
Authors: ROZEMA J
Published: August 2012

Purpose To present the current status of the Project Gullstrand study, aimed at measuring a large amount of biometric and visual function data in multiple centers Europe‐wide.

Results At the time of writing (29/5/2012) 630 subjects have been measured in 12 participating sites located in 6 countries. One site has already finished recruiting. In order to give all other sites, some of which started recruiting only a few weeks ago, the chance to reach the targeted number of 200 subjects per site, the recruitment period has been extended to 31 December 2012. Given the current progress rates in the different sites it is very likely that the recruitment targets will be met at this time.

Conclusion The study is progressing well and is expected to reach its recruitment target by the end of the recruitment period.
Inflammatory optic neuropathies
Authors: BORRUAT FX
Published: August 2012

Acute inflammatory optic neuropathy result frequently from a demyelinating disorder, multiple sclerosis being often the underlying pathology. However, the possibility of other causes of inflammatory optic neuropathies should be entertained when the clinical presentation is atypical (for example, massive disc swelling, painless visual loss, bilateral simultaneous optic neuropathy or, relentless progression of visual loss). This presentation will discuss the clinical presentations and differential diagnosis of typical optic neuritis, including Devic’s syndrome (neuromyelitis optica), neuroretinitis, sarcoidosis, acute idiopathic blind spot enlargement, optic perineuritis, Leber’s hereditary optic neuropathy. At the end of the session, participants should be able to recognize the typical and atypical features of optic neuritis.
Optic neuropathy in Devic’s disease: a diagnostic challenge
Authors: VIGHETTO A
Published: August 2012

Neuromyelitis optica (Devic’s disease) is a severe inflammatory condition of the central nervous system, affecting the optic nerves and the spinal cord, that is distinct from multiple sclerosis by its pathophysiology and treatment. Serum antibody to aquaporin‐4 (AQP‐4 Ab) is a specific although inconstant biomarker of the condition. It helps also to identify among patients with isolated optic neuritis (ON) those who are at risk to convert to Devic’s disease. AQP4 Ab assessment is becoming routinely ordered in atypical ON. We present here our personal experience of the clinical phenotypes of isolated atypical ON that were associated to positivity for AQP‐4 Ab. Six cases were included. There were 4 females and two males, ranging in age from 24 to 68 (mean: 37.6). Follow up duration varied from 6 months to 9 years. Only one patient showed the prototypical monophasic bilateral simultaneous and non regressive visual loss. In the five other cases, presentation was less suggestive and covered a whole range of phenotypes of atypical ON. Thus, they presented with chronic‐relapsing bilateral ON (3 cases), monophasic acute and remitting unilateral ON (1 case) and monophasic progressive unilateral ON (1 case). The prototypical ON case experienced later on several attacks of myelitis. The five other cases remained monosymptomatic to date but were considered as having a high risk for developing myelitis and were kept on immunosuppressive treatments. In conclusion, the clinical spectrum of AQP4‐Ab‐ associated ON is larger than expected. AQP4‐Ab assay has to be performed in any case of severe or relapsing ON. Diagnosis has therapeutic implications. Long term treatment with immune suppressive agents may both improve or stabilize vision and prevent occurrence of myelitis.
Retinopathies
Authors: BOSCHI A
Published: August 2012

Purpose How recognize acquired and hereditary retinal disorders in patient with acute visual loss mimicking an optic neuritis.

Methods Presentation of clinical cases

Results Optic neuritis can be mimicked by other optic neuropathies, and by anterior segment, choroidal as well as retinal diseases. This is particularly challenging when retinal disorders involved the macula or the peripapillary area, like central serous retinopathy, hereditary retinal disorders, and white dots syndrome. A complete neuro‐ophthalmological examination and a detailed history are mandatory to differentiate optic nerve dysfunction from retinal disorders. Fluorescein angiography, OCT and electrophysiological testing might be relevant for the differential diagnosis particularly in case where the fundus appearance is completely normal.

Conclusion Through the presentation of various clinical case the different clinical clue that are helpful to differentiate the acquired and hereditary retinal diseases from optic neuritis will be argue.
Graft rejection in keratoplasty ‐ what are the benefits of systemic immune modulation?
Authors: GRUENERT A
Published: August 2012

Purpose Graft rejection is one of the major causes of corneal transplant failure after keratoplasty, especially in case of an ocular or systemic inflammatory disease. To reduce the patient’s immune reaction against the corneal allograft, topical or systemic immunosuppression is a clinical necessity. This talk provides an overview of the benefits of systemic immunosuppression and of its indications.

Methods The advantages and disadvantages of the use of systemic immunomodulatory drugs in the prevention of corneal allograft rejection after keratoplasty will be analyzed and demonstrated.

Results Various systemic immunomodulatory drugs are available to prevent or to reduce the risk of corneal allograft rejection. The use of systemic immunosuppressive drugs may be limited by side effects.

Conclusion Systemic immunosuppression prolongs corneal allograft survival and reduces the risk of graft rejections. While the use of systemic immunosuppressive drugs is beneficial in the perioperative stage, the long‐term‐use is restricted to high‐risk settings.
Graft rejection in keratoplasty ‐ is there a place for topical immune modulation?
Authors: PLEYER U
Published: August 2012

Topical corticosteroids, although effective in the treatment of ocular immune‐mediated diseases, are well known for their ocular side‐effects. Not surprisingly, a variety of alternative immunomodulatory agents have been tested for topical use including cyclosporin A (CsA), mycophenolate mofetil (MMF), tacrolimus (FK506), rapamycin (sirolimus) and leflunomide. Local application bears the possibility to avoid the severe side‐effects of systemic therapy. The effect of topical therapy is naturally restricted to local immune response mechanisms, such as antigen presentation by Langerhans and dendritic cells. Moreover, many immunomodulatory agents (e.g. CsA) are lipophilic and thus have low water solubility and penetrate insufficiently intra‐ocularly, often being stored in the lipophilic corneal epithelial barrier. Therefore, the therapeutical success is limited for intra‐ocular immune‐mediated diseases like anterior uveitis. However, a multitude of strategies have been introduced to circumvent these problems including complexing substances such as cyclodextrins (CDs) and liposomes. In the prevention and treatment of transplant rejection after keratoplasty, many attempts to introduce topical immunomodulatory therapy have failed; on the other hand, further therapeutic options not primarily expected are being evaluated today such as treatment of severe keratoconjunctivitis sicca. In our own studies, we investigated the pharmacokinetics of topical treatment with different agents including MMF and evaluated the efficacy of topical treatment in animal models for uveitis and keratoplasty. Taken together, topical immunomodulatory therapy will not replace systemic therapy but further treatment options can be expected.
Immune modulatory effects of gene therapy to corneal grafts
Authors: FUCHSLUGER T
Published: August 2012

Purpose To provide an overview of immune modulatory effects of gene therapeutival aproaches to corneal allografting.

Methods The immune reactions caused by corneal allografting will be summarized. Gene therapeutical approaches will be presented, e.g. after transduction of epithelial cells with anti‐apoptotic p35 in the mouse model.

Results Transduction with p35 leads to a reduced immune response. Further insight into the immune modulatory effects will be presented.

Conclusion Anti‐apoptotic gene transfer leads to a reduced immune response in corneal transplantation. This might offer a way to increase success rate after transplantation of a corneal allograft.
Definition and investigative techniques in advanced glaucoma
Authors: ZEYEN T
Published: August 2012

According to Hodapp’s criteria for visual field (VF) scoring, advanced glaucoma can be defined as having a VF mean deviation index (MD) < ‐12 dB. With those VF defects, the optic disc cupping is usually very distinct. Advanced glaucoma can also be defined on the basis of patient’s skills to perform daily activities. Functional tests are usually more useful than structural parameters to follow‐up patients with advanced glaucoma. An overview of the available investigative techniques in advanced glaucoma will be provided.
Treatment options in advanced disease
Authors: BRON A
Published: August 2012

Glaucoma is still the second cause of blindness worldwide. One of the main reasons is that since glaucoma is a symptom‐free disease, at least 50% of glaucoma patients are not aware of their disease. Therefore it is not uncommon to see at the consultation advanced glaucoma cases even in the Western world. The management of these advanced cases is very challenging because if at best the treatment can stop the loss of retinal ganglion cells (RGCs) while lowering intraocular pressure (IOP), it will not prevent from the natural age‐related loss of RGCs. Therefore many of these patients will go blind even with a “successful” treatment. The modalities of the treatment are controversial because when surgery is indicated, the fear of the so‐called whipe‐out syndrome is well known among glaucoma surgeons. Recent papers have highlighted that this complication may occur but may be at a lower rate that previously thought. In any case the treatment has to be customised according to the life‐expectancy of the patient, the local and systemic tolerance of IOP‐lowering drugs and the status of the other eye. A fair information given to the patients by the ophthalmologist is probably at least important that the suggested treatments for a given patient.
Differential diagnosis of advanced glaucoma
Authors: HOLDER GE
Published: August 2012

Purpose To discuss the value of electrophysiological investigation in the diagnosis of visual pathway disease with particular reference to glaucoma.

Methods Standardised ISCEV electrophysiological recordings to incorporate full‐field and pattern electroretinography and visual evoked potentials.

Results A case based presentation will be used to illustrate how appropriate electrophysiological investigation can be used to reach a diagnosis. The correct diagnosis will be discussed in some patients in whom an initial diagnosis of glaucoma was incorrectly made.

Conclusion The findings in patients with glaucoma are not diagnostic. Appropriate electrophysiological testing can usually reach a correct diagnosis when glaucoma is suspected but not present.
Protective role of steroids on mouse primary RPE cells under hypoxic stress
Authors: BEUERMAN R , CHEW J , WEON SR , BARATHI VA
Published: August 2012

Purpose Angiogenesis is a clinically critical aspect of the pathogenesis of many retinal neovascular diseases. Triamcinolone acetonide (TA) is an important anti‐angiogenic and anti‐inflammatory agent. This study has evaluated the effect of TA on the expression of pigment epithelium derived factor (PEDF), thrombospondin‐1 (TSP‐1) and vascular endothelial growth factor A (VEGF‐A) in cultured mouse RPE cells under hypoxic stress.

Methods Primary cultures of mouse RPE cells were grown in culture to passage 2‐3 and were then subjected to hypoxic stress. TA (50µg/ml) was used to determine the steroid effect under normoxic (95% air/5 % carbon dioxide) and hypoxic (95% nitrogen/5% carbon dioxide) conditions. Hypoxia was continued for 48 hrs with and without TA. Cells were harvested at 0, 24 and 48 hours and both RNA and protein were extracted. Real Time PCR was used to analyze expression levels of PEDF, TSP‐1 and VEGF‐A. The expression pattern of PEDF, TSP‐1 and VEGF‐A in the presence of TA were quantifie.

Results After 24 hours of hypoxia, mRNA expression levels of both PEDF and TSP‐1 were down‐regulated by 2‐fold. Hypoxic stress for 48 hours, resulted in 2.2‐fold down‐regulation of PEDF and a stronger down‐regulation of TSP‐1 of 3.4‐fold. VEGF‐A transcripts levels, on the other hand, showed an opposite response to hypoxic stress, an up‐regulation of 1.9‐fold at 24 hours and 2.7‐fold increase at 48 hours. Hypoxic RPE cells, when exposed to TA, led to the rapid recovery of PEDF and TSP‐1 transcripts at 24 hours after the initiation of hypoxia. VEGF‐A mRNA expression rebounded to control levels in TA treated hypoxic cells. Western blots showed that TSP‐1 protein levels correlated with the PCR results. TA significantly induced the expression of TSP‐1 protein in hypoxic cells, and the strongest expression was at 48 hours.

Conclusion The results suggests that TA has a protective effect on PEDF and TSP‐1 levels, and on the fine balance of PEDF, TSP‐1 and VEGF‐A levels.
R‐Ras in retinal angiogenesis
Authors: UUSITALO‐JÄRVINEN H
Published: August 2012

Purpose R‐Ras is a small GTPase belonging to the Ras family of proteins, that regulate cell migration, proliferation and survival. It has been shown to play an important role in vessel maturation. The purpose of this study was to evaluate role of R‐Ras in retinal angiogenesis and vascular stability in oxygen induced retinopathy (OIR) model.

Methods Immunohistochemistry, confocal microscopy and qPCR we used to study expression pattern of R‐Ras in mouse retinas. R‐Ras deficient mice were used to study function of R‐Ras during retinal angiogenesis. Retinal vascular permeability was measured using Miles assay where Evans blue (EB) dye is injected into circulation whereafter amount of albumin bound EB in retinas is quantified by spectrophotometer.

Results R‐Ras is expressed in retinal vessels during developmental angiogenesis as well as during pathological angiogenesis in OIR model. In R‐Ras deficient mice retinal angiogenesis was enhanced in OIR model compared to wt mice. Furthermore, retinal vascular permeability was significantly enhanced in R‐Ras mice compared to wt mice in OIR model suggesting that R‐Ras can effectively stabilize unstable retinal vessels and reduce the leakiness.

Conclusion R‐Ras provides potentially a very interesting new therapeutic target for the treatment of neo‐vascular eye diseases.
Surgical skills among European students
Authors: CREUZOT C
Published: August 2012

Purpose To assess surgical skills of European students at the end of their training

Methods A questionnaire was given to all the students who passed the exam at the end of EBO examination in may 2011. The questions were about the duration of the training program, the beginning of surgical training, the number of different procedures performed by the students like intravitreal injections, lid surgeries, refractive and cataract surgeries. Students were questioned anonymously but they had to precise the country where they have spent their training.

Results We collected 150 questionnaires from the 331 students who have passed the exam. The results showed a great heterogeneity among countries with no surgical training during the residency in some countries while some students have performed more than 50 cataract surgeries without any help at the end of their residencies. Most of the countries do not organize a formal surgical level assessment at the end of the training.

Conclusion These results showed that the organization of surgical training is different among countries in Europe.
UEMS‐EACCME's new criteria for the accreditation of Live Educational Events (LEEs)
Authors: BARISANI‐ASENBAUER T
Published: August 2012

The criteria set out in its document "The Accreditation of Live Educational Events by the EACCME" (UEMS 2011/30) are a significant change to the standards required for accreditation. The aim is to encourage greater transparency and accountability regarding the financial support of educational activities in the field of healthcare. During the presentation the new criteria and the changes necessary for LEEs will be shown.
I have passed the exam
Authors: MUSELIER A
Published: August 2012

Abstract not provided
A strategy for molecular diagnosis and search for new genes/loci in autosomal dominant retinitis pigmentosa
Authors: MANES G , DHAENENS CM , BOCQUET B , MARQUETTE V , BAUDOIN C , RICHARD AC , HEBRARD M , MEUNIER I , HAMEL C
Published: August 2012

Purpose Autosomal dominant retinitis pigmentosa (adRP) affects approximately 1 in 12,000 individuals. To date, 24 adRP genes have been identified accounting theoretically for 44.7% of adRP families; therefore, genetic defects in many patients are yet to be identified. This study was intended to provide information on prevalence of known adRP genes in France and to localize new genes and loci.

Methods The 10 most frequently mutated adRP genes (in full for RHO and RDS, in hot spots only for PRPF31, RP1, PRPF8, IMPDH1, NRL, PRPF3, NR2E3 and SNRNP200) were screened by systematic sequencing to determine the causative mutation in a cohort of 232 French families affected by adRP. We also performed a pilot experiment on 12 families by using whole exome sequencing (WES).

Results The direct sequencing approach was performed on 232 proband DNAs. A causative mutation was found for 99 families (42.7 %), among which 35 out of 68 (51.5 %) were novel. Among the 133 remaining families with no mutation (57.3 %), 12 probands were subjected to WES. This allowed to identify 7 additional families with a causative mutation.

Conclusion The prevalence of the genes was similar to that of the literature for most genes (e.g. RHO with 16 %), but were unexpected for others (e.g. NR2E3 with 3.9 %). The WES approach allowed us to identify a causative gene in 58.3 % of a population previously screened by direct sequencing approach. The 5 remaining families, negative with WES screen, are potentially carrying a mutation in one or more new adRP genes although an intronic mutation cannot be excluded. These 5 families are under active investigation.
Search for the identification of new genes causing autosomal recessive retinitis pigmentosa
Authors: BOCQUET B , MARZOUKA N , HEBRARD M , MANES G , SENECHAL A , BAUDOIN C , MARQUETTE V , MEUNIER I , HAMEL C
Published: August 2012

Purpose The molecular diagnosis of autosomal recessive Retinitis Pigmentosa (arRP) is challenging because of the large genetic and clinical heterogeneity of this disease: to date, 36 arRP genes as well as 3 loci have been identified accounting for approximately 60 % of arRP families. Two major genes, USH2A and EYS, are responsible for 13 to 19 % of the cases, the other genes being minority. Here, we developed a strategy to search for new genes/loci causing arRP in a series of consanguineous families.

Methods Inbred families were genotyped using microsatellite markers specific for USH2A and EYS genes. Families resulting from this first screening were analyzed using 250K SNP microarrays with TASE software (Transmitted Allele Search Engine). Known genes in homozygous regions were PCR/sequenced. Whole Exome Sequencing is running for a few families.

Results A total of 44 inbred families were analyzed. Among them, 14 (32 %) were fully or partly homozygous for EYS or USH2A markers. We selected 16/30 of the remaining families for SNPs genotyping and homozygosity mapping. We found the causative mutation in 7 families (43 %) in a known gene (RP1, RLBP1, NR2E3, CNGB1, IMPG2, PDE6A) while in 6 others sequencing of known genes in homozygous regions is still ongoing. For the 3 remaining families, potentially new loci were found (in chromosomes 3, 10 and 21) for which the results of whole exome sequencing is being analysed.

Conclusion About 43 % of the tested consanguineous families had a positive molecular diagnosis and a candidate gene approach is ongoing for the 3 loci.
Detection of a novel premature stop codon in the OPA1 gene in autosomal dominant optic atrophy
Authors: OLDAK M , FEDEROWICZ A , SZULBORSKI K , WIERZBOWSKA J , KOSINSKA J , PIOSKI R , SZAFLIK JP , SZAFLIK J
Published: August 2012

Purpose Autosomal dominant optic atrophy (ADOA) is a genetically heterogeneous disease, with OPA1, OPA4, and OPA5 representing the main ADOA loci. The aim of the study was to identify genetic etiology of inherited optic neuropathy in a Polish family.

Methods We report on a 2‐generation Polish family with ADOA in which nine family members are affected. MRI and detailed ophthalmological examination with visual field and electrophysiological testing were performed. DNA was obtained from blood samples and linkage to known ADOA loci as well as sequencing of 29 OPA1 exons were conducted. Amplified fragments were analyzed on an automatic DNA sequencer.

Results MRI and ophthalmological examination confirmed the diagnosis of bilateral optic neuropathy. Pattern visual evoked potentials (PVEP) presented delayed P100 wave latency, reduced N75/P100 amplitude and abnormal morphology of waves. Pedigree analysis demonstrated a dominant mode of inheritance. Linkage studies allowed the exclusion of OPA4 and OPA5 loci but revealed linkage to the major OPA1 locus in the investigated family. Sequencing of the OPA1 gene identified a novel C‐to‐T transiton in exon 2 prediciting a premature stop codon (Q31X). The mutation co‐segratated with the phenotype in this family. No other alteration was found in the OPA1 gene.

Conclusion Occurrence of the premature termination codon at the beginning of the transcript strongly suggest that ADOA in the investigated family is a consequence of OPA1 haploinsufficiency. The novel variant broadens the spectrum of the reported OPA1 mutations causing ADOA.
Light flicker and oxygen saturation in diabetes
Authors: HAMMER M , HELLER T , JENTSCH S , MANDECA A , SCHWEITZER D , MüLLER UA
Published: August 2012

Purpose To evaluate the retinal vessel oxygen saturation and its change upon flicker stimulation in patients with diabetic retinopathy.

Methods Dual wavelength oximetry was performed in 41 diabetic patients (65±12.3 years) with mild non‐proliferative though proliferative diabetic retinopathy (DR) and 12 healthy controls (61.3±6.2). In a second study, oximetry and vessel diameter (central retinal artery and vein equivalents, CRAE and CRVE respectively) readings were taken before and 90 s after onset of flicker light stimulus in 18 patients with non‐proliferative diabetic retinopathy (62.2±8.3 years) and 20 controls (71.2±7.5 years).

Results The venous oxygen saturation was increased in diabetic patients with the severity of the retinopathy: Controls 63±5%, mild non‐proliferative DR 69±7%, moderate non‐proliferative DR 70±5%, severe non‐proliferative DR, 75±5%, and proliferative DR 75±8%. Flicker light increased CRAE, CRVE, and venous SO2 by 1.42%±3.72%, 2.80%*±2.70%, and 2.03%*±2.43% in the patients as well as 4.98%*±6.23%, 8.94%*±5.26%, and 4.20%*±3.71% in the controls (*: p<0.05). This increase was significantly higher in the controls vs. patients for all parameters (t‐test, p<0.05). The arterial SO2 remained unchanged in both groups. After adjustment for the subject’s age, the increase of the venous SO2 correlated significantly (p=0.035) with that of the CRAE in the controls but not in the diabetics.

Conclusion Retinal blood flow regulation and oxygen supply seem to be impaired in DR. As a key player in blood flow regulation, the vascular endothelium may be involved. Subsequent micro‐vascular alterations (occlusions and obliterations in the capillary bead, formation of arterio‐venous shunts) may result in a deficient oxygen supply to the retina.

Commercial interest
Diabetic retinopathy and oximetry
Authors: BEK T
Published: August 2012

Abstract not provided
Extraneous factors affecting retinal oximetry
Authors: HUDSON C , PATEL SR , SHAHIDI AM , KULASEKARA S , FLANAGAN JG
Published: August 2012

Purpose To identify extraneous factors that can impact the outcome of retinal oximetry calculations and to discuss how these factors might be negated.

Methods 1. Empiric observation of extraneous factors suspected to impact the outcome of retinal oximetry. 2. Controlled studies of established and suspected extraneous factors.

Results 1. The repeatability of a manual oximetry technique was found to be good. The standard deviations of Optical Density (OD) values ranged from 0.01 to 0.06 OD units and from 0.01 to 0.07 OD units for first degree arterioles and venules, respectively. The Co‐efficient of Repeatability (CoR) ranged from 0.02 to 0.11 OD units (relative to a mean OD of 0.15 [0.06‐0.23] OD units) for arterioles and 0.03 to 0.14 OD units (relative to a mean OD of 0.25 [0.17‐0.31] OD units) for venules. Good reliability (p<0.001) was found for arterioles and venules. 2. Dual ratiometric calculations of retinal oxygen saturation (SO2) demonstrated a significant decrease of arterial SO2 during hypoxia. 3. The order of acquisition of spectral images did not influence the outcome of retinal oximetry results. 4. The manual calculation of SO2 values from reflectance data was significantly influenced by the selected retinal locations within and either side of a given retinal vessel. Other extraneous factors included: 5. Variation in retinal pigmentation; 6. Density of retinal pigmentation); 7. Instrument flash intensity; 8. Lenticular irregularities; 9. Tear film irregularities.

Conclusion Although the assessment of retinal SO2 in ocular diseases would seem to be of clinical value, a number of extraneous factors must first be taken into account to avoid erroneous conclusions.

Commercial interest
Clinical aspects of retinal oximetry
Authors: GIBSON J
Published: August 2012

Purpose To review the current and future role of retinal oximetry in the clinical management of retinal disorders.

Methods By review of the published literature.

Results Examples of retinal oximetry use in retinal and retinovascular disorders will be presented.

Conclusion In the age of widespread use of anti‐VEGF agents in retinal disorders, retinal imaging has become paramount for the treating ophthalmologist. Retinal oximetry enables retinal imaging to be coupled with an assessment of metabolic function of the retina and this may permit more targeted therapies to be given.
Novel therapeutic targets in diabetic retinopathy
Authors: SCHLINGEMANN RO
Published: August 2012

The present armatorium for the prevention or treatment of diabetic retinopathy (DR) comprises modulation of systemic factors, laser, surgical approaches, anti‐VEGF agents and corticosteroids. In designing new therapies, the clinical targets of the various stages of DR should be clearly defined: these are vasoregression in pre‐clinical DR, blood‐retinal barrier loss, inflammation and retinal ischemia in macular edema, and angiogenesis and fibrosis in proliferative DR. With regards to early vasoregression, glucose‐induced alterations in biochemical pathways, growth factors such as CTGF and Angiopoeitin‐2, and leukocyte adhesion are under investigation as targets for prevention, whereas stem cell approaches have been suggested to allow repair of already degenerated retinal capillaries. For non‐proliferative DR and macular edema, inflammatory targets such as TNF‐alpha, IL‐6, IL‐10 and the Kallikrein‐Kinin system are under investigation as targets for alternative or adjunct treatments for anti‐VEGF and laser. However, the growing understanding of the cellular mechanisms of blood‐retinal barrier loss may also allow for more directed therapies aimed at the paracellular or transcellular pathways of leakage, while new neuroprotective agents may restrict the ongoing neuronal loss in this stage of DR. For inhibition of angiogenesis in proliferative DR, several novel agents are available to enter clinical development. Finally, recent new insights in the pathogenesis of the angio‐fibrotic switch and scarring have identified CTGF and other factors as potential therapeutic targets for prevention of this final blinding phase of DR.
Investigator‐initiated trials: a corporate perspective
Authors: LAMBROU G
Published: August 2012

The scope, size and regulatory sponsor requirements for Clinical Trials related to Medicinal Products have reached, over the past two decades, a degree of complexity making them increasingly difficult to implement by non‐industrial sponsors. In recent years, however, these difficulties are being recognized, and various initiatives and guidelines to facilitate Investigator‐Driven Clinical Trials indicate that the situation may be gradually changing. Novartis recognizes that scientifically rigorous Investigator‐Initiated Trials with a sound medical rationale can provide essential contributions in furthering knowledge about diseases and their treatments. It therefore encourages implementation by the Healthcare Community of meaningful Clinical Research that adds to better understanding of medical needs and how to address them, with the ultimate purpose of optimizing patient care and treatment outcomes. In this presentation the concept of Investigator‐Initiated Trials will be discussed from an industry perspective. The regulatory guidelines and Novartis processes for supporting such trials will be explained, using examples from the field of Ophthalmology, and the potential areas of interest in Retinal Vascular Diseases will be outlined.
Identifying progression of retinal disease in eyes with NPDR in diabetes type 2 using non‐invasive procedures. Protocol nº ECR‐RET‐2010‐02. ClinicalTrials.gov Identifier: NCT01145599
Authors: CUNHA‐VAZ J
Published: August 2012

Purpose To identify eyes that show worsening and disease progression (progressor phenotypes)

Methods To identify Diabetic Retinopathy “progressors” to clinically significant retinal edema in type 2 diabetic patients with early NPDR, from baseline to the 12‐month visit, assessed by biomarkers. Primary Outcomes: Microaneurysms turnover computed from color fundus photographs using the RetmarkerDR software; Retinal thickness increase in the central subfield. Secondary Outcomes: BCVA changes; ETDRS step changes; and rescue treatment.

Results Observational study with a follow‐up at 0, 3, 6 and 12 months in eyes with NPDR (≤35). Color fundus photographs analyzed with the RetmarkerDR software for automated assessment of microaneurysms turnover (MA formation and disappearance rate). Retinal thickness measured with Frequency Domain Optical Coherence Tomography (FD‐OCT).
Prospective, randomized, multicenter, open label, phase II / III study to assess efficacy and safety of ranibizumab 0.5 mg intravitreal injections plus panretinal photocoagulation (PRP) versus and PRP in monotherapy in the treatment of patients with high risk proliferative diabetic retinopathy. PROTEUS
Authors: FIGUEIRA J
Published: August 2012

Purpose To compare efficacy and evaluate safety of intravitreal (ITV) injection of ranibizumab (0.5 mg) plus PRP versus PRP alone in the regression of retinal neovascularization (NV) in eyes with high‐risk proliferative diabetic retinopathy (HR‐PDR).

Methods Primary Outcome: Regression of neovascularization (NV). Secondary Outcomes: 1) Best‐Corrected Visual Acuity (BCVA) loss – changes from baseline; 2) Time to NV regression; 3) Recurrence of neovascularization; 4) Macular retinal thickness by Optical Coherent Tomography (OCT) – changes from baseline; 5) Laser needed for Diabetic Macular Edema (DME); 6) Vitrectomy needed due to the occurrence of vitreous hemorrhage or retinal detachment; 7) Drug safety profile.

Results This is a prospective, randomized, multicenter, open label, phase II / III study to assess efficacy and safety of ranibizumab plus PRP versus PRP alone in the treatment of subjects with HR‐PDR. Number Patients: 94 eyes from 94 diabetic patients: Randomized 1:1; Group 1: 47 eyes (PRP group); Group 2: 47 (ranibizumab + PRP).
Interface quality of endothelial keratoplasty buttons obtained with optimised femtosecond laser settings
Authors: BOURGES JL
Published: August 2012

Abstract not provided
Inflammasome activation by oxidative stress in ARPE‐19 cells
Authors: KAUPPINEN A , LAAKSO N , KINNUNEN K , SALMINEN A , KAARNIRANTA K
Published: August 2012

Purpose It is known that oxidative stress and inflammation are associated with the age‐related macular degeneration (AMD). Retinal pigment epithelial (RPE) cells are responsible for the immune defense of retina, and they are constantly exposed to oxidative stress, a condition where the amount of intracellular oxidizing agents becomes increased with a concurrent decline in the cell´s defensive systems. Inflammasomes are intracellular protein complexes which become activated by danger signals encountered by the cell. They play a major role in innate immunity responses but their detailed contribution has still largely remained to be elucidated. In the present study, we have examined the association of oxidative stress with the inflammasome activation in human ARPE‐19 cells.

Methods The cells were pre‐treated or not treated with the bacterial endotoxin LPS, and thereafter exposed to the lipid peroxidation end product 4‐hydroxynonenal (HNE).

Results Our data show that HNE significantly increased the production of proinfammatory cytokines IL‐1beta and IL‐18 but LPS by itself did not. Pretreatment of the cells with LPS, however, further enhanced the HNE‐stimulated cytokine production. PCR analysis revealed that HNE induced a significant increase in the amount of the receptor component NLRP3 mRNA compared to control cells. The amount of NLRP1 mRNA remained unchanged.

Conclusion Our results suggest that LPS provided the first signal needed for the inflammasome activation. Thereafter, HNE triggered the assembly of the NLRP3 inflammasome complex.
IL‐17A as a possible target of anti‐inflammatory and anti‐parasitic treatment in toxoplasmic uveitis
Authors: SAUER A , PFAFF A , CREUZOT‐GARCHER C , DALLE F , CHIQUET C , PELLOUX H , SPEEG‐SCHATZ C , CANDOLFI E , BOURCIER T
Published: August 2012

Purpose Toxoplasmosis is the most common cause of posterior uveitis in immunocompetent subjects. Taking into account the opposing needs of limiting parasite multiplication and minimizing tissue destruction, the immune imbalance implies especially Th17 and T regulatory (Treg) cells.

Methods In a multicenter prospective clinical study of intraocular inflammation (PHRC 3964), we evaluated the cytokine pattern in aqueous humors of 10 T. gondii infected patients. To determine the immunological mechanisms, we evaluated intraocular inflammation, parasite load, and immunological responses using mRNA and protein levels in a mouse model. Anti‐IL‐17A monoclonal antibodies (mAbs) were administered with the parasite in order to evaluate the role of IL‐17A.

Results We observed severe ocular inflammation and cytokine patterns comparable to human cases, including IL‐17A production. Neutralizing IL‐17A decreased intraocular inflammation and parasite load in mice. Detailed studies revealed upregulation of Treg and Th1 pathways. When IFN‐γ was neutralized concomitantly, the initial parasite multiplication rate was partially restored.

Conclusion Local IL‐17A production by resident cells plays a central role in the pathology of OT. The balance between Th17 and Th1 responses (especially IFN‐γ) is crucial for the outcome of infection. This data reveals new in vivo therapeutic approaches by repressing inflammatory pathways using intravitreal injection of IL‐17A mAbs.
Intracranial pressure and glaucoma
Authors: JONAS JB
Published: August 2012

Purpose There are facts and myths. The fact is, that the orbital cerebrospinal fluid pressure (CSF‐P) is the real counter‐pressure against the intraocular pressure across the lamina cribrosa. The myth is that an abnormally low orbital CSF‐P is involved in the pathogensis of normal‐(IOP)pressure glaucoma.

Methods The talk will present the results of recent studies which may shed some light on the question wherther CSF‐P is related to glaucoma
Autonomic nervous system dysfunction in glaucoma
Authors: GHERGHEL DOINA
Published: August 2012

Although abnormal intraocular pressure (IOP) is the main risk factor for the development of primary open‐angle glaucoma (POAG), other culprits including ocular microvascular dysregulation and systemic vascular abnormalities have been implicated in its etiology. The status of autonomic nervous system (ANS) is an important determinant of the systemic hemodynamic parameters implicated in glaucoma pathogenesis. Nevertheless, assessing the ANS function is not a practice in glaucoma diagnosis and management. Consequently, there is a lack of alternative therapies tailored to address associated systemic risk factors for POAG on a case and chronological wise basis; this approach could possibly be more effective in preventing the progression and visual loss in selected glaucoma cases.
Retinal vessel analysis and oximetry ‐ technical advances and clinical applications
Authors: HAMMER M
Published: August 2012

Purpose To develop and evaluate a method for simultaneous measurements of retinal vessel oxygen saturation and vessel diameter change upon flicker light stimulation.

Methods Dual – wavelength (548 nm and 610 nm) fundus images were taken before (baseline) and during luminance flicker stimulation (12.5 Hz, modulation depth: 1:25). Retinal vessel oxygen saturation (OS, dual – wavelength optical oximetry) and diameters (central retinal arterial and venous equivalents – CRAE and CRVE) were determined. Investigations were performed in 19 healthy volunteers (mean age: 26 ± 2.5 years), 18 patients with diabetic retinopathy (62.2±8.3 years), 16 glaucoma patients with IOP (≤22 mmHg, mean 16±3.5 mmHg, mean age 66±14 year), and 20 age matched controls (71.2±7.5 years).

Results In the young population, the flicker increased CRAE, CRVE, and venous OS statistically significant from 193 ± 20 µm, 228 ± 20 µm, and 60 ± 5.7% at baseline to 202 ± 19 µm, 242 ± 17 µm, and64 ± 5.9% (all p<0.0005).. Flicker light increased CRAE, CRVE, and venous OS by 1.42%±3.72%, 2.80%*±2.70%, and 2.03%*±2.43% in the patients as well as 4.98%*±6.23%, 8.94%*±5.26%, and 4.20%*±3.71% in the controls (*: p<0.05). Also in glaucoma patients, the increase of venous OS upon flicker was smaller in the patients than in the controls (1.9±4.9%).

Conclusion Oxygen supply or consumption is reduced in diabetic retinopathy as well as glaucoma. The simultaneous measurements of retinal vessel oxygen saturation and vessel diameter change upon flicker light stimulation should be considered for the investigation of such impairment of oxygen supply.

Commercial interest
Genetic analyses of uveal melanoma metastases
Authors: SAULE S , COUTURIER J , STERN MH , MARIANI P , DESJARDINS L , ROMAN‐ROMAN S , BARILLOT E , PIPERNO‐NEUMANN S , LAURENT C
Published: August 2012

Purpose To identify genes linked to metastasis development in uveal melanoma (UM), transcriptome analysis linked to comparative genomic hybridization was performed with 63 primary tumors and 115 liver metastasis. 9 primary tumors and their matched metastasis (couples) were also analyzed. A biostatistical approach was used to define the genetic prognosis parameters. BAP‐1 mutations reported to be frequently present in class 2 UM were investigated.

Results Fifteen percent of the metastases were found disomic for the chromosome 3 (suggesting a class1 profile) and the couples were monosomic for chromosome 3 (suggesting a class2 profile). Examination of the genomic imbalances in couples (all with monosomy 3, suggesting a class2 profile) indicated that no major alterations occurred at the metastatic step. Very few genes (30) were found differentially expressed between the primary tumor and the metastasis after removal of liver expressed genes.

Conclusion These results suggest that the events leading to the metastasis spreading are already present in the primary tumor.
Prediction of metastasis
Authors: DAMATO B , COUPLAND SE
Published: August 2012

Purpose To describe the Liverpool approach to the prediction of metastasis from uveal melanoma.

Methods The Liverpool Ocular Oncology Research Group (LOORG) has developed the Liverpool Uveal Melanoma Prognosticator Online (LUMPO), which is available free on the internet at www.ocularmelanomaonline.com. This estimates the survival probability according to age, sex, largest basal tumour diameter, tumour thickness, ciliary body involvement, extraocular spread, melanoma cytomorphology, mitotic count, extravascular matrix pattern and chromosome 3 status. An all‐cause survival curve is generated using the accelerated failure time mathematical model. A survival curve for the general British population of the same age and sex is also generated. By subtracting one curve from the other it is possible to estimate metastatic mortality.

Results LUMPO has been developed with data on more than 3000 patients and has been thoroughly validated. The results depend greatly on the accuracy of clinical measurements, mitotic counts and genetic typing. We have found FISH to be inadequate and have replaced this with MLPA and MSA, reserving the latter for small biopsy samples. Biopsy techniques have also improved and these have enhanced the results of prognostication.

Conclusion With advances in biopsy, genetic testing and multivariate analysis, we are now able to provide personalised prognostication. This enhances the quality of life of patients with a good prognosis while enabling us to target intensive care,such as counselling and screening, at high‐risk patients. Improved prognostication has also enhances opportunities for basic science research, facilitating the identification of molecular abnormalities influencing the metastatic process.