bluuebunny/crossref_metadata_2025 huggingface dataset:
RIP Kinases, necroptosis and redundancy in neuronal cell death
Authors: VAVVAS D , MURAKAMI Y , KAYAMA M , MILLER JW
Published: August 2012

Purpose Neuronal cell death is the major cause of vision loss in many eye diseases. The exact mechanism remains unknown. Apoptosis has been thought to be the major form of regulated cell death and the main modality of neuronal cell death in degenerative ailments. However, neuroprotective strategies based on apoptosis have failed to materialize. We wanted to investigate the presence of alternative cell death modalities in various models of degenerative eye diseases.

Methods Neuronal cell death was studied in a variety of animal models, including retinal detachment, RD10 juvenile degeneration, Cx3Cr1/CCL2/rd8 triple mutant, optic nerve crush, and chemical toxicity models (NMDA, PolyI:C, Na‐Iodate, Lipid peroxide, and chloroquine). Analysis of cell death was performed by transmission electron microscopy (TEM), TUNEL staining and standard molecular techniques.

Results Caspase dependent apoptosis was the major cell death modality in most models of cell degeneration. However, RIP regulated necrosis accounted for a significant portion of cell death morphology. Under conditions of selective caspase inhibition, RIP regulated necrosis became the predominant cell death modality. Simultaneous caspase and RIPK inhibition lead to significant neuroprotection. Autophagy accounted for small portion of cell death in the models that it was examined.

Conclusion RIP Kinase regulated necrosis (necroptosis) is a significant redundant cell death pathway in many animal models of ocular degenerative diseases. It becomes the predominant form of cell death under conditions of caspase inhibition. Combination treatments may be needed for successful neuroprotection.

Commercial interest
Neuroprotection and autoimmunity in glaucoma
Authors: GRUS F
Published: August 2012

In glaucoma, the elevated intraocular pressure cannot explain the disease in all patients. However, the pathogenesis of the disease is widely unknown. Biomarker research could be help to understand the disease process. Beside some genetic and proteomic biomarkers, immunoproteomics could play a significant role. Several studies could provide hints for an involvement of autoantibodies in the pathogenesis of the disease. The complex profiles of natural occurring autoantibodies were analyzed by Western Blotting and mass spectrometry based techniques combined with multivariate statistics and artificial neural networks. In several studies we could demonstrate consistent up‐ and down‐regulations of immune reactivities against ocular antigens in glaucoma patients. These findings could lead to a better understanding of the pathomechanisms involved in glaucoma, but could also lead to new innovative ways of early detection and neuroprotective treatment options of the disease.
Molecular pathology of inflammation in age‐related macular degeneration
Authors: CHAN C
Published: August 2012

Purpose To review molecular pathology of inflammation in age‐related macular degeneration

Methods Personal and collaborative research in addition to literature review

Results Risk for AMD is multifactorial, relating to age, environmental and genetic factors. Genome‐wide and targeted genetic association studies have identified various polymorphisms important for AMD susceptibility. Many are within immune‐related genes, including complement factors, e.g. CFH, C2, C3, CFB, and CFI; Toll‐like receptors, e.g., TLR‐3 and TLR‐4; and chemokines and receptors, e.g., CX3CR1 and CCR3. In addition, copy number variation/polymorphism, miRNA and epigenetics related to immune relevant genes could also contribute to AMD pathogenesis and patient responses to specific therapies. Inflammatory cells (mainly macrophages and microglia) and inflammatory factors (complement factors, cytokines/chemokines, oxidative stress‐related inflammatory products) are demonstrated in AMD lesions at various stages.

Conclusion The molecular characterization of AMD captures the localizations and interactions among the inflammatory elements, relevant molecules (e.g., oxidative stress products and lipoprotein), and retinal/choroidal cells, in particular, the photoreceptors and RPE.
Why should we care about rate of progression in glaucoma management?
Authors: STALMANS I
Published: August 2012

During this short introduction, the meaning and importance of measuring the rate of progression in glaucoma care will be explained and illustrated with a patient example.
Detecting progression using visual fields
Authors: ROSSETTI L
Published: August 2012

Abstract not provided
Linking it together: structure‐function correlation
Authors: SUNARIC MEGEVAND G
Published: August 2012

In this part of the course we will discuss the implication of the combination of the structural and functional measurement. In glaucoma structural and functional measurements provide largely independent information, and most studies indicate that their agreement is generally poor. There is some evidence in the literature that structural damage may precede a correlative functional deterioration. However as concordance of measures is limited, combining longitudinal information from structural and functional tests can improve detection and assessment of glaucoma progression. New technological tools and statistical modeling approach combining structure and function may improve detection of progression today.
Strabismus surgery: minimally invasive or not?
Authors: MOJON D
Published: August 2012

Purpose To present the advantages and disadvantages of minimally invasive strabismus surgery (miSS).

Methods Review of available literature and experience from surgeons starting with MISS.

Results MISS has the following advantages: less visibility of surgery, decrease of postoperative discomfort and pain, hospital stay and working disability, and preservation of limbal stem cells. Disadvantages of MISS are: long learning curve, need of microscope, difficulties visualizing anatomical variations, and increased risk of globe penetration.

Conclusion For skilled surgeons with already experience in microscope assisted strabismus surgery transition to MISS will be easier.
Controversies related to mfVEP use
Authors: CASTELO‐BRANCO M , REIS A
Published: August 2012

Purpose To address the usefulness of mfVEP use in clinical research on neurophthalmology, with a focus on optic neuropathies (Leber and Kjer Optic Neuropathies) as well as acquired cortical scotomas.

Methods We have tested a sample of 17 asymptomatic Leber’s hereditary optic neuropathy (LHON) who were mtDNA 11778G>A mutation carriers from two generations of the same pedigree (mean age ± SD = 27.94 ± 12.97 years; mean visual acuity ± SD= 1.25 ± 0.11). We included an age‐matched control group (n=18; mean age ± SD = 33.29 ± 14.22 years; mean visual acuity ± SD= 1.09 ± 0.14). We have also studied 22 subjects (44 eyes) from 13 families with Autosomal Dominant Optic Atrophy (ADOA) submitted to OPA1 mutation analysis. Quantitative psychophysical methods were used to assess konio and parvocellular chromatic pathways. Electrophysiological assessment included the Multifocal Electroretinogram (mfERG) and Pattern Electroretinogram (PERG), respectively. Global Pattern and Multifocal VEP (visual evoked potentials) were used to assess retinocortical processing. Finally we performed multimodal studies (mfVEP and structural and functional MRI) to study visual loss in a patient with a cortical scotoma.

Results We found evidence for functional impairment in color vision pathways in LOHN carriers, with relative preserved VEP and mfVEP responses. In ADOA mfVEP showed distinct evidence for cortical impairment that is only moderately explained by the retinal phenotype, suggesting additional damage mechanisms at the cortical level. fMRI based visual field cortical mapping revealed changes in retinotopic organization that were more difficult to identify using mfVEP.

Conclusion mfVEP is an interesting tool in clinical research , but its application in the clinical diagnosis setting is still difficult.
Visual, ocular and refractive development in children
Authors: SCHAEFFEL F
Published: August 2012

Purpose To describe visual, ocular and refractive development in children, possible reasons for deviations and some of the underlying mechanisms.

Methods Literature review and own data.

Results Contrast sensitivity and visual acuity develop slowly, reaching adult‐like performance around 5 years of age. Refractive development is very different if measured with and without cycloplegia but typically emmetropization was successful at 5 years of age, before the risk of myopia comes in. These developments require continuous visual feedback. If the retinal image is not focused or clouded by cataract, irreversible amblyopia develops. Eye growth represents by no means a linear scaling of the initial ocular dimensions. The decline in optical power of the cornea levels off already in the second year of life but axial eye growth continues at least until puberty. There is a built‐in risk factor for myopia because the crystalline lens has limited capacity to compensate for further axial elongation. These observations do not explain the environmental input to myopia development. In animal models, further axial eye growth is triggered by negative defocus, loss of image contrast, or abnormal light cycles or intensities. The retina is the major controller of axial eye growth. It uses image focus to control the growth of the underlying sclera bi‐directionally, depending on sign of defocus. Growth inhibition, induced by positive lenses, involves a biochemically different mechanism which is very responsive ‐ but can apparently still not save the human eye from myopic.

Conclusion A lot can go wrong during postnatal ocular development since appropriate visual input is obligatory for normal development. Natural eye growth patterns include a built‐in risk factor for myopia development in early adolescence.
Myopia ‐ Its etiology and prevalence
Authors: SANKARIDURG P
Published: August 2012

Purpose Myopia (short‐ sightedness) is a significant health problem that is fast rising in prevalence in many parts of world including Europe and USA and at a much higher percentage for population in parts of Asia. Also high myopia is associated with the risk of developing other sight threatening eye conditions.

Methods An analysis of the published prevalence rates for myopia with the risks and morbidity associated with high levels of myopia. Also factors that are considered to play a role in the development and progression of the condition will be discussed with emphasis on published data for the role of these factors.

Results Whilst the role of individual factors is yet to be elucidated both environmental and genetic factors have been considered to play a role. An increased prevalence of myopia in urban versus rural populations, association with outdoor/indoor work, supports and provides evidence for the role of environment. In this regard, many of the previous efforts have focussed on accommodative effort and blur at the central retina during near visual tasks. More recent evidence suggests that the peripheral retina also plays a role in emmetropisation and development of refractive errors.

Conclusion This presentation will discuss the rates and differences in the prevalence of myopia across various populations. In addition, current hypotheses considering the aetiology of development and progression of myopia will be discussed.

Commercial interest
(New) Approaches to reduce progression of myopia with spectacles from Carl Zeiss Vision
Authors: KRATZER T
Published: August 2012

Purpose This talk will present a dedicated spectacle lens design that has indicated to reduce the progression of myopia in a group of Asian children in a randomized and double blind clinical study.

Methods In contrast to conventional spectacles lenses for myopes, the ZEISS MyoVision lens uses a special peripheral treatment zone to bring the peripheral focus back or in front of the retina while providing a clear and undisturbed asymmetric central vision. A clinical trial has been conducted to evaluate the performance of this new lens design.

Results The combination of a peripheral treatment zone and a clear central viewing zone in a single vision lens show positive results by indicating a reduction of the progression of myopia by 30% on average in Asian children age 6‐12years old with a history of parental myopia while providing stable and clear vision without adaption problems of the wearer.

Conclusion This lens has been successfully trialed in a randomized and double blind clinical study on Chinese school children. Modern spectacle lens designs with special treatment zones can lead to a reduction of the progression of myopia.

Commercial interest
A comparison of HLA genotype with inflammation in uveal melanoma
Authors: JAGER MJ , VAN ESSEN TH , BRONKHORST IHG , VERDUYN W , ROELEN DL , MAAT W , LUYTEN GPM
Published: August 2012

Purpose HLA (Human Leukocyte Antigen) polymorphisms have been associated with the development of autoimmune diseases. In uveal melanoma, a high expression of HLA class I and II and infiltration with lymphocytes and macrophages are associated with a bad prognosis, and Natural Killer cells are thought to play a role in the killing of metastasizing cells. The goal of this study is to determine whether specific HLA alleles are associated with increased inflammation.

Methods Records were analyzed of 45 patients who underwent enucleation for uveal melanoma. HLA typing, tumor HLA expression and tumor macrophage infiltration were determined in each case.

Results Before correction for multiple testing, macrophage infiltration was less in HLA‐A2 positive patients. Patients with HLA‐DR6 had a higher tumor cell expression of HLA‐DR. After correction for the number of analyses, no associations remained statistically significant.

Conclusion The results before correction suggest that the HLA genotype may influence inflammation as indicated by HLA expression and macrophage infiltration in uveal melanoma. Comparing HLA expression with the genetic presence of specific HLA alleles is a new approach to obtain insight into the role of the immune system in uveal melanoma.
Pre‐clinical analysis of Crizotinib in uveal melanoma
Authors: DE LANGE MJ , VERSLUIS M , JAGER MJ , LUYTEN GPM , VAN DER VELDEN PA
Published: August 2012

Purpose Uveal melanoma (UM) is an intraocular neoplasm with an annual incidence of 7 per million. UM originates from melanocytes just like cutaneous melanoma (CM) and similar to CM, the MAPK pathway is involved in the development of UM. However, not all UM seem to depend on the activation of this pathway. Loss of ERK signalling may be correlated with progression as the ERK negative cells are derived from UM metastasis. Here, tumours apparently use different mechanisms to proliferate and survive. In this study, we aimed to determine the pathway that is up‐regulated in UM metastases and to inhibit its function with targeted kinase inhibitors.

Methods We used pathway profiling to identify the pathways that are important in metastases. Furthermore, the c‐Met inhibitor (Crizotinib) was used to inhibit the c‐Met receptor and to identify downstream targets. Colony formation assays and 3D sphere assays were used to characterize UM cells in a three dimensional environment.

Results Reduced c‐Met activation rather than reduced expression was induced with Crizotinib treatment. Subsequently, c‐Met inhibition was correlated with reduced colony formation. c‐Met positive UM cells captured in 3D spheres revealed a reduced capacity to migrate upon Crizotinib treatment compared to cells that lack activated c‐Met.

Conclusion c‐Met activation was observed in metastasizing UM where it serves as biomarker for Crizotinib treatment. Efficacy of treatment was shown by inhibition of growth and migration. Combined our data reveals c‐Met signalling in progression of UM and support the use of Crizotinib for UM metastasis.
Primary transpupillary thermotherapy for small suspicious choroidal nevi
Authors: TURCOTTE S , BERGERON D , ROUSSEAU A , MOURIAUX F
Published: August 2012

Purpose The purpose of this study was to assess the ocular and systemic outcomes of patients treated by transpupillary thermotherapy (TTT) for suspicious choroidal nevi at our oncology centre.

Methods A retrospective chart review was conducted for all patients with a newly diagnosed small suspicious choroidal nevus treated by TTT at our oncology centre from the date of acquisition of the laser (2002) to September 2011. Standard treatment consisted of three TTT sessions. Patients with two or more risk factors for tumour growth were systematically treated. Ocular and systemic outcomes were reviewed and compared with those of similar patients that were observed between 1990 and 2008.

Results Our preliminary data include 8 patients treated by TTT and 56 patients that were followed‐up without treatment. Of the treated patients, 3 (37.5%) showed progression with a mean time to recurrence of 13 months. Of the observed patients, 23 (41%) showed progression with a mean time to recurrence of 41 months. There were no reported deaths in the treated group, and 3 (5.4%) deaths due to metastatic melanoma in the observation group.

Conclusion Despite careful patient selection, primary TTT for small suspicious choroidal nevi showed poor local tumour control. No deaths due to metastatic melanoma were reported in the follow‐up of treated patients, and mortality remained low in the observation group.
Genetics and treatment of Stargardt disease
Authors: ALLIKMETS R
Published: August 2012

Purpose When the adenosine triphosphate (ATP)‐binding cassette (ABC) transporter gene, ABCA4 (originally named ABCR), was cloned and characterized in 1997 as the causal gene for autosomal recessive Stargardt disease (STGD) it seemed as if just another missing link was added to the extensive table of genetic determinants of rare monogenic retinal dystrophies. Now, 14 years later, the ABCA4 gene continues to emerge as the predominant determinant of a wide variety of retinal degeneration phenotypes, such as STGD, cone‐rod dystrophy, retinitis pigmentosa, and age‐related macular degeneration.

Methods A combination of genetic, molecular biology, gene‐ and small molecule therapy approaches.

Results ABCA4 has caused exciting and sometimes intense discussions among ophthalmologists and geneticists, resulting in more than 300 publications during this time. In my presentation I will summarize our current knowledge of the role of ABCA4 in retinal disease and review the substantial progress in diagnostic and therapeutic applications for ABCA4‐associated disorders which most recently seemed impossible.

Conclusion Although ACBA4 has proven to be a complex and difficult research and therapeutic target, I hope to convince the audience that treatment of all ABCA4‐associated disorders, and especially STGD, should be possible in the near future.
Prevention of endophthalmitis in cataract surgery
Authors: MONTAN P
Published: August 2012

Purpose To review data from the Swedish prospective endophthalmitis (E) registry which is linked to the National Cataract Register.

Methods 14 years of reporting was reviewed.The registry contains data on demographics, type of surgery,the prophylactic protocol and surgical complications

Results Thanks to the introduction of intracameral cefuroxime, the rate of E. in Sweden has not exceeded 0.05% which is considerably lower than other nation‐wide reports. In the most recent 3‐year period, the rate has approached 0.02% which has been parallel to a decline in capsule breaks and procedures in patients aged > 85 years, two independent risk factors for E. Moreover, an intracameral antibiotic, mainly cefuroxime, is practically always employed nowadays and alternative agents to cefuroxime are presently tried.

Conclusion Analysing the effect of prophylactic disinfecting protocols in large‐scale clinical observational studies is necessary to reach a well supported strategy aimed at preventing E.In addition, identifying risk factors for E and avoiding them is a supplementary means to reduce the rate of this dreaded complication.
Microbiological diagnosis of bacterial endophthalmitis
Authors: CHIQUET C
Published: August 2012

Purpose The systematic microbiological documentation of endophthalmitis allows the confirmation of the infectious nature of the disease and the possible adaptation of treatment at the individual level and, at the collective level, the epidemiological characterization of the bacterial spectrum of endophthalmitis.

Methods different microbiological techniques will be presented: conventional techniques (media), eubacterial PCR, real time PCR

Results It is preferable to inoculate intraocular samples into culture media (a paediatric blood culture bottle or in Brain Heart Infusion (BHI) broth) under sterile conditions in the operating room and to transfer the sample intended for PCR into a sterile tube without residual DNA (DNA‐free) and with a screw cap. Bacterial identifications and antibiograms are then obtained using phenotypic methods. Real time PCR is more sensitive than culture, allows the detection and identification of specific micro‐organisms, DNA quantification, and has a faster turn around time (no post‐PCR step). The PCR amplification of 16S rDNA uses consensus primers (panbacterial PCR) and is followed by identification from analysis of 16S rDNA sequence. This technique has the advantages of amplification of DNA from all bacteria, and identification of bacteria difficult to identify phenotypically (e.g. coagulase‐negative Staphylococcus species). However drawbacks are the possible contaminations, the duration (2‐3 days including sequencing), and the impossibility of differentiating mixed bacterial species in the same clinical sample.

Conclusion PCR techniques are complementary tools to culture. New techniques of PCR are needed in order to be faster and more sensitive. Genomic characterization of strain virulence of bacteria involved in endophthalmitis will be further studied.
Management of postoperative endophthalmitis
Authors: BRON A
Published: August 2012

Postoperative endophthalmitis remains a devastating condition both for the patient and the surgeon. Even with careful prophylaxis such an ocular infection may occur. The EVS (Endophthalmitis Vitrectomy Study) has shed light and provided robust guidelines for the management of acute postcataract endophthalmitis. However since the publication of the EVS in 1995 we may wonder whether the findings of this major trial are still valid in 2012. Vitrectomy techniques have improved, the choice of the systemic antibiotics used in the EVS was not optimal and the widespread use of local antibioprophylaxis may have changed the presentation and prognosis of postoperative endophthalmitis. Others questions are not fully answered; what about the use of intravitreal corticosteroids, how do the EVS data apply to other endophthalmitis presentations (traumatic, glaucoma or chronic endophthalmitis?). In this presentation we will give some very practical and useful clinical tips for postoperative endophthalmitis management, mainly based on the FRIENDS group (FRench Institutional ENDophthalmitis Study) which has gathered about 100 cases of endophthalmitis.
Biofilms in ocular infection
Authors: SHANKS RM , ROMANOWSKI E , KOWALSKI R
Published: August 2012

Purpose To discuss the evidence for microbial biofilms in ocular infections.

Methods A description microbial biofilms and a review of the evidence in the literature for bacterial biofilms in ocular infections.

Results Microbial biofilms are surface attached communities of microbes that are recalcitrant to antibiotic therapy and associated with a wide number of human diseases including, but not limited to as cystic fibrosis, dental caries, otitis media, osteomyelitis, and chronic wounds. There is an increasing body of evidence supporting the potential role of microbial biofilms in ocular infections.

Conclusion The model that biofilms contribute to ocular infections is an exciting new arena of study.
Non‐IOP lowering treatment
Authors: MOZAFFARIEH M
Published: August 2012

The classical glaucoma treatment focuses on IOP reduction. Better knowledge of the pathogenesis has opened up new therapeutical approaches. Whilst most of these new avenues of treatment are still in the experimental phase, others, are already used by some physicians. Blood pressure dips can be avoided by intake of salt or fludrocortisone. Vascular regulation can be improved locally by carbonic anhydrase inhibitors, systemically with magnesium or with low doses of calcium channel blockers. Experimentally, glaucomatous optic neuropathy (GON) can be prevented by inhibition of astrocyte activation, either by blockage of epidermal growth factor receptor or by counteracting Endothelin. GON can also be prevented by nitric oxide‐2 synthase inhibition. Inhibition of matrix metalloproteinase‐9 inhibits apoptosis of retinal ganglion cells and tissue remodelling. Upregulation of heat shock proteins protects the retinal ganglion cells and the optic nerve head. Reduction of oxidative stress especially at the level of mitochondria also seems to be protective. This can be achieved by gingko, dark chocolate, polyphenolic flavonoids occurring in tea, coffee or red wine and anthocyanosides found in bilberries.
Biomechanical concepts in Glaucoma
Authors: KOTECHA AACHA
Published: August 2012

Purpose Title: Corneal biomechanics and glaucoma risk‐ where are we now?

Methods The impact of central corneal thickness (CCT) on intraocular pressure (IOP) measurement accuracy has been well documented, and CCT has become part of the routine work up of a glaucoma suspect patient. What is relatively unclear is whether corneal properties, such as CCT and in vivo measures of corneal biomechanics, give an indication of the risk of glaucoma susceptibility. This talk will consider whether there is a role for the cornea that lies beyond the limits of IOP measurement accuracy, discussing the evidence as to whether current measures of corneal biomechanics may be used as a surrogate marker of optic nerve compliance.
Coats’ disease : classification and current treatment
Authors: MUNIER F
Published: August 2012

Purpose Coats’ disease is characterized by idiopathic telangiectasia with lipid exudates and retinal ischemia. Advanced cases develop total retinal detachment (RD)(stage 3B) and neovascular glaucoma (stage 4), resulting in enucleation in 7% and 78% of cases respectively.

Methods Nine consecutive cases of Coats’ disease stage 3B (n=5) and 4 (n=4) received 1 or more intravitreal injections of 0.5 ml ranibizumab. In 3 cases, subretinal fluid drainage by sclerotomy was performed. Mean age at diagnosis was 17.9 months (range 1‐38). At the end of treatment, ERG was recorded (n=4) and amblyopia treatment was attempted in 6 patients. Mean follow‐up was 42.9 months.

Results Rubeosis disappeared during the first week with the retina reattaching within 4 months, rendering pathological vessels and ischemic retina accessible to conventional therapy. A single injection was sufficient in 6 cases, 2 injections were necessary in 1 patient and another needed 4. One patient developed 10 months after complete retinal reattachment a severe fibrous vitreo‐retinopathy evolving to subtotal tractional RD. Amblyopic treatment was performed in 4 patients and restored measurable visual acuity in two patients. Scotopic ERG was unrecordable with a severely reduced photopic b wave in 3 patients. The last patient had a reduced scotopic b wave (50%) and a normal photopic ERG with slightly increased implicit time.

Conclusion There is an increasing interest in anti‐VEGF therapy in Coats' disease. To our knowledge, this is the largest series of stage 4 and 3B Coats' disease treated by ranibizumab, demonstrating that it is a well‐tolerated and safe therapy in young children with advanced disease. Ranibizumab facilitates the management by suppressing rubeosis in stage 4 and decreasing exudation.
Choroidal hemangioma : photodynamic vs. radiotherapy
Authors: ZOGRAFOS L
Published: August 2012

Abstract not provided
Predicting chromatic sensitivity in normal trichromats and in subjects with congenital deficiency
Authors: BARBUR JL , RODRIGUEZ‐CARMONA M
Published: August 2012

Purpose Differences between M‐ and L‐class variant pigments arise largely because amino acid substitutions in M‐class pigments contribute less to the corresponding shifts in spectral responsivity. Other factors such as the relative numbers of L and M cones, their optical density and the midpoint between their spectral peaks can also contribute to the subject’s overall, red/green (RG) chromatic sensitivity. The purpose of this study was to examine how these differences affect chromatic sensitivity in normal trichromats and in subjects with deutan‐ and protan‐like deficiency.

Methods RG thresholds were measured in 269 deutans, 132 protans and 330 normal trichromats using the CAD test. The colour vision of every subject was also examined using the Nagel anomaloscope. Classification into normal, deutan and protan classes was based on the results obtained on CAD and anomaloscope tests.

Results RG thresholds measured within each group were ranked in increasing order. Samples equal to the number of subjects within each group were taken from a single Gaussian distribution, in the case of normal trichromats, or from more than one distribution in the case of deutan and protan groups. The distribution parameters were optimised to predict the rank order of the measured RG thresholds in each group.

Conclusion The rank order of thresholds measured in normal trichromats can be predicted by a single Gaussian distributions. Deutans produced the most complex rank order which could only be predicted adequately with a minimum of four Gaussians. In contrast, the rank order for the protan group was much simpler and could be predicted well with only two or at most three Gaussian distributions.
Effects of viewing time of pseudoisochromatic plates
Authors: KRASTEL H , LEERS S , KALTAKJI F , KIRCHHUEBEL R , JONAS JB
Published: August 2012

Purpose Effects of viewing time on the recognition of red/green and blue/green pseudoisochromatic plates were evaluated to improve clinical application.

Methods Special pseudoisochromatic “C” or “E” plates (in following referred to as “spic‐plates”) allow repeated exams with identical demands on color vision. The study included 5 daltonian subjects with a best corrected visual acuity BCVA of 1.0, 5 diabetic patients with non proliferative diabetic retinopathy NPDR, BCVA 0.8 or better, and 10 normal observers. Under standard illumination and viewing distance, the viewing time was 1 s, 3 s, or unrestricted until the subject had arrived at his or her final estimate.

Results Daltonian subjects were unable to recognize the red / green spic‐plates during a viewing time of 1 s or 3 s. Under unrestricted observation, 3 of 5 daltonian subjects deciphered the red/ green spic plates. Blue/green spic‐plate results in the daltonian subjects matched those of normal observers. 3 of 5 diabetic patients failed in the blue/green spic plate at 1 s, one at 3 s of viewing time. With one exception at 1 s, the diabetic patients passed the red/green spic plates, as normal observers did.

Conclusion Besides the angle of observation and the level and spectral composition of illumination, the viewing time has an influnence on the results of color vision testing by pseudoisochromatic plates. In clinical application, viewing time should be considered e.g. following Ishihara’s advice of 3 s

Commercial interest
Detection of colour vision changes in patients with systemic diseases that can affect the eye
Authors: KEUKEN A , RODRIGUEZ‐CARMONA M , BARBUR JL
Published: August 2012

Purpose Changes in colour vision can provide the earliest signs of vision loss caused by either retinal or systemic disease (Expert Rev.Ophthalmol. 6(4):409‐420,2011). Both yellow‐blue (YB) and red‐green (RG) mechanisms are affected in acquired deficiency, but some diseases may cause different patterns of colour vision loss. Patients with different systemic diseases were examined to discover abnormal changes in colour vision using a newly developed, age‐corrected system for colour assessment.

Methods 334 subjects (age range: 41 to 91years) were investigated. The subjects were classified as normal, hypertensive, diabetic, diabetic and hypertensive, idiopathic and other systemic conditions. RG and YB colour thresholds were measured monocularly in each eye using the Colour Assessment and Diagnosis (CAD) test.

Results Subjects with early stage pathology were excluded using a number of criteria including the discovery of right / left eye asymmetric loss in colour sensitivity. Age‐corrected limits of normal colour vision were employed to detect significant changes in chromatic sensitivity. The results reveal significantly higher RG and YB thresholds in all groups (including the idiopathic and other systemic conditions group).

Conclusion The use of age‐corrected normal limits of chromatic sensitivity makes it possible to detect reliably significant loss of colour vision in systemic disease. Loss of chromatic sensitivity that precedes retinopathy is present in every systemic condition examined. Further studies are needed to discover the extent to which the pattern of selective RG and YB losses can be attributed to specific diseases of the eye.
Efficacy of surgical simulator training versus traditional wetlab training on the complication rate during capsulorrhexis portion of cataract surgery in trainees
Authors: DALY MK , SIRACUSE‐LEE D , LEGUTKO PA
Published: August 2012

Purpose The purpose of this study is to determine the translational effectiveness of surgical simulation as part of resident training on their performance on the task of casulorhexis during their first surgeries, as compared to traditional wetlab training.

Methods Second Year Residents on rotation at the Veterans Affairs Boston Healthcare System were randomized to continuous capsulorrhexis training (CCC) in the traditional wetlab (n=10) with silicone eye versus on the EYESI surgical simulator (n=11). After completion of the training, residents' initial CCCs in the operating room on real patients were videorecorded. Videos were reviewed and scored by two anterior segment attending surgeons.

Results Scores on 12 measures of performance were reasonably close in all cases; there was no statistical significance in any of the differences in individual scores. Correlation across all 12 measures of performance is 0.919 (p<.001). Overall score was calculated as the sum of the 12 individual performance scores. There was no significant difference in overall score between the two groups (p=.527).

Conclusion Study suggests surgical simulator training when compared to traditional wetlab training is a safe, non‐risk method of preparing trainees to perform capsulorrhexis during their initial surgical experiences on real patients in the operating room.
Clinical markers of inflammation
Authors: COSCAS G
Published: August 2012

Abstract not provided
Revisiting transconjunctival sutureless 25 gauge vitrectomy for macular surgery
Authors: GOTZARIDIS S , LIAZOS ST , MORPHIS G
Published: August 2012

Purpose To report the results of 25g vitrectomy with ILM peeling, SF6 tamponade and strict face down posturing for the treatment of idiopathic macular holes.

Methods This is a retrospective study of 106 eyes with idiopathic macular hole, treated with 25g PPV, brilliant peel assisted ILM peel , SF6 gas tamponade and face down posturing for 1 week. The patients were followed up at 1 day, 1 week, 1 month, 3 months and 9 months postoperatively clinically and with OCT. Preoperative and postoperative logMAR visual acuity was recorded

Results 106 eyes were included in this study. 88 phakic (83%) and 18 pseudophakic (17%). 32 males (30%) and 74 females (70%). Mean age was 66.5 years. Mean preoperative visual acuity was 0.69 logMAR and improved at 0.39 logMAR at 9 months postoperatively.Anatomical macular hole closure rate was 100% (106/106). 102/106 patients (96%) had anatomical closure of the hole after the 1st operation. 4/106 patients had an open hole noticed at 1 week and received an additional SF6 injection at the office and strict face down posturing for another week. 4/4 patients had the hole closed at month 1. Postoperative complications included a case of macular toxicity due to accidental intravitreal leak through the sutureless port of gentamycin which was injected subconjunctivaly at the end of surgery. Early postoperative raised intraocular pressure was noticed in 6 patients (5.6%) . No retinal detachment and no case of endophthalmitis was noticed.

Conclusion 25g PPV, ILM peeling, SF6 gas tamponade and posturing is a safe and effective technique for the treatment of idiopathic macular holes. Additional gas injection combined with extended strict posturing can increase the anatomical closure rate without the need of additional surgery.
Myopic foveoschisis: OCT findings, surgical indications and results
Authors: GAUDRIC A
Published: August 2012

Abstract not provided
Morphology of surgical ILM‐specimens in epiretinal membranes, macular holes, and diabetic retinopathy
Authors: POURNARAS CJ
Published: August 2012

Purpose Myofibroblasts play a major role in the production of retractile phenomena causing contraction or shrinkage of the epiretinal membranes (ERM) in proliferative vitreoretinopathy and diabetic retinopathy. The purpose of our study was to evaluate the expression of myofibroblasts on epiretinal tissues in eyes with epiretinal membranes, diabetic macular edema (DME) or macular holes.

Methods Samples of ERM and ILMs (internal limiting membranes) following macular epiretinal membrane removal in eyes with diabetic maculopathy, refractory to conservative treatment, idiopathic epiretinal membrane and macular holes, were collected. Double immunofluorescence staining, with antibodies recognizing a smooth muscle actin (a‐SMA) and fibronectin (ED‐A FN) or vimentin in myofibroblasts, followed by confocal and electronic microscopy was performed.

Results a‐SMA in association with either ED‐A FN or vimentin were detected in all ERM specimens. a‐SMA and ED‐A FN were also detected in ILMs removed in cases of stage IV macular holes. ED‐A FN was expressed in close relation to a‐SMA–positive myofibroblasts, predominately located close to the border of the macular hole area. In all idiopathic ERMs, ED‐A FN was expressed in close relation to a‐SMA–positive myofibroblasts. In those cases, no a‐SMA staining was observed in ILM specimens.

Conclusion Scanning electron microscopy indicated that active contraction mechanisms are always expressed in epiretinal macular membrane and underling ILM tissues in eyes with diabetic maculopathy and late stages of macular hole.ILM folding seems to be myofibroblast‐independent in idiopathic epiretinal membrane cases.
Immunological aspects of age‐related macular degeneration: implications for treatment
Authors: CHAN C
Published: August 2012

Purpose To review immunological aspects of AMD with implications for treatment

Methods literature review and personal collaborative studies

Results As inflammation is recognized to play a role in AMD pathogenesis, systemic and local anti‐inflammatory therapies have been recently used for disease prevention and/or in combination with anti‐VEGF medications for the treatment of exudative/neovascular disease. Several small AMD clinical trials have demonstrated potential benefits of immunomodulatory medications such as corticosteroids, non‐steroidal anti‐inflammatory drugs (NSAID), immunosuppression (methotrexate and sirolimus), and biologics (infliximab and daclizumab); ongoing studies are now investigating complement component inhibitors.

Conclusion Since inflammation is only one component of most retinal diseases, current anti‐inflammatory therapies merely provide palliative treatment. Further investigation of adverse effects and long‐term follow‐up on the anti‐inflammatory medications are warranted.
Individual ONH blood flow patterns during changes in perfusion pressure
Authors: SCHMETTERER L
Published: August 2012

Purpose Abnormal optic nerve head (ONH) blood flow autoregulation has been implemented in the pathogenesis of glaucoma since decades. In fact, however, the regulation of ONH blood flow is poorly characterized and the mechanisms of autoregulation remain obscure.

Methods Several studies were performed to investigate the behavior of ONH blood flow during changes in perfusion pressure in healthy subjects. In all these studies laser Doppler flowmetry was used to measure ONH blood flow. Interventions included squatting and handgripping to increase ocular perfusion pressure and use of a sclera suction cup to reduce ocular perfusion pressure.

Results During both an increase and a decrease in perfusion pressure the ONH shows some autoregulatory capacity. Data during combined change in arterial pressure and venous pressure indicate that ONH blood flow is not only dependent on the level of perfusion pressure but also on the absolute levels of pressures in the arterial and venous tree. In addition, there is a wide inter‐individual variability in the responses. In some subjects a temporal reduction in ocular perfusion pressure is associated with a pronounced decrease in ONH blood flow.

Conclusion Regulation of ONH blood flow is more complex than previously thought. Some subjects show pronounced ischemia during fluctuations in ocular perfusion pressure. Whether this pre‐disposes to ONH disease remains unclear.
The LDL receptor in the retina: the missing link in aging, the new target in dietary prevention
Authors: BRETILLON L , SIMON E , ACAR N , BRON A , CREUZOT‐GARCHER C
Published: August 2012

Purpose The discovery of the LDL receptor (LDLR) in 1985 by Brown and Goldstein was awarded by a Nobel Prize. The LDLR has initially been identified for its role in mediating the endocytosis of LDL particles in the vascular endothelium. The deposition of lipids, including cholesterol and cholesteryl esters in Bruch’s Membrane in the one hand, and in the vessel intima in the other hand, is one of the common features of age related macular degeneration (AMD) and cardiovascular disease (CVD). Dietary habits with high intakes of omega 3 long chain fatty acids (LCFA) have been associated with AMD prevention. Similar effects have been demonstrated in CVD prevention. The mechanisms behind this association in AMD remain partly unknown.

Methods The present paper highlights our recent findings on the pivotal role of LDLR in aging of the retina, and modulation of LDLR expression by dietary omega 3 LCFA.

Results In a humanized mouse, we have shown that the lack of LDLR was associated with the presence of the main characteristics of aging of the human retina: fundus autofluorescence, deposition of cholesteryl esters in Bruch’s Membrane, and impairment of the retinal function. We further questioned whether following the dietary guidelines on omega 3 LCFA would modulate gene expression, including LDLR. Expectedly, we found that increasing the intake in omega 3 LCFA and lowering linoleic acid increased LDLR expression and improved the incorporation of omega 3 LCFA.

Conclusion Altogether, our data are consistent with the crucial importance of LDLR in the aging process in the retina. We also strongly support the idea that the modulation of LDLR expression is one of the mechanisms of the preventive effects of omega 3 LCFA in AMD.
Lutein decreases complement factor D in age‐related macular degeneration
Authors: BERENDSCHOT T , TIAN Y , VAN DER VEEN R , MAKRIDAKI M , MURRAY I , KIJLSTRA A
Published: August 2012

Purpose The complement system plays an important role in the pathogenesis of Age‐related Macular Degeneration (AMD). In this study we examined the effect of lutein on circulating levels of Complement Factor D (CFD), a rate limiting component of the alternative pathway of complement activation.

Methods Blood samples were collected from 82 early AMD patients from The Netherlands and the UK that took part in a one year multi centre, double masked, placebo controlled intervention trial with lutein supplementation. CFD was measured by ELISA.

Results We found a significant 0.12 μg/ml monthly decrease in serum CFD concentration in the lutein group (p<0.001), resulting in a 61% decrease from 2.33 μg/ml at baseline to 0.91 μg/ml at 12 months. We found no change in the placebo group.

Conclusion Lutein supplementation markedly decreases circulating CFD levels thereby offering a simple method to control the alternative complement pathway.
Relevance of complement factor H polymorphisms in the response to intravitreal bevacizumab in exudative age‐related macular degeneration
Authors: BOLTZ A , JONAS JB , PALKOVITS S , TAO Y , RENSCH F , WEGER M , GARHöFER G , FRANTAL S , EL‐SHABRAWI Y , SCHMETTERER L
Published: August 2012

Purpose There is increasing evidence that the complement system, in particular the complement factor H (CFH) plays a significant role in the pathogenesis of age‐related macular degeneration (AMD). Over the last decade the use of antibodies against vascular endothelial growth factor has revolutionized the therapy for exudative AMD. However, about 10 to 15% of the patients seem to be poor‐ or non responders and do not profit from such treatment. The present study investigated whether treatment outcome of intravitreally administered bevacizumab is dependent on 6 common CFH polymorphisms.

Methods In this prospective cohort study 185 eyes of 141 treatment naïve patients with exudative AMD were included. Study eyes were injected with bevacizumab using the as needed regimen. At each follow up visit a complete ophthalmic examination as well as optical coherence tomography was carried out. CFH polymorphisms for rs1061170, rs393955, rs800292, rs1329428, rs1410996 and rs3753394 were determined using real‐time PCR. Visual acuity outcome, number of injections and overall time of treatment were analyzed in dependence of the CFH genotype.

Results Patients received up to 15 injections with bevacizumab and the respective total treatment period ranged from 42 to 1182 days. Neither visual acuity, number of treatments nor duration of treatments correlated with any of the 6 CFH polymorphisms.

Conclusion None of the investigated polymorphisms of the CFH gene seem to play a statistically significant role regarding treatment success of bevacizumab in patients with exudative AMD.
Limbal stem cell deficiency in children
Authors: YEUNG A
Published: August 2012

Abstract not provided
Noninvasive assessment of the tear film stability in children
Authors: GICQUEL JJ , PISELLA PJ , BREMOND‐GIGNAC D
Published: August 2012

Purpose To evaluate tear break‐up time (BUT) with repeated higher order wavefront aberrations (HOA) measurements in children with Meibomian Gland Dysfunction(MGD).

Methods Wavefront aberrations up to the sixth order for a 4‐mm pupil were measured in 10 normal children (Group 1) and 10 children with severe MGD (Group 2) with corneal involvement, using the IRX3 (Imagine Eyes, Orsay, France) Hartmann‐Shack (H‐S) aberrometer. The aberrometry was performed once every second for up to 20 seconds. HOA measurements were performed 3 times in a row. HOA variations were compared with the BUT by the conventional fluorescein method (CFM°.

Results There was an excellent correlation between the HOA variation and the BUT recorded by the CFM in both groups. There was also an excellent reproducibility of the HOA measurements in all patients. BUT was significantly decreased (P<0.005) in all children in Group 2 compared to the normal tests subjects (Group 1).

Conclusion HS aberrometry is a non ivasive method, that has been used for the last decade for the assessment of the quality of vision in patients undergoing refractive surgery and cataract or clear lensextration. Studying the HOA variation is a valuable method for evaluating both the quality visionand the BUT in children with MGD.