bluuebunny/crossref_metadata_2025 huggingface dataset:
Classification of uveitis
Authors: ANDROUDI S
Published: August 2014

Classification and standardization of uveitis is important, as it enhances the precision and comparability of clinical research from different centers and assists in the development of a complete picture of the course of the disorders and their response to treatment. Attempts have been made to standardize some aspects of uveitis, and various classification criteria, inflammation grading schema, and outcomes criteria have been described. The most widely used classification of uveitis is the one devised by the International Uveitis Study Group (IUSG) in 1987, based on the anatomical location of the inflammation. This classification includes anterior uveitis (iritis, iridocyclitis, and anterior cyclitis), intermediate uveitis (pars planitis, posterior cyclitis, and hyalitis), posterior uveitis (focal, multifocal, or diffuse choroiditis, chorioretinitis, retinitis, and neuroretinitis) or panuveitis (anterior chamber, vitreous, retina, and choroid). In 2005, the Standardization of Uveitis Nomenclature (SUN) Working Group standardized a grading schema for aspects of intraocular intraocular inflammation, that is, anterior chamber cells, anterior chamber flare, and vitreous haze, was developed. Standardized definitions of outcomes, including reporting visual acuity outcomes, were approved. Today’s uveitis nomenclature has been revised regarding the anatomical location and the grade of inflammation, and supplemented by the inclusion of definitions for onset, duration and course.
Inflammatory and infectious causes of acute visual loss
Authors: SZATMARY G , POLGAR T
Published: August 2014

In this course comprehensive review of inflammatory and infectious causes of acute visual loss will be presented. This will include pre‐and retrochiasmal‐chiasmal visual pathway lesions. The lecture will focus on clinical presentation with localizing symptomatology and signs, recommended diagnostic tests, differential diagnosis and treatment possibilities. Also, known pathophysiology of various disorders will be discussed. At the conclusion of presentation the audience will be familiar with the wide range of neuro‐ophthalmological disease states that can result in acute visual loss.
Vascular causes of acute visual loss
Authors: KAWASAKI A
Published: August 2014

Acute optic neuropathy due to a vascular cause is essentially a syndrome of ischemic optic neuropathy. The mechanism of ischemic optic neuropathy involves a fall in perfusion pressure to the optic nerve which, in susceptible individuals, leads to infarction of the prelaminar or retrolaminar portion of the optic nerve. Ischemic optic neuropathy can be subdivided into anterior ischemic optic neuropathy and posterior ischemic optic neuropathy . A special category is post‐operative ischemic optic neuropathy. This lecture will discuss the clinical features that distinguish these forms of ischemic optic neuropathy , the risk factors associated with them and the approach to their management.
Variations and repeatability of macular pigment and its spatial profiles in south Asian and white subjects
Authors: HUNTJENS B , CTORI I
Published: August 2014

Purpose To investigate variations in macular pigment optical density (MPOD) between south Asian and white subjects and explore the repeatability of the MPOD spatial profile.

Methods MPOD was measured by heterochromatic flicker photometry in 77 south Asian and 60 white healthy volunteers aged 18 to 39 years, and repeated at a second visit in 24 subjects. The MPOD spatial profile was classified as typical exponential, or atypical ring‐like or central dip (IOVS 2014;55:1440‐1446).

Results We report excellent MPOD spatial profile repeatability (96%) between visits. Our findings showed 67% of all subjects with atypical ring‐like or central dip profiles were south Asian. Average integrated MPOD up to 1.8° (MPODav0‐1.8) was increased in subjects with atypical profiles (P < 0.0005). Half peak MPOD value occurred at an average 1.8 ± 0.7° for the typical profile group, which was significantly broader than that for the atypical ring‐like (1.5 ± 0.3°) or central dip profiles (1.4 ± 0.3°, P = 0.01). South Asian subjects had greater MPODav0‐1.8 (0.39 ± 0.13) compared to whites (0.32 ± 0.13 log units, P = 0.01) after controlling for age. White subjects with dark eyes had higher MPODav0‐1.8 than those with light eyes (P = 0.012).

Conclusion Classification of the MPOD spatial profile was highly repeatable. Since half peak MPOD value occurred within 1.8° eccentricity, the spatial profile and MPODav0‐1.8 together best describe the distribution of MPOD over the central area where macular pigment has its maximum effect. Further, atypical MPOD profiles offer increased MPOD over a more concentrated area centred on the fovea. Both parameters showed significant variations between the two ethnic groups.
Macular pigment optical density in a French population over 75 years old (MONTRACHET’s study: Maculopathy, Optic Nerve, nuTRition, neurovAsCular and HEarT diseases)
Authors: FLECK O , KOEHRER P , DANIEL S , BINQUET C , BRETILLON L , ACAR N , TZOURIO C , BRON AM , CREUZOT‐GARCHER C
Published: August 2014

Purpose The aim of our study was to describe the frequency of macular pigment distribution patterns in a french population‐based study over 75 years old.

Methods Three city study (3C) included 9294 subjects aged 65 years or more from three cities (Bordeaux, Dijon and Montpellier) in 1999. After a 10 year follow‐up, Dijon’s cohort had a complete ophthalmic examination in the MONTRACHET study. 1153 patients over 75 years were included. All patients had fundus photographs and macular pigment optical density measured by two‐wavelength autofluorescence. Pseudophakic patients without any retinal pathological conditions were included. In each patient, the eye with the best autofluorescence image quality was included.

Results One hundred fourty three eyes were selected (81 right eyes and 62 left eyes). Mean age was 82.0 ± 3.9 years, 71% (102) were women. Macular pigment optical density was 0.93 ± 0.22 density unit at the foveal center, 0.71 ± 0.20 density unit at 0.5° eccentricity, 0.59 ± 0.17 at 1°, 0.36 ± 0.12 at 2° and 0.09 ± 0.03 at 6°. Nineteen patients (13.3%) had ring‐like structure at mean 0.87 ± 0.19° eccentricity, 21 patients had intermediate distribution in density profile, 103 patients had strictly monotonic decline of macular pigment from the center to the periphery. There was no significant correlation between gender and macular pigment pattern (p = 0.36).

Conclusion This is the first study describing the frequency of the patterns of macular pigment distribution in an elderly pseudo‐phakic population. It would be useful to establish normative values in this age subgroup.
Human retinal pigment epithelial cells dying through autophagy are engulfed by professional and non‐professional phagocytes
Authors: TÓTH M , KRISTÓF E , DORÓ Z , VERÉB Z , ALBERT R , FÉSÜS L , PETROVSKI G
Published: August 2014

Purpose Inefficient removal of dying retinal pigment epithelial (RPE) cells by professional and non‐professional phagocytes can result in debris formation and development of age‐related macular degeneration (AMD). We aimed to study the clearance of autophagic dying RPE cells serving as a model for dry and wet type of AMD, respectively.

Methods Autophagic cell death was induced by serum deprivation and H2O2 co‐treatment in ARPE‐19 and primary human RPE (hRPE) cells. Annexin‐V FITC/PI labelling was used to determine the cell death rate, while autophagy detection was achieved by Western blot quantification of LC3 II/LC3 I ratio. The clearance of autophagic dying cells by non‐professional and professional phagocytes was quantified using flow cytometry.

Results An increasing percentage of dying RPE cells was observed in a time‐ and concentration dependent manner upon H2O2 treatment. Paralelly, an induction of autophagy could be detected within 2hrs of H2O2 treatment. Phagocytosis studies found autophagic dying cells to be efficiently and increasingly engulfed by both professional and non‐professional phagocytes over time.

Conclusion The clearance of autophagic dying RPE cells can be used as a model for studying both dry and wet type of AMD in vitro, as well as for testing future pharmacological agents for treating this disease.
Study of anti‐proliferative activity of ranibizumab, bevacizumab, pegaptanib and aflibercept on fibroblast‐like cell strain in vitro
Authors: LYTVYNCHUK L , S A
Published: August 2014

Purpose To evaluate the anti‐proliferative action of drugs that block vascular endothelial growth factor (anti‐VEGF: ranibizumab, bevacizumab, pegaptanib and aflibercept) upon fibroblast‐like cells, as in vitro model for studying their implication on fibroblast‐containing choroidal neovascular membranes (CNV).

Methods The cellular anti‐proliferative effects of the four anti‐VEGFs (cellular survival, mitotic‐ and polykaryocyte index, level of apoptosis) were evaluated over 5 days on the fibroblast‐like cell strain L929. Cellular growth‐kinetics indices (specific growth velocity (µ), population number doubling time (td) and reproduction velocity (n)) were calculated and used to reveal dose‐dependence of their anti‐proliferative activity.

Results The anti‐VEGFs could inhibit cellular survival, mitotic activity, and increase cellular heterogeneity of L929 cells in a dose‐dependent manner. The anti‐proliferative activity of the anti‐VEGFs was dose‐dependent, while the apoptosis level was proportional to the dose increase in all four cases. The cellular growth‐kinetics distinguished ranibizumab for having less aggressive anti‐proliferative action with increasing doses, which was due to compensation of cell death by proliferation; the rest of the anti‐VEGFs had anti‐proliferative and apoptotic activity prevail the cellular survival. Different concentrations of aflibercept caused insignificant effect upon the cellular mitotic index compared to controls.

Conclusion All four anti‐VEGF drugs exhibited marked anti‐proliferative and apoptotic activity upon fibroblast‐like cells in vitro. Overall, the explored effects might explain the fibroblast‐like response to anti‐VEGF drugs in vivo and be the cause for involution of CNVs.
Energy supply is critical for Müller cells ability to transport glutamate
Authors: KOLKO M
Published: August 2014

Purpose To study the effect of energy deprivation in Müller cells ability to maintain their function as well as their ability to protect retinal ganglion cells (RGC).

Methods The human Müller cell line, MIO‐M1 and primary mouse Müller cells were used to study changes in glutamate uptake, glutamate release, excitatory amino acid transporter (EAAT) protein expression, ATP levels and glycogen content, when cells were compromised from energy. Moreover, a co‐culture system of primary RGC cultures and primary Müller cells, separated by an insert, was used to evaluate the role of Müller cells in RGC survival.

Results EAAT1 and EAAT2 proteins were up‐regulated in energydeprived Müller cells and glutamate uptake was significantly increased in the absence of glucose, as opposed to conditions with sodium depletion or in the presence of the EAAT‐inhibitor tfb‐TBOA, in which glutamate uptake was decreased. The intracellular glycogen content decreased in a time‐dependent manner, whereas the ATP levels were sustained following energy deprivation. Co‐cultures of RGC and Müller cells revealed better survival of glutamate treated RGC in the presence of Müller cells compared to controls. Energy deprivation of Müller cells enhanced their ability to protect RGC.

Conclusion The present findings revealed an up‐regulation of EAAT1 and EAAT2 in energy compromised Müller cells as well as an increased ability to remove glutamate from the extracellular space. Co‐cultures of RGC and Müller cells revealed a protective role of Müller cells when RGC were exposed to glutamate. Hence, energy failure may result in an increased ability to protect RGC from glutamate‐induced excitotoxicity, whereas malfunction of glutamate uptake in Müller cells may contribute to RGC death.
Activation of cannabinoid receptor CB2 in ARPE‐19 cells stimulates the release of inflammatory cytokines via activation of the ERK pathway
Authors: HYTTI M , PIIPPO N , KORHONEN E , SALMINEN A , KAARNIRANTA K , KAUPPINEN A
Published: August 2014

Purpose Endocannabinoid receptors have been suggested to be a possible therapeutical target in age‐related diseases. Particularly CB2, the receptor primarily responsible for the immune modulatory effects of cannabinoids, might be a valuable target in diseases, such as age‐related macular degeneration, where inflammation is known to be a key player. In this study, we have evaluated the effects of CB2 activation on the viability and inflammatory response of retinal pigment epithelial cells.

Methods We cultured ARPE‐19 cells until confluent and treated the cells with the selective CB2 agonist JWH‐133. To assess the effect of CB2 activation on oxidatively stressed cells we treated some cells with the lipid peroxidation end product 4‐Hydroxynonenal (HNE) after the JWH‐133 stimulation. The effects of the treatments on cell viability were assessed and inflammatory cytokine expression and signaling protein activation were measured by ELISA.

Results Our results show that 10µM JWH‐133 robustly increased the production of interleukin (IL) 6 and IL‐8 in both HNE‐treated and untreated cells. Investigation of the MAPK signaling pathway showed that JWH‐133 at this concentration increased the phosphorylation of ERK1/2.

Conclusion Our results show that JWH‐133, a selective agonist of the cannabinoid receptor CB2, stimulates an inflammatory response in ARPE‐19 cells. The release of inflammatory cytokines seems to be mediated by the increased activity of the MAPKinase ERK1/2. Taken together, our results suggest that CB2’s role as a potential therapeutical target in retinal pigment epithelium should be more carefully analyzed in future studies.
Pathophysiologic mechanisms based treatment for RVO related macular edema
Authors: POURNARAS C
Published: August 2014

The retinal vein occlusion (RVO) related to visual loss, results from changes in the blood‐retina barrier leading to the formation of an extracellular retinal edema; and conconmmitant arteriolar vasoconstruction, leading to tissue hypoxia, intracellular retinal edema and neuronal cell death. Patient’s evaluation requires the definition of the pathogenic role of systemic diseases affecting the retinal vessels wall. In addition, hemodynamic modifications of the retinal blood flow and primary and secondary thrombophilias, may trigger the manifestation of the RVO occlusive event. Current treatment of acute RVO aims to restore venous circulation. In that sense, isovolemic hemodilution leads to an increase of ocular blood flow and regression of tissue hypoxia. Grid macular photocoagulation, reversing the inner retinal tissue hypoxia, improves visual prognosis in eyes with macular edema following branch RVO. The intra‐vitreal treatments using anti‐VEGF and anti‐inflammatory drugs, reverse the veins abnormal permeability, relieve the macular edema, either in branch or central RVO, offering new insights for the management of those pathologies.
BRVO treatments in 2014
Authors: PETROPOULOS IK
Published: August 2014

Until recently, laser photocoagulation was the standard of care for branch retinal vein occlusion (BRVO). The recent development of intravitreal pharmacotherapy has revolutionized the management of BRVO and has expanded our treatment options. Intravitreal anti‐VEGF agents (ranibizumab, bevacizumab, aflibercept) and a sustained‐release dexamethasone implant have been shown effective to treat BRVO‐related macular edema by randomized studies and/or case series, offering favorable anatomical and visual outcomes. Still, long‐term repeated injections may be needed and head‐to‐head comparisons of these treatment modalities have not been performed. As for treatment duration, new data suggest that half of the patients may be cured after 2 years from the onset of the disease, whereas the other half will probably need repeated injections for at least 4 years. A better control of the underlying systemic disease (mostly arterial hypertension) and the identification of the proper time to perform laser photocoagulation could further improve prognosis. Safety and efficacy profiles and updated indications of each treatment modality with representative examples will be discussed.
A standardised ‘off the shelf’ substrate for enhanced tissue engineering
Authors: HOPKINSON A , BRANCH MJ , DUA A
Published: August 2014

Purpose Amniotic membrane (AM) is a popular ophthalmic tissue engineering adjunct. We previously developed a highly effective thermolysin‐based denuding technique that preserves basement membrane integrity This technique has been validated clinically using fresh frozen AM (FAM). We now propose a standardised dry‐prepared ‘off the shelf’ AM tissue engineering substrate.

Methods Dry preserved thermolysin denuded AM (DAM), and FAM denuded with ethylenediaminetetraacetic acid (EDTA), and dispase ‐based methodologies were prepared. Denuding efficiencies were compared using electron microscopy. The effect of denuding on AM molecular composition was investigated and characterised using proteomics. The propensity of DAM to support stem cells was explored using fluorescent immunohistochemistry for defined markers.

Results Electron microscopy demonstrated thermolysin denuding efficiency was comparable in FAM and DAM. Proteomic analyses showed effective removal of epithelial cell proteins in DAM, but not EDTA–based denuding techniques. Whilst similar enzymatic activity to thermolysin, mechanical scraping reduces the efficacy of dispase denuding. Collagens IV, VI, periostin, βig‐h3 and VLA‐6 are targets of thermolysin activity. DAM maintains stem cell characteristics and is most effective in preventing differentiation.

Conclusion Conventional EDTA and dispase procedures for preparing AM for tissue engineering are ineffective at removing cells whilst preserving the basement membrane. Combining our novel thermolysin denuding and dry preservation techniques improves the overall quality of AM for tissue‐engineered constructs. Therefore, we propose a fist of its kind, stable and dry‐stored ‘off the shelf’ construct for enhanced ocular surface tissue engineering.
Corneal endothelial cells from old donors: differentiation, senescence, proliferative capacities and optimized culture conditions
Authors: HA THI B , HE Z , FOREST F , THURET JY , PISELLI S , PERRACHE C , PEOC'H M , DUMOLLARD JM , ACQUART S , GAIN P , THURET G
Published: August 2014

Purpose The intrinsically low proliferative capacity of human corneal endothelial cells (CECs) and their rapid senescence in in vitro culture constitute major limitations for cell bioengineering destined to treat endothelial dysfunctions. In Europe, the mean donor age of 70 adds a supplementary difficulty to the complex equation. Aim: to clarify whether old donor corneas could be however used for cell expansion

Methods Morphology and differentiation of central and peripheral CECs were analyzed by immunostaining of ion transport‐related proteins, progenitor and neuronal markers in corneas retrieved in donor >50 years. The proliferative capacity of CECs from organ‐cultured corneas was quantified by EdU proliferation assay. The differences of central vs peripheral CECs were further characterized in vitro by studying their migration, proliferation and differentiation in serum‐containing medium.

Results Central CECs highly expressed specific ion transport‐related proteins, and had a high senescence level. On the contrary, CECs located in the periphery or extreme periphery were less specialized, expressed progenitors and neuronal markers and were more prone to endothelial‐mesenchymal transformation in serum‐containing medium. With a new culture sequence that limited proliferation and maintained differentiation, corneas from donors >70 yo, could successfully be used to reconstitute a monolayer of stable endothelial phenotype with ECD of 2000 cells/mm2 but require pooling of corneas.

Conclusion This work could allow to “recycle” the 20% of corneas usually discarded by eye banks because of age‐related ECD decline
Ocular chronic graft versus host disease after allogeneic hematopoietic stem cell transplantation – preliminary data
Authors: JEPPESEN H , LINDEGAARD J , SENGELOEV H , JULIAN HO , PRAUSE J , HEEGAARD S
Published: August 2014

Purpose Allogeneic hematopoietic stem cell transplantation(HSCT) is a curative therapy for a number of malignant and non‐malignant hematological diseases. Allogeneic HSCT can be performed in several ways; donor cells can be obtained from bone marrow(BMT), peripheral blood(PBSCT) or cord blood(CBT). Ocular chronic graft versus host disease(cGVHD) is a major contributor to long‐term morbidity after HSCT. The purpose of this study was to report the frequency of ocular cGVHD after allogeneic HSCT.

Methods Retrospective examination of 233 charts of patients (adults>15years) who underwent consecutive allogeneic HSCT from January 2000‐june 2011 at Copenhagen University Hospital (Rigshospitalet). All allogeneic HSCT in Denmark are performed at this hospital. All patients were examined ophthalmologically before the transplant, yearly after the transplant and ad hoc if any ophthalmic problems occurred. The diagnosis of ocular cGVHD was made according to the NIH consensus criteria.

Results Fifty‐eight(25.3%) fulfilled the diagnostic criteria of ocular cGVHD, 16 out of 78(20.5%) in the BMT group, 41 out of 152(27.0%) in the PBSCT group and 1 out of 3(33.3%) in the CBT group. Male:female ratio was 40:18(2.22) (in the cohort 146:87(1.68)). Median time of onset was 24.3 months after HSCT(range 4.9‐146.1). In the cohort median age was 45.2 years(rage 15.2‐71) at transplantation time and 55.5 years(18.43‐69.0) when ocular cGVHD was diagnosed. Median time of follow‐up was 24.8 months(range 0.4‐147.6).

Conclusion Out of 233 patients who received allogeneic HSCT, 59(25.3%) developed ocular cGVHD. The median time of onset was 24.3months after transplantation and median age at onset was 55.5 years.
Filtering blebs functionality after trabeculectomy: a clinical and in vivo confocal microscopy study
Authors: VIEIRA L , SANTOS A , LISBOA M , AMARAL A , CUNHA JP , MADURO V , REINA M
Published: August 2014

Purpose To evaluate macroscopic and microscopic morphological features of filtering blebs after trabeculectomy with Mitomycin C (MMC) or 5‐Fluorouracil (5‐FU) and correlate them with function.

Methods Retrospective case control study of 28 eyes (21 patients) submitted to trabeculectomy (15 with MMC and 13 with 5‐FU) and 11 eyes (10 patients) treated medically. Ophthalmologic examinations included Goldmann applanation tonometry, slit‐lamp examination and photography (Moorfields bleb grading system classification) and in vivo confocal microscopy (Heidelberg Retina Tomograph II, Rostock Cornea Module). Eyes were classiﬁed into 3 groups: control, functioning blebs (Intraocular pressure (PIO)<21mmHg without therapy) and nonfunctioning blebs (PIO<21mmHg with therapy or ≥21mmHg).

Results Biomicroscopically, functioning blebs, in comparison to nonfunctioning blebs, showed a significant increase in the central (p=0,009) and maximal (p=0,017) bleb area and a decrease in central (p=0,021) and maximal (p=0,028) bleb vascularization. When comparing successful with failed blebs, in vivo confocal microscopic showed a significant increased number of epithelial microcysts (p=0,014), a liquid content of epithelial microcysts (p=0,008), a lower density of stromal connective tissue (p=0,039) and a decreased number (p=0,041) and diameter (p=0,045) of the vessels. All morphological findings were similar when comparing the usage of MMC with the usage of 5‐FU (p>0,05).

Conclusion This study suggests that both biomicroscopy and in vivo confocal microscopy findings can lead to a better understanding and management of filtering blebs.
Self‐tonometry is useful to detect IOP elevations in DALK patients with apparently normal intraocular pressures
Authors: SMEDOWSKI A , TARNAWSKA D , WYLEGALA E
Published: August 2014

Purpose To perform increased intraocular pressure (IOP) screening in non‐glaucomatous patients after deep anterior lamellar keratoplasty (DALK) due to keratoconus with normal IOP measured during control visits.

Methods Ten non‐glaucomatous patients, who underwent DALK procedure due to keratoconus were included into study. Patients were measuring IOP using self‐tonometer Icare One (Icare, Finland) continuously for 30 days, 3 times per each day. Additionally patients were checked by ophthalmologist 3‐times during follow‐up time in Outpatient Clinic, where applanation tonometry and central corneal thickness measurements were performed. After 30‐days, self‐measured IOP was evaluated for rises above 21 mmHg as well as rises above mean GAT values measured during control visits.

Results Mean IOP measured with GAT and adjusted according to CCT was 15 mmHg and ranged between 11 and 19 mmHg. There were no values above 21 mmHg reported during follow‐up time. In Icare One measurements, all patients showed incidents of IOP values higher than measured with GAT, however mean values ranged between 10‐18 mmHg. Six out of 10 patients revealed to have IOP elevations higher than 21 mmHg between control visits (with maximum values up to 46 mmHg), and this elevated values constituted from 3.3 up to 20.0 % of all self‐measurements.

Conclusion Self‐tonometry with Icare One might be useful tool to identify patients who develop undetectable IOP increases between control visits. This can help in prevention of vision loss and transplant procedure failure in DALK patients.
Infectious uveitis
Authors: PLEYER U
Published: August 2014

The differential diagnosis of infectious uveitis is broad and an essential step in any initial work‐up. Underlying organisms include all types of infectious agents. The more common infectious causes of uveitis include viruses, T. gondii, T. pallidum, Mycobacterium tuberculosis that will be covered in this course. Based on clinical features further diagnostic tools will be discussed and critically reviewed. In particular newer evolving techniques in the investigations will be included, e.g. intraocular fluid evaluation for polymerase chain testing for the genome and antibody synthesis against the causative organisms.
Subretinal Mononuclear Phagocyte survival and accumulation in AMD
Authors: SENNLAUB F
Published: August 2014

The subretinal space, located between the RPE and the photoreceptor outer segments, is a zone of immune privilege as a consequence of immunosuppressive RPE signals, possibly to limit or subvert inflammatory damage. Age related macular degeneration (AMD) is associated with a breakdown of the subretinal immunosuppressive environment and infiltration and activation of mononuclear phagocytes (MPs, a family of cells that include microglial cells, monocytes, and macrophages) in both late forms of AMD. The molecular mechanisms that provoke the breakdown of local immuno‐suppression in AMD are unknown. Our recent data indicates that Apolipoprotein E (APOE), a lipoprotein that exists in three isoforms in human, participates in this process. We demonstrate that increased APOE secretion from MPs, observed in MPs carrying the AMD‐associated APOe2 allele, leads to prolonged subretinal MP survival and accumulation. We show that subretinal MP accumulation in APOe2 mice is associated with photoreceptor degeneration and excessive experimentally induced choroidal neovascularization, major hallmarks of late AMD. Our results provide a molecular mechanism of local breakdown of immuno‐suppression rationale for the increased AMD‐risk of APOe2 carriers.
Radiation effects on light scattering and cataract formation in the lenses of interventional radiologist and cardiologists
Authors: WEGENER A , HÖCK A , SCHEIDEMANN‐WESP U , CÁMARA R , HAMMER GP , VOßMERBÄUMER U , LASER‐JUNGA H , SINGER S
Published: August 2014

Purpose There is little information about exposure to dosages below 500 mSv. This pilot study aimed at investigating the effects of low dose radiation on lens transparency in occupationally exposed interventional cardiologists and radiologists.

Methods Physicians who have performed fluoroscopically guided procedures for at least 5 years were recruited in the areas of Cologne‐Bonn and Rhine‐Main together with their non‐exposed colleagues. A questionnaire has been developed to estimate occupational exposure. Exclusion criteria comprised corticosteroid treatment, radiotherapy, chemotherapy and glaucoma. Changes in lens transparency and cataract formation were determined by slit lamp microscopy including LOCS III grading, slit lamp photography and Scheimpflug/Pentacam® imaging.

Results The prevalence of lens opacification mainly found in the nuclear region was 52% (95% CI: 30‐74%) among interventional physicians and 31% (95% CI: 9‐61%) among their non‐exposed colleagues. Densitometric analysis of the cornea demonstrated a mean value 52,8% (SD: 7,4) in exposed participants compared to 45,9 % (SD: 7,2) in non‐exposed colleagues. In the lenses layers 4 (deep cortex) and 5 (supra‐nuclear layer) evidenced higher mean densities (40,5% (SD: 3,9%) vs. 31,6% (SD: 6,9%) in layer 4 and 27,5% (SD: 1,9%) vs. 23,7% (SD: 4,3%) in layer 5).

Conclusion The data from the ophthalmological examinations demonstrated generally normal findings. However, classification of the mostly small cataracts and densitometric analysis of cornea and lens evidenced that low dosage exposure to ionizing radiation has an effect on corneal and lenticular transparency, albeit on a subclinical level.
Strategies to reduce cytokine levels could suppress PCO progression
Authors: ELDRED JA , SPALTON DJ , WORMSTONE IM
Published: August 2014

Purpose Posterior capsule opacification (PCO) develops after cataract surgery. Open bag IOLs, in contrast to current IOL devices, separate anterior and posterior capsules (PC) and are proposed to aid wash out of cytokines in the capsular bag that may promote PCO. The current study assessed the correlation between cytokine availability and cell growth on the human capsular bag.

Methods To assess cell growth in different volumes (1.5 Vs 6ml) of Serum‐Free (SF) EMEM we employed a human capsular bag model. We further adapted the capsular bag system, such that radial incisions were made in the anterior capsule, which was then folded back and secured to a dish (a fully open bag model). Cell growth was observed by phase‐contrast microscopy and quantified by ImageJ software. Cytokines were detected by Bioplex suspended bead array at culture day 2. Immunocytochemistry was used to detect myofibroblasts (using the marker alpha smooth muscle actin;αSMA) and cell density.

Results Increasing media volume significantly reduced the cell coverage rate on the central PC. A significant cytokine reduction was observed (9 of the 27 assessed) in 6ml cultures compared to 1.5ml counterparts; no cytokines were significantly elevated. At end‐point (28 days) capsular bags maintained in 6ml of media exhibited decreased cell density in the peripheral PC and reduced αSMA expression. Fully open capsular bags cultured in 1.5 or 6ml SF EMEM had limited cell progression onto the PC in both volumes. Fully open capsular bags exposed to 5% human serum demonstrated rapid colonisation of the PC

Conclusion Reduced cytokine availability is associated with impaired cell growth on the capsular bag. It is likely that open bag devices will restrict cytokine levels and improve the management of PCO.
Safety and efficacy of intra‐operative sub‐Tenon injection of 2% lidocaine in cases of unexpected intra‐operative floppy iris syndrome (IFIS)
Authors: KLYSIK A , KORZYCKA D
Published: August 2014

Purpose To report safety and efficacy of intra‐operative injection of 2% lidocaine during small incision cataract surgery in cases of unexpected intra‐operative floppy iris syndrome.

Methods 4 patients, undergoing routine cataract surgery, who were exposed to alfa‐adrenergic inhibitors, and it was not known pre‐operatively, and in whom intra‐operative floppy iris syndrome occurred unexpectedly. 2.5 ml of 2% lidocaine was injected into the sub‐Tenon space in response to intra‐operative iris prolapse and pupillary constriction. Injection was performed following hydrodissection in 3 of 4 cases and hollowing capsulorrhexis in 1 of 4 cases. The surgery was video‐taped from the beginning of the injection.

Results No further iris prolapse was noted in any case, nor further pupillary constriction. Iris plane was stabilized. There were no further complications of cataract surgery. Patients were comfortable and pain free for the rest of the procedure.

Conclusion Intra‐operative injection of 2% lidocaine into the sub‐Tenon space is a safe way of reversing iris floppiness and the tendency to iris prolapsed in cases of unexpected intra‐operative floppy iris syndrome. It is an alternative to other intra‐operative techniques to manage IFIS, which provides pain relief as well as iris stabilization.
Topical caffeine induces mydriasis in animals under ketamine‐xylaxine anesthesia
Authors: SÖDERBERG P , YU Z , TALEBIZADEH N , KRONSCHLÄGER M
Published: August 2014

Purpose To determine the effect of topically applied caffeine on the pupil diameter during ketamine‐xylazine anesthesia

Methods Six‐week‐old Sprague‐Dawley rats were anesthetized with ketamine xylazine intraperitoneally. Caffeine, 72 mM, dissolved in vehicle, 9 mg/ml, hydroxypropylmethyl cellulose dissolved in water, or the vehicle only, was topically applied. Animals were kept under room light conditions. In experiment I, caffeine in vehicle was topically applied to one eye and vehicle only to the other eye in 10 animals. In experiment II, caffeine in vehicle was applied to both eyes in one group of 10 animals and vehicle only to another group of 10 animals. In both experiments, pupil diameter was measured on both eyes. Measurements were taken immediately after initiation of the anesthesia, and 10, 20, 40 and 60 min. later.

Results In experiment I, vehicle only caused a slight transient increase of pupil diameter, peaking around 20 min. after initiation of anesthesia and then decreased below baseline. Caffeine in vehicle caused an initial fast decrease in pupil diameter and the decrease rate leveled out towards 60 min. after initiation of anesthesia. In experiment II, vehicle to both eyes induced a transient increase in pupil diameter that returned to baseline. Caffeine and vehicle on both eyes induced an exponentially declining decrease towards asymptote miosis. The miosis reversed to mydriasis after topical application of tropicamide 5 mg/ml.

Conclusion Topically applied caffeine induces miosis in a ketamine‐xylazine anesthetized rat. There is some systemic effect on pupil diameter of the currently used topical application of caffeine. The miotic effect of topically applied caffeine is reversed by tropicamide.
Müller cells ‐ structural and physiological functions
Authors: REICHENBACH A
Published: August 2014

In 1851, Heinrich Müller discovered what he called ‘radial fibers’ and what we now call Müller cells, as the principal glial cells of the vertebrate retina. During the past decades it became evident that they are essential constituents of the retinal tissue. Müller cells appear to constitute the ‘core’ of columnar units of clonally and functionally related groups of neurons. Their primary function is to support neuronal functioning (by increasing the signal‐to‐noise ratio of information processing) and survival (by maintaining a metabolic ‘symbiosis’ with the neurons). Much of this dual role of glial cells involves specific homeostatic mechanisms. Current progress in the field is achieved by the application of various novel experimental methods (cellular electrophysiology, imaging methods, optical and biomechanical measurements, and others). Herewith it was shown that Müller cells increase the signal‐to‐noise ratio of retinal information processing by, for instance, (i) guiding the light towards the photoreceptor cells, (ii) removing excess neurotransmitter molecules from extracellular space, and (iii) performing an efficient clearance of excess extracellular potassium ions after neuronal excitation.
Microglial cell reaction after optic nerve lesions
Authors: VILLEGAS PEREZ MP , GALINDO‐ROMERO C , VALIENTE‐SORIANO FJ , JIMENEZ‐LOPEZ M , SOBRADO‐CALVO P , AGUDO‐BARRIUSO M , VIDAL‐SANZ M
Published: August 2014

Microglial cells may be involved in the degeneration and regeneration processes of Retinal Ganglion Cells (RGCs). Optic nerve (ON) lesions induce microglial cell activation both in goldfish (an animal with important regeneration capabilities; Salvador‐Silva et al., 2000) and rodents (animals with limited regenerating capabilities; Sobrado‐Calvo et al., 2007; Galindo‐Romero et al., 2013). The microglial cell reaction after an ON lesion is common to all the animal models studied and typically includes: increased enzyme activities, morphologic changes and cell hyperplasia. Because these reactions are found in regenerating and non‐regenerating animal models, they may represent a general response of the microglia that is directed towards helping the regeneration process. However, the location, severity and timing of the reaction varies depending on the animal model, amount of RGC death and type of lesion used and on other factors such as whether other eye lesions, trophic or other factors are administered concomitantly. Therefore the microglial cell reaction after an ON lesion can be modified externally and may subsequently influence the degeneration and regeneration processes.
The influence of ocular hypertension on retinal glial cells
Authors: ROJAS B , GALLEGO B , DE HOZ R , RAMIREZ AI , SALAZAR JJ , TRIVINO A , RAMIREZ JM
Published: August 2014

We describe the effects of unilateral laser‐induced ocular hypertension (OHT) in the macroglia and microglia of eyes with OHT and their contralateral normotensive untreated eyes. In both eyes, the glia was reactive even though, contrary to OHT‐eyes, no retinal ganglion cell loss or abnormalities in the electroretinogram were found in contralateral eyes. With respect GFAP immunostaining there were differences between contralateral and OHT‐eye. Signs of microglial activation in contralateral and in OHT‐eyes affected all retinal layers, including: morphological changes, migration, increased cell number, upregulation of activation markers and quantification of the area occupied by Iba‐1+ cells and of the arbor area of Iba‐1+ cells. In microglia, MHC‐II upregulation in contralateral eyes was similar to that in OHT‐eyes. By contrast, MHC‐II upregulation in macroglia was observed mainly in astrocytes in contralateral eyes and in Müller cells in OHT‐eyes. Only eyes with OHT had rod‐like microglia and rounded Iba‐1+ CD68+ CD86+ cells. Glial differences between contralateral and OHT‐eyes could help us to understand glaucoma pathophysiology and develop new strategies for treatment.
Ocular immunology and vitreoretinal surgery “face to face"
Authors: NERI P , ARAPI I , PIRANI V , CARBONARI G
Published: August 2014

The clinical assessment of most of vitreo‐retinal (VR) inflammations is often challenging: the clinical picture of such diseases can be overlapping and, despite the advances in medical technologies, the diagnostic tools might not provide data which can be conclusive. At this point, the possibility to take a vitreous tap via pars plana can help the ocular immunologist to differentiate between different sub‐sets of infectious diseases and masquerade syndrome. The term "Masquerade Syndrome" was first used in 1967 to describe a case of conjunctival carcinoma that manifested as chronic conjunctivitis. Masquerade syndromes are disorders that occur with intraocular inflammation and are often misdiagnosed as a chronic idiopathic uveitis. Very often mesquerade syndrome is a synonymous of intraocular lymphoma which can present insidious clinical pictures, which are very often confused. The possibility to test the interleukines' ratio and to analyze the cytology represents a great scientific advance. A clearer role of VR surgery is played for all the complications of uveitis, such as uveitic retinal detachment, inflammatory macular pucker and dense persistent vitritis. VR surgery can warrant an important contribution to the clinical outcome.
Vitrectomy in uveitis
Authors: MARIOTTI C , SAITTA A , NICOLAI M
Published: August 2014

Today, pars plana vitrectomy (PPV) for ocular inflammatory diseases represents a powerful tool for those cases non responding to medical treatment. PPV has been increasingly performed for both diagnostic and therapeutic purposes in the management of patients with uveitis. PPV offers a surgical option in clearing vitreous opacities and repairing inflammatory related complications, such as epiretinal membrane, retinal detachment, vitreous haemorrhage, cyclitic membrane removal for non‐responsive hypotony. The evolution of both technology and surgical techniques for PPV has been very important in order to develop a step forward in approaching and treating ocular inflammatory diseases.
The role of retinal and choroidal biopsy
Authors: DA CRUZ L
Published: August 2014

Chorio‐retinal biopsy is relatively infrequently used for the diagnosis of infiltrative processes of the posterior segment. It is used in cases where local and systemic clinical features are insufficient to determine whether the infiltration is inflammatory, infective or neoplastic. In most of the few cases described in the literature the aim is to exclude or diagnose lymphoma. The cases published to date suggest the diagnostic pick‐up rate is good relative to vitreous biopsy and it is possible that the diagnosis is confirmed from Chorioretinal tissue biopsy when the vitreous biopsy from the same operation is negative. Diagnoses of many types of pathology including viral and non‐viral retinitis, lymphoma, tuberculosis and non malignant inflammatory infiltration have all been described in the literature. In the majority of cases reported in the literature the diagnosis of lymphoma is clearly made or excluded definitively. The technique of carrying out the surgery has been well described and the reported morbidity of the procedure is minimal. In this presentation The technique, surgical issues and complications will be discussed as well as the outcomes from the published literature concerning these cases.
Clinical manifestations of NMO
Authors: YU‐WAI‐MAN P
Published: August 2014

Neuromyelitis optica (NMO), also known as Devic’s disease, is an idiopathic inflammatory demyelinating disease of the central nervous system (CNS) that preferentially targets the optic nerve and the spinal cord. Due to the significant risk of permanent visual and neurological impairment in NMO, rapid diagnosis and the prompt initiation of the most appropriate treatment are essential The current diagnostic criteria require a clinical history of optic neuritis and transverse myelitis accompanied by at least two of the following three supportive criteria: (i) brain MRI not diagnostic of multiple sclerosis (MS); (ii) spinal cord MRI with contiguous lesion over three or more vertebral segments; and (iii) IgG seropositivity against the aquaporin‐4 (AQP4) water channel. The development of optic neuritis and transverse myelitis can be simultaneous or sequential. In this presentation, the classical clinical features of NMO will be reviewed and put in the context of other demyelinating CNS disorders. Recent clinicopathological studies have revealed striking differences between NMO and prototypic MS, establishing them as distinct entities, and with important practical implications for the management of these two disorders.
Overview of treatment of NMO
Authors: DE SEZE J
Published: August 2014

Recent studies has shown that neuromyelitis optica (NMO) is clearly a different disease compared with multiple sclerosis (MS). Several MS drugs may increase inflammation process in NMO, especially interferon beta, natalizumab and fingolimod. This fact has 2 important consequences : First the diagnosis of NMO has to been done as soon as possible in order to differentiate NMO and MS patients. Second, as NMO is an antibody mediated disease immunosuppressive grugs should be proposed if the diagnosis is done. First step therapy is based on azathioprine, mycophenolate mofetil and methotrexate. Second step therapy are Rituximab, cyclophosphamide and mitoxantrone. Several drugs (with atarget on complement subunites or several cytokine, especially IL6 or IL17) are currently tested in phase II or III trials. Symptomatic treatments directed against fatigue, urinary or bowel dysfunctions, pain remains also of importance.

Commercial interest
Dysregulated para‐inflammation in the pathogenesis of AMD
Authors: XU H
Published: August 2014

Para‐inflammation is an adaptive response of the immune system to low‐degree noxious tissue insults. The physiological purpose is to maintain homeostasis and restore functionality. During ageing, retina suffers from low levels of sustained oxidative insults. As a result, a para‐inflammatory response characterised by microglial activation, subretinal migration and complement activation, is initiated. We propose that a dysregulated para‐inflammatory response may turn into a detrimental chronic inflammation, which may contribute to tissue damage and disease progression. The role of dysregulated para‐inflammation in the pathogenesis of age‐related macular degeneration will be discussed in this presentation.
Testing vision: one cone at a time
Authors: ROORDA A
Published: August 2014

In humans, gaining experimental access to single sensory receptors ‐ photoreceptors specifically ‐ is a challenge, yet it is crucial for learning how the signals arising from each receptor are transformed into perception. By combining adaptive‐optics microstimulation with high‐speed eye tracking, we show that retinal function can be probed at the level of the individual cone photoreceptor in living eyes. This talk will describe the development and applications of our adaptive optics confocal imaging system which we use to track, target and deliver visible light stimuli to single cones or selections of cones. Highlighted applications will include our ongoing efforts to learn about the neural circuits that underlie human spatial and color vision.
Secondary polypoidal choroidal vasculopathy (PCV)
Authors: DONATI G , POURNARAS C
Published: August 2014

Polypoidal choroidal vasculopathy (PCV) was first described as polypoidal, subretinal, vascular lesions associated with serous and hemorrhagic detachments of the retinal pigment epithelium (RPE) in a series of patients (10/11 were women) by Yannuzzi. PCV is most commonly diagnosed in patients between the ages of 50 and 65 years. Although more frequently being an primary disease associated to high blood pressure, it may also be secondary to others diseases such as AMD, Central Serous Chorioretinopathy (CSC), ocular radiotherapy, Pseudoxanthoma Elasticum not related to systemic hypertension. Secondary PCV was first reported to occur in AMD patients. Prevalence rates of 4%, 7.8%, 8.2%, and 9.8% have been reported in Caucasian patients with presumed age‐related macular degeneration (AMD). In Asian patients with diagnosed AMD the prevalence rates are even higher, between 23.9% and 54.7%. PCV was categorized as a subtype of neovascular AMD. Vascular proliferative changes associated with PCV in AMD form a network of vessels ending with saccular polypoidal lesions. ICG angiography can be used to distinguish it from classic or occult CNV as usually seen in AMD. PCV is demonstrated by ICG angiography as a prominent vascular network in the early stages of the study and an area of clearing or so called “washout” of the dye in the late stage. On OCT examination the polypoidal lesions are seen as more steep domelike elevations of the highly reflective RPE layers with underlying moderate reflectivity then seen in PEDs. The regions of the branching choroidal vascular networks are visualized as double reflective layers comprising nodular RPE and another highly reflective layer beneath the RPE. According to the EVERST and LAPTOP studies either Anti‐VEGF monotherapy alone or associated to Photodynamic therapy is the best therapeutic option actually available to treat PCV in AMD patients and should be considered as first line therapy in all secondary cases.