bluuebunny/crossref_metadata_2025_split huggingface dataset:
White dot syndromes
Authors: ANDROUDI S 
Published: November 2010

Abstract Purpose The white dot syndromes (WDS) are a group of distinct clinical entities characterized by one common underlying feature: the presence of multiple “spots” in the fundus, usually in the deep retina or choroid without any other systemic manifestations. Methods The disorders are relatively rare and include the following entities: acute posterior multifocal placoid pigment epitheliopathy (APMPPE), multiple evanescent white dot syndrome (MEWDS), birdshot retinochoroidopathy (BSRC), serpiginous choroidopathy (SC), multifocal choroiditis and panuveitis (MCP), punctate inner choroidopathy (PIC), subretinal fibrosis and uveitis syndrome, and presumed ocular histoplasmosis syndrome (POHS). Results Despite the fact that many infectious and noninfectious inflammatory diseases may present with multifocal chorioretinal lesions, the entities included in the WDS share some features which make them a particular group of ocular disorders. In fact, the WDS would be better labeled as idiopathic inflammatory multifocal chorioretinopathies, since with the exception of diffuse unilateral subacute neuroretinitis, their causes are still unknown. Conclusion Because the specific diagnosis may have profound implications on therapy and prognosis, it is important to narrow the diagnosis to the greatest extent possible, even in patients with seemingly atypical findings. The correct diagnosis of WDS is important because the management is totally different from one another. Some of them are self‐limited and have good visual outcomes without treatment, while others are associated with serious retinal and choroidal sequelae, which can result in severe visual loss even after adequate immunosuppressive therapy.
Immunosuppressors and biologic agents
Authors: DICK AD 
Published: November 2010

Abstract Purpose To overview the contemporary therapeutic approaches to treatment of non‐infectious non‐infective ocular inflammatory disease. Treatment of non‐infectious uveitis has over past 15 years expanded from the use of traditional therapies including corticosteroids and immunosuppressants to the deployment of targetting the immune response with biologic therapies with monoclonal antibodies and immunoadhesins. Methods The talk will overview the evidence of effect of immunosuppressants in the treatment of uveitis, the role of predicting steroid responsiveness, the use of monotherapy with immunosuppression and finally the pathways and evidence of success of biologic therapy. Results The concommitant use of immunosuppression is an important aspect to the adequate treatment of uveitis. This ensures adequate control of inflammation whilst reducing the need for comcomitant steroids thereapy. Moreover, monotherapy is equally efficacious in the control of some forms of uveitis. Neverthless there are patients who remain refractory to therapy, and in particular treatment of sight threatening Cystoid macular oedema. The use of targetted biologic therapy has gained increasing evidence to now lead to clinical trials in the use of anti‐TNF and anti‐IL17 agents. Conclusion There is now a recognised algorithm to treat aggressively and early patients with sight threatening disease. The appropriately timed use of immunosuppression and moreover increasingly earlier intervention with biologics has the promise to alter prognosis and outcome of such blinding disorders.
Take home messages
Authors: BODAGHI B 
Published: November 2010

AbstractThis basic level course addressed the pathophysiology of ocular inflammation, its classifications and the major subtypes of uveitis, highlighting some of the new developments in uveitis that have become available in the past years and have contributed to the improvement in the care of the patients. It put forward clinical knowledge in uveitis, diagnostic tools as well as therapeutic strategies that allow ophthalmologists to go further in the precision of the assessment and monitoring of intraocular inflammatory activity as well as in therapeutic intervention.
Ultrastructural features of camel cornea
Authors: ALMUBRAD TM , KHAN F , AKHTAR S 
Published: November 2010

Abstract Purpose Epithelium, Bowman’s layer, stroma, Descemet’s membrane and endothelium constitute important layers of cornea. We report here ultrastructural features of camel cornea. Methods Four camel corneas were fixed in 2.5% glutaraldehyde containing cuprolinic blue in sodium acetate buffer and processed for electron microscopy. Tissues were embedded in LR White to measure the diameters of collagen fibrils. Results The camel cornea consists of 4 layers, the epithelium, stroma, Descemet’s membrane and endothelium. The epithelium was covered by a thick layer (1.5µm) of glycocalyx. The epithelium was very thick (226µm) and constituted 36% of the camel cornea (610µm) where as the corneal stroma (379µm) constituted 62% of the corneal thickness. Hemidesmosomes (20nm) were well developed followed by basement membrane (80nm). Below the basement membrane a thin layer (650nm) similar to BW was present. This layer was closely associated with anterior stroma which contained interlacing lamellae. There was bifurcation of lamellae observed in the anterior stroma. Lamellae ran parallel to each other in the middle and posterior stroma. PGs were decorated on the longitudinally running collagen fibrils. The collagen fibril diameter was 29 nm and interfibrillar spacing 40nm. Very small electron dense particles were observed within the collagen fibrils. Descemet’s membrane was not homogenous, instead it contained fibrillar structures. Endothelial cells contained all the normal cell organelles. Conclusion The structure of camel cornea is very different from human and other animal. This unique structure of the cornea might help the camel to adapt in the hot and dry climates. Camel cornea can be a good model to understand the affect of hot dry climates on the cornea.
Long‐term effects of plasma membrane hyperpolarization on cell‐junction stability of corneal endothelial cells in organ and cell culture
Authors: MARTINEZ‐GARCIA C , EVANS F , GALLEGO P , MERAYO‐LLOVES J , CHIFFLET S 
Published: November 2010

Abstract Purpose One of the most important challenges in corneal preservation is to maintain the epithelial and endothelial integrity. In previous work (Cell Motil. Cytoskeleton 66:1087, 2009) we found that short term (1 hour) hyperpolarization of the plasma membrane potential (HPMP) produces a reorganization of the actin cytoskeleton and increases the stability of cell‐cell junctions of bovine corneal endothelial (BCE) cells in organ and cell cultures. The purpose of this work is to study the effect of long term (several days) HPMP on cell viability, actin organization and intercellular junction stability in cell and organ culture, with the general objective of designing appropriate solutions to use in the maintenance of corneas. Methods Cells and corneas were grown in culture media supplemented by hyperpolarizing agents (valinomycin, choline chloride, lithium chloride). We studied their effects on plasma membrane potential (oxonol V), cell viability (propidium iodide and Tunel), actin organization (FITC‐phalloidin) and cell junction stability (response to calcium deprivation). Results The results showed that cells maintained up to three days in media supplemented with 0.1 µg/mL valinomycin improved their viability in culture and increased the stability of their intercellular junctions, similarly to that obtained in short‐term HPMP treatments. Accordingly, the corneal epithelium and endothelium of treated corneas in culture were better preserved than control ones Conclusion These results suggest that HPMP solutions might be useful in the design of media for preservation of corneas that will be used in transplants.
Thioredoxin‐like protein 6 (TXNL6) is an H2O2‐inducible reducing system for methionine sulfoxide reductase A (MsrA) repair of oxidized proteins whose expression increases upon aging in the human lens
Authors: LEE KANTOROW W , BRENNAN L , MCGREAL R , KANTOROW M 
Published: November 2010

Abstract Purpose TXNL6 is a thioredoxin‐like protein and we hypothesized that it could function as a reducing system for MsrA repair of methionine sulfoxide inactivated proteins. We therefore examined the levels of TXNL6 in multiple tissues, its subcellular localizatioin in lens cells, its oxidative‐stress induction in lens cells and its ability to serve as a reducing system for MsrA repair of the two key lens proteins α‐crystallin and cytochrome c (Cyt c). Methods TXNL6 mRNA and protein levels were analyzed in human lens epithelia and fiber, and its protein levels evaluated in aging whole human lenses. TXNL6 was localized in human lens epithelial (HLE) cells. TXNL6 induction was evaluated in HLE cells exposed to H2O2. The ability of TXNL6 to serve as a reducing system for MsrA repair of met‐oxidizedα‐crystallin and Cyt c was evaluated. Results TXNL6 was expressed at both the transcript and protein levels in lens epithelia, lens fiber cells and multiple other human tissues. Interestingly, protein levels of TXNL6 increased with age in human lenses. TXNL6 was localized to the mitochondria and cytosol of lens cells. TXNL6 was highly induced by H2O2‐oxidative stress treatment. TXNL6 served as a reducing system for MsrA repair of α‐crystallin and Cyt c in vitro. Conclusion TXNL6 is expressed by the human lens. Its levels increase in the lens with age and it is induced at high levels upon oxidative stress treatment. Importantly, TXNL6 can act as a reducing system for MsrA repair of critical lens proteins suggesting it plays a critical role in lens repair, defense against oxidative stress and prevention of cataract formation.
Resident autofluorescent perivascular macrophages have a scavenger function and may contribute to the maintenance of the blood‐retinal barrier
Authors: MENDES‐JORGE L , RAMOS D , LOPEZ‐LUPPO M , NACHER V , NAVARRO M , CARRETERO A , TAFURO S , BAESA‐RODRIGUEZ A , ESPERANCA‐PINA JA , BOSCH F , RUBERTE J 
Published: November 2010

Abstract Purpose The retina contains two distinct populations of monocyte‐derived cells: perivascular macrophages and microglia. In this work we describe the presence in mouse and human healthy retinas of a new subtype of perivascular resident macrophages, present in the perivascular space and different from microglia. Methods CD1 mice and human retinas were used. Perivascular macrophages were characterized by means of confocal microscopy, electron microscopy, and flow cytometry analyses. Two murine models of blood‐retinal barrier breakdown and photoreceptor degeneration were also used. Results These perivascular cells emitted specific autofluorescence and constitutively expressed the scavenger receptor class A. They were seen to move in an oscillatory manner along blood vessels, providing an additional coating to thinner areas of the vascular wall. These macrophages also accumulated blood‐borne horseradish peroxidase and acetylated low‐density lipoprotein without blood‐retinal barrier pathological disruption. Furthermore, they were early detected at lesions during photoreceptor degeneration. Conclusion Taken together these findings suggest that these perivascular cells fulfil a major role in the scavenging of blood‐borne molecules contributing to blood‐retinal barrier function, and may have a possible role in the onset and development of retinopathy. All these features are consistent with those described for brain Mato cells. Thus, this study reveals the presence of autofluorescent perivascular Mato cells in the retina.
AO imaging in AMD
Authors: MASSAMBA N 
Published: November 2010

Abstract Purpose Two different systems, adaptive optics scanning laser ophthalmoscope (AOSLO), and Spectral Domain Ophtalmoloscopy (SD‐OCT) were used to visualize cones in the outer neurosensory retina overlying soft macular drusen and the surrounding retinal areas. Methods High resolution images were obtained with Adaptive Optics (AO) in addition to complete ophthalmic examination including BCVA on ETDRS chart, biomicroscopic examination, autofluorescence imaging, fluorescein and indocyanine angiographies (HRA2 Heidelberg ,Germany) and SD‐OCT. The AO image are then compared with conventional infrared and SD‐OCT. Soft macular drusen from 50 patients (age between 65 and 85) visible on the scanning laser ophthalmoscope(SLO) examination were evaluated included in the study Results The soft drusen were visible in AO images as generally round areas delimited by a peripheral low‐reflectance line. The highly reflective photoreceptor inner/outer segment junction (IS/OS) can be used as a pattern of photoreceptors integrity in SD‐OCT images. In areas where the IS/OS junction is absent on SD‐OCT, no cones are visualized in registered AOSLO images. In the inner area of many drusen, hyper reflective spots of a size between 2 and 15 µm were sometimes isolated, sometimes grouped into tight aggregates of 2 to 40 components. Cone photoreceptors were visible in areas between drusen in most AO images, however the mosaic image sharpness was significantly less uniform in these elderly patients than previously observed in younger, healthy retinas. Conclusion This study shows the synergistic nature of these two high‐resolution retinal imaging systems The microscopic characteristics of soft drusen on AO imaging suggest some analogy with the anatomopathologic characteristics. AO technology will be a powerful tool to refine their clinical classification
AO adapted to SD‐OCT
Authors: DREXLER W 
Published: November 2010

Abstract Purpose Optical coherence tomography (OCT) has emerged as a leading technique in ophthalmic imaging due to its capability to non‐invasively resolve tissue morphology with high sensitivity and high axial resolution. Despite increases in axial resolution, monochromatic ocular aberrations limited the transverse resolution for retinal imaging to ~20 μm, which is too large for visualization of cellular structures. Adaptive optics (AO) may be used to correct such aberrations, leading to an improvement in image contrast and lateral resolution. Methods A successful combination of ultra‐high speed (120,000 depth scans/s), ultra‐high resolution optical coherence tomography with adaptive optics and an achromatizing lens for compensation of monochromatic and longitudinal chromatic ocular aberrations, respectively, allows for non‐invasive volumetric imaging in normal and pathologic human retinas at cellular resolution. Results The capability of this imaging system is demonstrated through preliminary studies by probing cellular intraretinal structures that have not been accessible so far with in vivo, non‐invasive, label‐free imaging techniques, including pigment epithelial cells, micro‐vasculature of the choriocapillaris, single nerve fibre bundles and collagenous plates of the lamina cribrosa in the optic nerve head. In addition, the volumetric extent of cone loss in two colour‐blinds can be quantified for the first time. Conclusion AO OCT might provide opportunities to enhance the understanding of retinal pathogenesis and early diagnosis of retinal diseases.
Commercial interest
Role of prophylactic topical nepafenac in prevention of post pars‐plana vitrectomy macular edema
Authors: MISHRA S , NAITHANI P , VASHISHT N , GARG SP 
Published: November 2010

Abstract Purpose To evaluate the effects of topical nepafenac in patients undergoing pars plana vitrectomy (PPV) with special emphasis on its role in post PPV macular edema. Methods 108 patients undergoing PPV were randomized to receive either topical nepafenac 0.3% (53 eyes) or placebo (55 eyes) from 3 days preoperatively till 4 weeks postoperative in addition to topical steroids and antibiotics in this single center investigator masked study. Optical coherence tomography (OCT) was done at week 2,4,6 and 8 post operatively. Results Patients taking nepafenac and those taking placebo had mean postoperative day 1 pain scores of 0.25 and 1.08 (P=0.03) and mean inflammation grades of 0.49 and 1.34 (P=0.002) respectively. Although centre subfield macular thickness (CSMT) was lesser in nepafenac group as compared to placebo group (260.56 µm Vs 270.70 µm at week 2, 228.44 µm Vs 236.21 µm at week 4, 215.02 µm Vs 218.74 µm at week 6 and 205.35 µm Vs 205.17 µm at week 8 respectively), the difference did not reach statistically significant levels (P>0.05) at any visit. There was also, no statistically significant improvement in best corrected visual acuity between the nepafenac group and the placebo group at any postoperative visit. Conclusion Although addition of 0.3% nepafenac decreased postoperative pain and inflammation, it did not reduce incidence of macular edema in patients undergoing PPV. Topical nepafenac was well tolerated and safe but did not improve visual recovery in this set of patients.
Transferrin and transthyretin in vitreoretinal surgery
Authors: ARNDT C , RAMON L , BOULAGNON C , DUCASSE A , BONNAY G 
Published: November 2010

Abstract Purpose The concentration of transferrin in the vitreous is known to be higher than in plasma or aqueous humor. This has been related to a local synthesis of transferrin by the ciliary body. Increased levels have been found in vitro‐retinal proliferation. A relationship between the level of transthyretin and the functional outcome has been previously reported. The purpose of the study was to look for a relation between transferrin and transthyretin. Methods Patients with epiretinal membrane and rhegmatogenous retinal detachment were prospectively enrolled. The vitreous samples were obtained without intraocular infusion. The levels of transferrine and transthyretin (prealbumin) were determined in all cases. Results In the group of patients with retinal detachment (n=18), two groups could be identified: the transferrin levels were either low between 40 and 70 mg/l with low transthyretin (<17,8 mg/l)(n=6) or high (>400 mg/l) with transthyretin levels between 200 and 400 mg/l (n=12).No relationship to any clinical parameters (extension of the detachment, onset of symptoms or degre of vitreo‐retinal proliferation) could be demonstrated. In patients with epiretinal membranes (n=6), the transferrin levels <40 mg/l, transthyretin < 17,8 mg/l. Conclusion Increased transferrin seems to correlate with increased transthyretin levels in the vitreous. The clinical signification of this relationship remains to be demonstrated and probably requires a larger patient sample.
Ghrelin concentration in the aqueous humour and plasma in open angle glaucoma patients
Authors: KATSANOS A , DASTIRIDOU A , GEORGOULIAS P , CHOLEVAS P , KOTOULA MG , TSIRONI E 
Published: November 2010

Abstract Purpose Ghrelin is a peptide hormone that exerts metabolic and smooth muscle‐relaxant effects in ocular tissues. The aim of this study was to compare aqueous humor and plasma levels of ghrelin in patients with open angle glaucoma (OAG) and controls. Methods Twenty four OAG, including 7 pseudoexfoliation (PXG) and 17 primary open‐angle glaucoma (POAG) patients, and 30 controls were included. All participants were patients scheduled for cataract or glaucoma surgery. Patients with other concomitant ocular disease, previous ocular surgery or diabetes were excluded. Blood samples were collected before cataract surgery. Aqueous humor was aspirated from the anterior chamber through a paracentesis with a 27 G needle under sterile conditions. Ghrelin levels in both samples were measured quantitatively with commercially available Radioimmunoassay (RIA) kits. Results Mean±SD age was 71.0±9.3 and 69.6±6.6 years in the OAG and control groups, respectively (p=0.6). Plasma levels of ghrelin were 495.6±157.7 pg/ml in the OAG and 482.2±125.4 pg/ml in the control group, respectively (Mann‐Whitney test, p=0.9). Aqueous humor levels of ghrelin were 85.5±15.4 pg/ml and 123.4 ±25.5 pg/ml in the OAG and control groups, respectively (Mann‐Whitney test, p<0.01). The ratio of plasma/aqueous concentration in ghrelin was higher in the OAG versus the control group (5.82± 1.94 versus 4.00±1.04, Mann‐Whitney test, p<0.01). There was no difference neither in plasma nor in aqueous humor levels of ghrelin between POAG and PXG patients (p>0.5). Conclusion Aqueous humor levels of ghrelin were significantly lower in OAG patients. This difference may manifest a role of ghrelin in the disease process or a consequence of antiglaucoma treatment.
Human pluripotent stem cells provide excellent source of functional pigment epithelial cells
Authors: SKOTTMAN H , VAAJASAARI H , ILMARINEN T , JUUTI‐UUSITALO K , NARKILAHTI S , SUURONEN R , UUSITALO H 
Published: November 2010

Abstract Purpose Defined differentiation of functional RPE cells from human embryonic (hESC) or induced pluripotent stem cells (iPSC) is a prerequisite for their use in individualised disease modelling, drug discovery and transplantation for retinal diseases. In this study we report differentiation of RPE cells from hESC and iPSC in condition enabling easy translation to clinical quality cell production. Methods Pluripotent stem cells were produced on human fibroblast feeder cells in serum‐free medium. The differentiation of the cells was induced using bFGF and feeder cell removal approach under serum‐free conditions. The pigmentation and RPE morphology of the cells were analysed and the expression of genes and proteins characteristics for RPE cells were studied. The in vitro functionality of the cells was analysed using ELISA measurements and phagocytosis of photoreceptor outer segments. The integrity of the generated RPE layer was analysed using transepithelial electric resistance (TEER) measurements. Results With our differentiation method, we were able to generate RPE cells with satisfying efficiency. The typical pigmented cobblestone‐like morphology and expression of RPE specific markers were confirmed at gene and protein level. The differentiated cells were able to phagocytose and secreted growth factors typical for RPE cells. In addition, cells formed a well polarized epithelium with high integrity, exhibiting good TEER values. Conclusion We have developed progressive differentiation protocol for production of functional RPE cells from hESC and iPSC. The developed production method is currently translated to defined and animal component free conditions enabling clinical grade cell production.
Arachnoid cell changes following elevated pressure and oxidative stress: new implications for optic nerve degeneration
Authors: NEUTZNER A , XIN X , FAN B , FLAMMER J , MILLER NR , KILLER HE , MEYER P 
Published: November 2010

Abstract Purpose The study of meningothelial cells (MCs) and their connection to optic nerve function. MCs line the arachnoid layer of the meninges and form a barrier between the CSF and the blood circulation. A previous study revealed a significantly increased proliferation of MCs in the arachnoid surrounding the optic nerve glaucoma patients. Methods To explore a possible role of these cells in the pathogenesis of diseases of the optic nerve, we studied the effect of elevated hydrostatic pressure and oxidative stress on MCs using rotenone to inhibit mitochondrial function and compared them to untreated control cells. Cell viability and proliferation were measured using a MTS‐based assay. As a measure of barrier function, we assessed the endocytotic activity of MCs by fluorescence and confocal microscopy following fluorescent‐latex bead uptake. Results Exposure of MCs to elevated hydrostatic pressure caused significant cellular proliferation and a dramatic decrease in endocytotic activity. Furthermore, mild oxidative stress severely inhibited endocytosis, thus negatively impacting MC barrier function. Conclusion MCs surround the optic nerve, thereby shielding it from but also conditioning the microenvironment of this sensitive area. As elevated pressure and oxidative stress occur in patients with increased intracranial pressure who have papilledema and probably in some cases of normal‐tension glaucoma, these phenomena may impact the function of MCs and thus, contribute to the loss of retinal ganglion cells in the course of these and, perhaps, other optic nerve diseases.