bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnosis of adult ophthalmic tumours: role of clinical history, symptoms and signs
Authors: KIVELÄ T
Published: November 2010

Purpose To summarise signs and symptoms useful in diagnosing adult ophthalmic tumours.

Methods Personal experience of the author as a member of the European Ophthalmic Oncology Group.

Results According to studies from the United Kingdom, Finland and United States, 28‐42% of adult patients with intraocular tumours may experience delays because the lesion is either misdiagnosed (e.g. as macular degeneration, naevus, rhegmatogenous retinal detachment) or missed at the initial visit. Of these patients, 72‐87% have symptoms attributable to the tumour such as blurred vision, photopsia, floaters, metamorphopsia, and visual field loss. These symptoms can also be caused by many benign conditions (e.g. vitreous detachment) but should not be interpreted as innocent without thorough clinical examination. Signs specific for iris and ciliary body tumours include a tumour mass, sentinel vessels, acquired astigmatism, and cataracts. Choroidal tumours may induce serous retinal detachments, subretinal and vitreous bleedings and, sometimes, lipid exudation. Finally, orange subretinal pigment suggests the diagnosis of a uveal melanoma whereas many drusen point to a long‐standing naevus.

Conclusion Signs and symptoms of ophthalmic tumours are mostly nonspecific, necessitating an appropriately high level of suspicion and a systematic approach to clinical examination to avoid delayed or missed diagnoses. Earlier diagnosis could be achieved especially if dilated fundus examinations were performed without exception and if all suspicious naevi were referred for a second opinion.
Diagnostic tools for adult intraocular tumours
Authors: ZOGRAFOS L
Published: November 2010

Purpose Fundus examination completed with Fundus drawings and panoramic, fundus pictures, standard and panoramic fluorescein angiography, standard and panoramic ICG, 10, 20 and 50 MHz ultrasonography, and OCT are the main diagnostic tools for intraocular tumours in adult’s patients.

Methods These various diagnostic techniques provide complementary informations contributing to the final diagnosis. A document tumour growth during a periodic observation may be recorded with standard or panoramic fundus pictures. The modifications of the pigmant epithelium as well as an increase permeability of the tumour vessels may be recorded with standard or panoramic fluorescein angiography. Intra‐tumoral and Peri‐tumoral with hemodynamic modifications may be recorded with standard and panoramic ICG.

Results Tumour shape, and tumour height is recorded with standard 10 or 20 MHz ultrasonography. The volume and the shape of anteriorly located intra ocular tumours are recorded with 50 MHz UBM.

Conclusion The presence of the retinal detachment in contact with the tumours may be recorded with modern OCT. Additional examinations which can be used in ocular oncology are: Fundus auto‐ fluorescence, MRI, and computed tomography. An intraocular biopsy can be required in specific cases.
Diagnosis of retinoblastoma
Authors: DESJARDINS L , GAUTHIERS‐VILLARS M
Published: November 2010

Purpose Retinoblastoma is the most frequent malignant intra ocular tumors in childhood. The incidence is one out of 15000 to 18000 births. The median age at diagnosis is 24 months for unilateral and 12 months for bilateral. The genetic predisposition is autosomal do

Methods In 1971 Knudson made the hypothesis that 2 genetic alterations in the same retinal cell were necessary. In bilateral disease there is one germline and one somatic mutation and in unilateral non hereditary, 2 somatic mutations. The Rb1gene is located on chromosome 13 q 1‐4 . The Rb 1 protein is a pocket protein involved in the cell cycle regulation

Results Most frequent symptoms are leukocoria and strabismus Later symptoms include heterochromia iridis,rubeosis, buphtalmia, pseudo hypopion, uveitis, inflammatory pseudo tumor and exophtalmia. Diagnosis of retinoblastoma is made by fundus examination. Imaging of the orbits and brain should be performed using MRI if possible. Ultrasonography with B and A scan is also useful as well as the use of Retcam . Differential diagnosis is sometimes easy when there is colobomas ,persistance of hyperplastic primary vitreous ,hamartomas or astrocytomas It can be difficult in cases of advanced Coats disease or when there is diffuse infiltrating retinoblastoma.

Conclusion We have made a retrospective study on patients sent for suspicion of retinoblastoma in our institute from January 2003 to December 2005 If we compare this serie to the serie published in the literature we can say that the pourcentage of well diagnosed retinoblastoma is improving. We have found 16% of wrong diagnostics. There was 30% in the serie of Balmer in 1988 and 42% in the serie of Shields in 1991. The most frequent differential diagnosis reported in all series is Coats disease
Diagnosis of phakomatosis
Authors: BECHRAKIS NE
Published: November 2010

Abstract not provided
History of disease, facial nerve grading systems & clinical evaluation
Authors: MAVRIKAKIS I
Published: November 2010

Obtaining an accurate history of the onset, progress and associated symptoms of newly acquired facial nerve palsy is extremely helpful in determining the potential cause of the palsy. More importantly it serves as a guide for prognosis and timing of any necessary surgical intervention. Acute versus chronic facial nerve palsy, complete versus incomplete facial nerve palsy, recovery and recurrence of the disease will be discussed. The gold standard for grading facial nerve function is the House‐Brackmann grading scale. Due to the limitations and subjectivity of this scale, several new scales of various degrees of objectivity and ease of use have been introduced. These include the Nottingham system, the Sunnybrook scale, the Yanagihara and the Sydney system, all with their advantages and disadvantages. Clinical evaluation of a patient with facial nerve palsy include evaluation of upper eyelid retraction, blink reflex, lagophthalmos, brow ptosis, paralytic ectropion, midface ptosis, mouth symmetry, platysma muscle strength, hearing, corneal sensation, Bell’s phenomenon, tear function and synkinesis.
Management of corneal exposure & lagophthalmos
Authors: BOBORIDIS K
Published: November 2010

Abstract not provided
Management of epiphora & facial synkinesis
Authors: CHARONIS G
Published: November 2010

Abstract not provided
Fluorescein angiography: first step for macular degeneration diagnosis
Authors: SOUBRANE G
Published: November 2010

Purpose To recall that fluorescein angiography (FA) is not only the basis of our knowledge but also mandatory to improve our understanding.

Methods Macular disciform lesions have been described and drawed since about 150 years. It is only in 1977 with the advent of fluorescein that the connection with choroidal new vessels (CNV) was performed. The identification of drusen as precursors of CNV was the following stage. With time a number of precursors and clinical forms of macular degeneration were described.

Results Currently, the precursors (Age‐Related Maculopathy) are distinguished from the neovasdcular or atrophic complications (Age‐Related Macular Degeneration). The precursors presenting an early hyperfuorescence can be either hard drusen or RPE atrophy distinguished from each other on the late phase of FA.The late hyperfluorescence of soft drusen particularly when confluent requires a careful analysis of the complete FA sequence to ensure the diagnosis. The neovascular stage presents mainly as sub epithelial occult lesions of which the other types develop that display different angiographic behaviours. Specific aspects have been described gradually based on their FA features. The atrophic stage of the disease seems to behave in a stereotyped way but sub goups are presently identified.

Conclusion The fluorescein features of the different component of AMD remain the reference for all other more recent imaging technics and helps to understand and differentiate the various aspects of the disease.
OCT: from single use to combined use in macular degeneration
Authors: CREUZOT C
Published: November 2010

Purpose Optical Coherence Tomography (OCT) plays a key role in the diagnosis and the treatment of Age Macular Degeneration (AMD). Authors will present the different signs observed in OCT in exudative AMD.

Methods Authors will present clinical cases to illustrate the place of the OCT in AMD diagnosis. OCT has progressively replaced the first‐line tool played by angiography especially for the following of the patient once the treatment initiated. The different schemas currently proposed emphasize the role of the OCT combined with visual acuity measurement and fundus examination.

Results However, the role of fluorescein and indocyanin green angiography remained essential especially to precise the clinical form before treatment. The combination of OCT and angiography remained a "key association" especially when there is some discrepancy between results or in case of treatment failure to consider another option. It is also the only opportunity for us to understand better the prognosis of these cases under treatment.

Conclusion OCT has dramatically changed the supervision of exudative AMD especially during treatment. However, the combination with fluorescein and indocyanin angiograms is highly recommended not only for initial diagnosis but also in difficult cases during follow‐up.
Autofluorescence: new tool to follow dry eye AMD?
Authors: MENKE MN , WOLF‐SCHNURRBUSCH U , WOLF S
Published: November 2010

Purpose In the pathophysiolgy of dry (atrophic) age related macular degeneration (AMD) aging of the retinal pigment epithelium (RPE) plays a key role. Accumulation of lipofuscin granules in the RPE cells represents a common downstream pathogenetic pathway in AMD. Lipofuscin is derived from chemically modified residues of incompletely digested photoreceptor outer segment discs. Detection of lipofuscin in vivo is possible by using fundus autofluorescence (FAF) imaging. The clinical application and possible implications of autofluorescence imaging in dry AMD will be discussed.

Methods When stimulated with light in the blue to green range, lipofuscin granules emit a characteristic yellow fluorescence. FAF imaging using a scanning laser ophthalmoscope allows visualization of the topographic distribution of lipofuscin over large retinal areas. Examples of FAF images will be presented to demonstrate various FAF patterns and to discuss the clinical significance of these findings.

Results In areas of geographic atrophy FAF images show very low autofluorescence intensity. This is due to the loss of RPE cells including the lipofuscin granules. In the junctional zone between atrophic and normal retina, levels of increased autofluorescence intensity may occur due to excessive accumulation of lipofuscin in the RPE cells. Longitudinal observations further suggest that the extension of the total area with increased autofluorescence intensity surrounding atrophy at baseline has a strong positive correlation with atrophy progression rate over time.

Conclusion FAF imaging is an important diagnostic tool to follow the progression of dry AMD and other degenerative macular diseases and should always be considered in cases were the status of the RPE is unknown.
The author, the reviewer and the associate editor: a literary drama triangle
Authors: KIVELÄ T
Published: November 2010

Purpose To provide an insight into interactions between authors, reviewers and editors.

Methods Personal experience of the author as a writer, reviewer and associate editor is used to discuss the scholarly interaction involved in having a manuscript reviewed and eventually published.

Results The drama triangle is a psychological model of human interaction first described by Karpman. It proposes three ancestral psychological roles which people often take in a social situation: 1. The person who is treated as, or accepts the role of, a victim, 2. the person who pressures or persecutes the victim, and 3. the rescuer, who intervenes to help the situation or the underdog; this role often is one of a mixed or covert motive. The scenario of most novels, plays and movies is based on the drama triangle. Moreover, most of us are neurologically programmed to play any of the three roles. Depending on the context, we will thus ‐ consciously or unconsciously ‐ choose one of them. The roles can consequently also insinuate into the manuscript review process: the author is liable to become the victim and the reviewer the villain; the editorial staff member may then assume the role of the rescuer. Be as it may, the editors should try to identify reviewers whose comments are ‐ often unconsciously ‐ hostile from those whose advice is constructively critical, and then filter these in their targeted advice, keeping a neutral position. Sometimes he may need to guide an author who declares himself a victim or a reviewer who plays rescuer.

Conclusion The best way to avoid being trapped in a drama triangle is by being watchful not take one of the three roles. Ideally, all three players work in unison toward a paper which makes best use of the data and of the talent of the authors and reviewers.
White dot syndromes
Authors: ANDROUDI S
Published: November 2010

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

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

This 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

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

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

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

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

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

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

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

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

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

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

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.
Influence of Hsp90 and HDAC inhibition and tubulin acetylation on perinuclear protein aggregation in human retinal pigment epithelial cells
Authors: KAARNIRANTA K , RYHÄNEN T , VIIRI J , HYTTINEN J , UUSITALO H , SALMINEN A
Published: November 2010

Purpose Retinal pigment epithelial (RPE) cells are continually exposed to oxidative stress that contributes to protein misfolding, aggregation and functional abnormalities during aging. The protein aggregates formed at the cell periphery are delivered along the microtubulus network by dynein dependent retrograde trafficking to a juxtanuclear location.

Methods Cellular organelles were analysed by transmission electron microscopy of ARPE‐19 cells exposed 5 µM MG‐132, 0.25 µM geldanamycin (GA), 1 µM trichostatin A (TSA), 1 µM taxol (TAX) or 5 µM nocodazole (NOC) for 24 hours. In addition, the cells were treated simultaneously with GA or TSA or TAX or NOC and MG‐132 up to 24 hours. Ubiquitin, Hsp90, Hsp70, acetylated tubulin and Hsc70 protein levels were analyzed by western blotting.

Results Hsp90 inhibition by geldanamycin can effectively suppress proteasome inhibitor, MG‐132 –induced protein aggregation in a way that is an independent of HDAC inhibition, or the tubulin acetylation levels in ARPE‐19 cells. However, the tubulin acetylation and polymerization state affects the localization of the proteasome‐inhibitor –induced aggregation.

Conclusion Hsp90 inhibition is effectively related to regulation of protein aggregation that is independent of HDAC inhibition or tubulin acetylation levels in the RPE cells. Our findings open new perspectives for understanding the pathogenesis of protein aggregation in retinal cells and can be useful for the development of therapeutic treatments to prevent retinal cell deterioration.
Descemet´s membrane detachment 16 years after PK and 10 months after phaco
Authors: FERNANDEZ MENDY JO , ARASANZ F
Published: November 2010

Purpose The purpose of this paper is to present an unusual case of DMD and analyze this complication

Methods A 57‐year‐old woman, who had bilateral keratoconus, underwent three penetrating keratoplasties (PK) on her RE in 1981, 1993 and 1995 resulting in ptisis bulbi. In her LE she underwent two PK (1981, 1994) follow by arcuate incisions (1995) and an uneventful phacoemulsification in 2007. 10 months after cataract surgery, she begun with blurred vision, the BCVA was 20/400 and was seen by 3 ophthalmologists who made the diagnosis of endothelial failure and suggested a new PK or a DSAEK. We performed an Optical Coherence Tomography, diagnosing a complete Descemet´s membrane detachment (DMD). An intracameral gas injection of C3F8 at 16% was performed in the operating room, and the patient was instructed to maintain a supine position. After 24 hours VA improved to 20/80 and after 72 hours 20/30 UCVA. A small bubble was present in the anterior chamber for more than 3 weeks. One month later she achieved 20/20 with Contact Lens. During the first year after reattachment it was necessary to change the CL due to an increasing with the rule astigmatism from 3D to 5D.

Results Two years after gas injection BSVA is 20/25 because she is no longer using CL, Descemet´s membrane still remains well attached, even thought we realized that there was a trend to steepen the vertical meridian due to the widening of a nasal arcuate incision, that we think was the origin of the DMD.

Conclusion DMD is a rare complication of Phacoemulsification, seen immediately after the surgery. So far there has not reported any complete DMD after phaco after PK. We think that it is mandatory to perform a corneal OCT in all cases of PK and stromal edema; it could probably be a DMD.
Intracorneal lenses for the treatment of presbyopia using femtosecond laser: visual outcomes and safety
Authors: PALLIKARIS IG , LIMNOPOULOU A , KYMIONIS G , PANAGOPOULOU S , BOUZOUKIS D
Published: November 2010

Purpose To investigate the visual outcomes and safety of Intracorneal lenses (Flexivue Micro‐Lens, Presbia, CA)) for the treatment of presbyopia.

Methods This was a prospective clinical study. An intrastromal corneal tunnel was created using femtosecond laser (Intralase 150, AMO , CA). The lens was inserted within the cornea tunnel of the non‐dominant eye of 10 presbiopian patients. Mean age was 51,23 years old ± 3,11 (5 males and 5 females). The follow‐up was up to 12 months.

Results In the operated eye, mean uncorrected visual acuity for distance (UVA‐D) preoperatively, one day, one week one month, three months and six months, and 1 year after surgery was 20/20, 20/40, 20/40, 20/32, 20/32, 20/32 and 20/32 respectively, whereas for near (UVA‐N) was 20/50, 20/40, 20/30, 20/30, 20/25, 20/25 and 20/30. Binocular far vision was not altered. No tissue alterations of the cornea were found using corneal confocal microscopy. No intra or post‐operative complications were demonstrated up to one year after surgery.

Conclusion Intracorneal lenses for the correction of presbyopia using femtosecond laser seems to be a safe and effective method to correct presbyopia in patients aged between 45 to 55 years old; a target group which is considered too old for refractive laser surgery and too young for clear lens extraction. Longer follow‐up and a larger population are necessary in order to draw more significant results of this new surgical approach for the treatment of presbyopia.

Commercial interest
Can we treat glaucoma by non‐IOP related approaches?
Authors: STALMANS I
Published: November 2010

Intra‐ocular pressure is the main risk factor for the progression of glaucoma. However, intra‐ocular pressure lowering is not always sufficient to halt the progressive ganglion cell loss. Indeed, additional risk factors have been identified for glaucoma progression that can explain why some patients progress despite rigourous intra‐ocular pressure lowering. Vascular risk factors, such as low perfusion pressure, can be taken into account in the management of our glaucoma patients. The treatment options for these vascular risk factors will be discussed during the lecture. Moreover, neuroprotective strategies might open therapeutic perspectives to directly support the ganglion cells and thus help stabilizing the disease. Possible neuroprotective agents will be highlighted.
Are all glaucoma drugs equally effective?
Authors: SCHMETTERER L
Published: November 2010

Purpose It is only in the recent years that we have got evidence that reducing intraocular pressure (IOP) is beneficial in terms of preventing glaucoma progression in all types of glaucomatous disease. Nowadays we do have numerous data from large clinical outcomes trials clearly indicating that the lower the IOP the better the visual field preservation. There is, however, less data available comparing outcomes of different pharmacological regimen.

Methods Only few head‐to‐head comparisons of two drugs that are equally effective in lowering IOP have been published. It is generally assumed that such trials would yield similar results in visual field preservation with both regimen. Looking into the literature there is, however, some evidence for the opposite.

Results One clinical trial indicates that betaxolol may be superior to timolol in terms of visual field perservation. Another trial indicates that a combination of dorzolamide and timolol is assocaited with less visual field detoriation than a combination of brinzolamide and timolol. In this study the risk of disease progression was closely linked to low blood velocities in retrobulbar vessels.

Conclusion In light of these results and the lessons we have learned from other fields there is a need for further studies comparing the outcomes of different antiglaucoma drugs head‐to‐head. Given that the pathophysiology of glaucoma is only poorly understood it can not generally be expected that all glaucoma drugs are equally effective in perserving visual fields.

Commercial interest
New aspects of the Slug Mucosal Irritation (SMI) assay: Detecting ocular stinging, itching and burning sensations
Authors: LENOIR J , ADRIAENS E , CLAERHOUT I , KESTELYN P , REMON JP
Published: November 2010

Purpose Our eyes are one of the most important senses. They are very sensitive and irritations may occur easily. A screening method for ocular discomfort would be very helpful in the development and refinement of formulations. In the past, the Slug Mucosal Irritation (SMI) assay demonstrated a relation between an increased mucus production (MP) in slugs and an elevated incidence of stinging, itching and burning (SIB) in human eyes. The aim of this study is to compare subjective ocular discomfort caused by shampoos evaluated in volunteers with results of the SIB‐procedure.

Methods The stinging potency of 1 artificial tear and 10 shampoos was evaluated with the SIB‐procedure by placing 3 slugs per treatment group 3 times on 100 µl of the test item. After each 15 min contact period, MP was measured. Evaluation of the results is based upon the total MP during 3 repeated contact periods. Experiments were repeated 3 times. A Human Eye Irritation test with the same test items will be set up (12‐period cross‐over study, 24 volunteers, study approved by an independent Commission for Medical Ethics, associated with Ghent University Hospital). The participants are dripped 10 µl of a 5% or 10% shampoo dilution in water or the artificial tear in 1 eye, while in the other eye 10 µl of water is administered. The evaluation of the test substances is done both by participants and the ophthalmologist at several time points.

Conclusion With the obtained results we will be able to improve the newly developed protocol and examine the predictability with reference to non‐ and mildly irritating formulations in humans. We hope to conclude that the SIB‐procedure is a good tool to predict clinical ocular discomfort.