bluuebunny/crossref_metadata_2025 huggingface dataset:
Limbal stem cell transplantation techniques
Authors: GICQUEL JJ
Published: December 2011

Limbal epithelial stem cells (LSC) are essential for the regeneration of the corneal epithelium. Limbal stem cell deficiency (LSCD) that can develop in traumatic, immunologic, or genetic diseases affecting the ocular surface is a major cause of corneal transparency loss.Limbal stem cell transplantation (LSCT) aims to restore a corneal epithelial phenotype, essential to maintaining the corneal transparency. The source of donor tissue containing LSC for in vivo expansion, can be the healthy fellow eye (Conjunctivo Limbal Autograft (CLAU)), living‐related (LR) Conjunctivo Limbal Allograft or cadaveric (Kerato Limbal Allograft (KLAL)). Sheets of ex vivo expanded bioengineered epithelial cells (from autologous origin (LSC / oral mucosa) or LR (LSC) are an alternative. Before and after transplantation a proper control of the ocular surface inflammation is essential. Systemic and topical immunosuppressive treatment is also needed in all allograft recipients. In order for the surgical restoration of the corneal transparency to be complete, lamellar and penetrating keratoplasty are often required.
Penetrating Keratoplasty
Authors: DIGHIERO P
Published: December 2011

Abstract not provided
Anterior and posterior lamellar Keratoplasty
Authors: NUBILE M
Published: December 2011

Abstract not provided
Indications and limitations of amniotic membrane transplantation
Authors: DUA H
Published: December 2011

Abstract not provided
Pathophysiology of Uveitis
Authors: DICK A
Published: December 2011

Purpose This talk will overview the pathophysiology of non‐infectious uveitis in relation to recent SUN (standardised uveitis nomenclature) disease classification.

Methods The experimental and translational human evidence of autoimmunity and activation of immunity will be discussed. In addition the talk will highlight the pathways and mechanisms of tissue damage that results in sight‐threatening disease.

Results Traditionally, despite active immune regulatory mechanisms operative within the ocular environment, inflammation still occurs. Activated antigen and non‐antigen specific T cells are generated in uveitis. The interplay with innate immunity and in particular cells of myeloid lineage both systemically and within the local environment dictate the severity and extent of pathology we observe

Conclusion The understanding of immune responses during the uveitis open many avenues to potential novel immunotherapies that not only suppress inflammation but attempt to redress immune balance, tolerance and local homeostasis within ocular tissues
Symptoms and signs of anterior uveitis
Authors: NERI P , ARAPI I
Published: December 2011

Purpose To review the symptoms and signs of anterior ueveitis (AU), based on the anatomic classification of uveitis, iritis and iridocyclitis.

Methods Review of symptoms and signs of AU.

Results Perikeratic injection, small keratic precipitates (KPs), cells and flare in the anterior chamber are peculiar findings of alternating unilateral acute non‐granulomatous anterior uveitis, which is commonly described in association with HLA‐B27 antigen and spondyloarthropaties. In such cases, hypopyon or fibrinous exudate can also occur. Patients presenting acute anterior uveitis typically show red eyes, photophobia, ocular pain, and often blurred vision. In chronic anterior uveitis, the onset is usually subtle and patients may be asymptomatic until the development of complications. Chronic flare, Koeppe and Busacca nodules of the iris, medium‐size KPs or large mutton‐fat KPs, peripheral anterior synechiae and broad‐based posterior synechiae represent hallmarks of granulomatous anterior uveitis which tends to chronicity. Viral anterior uveitis is typically unilateral, characterized by recurrent episodes of anterior uveitis. Endotheliitis, high intraocular pressure, and patchy/sectoral iris atrophy are also present. Juvenile Idipoathic Arthritis (JIA)‐associated anterior uveitis is peculiarly a bilateral non‐granulomatous chronic anterior uveitis, frequently worsened by several complications.

Conclusion The typology of AU influences its clinical presentation: the clinical findings can vary on the basis of its acute or chronic, granulomatous or non‐granulomatous nature. Specific AU subtypes are characterized by a large number of distinct ocular signs.
Symptoms and signs of posterior uveitis
Authors: KHAIRALLAH M , KAHLOUN R
Published: December 2011

Purpose Posterior uveitis (PU) is an important anatomic form of uveitis in which the primary site of inflammation is the choroid or retina, with or without subsequent vitreous involvement.

Methods Review of symptoms and signs of PU

Results The onset of PU can be sudden or insidious, involving one or both eyes. Most common ocular symptoms include blurred vision, loss of vision, and floaters. PU is usually associated with vitritis. Both vitreous cells and flare should be graded according to standardized grading systems. Other vitreous changes may include vitreous strands, vitreous hemorrhage, vitreous traction, and posterior vitreous detachment. Depending on the primary site of inflammation, PU can present in the form of retinitis, choroiditis, retinochoroiditis, or chorioretinitis. Retinal and/or choroidal inflammation can be focal, multifocal, or more diffuse, involving the periphery or posterior pole. It is important to distinguish between active and inactive chorioretinal disease. Retinal vasculitis can occur in the setting of several PU entities involving retinal veins or arteries. It appears as focal, multifocal, or diffuse vascular cuffing or sheathing Other retinal vasculitic changes include retinal hemorrhages, features of retinal vascular occlusion, retinal/optic disc neovascularization, and aneurysms. Macular involvement may result from direct inflammatory infiltration, macular edema, serous retinal detachment, retinal ischemia, epiretinal membrane, or macular hole. Optic nerve involvement may include optic disc hyperemia, optic disc edema, optic neuritis, neuroretinitis, optic disc exudate, and optic disc granuloma.

Conclusion Clinician should be aware of the array of ocular symptoms of signs and their importance in orienting work‐up.
Imaging : techniques and indications
Authors: HERBORT C
Published: December 2011

Abstract not provided
Diagnostic of adult ophthalmic tumors: role of clinical history, symptoms and signs
Authors: KIVELÄ T
Published: December 2011

Abstract not provided
Diagnostic techniques for adnexal tumors
Authors: SEREGARD S
Published: December 2011

Abstract not provided
Diagnostic of retinoblastoma
Authors: DESJARDINS L
Published: December 2011

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 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 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 Conclusions 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
Diagnostic of phakomatosis
Authors: BECHRAKIS NE
Published: December 2011

Abstract not provided
History of Disease, Facial Nerve Grading Systems & Clinical Evaluation
Authors: MAVRIKAKIS I
Published: December 2011

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.
Periocular Cosmesis & Facial Dynamic Procedures
Authors: PANTELIDIS E , LINARDOS EP , PANTELIDIS EMM
Published: December 2011

Purpose To present Periocular Cosmesis & Facial Dynamic Procedures, that can be performed in severe and refractory facial nerve palsy cases.

Methods Didactic course lecture

Results Facial reanimation using dynamic procedures is a multidisciplinary rehabilitative type of management which may be undertaken in longstanding and severe facial nerve palsy. This management includes facial nerve repair, facial nerve substitution and temporalis muscle transfers. Peri‐ocular aesthetic issues need to be addressed in severe and refractory facial nerve palsy cases. Brow lift, midface lift and facial lift can be performed to improve functionality and cosmesis.

Conclusion These procedures can provide a moderate to significant degree of improvement in facial nerve functionality and periocular cosmesis
Can amniotic membrane help treating severe corneal infections
Authors: DIGHIERO P
Published: December 2011

Abstract not provided
Introduction to KPros
Authors: LIU CS
Published: December 2011

Abstract not provided
Psychological assessment
Authors: BUSUTTIL A
Published: December 2011

Abstract not provided
Management of Boston Type 1 KPro complications
Authors: ETXEBARRIA J
Published: December 2011

Abstract not provided
Infectious anterior uveitis
Authors: PLEYER U
Published: December 2011

Abstract not provided
Behçet disease, sarcoidosis, VKH
Authors: ABU EL ASRAR A
Published: December 2011

Abstract not provided
White dot syndromes : from MEWDS to Serpiginous choroiditis
Authors: HERBORT C
Published: December 2011

Abstract not provided
Azithromycin; clinical efficacy and safety in infants
Authors: BREMOND‐GIGNAC D
Published: December 2011

Purpose Purulent bacterial conjunctivitis affects all ages with high frequency in newborns and children. Our aim was to analyze in children especially in infants, the efficacy and safety of azithromycin 1.5% eye‐drops in the treatment of this disease.

Methods Two multicenter, randomized, investigator‐masked, parallel‐group study, included infants, children and adolescents presenting a purulent conjunctivitis comparing azithromycin 1.5% eye‐drops twice daily for 3 days and tobramycin 0.3% 1 drop every two hours for 2 days then four times daily for 5 days. Cultures, signs and symptoms were studied and safety and efficacy were evaluated at baseline, Days 3 and 9.

Results Results in term of positive cultures, signs and symptoms are exposed. Bacterial strains were identified precisely. Both treatments were effective. No adverse effects were noted on the ocular surface.

Conclusion The distribution of positive culture in bacterial conjunctivitis in infants and children is of interest for a better understanding of bacterial conjunctivitis. A short‐treatment course can be easily used in children, thus improving the quality of life of them and their parents.

Commercial interest
Transduction of mesenchymal stem cells with an ecdysone inductible lentiviral vector expressing luciferase gene
Authors: FAVARD A , BELLICAUD D , NOCHEZ Y , COLLIN C , PISELLA PJ , GABISON EE , PAGES JC
Published: December 2011

Purpose Several studies, using limbal stem cells or mesenchymal stem cells (MCSs), have confirmed the usefulness of these cells to repair epithelial and stromal corneal tissue. However the reparation process might be hampered by a strong inflammatory reaction inducing non‐physiologic remodelling of healing tissue. The use of genetically modified cells with inducible gene to control the stromal reaction might offer an opportunity to improve new treatments in ophthalmology.

Methods We aimed at transducing MSCs with an Ecdysone inducible lentivirus. To the end, we generated a conditional expression vector, expressing the luciferase under an ecdysone expression system. We have transduced MSCs and evaluated their ability to synthetize on « demand » the luciferase. Following validation of the process in cultured cells, the genetically modified cells will be evaluated in vivo, in rat.

Results Using an in vitro recombination system, we generated a lentiviral vector containing the luciferase as transgene, placed under an Ecdysone promoter (« E/Luc »). To obtain an effective control of the luciferase, we generated a second vector containing the RXR gene and VgEcR gene under a constitutive promoter (« V/R »). Viral recombinant vectors were produced through 293T cells. MSCs were first transduced by the « V/R » vectors followed by the “E/Luc” lentiviruses. Finally, we have tested the responsiveness of the Ecdysone system in MSCs by adding Ponasterone and enzymatic activity of the Luc gene.

Conclusion We predict that it could be applied to follow in vivo MSCs after their corneal engraftment. Upon validation of the system, the use of inducible gene expression could be applied to pathological wound‐healing.
Interleukin‐10 promotes macrophage infiltration in mouse retina
Authors: MENDES‐JORGE L , RAMOS D , VALENCA A , NACHER V , RODRIGUEZ‐BAEZA A , ALMOLDA A , CAMPBELL IL , GONZALEZ B , CASTELLANO B , RUBERTE J
Published: December 2011

Purpose Inflammation, specifically macrophage infiltration, is known to promote a number of pathologic processes including eye neovascularization. In the current study, we explored the macrophage retinal infiltration in a mouse model that over‐expressed interleukin‐10 (IL‐10) in the retina.

Methods A transgenic mouse model in C57BL6 background that overexpress IL‐10 under the control of the glial fibrillar acidic protein (GFAP) promoter was analysed. Retinas from transgenic and their wild type (wt) littermates were studied by immunohistochemistry.

Results The IL‐10 transgenic mice (tg‐IL10) expressed higher levels of IL‐10 in the retina compared to wild type mice. Histologically, when compared to wt, the cytoarchitecture of the transgenic retinas did not show any differences. The only morphological alteration observed was a CD11b+ macrophage infiltration in the retina and the irido‐corneal angle of tg‐IL10. These macrophages were fully loaded with melanin. Our observations show that the number of macrophages in tg‐IL10 retinas was approximately ten fold superior than in wt. Interestingly, the 80% of macrophages in tg‐IL10 retinas were localized along blood vessels. This finding supports previous work in other paradigmas reporting infiltrated macrophages located along blood vessels, which may be involved in the modulation of blood vessel growth and regression.

Conclusion A significant increase in the number of macrophages aligning along blood vessels has been observed in the retina of a transgenic model that produces IL‐10 under the control of GFAP promoter. This preliminary result suggests that IL‐10 promotes macrophage perivascular infiltration in mouse retina.
Effect of Autocrine Vascular Endothelial Growth Factor on the Survival of Retinal Müller Cells under Oxidative Stress
Authors: KIM NR , KIM CY , RHO SS , OH JH , MOON YS , CHIN HS , HONG S , SEONG GJ
Published: December 2011

Purpose Autocrine vascular endothelial growth factor (VEGF‐A) is a known survival factor for the developing and mature retina, stimulating both endothelial and neural cells. We examined whether survival of Müller cells under oxidative stress was related to stress‐induced VEGF‐A synthesis.

Methods Rat Müller cells were treated with hydrogen peroxide, and cell survivals were analyzed with a flow cytometry with annexin V‐fluorescein isothiocynate and LDH assay. The expression of VEGF‐A, VEGF‐R1, and VEGF‐R2 was determined by semiquantitative RT‐PCR or Western blot analysis.

Results Hydrogen peroxide–induced cell death was increased with dose dependent manners. Treatment of hydrogen peroxide on rat Müller cells induced the expression of VEGF‐A, VEGF‐R1, and VEGF‐R2 with dose dependent manners.

Conclusion In the present study, survival of Müller cells under oxidative stress was related to stress‐induced VEGF‐A synthesis. Further study is needed to reveal the protective role of VEGF‐A on retinal Müller cells.
Role of toll‐like receptor 2 and 4 of keratocytes on corneal innate immunity
Authors: CHOI HJ , LEE HJ , JEONG HJ , KIM MK , WEE WR
Published: December 2011

Purpose To investigate the role of keratocytes in corneal innate immune system and cross‐talk of keratocytes with resident antigen presenting cells (APCs), especially through toll‐like receptor (TLR)2 and TLR4.

Methods Firstly, primary cultivated C57BL/6 (B6) mouse keratocytes were stimulated by Pam3CSK4 (TLR2 agonist) or lipopolysaccharide (LPS; TLR4 agonist) and then were evaluated for their cytokine secretion. To demonstrate the cross‐talk between B6 keratocytes and APCs, cytokine changes under Pam3CSK4 or LPS challenge were assessed in co‐culture condition of B6 keratocytes with mouse dendritic cell line (DC 2.4) or mouse macrophage cell line (Raw 264.7). The reversal effect was checked out using keratocytes from TLR2 knockout (KO) or TLR4KO mice.

Results Primary cultivated keratocytes from B6 mice per se actively secreted pro‐inflammatory cytokines, especially interleukin (IL)‐6, with a dose‐dependent manner in response to Pam3CSK4 or LPS challenge. With co‐culture of keratocytes with APCs, secretion of IL‐6 and tumor necrosis factor (TNF)‐α was markedly increased and it was counterbalanced by concurrent increase in IL‐10 and tumor growth factor (TGF)‐β1. After Pam3CSK4 or LPS stimulation, this cytokine balance was completely broken down by overwhelming amplification of IL‐6 and TNF‐α secretion, especially in co‐culture of keratocytes with macrophages, rather than with dendritic cells. Using keratocytes from TLR2KO or TLR4KO mice, we could find the reversal of Pam3CSK4 or LPS‐responsive dose‐dependent increment pattern in IL‐6 and TNF‐α.

Conclusion These results implied that keratocytes and their TLRs could be key components for the ocular homeostasis and pathogen‐associated ocular innate immunity.
Metabolism of cholesterol in health and disease of the retina
Authors: BRETILLON L
Published: December 2011

Purpose Cholesterol is the main sterol in the vertebrate retina.

Methods Deposits of free cholesterol and cholesteryl esters at the basement of RPE are hallmarks of aging in humans, and AMD, the leading cause of vision loss in the Western world.

Results Cholesterol in the neuroretina originates from in situ synthesis and extra‐retinal sources. The relative contribution of cholesterol coming from the circulation and local biosynthesis remains unknown. Tight junctions between retinal pigment epithelial (RPE) cells limit the intercellular movements of molecules to water and small molecules. RPE cells express various lipoprotein and scavenger receptors which can promote the recognition of cholesterol‐rich lipoprotein and enhance the entry of cholesterol in the neurosensory retina. Both the neurosensory retina and RPE cells express proteins which participate to cholesterol export in other tissues than the retina, including CYP46A1. CYP46A1 would represent a mechanism of cholesterol removal from neurons, by catalyzing the hydroxylation of cholesterol at position C24. Other mechanisms than CYP46A1 have been described in the retina, including formation of 7‐ketocholesterol or 27‐hydroxycholesterol.

Conclusion Interestingly a single nucleotide polymorphism in cyp46a1 gene was associated with a significant risk for glaucoma, the second leading cause of blindness worldwide.
Cholesterol and neurodegeneration
Authors: PFRIEGER FW
Published: December 2011

Purpose Based on our previous studies (Mauch et al., 2001 Science; Nieweg et al., 2009 J Neurochem), we hypothesized that retinal ganglion cells (RGCs) depend on the endocytotic import of glia‐derived cholesterol and that a breakdown of this import causes neurodegeneration (Pfrieger, 2003). The membrane protein Niemann‐Pick C1 mediates the exit of externally acquired cholesterol from the endosomal‐lysosomal system. Therefore, we studied, whether mice lacking Niemann‐Pick typ C protein1 (NPC1) due to a spontaneous mutation, show pathologic changes in RGCs and elsewhere in the retina. These mice are a model for the lysosomal storage disorder Niemann‐Pick type C.

Methods We analysed the retinal phenotype of NPC1‐deficient mice by electroretinography, scanning laser ophthalmoscopy and histologic analysis.

Results We observed striking signs of degeneration in retinae from two‐months‐old NPC1‐deficient mice. This included impaired visual function, accumulation of lipofuscin in the retinal pigment epithelium (RPE) layer, degeneration of photoreceptor outer segments, disruption of synaptic layers and upregulation of proteins that mediate cellular cholesterol release under the transcriptional control of the liver X receptor (Claudepierre et al., 2010 MCN). Notably, we observed an increase in LC3, an autophagy marker, specifically in the ganglion cell layer and in the RPE.

Conclusion Our results support the idea that cells in the retina depend on the intercellular exchange of cholesterol via lipoprotein‐mediated transport. Moreover, our results suggest that disturbance of lipid metabolism in the retina contributes to neurodegeneration.
Visual impairment in leber hereditary optic neuropathy carriers of the same family
Authors: REIS A , MATEUS C , SILVA ED , CASTELO‐BRANCO M
Published: December 2011

Purpose To characterize the visual phenotype of asymptomatic Leber’s hereditary optic neuropathy (LHON) associated with mtDNA 11778G>A mutation in carriers from the same family.

Methods Computerized psychophysical assessment methods (CCT ‐ Cambridge Colour Test and CSF ‐ Metropsis Contrast Sensitivity Function Test) were used to evaluate visual function in a population of 17 subjects of two generations of the family mentioned above (mean age ± SD = 27.94±12.97 years; mean visual acuity ± SD = 1.25±0.11) which was compared with an age‐matched control group. This evaluation was completed with electrophysiological assessment (Multifocal ERG, Pattern ERG and Pattern VEP). Stratus‐OCT3 was used for structural evaluation. Statistical analysis at a significance level of p<0.05 was performed using ANOVA, when applicable (otherwise Mann‐Whitney was used).

Results CCT showed evidence for damage of all cone populations (0.0001<p<0.006), implying concomitant damage of parvo/ koniocellular pathways. No significant damage occurred in the achromatic contrast sensitivity across the spatial frequency channels studied, suggesting a relatively preservation of achromatic pathways. PERG results were normal, while mfERG (testing preganglionic pathways) showed a decrease in central ring amplitudes (p=0.006), corroborating central cone damage. Retinal thickness was decreased in the inner rings (R1:p=0.012; R2:p=0.04), irrespective of changes in macular nerve fiber layer thickness. Cortical responses (VEP) were delayed (60':p=0.002 / 15’:p=0.02) with normal amplitudes.

Conclusion Our results suggest that, besides the classical concept of ganglion cell dysfunction, damage to outer retinal circuits could also contribute to subclinical impairment in LHON carriers.
Retinal ganglion cell neurodegeneration in mitochondrial optic neuropathies: a comparative structural study
Authors: MATEUS C , REIS A , SILVA ED , CASTELO‐BRANCO M
Published: December 2011

Purpose to compare structural measurements of retinal degeneration between the most frequent hereditary diseases of retinal ganglion cells (RGCs), Leber Hereditary Optic Neuropathy (LHON) and Autosomal Dominant Optic Atrophy (ADOA).

Methods Peripapillary retinal nerve fiber layer (RNFL) and retinal thickness (RT) were assessed by Spectralis OCT (Heidelberg Engineering, Germany) in 14 patients (28 eyes; age=37.57+16.43 years) with ADOA and 15 patients (30 eyes; age=29.27+13.27 years) with LHON (unaffected carriers with gene mutation). These data were compared with age‐matched control group. Statistical analysis was performed using Mann‐Whitney test at a significant level of p<0.05.

Results ADOA group showed a significant reduction in RNFL (p<.0001 for all quadrants and average) and RT (p<.0001 for average, all quadrants and rings; except ring 1, p=.001), when compared with control group. LHON group yielded an increase in RNFL for inferior (p=.0051) and temporal (p=.0129) quadrants and for average (p=.0014); but a significant decrease in RT (temporal quadrant p=.0079; ring 1 p=.0016; ring 2 p=.0011; average p=.0283), comparing with controls. Comparing with ADOA group, LHON showed a significant increase in RNFL (p<.0001 for all quadrants and average) and also for RT (p<.0001 for all measures), except for ring 1 (no significant differences was found between study groups).

Conclusion As expected, ADOA group presents a significant loss of peripapillar RGCs and consequently a significant reduction in RT. LHON group shows an increase in RNFL, which is consistent with a documented swelling of the papillomacular bundle. Surprisingly, we found a decrease in RT that suggests retrograde involvment of other retinal cell type.
Differential effects of irradiation with X‐Rays and carbon ions on normal and tumoral uveal melanocytes
Authors: CALIPEL A , LUX AL , MOURIAUX F
Published: December 2011

Purpose The local treatment of uveal melanoma (UM) proposed is in the majority of the cases the protontherapy or the radiotherapy of contact by patches. However, these treatment ends in blindness in 60 % of the cases. Indeed, the hadrons which are proton and carbon ion possess a Transfer of Linear Energy (LET) higher than the conventional radiotherapy (X‐rays and γ). Our previous findings highlight the key role of the WTB‐Raf/MEK/ERK pathway in the control of proliferation of UM cells. Our project investigate the positive and negative effects of the irradiation on the UM and healthy uveal melanocytes. It thus seems interesting to analyze the effects of the irradiation on ERK1/2 activation and the link between these pathways with the cell cycle.

Methods We characterize the radiosensibilities, after irradiation by X‐rays and carbon ion, of six UM cell llines (92.1, Mel 270, SP6.5, MKT‐Br, µ2 and TP17) and two types of healthy cells: the human uveal melanocytes (NUM) and the epithelial cells of the human retina (ARPE19).

Results We showed that carbon ion present with regard to the X‐rays a relative biological effectiveness (RBE) of 1.86 to 2.46 at 10% survival. We showed that the irradiations X and carbon had the same effects by provoking a stop of the cellular cycle in phase G2 / M until 120 hours. According to the type of irradiation, two mechanisms are observed on the ERK1/2 signaling pathway. X‐ray induced a transitory suractivation of ERK1/2. Whereas, ERK1/2 activation was constantly inhibited by carbon beam

Conclusion These preliminary results show that the carbon beam present a better biological efficiency than X‐rays in uveal melanoma cells leading a sustain inhibition of ERK1/2 pathway.
Resveratrol, rapamycin and MG‐132 as inducers of autophagy in ARPE‐19 cells
Authors: PETROVSKI G , BERENYI E , ALBERT R , MOE MC , FESUS L , BERTA A
Published: December 2011

Purpose To investigate the effect of the polyphenol resveratrol (3,5,4'‐trihydroxy‐trans‐stilbene), rapamycin (RAP) and proteasome inhibitor MG‐132 on cell death and autophagy in human retinal pigment epithelium‐derived ARPE‐19 cells.

Methods ARPE‐19 cells were exposed to different treatment regimens: 10‐50microM resveratrol, 50‐100 nM RAP, 50 microM chloroquine (CQ) and 50‐100 nM MG‐132 over 48 hours. The levels of LC3‐II, mammalian target of rapamycin (mTOR), Hsp70, p62 were determined by Western blot analysis; autophagic vacuoles (AVs) formation was detected by acridine orange, pDendra2‐hLC3 expression and transmission electron microscopy; cell death was quantified using annexin‐V‐FITC/propidium iodide (PI) labeling on flow cytometry.

Results Exposure to RAP and MG‐132 caused a time‐ and concentration dependent induction of autophagy that could be inhibited by 3‐methyladenine (3‐MA), while the induction of an active autophagic flux could be verified with CQ treatment, a blocker of the autophagosome‐lysosome fusion. Similarly, resveratrol alone could induce autophagy in ARPE‐19 cells, serving as a pro‐survival signal in ARPE‐19 cells. Inhibition with 3‐MA increased the death rate of resveratrol treated ARPE‐19 cell, further proving the autophagy‐related protective role of resveratrol.

Conclusion Resveratrol at lower concentrations, RAP and MG‐132 can provide a pro‐survival stimulus to ARPE‐19 cells by inducing autophagy. This property can possibly be used for prolonging the lifespan of retinal pigment epithelium in diseases such as age‐related macular degeneration.
Quantification of GFAP and NF‐200+ retinal ganglional cells in contralateral mice retina to experimental glaucoma
Authors: ROJAS B , DE HOZ R , SALAZAR JJ , RAMIREZ AI , GALLEGO BI , RAMIREZ JM , SALINAS‐NAVARRO M , ORTIN‐MARTINEZ A , TRIVINO A
Published: December 2011

Purpose To analyze the effects of laser‐induced ocular hypertension (OHT) in the macroglia and retinal ganglion cells (RCGs) of eyes with OHT (OHT‐eyes) and contralateral eyes two weeks after lasering

Methods Adult Swiss mice were divided into two groups: naïve (n=6) and lasered (n=6). Retinal whole‐mounts were immunostained with antibodies against GFAP and NF‐200, the latter used to analyze the presence of degenerated RGCs. The GFAP‐labeled retinal area (GFAP‐RA) and the number of astrocytes and NF‐200+RGCs were quantified

Results In comparison with naïve: i) astrocytes were more robust in contralateral eyes and had less GFAP immunoreaction and secondary processes in OHT‐eyes; ii) GFAP‐RA was increased in contralateral eyes (p<0.032) and decreased in OHT‐eyes (p<0.001); iii) in both contralateral and OHT‐eyes, GFAP was upregulated in Müller cells. No differences in astrocyte number were found among naïve, contralateral, and OHT‐eyes. NF‐200+RGCs were observed in OHT‐eyes (503+/‐145 cells) with a trend for the GFAP‐RA to decrease and for the NF‐200+RGC number to increase from the center to the periphery (r=‐0.448)

Conclusion Two weeks of laser‐induced OHT produced macroglial retinal changes in both contralateral and OHT eyes. The differences in NF‐200+RGCs counting among contralateral and OHT‐eyes support a possible contribution of retinal macroglia to neuronal homeostasis in contralateral eyes. On the basis of the macroglial changes detected in the present work, the use of the contralateral eye as an internal control in experimental induction of unilateral OHT should be reconsidered
T Cells and the Eye
Authors: DICK A
Published: December 2011

Purpose Experimental Autoimmune uveoretinitis (EAU) is a clinico‐pathological model of human non‐infectious uveitis. This review is to illuminate the dynamics of T cell infiltration in the eye during the course of EAU, the control of T cell activation and proliferation of T cells at the target site and ultimately control of inflammation.

Methods Using models of EAU we are able to accurately dissect and enumerate T component, cyokine liberation and interrogate interactions of myeloid‐T cell compartment within the local environment during autoimmune inflammation.

Results During the course of EAU, the early T cell infiltrate is seen prior to clinical disease. During acute inflammation there is a mixed T cell response, predominantly CD4+ Th1 and Th17 response. In later stages, Treg cells accumulate along with minor populations of CD8+ and NK T cells. Throughout there is close interaction with myeloid‐derived cells governing response of T cell activation and proliferation and vice versa mediated in part by TNF and TSP.

Conclusion The cellular interactions within the local microenvironment regulate T cell expression.
Macrophages and the Eye
Authors: JAGER MJ
Published: December 2011

The members of the antigen‐presenting cell family are known under many names, such as macrophages, Langerhans cells, dendritic cells and monocytes. They can be found in all ocular tissues, and depending on their activation state and characteristics, these cells can either stimulate or inhibit immune responses. Furthermore, macrophages may play a role in wound healing or angiogesis. These differential roles will be illustrated by showing their function in ocular tumors and in corneal diseases.
PMNs and the Eye
Authors: ATHERTON S , ZHENG M
Published: December 2011

Polymorphonuclear leukocytes (PMNs) are an important modulator of many types of infection. The purpose of this presentation will be to review the characteristics and functional capabilities of these cells and to discuss their role in the pathogenesis of HSV‐1 ocular infection.
Ultrastructural organisation of stingray and shark corneal stroma
Authors: ALIBRAHIM A , ALMUBRAD T , AKHTAR S
Published: December 2011

Purpose Collagen fibrils and proteoglycans are the main components of the corneal stroma. We report here ultrastructural organisation of collagen fibrils and proteoglycans of corneal stroma in stingray and shark.

Methods Four corneas of stingray and shark were fixed in 2.5% glutaraldehyde containing cuprolinic blue in sodium acetate buffer and processed for electron microscopy. Tissues were embedded in TAAB 031 resin. Measurements were carried out by using the ‘AnalySIS LS Professional program’.

Results The corneal stroma of shark is thicker (336µm) compared to stingray stroma (143µm). The corneal stroma in both fish consists of parallel running lamellae containing collagen fibrils and proteoglycans. The lamellae in sharks are thicker in the anterior stroma (12.14µm), middle stroma (18.3µm) and posterior stroma (13.0µm) compared to stingray lamellae in anterior stroma (7.6µm), middle stroma (8.9µm) and posterior stroma (5.2µm). In both fish lamellae of middle stroma was thicker compared to anterior and posterior stroma. In both fish, lamellae were obliquely crossed by bundles of collagen fibrils, which are known as sutures. Proteoglycans are larger in stingray compared to shark.

Conclusion The presence of sutures is the unique feature of these fish. It has been reported that these sutures inhibit the swelling of the cornea in sharks.
Corneal ulcerations associated with allergy and meibomian gland dysfunctions
Authors: DOAN S
Published: December 2011

Abstract not provided
Herpes Simplex and Herpes Zoster associated corneal ulcerations
Authors: LABETOULLE M
Published: December 2011

Corneal ulcerations are the landmark of viral infections of the ocular surface. The clinical patterns of these ulcerations may vary according to the virus, the type of infection (epithelial or stromal) and the history of the patient. Dendritic ulcers are the most typical findings of Herpes Simplex Virus (HSV) infection, but may also be seen during Varicella‐Zoster Virus (VZV) infection. They share common feature such as rapid diffusion of fluorescein beneath the edges of the ulcer. Inversely, this diffusion is usually not seen in pseudo‐dentritic ulcers, which may be related to either some other infectious agents, or toxicity of eyedrops, or corneal denervation. Geographic ulceration is usually due to HSV infection mistreated with topical steroids, especially if the size of the defect is rapidly progressing. In contrast, a slowly progressing geographic ulcer, with amorphous margins, rather results from neurotrophic conditions. Finally, deep corneal ulcerations, involving both the epithelium and the stroma should be first treated as HSV or VZV necrotic keratitis, but other agents like bacteria, acanthameba and even fungi may lead to similar findings. Such cases thus need a daily control of the evolution to find optimal treatment.
Use of imaging techniques to reveal connectivity within the human fovea and to predict consequences of lesions.
Authors: SJÖSTRAND J , POPOVIC Z
Published: December 2011

Purpose A knowledge of connectivity from the central photoreceptors and their axons, via the bipolar cells to the retinal ganglion cells (RGC), is required to understand the consequences of lesions in different locations of the human fovea. The purpose was to create a model of the connectivity within the fovea based on information available in recent non‐invasive studies of the normal fovea with optical coherence tomography (OCT) and adaptive optics (AO).

Methods OCT data from the study by Lujan et al. (2011) of the thickness of the Henle fiber layer (HFL) at various eccentricities was used in combination with data of cone density and visual resolution obtained from AO studies. An angle of 6 degrees was assumed between the cone axons and the external limiting membrane, at eccentricities between 0.2 and 1 mm, to calculate the lateral displacement from the cone photoreceptor cell body to the cone pedicle. Cone density and visual resolution was obtained from published AO studies (Wolfing et al., 2006; Rossi & Roorda, 2010).

Results The thickness (HFLt) versus eccentricity along the horizontal meridian was derived from Lujan et al. (2011) and used to calculate the lateral displacement of cone pedicles. Zones in the cone pedicle layer and RGC layer connected to corresponding regions of the cone mosaic (0‐0.2 mm, 0.2‐0.4 mm, 0.4‐0.6 mm) were calculated and related to AO estimates of visual resolution.

Conclusion Our model may be useful to visualize functional connectivity and to predict the effect of lesions within the fovea. A maximal effect of lesions in the bipolar and RGC layers, due to the displacement caused by the cone axons, may be anticipated at an eccentricity of about 0.5 mm or 2 degrees.
Monitoring the eye lens
Authors: BEHRENS R
Published: December 2011

Purpose To prevent the induction of cataracts by ionizing radiation (photons or betas), the International Commission on Radiological Protection (ICRP) has lowered the annual dose limit for the eye lens from 150 mSv down to 20 mSv for occupational exposures. Thus, protecting the eye and monitoring the lens dose to prevent exceeding the dose limit is more necessary than formerly assumed.

Methods Different kinds of dosemeters were investigated to give guidelines on monitoring the lens dose when necessary.

Results Hp(0.07) dosemeters are constructed to monitor the local skin dose in 0.07 mm depth as the radiation‐sensitive epidermis lies about 0.07 mm below the surface. In pure photon radiation fields, e.g. in interventional radiology, Hp(0.07) dosemeters are appropriate to monitor the lens dose when worn near the eye and if the back of their case consists of thin plastic. In beta radiation fields, e.g. in nuclear medicine, Hp(0.07) dosemeters may overestimate the lens dose by a factor of 100 or more. Thus, they are unsuitable here. Hp(3) dosemeters are constructed to monitor the lens dose as the radiation‐sensitive part of the lens lies about 3 mm within the eye. Only very few Hp(3) dosemeters exist, but, by construction, they should monitor the lens dose also in beta fields correctly. However, this has not yet been demonstrated. Hp(10) dosemeters are constructed to monitor the whole body dose as the inner organs are assumed to lie about 10 mm within the trunk. Hp(10) dosemeters usually underestimate the lens dose and are, thus, unsuitable.

Conclusion Protection measures such as lead glass shields or glasses should be used. In case exposures cannot be avoided, appropriate dosemeters must be worn near the eye behind devices used to shield the eyes but not behind a shield worn on the trunk (e.g. a lead apron).
Novel methods to maintain corneal transparency while increasing the strength of LASIK flaps
Authors: KAMMA‐LORGER CS , DOOLEY EP , DU Y , DAVIES L , MI S , FUNDERBURGH JL , STEPHENS P , MEEK KM
Published: December 2011

Purpose To reduce the incidents of keratectasia after LASIK we have been attempting to increase the strength of the flap using various methods1. We now are aiming to improve this by transplanting stromal fibroblasts, oral fibroblasts (a scarless reparative cell type) or stromal progenitor cells into LASIK corneas.

Methods LASIK flaps were created in ovine corneas and human oral fibroblasts or human stromal progenitor cells were applied on the flap bed. Stromal flaps in bovine corneas were treated with stromal fibroblasts from the same species. LASIK corneas without any treatment acted as controls. All samples were placed in organ culture and allowed to heal for up to 3 weeks. The mechanical strength of the flaps was measured using a vertical extensometer in a “pull to break” test. Transparency was assessed by making spectorphotometric measurements across the visible spectrum. Cell phenotype was examined by anti‐alpha smooth muscle actin immunostaining.

Results All approaches improved the strength of LASIK flaps but the bovine stromal fibroblasts compromised the tissue’s transparency. Both human cell types maintained corneal transparency but the oral fibroblast approach was the most efficient one in the 3 week culture period, perhaps due to the scarless reparative phenotype of these cells.

Conclusion LASIK flap strength can be increased biologically but the challenge now is to apply these methods in an animal model to assess the long term of the efficacy of increasing flap adhesion strength and maintain corneal transparency and its potential use in medical intervention. 1. Mi S, Dooley EP, Albon J, Boulton ME, Meek KM, Kamma‐Lorger CS. J Cataract Refract Surg. 2011; 37(1):166‐72
A new method of the eye refraction correction under non‐ablative laser radiation
Authors: BOLSHUNOV A , SOBOL E , AVETISOV S , BAUM O , SIPLIVY VLAD , OMELCHENKO A , FEDOROV A
Published: December 2011

Purpose The aim is to present a new approach of cornea reshaping using termomechanical effect of pulse repetitive laser radiation both on sclera and cornea.

Methods Experiments were performed in vitro with eyes of pigs, rabbits, cadavers, and in‐vivo with rabbit eyes using an Erbuim glass fiber laser of 1.56 microns in wavelength. Thermomechaniucal properties of sclera and cornea during laser heating were studied with an indenter test and using thermo mechanical analyzer. The alterations in eye refraction was measured with various optical techniques including coherent tomography, confocal microscopy and shlieren visualization. Histological technique was used to study possible alterations in tissues structure.

Results The results have shown different thermomechanical properties of cornea and sclera allowing to change eye refraction under nondestructive laser irradiation. Denaturation thresholds for stromal collagen of the cornea were measured for various laser wavelengths. Optimal laser settings were established allowing obtain vision correction without visible damage and denaturation of the eye tissues. The maximal change of eye refraction obtained was of 6 diopters. The stability of rabbit eye refraction was established during at least 6 months. Hystological analysis did not revile substantial alterations in cornea structure.

Conclusion The advantages of the new approach are provided by the following factors (1) noninvasive and potentially reversible nature of exposure on the cornea and sclera, (2) minimal exposure on the central zone of the cornea, (3) availability of a feed back control system that prevents denaturation and damage of the cornea, (4) possibility of a repeated procedure.
Comparative evaluation of photorefractive keratectomy with the use of an excimer laser and a solid state laser system
Authors: KONTADAKIS G , KOUNIS G , KYMIONIS G , PLAKA A , STRATOS A , DIAKONIS V , PALLIKARIS IG
Published: December 2011

Purpose To compare refractive results of photorefractive keratectomy (PRK) with the Solid State laser and Excimer laser.

Methods This retrospective cohort study comprised eighty patients (153 eyes) who received PRK with the excimer laser Allegretto 400 Wave Eye‐Q (group 1), and 79 (156 eyes) who received PRK with the solid state laser Pulzar Z1 (group 2). All patients had a complete ophthalmic examination preoperatively to exclude ocular disease. All procedures were performed using an identical technique. Groups were matched in terms of age sex, preoperative refraction and visual acuity (VA).Preoperative and postoperative assessments included uncorrected distance VA, corrected distance VA, manifest and cycloplegic refractions, slitlamp examination and corneal topography.

Results No statistically significant differences were found 1 year postoperatively between the two groups in terms of patient’s corrected distance VA (p=0.23), uncorrected distance VA (p=0.20),and remaining refractive error (difference between achieved and attempted correction) (p=0.60).

Conclusion Both systems performed similarly in terms of efficacy and predictability. The use of the Solid State laser for the correction of myopia with photorefractive keratectomy is an effective alternative for the Excimer laser.
Evaluation of tear film osmolarity after mechanical lasik, femtosecond laser‐assisted sub‐bowman keratomileusis and lasek
Authors: CANADAS SUAREZ P , GARCIA‐GONZALEZ M , ORTEGA MARIA , TEUS M
Published: December 2011

Purpose To evaluate the tear osmolarity in patients that underwent LASIK (performed with a microkeratome or a femtosecond laser) or LASEK three months before.

Methods We performed a prospective observational study of consecutive eyes that had LASIK performed with a mechanical microkeratome (MM‐LASIK), with a femtosecond laser (FS‐LASIK) or that had LASEK. Three months postop, tear osmolarity was measured with the TearLab TM Osmolarity System. This measure was performed only in one eye per patient. A normality value of 308 ± 5 mOsm/L (provided by the manufacturer) was used to clasify the tear osmolarity.

Results 105 eyes of 105 patients were included in the study (35 eyes in each group). No significant differences were found in the mean preoperative refractive defect and patient age between groups. Three months postop, mean osmolarity values were 304.8 ± 20.2 mOsm/L (range, 275 to 371) in the MM‐LASIK group; 306.8 ± 17.7 mOsm/L (range, 280 to 342) in the FS‐LASIK group and 307.9 ± 17.6 mOsm/L (range, 280 to 374) in the LASEK group. After three months, there was no statistically significant difference in tear osmolarity between the groups.

Conclusion Our results suggest that tear film osmolarity measured with the TearLabTM Osmolarity system tends to achieve normal values three months after MM‐LASIK, FS‐LASIK and LASEK.