bluuebunny/crossref_metadata_2025 huggingface dataset:
Can dogs carry the global pandemic candidate avian influenza virus H9N2?
Authors: Amirsalehy H , Nili H , Mohammadi A
Published: August 2012

Background

H9N2 avian influenza virus (AIV) is one of the most widely circulating viruses in Eurasia. Recent studies have shown that the molecular recombination of H9N2 and H1N1 could pose a pandemic threat. Mammals that are susceptible to subtype H9N2 may contribute to the spread of the virus.

Objective

To determine the susceptibility of 1‐year‐old dogs to H9N2 AIV.

Procedure

H9N2 AIV infection was experimentally reproduced in 1‐year‐old dogs. The animals were intranasally inoculated with a titre of 107.5 (50% egg infective dose) of H9N2 AIV isolated from a broiler farm during an outbreak. The animals in the contact group were exposed to contaminated surfaces.

Results

Clinical signs including sneezing, coughing and nasal discharge were observed in the inoculated and contact groups. The virus was detected in nasal swab, faecal and buffy coat samples of dogs in both the inoculated and contact groups and both groups developed antibody titres against AIV H9N2 subtype.

Conclusion

H9N2 AIV isolated from outbreaks in a broiler farm can easily infect dogs and infected animals shed the virus. Because many Asian countries are facing frequent outbreaks of H9N2 infection in the poultry industry, dogs could be a potentially important source of virus transmission within and between poultry farms.
Physically Based, Hydrologic Model Results Based on Three Precipitation Products1
Authors: Chintalapudi Singaiah , Sharif Hatim O. , Yeggina Subash , Elhassan Almoutaz
Published: August 2012

Abstract:  The main objective of the study is to examine the accuracy of and differences among simulated streamflows driven by rainfall estimates from a network of 22 rain gauges spread over a 2,170 km2 watershed, NEXRAD Stage III radar data, and Tropical Rainfall Measuring Mission (TRMM) 3B42 satellite data. The Gridded Surface Subsurface Hydrologic Analysis (GSSHA), a physically based, distributed parameter, grid‐structured, hydrologic model, was used to simulate the June‐2002 flooding event in the Upper Guadalupe River watershed in south central Texas. There were significant differences between the rainfall fields estimated by the three types of measurement technologies. These differences resulted in even larger differences in the simulated hydrologic response of the watershed. In general, simulations driven by radar rainfall yielded better results than those driven by satellite or rain‐gauge estimates. This study also presents an overview of effects of land cover changes on runoff and stream discharge. The results demonstrate that, for major rainfall events similar to the 2002 event, the effect of urbanization on the watershed in the past two decades would not have made any significant effect on the hydrologic response. The effect of urbanization on the hydrologic response increases as the size of the rainfall event decreases.
Classification of uveitis
Authors: ANDROUDI S
Published: August 2012

Purpose Classification and standardization of uveitis is important, as it enhances the precision and comparability of clinical research from different centers and assists in the development of a complete picture of the course of the disorders and their response to treatment

Methods Attempts have been made to standardize some aspects of uveitis, and various classification criteria, inflammation grading schema, and outcomes criteria have been described.

Results The most widely used classification of uveitis is the one devised by the International Uveitis Study Group (IUSG) in 1987, based on the anatomical location of the inflammation. This classification includes anterior uveitis (iritis, iridocyclitis, and anterior cyclitis), intermediate uveitis (pars planitis, posterior cyclitis, and hyalitis), posterior uveitis (focal, multifocal, or diffuse choroiditis, chorioretinitis, retinitis, and neuroretinitis) or panuveitis (anterior chamber, vitreous, retina, and choroid). In 2005, the Standardization of Uveitis Nomenclature (SUN) Working Group standardized a grading schema for aspects of intraocular intraocular inflammation, that is, anterior chamber cells, anterior chamber flare, and vitreous haze, was developed. Standardized definitions of outcomes, including reporting visual acuity outcomes, were approved.

Conclusion Today’s uveitis nomenclature has been revised regarding the anatomical location and the grade of inflammation, and supplemented by the inclusion of definitions for onset, duration and course.
Symptoms and signs of posterior uveitis
Authors: KHAIRALLAH M , KAHLOUN R
Published: August 2012

Purpose Posterior uveitis (PU) is an important anatomic form of uveitis in which the primary site of infl ammation 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 fl are 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 diff use, 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 diff use 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.
Laboratory work‐up and specialized investigations
Authors: PLEYER U
Published: August 2012

Based on the anatomical involvement of the eye intraocular inflammation is classified into anterior, intermediate, posterior and panuveitis. All subtypes of uveitis are potentially related to infectious and noninfectious etiologies. This presentation will assist the participants in accurately diagnosing uveitis in a step latter approach including physical and laboratory investigations. In addition, a tailored approach based on confounding clinical observations with specialized investigations will help to further differentiate clinical entities. In cases of suspected intraocular infections the option of intraocular fluid evaluation for antibody testing and polymerase chain testing against the causative agent will be presented. Taken together, this part of the course will provide a rational decision‐making strategy for diagnosis of patients with uveitis.
Morphological techniques for endothelial cell analysis of corneal grafts
Authors: THURET G
Published: August 2012

Abstract not provided
Diagnosis
Authors: BODAGHI B
Published: August 2012

Abstract not provided
Indications and limitations of amniotic membrane transplantation
Authors: YEUNG A
Published: August 2012

Abstract not provided
To analyse the role of vitreous in a retinal detachment
Authors: BERROD JP
Published: August 2012

Abstract not provided
How to prevent proliferative vitreoretinopathy ?
Authors: JONAS JB
Published: August 2012

Purpose Proliferative vitreoretinopathy (PVR) is a serious complication of any rhegmatogenous retinal detachment.

Methods Besides an early intervention to close the retinal defect by either an episcleral buckling procedure or by vitrectomy and internal tamponade, additional medical regimens may be sought after to prevent the proliferation of intravitreally intruded retinal pigment epithelium cells and other cells.

Results Itravitreal medical therapy, including drugs such as triamcinolone, microplasmin or anti‐VEGF drugs ma ybe discussed for their rol ein the prevention of PVR.

Conclusion Potential procedures to reduce the risk of PVR will be discussed.
How to prevent postoperative complication?
Authors: CREUZOT C
Published: August 2012

Retinal detachment can lead to early and delayed post‐operative complications. The purpose of the course is to present the different complications following retinal detachment surgery with their appropriate treatments. The postoperative complications will be divided according to the presentation of the patient (ie inflamed, painful eye or white painless eye) with or without visual loss.Then, IOP measurement and the results from slit lamp and fundus exam will provide us with the main signs useful for diagnosis. With a painful red eye, the main severe diagnoses will be the different causes of increased IOP and endophthalmitis. The main cause of increased ocular pressure is related to the internal tamponade used during surgery (gas or silicone). However, the diagnosis of the presence of silicone in the anterior chamber should be difficult. Hyphema or cataract due to gas should prevent us from a good fundus examination. This course will mainly focus on the different early and more delayed complications after retinal detachment surgery and will try to give some rules to decrease this risk.
Margins or not margins
Authors: MOURIAUX F
Published: August 2012

Purpose Management of malignant eyelid tumors needs to be individualized, taking into account patient factors, tumor characteristics, and histological subtype. Several treatment modalities have been proposed, but surgical excision with monitoring of excision margins has the highest cure rate. The basis of ideal resection margins is almost completely from retrospective data. Moreover, resection margins of basal cell carcinoma are less extensive than spindle cell carcinoma, Merkel carcinoma or others. In another hand, Mohs surgery or complete surgical excision with frozen‐section control of the margins offers the lowest tumor‐recurrence rate.

Methods The course will discuss of margins, Mohs and Frozen‐section control in malignant eyelid tumors especially for basal cell carcinoma
White dot syndromes
Authors: MARKOMICHELAKIS N
Published: August 2012

Abstract not provided
Paediatric uveitis
Authors: BODAGHI B
Published: August 2012

The etiology and treatment of uveitis in children remains different from adults. Infectious and auto‐immune conditions must be identified. Juvenile idiopathic arthritis‐associated uveitis is the main etiology of chronic anterior uveitis. Pars planitis is another frequent etiology of bilateral auto‐immune uveitis. On the other hand, toxoplasmic retinochoroiditis, ocular toxocariasis and cat scratch disease should be excluded in children with unilateral posterior uveitis. Case reports will be presented in order to illustrate th management of different pediatric uveitis entities. Methods
Experimental models of intraocular inflammation
Authors: BEUERMAN R , YUAN ZH
Published: August 2012

Purpose Intra‐ocular surgery is usually followed in the near term post‐operative perios by a course of steroids or NSAIDS. However, the nature of post‐surgical inflammation is not well known due to the problems with developing an useful model. This talk describes the issues and outcomes using a mouse model of cataract surgery.

Methods Cataract surgery was simulated by an approach 0.4mm posterior ttp to the limbus using a sapphire knife. Pupillary dilation was achieved by using 1% tropicamide and 2.5% phenylephrine. A corneal incision, of ∼30–60°, was made, and 1% sodium hyaluronate was inserted into the anterior chamber. The corneal incision was then extended to ∼90°, and an anterior curvilinear continuous capsulorrhexis was performed and lens was removed by forceps. The anterior chamber was filled with 1% sodium hyaluronate, and the corneal wound was closed using interrupted sutures. Topical 2.5% phenylephrine, 1% tropicamide, and 1% atropine were administered at the end of the surgery. Antibiotics were administered after surgery three times/day.

Results In vivo confocal microscopic analysis showed cell infiltration was not observed in the anterior chamber in the control eye, but seen in the wounded eye at PO day 1(66±5 cells). Cells in the anterior chamber peaked at day 3 (316±52 cells), and decreased over time to day 7 (3±1 cells). RT‐PCR showed that S100A8/9 mRNA levels in the iris were up‐regulated significantly (p<0.05) at PO day 1, peaked at day 3, and remained elevated to day 7. mRNA levels of S100A8/9 in the cornea, HMGB1 in the cornea and iris increased significantly (p<0.05) at PO day 1 and decreased over time. Immunostaining for S100A8/9 and HMGB1 corroborated the RT‐PCR results. There was no detectable S100A8/9 or HMGB1 in the unwounded iris. The expression of S100A8/9 and HMGB1 was stimulated in the cornea stroma and iris, with a peak at PO day 3, and decreasing over time.

Conclusion A mouse model and potentially other animal models of cataract surgery could be useful to develop new methods for control of intra‐ocular inflammation.
Femtolaser assisted preparation and quality of endothelial button
Authors: BOURGES JL
Published: August 2012

Abstract not provided
FEMTO‐DSEK: is endothelial cut possible?
Authors: BAIKOFF G
Published: August 2012

The interest of the Femtosecond laser is its ability to cut parallel and regular corneal surfaces with great precision. The most common example we have is its routine use for lasik flaps for which the standard thickness is around 100µm. The difficulty of deep cuts with the Femtolaser gave rise to a number of irregularities, leading the author to use a posterior trans endothelial cut. The advantage of the VisuMax is that it applies very little pressure on the endothelium, the endothelial cells undergo very little alteration and with a cell loss of approximately 5% to 7%. After surgery (endothelial graft) the smoothness of the cut is not perfect (high resolution OCT) and a number of endothelial graft irregularities are visible. These irregularities can be due to the viscoelastic interface used to protect the endothelium when the aplanation cone comes into contact with the graft or else due to the bubbles that appear to be more important in the posterior stromal tissue than in the anterior one. The corneal graft is still swollen and the slack substance of this posterior tissue has a different reaction than when cutting a lasik flap in the anterior stromal tissue which is much denser. A certain number of methods are possible in order to try and reduce these irregularities. They will be discussed during the presentation.
Rho Kinase Inhibitors: the end of endothelial keratoplasty?
Authors: GICQUEL JJ
Published: August 2012

The human corneal endothelium shows poor regenerative abilities. In cases of pseudophakic bullous keratopathy or Fuchs’ dystrophy, descemet striping automated keratoplasty brings considerable clinical benefits. However there are still allograft rejections and the shortage of donor corneas is a problem that still needs to be solved. The Rho/Rho kinase (ROCK) inhibitors may help establishing ex vivo endothelial cell cultures and may also give birth to new pharmacological treatments of corneal endothelial dysfunction.
Corneal bacterial infections
Authors: GICQUEL JJ
Published: August 2012

Because of their potential to permanently impair vision or perforate the eye, bacterial corneal ulcers are an ophthalmologic emergency. They usually follow an insult (sometimes minor) in the corneal epithelium that provides an entry for bacteria. The increased use of soft contact lenses in recent years has led to an important rise in the occurrence of bacterial ulcers (especially aggressive Gram‐ bacteria). In this course you will learn about the new concepts in bacterial ulcers diagnosis and treatment.
Cranial nerves 3,4 and 6: from brainstem to orbit
Authors: KAWASAKI A
Published: August 2012

Purpose To review the pertinent anatomy of the ocular motor cranial nerves in correlation with their clinical presentation

Methods didactic lecture and cass

Results The nucleus of the oculomotor nerve (CN3) is composed of several subnuclei. The central caudal subnucleus innervates the levator palpebrae bilaterally. Fibers from the superior rectus subnucleus decussate and innervate the SR muscle of the contralateral eye. Axonal fascicles from each subnucleus remain topographically arranged as they traverse the midbrain. Autonomic fibers (pupil and accommodation) orient dorsomedially in the peripheral nerve as it exits the peduncles of the ventral midbrain. The clinical presentation of a nuclear, fascicular and peripheral lesion of CN3 are distinctive and localizing. The trochlear nerve (CN4) is the smallest cranial nerve yet has the longest pathway. It is susceptible during closed head injury. The abducens nerve (CN6) exits the ventral pons and ascends the clivus to reach the cavernous sinus. It is prone to injury with changes in intracranial pressure. Lesions of the clivus can also cause bilateral abducens palsy.

Conclusion Understanding the anatomic pathway of the ocular motor nerves can help focus the etiology and location of the lesion.

Commercial interest
Supranuclear eye movement disorders
Authors: BORRUAT FX
Published: August 2012

Supranuclear disorders of eye movement result from a relative deafferentiation of oculomotor nuclei (III, IV, VI) in the presence of intact nuclei, cranial nerves and extraocular muscles. In supranuclear oculomotility disorders there is often a dissociation of eye movements (for example, gaze palsy with preserved vestibulo‐ocular reflex, or saccadic palsy with preserved pursuit). This presentation will discuss the most important supranuclear disorders, including internuclear ophthalmoplegia, dorsal mesencephalic syndrome, skew deviation, and progressive supranuclear palsy. At the end of the session, participants should be able to recognize and provide a differential diagnosis for the aforementioned supranuclear disorders.
Suspicious choroidal naevi
Authors: KIVELÄ T
Published: August 2012

Purpose To summarize salient characetristics of suspicious uveal naevi and guidelines for their management.

Methods Review of literature and personal experience.

Results The differential diagnosis of uveal naevi and melanoma is based on clinical examination with the slit lamp and indirect ophthalmoscope together with ultrasonography of the eye. Large to medium‐sized melanomas are reliably differentiated from naevi using these methods. The challenge lies in early detection of small melanomas which are more difficult to tell from presumed naevi. A useful mnemonic 'To Find Small Ocular Melanomas' reminds the general ophthalmologist to look for tumour Thickness of more than 2 mm, subretinal Fluid, visual Symptoms, Orange pigment and location of the tumour Margin at the optic disc. Optical coherence tomography and fundus autofluorescence imaging help in identifying subretinal fluid and orange pigment and in measuring the thickness of thin choroidal naevi and melanomas. Each of the risk characteristics roughly doubles the likelihood of growth so that the risk for growth is about 30 times higher when all five characteristics are present as compared to their absence. In addition, a low acoustic profile, the absence of a halo around the tumour and the absence of drusen over it increase the likelihood of growth. The trend is toward taking a biopsy of suspicious small choroidal tumours as an alternative to documenting growth before treating them as melanomas.

Conclusion Patients with a choroidal melanocytic tumour with at least one risk characteristic benefit from referral to an ocular oncologist. The rest of the patients can be made aware of their presumed naevus and that they should be observed periodically. The patients should be told to return immediately if they develop new visual symptoms.
Malignant melanoma of the uvea: radiotherapy techniques
Authors: DESJARDINS L
Published: August 2012

Purpose Malignant melanoma of the uvea is a relatively radioresistant tumor which can be treated with radiotherapy only with high dose. For this reason only radiotherapy techniques with precise location of the radiation doses are used

Methods Proton beam therapy has been used since 1975 by Gragoudas in Boston and the in Europe since 1983.Because of the Bragg pick, the use of an accelerated proton beam allows delivering homogenous high dose to the tumor while sparing the normal tissue around. Brachytherapy is also widely used. It consists to suture to the sclera against the tumor a radioactive plaque that can contain iodine 125 seeds or ruthenium. Iodine 125 is a low energy gamma emmeting isotope; the radiation is totally stopped by heavy metals like gold .The seeds need to be changed every two months because of its half life. Ruthenium 106 is a beta emmiting isotope. Its low penetration prevents its use for the bigger tumors. With brachytherapy the dose of 90 grays is usually delivered to the top of the tumor while the base receives more than 300grays.

Results Tumor control is excellent with proton beam (less than 5% recurrence at 5 years) and good with brachytherapy (less than 10% recurrence at 5 years) Globe preservation is possible in more than 90% of treated patients. The visual acuity depends of the size and location of the tumor. Mortality by metastasis is equal after conservative management by radiotherapy or enucleation.

Conclusion Various techniques of radiotherapy can achieve good local control and globe preservation in patients with uveal melanoma
Malignant melanoma of the uvea: surgical techniques
Authors: DAMATO B
Published: August 2012

Purpose To describe the surgical techniques in the management of uveal melanoma.

Methods The surgical techniques include: excision‐, incision‐, and aspiration‐biopsy; various forms of exo‐resection and endoresection; enucleation and exenteration. Local resection and enucleation can be primary or secondary.

Results Biopsy greatly enhances prognostication by allowing multivariate analysis of clinical, histological and genetic predictors of metastasis. Primary local resection is indicated in only a minority of patients, in whom radiotherapy is unlikely to be successful, because of tumour size or location. The role of neoadjuvant radiotherapy is controversial. Secondary local resection can salvage eyes with local tumour recurrence or the toxic tumour syndrome after radiotherapy. Enucleation may be necessary because the tumour is too extensive when the patient presents or because of complications after conservative forms of therapy.

Conclusion The results of biopsy and surgical treatment are highly surgeon‐dependent and require appropriate skills if complications are to be avoided. Intensive efforts are required to ensure that skills are transferred between surgeons so that technical advances are not forgotten.
Anterior segment problems with vitreous substitutes
Authors: HEIMANN H
Published: August 2012

Abstract not provided
Photophobia in neuro‐ophthalmological conditions
Authors: KAWASAKI A
Published: August 2012

Purpose To understand the clinical presentation and possible mechanism of photophobia in neuro‐ophthalmological conditions. migraine and meningitis and lesions along the anterior visual pathway.

Methods case studies, literature review

Results Photophobia is a symptom that commonly accompanies migraine and meningitis. It occurs occasionally with lesions along the anterior visual pathway and in particular with suprasellar mass lesions, even if there is no evidence of chiasmal dysfunction. Such patients complain of a variety of symptoms related to excessive light perception. These take the form of photopsias, glare, dazzle, light aversion and photooculodynia.

Conclusion Recent evidence and new physiologic concepts related to centrally‐mediated light sensitivity and intolerance point to the thalamus as an integrating center for light and nociceptive signals. We will review these "photophobia circuits" and examine their application in clinical neuroophthalmology

Commercial interest
The role of electrophysiology
Authors: HOLDER GE
Published: August 2012

Purpose To demonstrate the role of electrophysiological assessment in the investigation and management of the patient with photophobia, or whose vision is worse under bright lighting conditions.

Methods The ISCEV standard techniques for ERG, PERGm, mfERG and EOG recording will be described, as will any necessary non‐standard protocol additions.

Results Selected cases will be used to illustrate the value of the objective data provided by electrophysiology.

Conclusion The objective data provided by electrophysiological assessment is important to the assessment, diagnosis and management of this group of patients.
Donor bone marrow derived dendritic cells promote corneal allograft survival in the rat
Authors: O'FLYNN L , TREACY O , RYAN A , MORCOS M , NOSOV M , RITTER T
Published: August 2012

Purpose Glucocorticoid treatment of ex‐vivo generated donor bone marrow derived dendritic cells (BMDCs) will promote graft survival upon injection into corneal transplant recipients.

Methods BMDCs were propagated from Dark Agouti (DA) rat BM precursor cells and for glucocorticoid treated BMDCs, dexamethasone (Dexa) 10e‐6M was added to the culture. BMDCs +/‐ Dexa phenotype, APC function and immunostimulatory capacity were examined. A fully allogeneic rat corneal transplantation model (DA to LEW) was used for in‐vivo studies. BMDCs +/‐ Dexa were harvested and 1x10e6 cells injected intravenously into recipients 7 days prior to corneal transplantation. Graft survival and development of opacity, edema and neovascularisation were monitored. On the average day of rejection graft infiltrating cell populations were analysed.

Results Ex‐vivo generated BMDCs have a semi‐mature phenotype and can be treated with Dexa to maintain their immature phenotype (n=5 p<0.05). BMDCs are capable of activating allogeneic lymphocytes, efficiently presenting antigen and activating antigen specific T cells however, there is a reduction in the level of proliferation (n=4, p<0.05). When applied in‐vivo BMDCs and Dexa BMDCs significantly prolong corneal allograft survival (MST> 30d, n=14 p<0.0004 and n=24 p<0.0001 resp.) compared to untreated allogeneic controls (MST 18d, n=11). A significant reduction in the total number of graft infiltrating cells was observed for both treated groups (p<0.05).

Conclusion Our results demonstrate a significant therapeutic effect of donor‐derived BMDCs with and without glucocorticoid treatment to prolong corneal transplant survival which represents a novel therapeutic approach for the prevention of corneal allograft rejection.
The fish scale‐derived Biocornea as a scaffold for human corneal cells
Authors: VAN ESSEN TH , SPARKS SJ , LIN CC , HUSSAIN AK , COMMANDEUR S , HORNG JL , LUYTEN GPM , GHALBZOURI AEI , JAGER MJ
Published: August 2012

Purpose Collagen matrices are a promising alternative for corneal donor transplants. Existing collagen matrices are synthesized or derived from animal corneas. We investigated whether fish scale‐derived collagen type I matrix could serve as a scaffold for in vitro corneal regeneration.

Methods Primary human keratocytes were cultured for 2 weeks onto uncoated and collagen type IV coated scaffolds. Additionally a cell line of human corneal epithelial cells (HCEC) were co‐cultured with the scaffold. Cell morphology and tissue organization were assessed using fluorescence staining. Furthermore, epithelial morphogenesis, cell proliferation, cell infiltration and the effect of different protease treatments on scaffold permeability were analyzed as well.

Results Keratocytes and HCECs cultured onto the micro‐patterned side covered the whole surface of the scaffold as well as keratocytes cultured onto the smooth side of the scaffold. No difference in cell attachment was observed between the uncoated and coated scaffolds. Cross sections showed no cellular infiltration into the scaffold. Dispase treatment separated the lamellae at the edges of the scaffold, but this did not induce cell penetration.

Conclusion The fish scale‐derived scaffold is biocompatible with human corneal epithelial and stromal cells and could therefore be a promising non‐expensive basis for corneal regeneration. Additional stromal‐scaffold interaction and cell infiltration studies will be the focus of our research.

Commercial interest
Cultivation and characterization of corneal limbal epithelial stem cells on lens capsule in animal material‐free medium
Authors: ALBERT R , VEREB Z , CSOMOS K , MOE MC , JOHNSEN EO , NICOLAISSEN B , RAJNAVOLGYI E , FESUS L , BERTA A , PETROVSKI G
Published: August 2012

Purpose To develop simple, reproducible and animal‐materials free method for cultivating and differentiating human limbal stem cells (LSCs) into corneal epithelium on human lens capsule (LC) for clinical transplantation.

Methods Limbal tissues (2x2x0,25 mm) were harvested from cadavers (44 males and 33 females, age 70,5+9,3 years) within 12 hours of biologic death. All tissue collection complied with the guidelines of the Helsinki Declaration and was approved by the Regional Ethical Committee. Cell viability was measured with the MTT and annexin‐FITC/propidium iodide assays. Characterization of the growing cells was performed by RT‐qPCR and immunfluorescence stainings accordingly.

Results Cell outgrowth at the edge of the explants was observed within 24 hours of cultivation and achieved viable outgrowth (>97% viability as measured by MTT assay and flow cytometry) within two weeks. The outgrowing cells were tested for positivity for markers of stemness (P63, ABCG2, CK19, ITGA9, VIM), proliferation (Ki‐67), limbal epithelial cells (CK 8/18 and 14) and differentiated cornea epithelial cells (CK 3 and 12). Immunostaining revealed the non‐hematopoietic, ‐endothelial and ‐mesenchymal stem cell phenotype, while the cell adhesion molecules, integrins and lectin‐based surface carbohydrate profiling showed a specific pattern on the LESCs.

Conclusion We report a method for isolating and expanding cornea LESCs from cadavers or alternatively from autologous donors capable of producing viable cell outgrowth on LC for possible treatment of LESC deficiency.
Identification of label‐retaining endothelial cells in adult human corneas: a new clue for the existence of endothelial stem cells
Authors: HA THI BM , HE Z , CAMPOLMI N , PISELLI S , GAIN P , PEOC'H M , DUMOLLARD JM , ACQUART S , GARRAUD O , THURET G
Published: August 2012

Purpose The lack of self‐renewal capacity of human corneal endothelial cells (EC) in vivo was explained by cell cycle arrest in the G1‐phase due to cell contact inhibition, TGF‐beta signaling, and stress induced premature senescence. Nevertheless, their residual ability to divide in primary culture suggests the existence of progenitor cells, probably located at the endothelial periphery (Whikehart.MolVis2005; He.StemCells2012). Stem cells are slow‐cycling cells characterized by their quiescent state in niches and their ability to retain for a long time markers of S‐Phase like BrDU or EdU. Aim: to search for the presence of label‐retaining EC in human corneas

Methods Label retaining EC were searched by 5‐Ethynyl‐2’‐Deoxyuridine (Click‐it EdU) incorporation during long‐term culture: 30 days for organ cultured human corneas (n=10) or 15 days for in vitro primary cultured EC (n=5), both followed by a 30‐day culture without EdU. Flat‐mouted corneas and EC cultures were observed with an inverted fluorescent microscope

Results Label‐retaining EC were observed in the peripheral area of all OC corneas, varying from 1 to 50. Numerous label‐retaining EC were also present in all primary cultures, always attached to Descemet membrane fragments

Conclusion The presence of label‐retaining EC constitutes a new clue for the existence of corneal endothelial stem cells in human. Their apparent scarcity is consistent with the inability of the human corneal endothelium to repair in vivo, but isolation and expansion of these endothelial stem cells or progenitors could allow development of bioengineered endothelium
Coupling innovative imaging: in vivo multilaser confocal microscopy and ex vivo confocal Raman spectroscopy of cornea and skin in nephropathic cystinosis
Authors: ESPINASSE M , CINOTTI E , PERROT JL , LABEILLE B , CAMBAZARD F , DUMOLLARD JM , PEOC'H M , CAMPOLMI N , THURET G , GAIN P
Published: August 2012

Purpose Nephropathic cystinosis is a rare, autosomal‐recessive inherited disease, characterized by lysosomal accumulation of cystine crystals in almost all tissues. Aim: to describe an innovative in vivo confocal microscopy (IVCM) of crystals in the skin, the cornea and the conjunctiva as well as raman spectroscopy of the crystals in skin and cornea

Methods A 36 year‐old women with advanced nephropatic cystinosis underwent penetrating keratoplasty for severe visual loss and chronic ulceration in her left eye. The only dermatology symptom was skin dryness. Cornea and skin was analysed with IVCM using the innovative multilaser (488, 658 and 785 nm) confocal microscope Vivascope 1500 and the handeld monolaser Vivascope 3000 (MAVIG GmbH). In order to obtain the chemical composition, ex vivo Raman spectroscopy (LabRAM ARAMIS,Horiba Jobin‐Yvon,France) was performed on corneal button retrieved during keratoplasty and on a skin sample, both immediately frozen in liquid nitrogen without adjuvant

Results Multilaser and monolaser IVCM showed reflective crystals in the corneal epithelium, stroma, tarsal conjunctiva and forearm skin with the highest resolution obtained at 488nm. Ex vivo Raman spectra were obtained in skin and cornea

Conclusion Combination of IVCM with Raman spectroscopy may improve the diagnosis and follow‐up for other metabolic diseases with skin and corneal thesaurismoses like amylosis, Wilson disease, Fabry disease or mucopolysaccharidosis
Potential role of transporters in ocular pharmacokinetics
Authors: URTTI A
Published: August 2012

Traditionally pharmacokinetics has been considered to be dominated by passive drug diffusion and metabolism. During the last decade pharmacokinetic research has shown that active drug transport by membrane transporter proteins is much more common than previously thought. The role of membrane transporters in ocular tissues is poorly known, but literature search on transporter interactions of ocular drugs reveals that there is high potential for such interactions, but expression of membrane transporters in the ocular tissues is not well understood. Drug concentrations relative to the affinity of the transporters is another factor that affects the importance of these interactions. Pharmacokinetic simulations reveal that the active transporters probably have important role in the access of systemic drugs to the eye (across blood retina barrier) and in the case of controlled release formulations. For drug absorption from the regular eye drops transporters seem to have relatively minor influence.
Genetic basis of glaucomas
Authors: TEKELI OYA
Published: August 2012

Glaucoma is characterized by a progressive loss of retinal ganglion cells. The exact cause of the glaucoma is still unknown.The glaucoma is a multifactorial disease and affected by multiple genetic and environmental factors. Ethnic differences in the prevalence of glaucoma and positive family history support the inheritance of glaucoma. There is evidence showing that genetic factors may play an important role in the pathogenesis of the disease. Here we aim to emphasize the genetic basis of glaucoma.
Vascular issues in glaucoma
Authors: KOCABORA S
Published: August 2012

A literature review is done to analyze relevant data about the role of blood flow abnormalities in the pathogenesis of glaucomatous optic nerve damage. Elevated intraocular pressure that is incontestably the major risk factor for glaucomatous optic nerve damage alone cannot explain all glaucoma cases since despite low intraocular pressure some glaucoma cases continue to progress.The results of several studies suggest that ocular hemodynamic abnormalities also play a role in the pathogenesis of glaucomatous optic neuropathy.Another issue relevant to vascular factor is oxidative stress.Reduced blood flow may lead to hypoxia and consequently to accumulation of prooxidants leading to the optic nerve damage. The capillaries in the anterior optic nerve possess local autoregulatory mechanisms to maintain relatively a constant blood flow over a wide range of perfusion pressure.The role of endothelium generated vasoactive molecules in controlling vascular supply within the optic nerve head is important.The decreased perfusion in the anterior optic nerve and the failure of autoregulation in overcoming this decrease are the main mechanisms that compromise the blood supply to the optic nerve head. Intraocular pressure fluctuations and decreased ocular perfusion pressure may synergistically cause instability and decrease in blood flow. Although several methods exist to examine different aspects of the ocular blood flow in different vascular beds, there is no a standard method for blood flow measurements and the clinical role of this measurement in glaucoma is not still well determined. The data from future prospective, randomized and long‐term clinical trials are required to well understand the role of ocular blood flow deficiencies in the development and progression of glaucoma.
Damage integrity from eye to visual cortex
Authors: ENGIN K
Published: August 2012

Ever since the initial reports on the impacts of glaucoma on the optic nerve (ON), corpus geniculatum laterale (CGL) and visual cortex, its damage beyond the retinal ganglion cells into the brain substance became increasingly evident. In 2 consecutive studies, we aimed to evaluate the structural and functional extent of glaucomatous neurodegeneration in an attempt to develop techniques feasible for routine clinical application. Original diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) techniques with 1,5T MRI system were applied in retrobulber imaging and evaluation. fMRI detects increased neuronal activity via changes in blood oxygenation, DTI is based on the movement principle of fluids in a plane connected to the nerve. ON damage and cortical hypofunction were imaged. Most importantly, optic coherence tomography (OCT), central visual field (CVF) findings show statistically significant positive and negative correlation with particular diffusion parameters of ON and CGL, respectively. Aside from the classical treatment methods based on management of the IOP, new strategies focusing on the area beyond the optic nerve head are needed to be developed. Better understanding of retrobulbar glaucomatous damage will enable us to develop more effective diagnostic and treatment strategies for glaucoma management, and possibly shed a light on the current unanswered questions about glaucoma.
Biomaterials for ocular surface reconstruction
Authors: FUCHSLUGER T
Published: August 2012

Purpose To provide an overview over the clinical need and recent developments regarding biomaterials for ocular surface reconstruction.

Methods Epithelial and stroma substitutes will be presented, as well as own data generated by electrospinning of a biodegradable elastomer.

Results Biofilms can be created and are sucessfully applied both on a research and on a clinical level.

Conclusion Biomaterials will become a reality in ophthalmosurgery.
European study on reliability assessment of endothelial cell count in eye banks: the Euro‐Keratotest study
Authors: THURET G , HE Z , BERNARD A , CAMPOLMI N , HA THI BM , PEOC'H M , DUMOLLARD JM , DELESALLE N , GAIN P
Published: August 2012

Purpose In European eye banks, 15‐20% of corneas are discarded for inappropriate ECD. Given the importance of a precise, robust and reproducible ECD, we organized an international survey of the quality of ECD determination

Methods The Euro‐Keratotest study reproduced 2 surveys driven in 2003 and 2008 by our team in the 18 French eye banks (Transplantation2004), with substantial improvements: test slides (3rd generation keratotests) were fabricated with technologies employed in micro‐optics, from images of real human corneas (Optics Letters2012). Twelve different mosaics with ECDs covering the usual range observed in eye banks, were created in a 8x8 mm quartz square. Keratotests, observable with transmitted light or specular microscopes, were sent simultaneously to all volunteer eye banks (n=100). Each technician had to determine ECD and morphometry of the 12 mosaics with his/her standard counting method. Data were collected on a specific website

Results A first analysis of 120 technicians of 38 eye banks will be presented. It allowed identification of inter and intra bank variability and of bias likely involved (inappropriate counting strategy or wrong microscope calibration) and susceptible to be improved

Conclusion Participation of the eye banks to this survey using 3rd generation keratotests improves our knowledge on the reliability of cell counting methods in eye banks, and help standardize graft quality assessment. Keratotests are also perfect tools for the initial formation and continuous training of eye banks technicians, as well as for the eye banks certification. Grant: Interregional Hospital Clinical Research Project 2011, Ministry of Health, DIRC Rhônes‐Alpes
A new and quantitative method to evaluate the overall quality of corneal tissues for clinical applications and research testing
Authors: PAREKH M
Published: August 2012

Purpose To demonstrate the validity of a new evaluation technique for measuring the overall quality of the cornea and check the efficacy of this quantitative approach in a comparative study of corneas preserved in CorneaCold® (new formulation) or Optisol‐GS.

Methods 24 pairs of unsuitable corneas with intact epithelial layer and good morphology were collected. Right corneas were placed in CorneaCold® (Eurobio‐France) and left corneas in Optisol‐GS (Bausch&Lomb‐USA) from the same donor and vice‐versa for a 4 week comparative study. The study was divided into 2 phases, where phase 1 was open and phase 2 was blinded. Cells were stained with trypan blue and counted under an optical microscope to check the mortality and cell density. Difference between epithelial and endothelial layer was evaluated microscopically for thickness measurement. A transparency device was used for calculating the degree of transparency. All the above subjective parameters were converted to objective values for determining the overall quality of the cornea.

Results The conversion to objective values from subjective analysis helped to evaluate the quality of corneas at different time intervals of preservation in different media. Students t‐test at week 2 (p=0.001) and week 4 (p=7.563E‐09) showed statistically better results when corneas were preserved in CorneaCold® rather than in Optisol‐GS.

Conclusion The overall quality evaluation of cornea presented here is efficient, consistent and easy. This new technique could be useful for comparative studies and to value corneas for eyebanks, biobanks and research or transplantation purposes. CorneaCold® is a promising corneal preservation medium for hypothermic storage with slightly longer preservation time.

Commercial interest
Novel interpretation of fundus autofluorescence (FAF) findings in choriocapillaritis
Authors: MANTOVANI A , STAURENGHI G , HERBORT CP
Published: August 2012

Purpose To determine the significance of increased fundus autofluorescence (FAF488) in choriocapillaritis, comparing photobleaching process, SD‐OCT and melanin‐related fundus autofluorescence (FAF787) findings

Methods FAF488 signal depends on both the amount of bisretinoids in the RPE and the absorbion of light by photoreceptor pigments, macular pigment and RPE melanin. During the photobleaching process (absorbion of photons by photopigment in the outer photoreceptor segments), there is a reduction of the photopigment density and so an increase of the visualization of the autofluorescent signal

Results In MEWDS and MFC, the more striking FAF488 alteration is an increase of the autofluorescent signal and SD‐OCT shows a disruption of IS/OS junction, probably sign of dismanting outer photoreceptor segments; there is not an increase of FAF787 and after the photobleaching process, the areas of increased FAF488 become isofluorescent. This could mean that the areas of hyperautofluorescence are due to a better visualization of the autofluorescent signal because there is a reduction of the visual pigments and not to an increase of the fluorophores. In the APMPPE group, during the convalescent stage, increased FAF488 and FAF787 are often seen in the center of chorioretinal scars, corresponding to accumulation of fuorophores debris and to hypertrophy/hyperplasia of RPE cells

Conclusion In MEWDS and MFC, photobleaching process, FAF787 and spectral‐domain OCT findings may explain the increased FAF488 present in the acute phase of the diseases as a loss of the photopigments and not to an increase of fluorophores, because there is a limited pertubation of choriocapillaris circulation with a slight ischaemic insult to outer retina.
Paediatric rheumatology clinic outcome at Leeds Teaching Hospitals, UK
Authors: JEEVA I , HARDISTY A , KOLB S , HOOLE J , LONG V , WOOD M
Published: August 2012

Purpose Present 1‐year data of the combined ophthalmology and rheumatology pediatric uveitis clinic at Leeds Teaching Hospitals.

Methods Retrospective data collection

Results An estimated 230 patients with JIA were screened by ophthalmology in this time period.21 different paediatric patients with iritis were managed from June 2011 to May 2012 in the joint clinic.8(38%) patients were male and 13(62%) female with age at diagnosis ranged from 0.5 – 12 years. 11 patients (52%) were diagnosed with oligoarticular and 5(23%) with polyarticular JIA,3 patients were ANA +, 3(14%) did not have any joint involvement.9 patients(43%) presented with vision of 0.2logMar or worse, and 4 continued to have vision worse than 0.2 logMar while 17 patients (81%) improved or maintained stable vision of 0.1 or better.3 patients had intermediate uveitis,1 had panuveitis and 1 had papillitis with iritis.2 had eye complications of lens opacities and 1 patient had retinal detachment.17(81%) patients received systemic treatment, with 12 receiving methotrexate +/‐ mycophenolate mofetil and 5(29%) receiving anti‐TNF α therapy (infliximab or adalimumab) in addition to methotrexate +/‐ mycophenolate mofetil. 13/16 patients with JIA (81%) had iritis associated with their joint flare‐ups. 9 patients (50%) out of 18 with joint pathology received intra‐articular steroid injections during this period and 6 received (28%) periocular steroid injection. A survey of the joint clinic by the patient and medical staff showed significantly high satisfaction rate.

Conclusion The joint clinic has numerous benefits and is the right approach to manage a condition where communication is crucial between team monitoring (ophthalmology) and managing (rheumatology) the condition