bluuebunny/crossref_metadata_2025 huggingface dataset:
The “strange story” of Interferon‐α: A very peculiar biologic agent
Authors: BODAGHI B
Published: November 2013

Biologic agents are widely used in patients with uveitis. Interferon alpha is one of the first agents tested in this indication. Its efficacy was reported in the early 90's in patients with severe and refractory Behçet's disease‐associated uveitis. Several other studies from different centers have confirmed the initial results. However, this agent is mostly used in Europe. Severe posterior, intermediate and panuveitis may respond to interferon alpha. Some infectious entities such as herpetic viral retinopathies are also appropriate candidates. Doses vary between centres and countries. Tolerance is a major factor to consider. The drug may be discontinued in up to 40% of cases for various side effects. Interferon alpha is a double‐edged sword in a few situations. LOng‐term remission or healing may be obtained after long‐term use of the drug.
Electrophysiology and imaging
Authors: HOLDER G
Published: November 2013

There have been major advances in retinal imaging techniques in recent years, with both fundus autofluorescence imaging and spectral‐domain optical coherence tomography adopting increasingly important roles in management and diagnosis. This presentation will utilise a case‐based format address the relationship between structure and function in various acquired and inherited disorders.
A new and standardized method to sample and analyse vitreous biopsies by the Cellient® automated cell block system
Authors: VAN GINDERDEUREN R , VAN CALSTER J
Published: November 2013

Purpose In this prospective study a universal protocol for sampling and analysing vitreous material was investigated. Vitreous biopsies are difficult to handle because of the paucity of cells and the gelatinous structure of the vitreous. Histopathological analysis of the vitreous is useful in difficult uveitis cases to differentiate uveitis from lymphoma or infection and to define the type of cellular reaction

Methods 170 consecutive vitreous samples were analysed with the Cellient® tissue processor (Hologic). This machine is a fully automated processor starting from a specified container with PreservCyt® (fixative fluid) with cells to paraffin. Cytology was compared with fixatives Cytolyt® (contains a mucolyticum) and Preservcyt®. Routine histochemical and immunostainings were evaluated

Results In 92% of the cases, sufficient material was found for diagnosis. In 14%, a Cytolyt® wash was necessary to prevent clotting of the tubes in the Cellient® due to the viscosity of the sample. In 23% the diagnosis was an acute inflammation (presence of granulocytes), in 33% chronic active inflammation (presence of T‐lymphocytes), in 33% low‐grade inflammation (presence of CD68 cells, without T‐lymphocytes); and in 3% a malignant process

Conclusion A standardized protocol for sampling and handling vitreous biopsies, fixing in PreservCyt® and processing by the Cellient® gives a superior result in morphology, number of cells, and possibility of immuno‐histochemical stainings. The diagnosis can be established or confirmed in more than 90% of cases
ME and Visual Acuity
Authors: TADAYONI R
Published: November 2013

Abstract not provided
Clinics, biopsy and pathology
Authors: ROBERT P
Published: November 2013

Etiological diagnosis of orbital inflammation drives the general handling, states on specific/non specific status of inflammation, and may lead to simple survey of long‐lasting immunosuppressive treatment. Handling a orbital patient is always challenging for the clinician, but specific signs from clinical exam, imaging, biological checkup or histological samples may be critical. Clinical exam of the orbit must be directed towards ocular inflammation, sensitive and oculomotor signs, optic nerve function, and comparative orbital morphology. Imaging can disclose vascular, inflammatory, compressive, or bone‐desctructive lesions. Biological and systemic checkup must target signs of granulomatous, vasculitis, infectious, hematological and immunological diseases. Fine‐needle biopsy is still controversial since it allows a first histological exploration under local anesthesia, but may be at risk of bleeding, perforating a noble organ (globe, muscle, optic nerve, lacrimal gland) or misdiagnosing a heterogenous or small lesion, when compared to explorative biopsy under general anesthesia. Progresses on immunohistochemistry and histological markers have made the proportion of “non‐specific” orbital inflammation decrease these 10 last years We review these techniques through demonstrative clinical cases.
Inflammatory orbital lesions (IOI)
Authors: DE KEIZER RJW , BIJLSMA WR
Published: November 2013

Idiopathic orbital inflammation is a diagnosis by exclusion and therefore a rather heterogeneous patient group. By definition the terms exclude lesions with an identifiable aetiology as bacterial, fungal and parasitic infections. Many classification schemes for IOI exists, but we didn’t know which one is best so we like to share with the audience the outcome of our quest for the best classification system for idiopathic orbital inflammation. The classification systems could be tested for the five properties of a good classification system being Reliability , Feasibility, Face validity, Content validity, Distinction. A combined histology/imaging localization classification system is best for idiopathic orbital inflammation. The presentation will be including the topics idiopathic inflammatory orbital disease, which has to differentiate from the vasculitis and isolated sclerosing pseudotumor. The new classification schedules of the international vasculitis group will be shortly outlined. Also some research findings, where several attempts were done, to find relations with
The endolysosomal system and AMD: Insights from a novel genetically engineered mouse model
Authors: SINHA D , VALAPALA M , ZIGLER JS , HOSE S
Published: November 2013

In phagocytic cells, the endolysosomal system is a crucial regulator of both phagocytosis and autophagy, thereby helping to maintain cellular homeostasis. Prime examples of this are retinal pigmented epithelial (RPE) cells, which are not only among the most actively phagocytic cells, continuously phagocytosing shed photoreceptor outer segments (OS), but also are post‐mitotic cells having high metabolic activity and a high rate of autophagy. For proper RPE function, and to ensure the functional integrity of the neural retina, both phagocytosis and autophagy need to be in balance. We show that in the RPE, bA3/A1‐crystallin is required for normal lysosomal‐mediated waste removal. Our studies suggest that bA3/A1‐crystallin acts via the AMPK‐mTORC1 signaling pathway. Based on our findings, we postulate that loss of bA3/A1‐crystallin inhibits these signaling pathways, leading to a defect in the V‐ATPase‐mediated acidification of the lysosomal machinery. Since bA3/A1‐crystallin has been reported to be present in human drusen and a possible role for lysosomes in age‐related macular degeneration (AMD) has been suggested, it is possible that perturbation of normal phagocytosis/autophagy in RPE could cause some manifestations of AMD.
A novel role for the immunoproteasome in retinal function
Authors: FERRINGTON D
Published: November 2013

The immunoproteasome (i‐proteasome) is a protease that is abundant in cells of the immune system and is known to generate peptides for MHC class I presentation. I‐proteasome is also present in tissues outside the immune system, including retina and RPE cells, suggesting alternative functions are possible. We have previously shown that i‐proteasome is upregulated in the retina of donors with AMD, in response to acute injury in the retina and brain, and chronic oxidative stress in cultured RPE. These results suggest a novel role in the cellular stress response. Our recent focus has been on defining how i‐proteasome is involved in regulating two key stress response pathways, NFkB and autophagy. To investigate i‐proteasome’s role, we used RPE cells derived from WT and KO mice lacking either one (lmp2‐/‐) or two (lmp7‐/‐/mecl‐/‐) i‐proteasome catalytic subunits. Results show that cells deficient in the LMP2 subunit demonstrate differences in the alternative pathway of NFkB signaling, as well as a diminished response to autophagic stimuli. Thus, i‐proteasome upregulation with AMD, and with chronic and acute injury, may be a compensatory response that is required to help regulate these two stress response pathways.
Baseline characteristics predictive of pharmacologic vitreomacular adhesion resolution in the ocriplasmin MIVI‐TRUST program
Authors: GANDORFER A
Published: November 2013

Purpose The ocriplasmin MIVI‐TRUST program included two phase III, multicenter, randomized, double‐masked trials to determine the efficacy and safety of ocriplasmin for the treatment of vitreomacular traction (VMT). We sought to identify baseline characteristics that were predictive of pharmacologic vitreomacular adhesion (VMA) resolution at Day 28 after an injection of ocriplasmin or placebo.

Methods Patients with OCT‐confirmed VMA were randomized to receive a single intravitreal injection of ocriplasmin 125 µg (n=464) or placebo (n=188). The primary end point was VMA resolution at 28 days post‐injection. A multivariate regression analysis was performed to determine independent baseline anatomic and non‐anatomic characteristics that were significantly associated with pharmacologic VMA at Day 28.

Results Pharmacologic VMA resolution at Day 28 was observed in a significantly larger proportion of patients in the ocriplasmin group (26.5%) compared with placebo (10.1%; p<0.001). Independent baseline anatomic characteristics predictive of VMA resolution included the presence of a full‐thickness macular hole (equivalent to stage II; p=0.019), VMA diameter ≤1500 µm (p<0.001), phakic lens status (p<0.001), and the absence of an epiretinal membrane (p<0.001). Independent non‐anatomic baseline characteristics predictive of VMA resolution included treatment with ocriplasmin (p<0.001) and age <65 years (p<0.001).

Conclusion The identification of specific baseline anatomic characteristics predictive of response is informative in the consideration of treatment options for patients with VMT.

Commercial interest
Myths and misconceptions about glaucoma blindness
Authors: HONDEGHEM K
Published: November 2013

Blindness is a major global problem, with many associated socioeconomic impacts. Glaucoma is responsible for much of this worldwide blindness. Glaucoma is the leading cause of irreversible vision loss. We will take a closer look at ten common myths and misconceptions about (glaucoma) blindness. We will also briefly discuss some exciting new technologies that can be a tremendous aid to the blind.
Myths and misconceptions in treatment adherence
Authors: KOTECHA A
Published: November 2013

Once diagnosed, the glaucoma patient requires lifelong treatment, usually with topical IOP lowering medication. The aim of glaucoma treatment is to reduce IOP, a ‘clinician‐based’ measure, and thus treatment has no obvious effect on the patient’s vision or their ability to carry out every‐day tasks. There is evidence to suggest that medication underuse occurs in patients with glaucoma. Deliberate medication underuse occurs when the patient is concerned with aspects relating to either the treatment safety, or treatment efficacy and necessity. In glaucoma, medication misuse may lead to inappropriate conclusions regarding treatment inefficacy, resulting in unnecessary changes and additions to treatment, and, more seriously, avoidable, irreversible visual loss. Improving patient adherence to their treatment is a complex issue influenced by a number of factors. This talk will explore some of the issues regarding glaucoma medication misuse and the role of the 'doctor‐patient' relationship in promoting adherence to treatment.
Novel strategies for angioregression at the ocular surface
Authors: BOCK F , CURSIEFEN C
Published: November 2013

The normal human cornea is avascular. This avascularity is actively maintained by expression of antiangiogenic and antilymphangiogenic factors. Corneal neovascularization (NV) can occur after numerous corneal diseases and leads to decreased visual acuity and poor prognosis in subsequent corneal transplantation since corneal immune privilege is lost. We recently demonstrated that bevacizumab eye drops significantly inhibit progressive corneal angiogenesis. In contrast, limited treatment options exist for mature corneal vessels, which — because of their pericyte‐covered vessel wall—do not depend on VEGF anymore. Here, we report on the short‐ and long‐term visual acuity changes and changes in vascularized corneal area after e.g. feeder vessel coagulation combined with topical bevacizumab application for the treatment of mature pathological corneal NV . These angioregressive therapies may not only improve corneal transparency but also “preconditions” such a cornea for future keratoplasty.
Transcriptional profiling of human corneal epithelium using laser capture microdissection and massive parallel sequencing
Authors: BATH C , MUTTUVELU D , EMMERSEN J , VORUM H , HJORTDAL J , ZACHAR V
Published: November 2013

This study was conducted to perform global transcriptomic profiling and biomarker discovery on undisturbed human corneal epithelial subpopulations using a novel approach combining laser capture microdissection (LCM) and RNA sequencing. LCM facilitated the harvest of four cellular compartments along the corneal epithelial differentiation pathway: Stroma, basal limbal crypt (BLC), superficial limbal crypt (SLC), and cornea. Compartments were analyzed using massive parallel sequencing and bioinformatics. Specificity of LCM was confirmed by imaging, expression of epithelial markers, and gene ontology analysis of biological processes. Interestingly, many significant upregulated genes in SLC mapped to processes involved in regulation of vasculature like sFLT1. In contrast, BLC had many upregulated genes mapping to neurogenic and developmental processes. The primitive nature of BLC was confirmed by KEGG pathway analysis. We present full gene lists of unique expressed genes in both BLC and cornea representing candidate biomarkers. Possible novel regulators of limbal epithelial stem cells (LESCs) include Lrig1 and SOX9. The presented molecular insight in LESC biology is expected to be beneficial for both research and clinical translation.
Suitability of a fish scale‐derived collagen matrix (FSCM) as artificial cornea
Authors: VAN ESSEN TH , VAN ZIJL L , SPARKS SJ , CHEN G , LIN CC , LAI HJ , LUYTEN GPM , GHALBZOURI AEL , JAGER MJ
Published: November 2013

Purpose: A naturally occurring, easily obtainable fish scale‐derived collagen matrix (FSCM) may be a cheap alternative to current keratoprostheses. We assessed its suitability by measuring light transmission, scattering, and immunogenicity. Methods: Light transmission and scatter characteristics of the FSCM were measured. The FSCM was implanted subconjunctivally in rats, to assess swelling and neovascularization, and subcutaneously to observe the cellular immune response. Results: The FSCM had a light scattering of log(s) =1.62 and a light transmission of 90%. Local swelling and neovascularization appeared similar to an implant already used in glaucoma surgery. Both subcutaneous implants elicited an initial and mild immune reaction with only a few lymphocytes after 2.5 months, and did not induce immune sensitization. The FSCMs were well tolerated, while a small fibrous capsule was also observed. Conclusions: We demonstrate that the first prototype of this easily obtainable, naturally occurring FSCM has proper optical clarity, and low immunogenicity. These properties demonstrate its potential as a candidate for reconstructing the avascular cornea.

Commercial interest
Small molecule induction promotes corneal epithelial cell differentiation from human pluripotent stem cells
Authors: SKOTTMAN H , MIKHAILOVA A , UUSITALO H , ILMARINEN T
Published: November 2013

Purpose Corneal epithelium is maintained by limbal stem cells, and their transplantation has been used to treat limbal stem cell deficiency (LSCD). However, this is only possible if enough healthy limbal tissue is available. Thus, novel cell sources for treating LSCD are needed. Human induced pluripotent stem cells (hiPSCs) provide unique opportunities for differentiation of limbal and corneal epithelial cells for cell transplantations.

Methods In order to improve the efficiency and reproducibility of hiPSCs differentiation towards corneal epithelial progenitor cells, signaling cues active during ocular surface ectoderm development was replicated with two small‐molecule inhibitors in combination with growth factors. The extent of differentiation was evaluated by following the expression of key markers using immunocytochemistry and qPCR at several time‐points.

Results Small‐molecule induction down‐regulated the expression of pluripotency marker OCT4 while up‐regulating the eye‐field transcription factor PAX6. Protein expression of the corneal epithelial progenitor marker p63 was greatly enhanced, with up to 95% of cells being p63‐positive after five weeks of differentiation. Finally, after a total of six weeks in differentiation culture, the two markers specific to terminally differentiated corneal epithelium, cytokeratins 3 and 12, were expressed in an average of 35% and 71% of cells, respectively.

Conclusion In contrast to all earlier studies, corneal epithelial cells were differentiated in serum‐free culture conditions without the use of amniotic membrane or other undefined culture substrates. This highly efficient differentiation method could potentially be used for treating LSCD in the future.

Commercial interest
Comparative gene expression analysis of corneal stroma mesenchymal stem cell‐like cells, limbal epithelial stem cells and bone marrow‐derived mesenchymal stem cells
Authors: VEREB Z , POLISKA SZ , ALBERT R , OLSTAD OK , MOE MC , FESUS L , PETROVSKI G
Published: November 2013

Purpose Purpose Stem cells in the central part of the cornea serve an important regenerative and homeostatic function. We aimed to describe the genetic fingerprint of these cells and compare that to limbal epithelial stem cells (LESC) and bone marrow‐derived MSCs (bmMSCs).

Methods Corneal tissue and bmMSCs were harvested from cadavers and healthy donors, respectively (according to the Guidelines of the Helsinki Declaration) and cultured ex vivo. MSC‐specific cell surface markers‐ and genome‐wide microarray analysis were performed using FACS and Affymetrix GeneChip Human Gene 1.0 ST Array (~23,000 gene transcripts).

Results Genes related to stemness (228), differentiation and lineage (220), cell cycle (108) and HOX, SOCS, Notch signaling (218) were collected into functional groups and clustered hierarchically: 45 genes were found to be specific for corneal stroma (CS)‐MSCs, 62 for LESCs and 9 for bmMSCs. The hierarchical clustering clearly separated the CS‐MSCs from the LESCs and bmMSCs, but formed a higher cluster with the later. The top 10 genes related to the differences were VCAM1, FNDC1, MFAP5, SFRP2, IGF2, MMP, ITGA2, COLEC12, SEMA3A and MGARP. Number of molecules functioning in cellular movement (381), cellular growth and proliferation (408), development (370) and cellular development (360) were found with top biological functions in CSMSCs compared to LESCs or bmMSCs (p<0.001).

Conclusion Our data show clear distinction between the studied stem cells based upon their gene expression patterns and strengthen the hypothesis that CSMSCs are derived from bmMSCs and not from LESCs.
How to go further? From fundamental research to clinical practice
Authors: DELMAS D , LAYANA A
Published: November 2013

Abstract not provided
Step by step limbal stem cell transplantation techniques
Authors: GICQUEL J , DUA HS
Published: November 2013

Abstract not provided
Strabismus and diplopia revealing rhabdomyosarcoma in a 7‐year‐old girl
Authors: AZIZ A , MATONTI F , FAKHOURY O , DENIS D
Published: November 2013

Purpose This case report presents the diagnosis and management of seven‐years‐old girl with persistant diplopia revealing orbital rhabdomyosarcoma ,a rare and malign type of tumor among children. Few cases have been reported.The clinical presentation, complementary exams, and treatment for this condition are reviewed.

Methods A 7‐year‐old girl was referred to our department for persistant diplopia ,and unilateral exophtalmia on her left eye that had been lasting for 5 months.The orthoptic examination showed no visual acuity loss, vicious head tilt bent on the left side, exotropia with quick restitution, limitation of abduction and elevation on left eye. The Lancaster test confirmed the limitation.The eye fundus examination revealed signs of extrinsic compression.

Results Magnetic resonance imaging, and ocular and orbital echography showed an intra conical tumor of 18x21millimeters, displacing the ocular nerve and invading the superior rectus muscle. Tumor biopsy revealed undifferenciated rhabdomyosarcoma. Metastatic work‐up was negative and included thoracic and abdominal CT, bone scintigraphy and bone marrow biopsy. The treatment consisted in chemotherapy and permitted tumor volume regression of 85%. The patient has successfully manage with muscle surgery, not on the cicatricial site but on the other eye.

Conclusion Ocular rhabdomyosarcoma is a rare tumor among children, but the most frequent malign orbital tumor, with possible secondary localisation. Early diagnosis and early treatment are determinant for the prognosis and the survival rate of these patients. This case report shows all the utility of strabismological examination to detect the first signs of the condition, even without any symptoms relative to visual acuity.
Non graves orbital inflammations: Rationale for a diagnostic approach
Authors: FISCH AL , GAVARD PERRET A , LAGIER J , ROBERT PY
Published: November 2013

Purpose To propose a diagnostic approach for clinicians who manage a patient with non Graves’ orbital inflammation.

Methods A review of the diagnostic process for sixty one patients with diagnostic of orbital inflammation between january 2002 and january 2013 at Niceand Limoges Universitary Hospitals.

Results Sixty one patients presenting with orbital inflammation were included. More common presentations were orbital fat inflammation (60%), myositis (26%) and lacrimal gland enlargement (18%). In few cases, optic nerve and sclera were involved (respectively 9,8 and 3,2%). The final diagnostic was idiopathic orbital inflammation (25 patients), specific orbital inflammation (17 patients) and orbital lymphoma (19 patients). Thirty six patients had biopsy first and 25 patients did not, in first, but only after failure to the initial therapy. Our results showed that doing biopsy in the initial management of orbital inflammation provides a more great number of specific diagnosis than doing treatment tests directly after blood tests or CT scans ( p>0,01).

Conclusion The diagnostic process of orbital inflammation must include blood testing, imaging of the orbit and sinuses, and biopsy in first intention as far as possible.
Mitochondrial dynamics in mitochondrial optic neuropathies
Authors: POULTON J , LIAO C , ASHLEY N
Published: November 2013

OPA1 mutations are the commonest cause of dominantly inherited optic atrophy (DOA) and so‐called DOA plus. The Opa1 protein is essential for normal mitochondrial fusion. In mouse DOA, autophagy (recycling of spent cellular components) is dysregulated in retinal ganglion cells (RGCs), and mitophagy (mitochondrial recycling) has been implicated. We validated and used novel ImageStream technology to quantitate mitophagy in primary cells. Co‐localisation of mitochondria and autophagosomes was increased in fibroblasts in five patients from four families with severe OPA1 phenotypes indicating increased mitophagy. ImageStream also showed that basal mitophagy was increased when control cultures were depleted of Opa1 by siRNA. Western blotting confirmed increased basal autophagy and autophagic flux in the presence of activators. Increased mitochondrial fragmentation, mitophagy and failure of mitochondrial transport may together cause local depletion of mitochondria in critical regions of the retinal ganglion cells, such as axons or synapses. Fragmentation may also impair stress induced mitochondrial hyperfusion. Increased mitochondrial fragmentation, mislocalisation and mitophagy thus link low OPA1 to neurodegeneration.
Consequences of storage on the donor corneal tissue
Authors: ARMITAGE J
Published: November 2013

No storage method for biological materials preserves the full functional integrity of all cells in a given population. The loss of cells during storage of tissues for transplantation has to be accepted and the purpose of storage is to minimize both cell loss and maintain functional integrity. This is especially important for tissues where integrated cellular function is essential for normal, overall physiological function of the tissue. This is the case for cornea intended for transplants that require an intact and functioning corneal endothelial monolayer, such as for endothelial disease. The three main approaches to corneal preservation, viz., organ culture, hypothermic storage and cryopreservation, all pose their own unique challenges to cells and present a range of differing mechanisms of damage. Hypothermia relies on the suppression of metabolism by reduced temperature. Organ culture attempts to maintain metabolism. Cryopreservation completely suppresses all biochemical reactions and offers the prospect of indefinite storage. A better understanding of these mechanisms may lead to improvements in the quality of tissue after storage.
The therapeutic impact of office‐hours diurnal pressure measurements in the management of glaucoma patients
Authors: LAMPE M , POURJAVAN S
Published: November 2013

Purpose To assess, primarily, the impact of office‐hours diurnal IOP measurements on our clinical treatment attitude for glaucoma patients. Secondly, to determine, specific risk factors which allow us to select the group of patients where performing an IOP diurnal curve can be useful.

Methods 20 patients were included in this retrospective study. We examined the files of the patient who underwent a diurnal IO pressure curve between 01/01/2012 and 01/03/2013. Age, gender, race, diagnosis, the ophthalmological surgical and medical history, number of IOP measurements and the length of the diurnal curve on the examination day, the min and max IOP, and finally the therapeutic impact of these measurements and change in the treatment of patients.

Results The mean age was 58.6 ± 14.8 years. There was min 4 to max 5 IOP measurements during 8.4 ± 0.5 hours. The mean IOP of all the patients was 17.7 ± 3.2 mmHg with a variation 2.3 ± 1.4 mmHg (1 to 6 mmHg max) during the day. There were only 50% of the measurements which led to a change of the clinical treatment. In this group of patients the higher max IOP during the day and the higher IOP variation were the common feature.

Conclusion In our study we found that only 50% of the office‐hours diurnal intraocular pressure curve led to a new clinical treatment. The patient selection should be stricter because of the time‐consuming examination. Patients with higher IOP should be taken into account for diurnal IOP measurements where there are signs of progression.
Spectral analysis of ocular pulse amplitude recordings obtained using a contact lens sensor
Authors: HIRN C , RUSSELL RA , LAMPARTER J , LASCARATOS G , HO T , GARWAY‐HEATH DF
Published: November 2013

Purpose The aim of this study was to investigate whether the ocular pulse amplitude (OPA) can be detected in fluctuation curves recorded with the Sensimed Triggerfish® Sensor (TS), and analysed by Fast Fourier Transform (FFT).

Methods 40 subjects (20 open angle glaucoma [OAG], 20 healthy) underwent one hour of TS monitoring. Intraocular pressure and OPA were measured by dynamic contour tonometry (DCT) and DCT OPA was used as the reference. Segments of TS OPA fluctuations were visually identified (VI), and the amplitude (mVequ) was measured (VI‐TS OPA). In addition, FFT signal analysis, which reduces a periodic function into its frequency components, was performed on VI segments, and the amplitude (arbitrary units [AU]) of the fundamental measured (FFT‐TS OPA). The correlation between VI‐ and FFT‐TS OPA was investigated. VI‐ and FFT‐TS OPA were compared with DCT OPA.

Results In 3 subjects, TS recording failed. In 8 subjects, either no OPA or no fundamental could be identified. For the remaining 29 subjects (13 OAG, 16 healthy), both mean (±standard deviation) VI‐ and FFT‐TS OPA were lower in OAG (9.0±3.9mVequ and 184.6±303.7AU) than in healthy subjects (10.2±4.5mVequ and 303.3±292.0AU). Mean DCT OPA was higher in OAG (2.7±0.8mmHg) than in healthy subjects (2.3±0.6mmHg) (p>0.05 for all). There was a significant correlation between VI‐ and FFT‐TS OPA (Spearman's rho=0.84; p<0.0001). In OAG subjects only, the correlation between VI‐TS OPA and DCT OPA (Spearman's rho=0.52, p=0.072) and FFT‐TS OPA and DCT OPA (Spearman's rho=0.48, p=0.099) approached significance.

Conclusion It is possible to identify OPA in TS fluctuation curves and to analyse OPA by FFT. There is a weak association between TS OPA and DCT OPA in OAG.
Molecular techniques in ocular pathology
Authors: COUPLAND S
Published: November 2013

The roles of molecular techniques in ocular pathology include: a) aiding the understanding of disease pathogenesis; b) establishing diagnoses; c) predicting prognosis; d) predicting therapy response; and e) detecting residual disease. Examples of recent developments in molecular pathology include better understanding of the sonic hedgehog pathway in BCC; polyomavirus MCPyV in Merkel cell carcinoma; microsatellite instability in sebaceous carcinoma; fusion oncogenes in adenoid cystic carcinoma and mucoepidermoid carcinoma; and A20 gene deletions in conjunctival MALT lymphoma. Molecular techniques, such as IgH‐PCR and TCR‐PCR, are required regularly for the confirmation of the diagnosis of ocular B‐ and T‐cell lymphomas, respectively. Molecular methods are used for prognostication in uveal melanoma, in combination with the clinical and histomorphological features of these tumours. The presence of monosomy 3 and polysomy 8 was initially detected using FISH but MLPA, aCGH, aSNP and GEP, have been introduced in various ocular oncology centres, providing more detailed information. It is hoped that next generation sequencing will provide potential targets for improved therapies in ocular malignancies.
Neuro‐ophtalmic complications of cancer chemotherapy
Authors: KAWASAKI A
Published: November 2013

Cancer patients nowadays have longer periods of remission and higher rates of cure. The greater number of efficacious chemotherapeutics agents has no doubt contributed to prolonged survival rates for cancer patients but this has also led to a greater number of adverse and neurotoxic effects of chemotherapy. Sometimes, it is not easy to determine the exact etiology of a neuro‐ophthalmologic disorder as these patients have multiple potential causes : metastasis, nutritional or metabolic derangement, vasculopathy, paraneoplastic syndrome, complication of radiation. Nevertheless, it is important for the ophthalmologist to have some familiarity with the more commonly reported neuro‐ophthalmologic complications of chemotherpay. This lecture will discuss agents that have been associated with optic disc swelling, increased intracranial pressure, cranial nerve palsy and acute cerebellar syndrome.
Using ‘big data’ to examine visual field follow up in glaucoma
Authors: CRABB D
Published: November 2013

Monitoring glaucoma patients represents a significant burden on clinical services, with an estimated one million visits annually in the UK alone. Visual field (VF) tests are routinely used for detecting worsening of vision. We aimed to estimate VF loss during patient's predicted lifetime by examining around 250,000 VF tests from three different glaucoma clinics in England. Patients were excluded if they had too few VFs or insufficient follow‐up (less than 3 years). Levels of VF loss were summarised using the Mean Deviation (MD) index from each test. MD at diagnosis and MD loss during predicted remaining lifetime, using a linear rate of MD deterioration (dB/year) and residual life expectancy tables, were calculated and plotted on motion graphs. Most patients followed in clinics have stable disease. Four percent (95% confidence interval: 3 to 5%) of patients were predicted to be at risk of statutory blindness in their lifetime. Likelihood of a patient suffering serious visual impairment in their lifetime is linked to level of VF loss at presentation. These findings from retrospective analysis of ‘big data’ could help inform planning of follow‐up in glaucoma and also illuminate the importance of detecting the disease in primary care.
Conception and optimization of a corneal bioreactor
Authors: TRONE MC , CAMPOLMI N , GAUTHIER AS , NEFZAOUI C , BERNARD A , NAIGEON N , NANGOUM‐FOSSO T , PISELLI S , GARRAUD O , ACQUART S , THURET G , GAIN P
Published: November 2013

Purpose Restoration of a trans‐corneal pressure (P) gradient and continuous circulation of fluids on both sides of the cornea could improve endothelial cell survival and reduce stromal swelling and Descemet folding during long‐term corneal storage. Aim: to present the technical requirements and the technical choices we made during the development of an innovative corneal bioreactor (BR)

Methods Main functions were defined with a process of functional analysis of needs in collaboration with eye bankers. Successive prototypes were built using 3D printing with biocompatible resins, and machining of PMMA blocks, and windows made out of optical grade glass were glued. Different types of connecting tubes were assessed. Efficiency was analysed in term of capacity of maintaining the cornea perfectly tighten in order to create 2 hermetic endo and epi compartments. P (adjustable from 0 to 50 mmHg with a mini‐LCD screen for live display) was regulated by a continuous irrigation from a disposable infusion system associated with a P sensor and a micro‐solenoid valve driven by a customized microcontroller

Results The 3 most challenging points were: 1/waterproofness between epi and endo chambers that require to use corneas with at least a 16 mm diameter regular scleral rim 2/ biocompatibility of glues 3/ oxidation and alcalinization of storage medium caused by materials permeable to atmospheric gases. Since 2 years, 9 successive prototypes allowed selection of efficient solutions

Conclusion Our innovative BR will be useful for both laboratory research and corneal storage by eye banks in a next future. Grant: ABM 2012, EFS 2012, ANSM 2012. PG, GT and SA patented the BR
Setting up organ‐cultured corneas pre‐cutting by a French blood center‐eye bank
Authors: CAMPOLMI N , GAUTHIER AS , MONTARD R , ACQUART S , THEILLIERE C , PEIRERA S , GARRAUD O , HE Z , PISELLI S , THURET G , DELBOSC B , GAIN P
Published: November 2013

Purpose In France, the cutting of endothelial graft for DSAEK is almost exclusively performed by surgeons directly in the operating room whereas in the US more than 2/3 are now precut by eye banks (EB) technicians using 4°C storage. Among the French Blood Center EB, the EB of St‐Etienne received the first agreement from the French National Agency for Medicines and Health products for precutting and distribution of corneas. Aim: to report our first experience with DSAEK precut by technicians using organ‐cultured (OC) corneas

Methods OC corneas with an initial endothelial cell density (ECD) >2200 cells/mm2 (by image analysis) were precut by two trained technicians using a Moria microkeratome. Corneas were stored in CMax (Eurobio) and deswelled in CJet (5% Dextran T500) 20h prior to pre‐cutting. Central corneal thickness (CCT) was measure by ultrasound before and after cut with a single pass of the 350μm head. Microbiological testing was done with blood culture bottles 24h after precutting

Results Twelve corneas with initial ECD of 2724±269 cells/mm2 (mean±SD), 19±4 days of OC and CCT of 548±50 μm were cut and sent to 4 centers (Feb to May 2013). Final CCT was 194±33μm (166 to 277). All surgeries were uneventful but rebubbling was necessary in 6 cases and 1 graft with eccentric trephination by the surgeon did never adhere

Conclusion Precutting of OC corneas by EB allows quality and microbiology controls. Three improvements are ongoing: OCT thickness map before, during and after cut, use of the microkeratome double‐pass technique, and ink marking of the centre to guide final trephination by surgeons. Grants: ONDAINE, AOL CHU 2012
Isolated and combined hamartomas of the RPE
Authors: SCHALENBOURG A
Published: November 2013

RPE hamartomas are rare, presumed congenital proliferations of the RPE (isolated) or both the RPE and neuroretina (combined), without malignant potential. Isolated hamartomas are well delineated, small, pigmented and asymptomatic lesions, most often in the macular region and not requiring any treatment. Combined hamartomas are unilateral malformations consisting of a densification of the RPE and vascularized gliosis of the overlying neuroretina. Its location at the posterior pole is correlated with varying degrees of visual impairment, for which epiretinal membrane peeling remains controversial. Treatment is occasionally required in case of complications such as neovascular membrane, vitreous haemorrhage, retinal detachment or macular hole. Being benign, it is crucial that RPE hamartomas are differentiated from other pigmented lesions, and most importantly choroidal melanoma, to avoid unnecessary radiotherapy or even enucleation in the –usually young‐ patients that present them.
How to study heterophagy in RPE cells
Authors: SINHA D
Published: November 2013

RPE is one of the most active phagocytic cell types in the body, phagocytosing 10% of total photoreceptor volume daily. Phagocytosis of the shed discs is essential to the survival of photoreceptor cells. This phagocytosis process can be divided into four distinct stages: 1) recognition and attachment of the OS; 2) ingestion of the OS; 3) formation of the phagosome and fusion with lysosomes; and 4) finally, digestion. Once OS are internalized by the RPE cells, the phagosome proceeds through a maturation process, followed by fusion with a lysosome to form a phagolysosome where degradation occurs. This pathway remains poorly understood in RPE. We have provided evidence that bA3/A1‐crystallin has no apparent role in recognition or ingestion of the OS. However, loss of bA3/A1‐crystallin in RPE has an impaired ability to degrade OS, perhaps resulting from a defect in the phagolysosomal pathway. The overall experimental design will be to determine the following parameters by modulating the expression of bA3/A1‐crystallin in RPE: (1) Expression levels of proteins involved in phagosome maturation; (2) Interaction of phagocytic vacuoles with early and late endosomes; and (3) Phagosome‐lysosome fusion as assessed by live cell imaging
Techniques to demonstrate immunoproteasome in retinal functions
Authors: FERRINGTON D
Published: November 2013

The catalytic core of the proteasome contains three pair of catalytic subunits that perform distinct proteolytic activities referred to as caspase‐like, trypsin‐like, and chymotrypsin‐like. In the standard proteasome, the catalytic subunits are β1, β2, and β5. These subunits can be replaced in nascent proteasomes by the subunits LMP2 (β1i), MECL‐1 (β2i), and LMP7 (β5i), which form the core of the immunoproteasome. The immunoproteasome is a proteasome subtype that is abundant in immune cells and also present, albeit in low concentrations, in cells outside the immune system. A well‐described function of immunoproteasome is to generate peptides for MHC class I for display on the cell surface. Functions of immunoproteasome that go beyond its role in generating antigenic peptides are emerging from studies in immunoproteasome‐deficient mice and from human diseases linked to mutations in immunoproteasome subunits. Notably, oxidative stress and pro‐inflammatory cytokines, conditions that predominate in retinal diseases, are associated with immunoproteasome upregulation. Multiple methods used to investigate immunoproteasome function in the retina and in cultured retinal pigment epithelial cells will be discussed in detail.
Is there a need for a general workup of RVO patients?
Authors: HERON E
Published: November 2013

The pathophysiology of retinal vein occlusion (RVO) remains unclear, the precise cause of venous flow obstruction being still unknown. Established and potential risk factors of RVO, according to the pusblished literature, will be reviewed and discussed with a rapid focus on thrombophilia. Recent new insight in the field of blood viscosity in RVO patients and its possible therapeutic implications will be presented. This will lead to conclude on which reasonable general work‐up to be proposed to RVO patients.
The issue of chronic macular edema
Authors: GIRMENS JF
Published: November 2013

With availability of dexamethasone implant and ranibizumab, specifically indicated for the treatment of macular edema complicating RVO, a trend could be to treat as quickly as possible all retinal thickenings by intravitreal injections (more or less often, depending on duration of action of selected product). However, all retinal thickenings are not identical, nor from the same origin. Fine semiological analysis allows to distinguish different types : in addition to macular edema by blood‐retinal barrier rupture (most common), we will describe other involved mechanisms, like macro‐aneurysms, ischemia, diffusion of papilledema, epi‐retinal membrane. Differentiation of mechanism is important because involving different therapeutic approaches.
Fitting tips and tricks of challenging cases of keratoconus
Authors: ABOU SAMRA W
Published: November 2013

Purpose to discuss the fitting tips and tricks of challenging cases of keratoconus with a special design of RGP lens namely Rose K2 lens

Methods The study was carried on 52 keratoconic eyes fitted with Rose K2 lens. They were topographically classified into low cones, small steep cones, early cones, advanced cones and toric cones. The appropriate lens parameters were selected accordingly. Successful fitting was evaluated by lens position, movement, fluorescein pattern, visual acuity, residual astigmatism, patient comfort, maximum wearing time per day and corneal integrity.

Results The keratoconic eyes were successfully fitted as follow: lenses with bigger diameter and considerably flatter base curve than normal were used to fit the low cones, lenses with flatter base curve, minimum diameter and maximum edge lift were used in small steep cones. Keeping the lens as small as possible and considerably steeper base curve than normal were used in advanced cones. Early cones were fitted with larger diameter lenses with decreased edge lift. Toric or astigmatic corneas were fitted acceptably either by reducing the overall diameter of the lens or using toric RGP lens. With the previous lens parameters, most of patients (96%) tolerated their lenses with maximum wearing time per day 11± 2.5 hours. No corneal staining or abrasion was encountered in studied eyes. Lenses were centrally positioned with adequate movement and acceptable fluorescein pattern. Best corrected visual acuity was significantly increased compared to the baseline visual acuity with significantly decreased astigmatism.

Conclusion Patients with keratoconic corneas are sometimes challenging to fit and time consuming, but if well fitted with appropriate lens parameters, they appreciate the benefits provided by their contact lenses i
Current phenotype of keratoconus patients at King Khaled Eye Specialist Hospital
Authors: AL‐SWAILEM S , YIU S , AL ASSIRI A , ASGHAR N , AL QASSIMI A
Published: November 2013

Purpose To identify the characteristics of Keratoconus (KC) patients referred to the largest tertiary eye institute in Saudi Arabia (SA).

Methods Chart review of 483 patients from Jan. to Dec 2010. Amsler‐Krumeich classification was used for severity staging.

Results The mean age of 944 eyes at diagnosis and referral were 21.6 and 28.1 years, respectively. Male to female ratio was 2:1. Mean central corneal thickness was 390 (range, 221‐619) um. Staging asymmetry between both eyes in bilateral (95.4%) cases were present in 53.8%. Male patients were diagnosed in mild stage (stage1), while, female patients in advanced one (stage 4). Advanced stage was significantly diagnosed at mean age of 19.76 years. Uncorrected visual acuity decreased with increasing disease staging (≥20/80 in 46.4% of stage 1, while < 20/200 in 39.1% of stage 4). Best corrected visual acuity, with either spectacles or contact lenses (CL), was ≥ 20/40 in 79.7% of eyes. Less eyes achieved 20/40 with spectacles in comparison to those fitted with CL. Single or combined management included: spectacles (15.4%), CL (57.6%), corneal collagen cross‐linking (3.9 %%), corneal rings (10.6%) and keratoplasties (39.3%). Corneal rings were required in mild (62%), moderate (35%), and advanced (3%) stages. Sub‐epithelial and deep stromal scarring was present in 61.2% of eyes which required keratoplasties, and 2/3 of which were having moderate and advanced stages. Male patients tended significantly to have keratoplasty done at 20‐30 years, while, female patients at >30 years of age.

Conclusion Our KC patients are similar to those reported in Indians with regards to early disease‐onset, advanced stages, rapid progression, more scarring & lower contact lens wearers.
Quantification of cone loss after macula‐involving retinal detachment using the RTX‐1 Adaptive optics camera
Authors: FLORES M , DEBELLEMANIERE G , MEILLAT M , TUMAHAI P , SCHWARTZ C , MONTARD M , DELBOSC B , SALEH M
Published: November 2013

Purpose To image the macular cone photoreceptors in eyes with successful repair of retinal detachment (RD) and in healthy fellow eyes using the RTX‐1 Adaptive optics camera from Imagine Eyes™ and to correlate the results to clinical outcomes.

Methods Patients operated for macula‐off RD were imaged 6 weeks after surgery. The images were analyzed using AO Detect v.0.1. Cone density, spacing between cells, and the nearest‐neighbor analysis were measured 1° nasally and temporally from the fovea. Best corrected Visual acuity (BCVA) and thickness of the photoreceptor inner and outer segment junction (IS/OS) line imaged by SD‐OCT were also measured.

Results Twenty one patients (42 eyes) were studied. The parafoveal cone density was decreased in eyes operated for RD (mean±SD: 14,576±4035/mm2) compared to fellow eyes (20,589±2350/mm2) (Wilcoxon matched pairs test, p=0.0001). There was also an increase in cone spacing (10.3±2.6 vs. 8.0±1.0.9 μm, p<0.0001). The Voronoï analysis revealed a reduction in the percentage of cones with six neighbors (36.5±4.2 vs. 42.7± 4.6%, p=0.0003). The IS/OS line thickness was correlated to the cone density in the same area (r=0.62, p< 0.0001). BCVA was significantly correlated to cone density and inversely to intercone spacing, and in a lesser proportion to the percentage of cones with six neighbors (r=0.8, −0.71 and 0.49, respectively, p<0.001).

Conclusion There was a decrease in the cone density after RD with an estimated loss of one‐third of the cones in comparison with fellow eyes. Visual acuity was highly correlated with the parafoveal cone density and cone spacing. AO may be a valuable prognostic tool after RD surgery.