bluuebunny/crossref_metadata_2025 huggingface dataset:
Debate: Challenging cases of retinal pigment epithelium lesions: How to diagnose? How to manage?
Authors: GARCIA‐ARUMI J , DAMATO B , DESJARDINS L , SCHALENBOURG A , ZOGRAFOS L
Published: November 2013

Abstract not provided
Techniques for studying mechanisms of autophagy in RPE cells
Authors: KAARNIRANTA K
Published: November 2013

Autophagy is basic catabolic mechanism which ”self eats” cellular components that are unnecessary or dysfunctional to the cell. Autophagy comprises three intracellular pathways in eukaryotic cells, which are macroautophagy, microautophagy and chaperone‐mediated autophagy. These forms of autophagy are mechanistically different from each other, but finally they all lead to lysosomal degradation of intracellular material. Autophagy is triggered as an adaptive response during AMD‐associated stress conditions such as hypoxia, oxidative stress, the unfolded protein response or inflammation. Macroautophagy process begins with the formation of isolation membranes called phagophores at the phagophore assembly site. The phagophores then become elongated and surround a portion of the cytosol to form mature double membrane autophagosomes that can engulf portions of cytoplasm containing oligomeric protein complexes and organelles. The autophagosomes fuse with the lysosomes and their content is then degraded by lysosomal enzymes. Failure of autophagy in aged cells may accelerates degenerative processes. Recent methods to study autophagy are discussed with details in the course.
Discussion of clinical cases in real‐life practice
Authors: MAUGET‐FAYSSE M
Published: November 2013

In real‐life practice, in the light of the new concepts presented in this Special Interest Symposium, the management of retinal vein occlusion cases will involve: ‐ The classification of venous occlusion, ‐ The neovascular risk, ‐ The presence of macroaneurysms ‐ The general prognosis and treatment. Clinical cases concerning different types of venous occlusion will be presented to identify the cardinal signs for classification and treatment. In particular, we will present a case of central vein occlusion with peri venular whitening, a case with increased neovascular risk, a case with the cardinal signs for classification etc… At the end of the presentation, the audience will be able to recognize these cardinal features and the elements of the new classification.
What research tells us about the impact of glaucoma on the patient
Authors: RAMULU P
Published: November 2013

Understanding the impact of glaucoma on the person is critical for treatment and public policy decisions. The functional domains impacted by glaucoma include mobility, driving, reading, and search‐related tasks. A major impact of glaucoma is falls, and a one in three glaucoma patients experiences an injury resulting from a fall in a given year, likely as a result of balance impairment. The result is significantly more fear of falling than normally‐sighted individuals, leading to significant restriction of physical activity, walking, and travel outside the home. Individuals with glaucoma are also more likely to stop or restrict their driving resulting in decreased independence, while those who continue to drive have higher rates of motor vehicle accidents. Glaucoma is associated with slower reading speeds, particularly when reading out loud, reading over longer durations, or reading low contrast materials. Finally, glaucoma affects a broad array of other abilities important in daily life including searching for objects, reaching and grasping objects, and recognizing individuals or objects. These impairments decrease quality of life for the individual and confer additional health risks, i.e. from fall or accident‐related injury.
The art of healthcare: the importance and impact of effective Patient and Public Involvement (PPI)
Authors: PORTEOUS C
Published: November 2013

Patient and Public Involvement (PPI) is a central component to health and social care research carried out in the UK, Europe, North America and Australia. It has a long history, from its roots in social activism and in patient movements through to clinical and political policy changes. However, PPI is yet to emerge as an important consideration in research and development within ophthalmology. The presentation will explore the some of the basics of patient and public involvement, including what it is, who it encompasses, and why PPI has an important role in research. The presentation will review the outcomes of the recent ‘Glaucoma Day’ held in London as an illustration of the importance of involving the public in research. Finally, the challenges and impact of PPI on eye research will be discussed
What glaucoma means to me: The patient's perspective
Authors: KOTECHA A
Published: November 2013

The patient’s perspective is becoming increasingly important within ophthalmology, with a wide variety of instruments available to ‘measure’ the patient’s response and attitudes to their disease status, and the impact of new treatments on their well‐being. The results of these are often used to facilitate change in how conditions are managed. However, they don’t always fully capture the patient experience. This talk will consist of a series of short interviews with patients suffering with glaucoma to give a snapshot of what really matters to them, how they manage in every day life with their condition, what they think of their hospital visits and how they perceive the role of their caring clinician in the management of their disease.
Influence of growth factors on keratocyte phenotype in serum free media
Authors: LYNCH A , O’SULLIVAN F , AHEARNE M
Published: November 2013

Purpose Most studies examining the influence of growth factor on keratocytes in vitro have used serum supplemented media which promotes fibroblastic differentiation. The purpose of this study was to evaluate the effect of growth factors on the regulation of the keratocyte phenotype and extracellular matrix (ECM) production in vitro using a serum free media that has been shown to promote a keratocyte phenotype.

Methods Human keratocytes were cultured in keratocyte media (KM) consisting of Advanced DMEM, supplemented with GlutaMax, FGF‐2 and L‐ascorbic‐2‐phosphate. Cells were cultures for 14 days and supplemented with IGF‐1, TGFβ‐1 or TGFβ‐3. DNA, sGAG and collagen synthesis were determined via biochemical assay. Expression of corneal, fibrotic and ECM related genes were examined by real‐time PCR. ECM production was also examined by histological and immunofluorescent staining.

Results TGFβ‐3 stimulated the highest level of proliferation and sGAG synthesis. In contrast, IGF‐1 and TGFβ‐1 showed significantly lower levels of DNA synthesis and sGAG production, comparable to KM alone. KM and TGFβ‐3 showed the highest level of expression for keratocan. ECM and collagen production was evident for both the KM and TGFβ‐3 group. The expression of αSMA was greatest for TGFβ‐3, while KDM demonstrated the highest expression levels for both collagen type I and III.

Conclusion These results demonstrate the influence different growth factors have on the phenotypic behaviour of keratocytes in serum free media. Further study in 3D culture will provide a useful model to further understand the effect growth factors have on keratocyte behaviour.
Communicating your research and presenting your data
Authors: DAMATO B
Published: November 2013

This presentation will focus on oral communications and scientific papers. An oral presentation must catch and hold the audience's attention, communicating the message unambiguously, succinctly, and memorably. Scientific papers must include all relevant methods and results, which must not only be honest but also convincing. The introduction must be sufficiently informative to educate the inexpert reader. The discussion must answer the most likely questions to be asked by the readership. Oral and written communications are most likely to succeed if they conform to conventional style. This talk will include tips and tricks for preparing effective oral presentations and scientific papers, with special attention being given to the presentation of data in the text, tables and figures. Useful sources of information will also be identified. It is tragic when important research is wasted because of poor communication. By adhering to simple rules, scientists can indeed bring their research projects to a successful conclusion, which is to disseminate new knowledge widely and effectively, by delivering inspirational presentations at influential conferences and publishing much‐cited articles in high‐impact journals.
Mid‐term efficacy and safety of adalimumab in refractory pediatric uveitis : A retrospective monocentric study
Authors: PENAUD B
Published: November 2013

Purpose Evaluate the mid‐term efficacy and safety of adalimumab in the pediatric population with severe uveitis.

Methods We retrospectively analysed 18 children with severe uveitis, who were treated with adalimumab (20 or 40 mg every two weeks) when the previous immunosuppressive therapy has been ineffective. It consisted of systemic corticosteroids (n=18), methotrexate (n=18), azathioprine (n=8), infliximab (n=6), etanercept (n=6), interferon‐alpla (n=1). Primary outcome was to assess laser flare photometry values after adalimumab therapy compared with baseline. Clinical features (SUN criteria, macular edema and papillitis), oral prednisone threshold, visual acuity, side effects and complications of treatment were also considered.

Results Median age was 13.1 years (range 6‐20.8),sex ratio (F/M) was 3. Median duration before adalimumab therapy was 82.6 months (range 16‐262). The mean follow‐up was 35.5 months (range 23‐63) and the final median laser flare photometry value was significantly reduced from 149.5 ph/ms (range 24‐335) to 81.3 ph/ms (range 4‐224) p<0.005. Median oral prednisone decreased from 10.3 mg/day (range 0‐30) to 1.7 mg/day (range 0‐15) p<0.05. Uveitis was controlled in 10 cases (55.5%). Relapses occurred in 2 cases (11%), adalimumab was ineffective in 3 cases (17%) and was stopped in one patient who had excellent control of inflammation. Three children (17%) discontinued treatment due to severe side effects.

Conclusion Adalimumab appears to be an effective and well tolerated treatment for refractory pediatric uveitis, with prolonged control of inflammation over several years, even after failure of other anti‐TNF alpha agents. A prospective randomized double blind study is ongoing.
Tocilizumab for uveitic macular edema
Authors: MESQUIDA M , LLORENÇ V , ADAN A
Published: November 2013

Purpose To report the outcomes of tocilizumab (TCZ) treatment for uveitic cystoid macular edema (UCME) refractory to immunomodulatory therapy.

Methods Five refractory patients with UCME who received TCZ between January and August 2012 were identified by retrospective chart review. All patients received 8 mg/kg TCZ at 4 week intervals. Data regarding patient demographics, use of immunosuppressive (IS) drugs, biologic agents or intravitreal therapies prior to TCZ infusions were gathered. Main outcome measures: Central foveal thickness (CFT) measured by optical coherence tomography, degree of anterior and posterior chamber inflammation (Standardization of Uveitis Nomenclature Working Group criteria), and visual acuity (logarithm of the minimum angle of resolution [log‐MAR]) were recorded at month 1, 3, and 6.

Results Eight eyes from 5 patients (all females) were included. Mean age was 49.4 years (range, 30‐68). Mean follow‐up was 8.4 months (range, 6‐12). Before TCZ, all patients received and failed conventional IS therapy and had received at least 1 another biologic agent. Uveitis diagnoses were: Birdshot chorioretinopathy (n=3), juvenile idiopathic arthritis‐associated uveitis (n=1), and idiopathic panuveitis (n=1). Mean baseline CFT (95% confidence interval) was 602 ± 236 μm in baseline, 386 ± 113 μm at month 1 (p= 0.006), 323 ± 103 μm at month 3 (p= 0.026) and 294.5 ± 94.5 μm at month 6 (p= 0.014). Median log‐MAR best‐corrected visual acuity (BCVA) improved from 0.66 ± 0.57 in baseline to 0.47 ± 0.62 at month 6 (p = 0.035). After 6 months, an improvement of ≥ 2 lines of BCVA was observed in 50% of eyes (p= 0.028). Sustained uveitis remission was achieved in all patients. No AE were reported.

Conclusion These data suggest that TCZ is effective for treating UCME in otherwise refractory cases.
Evaluation of cone photoreceptor density using adaptive optics retinal imaging in patients under treatment with hydroxychloroquine
Authors: DEBELLEMANIèRE G , TEA S , TUMAHAI P , MEILLAT M , FLORES M , BIDAUT GARNIER M , SCHWARTZ C , MONTARD M , DELBOSC B , SALEH M
Published: November 2013

Purpose Hydroxychloroquine is a common treatment of many inflammatory diseases and is sometimes responsible of irreversible macular toxicity. Early screening is essential. Our study aimed to evaluate feasibility of adaptive optics imaging in this population and to measure parafoveal cone density.

Methods Patients under treatment or consulting for a pre‐treatment checkup where included. A complete ophthalmologic examination was performed, as well as a high‐definition fundus photography using adaptive optics retinal camera rtx‐1™ (Imagine Eyes, Orsay, France). Cumulative dose of hydroxychloroquine was calculated. Parafoveal cone density, cellular spacing, and percentage of hexagonal cells calculated using Voronoi diagrams were calculated using AODetect v0.1 software (Imagine Eyes, Orsay, France).

Results Sixty eyes of 30 patients (27 females, 3 males) were imaged. There was a significative correlation between maximal parafoveal cone density and cumulative dose of hydroxychloroquine. (R² = 0,20, p = 0,029). This relation was also found with cellular spacing (R² : 0,2, p = 0,03) and hexagonal cells percentage estimated on Voronoi diagram (R² : 0,19, p = 0,03). By contrast, no statistically significative difference was found by comparing the group “cumulative dose < 1000g” with the group “cumulative dose > 1000g (Mann‐Whitney test,p = 0,14).

Conclusion Parafoveal cone density mesure using adaptive optics retinal camera is achievable in this population. Our study seems to highlight a relation between cumulative dose and parafoveal cone density. Age and axial length are possible confusion factors that could not be studied in this study.
Anatomy of afferent visual pathway
Authors: KAWASAKI A
Published: November 2013

The afferent visual pathway encodes and transmits all aspects of image perception from retina to occipital lobe. A critical feature of this pathway is the topographic organization of the fibers that make up the afferent visual pathway. Knowledge of the anatomy and topography of the afferent visual pathway will aid recognition and localization of specific patterns of visual field defects.
Principles of automated perimetry
Authors: SZATMARY G
Published: November 2013

Principles of Automated Perimetry: Types and Uses Background: Visual field testing is sensitive and has localizing value, therefore is an essentially part of the clinical evaluation of every patient with complaint related to the afferent visual system. Objective: To review the most informative available kinetic and static visual field methods. Indication, basic principles, advantages and disadvantages of the various methods will be discussed. Methods: Retrospective review of the literature on perimetry methods presented along with representative cases. Results: Apart from availability, indication that is based on clinical suspicion, should determine the applied perimetry method in a particular patient's evaluation. Sensitivity of visual field testing supersede most other available diagnostic methods even magnetic resonance imaging. Conclusion: Familiarity with broad range of perimetry methods is essential in the initial clinical assessment and follow up care of patients with afferent visual system complaints.
Reduction of oxidative stress: Importance for age‐related diseases
Authors: GARHOFER G
Published: November 2013

Abstract not provided
Fluid from the retinal origin
Authors: WOLF‐SCHNURRBUSCH U
Published: November 2013

Macular edema is a nonspecific but very common final pathway for many ocular diseases and not a specific entity. Related ocular disorders include diabetic retinopathy, vascular occlusions, post surgical situations and inherited disorders. The retinal fluid accumulation could be intracellular or an extracellular. Extra cellular fluid accumulation, which is more frequent and more clinically evident, is directly associated with an alteration of the blood‐retinal barrier (BRB). Intracellular fluid accumulation leads to a cellular damage because of cytotoxic alterations of the cellular ionic distribution. These mechanisms may be complicated by the release of various cytokines, significant inflammation and/or ischemic processes. The influence fluid from the retinal origin should be illustrated with various diseases. Examples for typical findings of diagnostic tools like fluorescein angiography (FA) and optical coherence tomography (OCT) were given for each entity and described. We will discuss the different mechanisms of occurrence, the various clinical forms of fluid accumulation and the mechanisms of action.
Anti VEGF: When, which effect?
Authors: LOEWENSTEIN A , FLEISSIG E
Published: November 2013

Fluid accumulation in the retina is a multi‐factorial process that involves the breakdown of the blood‐retina barrier in retinal capillaries or the retinal pigment epithelium. Hydrostatic pressure gradient and the colloid osmotic pressure gradient lead to diffusion of fluid across capillary walls. Damage to tight junctions enhances the rate of capillary filtration, which exceeds the rate of fluid removal from the retina. Fluid accumulates in the outer plexiform layer and pools into cystic space. Accumulated fluid is visible on optical coherence tomography and fluorescein angiogram, but unlike clinical edema, its finding on imaging studies does not always correlate with changes in visual acuity. For that reason, periodical follow‐up is required. Decision to initiate treatment or re‐treatment to prevent progression to edema with subsequent deterioration of visual acuity may be difficult. Intravitreal injections with anti‐VEGF agents have become the first‐line treatment for macular edema. Combination therapy with corticosteroids may be successful in chronic edema that has been found to be somewhat resistant to treatment. Early treatment for macular edema was shown to be beneficial for optimal visual outcomes.

Commercial interest
Steroids: How does it work?
Authors: BEHAR‐COHEN F
Published: November 2013

Glucocorticosteroids (CGs) are widely used to reduce macular edema of any origin. GCs induce a quick (within hours) reduction in macular thickness, not well correlated to vascular leakage. Kinetic of action suggests that GCs are involved in fluid elimination from the retina but their mechanisms of action remain poorly understood. GCs act through activation of gluco and mineralocorticoid receptors that are co‐expressed in retinal cells such as retinal glial Muller cells and retinal pigment epithelial cells, both involved in hydro‐ionic balance in the retina. Through binding to either gluco and/ or mineralocorticoid receptors, CGs exert a direct regulation of ions and water movement through expression and distribution regulation of Kir 4.1, ENac and AQP4 channels in retinal glial Muller cells. Depending on their differential affinity for gluco or mineralocorticoid receptors and depending on the dose, different GCs act differently on hydro ionic regulation. These findings open new insight in the mechanisms of action of GCs on retinal edema and suggest that a more rationale use of GCs could help optimize the ratio efficacy/side‐effects of GCs.
RGC degenerations. A neural substrate for reversing glaucomatous damage?
Authors: MORGAN J
Published: November 2013

The demonstration of retinal ganglion cell (RGC) dendritic remodelling and pruning in glaucoma raises the possibility that this could provide a neural substrate for the recovery of retinal ganglion cells. The associated reduction in the size of the retinal ganglion cell receptive field can arise as a result of the loss of dendrites but also due to the loss of synaptic connections. Since RGCs appear to maintain their central neural connections during the early stages of this degenerative process, the creation of conditions for the regrowth of RGC could allow the establishment of novel connections within the inner plexiform layer and the recovery of visual sensitivity. There is compelling evidence that the perineuronal environment within the retinal ganglion cell layer requires disruption as a first step to the promotion of dendritic plasticity and regrowth in the mature retina. I will discuss how that might be achieved using the rat glaucoma model as an example. In particular, I will address technical challenges that must overcome if we are to provide convincing data that RGCs have recovered in experimental glaucoma.
Genetics of the stromal corneal dystrophies
Authors: NOWINSKA A
Published: November 2013

Genes connected to the occurrence of the stromal corneal dystrophies include: TGFBI (Transforming growth factor, beta‐induced), CHST6 (Carbohydrate sulfotransferase 6), UBIAD1 (UbiA prenyltransferase domain containing 1), DCN (Decorin) and PIP5K3 (Phosphatidylinositol 5‐Kinase type III). The description of each stromal corneal dystrophy genotype and phenotype will be presented based on the known literature as well as on the examples of eyes of the patients originating from polish population.
Meesmann dystrophy in Denmark
Authors: NIELSEN K
Published: November 2013

Meesmann dystrophy is a rare corneal disease characterized by numerous epithelial microcysts. Three distinct families have been identified in Denmark (population 5.600.000 citizens). Clinical, histological and genetic similarities and differences will be discussed.
Long term result of transcleral FNAB for genetic analysis of uveal melanoma
Authors: MIDENA E
Published: November 2013

Aim: The aim of this study is to evaluate long‐term safety and efficacy of in‐vivo transcleral Fine Needle Aspiration Biopsy (FNAB) for cytogenetic testing of posterior uveal melanoma (UM). Methods: One hundred thirty‐nine consecutive patients affected by UM underwent in‐vivo 25‐G transcleral FNAB just before brachitherapy. Sampled material underwent both FISH (chromosome 3 and 6) and MLPA analysis using standard procedures. Follow‐up was longer than 36 months. Results: The use of 25‐G transcleral FNAB appears a long‐term safe and effective procedure for in‐vivo cytogenetic testing of posterior uveal melanoma. Combined analysis of both arms of uveal melanoma bifurcated pathway (‐3 and +6p) increase predictive value of FISH technique. MLPA allows obtaining more information than standard FISH in UM prognostication (partial chromosomes deletion). Conclusions: The biological and prognostic value of partial chromosome 3 deletion, as well as others subtle chromosomes alterations or complex MLPA results, remains unclear.
Incisional trans‐scleral biopsy of choroidal melanoma
Authors: DAMATO B
Published: November 2013

BACKGROUND: In our experience, trans‐scleral fine needle aspiration biopsy (FNAB) does not provide sufficient tissue for all the required histological and genetic investigations, especially with thin tumours. TECHNIQUE: The author has developed a simple technique for performing incisional choroidal tumour biopsy, immediately before ruthenium plaque insertion. Briefly, the tumour is localized by transillumination and its margins are marked on the sclera with a pen. A plastic plaque template is temporarily sutured to the sclera with releasable bows and its position checked by trans‐scleral transillumination and binocular indirect ophthalmoscopy. After removing the template, a rectangular, lamellar scleral flap is made, which is hinged posteriorly. A small incision is made in the deep sclera and several tumour samples are obtained with Essen forceps. The flap is closed with tissue glue, without suturing. The ruthenium plaque is then sutured to the sclera, using the pre‐placed sutures. DISCUSSION: Tumor samples yielded using this method are larger than obtained with FNAB. The glue prevents tumour seeding into orbit and the lamellar flap protects the delicate ruthenium plaque surface from damage by the hardened glue.
Telemedicine screening for diagnosis of retinopathy of prematurity in clinical practice
Authors: LUX AL , LASTENET F , DENION E
Published: November 2013

Purpose To compare the Retcam Shuttle used in telemedicine and performed by a non‐ophthalmologist with the “gold standard” of binocular indirect ophthalmoscopy performed by a referent ophthalmologist for the diagnostic of retinopathy of prematurity.

Methods Retrospective analysis of the archival data gathered in 18 months between 1 May 2011 and 1 November 2012 in two centers: one practicing telemedicine and one using indirect ophthalmoscopy. The same ophthalmologist was reading the images obtained by Retcam in the first center and performing the fundus examination in the other center. A total of 255 infants were examined, 74 by Retcam and 181 by indirect ophthalmoscopy, resulting in 570 examinations (141 and 429 respectively).

Results The mean birth weight of the infants was 1300 grammes (SD 340 grammes) in the center practicing telemedicine and 1130 grammes (SD 440 grammes) in the center using indirect ophthalmocopy. The mean gestational age were 28 weeks (SD 12 days) and 27 weeks (SD 19 days) respectively. A total of 1.8 examinations per infant were performed in the center practicing telemedicine, 2.4 in the other one. Retinopathy of prematurity was diagnosed in 13% of infants of the center using telemedicine and 20% of the other one.

Conclusion Telemedicine can be useful to diagnose retinopathy of prematurity especially in remote areas but it seems to have a lack of sensibility. A very tiny collaboration between the center practicing telemedicine and the ophthalmologist should be sought to improve the results of screening.
Utility of systematic ophthalmological screening in congenital toxoplasmosis: Epidemiological study of a French cohort between 1990 and 2011
Authors: SAUER A , CANDOLFI E , ESCANDE B , SPEEG‐SCHATZ C , SUBILIA‐GUIGNIER A
Published: November 2013

Purpose Ophthalmologic complications of congenital toxoplasmosis, such as retino‐choroiditis, are particularly feared. Any child with confirmed congenital toxoplasmosis is treated and regularly followed with many fundus examinations. The aim of our study is to describe the management and monitoring of a cohort of patients with congenital toxoplasmosis in Alsace, and the impact of this disease in terms of parental anxiety using a standardized questionnaire.

Methods Our study recorded 35 children with congenital toxoplasmosis, born between 1990 and 2011 in Alsace. All patients were followed by an ophthalmologist. A standardized questionnaire concerning the experience of pregnancy and post‐natal follow up were submitted to parents.

Results At birth, a retinochoroiditis was detected in 2 children, and only one child developed the disease during routine monitoring. Brain abnormalities were noted in 3 children at birth, none of them presented with retinochoroiditis to this day. An average score of 15 out of 23 was found by our standardized questionnaire, reflecting significant anxiety due to congenital toxoplasmosis.

Conclusion Parental anxiety due to congenital toxoplasmosis is obvious. A directed follow‐up by a complete pediatric examination at birth, including eye fundus, and good information on functional signs of ocular toxoplasmosis may improve the screening without impact on visual function.
Cataract morphology, visual function and quality of life: A prospective observational study of surgical section
Authors: ASPINALL P , KLIJN S , REUS NJ , DHILLON B
Published: November 2013

We sought to identify the relative importance placed on quality of life indicators amongst other patient‐specific determinants of cataract surgery in a 12‐month prospective study carried out at Princess Alexandra Eye hospital in Edinburgh attending 6 consultant teams. Data collection was carried out covering three major domains:visual function: (1) visual acuity, contrast sensitivity, retinal straylight measurement, (2) cataract morphology: Oxford cataract classification scale (3)quality of life:VF14, Massof and Sparrow Questionnaire. Patient factors predicting surgical selection reflective of current practice were best‐corrected visual acuity, brunescence grades and straylight measures, rather than quality of life scores across all grades of presenting severity for all consultant teams. Reducing thresholds for surgery and a "ceiling effect" may explain the poor predictive power of vision‐specific quality of life scales in current cataract surgical selection.
Simple novel surgical device to facilitate preparation of endothelial grafts for DMEK
Authors: MURAINE M , GUEUDRY J , TOUBEAU D , LEFEVRE S , AFFRIAT M
Published: November 2013

Purpose Descemet’s membrane and endothelial keratoplasty (DMEK) is the only technique to achieve a posterior corneal transplant without any interface. It is however difficult to achieve, mainly during the preparation of the graft. We propose a simple novel surgical device to facilitate this preparation.

Methods We used 20 corneas for research in this study. The device is in the form of a circular blade with a diameter of 8.5 mm. The blade is broken in two opposite points on 4 mm. The blade is applied to the cornea in order to cut Descemet's membrane and deep stroma. Preparation of the endothelial graft is performed on an artificial anterior chamber using a simple technique with a 27 gauge cannula to detach Descemet’s membrane. The dissection is performed under the microscope by a corneal bank technician in 8 cases, by a resident in 4 cases by a cataract surgeon in 8 cases. The three operators followed a specific course on the same day of dissection but had never tried to dissect a DMEK graft before. Endothelial cell density (ECD) was measured before dissection and 3 days after storage in organ culture. Histological analysis was performed.

Results Descemet graft could be easily dissected in 19 cases and resident failed dissection in one case. ECD was 2534±275 cells/mm² before dissection and 2412+/‐360 cells/mm², after 3 days in organ culture (p<0.01). Histological sections confirm that the cleavage was between DM and posterior stroma.

Conclusion We report here a reliable and efficient technique for the preparation of pure descemetic grafts.

Commercial interest
Allergic conjunctivitis related to cat and dog dander
Authors: ALMALIOTIS D , MICHAILOPOULOS P , GIOULEKA P , GIOULEKAS D , NAKOS E , XANTHOPOULOU E , KARAMPATAKIS V
Published: November 2013

Purpose A retrospective study on the prevalence of sensitization to cat and dog dander in patients with allergic conjunctivitis.

Methods 284 patients with allergic conjunctivitis (124 males‐160 females), with age from 18 to 70 years old (mean age: 42.30 for males, 41.35 for females), underwent skin prick tests (SPTs) to cat and dog dander according to current guidelines.

Results The results showed that more frequent allergens (positive SPTs) were cat dander 67/284 (23.59%), while dog dander showed lower positivity rates 44/284 (15.49%). As regards gender, 33 from 67 patients with positivity to cat dander were males and 34 were females. The numbers for sensitivity to dog dander were 20 males and the rest 24 females, indicating no sex predilection.

Conclusion Symptoms and signs of ocular allergy are very common and may be related to sensitization to cat and dog dander among other factors. The patients with allergic conjunctivitis included in our study tended to have positivity to cat rather to dog dander. No sex predilection was observed.
Myofibroblast biology and interactions with the environment
Authors: DESMOULIERE A
Published: November 2013

Normal tissue repair includes a number of overlapping phases. After injury, there is usually an early inflammatory step. Next, as granulation tissue forms, fibroblasts invade the wound and begin to replace the provisional matrix with a more mature wound matrix. As the granulation tissue phase proceeds, fibroblasts acquire a new phenotype with prominent microfilament bundles. These typical myofibroblasts (MFs) have been shown to develop a smooth muscle‐like phenotype, and are responsible for wound contraction. Lastly, in the resolution phase of healing, there is considerable loss of cell types including MFs, by apoptosis. Inappropriate delay of apoptosis, and thus increased survival of MFs activated during the healing process, may be a factor which leads to pathological situations and excessive scarring. In most situations, MFs derive from local connective tissue cells but it has now become clear that other cells can contribute to MF production. Both MF differentiation and apoptosis are dependent on cytokines, mechanical stress and more generally on cell‐cell and/or cell‐matrix interactions. The control of the MF activity represents an important target to promote healing and to limit excessive scarring.
Fibrotic alterations in glaucoma
Authors: WALLACE D
Published: November 2013

Glaucoma is the second leading cause of irreversible blindness worldwide, thought to affect 60 million people. It is a chronic progressive optic neuropathy with characteristic changes in the optic nerve head and subsequent visual field defects. In glaucoma, the lamina cribrosa (LC) region undergoes thickening and posterior migration in the early stages of the disease process, and later undergoes shearing and collapse of the LC plates leading finally to a thin fibrotic connective tissue structure/scar. This is characterised by the build‐up of extracellular matrix material and it is thought that this accumulation eventually results in elevated intraocular pressure and subsequent nerve damage. Here, we directly address the ongoing fibrotic pathology by use of alpha‐smooth actin expressing (myofibroblast‐like) human primary LC cells, including mechanisms of fibrosis and potential anti‐fibrotic therapies. Additionally we discuss the potential role of the Retinal Pigment Epithelial cell as a mediator of glaucomatous optic disc cupping / fibrosis through epithelial to mesenchymal transition.
Reducing high intraocular pressure with hypertonic saline before eye surgery
Authors: TORVINEN PIA
Published: November 2013

Purpose To compare the effect of intravenous hypertonic saline (IVHTS) on intraocular pressure (IOP) among patients with exfoliation glaucoma (ExG), primary open‐angle glaucoma (POAG), and ocular hypertension (OHT).

Methods A prospective, interventional trial. Included were patients with an IOP 24‐30 mmHg with or without topical medication. Excluded were patients using oral acetazolamide medication, those with heart or kidney failure, dementia or other systemic condition that markedly decreased physical performance. Participants received a bolus of 23.4% IVHTS trough an antecubital vein. Infusion rate was 1 ml/s and dosage 1.0 mmol/kg sodium in all patients. We measured IOP before we injected the bolus (baseline), every minute after injection for 10 minutes, and then less frequently for 2 hours.

Results A total of 35 patients participated (mean age 69 y, standard deviation [SD] 9); 16 ExG, 13 POAG, and 6 OHT patients. The baseline IOP 26.2 (SD, 1.7) mmHg was significantly reduced two minutes after treatment to 22.4 (SD, 2.6) mmHg (P<0.001). Maximum IOP reduction was achieved after 10 minutes, at which time IOP was reduced to 17.3 (SD, 2.9) mmHg (P<0.001), and the mean percentage IOP reduction was 34% (SD, 9). Mean IOP reduction was similar between groups (P=0.351; One‐Way ANOVA). Two hours after treatment, the mean percentage IOP reduction was 26% (SD, 14). Within 1‐2 minutes of treatment, 31 patients felt some sensation (pain, pressure) in the infusion arm, and 22 patients reported a feeling of warmth in their head.

Conclusion Hypertonic saline seems to be an effective and a rapid method to reduce IOP. This reduction seems to be independent of topical medication or glaucoma subgroup. IVHTS could be a practical method to reduce IOP before or during eye surgery.
Motion perception in early glaucoma
Authors: FRANCOZ A , CARLINI A , CREUZOT‐GARCHER C , POZZO T , BRON AM
Published: November 2013

Purpose The aim was to underline changes in the motion perception for early glaucoma. Our hypothesis consisted in inquiring if the impairment of the magnocellular pathway may modify the motion perception.

Methods We included 14 healthy subjects and 14 patients with early primary open angle glaucoma. A moving target was presented on a semicircular screen; participants were asked to localize the Ending Point (EP) of each motion. A stimulus consisted in a white dot moving horizontally. Two different laws of motion were displayed: a “biological” motion, consisting in a bell‐shaped velocity profile, and a “non‐biological” motion corresponding to a constant velocity profile. EP may be displayed in the peri‐central or peripheral visual field. The experiment was constituted by 192 trials. We calculated the PCE (Position Constant Error) which was defined as the average difference between the estimation of the EP indicated by the participant versus the true location of the target. The PVE (Position Variable Error) was defined as the standard deviation of the responses of each participant.

Results All the participants overestimated the EP (13.23±8.87 mm for healthy subjects and 17.06±13.07 mm for glaucoma patients, p=0.2518). The PVE was 28.14±6.86 mm for healthy subjects and 40.95±9.83 mm for glaucoma patients (p=0.0004). There was a significant difference in the PVE for both groups when stimulus moved accordingly to the “non‐biological” velocity profile (p=0.0001). Glaucoma patients had substantial PVE increase when the target image had a “non‐biological” speed profile (p=0.0388).

Conclusion The unexpected lack of difference between normal subjects and patients in localizing a moving stimulus suggested that the visual deficiency could be partly compensated by endogenous informations.
Transplantation of cultured limbal epithelial cells
Authors: BORDERIE V
Published: November 2013

Abstract not provided
Transplantation of cultured oral mucosal epithelium
Authors: BURILLON C
Published: November 2013

Abstract not provided
Bioengineering and stem cells for corneal endothelial cell therapy
Authors: THURET G , HE Z , SUFFEE N , BERNARD A , NAIGEON N , NANGOUM‐FOSSO T , CROUZET E , PISELLI S , HA THI BM , FOREST F , DUMOLLARD JM , PEOC’H M , GAIN P
Published: November 2013

The global planetary scarcity for corneal donation pushes research teams to develop substitution strategies. The worldwide success of endothelial keratoplasty (EK) has profoundly simplified the paradigm of corneal bioengineering since the technical and biological requirements for EK is far simpler than for full thickness corneas. Two main concepts have recently emerged: bioengineered endothelial cell (EC) sheets inserted into the anterior chamber or EC suspension ready to be injected. Review of the literature and personal works from our laboratory of corneal bioengineering. According to the local availability of donors, researchers either focus on the optimization of the use of human corneas or on the development of alternative substitutes comprising transformation of primarily non‐ocular human cell types (hECS, hIPS or MSC) and bioartificial or animal decellularized substrates as a carrier. We chose to use only human tissues and developped different methods able to multiply the EK available. With femtosecond laser cut, 5 to 7 EK seemed feasible with 1 donor. We also patented a corneal bioreactor helpful during the bioengineering process itself as well as for preclinical validation of the new advanced therapeutic medicinal products on ex vivo human corneas. Numerous proofs of concepts have been obtained and several preclinical animals studies done. The very first‐in‐man applications was done in Japan with injection of cultured EC. All these promising complementary strategies may constitute the tomorrow endothelial dysfunction treatments. Grants: ABM 2013, ANSM 2012, EFS 2012
Pluripotent stem cells (ES & iPS) for treatment of retinal dystrophies
Authors: GOUREAU O
Published: November 2013

The impaired or complete loss of function of photoreceptor cells or supporting retinal pigmented epithelium (RPE) is the main cause of irreversible blindness in retinal diseases, such as inherited retinal degenerations and age‐related macular degeneration (AMD). Rescuing the degenerated retina is a major challenge and cell replacement is one of the most promising approaches with the use of pluripotent stem cells. Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells that have the ability to be expanded indefinitely in culture whilst retaining their pluripotent status could be used as an unlimited source of retinal cells for tissue transplantation. The current challenge is actually to determine culture conditions for efficient and directed differentiation of human ES/ iPS cells into RPE or photoreceptors, so that large numbers of these cells might be transplanted at the optimal stage. We will present several approaches allowing the generation of RPE cells from human ES and iPS cells; and we will reported the ability of these stem cells to be committed into the neural retinal lineage, and further to be differentiated into photoreceptor cells following different protocols.
Development of uveal melanoma xenografts: From patient tumors to patient derived xenografts characterization
Authors: NEMATI F , LAURENT C , GENTIEN D , PIPERNO‐NEUMANN S , DESJARDINS L , MARIANI P , SASTRE X , ASSELAIN B , LANTZ O , ROMAN‐ROMAN S , DECAUDIN D
Published: November 2013

50% of uveal melanoma patients die from their metastatic disease showing the necessity to develop efficient therapeutic agents and useful and relevant tool for their preclinical assessment. Thus, we have established and characterized an in vivo panel of xenografts directly obtained from patient uveal melanoma tumors. 90 Samples obtained from patient primary tumors or metastases were subcutaneously grafted into SCID mice. 25 patient derived xenografts (PDX) were obtained and 16 have been characterized. UM histology of the PDX was confirmed by pathological analyses. NA17, Tyrosinase, and Melan‐A antigen expressions were positive in all samples. Bcl‐2 protein was overexpressed in almost all PDX. GNAQ, GNA11 and BAP1 mutations were observed in 4, 10 and 7 of 15 xenografts. The comparison of genomic alterations showed the same DNA damages as the corresponding patients and the differential genes expression observed was mainly due to difference of stroma between patient tumor and PDX. In vivo therapeutic assessments were being performed and will be presented. Our panel of PDX presents the characteristics similar to the patient’s originated tumors and could constitute a useful preclinical tool for testing new agents and protocols.
Age macular degeneration‐alzheimer disease in‐between correlations: One year screening, follow‐up and outcome
Authors: GONZALEZ C
Published: November 2013

Purpose To evaluate the evolution of the AMD‐AD correlations and their in‐between impact.

Methods PATIENTS: AMD patients: 240 patients, 3 Groups A, B, C. A: 70 AMD patients with first stage AMD,B: 64 Atrophy AMD patients with predominant atrophic areas, C:106 Neovascular AMD patients, with Neovascular AMD. AD patients: 240 patients, 4 groups.I:70 Normal,no significative patients;II:127 MCI patients,(4 subgroups: mild, moderate,intense,severe); III :29 Early AD; IV:14 AD. EXAM: ophthalmologic exam included ETDRS visual acuity (VA), complete ophthalmic examination, Fundus examination, autofluorescence imaging(FAF),(Region Finder Software,for atrophic areas),optical coherence tomography (Spectral Domain OCT) (OCT en face software), and fluorescein angiography (FA) and ICG when Neovascular complication. Cognitive evaluation is done with MMSE: Mini Mental State Examination (Folstein, GRECO), score allow to determine various groups and subgroups. Each AMD patient, would have besides cognitive evaluation,and each AD patients, ophthalmologic evaluation. Follow‐up was done every 4 months.

Results Cognitive impairment differ in each AMD subgroup: Normal score: mild in group A(37%),more in group B(23%)than in group C(35%).MCI was predominant(A:63%,B:77%,C:62%)and the most in group B. Early stage AD:3% only in group C.After1year follow‐up ,we observe more moderate cognitive impairment in Group B, few but the most severe worsening in Group C. AMD ophthalmologic signs are predictive and precursor for AD,and more than AD for AMD. Fundus examination and even more (FAF, OCT)are useful and needed to enhance AD screening and follow‐up.

Conclusion The AMD‐AD correlations are confirmed,enhance AMD as marker for AD,improve AMD and AD screening and knowledge.
Ophthalmological complications after treatment of carotid‐ophtalmic artery aneurysms using flow diverter
Authors: LECLERC O , BENAYOUN Y , ROUCHAUD A , AYOUB D , MOUNAYER C , ROBERT PY
Published: November 2013

Purpose To evaluate the ocular complications after insertion of a flow diverter " pipeline embolization device" (PED) to treat carotid‐ophtalmic artery aneurysms. PED is an endovascular implant designed as a stent to alter blood flow into the aneurysm. Therefore it may decrease the blood flow in the ophtalmic artery, and induce ophtalmological complications.

Methods 22 patients suffering from carotid‐ophtalmic artery aneurysm, treated by flow diverter were included. Every patient underwent retrospectively a complete ophtalmological examination including macular and optic disc OCT and visual field.

Results Among those 22 patients, 12 (54%) reported fonctional troubles: decreased visual acuity (6 patients), visual field loss (1), diplopia (1), amaurosis (1), photopsia or myodesopsia (3). 5 (23%) had clinical lesions: optic atrophy (3), distal embolism (2). No patient presented optic nerve compression after embolization as checked on MRI.

Conclusion After flow divertion insertion, ophtalmological complications are frequent and various. Ophtalmological complications are rather due to ischaemia than compression, and may lead to optic atrophy and loss of vision. However a majority of patients recover normal visual function
Idiopathic optico‐chiasmatic arachnoiditis (IOCA) – enigmatic or non existant disorder?
Authors: GRZYBOWSKI A , LESSELL S
Published: November 2013

Purpose There was a plethora of publications on idiopathic optico‐chiasmatic arachnoiditis (IOCA) between 1929 and 1980 but few if any subsequently, testifies to the paucity of cases in recent decades. Thus, the aim of the study was to analyse the original descriptions of the disease and verify its real nature.

Methods Study was based on the analysis of all historical descriptions of the diseases, including earliest articles, textbooks, etc.

Results A 1929 report by the Argentine neurosurgeon Manuel Balado and his ophthalmic colleague Paulina Satanowsky is generally considered the first description of IOCA. By 1937 there were documented 129 surgically verified cases (13 associated with syphilis and the remainder idiopathic). The published descriptions of the disease was characterized by the great heterogeneity of the epidemiology, symptoms and signs. The decline of IOCA cases coincides with the advent of computerized tomographic scanning in the early 1970s. This has continued as more sophisticated imaging has been introduced.

Conclusion IOCA did not and does not exist as a separate and distinct clinical entity.