bluuebunny/crossref_metadata_2025 huggingface dataset:
Healing of a resistant corneal neurotrophic ulcer using a new matrix therapy agent (RGTA)
Authors: PISON A , HAY A , DETHOREY G , BREZIN A , BOURGES JL
Published: November 2013

Purpose To report the case of a patient with a corneal neurotrophic ulcer, resistant to the usual therapies, who has been treated with a new matrix therapy agent (RGTA). CACICOL 20® is a new ophthalmic device, derived from RGTA based matrix therapy (large biopolymers engineered to replace heparan sulfates).

Methods We report the case of a monophtalm and deaf‐mute 48 years old woman, who presented with a central neurotrophic corneal ulcer, not responding to the first line therapies, including high dose lubricant eye drops and amniotic membrane graft. To avoid the profound confinement induced by tarsoraphy, a compassional treatment with RGTA CACICOL 20® has been proposed. CACICOL 20® was instilled once every other day for 2 weeks. Biomicroscopic pictures were recorded to follow the cicatrization time course.

Results Epithelialization was obtained within 2 weeks with a perfect tolerance. The regimen of instillation was incidently doubled, causing a recurrence, which healed within 2 weeks after the correct regimen was reintroduced.

Conclusion This case report is consistent with a strong effect of CACICOL 20® in the treatment of resistant neurotrophic corneal ulcers. The optimal posology and the indications needs to be refined.
Diagnostic traps based on nomenclature of inflammatory changes in corneal confocal microscopy in vivo
Authors: SMEDOWSKI A , WYLEGALA E , WOJCIK L
Published: November 2013

Purpose To present possible misdiagnosis of infectious keratitis in corneal confocal microscopy in vivo images based on typically used nomenclature.

Methods Retrospective analysis of in vivo confocal microscopy images from 155 patients with different diagnosis. 63 cases were diagnosed in confocal microscopy as various infectious inflammations and confirmed microbiologically or based on treatment response. 25 of them were recognized as bacterial, 25 as viral, 11 as fungeal and 2 as Acanthoamebal keratitis. For each type of inflammation we selected “key words” typically used for describing characteristic corneal changes. In next step we analyzed other, non‐inflammatory cases and selected images which could be described with nomenclature using typically for inflammatory changes describing (for example “cyst”, “fibers”, “round cells infiltration”, “dendritic/Langerhans cells presence”, etc.).

Results From 92 non‐inflammatory cases, 35 could be described with inflammatory “key words”. These cases represented 14 different pathologies: Cogan and Messmann dystrophy, stroma fibrosis, corneal transplant rejection, in‐growth epithelial syndrome, crystal and vortex kerathopathy, after LASIK and after PRK changes, neurotrophic ulcer, superficial nerves outgrowth, diffuse anterior lamellar inflammation after LASEK, ichtyosis and Thygesson inflammation.

Conclusion Diagnostic process using confocal microscopy examination cannot be based just on algorithmic analysis of corneal images. For reliable diagnosis microscopy images should be compared with clinical state and anamnesis.
Clinical neuroprotection in relation to ophthalmology
Authors: ROSSETTI L
Published: November 2013

Neuroprotection has been proposed as a possible therapeutic paradigm for the treatment of glaucoma. Unfortunately, despite the bulk of evidence coming from experimental animal research, very few data on effective neuroprotection in human glaucoma are available. A first problem is related to clinical trials on neuroprotection: the choice of study design, types of patients and study outcomes has often been debated. Then the question of the right compound is also a fundamental issue. As of today, to carry out a clinical trial potentially providing convincing evidence of neuroprotection in glaucoma is considered so expensive that no company would think to put money in it. On the other hand, there are some small studies showing surprisingly large effects on various outcomes relevant for glaucoma. Looking at the existing examples of clinical trial on neuroprotection in glaucoma (e.g. the memantine trial, the LoGTs, etc.), better designed studies should be proposed and research to validate new outcomes highly encouraged.
Pediatric uveitis
Authors: BODAGHI B
Published: November 2013

The etiology and treatment of uveitis in children remains different from adults. Infectious and auto‐immune conditions must be identified. Juvenile idiopathic arthritis‐associated uveitis is the main etiology of chronic anterior uveitis. Pars planitis is another frequent etiology of bilateral auto‐immune uveitis. On the other hand, toxoplasmic retinochoroiditis, ocular toxocariasis and cat scratch disease should be excluded in children with unilateral posterior uveitis. Case reports will be presented in order to illustrate the management of different pediatric uveitis entities.
Motion‐onset visual evoked potentials ‐ Important tool in vision and eye research
Authors: KUBOVA Z , KUBA M , KREMLACEK J , LANGROVA J , SZANYI J , VIT F , CHUTNA M
Published: November 2013

Purpose Despite quite a long history of visual evoked potentials (VEPs), their use has been limited so far almost exclusively to flash or pattern related responses of the primary visual cortex (mediated mainly via activation of the parvocellular system of the visual pathway. It is surprising that efforts to extend it to more complex testing including an examination of the motion processing system (magnocellular system and dorsal stream) are quite rare (e.g. Kuba and Kubová, Doc Ophthalmol, 1992, 80, 83‐89; Kubová et al., 1995, Vision Res, 35, 197‐205.

Methods Early or selective involvement of the motion processing system is suspected in many CNS disorders and we suggest that motion‐onset VEPs may recognize functional problems of this kind better than imagine techniques (Kuba et al., Vision Res, 2007, 47, 189‐202.

Results Motion‐onset VEPs display latency shortening up to the age of about 18 years representing very slow individually different maturation of the motion processing system (Langrova et al., Vision Res., 2006, 46, 536‐544. In early adulthood they start accelerated latency prolongation when compared to pattern‐reversal, which might be a good indicator of individual biological ageing (Kuba et al., Vision Res, 2012, 62, 9‐16.

Conclusion Since about 30% of pathological findings in our parallel pattern‐reversal and motion‐onset VEPs examinations in neuro‐ophthalmological patients display exclusively the motion‐onset VEPs pathology, we strongly recommend using them both in the theoretical vision research and ophthalmological diagnostics. Acknowledgement: Supported by the project PRVOUK ‐ P37/07.
Ophthalmic care – Reaching out to the ageing population. Experiences in Sweden
Authors: MARTIN L
Published: November 2013

Purpose To evaluate the suitability of a web‐based inter‐professional system for large‐scale screening for age‐related eye diseases in elderly people

Methods Current diagnostic devices, i.e. automatic perimeters and non‐mydriatic fundus cameras were installed in ~90 optician’s shops, and connected to a server. Visual acuity, refraction and intra‐ocular pressure were measured and entered into the system, together with general health history and family history of eye diseases. These data sets from 30 511 screening procedures in 24 002 customers in optician´s shops were evaluated by experienced ophthalmologists (n = 9), who produced a statement to the customer or, when needed, a recommendation of follow‐up visit or a referral note to conventional eye care.

Results ICD‐10 codes were recorded in 27 148 examinations. The most common code (56%) was Z01.0 Examination of eye and vision (n=15 079). Second most common diagnosis (21%) was Z71.1, i.e. suspected disease, but no diagnosis confirmed (n= 5 724). More than every fifth patient (n= 5 509 subjects) have undergone repeated screening(s). 1 760 subjects (6.5%) were referred to conventional eye care. The most common codes among these were H3, chorioidal and retinal diseases (n=643) and H4, glaucoma (n=208). A survey was performed of 123 randomly selected referral responses. In 121 cases the subjects had been recommended treatment or follow‐up at the clinic.

Conclusion The screening system, with examinations performed in optician’s shops and findings evaluated by ophthalmologists, detected the expected proportion of age‐related diseases with high sensitivity. The system appears to be suitable for large‐scale screening of elderly people.
Characterization of human corneal grafts’ transparency by optical coherence tomography and scattering measurements
Authors: HOFFART L
Published: November 2013

Purpose In clinical and graft sorting applications, cornea’s transparency is only subjectively qualified. The aim of this study is to bring tools to achieve transparency quantification regarding the evolution of edema within the tissue.

Methods The samples are human corneal grafts rejected from bank of tissue due to physiologic issues, which are submitted to swelling protocol to study their properties with edema. A multiscale analysis of the microstructure imaged by 1 µm resolved Optical Coherence Tomography (OCT) combined with a detailed characterization of backscattering properties is performed. Electromagnetical modelization is used to numerically link scattering measurements with structural defects observed with OCT.

Results Backscattered intensity measurements enable corneal grafts’ transparency evaluation (backscattering level increases with swelling). Moreover, microstructural tissue modifications occurring during swelling (microstructure disorganization and heterogeneities) are highlighted by OCT imagery. We show that the observed heterogeneities imply higher scattering levels and explain the experimental results.

Conclusion Combining both techniques allows linking the scattering behavior with the evolution of microstructures within the tissue and permits to quantify corneal grafts transparency. This study has to be extended to tissues eligible for graft but this characterization in the backscattered space could directly be applied to future study of tissues before removal or to in vivo diagnosis.
Retinal detachment without PVR
Authors: CREUZOT C
Published: November 2013

In patients suffering from a retinal detachment, the identification of all the breaks is crucial. In cases without any PVR, scleral buckling remains the first line treatment especially for ora dialysis or long standing Retinal Detachment (RD) linked to atrophic hole. However, the number, location and type of tears, the lens status will influence the selection of the treatment. The success rate is higher than 80% after one operation treated either with scleral buckling or pars plana vitrectomy but remains worse in pneumatic retinopexy. The main causes of failure are non identified retinal breaks and PVR.
Tractional retinal detachment
Authors: MASSIN P
Published: November 2013

Abstract not provided
Corneal bacterial infections: A practical approach
Authors: GICQUEL JJ
Published: November 2013

Because of their potential to permanently impair vision or perforate the eye, bacterial corneal ulcers are an ophthalmologic emergency. They usually follow an insult (sometimes minor) in the corneal epithelium that provides an entry for bacteria. The increased use of soft contact lenses in recent years has led to an important rise in the occurrence of bacterial ulcers (especially aggressive Gram‐ bacteria). The goal of this course is to present a practical, systematic approach of the management of bacterial corneal ulcers, as well as an update on new concepts in the diagnosis and treatment of those conditions.
Rod microglia is absent from microglial changes in mice retina contralateral to experimental glaucoma
Authors: GALLEGO B , DE HOZ R , RAMíREZ AI , SALAZAR JJ , ROJAS B , TRIVIñO A , RAMíREZ JM
Published: November 2013

Purpose The aim of the present study was to analyze the presence of rod microglia in a model of unilateral laser‐induced ocular hypertension (OHT.

Methods Adult albino Swiss mice were divided into two groups: naïve (age‐matched control; n=6) and lasered (n= 6). Retinal whole‐mounts were analyzed by immunostaining using antibodies against Iba1, MHC‐II, ED1 and NF‐200.

Results The nerve‐fiber layer (NFL) of contralateral and OHT‐eyes had ramified microglia related to blood vessels, similar to those of aged‐matched control eyes. However, only OHT‐eyes had rod microglia. Rod microglia lay parallel to and close to the axons and were related to retinal ganglion cells (RGCs) showing signs of degeneration (NF‐200+RGCs). In some instances, rod microglia processes surrounded the soma and proximal dendrites of NF‐200+RGCs and penetrated the underlying RGC layer and inner plexiform layer. Microglia had morphological signs of activation and MHC‐II expression up‐regulation in both, the contralateral and OHT‐eyes. However, only in OHT‐eyes did rod microglia show ED1 staining throughout the NFL. With respect both to morphological features and to ED1 immunostaining patterns, three stages of rod microglia were detected, with processes shortening, somas thickening, and ED1 immunostaining increasing progressively from stage 1 to 3.

Conclusion After 15 days of unilateral laser‐induced OHT, rod microglia was restricted to eyes with OHT and degenerated NF‐200+RGCs but absent in contralateral eyes. The microglia activation observed in contralateral eyes could be related with neuroprotection.
Modified connexin43 mimetic peptide shows higher efficacy in reducing retinal ganglion cell loss and vessel leak after retinal ischemia
Authors: RUPENTHAL I , CHEN YS , TEAGUE R , PERRETT J , DANESH‐MEYER H , TOTH I , GREEN C
Published: November 2013

Purpose Optic neuropathy is associated with retinal ganglion cell (RGC) loss leading to optic nerve damage and visual impairment. Transient block of connexin43 (Cx43) hemichannels by mimetic peptides (MP) after retinal ischemia has been shown to inhibit uncontrolled hemichannel opening and may provide improved RGC survival. However, high hydrophilicity and poor peptide stability can limit efficient delivery in a clinical setting. This study evaluated the efficacy of modified Cx43MP using a retinal ischemia reperfusion rat model.

Methods Retinal ischemia was created in the left eye (120 mmHg for 60 min) with the right eye serving as a control and Cx43MP formulations were injected intravitreally. Evan’s blue dye was injected intraperitoneally 4 h after reperfusion to visualize vessel leak using confocal microscopy. Retinal whole mounts were also labeled with Cx43, GFAP and Brn3a antibodies to quantify Cx43 and RGC densities.

Results Intravitreal injection of native and modified Cx43MP resulted in significantly reduced Cx43 levels compared to untreated eyes 8 h after ischemia, with Cx43MP containing two C12‐lipoamino acid groups reducing Cx43 counts almost down to baseline level. A similar trend was seen for RCG counts with the modified Cx43MP resulting in >93% RCG survival after 28 days compared to <70% for untreated eyes. Vessel leak was also noticeably reduced in Cx43MP treated eyes.

Conclusion C12‐lipoamino acid conjugation to Cx43MP increased peptide stability and may have also resulted in better tissue permeability, improving the overall efficacy of Cx43MP. Modified Cx43MP may therefore offer a clinically relevant treatment option for optic neuropathies.
Optic nerve head autoregulation during changes in arterial blood pressure
Authors: BOLTZ A , TOLD R , PALKOVITS S , SCHMIDL D , NAPORA KJ , GARHOEFER G , SCHMETTERER L
Published: November 2013

Purpose Previous studies in our laboratory have shown that an increase in blood pressure during isometric exercise leads to an increase in optic nerve head blood flow (ONHBF). An interesting phenomenon was found in some subjects when they were exhausted from isometric exercise and blood pressure decreased slightly. These periods were sometimes associated with a pronounced decrease in ONHBF even though ocular perfusion pressure (OPP) was still much higher than at baseline. The present study aimed to investigate this phenomenon in more detail and to gain insight in the regulatory mechanisms of ONHBF during short‐term fluctuations in OPP.

Methods 40 healthy subjects aged between 18 and 35 years were included in this study. Three periods of baseline measurements at rest and 3 periods of measurements during isometric exercise with a handgrip were alternated while ONHBF was measured continuously using laser Doppler flowmetry. Mean arterial blood pressure (MAP) was measured every minute and OPP was calculated as 2/3 MAP – intraocular pressure (IOP).

Results OPP significantly increased during handgripping compared to the resting periods (p<0.001), whereas ONHBF was not significantly altered during these changes in OPP indicating for autoregulation. Three subjects showed a decrease of more than 10% in ONHBF during recovery at all 3 periods of isometric exercise. Unexpectedly, however, 3 other subjects consistently showed an ONHBF reduction of more than 10% during isometric exercise.

Conclusion The present study indicates a complex regulation of ONHBF. Six subjects (15%) showed an abnormal ONHBF response during handgripping. This is most likely caused by an exaggerated vasoconstrictor response in order to counteract the increase in OPP.
What I should do before considering biologic agents
Authors: WILLERMAIN F
Published: November 2013

By definition, a biologic agent is a molecule produce by a living organism but chemically synthesized or modified product such as peptides or nucleotides are also sometimes include. Biological agents usually referred to molecules that precisely interact with crucial pathways involved in disease development. In the context of non infectious uveitis, and with the important exception of interferon's, biological agents are classically highly specific immunosuppressive agents. Some of them have been associated with tremendous clinical effects in severe non infectious uveitis patient. A common problem with their use is related to serious primary infection or reactivation of latent infectious diseases such as tuberculosis. The issue of worsening or inducing MS in intermediate uveitis in the case of anti‐TNF is also important as well as their high cost. They are thus usually proposed to patients resistant to conventionnal immunosuppressive treatment, after having eliminated infectious causes and latent systemic infection. However, their used as first line agent in certain uveitis conditions is often debated. In this SIS, we will review all those important general questions related to the use of biological agents in non infectious uveitis.
Effect of hypoxic stress on induction and plasticity of tumor‐induced immune cells in uveal melanoma
Authors: BRONKHORST IHG , JEHS TML , DIJKGRAAF EM , LUYTEN GPM , VAN DER VELDEN PA , VAN DER BURG SH , JAGER MJ
Published: November 2013

Purpose Highly malignant uveal melanoma contain increased numbers of lymphocytes and macrophages. We wondered whether hypoxia plays a role in the development of this inflammation. We analysed whether hypoxia induces uveal melanoma cells to release pro‐inflammatory cytokines, and whether tumor supernatant (TSN) affects monocyte migration and differentiation.

Methods The expression of pro‐inflammatory genes in freshly cultured uveal melanoma was studied in an in vitro 24 hour hypoxic culture system using qPCR. Cell lines were cultured under normoxic and hypoxic conditions. Chemotaxis was tested using a transwell system with purified monocytes and TSN. Differentiation was tested by adding TSN to a monocyte‐DC culture. CCL2, IL‐6 and PGE2 levels in TSN were determined by ELISA.

Results Exposure of freshly‐cultured uveal melanoma cells to hypoxia led to an increased expression of the pro‐inflammatory cytokines PLGF, TGFß, END1, ICAM1 and a lower expression of AIMP1 (EMAP2), CCL2 (MCP‐1), and IL1b. TSN from melanoma cells lines, cultured in normoxic as well as hypoxic conditions, was able to attract monocytes. Migration was independent of tumor‐produced CCL2. Uveal melanoma supernatant inhibits monocyte differentiation.

Conclusion Under hypoxic conditions, immune response genes are differentially expressed in cultured primary uveal melanoma cells. TSN from uveal melanoma cell lines is capable of affecting the chemotactic response of monocytes in vitro, irrespectively of the hypoxic or normoxic conditions. Our data suggest that the induction of immune cells is not dependent on intratumoral oxygen level, and the uveal melanoma TSN does not skew macrophage polarization phenotype.
Epigenetic regulation of the epithelial phenotype in uveal melanoma
Authors: VERSLUIS M , DE LANGE MJ , VAN PELT S , LUYTEN GPM , JAGER MJ , VAN DER VELDEN PA
Published: November 2013

Purpose The presence of epithelial cells is a bad prognostic factor in uveal melanoma (UM) and epithelial tumors are characterized by high expression of E‐cadherin. However, CDH1, the gene encoding for E‐cadherin, is located at chromosome 16q which is lost in UM with a bad prognosis. In order to solve this paradox we studied the underlying epigenetic mechanism of the spindle to epithelial transition and the accompanying E‐cadherin expression.

Methods UM cell lines were in vitro treated with methylation and deacetylation inhibitors, or were cultured under hypoxic conditions to mimic in vivo UM conditions to induce epigenetic reprogramming. RNA and DNA was isolated for gene expression, DNA methylation, and chromosome structure analysis, while cell lysates were used for E‐cadherin analysis.

Results Treatment with methylation and deacetylation inhibitors resulted in a phenotypic change from a spindle to more epithelial cell type. Furthermore, inhibition of methylation and hypoxia treatment both upregulated E‐cadherin expression in vitro and induced euchromatin formation at 16q22, where CDH1 is located.

Conclusion By revealing epigenetic regulation of CDH1 in UM we resolve a step in the dynamic process of spindle to epitheloid celltype switch in UM. Since this switch could be induced by hypoxia we establish a link between environmental stress and progression. With these data we provide evidence for epigenetic regulation of UM progression as well as an option for future treatment.
How to organise the follow‐up of patients with macular edema?
Authors: POURNARAS CJ
Published: November 2013

The results of clinical trials have demonstrated significant visual and anatomic benefits to intravitreal agents in the treatment of the macular edema (MO) related to retinal ischemic microangiopathies. Following the evaluation of non‐perfused capillary areas, on fluorescein angiography, spectral domain optical coherence tomography (OCT) helps to quantify the amount of cystoid macular edema. The clinical examination include VA assessment, biomicroscopy and OCT. Important differences exist in the protocols evaluating treatment for Diabetic MO, from the mandatory monthly anti VEGF injections, to either protocol, requiring injections during the first 4 study visits and prompt or deferral laser or in trials, where patients, after 3 mandatory monthly injections, had both a variable dose and injection, based on VA and OCT evaluation. The MO related to RVO should be monitored monthly for the first 3 months, and then every 2 months for the first year. During this monitoring period, patients should be instructed to return promptly whenever they notice a decrease in vision, a possible indication of macular edema, or the conversion to ischemia. Follow‐up after the initial 6 months will be required
Definition and diagnosis of advanced glaucoma
Authors: ZEYEN T
Published: November 2013

According to Hodapp’s criteria for visual field (VF) scoring, advanced glaucoma can be defined as having a VF mean deviation index (MD) < ‐12 dB. Advanced glaucoma can also be defined on the basis of the patient’s skills to perform daily activities. Functional tests are usually more useful than structural parameters to follow‐up patients with advanced glaucoma. An overview of the available investigative techniques in advanced glaucoma will be provided.
Treatment of advanced glaucoma
Authors: BRON A
Published: November 2013

Glaucoma is still the second cause of irreversible blindness worldwide. One of the main reasons is that since glaucoma is a symptom‐free disease, at least 50% of glaucoma patients are not aware of their disease. Therefore it is not uncommon to see at the consultation advanced glaucoma cases even in the Western world. The management of these advanced cases is very challenging because if at best the treatment can stop the loss of retinal ganglion cells (RGCs) while lowering intraocular pressure (IOP), it will not prevent from the natural age‐related loss of RGCs. Therefore many of these patients will go blind even with a “successful” treatment. The modalities of the treatment are controversial because when surgery is indicated, the fear of the so‐called whipe‐out syndrome is well known among glaucoma surgeons. Recent papers have highlighted that this complication may occur but may be at a lower rate that previously thought. Fair information given to the patients by the ophthalmologist is probably at least as important as the treatments
Orbital biopsies ‐ the pathologist's perspective
Authors: COUPLAND S
Published: November 2013

The orbital biopsies received by pathologists vary in size considerably according to surgical technique, suspected clinical diagnosis and subsequent surgical management. Presented is an overview of recommended "do's" and "don'ts" for ophthalmologists and their trainees when sending orbital samples to the pathology laboratory. This will include even the most simple aspects, such as adequate completion of the request form, communication with pathologist prior to sample sending, discussion about differential diagnoses and which one to prioritise initially during specimen workup, transport media and cassette recommendations, sample processing in the lab, and the variety of morphological, immunohistochemical and genetic testing available. This will be a "simple hands on" approach to orbital biopsies, with an opportunity for interaction by the audience and clarification of any unanswered questions.
OCT for VKH
Authors: NAKAI K
Published: November 2013

Background; The aim of this work was to investigate the choroidal morphologic changes of Vogt–Koyanagi–Harada (VKH) disease in vivo using high‐penetration optical coherence tomography (HP‐OCT) with a long‐wavelength light source (1,060 nm). Methods; Six patients with VKH disease were included in this study: 12 eyes of six patients with treatment‐naive acute VKH in the first 6–12 months after diagnosis. HP‐OCT was used to observe the deep choroid and sclera. The choroidal thickness was measured for 6‐12 months in eyes with acute disease. Results; In 12 eyes with acute VKH disease, the baseline choroidal thickness was significantly (p<0.0001) greater than in controls. After treatment, the choroidal thickness decreased over time. However, the choroidal thickness increased markedly again in four eyes with recurrent disease. The mean thickness at 12 months was significantly less than the normal value (p < 0.0001). Conclusions; Significant choroidal thickness changes underlie VKH disease, which progress over time. Objective measurement of the choroidal thickness using HP‐OCT may be useful for longitudinal evaluation of VKH activity.
Vogt‐Koyanagi‐Harada disease: Sunset‐glow fundus is not a fatality any more
Authors: HERBORT C
Published: November 2013

Vogt‐Koyanagi‐Harada disease (VKH) is a primary stromal choroiditis, meaning that the inflammtion is exclusively originating in the uvea and particularly in the choroid. Therefore management of the disease should include indocyanine green angiography (ICGA), the only way to monitor choroidal sublinical disease after the acute disease has regressed and is no more clinically apparent. Because this subclinical disease is progressing in an occult smoldering fashion, it is not astonishing that in close to 100% of studies evolution towards sunset glow fundus (SGF) is the rule. Thanks to ICGA it is now possible to detect occultly evolving choroiditis in VKH and adapt therapy accordingly.When ICGA assisted therapy of VKH is used,evolution towards SGF can be prevented showing that this is not the normal evolution in VKH but the result of insufficiently treated VKH. The purpose of this work was to show that close monitoring of choroiditis in VKH using ICGA can modify the phenotype of VKH by preventing the development of sunset glow fundus.
Oxidative‐induced RGC‐5 cell death culture involves mitochondrial dysfunction and can be attenuated by hydrogen sulphide
Authors: OSBORNE N
Published: November 2013

Exposure of cells in culture to light (1000lux, 400‐760nm) results in cell death but only if their mitochondria are functional. A comparison between the death mechanisms of RGC‐5 cells in culture caused by light or hydrogen peroxide (H2O2) showed them to be almost identical involving the stimulation of ROS and the activation and cleavage of both poly(ADP‐ribose) polymerase‐1 (PARP‐1) and apoptosis‐inducing factor (AIF) but not caspase‐3. Their death processes are inhibited by similar substances that included hydrogen sulphide (H2S). The protective mechanism for H2S appears to involve the preservation of mitochondrial function deduced from the analysis of ATP, the mitochondrial membrane potential, the release of cytochrome c and the analysis of oxidative phosphorylation components in cells exposed to H2O2. This supports the notion that one way for H2S to act as a protective agent is to channel electrons into the electron transport chain of mitochondria.
The unsolved genetics of LHON: Beyond mtDNA primary mutations what else?
Authors: CARELLI V
Published: November 2013

Leber's hereditary optic neuropathy (LHON) is a blinding disorder recognized as the most frequent mitochondrial disease. LHON is associated with mtDNA point mutations in complex I subunit genes, but remains characterized by poorly understood features such as tissue specificity, incomplete penetrance and male prevalence. Environmental factors (tobacco and alcohol) and specific mtDNA backgrounds (haplogroup J) are confirmed to play a role in modulating penetrance. We have also demonstrated that mitochondrial biogenesis and mtDNA copy number are major determinants on penetrance and gender difference in LHON. We are currently pursuing a multilayered "tour de force" to identify genetic modifiers by combining traditional tools, such as linkage analysis, with high‐throughput techniques, such as MitoExome sequencing, functional and tag SNPs genotyping and microarray expression studies. Our results indicate that penetrance in LHON is modulated by polymorphisms in different genes rather than by a single mutation. Co‐variates (age, sex, smoke and mtDNA copy number) have been instrumental to generating a list of candidate genes for which validation is currently ongoing.
Why what you have been taught about the optic disc may not be entirely true
Authors: CHAUHAN B
Published: November 2013

Clinicians evaluate neuroretinal rim health according to the appearance of the optic disc, the clinically visible surface of the optic nerve head (ONH). Recent anatomic findings with optical coherence tomography challenge the basis and accuracy of current rim evaluation for 3 reasons: (1) The DM is rarely a single anatomical structure or an identifiable junction, such as the inner edge of border tissue. In most eyes it corresponds variably to multiple anatomical structures. (2) In some regions of all ONHs, Bruch’s membrane extends internally beyond the DM (towards the centre of the ONH) and is both clinically and photographically invisible. Since in these areas the outer border of the rim is the termination of Bruch’s membrane and not the more external DM, the rim is narrower than that with clinical or photographic evaluation. (3) Because current rim width measurements are made in a fixed plane without reference to the orientation of the rim tissue, for the same number of axons, the rim width will be greater in cases where the orientation of the rim tissue is more horizontal (for example in the temporal sector of tilted optic discs) compared to when it is more perpendicular. This presentation will review and interpret ONH anatomy detected with optical coherence tomography pertaining to optic disc examination and demonstrate why a paradigm change for clinical assessment of the optic nerve head is now necessary.
Posterior vitreous detachment in highly myopic eyes undergoing vitrectomy
Authors: PHILIPPAKIS E , GUALINO V , GAUCHER D , GAUDRIC A , MASSIN P , TADAYONI R
Published: November 2013

Purpose To review the PVD status in highly myopic eyes requiring vitreoretinal surgery, using intraoperative observation

Methods In a retrospective study, patients presenting with high myopia with refractive error<‐6,00D, axial length>26mm or fundus signs of high myopia, who underwent their first intraocular vitreoretinal surgery in our department between 2009 and 2012 were included. Standard 25G‐pars plana vitrectomy was performed for all, with or without staining. The main outcome was the intraoperative identification of a PVD. Age at the time of surgery and preoperative slit‐lamp observation of PVD were also collected.

Results Ninety‐six eyes of 95 patients were included. Eyes were categorized by disease: myopic foveoschisis (FVS), epiretinal membrane (ERM), macular hole (MH), macular hole retinal detachment (MHRD) and rhegmatogenous retinal detachment (RD). Mean age was 62.15 years (range 29‐95). RE was available for 67 eyes: mean value ‐13.9D. Mean AL on 38 eyes was 29.2mm. A PVD was found in 52.1 % of the 96 eyes, and a dye was used in 81 eyes. In MH, FVS, MHRD, ERM and RD groups, the PVD rate were respectively 10%, 14.3%, 42.9%, 74.2% and 85%. Reliability of preoperative slit lamp examination in detecting the PVD showed a 70% sensibility, 76% specificity, 75% positive predictive value and 70% negative predictive value.

Conclusion In highly myopic eyes when ERM and RD groups the PVD rate was not so far from emmetropic eyes, in case of RDMH, MH and FVS this rate was found very low. Nearly 90% of highly myopic eyes with FVS or MH have their posterior vitreous cortex still attached. As the assessment of PVD in these eyes is very challenging, the use of any dye or visualization agent during theses surgeries seems then advisable.
Epiretinal membrane surgery in highly myopic eyes a case control study
Authors: BERROD JP , FAVEL C , BATTA B , SELTON J , TRECHOT F , CONART JB
Published: November 2013

Purpose To evaluate the anatomic and functional outcomes of epiretinal membrane peeling surgery in highly myopic eyes and to compare them with non‐highly myopic controls. Design: case control study in a retrospective cohort of 1776 patients undergoing surgery for epiretinal membrane alone or combined with cataract extraction.

Methods Fifty‐seven highly myopic eyes from 57 patients with axial length over 26 mm were included in the study. For each case studied, we selected from the same cohort one control matched for preoperative acuity, central macular thickness, and surgical technique. Best‐corrected visual acuity (BCVA), decrease of central macular thickness (CMT), impact of axial length on postoperative visual recovery and postoperative complications were studied.

Results The postoperative best‐corrected visual acuities improved by 0,37 LogMar in highly myopic eyes versus 0,39 LogMar in controls (NS). The mean postoperative foveal thickness decrease was 110 μm in highly myopic versus 77 μm in controls (p=0,0585). We did not found any correlation between axial length and improvement of BCVA. We had no difference in the incidence of complication between the two groups.

Conclusion ERM peeling gave good anatomical and functional results in highly myopic patients. The axial length has no impact on visual recovery, foveoal thickness decrease and postoperative complications.
Baseline characteristics and vitreoretinal interface features in patients with vitreomacular traction associated with macular hole from the MIVI‐TRUST clinical program
Authors: KOSHY Z , LABOURDETTE A , DUCHATEAU L , LESCRAUWAET B
Published: November 2013

Purpose There is limited published evidence on demographic and vitreoretinal interface (VRI) characteristics of patients with vitreomacular traction in association with macular hole (VMT+MH). Establishing insights into the characteristics of untreated VMT+MH may contribute to a better understanding of the burden of VMT disease To describe baseline patient characteristics and VRI features in patients with VMT+MH included in the phase 3 ocriplasmin studies

Methods Two randomized, double‐masked, placebo‐controlled trials designed to determine efficacy and safety of ocriplasmin for the treatment of VMT comprising 652 patients. Key baseline characteristics included patient demographics (age, gender); eye‐disorder (time since VMT diagnosis, visual acuity (VA) study eye (SE); non‐study eye (NSE), pseudophakia and/or ERM); VRI features (MH width; vitreous separation), VFQ‐25 composite score

Results VMT+MH was present in 153 patients (23.5%). Baseline characteristics were: 68.7 years (SD 7.1); 75.8% female. Time since diagnosis: 62 days (SD 131); VA: SE 55.9 (SD 10.5), NSE 77.8 (SD 14.3). Pseudophakes: 20.9%, concomitant ERM: 15.8%. Min‐max hole width: 272.7 (SD 127.7), vitreous adhesions attached at fovea and optic nerve (89.5%); VFQ‐25 composite score: 80.3 (SD 14.6)

Conclusion This analysis reports baseline characteristics of patients with VMT+MH, which can be used to demonstrate differences in VMT patients without MH
Misconception about the intraocular pressure
Authors: POURJAVAN S
Published: November 2013

There are still some strong misconceptions about the intraocular pressure among the specialists. Some of them are the conclusion of the large clinical randomized studies. The myth of 21 mmHg is one of the most common misconceptions. This talk will cover some of the large randomized studies and review critically the conclusions.
Generics are the same or similar?
Authors: STEVENS AM
Published: November 2013

This presentation will briefly summarize the requirements for bio‐equivalence according to the European legislation (E.M.E.A.) The different requirements for systemic and non‐systemic generics will then be clarified as well as their implications for topical ophtalmic medications. Six different elements that might interfere with therapeutic equivalence of brand and generic ophthalmic formulations are considered: inactive ingredients, bottle design and drop size, stabilizers, Ph stability, temperature stability, and presence of particulate matter. A number of studies comparing brand and generic opthalmic drugs will be presented. Finally, the cost saving aspect of generic ophthalmic drugs is analyzed with particular reference to the Belgian situation.
Suspicious choroidal naevi
Authors: KIVELÄ T
Published: November 2013

The speaker will summarize characteristics of and guidelines for referral of non‐suspicious and suspicious choroidal naevi, based on review of literature and personal experience. Recognition and characterisation of choroidal naevi is based on fundus examination with the slit lamp and indirect ophthalmoscope, supplemented with ultrasonography (thickness, acoustic profile), optical coherence tomography (subretinal fluid, thickness) and fundus autofluorescence (subretinal fluid, orange pigment). Large to medium‐sized melanomas are readily differentiated from naevi using these methods. The challenge lies in telling small melanomas from naevi. The mnemonic 'To Find Small Ocular Melanomas' reminds us to look for tumour Thickness of more than 2 mm, subretinal Fluid, visual Symptoms, Orange pigment and location of the tumour Margin at the optic disc. Each of these risk indicators approximately doubles the likelihood of growth and malignancy, but none of them is specific. Surveillance for growth, a biopsy, or both, may thus be needed after the initial evaluation.
Malignant melanoma of the uvea: Diagnosis, characterization and prognosis
Authors: MIDENA E
Published: November 2013

Purpose: To summarize available data on uveal melanoma biology, diagnosis and clinical characterization. Methods: Herein, we review diagnostic criteria, clinical characterization and therapeutic implications of the emerging molecular biology in posterior uveal melanoma/high risk indeterminate choroidal pigmented lesion. Results: The diagnosis of uveal melanoma is based on clinical examination with indirect ophthalmoscope and ultrasonograpy. The use of mnemonic "to find small ocular melanoma" is useful in risk stratification of small indeterminate melanocytic choroidal lesions. The use of optical choerence tomograpy and autofluorescence also help in identifying sub‐retinal fluid and orange pigment. In the cytogenetic era, tumor‐sampling procedures are becoming the main prognostic tools for uveal melanoma patients. Conclusions: Ophthalmic oncology is moving in the same direction as all other oncologic subspecialties, starting to determine the patient’s risk using sampling‐based laboratory techniques. However, it is essential to start treating patients earlier (in the premalignant tumor stage) and to develop consistent, selective and effective adjuvant therapy
Malignant melanoma of the uvea: Radiotherapy techniques
Authors: DESJARDINS L
Published: November 2013

Purpose Malignant melanoma of the uvea is a relatively radioresistant tumor For this reason only radiotherapy techniques with precise location of the radiation doses are used Methods Proton beam therapy has been used since 1975 by Gragoudas in Boston and the in Europe since 1983.Because of the Bragg pick, the use of an accelerated proton beam allows delivering homogenous high dose to the tumor while sparing the normal tissue around. Brachytherapy is also widely used. Iodine 125 is a low energy gamma emmeting isotope; the radiation is totally stopped by heavy metals like gold .The seeds need to be changed every two months because of its half life. Ruthenium 106 is a beta emmiting isotope. Its low penetration prevents its use for the bigger tumors. With brachytherapy the dose of 90 grays is usually delivered to the top of the tumor while the base receives more than 300grays. Results Tumor control is excellent with proton beam (less than 5% recurrence at 5 years) and good with brachytherapy (less than 10% recurrence at 5 years) Globe preservation is possible in more than 90% of treated patients
Malignant melanoma of the uvea: Surgical techniques
Authors: DAMATO B
Published: November 2013

Uveal melanoma can be excised by local resection or enucleation. Local resection comprises trans‐scleral 'exoresection' and trans‐retinal 'endoresection'. Variations of exoresection include: iridectomy; irido‐cyclectomy; cyclo‐choroidectomy and choroidectomy. Resection of melanomas involving ciliary body and/or choroid is usually followed by adjunctive brachytherapy, which is administered immediately after the excision procedure or several weeks later, once the eye has healed.Such adjunctive radiotherapy prevents local recurrence while avoiding the need for wide safety margins, thereby reducing ocular morbidity. Endoresection is performed through a retinotomy over the tumour or after raising a retinal flap. Enucleation is undertaken in the conventional manner, using the surgeon's preferred implant. Primary local resection is performed when radiotherapy is likely to cause excessive morbidity, because of large tumour size or proximity to the optic disc. Secondary resection is undertaken as a treatment for local tumour recurrence or the toxic tumour syndrome after radiotherapy. Surgical resection provides ample tumor material for diagnosis and prognostication, which may in future be useful therapeutically.
Role of glial activation in neuroprotection of the retina
Authors: VIDAL‐SANZ M , GALINDO C , GALLEGO B , ROJAS B , DE HOZ R , RAMIREZ AI , SALAZAR JJ , TRIVIñO A , AVILéS M , AGUDO M , VILLEGAS‐PéREZ MP , RAMíREZ JM
Published: November 2013

The effects of retinal injury on the neuronal and non‐neuronal cell population of the injured and the fellow‐uninjured retina were investigated in adult mice. Unilateral left eye retinal injury was induced by intraorbital optic nerve transection (IONT) or by laser‐induced ocular hypertension (OHT). Both retinas were prepared as wholemounts and immunostained with Brn3a, Iba‐1 and GFAP to identify, count and map the distribution of retinal ganglion cells (RGCs), microglia and astrocytes, respectively. OHSt was used to trace RGCs and to identify phagocytic microglia. By 2 wks after IONT or OHT, RGCs in the left retinas represented 20% of the original population. Following IONT, microglial cells in the left retinas increased with time from center to periphery and this response diminished with BDNF treatment, while in the fellow retinas phagocytic migroglial cells appeared at 3 days but their numbers were not modified with vehicle or BDNF. Following OHT there was a marked macro and microglial reactivity in both retinas. Thus, IONT and OHT induce changes in the macroglia and microglia of the injured and contralateral uninjured fellow retinas. The gliotic response in the fellow retinas could be immune related.
How inflammatory reactions affect POAG topical and surgical treatment?
Authors: LABBE A , BAUDOUIN C
Published: November 2013

There is a large body of evidence from clinical and experimental studies that the long‐term use of topical drugs may induce inflammatory ocular surface changes. The high prevalence of symptoms and signs of ocular surface disease (OSD) in patients with glaucoma or OHT has been demonstrated in several clinical studies. In parallel, inflammatory changes of the ocular surface directly impact the effectiveness of antiglaucoma medical and surgical treatments. Ocular surface side effects impact the quality of life and are significant barrier to adherence in patients treated for glaucoma or ocular hypertension. Moreover, as conjunctival wound healing is a major determinant for the success of glaucoma filtering surgery, ocular surface inflammation is a well‐known risk factor for surgery failure by subconjunctival fibrosis. Therefore, a better knowledge of ocular surface inflammatory changes with appropriate evaluation and management should thus become a new paradigm in glaucoma care.
Restoration of keratocyte cell phenotype through epithelial‐stromal cell interactions in a 3D hydrogel model
Authors: WILSON SL
Published: November 2013

Purpose In vivo, epithelial cells are connected both anatomically and functionally with stromal keratocytes. In vitro co‐culturing aims to recapture this cellular anatomy and functionality by bringing together two or more cell types within the same culture environment. The aim of this study was to investigate epithelial‐stromal cell signalling for the control of corneal stromal cell plasticity in 3D culture models.

Methods Corneal stromal cells were activated to their injury phenotype (fibroblasts) before being encapsulated in 3D collagen hydrogels. 3 different epithelial‐stromal co‐culture methods were then examined; epithelial explant; transwell; the use of conditioned media. Using non‐destructive monitoring tools we revealed how epithelial co‐culturing affects stromal cell differentiation in terms of construct contraction and elastic modulus measurements in a 3D collagen hydrogel environment for prolonged culture periods. Cell viability, phenotype, morphology and protein expression was investigated to corroborate our mechanical findings.

Results It was shown that activated stromal cells retain their plasticity in vitro. Activated corneal stromal cells that were fibroblastic in phenotype were successfully reverted to a non‐activated keratocyte cell lineage in terms of behaviour and biological properties; and then back again via TGF‐β1 media supplementation. It was then revealed that epithelial‐stromal interactions can be blocked via the use of wortmannin inhibition.

Conclusion A greater understanding of stromal‐epithelial interactions and what mediates them offers great pharmacological potential in the regulation of corneal wound healing, with the potential to treat corneal diseases and injury whereby such interactions are vital.