bluuebunny/crossref_metadata_2025 huggingface dataset:
New matrix therapy in chronic corneal ulcers resistant to conventional therapies
Authors: HUGNY LARROQUE C , DERRIEN S , COCHENER B
Published: November 2013

Purpose To determine the efficacy of a new ophthalmologic solution based on ReGeneraTing Agent technology (RGTA, Cacicol®) in the therapy of chronic corneal ulcers resistant to conventional therapies.

Methods This study included 20 patients with chronic corneal ulcers. There were various etiologies:two due to basic chemical burns,two neurotrophic keratitis, one Moreen ulcer, one pseudo‐Mooren, three on IntraCorneal Ring, nine on 9 grafts (one endothelial and 8 penetrating keratoplasties, one post surgery. All patients were previously treated with classical lacrymal substitutes, one with topical ciclosporine, corticoids, and/or A vitamin ocular ointment, and/or one/several amniotic membrane graft. Patients were treated with Cacicol® at a dose regimen of one drop daily every 2 or 3 days for one to three months. The primary outcome measure was healing. The ulcer’s diameter was measured at day 8,then once a month for 3 months.

Results Complete healing was observed for 13 patients, i.e. a cure rate of 65 %. For other patients, 6 failures (30%) and one improvement without complete healing (5%) were reported. In the healed group, time of reparation was : 4 in day 8, 4 in one month and 5 in 3 months.

Conclusion Cacicol was effective in the treatment of chronic corneal ulcers resistant to conventional therapies. Its efficacy remains to be proven in randomized double‐blind studies.
A RHO kinase inhibitor, AMA0526 improves corneal wound healing after alkali burn injury
Authors: SIJNAVE D , HOLLANDERS K , VAN BERGEN T , VAN DE VELDE S , VANDEWALLE E , MOONS L , STALMANS I
Published: November 2013

Purpose The aim of this study was to investigate the efficacy of a locally active ROCK‐inhibitor AMA0526 (Amakem NV) on corneal wound healing induced by alkali burn in an in vivo mouse model.

Methods Swiss mice were divided randomly into 3 groups after chemical cauterization of the cornea by alkali. Topical treatment was initiated after the injury and given once daily. All groups received 0.1% of the active ROCK‐inhibitor AMA0526 topical in one eye and vehicle, bevacizumab (2.5%) or dexamethasone (0.1%) in the contralateral eye. A forth group received no treatment and was used as control. Corneal opacity and corneal neovascularization were graded every other day according to a 0‐4 scoring. Blood vessel formation and corneal leukocytes infiltration after injury were assessed by immunohistochemistry.

Results Both corneal opacity and neovascularization were reduced after AMA0526 treatment compared to the vehicle treated eye. Infiltration of inflammatory cells and blood vessel formation were significantly inhibited at day 7. AMA0526 treated mice showed significant reduced corneal opacity and inflammation compared to mice treated with bevacizumab. AMA0526 proved to be as efficient as dexamethasone in reducing excessive corneal wound healing.

Conclusion Targeting ROCK with a local ROCK inhibitor, AMA0526 is efficacious in improving and preventing corneal opacity and neovascularization after alkali burn. The results presented indicate that ROCK is an appealing target to treat and prevent corneal scarring and neovascularization and illustrate the potential therapeutic benefits of the local ROCK inhibitor, AMA0526.
Experimental evidence of fluid secretion of rabbit lacrimal gland ductal epithelia
Authors: TOTH‐MOLNAR E , KATONA M , FACSKO A , VENGLOVECZ V , NEMETH L , HEGYI P
Published: November 2013

Purpose Authors developed a novel lacrimal gland (LG) duct isolation technique earlier (IOVS, 2007; 48:3746‐3755) which makes possible to obtain more information on the function and regulation of LG ductal cells. The role of LG ductal epithelium on fluid secretion is unknown. The aim of the present study was to investigate LG ductal fluid secretion by means of measurement of fluid secretion evoked by different agonists.

Methods Experiments were performed on isolated rabbit LG interlobular duct segments maintained in short term culture. The ends of the ducts sealed after overnight incubation forming a closed luminal space. Fluid secretion into closed intraluminal space as swelling response was analyzed using bright field videomicroscopy technique.

Results The secretory response to carbachol or to forskolin stimulation was measured in HEPES buffered and in HCO3‐/CO2‐ buffered solutions. Carbachol initiated ductal swelling. This result proves the cholinergic effect‐evoked ductal fluid secretion. Fluid secretion was biphasic consisting of a continuous swelling in the first 5 minutes followed by a plateau phase. Secretory rates did not show a substantial difference measured in HEPES and HCO3‐/CO2 ‐buffered solutions. In contrast to the biphasic effect of carbachol, forskolin stimulation resulted in a rapid, continuous swelling response. The secretory effect of forskolin did not differ in HEPES and HCO3‐/CO2‐buffered solutions.

Conclusion Fluid secretion of LG ductal cells induced by carbachol and by forskolin stimulations strongly supports the hypothesis, that LG ductal system is actively involved in lacrimal fluid secretion. Our results provide the first experimental evidence of secretory function of this epithelium.
Pharmacological strategies related to ocular neuroprotection
Authors: GARHOFER G
Published: November 2013

Ocular neuroprotection is a novel approach in the treatment of eye diseases, aiming to prevent or at least slow down loss of retinal neurons to avoid disease progression. Although ocular neurodegenerative diseases differ in their pathogenetic properties and risk factors from cerebral diseases, mechanisms behind neurodegeneration and cell death show similarities. As such, several new anti‐apoptotic agents, targeting the different mechanisms to induce neuronal cell death have been introduced in the last years. These mechanisms include but are not limited to excitotoxicity, oxidative stress and subclinical inflammation. From a clinical side of view the most commonly used target for neuroprotecive therapy in the past was glutamate excitotoxicity. As glutamate excitotoxicity is among the most important mechanisms to trigger cell death, much emphasis has been put into the development of glutamate antagonists. However, the clinical results of interventions studies fell short of expectations and other strategies came into focus of research. The talk aims to summarize the most promising pharmacological neuroprotective strategies.
Infectious uveitis
Authors: PLEYER U
Published: November 2013

The differential diagnosis of infectious uveitis is broad and an essential step in any initial work‐up. Underlying organisms include all types of infectious agents. The more common infectious causes of uveitis include viral causes, toxoplasmosis, syphilis, tuberculosis and endogenous endophthalmitis that will be covered in this course. Based on clinical features further diagnostic tools will be discussed and critically reviewed. In particular newer evolving techniques in the investigations will be included, e.g. intraocular fluid evaluation for polymerase chain testing for the genome and antibody testing against the causative organisms.
White dot syndromes
Authors: HERBORT C
Published: November 2013

"White dot syndromes" (WDS)is a term introduced around 1995 to describe posterior uveitis syndromes that were poorly understood such as MEWDS, APMPPE, multifocal choroiditis (MFC), serpiginous choroiditis (SC), birdshot retinochoroiditis (BRC) and many others depending on the extension with which the term is used. Unfortunatelly the term is of no utility as it is purely based on the the white dots most posterior uveitis exhibit and as it emcompasses entities that look alike but have nothing in common as far as mechanism is concerned. Thanks to indocyanine green angiography (ICGA) it became possible to get away from this pot‐pourri terminology and allowed to sort out choroiditis entities according to the pathophysiological mechanism subdividing choroiditis into diseases of the choriocapillaris (primary choriocapillaritis) including MEWDS, APMPPE, MFC, SC and atypical and overlapping entities on one side and stromal choroiditis on the other side including Vogt‐Koxanangi‐Harada disease (VKH), BRC, sarcoid and tubercular choroiditis. The appraisal of these diseases and the rationale of their new classification will be explained and examples will be given to illustrate this new comprehensive approach that should make WDS obsolete.
Pure neuroretinal dysfunction in diabetic retinopathy occurring prior to endothelial and vascular damage
Authors: REIS A , MATEUS C , MELO P , FIGUEIRA J , CUNHA‐VAZ J , CASTELO‐BRANCO M
Published: November 2013

Purpose To search for independent neural damage in type 1 diabetic patients, in the pre‐retinopathy stage of diabetic retinopathy (DR), with preserved blood‐retinal barrier (BRB) permeability.

Methods BRB permeability was objectively measured by Vitreous Fluorometry. Neuroretinal function was assessed by standard multifocal electroretinography (mfERG) and by chromatic/achromatic contrast sensitivity (CS) (CCT‐Cambridge Research Systems and Frequency Doubling Perimetry‐FDT, Zeiss), in a sample of 42 patients (age=26.6±5.3years) with preserved visual acuity (VA), divided into two groups:1.With no clinical signs of DR and normal BRB permeability (n=23eyes; VA=1.11±0.15); 2.With BRB breakdown, with no clinical signs of DR or with mild nonproliferative DR (n=61eyes; VA=1.09±0.15). These data were compared with those obtained in 25 age‐matched controls (27.4±5.8years). Non‐parametric statistical analysis was performed at a significance level of p<0.05.

Results Amplitude of neurophysiological responses was significantly decreased in all eccentricity rings in both patients groups, when compared with controls (p<0.0001). Changes in implicit time were also found in cases with preserved BRB (p<0.02). Impaired CS along the main chromatic axes was observed (p<0.03) and achromatic thresholds were also different between controls and both clinical groups (p<0.004). No correlation was found between the BRB permeability and the psychophysical and electrophysiological measurements (group with preserved BRB), confirming a lesion mechanism that is independent from endothelial/vascular changes.

Conclusion Retinal neuronal changes may occur in type 1 diabetes, independently of the breakdown of the BRB or onset of vasculopathy.
DR in myopic patients
Authors: TADAYONI R
Published: November 2013

Abstract not provided
Exudative retinal detachment
Authors: DE SMET MD
Published: November 2013

Active and passive retinal water transport mechanisms must be altered to cause an exudative detachment (ED). The retinal pigment epithelium (RPE) plays a critical role. Whenever the RPE pump becomes dysfunctional or its adhesive force is overcome, ED can follow. ED can occur in the presence of reduced pump function with excessive traction as can occur diabetes, retinal detachments (mainly pseudophakic) in the absence of a tear, or certain inflammatory disorders such as pars planitis. Thickened subretinal fluid can compromise the RPE pump as is seen with persistent serous detachments following buckle surgery. However, most cases are due to a generalized depression of the RPE pump coupled with excessive fluid influx ‐ idiopathic and steroid related central serous retinopathy, age related macular degeneration, idiopathic polypoidal vasculopathy, retinal vein occlusion, uveitis (sympathetic and VKH). Treatment will depend on the cause ‐ may include an attempt to stimulate pump function or the elimination of tractional components. In many cases, identifying the presence of an ED leads to a conservative follow‐up with excellent outcomes.
Herpes and Zoster infections update
Authors: LABETOULLE M , ROUSSEAU A
Published: November 2013

Herpes Simplex Virus (HSV) and Varicella‐zoster Virus (VZV) are the two leading causes of infectious acquired amblyopia. After a phase a latent infection in the trigeminal ganglia, they may reactivate to eventually infect the cornea. There are several common features of keratitis due to HSV or VZV. The most frequent forms involve the epithelium, with 4 different patterns: punctuate and diffuse, dendritic, geographic, and marginal. Stromal forms of keratitis are mostly non‐necrotic, and usually resolve with a combination of oral antivirals and topical steroids. In contrast, a necrotic stromal keratitis usually requires intravenous antiviral therapy. Endothelial forms of HSV/VZV keratitis are far less frequent. Three different types may be observed: disciform, diffuse or linear, the latter one being the most aggressive. After the acute phase of HSV/VZV keratitis, preventive treatment with oral antivirals may be given according to the clinical history. For VZV, a vaccine is now available. Its effectiveness has been shown for the prevention of herpes zoster ophthalmicus, but its place in patients with recurrent VZV infections of the eye remains to be clarified.
The particularities of corneal infectious diseases in children
Authors: BREMOND‐GIGNAC D
Published: November 2013

Ocular surface bacterial infections affect subjects of all ages with a high frequency in newborns and children. In infant, children and teenagers, the most common ocular pathogens, which differ from adults, are Haemophilus influenzae, Staphylococcus aureus, Streptococcus pneumoniae and also Moraxella species. These infections could lead to ulcers and sight‐threatening complications. Corneal infections are not common but can be difficult to diagnose because the pathology can develop without pain. In addition the examination may be difficult to perform. The treatment should be provided earlier and aims to eliminate the bacteria, virus or fungal pathogens. The specific epidemiology of pathogens will be detailed according to the age. Risks of visual impairment and amblyopia must be integrated. An update on topical antibiotics and current options will be reviewed with practical aspects, diverse clinical cases and considering quality of life of the children and parents.
iStent implant
Authors: AU L
Published: November 2013

istent is a novel device that canulates Schlemms canal to enhance physiological outflow and lowers intraocular pressure. Results of istent surgery combined with phaco would be presented, together with the results of intraoperative flow test. Results of multiple istents and istent Supra would also be presented. New device like the Hydrus would also be demonstrated.

Commercial interest
Trabectome surgery
Authors: LONGSTAFF S
Published: November 2013

Abstract not provided
Neuropeptide Y Y1 receptor is neuroprotective and modulates microglia reactivity in the rat retina
Authors: AMBROSIO AF , ELVAS F , MADEIRA M , BRUDZEWSKY D , MARTINS J , MARTINS T , CAVADAS C , SANTIAGO AR
Published: November 2013

Purpose Neuropeptide Y (NPY) is neuroprotective and can regulate inflammation. In the retina, microglia (MG) activation has been implicated in the pathogenesis of several diseases. We investigated whether NPY, particularly through Y1 receptor (Y1r) activation, is neuroprotective and modulates pro‐inflammatory responses in the retina.

Methods Immunocytochemistry, RT‐PCR, TUNEL and ELISA were used.

Results NPY and NPY Y1, Y2 and Y5 receptors were detected in retinal ganglion cells (RGC) and MG. The increase in TUNEL‐positive cells in the ganglion cell layer induced by exposure of retinal explants to NMDA was inhibited by Y1r activation. Exposure to LPS activated retinal MG, and NPY prevented MG morphological changes via Y1r. NPY or [Leu31, Pro34]‐NPY (LP‐NPY; Y1r/Y5r agonist) inhibited the increase in iNOS immunoreactivity triggered by LPS, and BIBP 3226 (Y1r antagonist) abolished the effect of LP‐NPY. LPS also increased the concentration of TNF‐alpha, IL‐1beta and IL‐6. NPY inhibited the increase in IL‐1beta and IL‐6, but not TNF‐alpha. Moreover, LP‐NPY inhibited the increase in TNF‐alpha, IL‐1beta and IL‐6, and BIBP 3226 abrogated the effect of LP‐NPY.

Conclusion In conclusion, RGC and MG express NPY and NPY Y1, Y2 and Y5 receptors. The activation of Y1r can exert neuroprotective effects in RGC and induce anti‐inflammatory effects in the retina, inhibiting MG activation. Support: FCT (PTDC/SAU‐NEU/099075/2008, PTDC/NEU‐OSD/1113/2012, PEst‐C/SAU/UI3282/2011‐2012, PEst‐C/SAU/LA0001/2011‐2012, SFRH/BPD/69123/2010, SFRH/BD/44817/2008), Portugal, and COMPETE‐FEDER.
Rescue therapy with subcutaneous anti‐TNF‐α agents for idiopathic non‐infectious uveitis
Authors: NERI P , ARAPI I , PIRANI V , CAPUANO V , GIOVANNINI A , MARIOTTI C
Published: November 2013

Chronic non‐infectious uveitis (NU) remains one of the most challenging problems in ophthalmology. Often, early and aggressive treatment is needed for a good visual acuity outcome. Local and oral corticosteroids remain the first line of treatment, even though side effects, such as glaucoma, cataract and Cushing Syndrome, can be serious and not tolerable. Therefore, a variety of immunosuppressive agents are used. Recently, new types of drugs, called “biologic agents”, are available. In the model of experimental autoimmuneuveitis (EAU) it has been demonstrated that tumor necrosis factor‐alpha (TNF‐α) may play a key role in uveitis. Beside the well known intravenous anti‐ TNF‐α agent called infliximab, other sub cutaneous anti‐ TNF‐α drugs have been introduced, such as Adalimumab and Golimumab. Adalimumab presents a stronger medical literature and it seems to present promising qualities. Few reports are available for Golimumab in uveitis at this time. Adalimumab can control uveitis unresponsive to the traditional immunosuppressive agents and, moreover, its subcutaneous administration makes the procedure user friendly. This drug can be used in selected cases as a rescue therapy for idiopathic non‐infectious uveitis.
A general introduction to the tests and abnormality localisation
Authors: LEROY B
Published: November 2013

Purpose: To illustrate which electrophysiological tests are available to the visual electrophysiologist, and to highlight when and where they can be used to learn more about the patient's condition. Methods: A systematic overview of the different electrophysiological tests will be given, including a physiological and anatomical correlation for each test. Results: Each of the different electrophysiological tests available allows the clinician to evaluate the function of different aspects of the retina and/or optic nerve. In so doing, essential information is obtained in order to pinpoint the exact location of the dysfunction, and make a correct diagnosis. Conclusions: Visual electrophysiology is essential to make a correct diagnosis both for acquired and inherited retinal and optic nerve diseases.
Electrophysiology in inherited disease
Authors: LEROY B
Published: November 2013

Purpose: To illustrate the added value of visual electrophysiology in the diagnosis of inherited retinal dystrophies and dysfunctions, and their management in the ophthalmic genetic clinic. Methods: A systematic overview with a case presentation format will be used to illustrate different genetically determined retinal dystrophies and dysfunctions. Case descriptions will include clinical and electrophysiological phenotypes as well as genotypes. Results: Phenotypes and genotypes of genetically determined retinal diseases are very different, and visual electrophysiology is essential in making a correct diagnosis. Conclusions: Taking a thorough history in combination with an extensive clinical examination and psychophysical and electrophysiological tests most often allows a to make a specific diagnosis when dealing with inherited retinal disease. Visual electrophysiology also allows to distinguish between progressive and stationary conditions, and it provides essential information regarding evolution of progressive disease.
Gain of chromosome 6 status does not influence HLA‐expression in uveal melanoma
Authors: VAN PELT S , VAN ESSEN TH , BRONKHORST IHG , VERSLUIS M , LUYTEN GPM , VAN HALL T , VAN DEN ELSEN PJ , VAN VELDEN PA , JAGER MJ
Published: November 2013

Purpose Chromosomal aberrations and the inflammatory phenotype have been identified as predictive factors for survival of uveal melanoma (UM). The mechanism by which these factors are linked remains obscure. We took the human leukocyte antigen (HLA), located on chromosome 6p as marker for inflammation and studied whether aberrations of chromosome 6p influenced the HLA expression in UM.

Methods SNP‐array copy number analysis and gene expression profiling were performed on 28 uveal melanomas of patients who underwent enucleation between 1999 and 2004 at the Leiden University Medical Center, Leiden, in The Netherlands. UM protein expression of HLA‐A, ‐B and –DR was measured with immunohistochemistry. The status of chromosome 3, 6p, and gene expression of HLA and HLA regulators were analyzed, as well as protein expression of HLA.

Results Gain of 6p was present in 8 cases (29%) and not related with survival. An increased gene expression was seen in the group who died due to metastatic UM for HLA‐A and –B, and B2M. Gene expression correlated with protein expression for HLA‐A, HLA‐B, but not with HLA‐DR. Tumors did not differ in level of HLA protein expression, HLA gene expression, and HLA regulator gene expression with regard to chromosome 6p status.

Conclusion High HLA gene‐ and protein expression in UM are not influenced by gain of 6p. Yet for the first time we demonstrated that in UM an increased expression of HLA class I genes correlated with the elevated protein expression of HLA class I.
Ophthalmic histopathology samples – are we sending enough?
Authors: DEV BORMAN A , HASSANI M , KESHARAJU R , NADERI K , GHAZI‐NOURI S
Published: November 2013

Purpose To ascertain the range of histopathological diagnoses made from tissues removed during ophthalmic surgical procedures over two years from one NHS Trust. During this period, joint recommendations were published by the Royal College of Pathologists (RCPath) and the Royal College of Ophthalmologists (RCOphth) in the United Kingdom, regarding the referral of ophthalmic pathology specimens, stating that in order to avoid delayed or missed diagnoses, with certain exceptions, all tissues obtained from ophthalmic surgical procedures should be sent for histopathological examination. This policy was implemented locally from January 2011.

Methods This was a retrospective case note review of the ophthalmic histopathology specimens sent between January 2010 and December 2011, at the Mid Essex Hospital Services NHS Trust. Patient demographics and histopathological diagnoses were determined for each.

Results Over the two‐year period, 268 specimens were sent for ophthalmic histopathological examination. In 2010, 112 samples were sent, with 18 malignancies detected (16.1%). In 2011, 156 samples were sent, with 30 malignancies identified (19.2%). The most common diagnosis was basal cell carcinoma, comprising 43/48 malignancies (89.6%).

Conclusion Since the local implementation of the joint guidelines from the RCPath and RCOphth, there was an increase in the number of ophthalmic histopathology specimens sent within this Trust, with a 3.1% increase in the number of malignancies detected. We believe that this improvement in detection of ocular malignancies justifies the increased burden on the histopathology service from the ophthalmology unit within this Trust.
Orbital melanocytosis and OTA naevus
Authors: DE KEIZER RJW , LAUWERS N , DE GROOT V
Published: November 2013

Purpose Presentation and discussion of a rarely reported location of orbital melanocytosis

Methods Case report

Results In a 54 year old man with an oculodermal melanocytosis (naevus of OTA), enucleation was performed for a choroidal melanoma. During the surgery spots of hyperpigmention, based on melanocytosis, were found in tendons, muscles and orbital fat. Oculodermal melanocytosis is classically described on the periocular skin, sclera, uvea, orbit, meninges, palate or tympanic membrane and is a well‐known risk factor to develop choroidal and orbital melanoma. Few reports describe the particular involvement of the orbital tissue. We show the pictures of orbital tissue and extraocular muscle pigmentation and explain it with embryology.

Conclusion Even after enucleation for a choroidal melanoma in an OTA naevus, the ophthaist should be alert that extraocular melanocytes can remain and potentially be the cause of an orbital melanoma.
Can we quantify macular edema outcome?
Authors: MASSIN P
Published: November 2013

Abstract not provided
Functional assessment of macular edema
Authors: MIDENA E
Published: November 2013

Aim Macular edema is evaluated using pure morphologic imaging tests and visual acuity as sole visual function test. Unfortutanetly, visual acuity just partly reflects visual function. A new integrated morpho‐functional approach seems useful. Methods Patients affected by macular edema were investigated using a multimodal/integrated imaging approach including currently available pure morphological retinal imaging techniques and microperimetry. Results The correlation between morphologic and functional imaging modalities strictly depends on the different involvement of retinal layers by the pathologic process. Data shows that visual function impairment is better quantified when microperimetry is added to the currently available diagnostic armamentarium. Conclusions Both in clinical trials and in daily clinical practice visual function needs to be better investigated to cope with patient’s requests. Adding reliable, topographically related visual functional data, currently obtained by microperimetry, to other pure retinal imaging investigations allows not only to better identify different “clinical phenotypes “ of macular disorders, but also to provide invaluable information about treatment and retreatment criteria.
How to select our treatments?
Authors: CREUZOT C
Published: November 2013

The analysis of associated circumstances to macular edema will help the clinician to select one among the different therapeutic options of macular edema (ME). The duration of ME, the efficacy of previous treatments, the ability of the patient to be examined regularly will influence this choice. The different options are grid laser, antiVEGF agents, steroids. Associated risk factors like severe glaucoma or lens status also need to be considered. The control of systemic conditions remain a key issue. The strategy can change during the follow‐up according to the efficacy and the recurrences observed with the treatments.

Commercial interest
Differnetial diagnosis
Authors: ANSARI E
Published: November 2013

There are many conditions that can mimic glaucoma. It is important to be aware of the differential diagnosis so that other conditions that can present with visual field defects and/or optic neuropathy can be detected and dealt with promptly. External ocular, retinal, optic nerve, systemic and visual pathway problems can present with features of glaucoma. A careful history and thorough examination will guide the clinician to making the correct diagnosis. Particuar emphasis should be made on the pattern of visual field defects, the optic disc cupping versus palor and whether the disc appearance correlates with the visual field defect. Timely medical advice should be sought to avoid sight/life‐threatening conditions in some of these cases.
Counselling in advanced glaucoma
Authors: ANSARI E
Published: November 2013

The loss of useful vision can be a very emotional experience for the patient and a massive challenge for the clinician. More time and a team‐orientated approach is vital in order to support the patient through such a crisis. Disciplines such as counselling are an essential part of the mamagement process for a patient with impaired vision and they can give advice on matters such as daily living, benefits, support groups and safety around the house. We have learnt that a separate multi‐disciplinary consultation away from the hustle and bustle of the main clinic is very helpful for the patient, relatives and carers.
ME and RVO
Authors: LOEWENSTEIN A
Published: November 2013

Abstract not provided
ME and Uveitis
Authors: LIGHTMAN S
Published: November 2013

Abstract not provided
Rationale for a diagnostic approach
Authors: GAVARD‐PERRET A , ROBERT PY
Published: November 2013

Purpose: to propose a diagnostic approach for clinicians who manage a patient with non Graves’ orbital inflammation. Patients&Methods: a review of the diagnostic process for 61 patients with diagnostic of orbital inflammation between january 2002 and january 2013 at Nice and Limoges Universitary Hospitals. Results: sixty one patients presenting with orbital inflammation were included. More common presentations were orbital fat inflammation (60%), myositis (26%) and lacrimal gland enlargement (18%). In few cases, optic nerve and sclera were involved (respectively 9,8 and 3,2%). The final diagnostic was idiopathic orbital inflammation (25 patients), specific orbital inflammation (17 patients) and orbital lymphoma (19 patients). Thirty six patients had biopsy first and 25 patients did not, in first, but only after failure to the initial therapy. Our results showed that doing biopsy in the initial management of orbital inflammation provides a more great number of specific diagnosis than doing treatment tests directly after blood tests or CT scans( p>0,01). Conclusions: The diagnostic process of orbital inflammation must include blood testing, imaging of the orbit and sinuses, and biopsy in first intention as far as possible.
ICGA features in VKH
Authors: BOUCHENAKI N , HERBORT CP
Published: November 2013

Indocyanine green angiography (ICGA) is a highly sensitive method to evaluate choroidal inflammatory lesions. We present standardized ICGA findings in Vogt‐Koyanagi‐Harada (VKH) disease. Six ICGA signs including choroidal perfusion inhomogeneity, early hyperfluorescent stromal vessels, hypofluorescent dark dots (HDDs), fuzzy or lost pattern of large stromal vessels, disc hyperfluorescence, and diffuse late choroidal hyperfluorescence identified earlier were analyzed. The most constant findings present in the acute phase were four: early hyperfluorescent stromal vessels, HDDs, fuzzy/ lost pattern of large stromal vessels and disc hyperfluorescence. These angiographic signs represent a precise and universal tool to precisely assess choroiditis and follow‐up VKH patients in the acute phase as well as in subacute disease, knowing that treatment of occult choroiditis in VKH is the key to avoid sunset glow fundus and even to “heal” VKH cases when treatment is given early and vigorously during a prolonged period.
The outcomes of mycophenolate mofetil therapy combined with systemic corticosteroids in acute uveitis associated with Vogt‐Koyanagi‐Harada disease
Authors: ABU EL ASRAR A
Published: November 2013

Purpose: To study the effectiveness of mycophenolate mofetil (MMF) as first‐line therapy in acute uveitis associated with Vogt‐Koyanagi‐Harada (VKH) disease. The outcomes in this group were compared with those of another group of patients who were treated with corticosteroid monotherapy. Methods: 19 patients(38 eyes) diagnosed with acute uveitis associated with VKH were included prospectively. Results: The mean follow‐up period was 27.0±11.1 months. Corticosteroid‐sparing effect was achieved in all patients. Ten patients discontinued treatment without relapse of inflammation. Visual acuity of 20/20 was achieved by 37.5% of the eyes in the corticosteroid group and by 73.7% in the corticosteroid + MMF group. Recurrent inflammation of 3 times or more was reduced significantly in the corticosteroid + MMF group as compared to corticosteroid group. Development of all complications was significantly higher in the corticosteroid group (42.6%) compared to the corticosteroid + MMF group (7.9%). None of the eyes in the corticosteroid + MMF group developed “sunset glow fundus”. Conclusions: Addition of MMF as first‐line therapy to corticosteroids improves clinical outcomes in patients with acute uveitis associated with VKH disease.
The expanding clinical spectrum of dominant optic atrophy
Authors: YU‐WAI‐MAN P
Published: November 2013

Autosomal dominant optic atrophy (DOA) is the most common inherited optic nerve disorder in the population and OPA1 is the major causative gene, accounting for about 60% of families. Visual loss starts in early childhood secondary to the highly tissue‐specific loss of one cell type – the retinal ganglion cell. Although progressive visual failure remains the defining feature of DOA, we recently described the expanding phenotypic spectrum associated with OPA1 disease. Up to 20% of mutational carriers developed a more severe “DOA+” phenotype characterised by prominent neuromuscular features such as deafness, myopathy, peripheral neuropathy, ataxia, and chronic progressive external ophthalmoplegia. Interestingly, we found a three‐fold increased risk of developing the more severe DOA+ phenotype with missense OPA1 mutations involving the GTPase domain compared with other mutational subgroups. Histochemical and molecular characterisation of skeletal muscle biopsies revealed the presence of cytochrome c oxidase deficient fibres and clear evidence of mitochondrial DNA instability. Dissecting the disease mechanisms leading to optic atrophy and multisystem tissue involvement in DOA will have important therapeutic implications.
Sensorineural hearing loss in OPA1‐linked disorders
Authors: BONNEAU D , MILEA D , LERUEZ S , DEFOORT‐DHELLEMMES S , CROCHET M , LAMBLIN J , LENAERS G , PROCACCIO V , REYNIER P , BONNEAU‐AMATI P
Published: November 2013

About 20% of OPA1 mutation carriers have complicated forms of dominant optic atrophy associating extra‐ocular features. Reviewing the files of 327 patients with an OPA1 mutation, we found 21 deaf patients (6.4%). In 10 patients deafness was detected under age 20, in 3 patients over age 20 and in 8 patients the age of onset was unknown. The severity of deafness ranged from mild and moderate. Audiological tests supported the diagnosis of auditory neuropathy in 8 cases. Seven different OPA1 mutations were identified in deaf patients. Three mutations, p.Arg445His, p.Gly401Asp and p.Leu243*, have been previously reported in patients with deafness. Two mutations, p.Val291_Phe328del and p.Ile463_Phe464dup, have been reported in patients with DOA without deafness. Finally, two novel OPA1 mutations, p.Arg437Glu and p.Ala357Leufs*4 were found. In the majority of patients with DOA and deafness, visual impairment occurred during the first decade while deafness appeared later. However, in 54% of patients deafness started prior to visual abnormalities. These observations suggest that audition should be carefully tested, including a specific search for auditory neuropahy in OPA1 mutation carriers.
Crosstalk of proteasomes and autophagy in RPE cells
Authors: KAARNIRANTA K
Published: November 2013

The pathogenesis of AMD involves impaired protein degradation in RPE cells. The ubiquitin‐proteasome pathway and the lysosomal pathway including autophagy are the major proteolytic systems in eukaryotic cells. Prior to proteolysis, heat shock proteins (HSPs) attempt to refold stress‐induced misfolded proteins and thus prevent the accumulation of cytoplasmic protein aggregates. Recently, p62/sequestosome 1 has been shown to be a key player linking the proteasomal and lysosomal clearance systems.The aging characteristics of the RPE involve lysosomal accumulation of lipofuscin and extracellular protein aggregates drusens. Molecular mechanisms behind protein aggregations are weakly understood. There is intriguing evidence suggesting that p62, together with autophagy, seems to have a role in the pathology of different degenerative diseases. In ARPE‐19 cells proteasomal inhibition caused accumulation of p62 bound irreversibly to perinuclear protein aggregates. The addition of the AMPK activator AICAR was pro‐survival and promoted cleansing by autophagy of the former complex. Human AMD donor samples showed strong p62 accumulation in the drusen rich macula revealing impaired autophagy flux.
Postoperative quality of life in macula‐off rhegmatogenous retinal detachment patients and its relation to visual function
Authors: VAN DE PUT M , WANDERS W , NOLTE I , HOOYMANS J , LOS L
Published: November 2013

Purpose To assess which aspects of postoperative visual function (visual acuity, contrast acuity, or color confusion) are correlated with visual function‐related quality of life measurements after successful surgery for macula‐off rhegmatogenous retinal detachment (RRD).

Methods In patients with a primary macula‐off RRD, best correct visual acuity (BCVA), color confusion indices (CCI saturé and desaturé), and contrast acuity were measured at 12 months postoperatively in both the RRD eye and the fellow control eye, and the 25‐item National Eye Institute Visual Function Questionnaire (VFQ‐25) was filled out.

Results Forty‐five patients with a primary unilateral macula‐off RRD were included. There was a significant difference between operated and fellow control eyes with regard to LogMAR BCVA (P < 0.0001), Log contrast acuity (P < 0.0001), saturé CCI (P = 0.018), and desaturé CCI (P = 0.018). Correlations were observed between the composite VFQ‐25 score and postoperative LogMAR BCVA (R = ‐0.53, P < 0.0005) and Log contrast acuity (R = 0.47, P = 0.001). In addition, correlations were found between postoperative LogMAR BCVA and Log contrast acuity and the following subscales: driving, near acuity, role difficulties, and general vision. Also, a correlation between the subscale mental health and LogMAR BCVA was found. No correlations were found between any VFQ‐25 scales and the CCIs.

Conclusion Postoperative BCVA, contrast acuity and color confusion in operated macula‐off RRD eyes were significantly worse compared to their fellow control eyes. Several vision‐related quality of life parameters were highly correlated with postoperative BCVA and contrast acuity.
Baseline characteristics and vitreoretinal interface features in patients with vitreomacular traction without macular hole from the MIVI‐TRUST clinical program
Authors: KOSHY Z , LABOUDETTE A , DUCHATEAU L , LESCRAUWAET B
Published: November 2013

Purpose There is limited published evidence on demographic and vitreoretinal interface (VRI) characteristics of patients with persistent vitreomacular traction (VMT). Establishing characteristics of untreated VMT may contribute to a better understanding of the burden of VMT disease To describe baseline characteristics and VRI features in patients with persistent VMT included in the phase 3 ocriplasmin studies. This analysis reports on VMT patients without macular hole (MH)

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 diagnosis, visual acuity (VA) study eye (SE), non‐study eye (NSE), presence of pseudophakia or ERM); VRI features (type of focal VMA, vitreous separation); VFQ‐25 composite score

Results VMT without MH was present in 499 patients (76.5%). Baseline characteristics were: 72.6 years (SD 9.8); 62.7% female. Time since diagnosis was: 268 days (SD 547); VA: SE 66.8 (SD 11.2); NSE 73.5 (SD 16.5). Pseudophakes: 38.7%, concomitant ERM: 46.3 %. The majority of patients presented with focal adhesion ≤1500 microns (69%) and with vitreous adhesions attached at fovea and optic nerve (92%); VFQ‐25 composite score: 78.0 (SD 15.2)

Conclusion Baseline characteristics and vitreoretinal Interface features in patients with vitreomacular traction without macular hole from the MIVI‐TRUST Clinical Program
Mesenchymal stem cells and corneal regeneration
Authors: HOPKINSON A , BRANCH M
Published: November 2013

Mesenchymal stem cells (MSC) are the subject of intensive research for regenerative medicine purposes. MSC can be isolated from a broad range of tissues, allowing use in both autologous or allogeneic stem cell transplantation. Furthermore, these cells are readily bankable and their numbers can be expanded in vitro. MSC possess an impressive functional‐repertoire as they are differentiated into a steadily growing number of cell types, including those found in the cornea. However the regenerative abilities of MSC extend beyond differentiation. MSC are able to modulate and supress localised immune responses encouraging graft acceptance and reducing occurrences of GVHD/rejection. Furthermore they are able to encourage regeneration by the host tissue using a multitude of paracrine signalling pathways. MSC have previously been shown to promote corneal wound healing both with and without incorporation into the host tissue. MSC have been found to reside in the limbal and peripheral corneal stroma. Although their role in normal corneal homeostasis and wound healing is unknown there have recently been tantalising glimpses into their potential for substantial corneal regeneration.
Congenital and other pigmented fundus lesions
Authors: CAUJOLLE JP
Published: November 2013

Purpose: To describe congenital and pigmented fundus tumors except nevi and melanomas. Methods: We analyse diagnostic approaches of thess tumors, their characteristics, the differential diagnosis and the follow up. Results: The main tumors include congenital tumors such as congenital hypertrophy of the retinal pigment epithelium (RPE), hamartoma of the RPE, combined hamartoma of the RPE and sensory retina. The other pigmented tumors are melanocytoma, adenoma or adenocarcinoma of RPE and pigmented choroidal metastasis. The differential diagnosis must be made from RPE hyperplasia, peripheral exsudative haemorrhagic chorioretinopathy and pseudo tumoral age related macular degeneration. Conclusions: These tumors must be known to be differenciated from melanomas and choroidal nevi. Moreover, although these lesions are mainly benign in their clinical behavior, some cases can have ocular complications, slow growth or malignant transformations.
Uveitis and glaucoma: A practical approach
Authors: BODAGHI B
Published: November 2013

Uveitis is a sight‐threatening condition with major therapeutic breakthroughs during the last decade. Control of inflammation is more frequently achieved. Therefore, blindness is often associated with secondary complications. Severe glaucoma is one of the most difficult situations to manage. Both inflammation and steroids may induce ocular hypertension in patients with uveitis. Most of cases are associated with anterior uveitis. New entities associated with viral infections have been identified during the last decade. Specific antiviral therapy is often sufficient to control both inflammation and high IOP. In noninfectious conditions, control of inflammation with immunosuppressors and biologic agents have dramatically changed the incidence of glaucoma in these patients. Prompt diagnosis and efficient treatment of uveitis have dramatically changed the outcome and long‐term prognosis of uveitis. Glaucoma surgery remains rarely necessary but sometimes the only possible strategy.
Culture optimisation of CD34‐positive corneal stromal stem cells and transdifferentiation into corneal epithelial cells
Authors: SIDNEY LE , BRANCH MJ , HASHMANI K , DUA HS , HOPKINSON A
Published: November 2013

Purpose The integrity of the corneal epithelium is essential for clarity of vision. Under normal circumstances, superficial epithelial cells are shed into the tear film and regenerated by epithelial stem/progenitor cells located at the limbus. Damage or depletion of the limbal cells leads to conditions such as limbal stem cell deficiency (LSCD). Current treatment involves transplantation of limbal epithelial cells expanded ex‐vivo; however cell numbers are limited. In this study, we identify a source of multipotent stem cells located in the corneal stroma that express CD34 upon isolation. These cells demonstrate an ability to transdifferentiate into corneal epithelial cells.

Methods CD34 expression diminishes during traditional tissue‐culture plastic propagation; in this study we optimised culture conditions for maintained and efficient expansion of CD34+ cells. We investigated the role of CD34 in epithelial transdifferentiation of stromal cells, using siRNA gene knockdown and analysis by immunocytochemistry, flow cytometry and qPCR.

Results Early results suggest a three‐dimensional environment and semi‐solid medium intended for hematopoietic culture demonstrated extended CD34 expression. When cells were transferred to epithelial differentiation medium they showed an epithelial morphology, significantly increased cytokeratin 3 and 19 expression, and considerable upregulation of genes related to corneal epithelial cells (ABCG2, DeltaN63, LEF1, HES1, FRZB1, KRT19, DTC and CDH1).

Conclusion This work will help produce methodologies to create cell banks for generation of corneal epithelium, from a corneal stromal stem cell source, leading to improved surgical and visual outcomes in LSCD patients.
Computational model of Ca2+ wave propagation in human retinal pigment epithelium
Authors: VAINIO I , ABU KHAMIDAKH A , PACI M , SKOTTMAN H , JUUTI‐UUSITALO K , HYTTINEN J , NYMARK S
Published: November 2013

Purpose Ca2+ signaling is relevant to most biological functions. In retinal pigment epithelium (RPE) a significant Ca2+ wave is produced by mechanical stimulation. To understand this process in detail, we modeled Ca2+ wave propagation in ARPE‐19 cells.

Methods Mechanically induced Ca2+ wave was recorded from ARPE‐19 cells by Ca2+ imaging. Based on the measurements, a mathematical model was constructed. The model assessed Ca2+ wave propagation by assuming that cells were experiencing different conditions depending on their location with respect to the stimulation site.

Results The model describes Ca2+ metabolism after stimulation as follows: 1) Cells near the stimulus site are likely to conduct Ca2+ through plasma membrane stretch‐sensitive Ca2+ channels and gap junctions. 2) The extracellular ligand and inositol 1,4,5‐trisphosphate (IP3) diffusion through gap junctions mediate the signal in all locations of the monolayer, ligand concentration decreasing with distance. 3) The kinase activity targeted to IP3 receptor defines the sensitivity of the cell to the ligand. The model predicts suramin drug effects on P2Y2 receptors suggesting that suramin accelerates the phosphorylation rate of the receptors by enhancing their desensitization.

Conclusion Our model is the first mathematical model of Ca2+ signaling in ARPE‐19 cells. The model enables the analysis of the Ca2+ signal propagation mechanisms, and predicts new pathways of suramin drug effects.
New evidence on nutritional supplements
Authors: CREUZOT C
Published: November 2013

Abstract not provided
Modern indications and limitations of amniotic membrane transplantation
Authors: YEUNG A
Published: November 2013

Abstract not provided