bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomic analysis of aqueous humor in retinoblastoma patients: a focus on intra‐arterial chemotherapy effects
Authors: MICHELI L , LANDI G , MORIGGI M , VANNONI D , VASSO M , MENICACCI F , GELFI C , LEONCINI R , HADJISTILIANOU T
Published: August 2014

Purpose Proteomics can be a useful tool to understand how therapies act and affect on the molecular composition of ocular fluids. In this retrospective study we focus on how the aqueous humor (AH) proteic pattern from retinoblastoma (RTB) patients is modified by intra‐arterial(IA)treatment.

Methods We enrolled 22 RTB patients(Reese stage VB or ABC group E)undergoing enucleation and 20 normal subjects undergoing cataract surgery(CTR).Five of 22 patients presented with associated secondary glaucoma (SG) whereas 17 had no secondary glaucoma (NSG);8 of 17 NSG received IA Melphalan (CHM). Pools were firstly investigated with Bradford method and SDS‐PAGE and then,analyzed using 2D‐DIGE coupled to mass spectrometer.DIA and BVA were fully automated with 2D DeCyder® and statistical analysis was performed with EDA® module.Significant spots were In‐Gel digested and identified with Maldi‐TOF/TOF.

Results According to Bradford method,CTR protein content was not significantly different from CHM.After melphalan treatment, total protein contents decreased about 70% while in respect to all non‐treated patients were significantly different(Tamhane p<0.01).PCA analysis underlines high distance either between CTR pool and SG/NSG pool or CHM and RTB.In particular the analysis of single protein shows that CHM pool is characterized by a high level of Crystallin and pro‐inflammatory proteins and CTR pool is characterized by a high level of Epithelium Growth Factor.

Conclusion IA chemotherapy with Melphalan modifies the AH proteic pattern revealing the presence of Crystallin family and pro‐inflammatory proteins. This opens new horizons to further explore local pharmacological effects of new drugs.
Intraocular Metastasis as presentation of unknown systemic neoplasia
Authors: SAORNIL ALVAREZ M , RAMOA R , GARCIA‐ALVAREZ C , MUNOZ M , LOPEZ‐LARA F
Published: August 2014

Purpose To assess the frequency of metastases as first presentation of systemic disease in a referral clinic, and to identify clinical characteristics.

Methods Retrsopective study of consecutive csees diagnosed of intraocular metastasis at the referral intraocular tumors Unit. General and clinical characteristics were registered in a database design in Noraybanks (software approved by the research committe. Descriptive analysis was performed with SPSS 20.0.

Results Between 1990 and 2013, 21 patients were diagnosed of intraocular metastasis with a mean age of 62.7 years (31‐89). Most frequent primary tumors were breast (47.6%) and lung (23.8%).Bilateral tumor was observed in 4 cases.The intraocular tumor was the first manifestation of the neoplasia in 13 cases (61.9%).Primary tumor was breast in 46.2% and lung in 38.5%, eshophagus in 7.7% and stomach in 7.7%.Reason for consultation was decreased vision in all cases. All 13 cases were unilateral and 75% as a solitary mass. Tumor was located at posterior pole in 69.2% and in all cases behind the equator.Diagnosis of primary tumor was performed by systemic studies and only one patient required intraocular biopsy. Ragrading the treatment, 7 cases were controlled with systemic chemotherapy, 4 cases required additional external beam radiotherapy and only one underwent to enucleation due to associated neovascular glaucoma

Conclusion When intraocular metastases are the first presentation of unknown neoplasia used to be solitary non pigmented mass with retinal detachment.Early diagnosis is essential to settle prompt treatment to preserve visual function and improve the patient's prognosis.
FRO 2014: Shine a light on glaucoma: an optogenetic approach towards retinal ganglion cell protection
Authors: DEKEYSTER E , GEERAERTS E , MOONS L
Published: August 2014

Our overall objective is to investigate whether modulation of neuronal activity in the superior colliculus (SC), the principal retinal target structure and main extraretinal neurotrophic factor source in mice, can protect against chronic RGC loss, experimentally induced using the well‐establised optic nerve crush (ONC) mouse model of glaucoma. For activity modulation, we will make use of the novel revolutionary technology of optogenetics. More precisely, in this project we aim to: 1) validate the genetic labeling of SC neurons with AAV vectors, carrying an stable‐step function opsin (SSFO) under control of a neuronal (CMV) promoter; 2) test the ability to chronically stimulate the transduced cells; and 3) evaluate the potential of chronic optogenetic modulation of SC neuronal activity to promote RGC survival in the optic nerve crush model.
FRO 2014: ROCK as a potential target in the treatment of different retinopathies
Authors: HOLLANDERS K , SPILEERS W
Published: August 2014

The aim of this project is to investigate the therapeutic effect of ROCK‐inhibition in two mouse models for ischemia‐related retinopathy, diabetic retinopathy (DR) and retinopathy of prematurity (ROP). 1) The first objective of this project is to elucidate the in vivo role of ROCK on the process of inflammation and angiogenesis in ischemic retinopathies. Therefore, the efficacy of a potent ROCK inhibitor will be compared to anti‐VEGF therapy (DC101), using two different mouse models. 2) The second objective is to evaluate the possible neuroprotective effect of ROCK inhibition.
FRO 2014: MMP‐2 as a potential benefactor in zebrafish optic nerve regeneration
Authors: LEMMENS K , BOLLAERTS I , MOONS L
Published: August 2014

The zebrafish retinotectal system proves to be a valuable research model to investigate regenerative strategies of damaged retinal ganglion cells (RGCs) and thus holds great promise towards identifying new regenerative molecules. Recent research performed in our lab shows that retinal broad‐spectrum MMP inhibition seriously reduces retinotectal regeneration after optic nerve crush (ONC) in the adult zebrafish. Based on preliminary results, we now intend to determine the exact role of MMP‐2 in zebrafish RGC axonal regrowth and identify underlying molecules, which might ultimately serve as new therapeutic targets for the injured mammalian CNS. Hereto, we will pursue the following goals: (1) Determination of the regenerative potential of RGCs after retinal MMP‐2 inhibition/knockdown in zebrafish subjected to ONC. (2) Proteomic identification of MMP‐2 regulated pathways underlying a successful regeneration in the zebrafish visual system.
FRO 2014: Automated detection, classification and notification of pathological corneas using the Oculus Pentacam
Authors: RUIZ HIDALGO I
Published: August 2014

To develop an automated classification system for normal and abnormal corneal topography based on data obtained from the Pentacam, which can be used for the following purposes: 1. To investigate the variability of corneal topography. 2. To automatically detect pathological corneas such as keratoconus, high astigmatism, post‐refractive surgery and early onset of edema or corneal dystrophies (e.g. Fuchs dystrophy) before it is visible with the slit‐lamp. 3. To create an add‐on program to the Pentacam software that gives a warning message with a probability of belonging to a disease group when a new patient is measured.
Comparison of ocriplasmin efficacy and treatment guidance as determined by European regulatory agencies
Authors: KOROBELNIK J
Published: August 2014

Purpose Ocriplasmin, a truncated form of human plasmin, has proteolytic activity against components of the vitreous body and the vitreoretinal interface.

Methods Results from placebo‐controlled trials designed to determine efficacy and safety of ocriplasmin for the treatment of VMT were used in the determination by the French National Health Authority (Haute Autorité de Santé, or HAS), the National Institute for Health and Care Excellence (NICE), and the Isntitute for Quality and Efficiency in Healthcare (Institut fur Qualitat und Wirtschaftlichkeit im Gesundheitswesen, or IQWiG). Different subgroups according to presence or absence of anatomic features and visual acuity (VA) were analysed.

Results All 3 regulatory agencies recommend ocriplasmin for the treatment of VMT including when associated with MH less than or equal to 400 microns. The HAS recommends ocriplasmin for the treatment of adult patients with VMT for whom symptomatology does not require immediately a vitrectomy, at the earlier stage of disease. IQWiG reported indication of an added benefit for patients with mild (VA >60 ETDRS letters) to moderate visual impairment (VA 35‐60 ETDRS letters). According to the NICE guidance, ocriplasmin is recommended as an option for treating VMT in adults only if an epiretinal membrane is absent, with or without severe symptoms.

Conclusion The benefit of ocriplasmin for the treatment of VMT including when associated with FTMH of 400 microns or less has been evaluated and confirmed by Europe’s leading regulatory agencies. Minor differences exist in the recommendations from each country, based on anatomic features (absence of ERM), visual acuity, and severity of symptoms.
Cytologic analysis in vitreo‐retinal surgery
Authors: ARNDT C , DUCASSE A , DIEBOLD MC , BOULAGNON C
Published: August 2014

Purpose Proliferative vitreoretinopathy (PVR) is the leading cause of failure in retinal detachment (RD)surgery. The migration of retinal pigment epithelial cells and the proliferation of the extracellular matrix has been associated with PVR. The purpose of this prospective study was to compare the cellular contents of the vitreous of patients undergoing RD surgery with patients scheduled for epiretinal membrane surgery (ERM).

Methods The vitreous samples of patients with ERM and RD were obtained at the initial phase of surgery. A immunocytochemical labeling was performed in all cases with AE1/AE3, CD68, Vimentin and GFAP antibodies. The cytological identification was performed by a trained pathologist unaware of immunocytochemical labeling. The concentration of vitreous cells were analyzed semi‐quantitatively.

Results 14 vitreous samples were analysed, 9 patients with RD and 5 undergoing ERM. In the RD group, the cytological findings correlated with the results of immunolabeling. Hyalocytes (labeled with vimentin only)were present in all cases, more abundant in RD cases. Macrophages (labeled with vimentin and CD68) were found in 10/14 cases. Macrophages were more abundant in RD cases (p<0,05). Only in one case of RD, GFAP positive cells were found, in which PVR was particularly severe. In 6/14 samples, glial cells were identified with AE1/AE3 without difference between RD and epiretinal membrane cases.

Conclusion Vitreous changes observed in patients with retinal detachment appear to involve particularly hyalocytes and macrophages, which could be identified with immunolabeling. Interestingly glial cells (GFAP positive)were only present in severe PVR. A link between this cell population in the vitreous and the clinical outcome remains to evaluated in a prospective study.
Treatment of vitreomacular traction with ocriplasmin in a non‐reimbursed setting
Authors: WILLEKENS K , PINTO LA , VANDEWALLE E , STALMANS I , STALMANS P
Published: August 2014

Purpose Vitreomacular adhesion can lead to vitreomacular traction (VMT) and macular hole (MH) formation. Intravitreal ocriplasmin provides a non‐surgical solution to release VMT with or without macular hole. A series of 37 patients treated with ocriplasmin is presented. Since ocriplasmin was used in a non‐reimbursed setting, the injection was only recommended when a high success chance was anticipated (e.g. excluding patients with a concomitant epiretinal membrane).

Methods An observational trial was conducted on 37 patients with VMT +/‐ MH treated with ocriplasmin with a minimal follow up time of 28 days. Patients had OCT scans of the macular and papillary region prior to the treatment and regularly in the following month. Data on papillary changes were also recorded by Heidelberg Retinal Tomography.

Results Overall, 38 eyes of 37 patients were treated (27 with VMT and 11 with VMT+MH). VMT resolved in 28 cases (74%) and macular holes closed in 4 cases (36%). The cup/disc ratio transiently became smaller, associated with a small increase in retinal nerve fiber layer thickness. Interestingly, formation of transient subretinal fluid was observed in the subfoveal and peripapillar region in some patients and a subfoveal drusenoid deposit disappeared in two patients after injection.

Conclusion A high success rate of VMT release can be obtained after injection of ocriplasmin when patients are carefully selected. Further research on observed transient changes in the appearance of subretinal fluid and the peripapillary nerve fiber layer thickness is needed.
Small "Big Bubble" Technique to optimize DALK results
Authors: BUSIN M
Published: August 2014

The small "big bubble" technique limits descemetic dissection to the central 6 mm optical zone but uses a 9mm graft with both graft and recipient wound edges cut by machine. Visual outcomes after DALK utilizing the small "big bubble" technique were evaluated in 88 eyes. After complete suture removal, BSCVA was ≥20/25 and refractive astigmatism was ≤4.5 diopters in in 21 of 27 eyes (30.7%). This variation of DALK technique can provide good visual results while limiting to a minimum the area of descemetic dissection.
Growth factor and interleukin concentration in amniotic membrane suspension (AMS) and amniotic tissue homogenates (AMTH)
Authors: SZENTMARY N , STACHON T , BISCHOFF M , HUBER M , ZAWADA M , LANGENBUCHER A , SEITZ B
Published: August 2014

Application of AMS or AMTH eye drops was suggested as a potential non‐surgical treatment alternative of therapy resistant corneal epithelial defects. We determined the concentration of growth factors EGF and FGFb and interleukins IL‐6 and IL‐8 in AMS and AMTH following different preparation methods. In AMTH EGF concentration was about 1.7‐17x and FGFb concentration about 1.2‐8.5x higher than in AMS. With higher EGF and FGFb concentrations and lack of IL‐6 and IL‐8 in AMTH, its use may be more appropriate in treatment of corneal epithelial defects. However, the most effective preparation method and the harvesting timepoint are yet to be determined.
What’s new about contact lens complications?
Authors: KUHN D
Published: August 2014

The results of a study about 2260 contact lens related complications reported in Germany between 2006 to 2013 shall be presented. The analysis was done with a questionnaire including the following topics: ‐ For how many years were the lenses worn before the damage appeared? ‐ Which kind of contact lenses is related to the highest incidence of complications? ‐ Where had the contact lenses been fitted and bought? ‐ Which was the wearing modality? ‐ What kind of cleaning solutions were used? ‐ How was the hygienic behavior of the wearer? ‐ Which were the ophthalmological findings? ‐ Which therapy was given? ‐ Was the contact lens wearer unable to work? The results are the following: contact lens complications occur rather in the first year of contact lens wearing and with monthly replacement lenses. Most of them are cheap lenses bought without prescription or any control through a contact lens specialist. Poor hygiene is another important risk factor as well as the kind of wearing modality. The most frequent ophthalmological finding was a contact lens associated red eye. Antibiotic drops are the most frequently prescribed therapy. The results will be discussed and recommendations will be given.
The proinflammatory cytokine high‐mobility group box‐1 mediates retinal neuropathy induced by diabetes
Authors: ABU EL ASRAR A , SIDDIQUEI M , NAWAZ M , GEBOES K , MOHAMMAD G
Published: August 2014

Purpose To test the hypothesis that increased expression of proinflammatory cytokine high‐mobility group box‐1 (HMGB1) in epiretinal membranes and vitreous fluid from patients with proliferative diabetic retinopathy and in retinas of diabetic rats plays a pathogenetic role in mediating diabetes‐induced retinal neuropathy.

Methods Retinas of 1‐month diabetic rats and HMGB1 intravitreally injected normal rats were studied using Western blot analysis, RT‐PCR and glutamate assay. In addition, we studied the effect of the HMGB1 inhibitor glycyrrhizin on diabetes‐induced biochemical changes in the retina.

Results Diabetes and intravitreal injection of HMGB1 in normal rats induced significant upregulation of HMGB1 protein and mRNA, activated extracellular signal‐regulated kinase 1 and 2 (ERK1/2) cleaved caspase‐3 and glutamate and significant downregulation of synaptophysin, tyrosine hydroxylase, glutamine synthetase and glyoxalase 1. Constant glycyrrhizin intake from the onset of diabetes did not affect the metabolic status of the diabetic rats, but it significantly attenuated diabetes‐induced upregulation of HMGB1 protein and mRNA, activated ERK1/2 , cleaved caspase‐3 and glutamate. In the glycyrrhizin‐fed diabetic rats, the decrease in synaptophysin, tyrosine hydoxylase and glyoxalase 1 caused by diabetes was significantly attenuated.

Conclusion These findings suggest that early retinal neuropathy of diabetes involves upregulated expression of HMGB1 and can be ameliorated by inhibition of HMGB1.
FRO 2014: Development of a new animal model for corneal endothelial research purposes
Authors: SIJNAVE D , SPILEERS W
Published: August 2014

1. To develop a new rabbit model for corneal endothelial dystrophy using an intracameral injection (ICI) of Mitomycin C (MMC) 2. To investigate new pharmacological therapies in the new optimized rabbit model.
FRO 2014: VEGF‐Trap as a novel antifibrotic strategy to prevent filtration failure after glaucoma surgery
Authors: VAN BERGEN T , STALMANS I
Published: August 2014

To explore the combined inhibition of VEGF and PlGF, by the use of VEGF‐Trap, as a new therapeutic strategy to prevent filtration failure: 1) To investigate the most optimal administration route for VEGF‐Trap 2) To compare the effects of VEGF‐Trap to those of the gold standard in clinical practice, mitomycin‐C (MMC) 3) To investigate the potential complementary effects of VEGF‐Trap and MMC 4) To compare the efficacy of VEGF‐Trap to bevacizumab (known to be effective in improving surgical outcome in a prospective randomized clinical trial)
FRO 2014: Inflammatory tear cytokine profile in acute HSV epithelial keratitis
Authors: ZAKARIA N
Published: August 2014

Herpetic eye disease presents a wide spectrum of pathology, from superficial ulceration to deep stromal scarring and vascularisation. The biomolecular changes that occur as the disease progresses are poorly understood. Therefore the aim of the project is to better characterise the acute cytokine changes in the tear film of patients with herpetic eye disease.
The long‐term benefit of new sustained delivery micro‐implant in patients with chronic DME
Authors: CUNHA‐VAZ J
Published: August 2014

Abstract not provided
Inhaled nitric oxide dilates retinal arterioles in minipigs
Authors: PETROPOULOS I , MARTIN AL , MANGIORIS G , MENDRINOS E , RIMENSBERGER PC , POURNARAS C
Published: August 2014

Purpose To investigate the effect of inhaled nitric oxide (NO) on the retinal arteriolar diameter in minipigs.

Methods Seven minipigs were anesthetized, intubated and mechanically ventilated. A Swan‐Ganz catheter was inserted for measuring cardiac output by the thermodilution technique. Fundus image (one eye per animal) was recorded in a digital videotape under stable hemodynamic and ventilatory conditions. After baseline recordings, NO was added to the breathing circuit first at 20 ppm for 30 minutes and then at 40 ppm for another 30 minutes. NO was then weaned off. Retinal arteriolar diameter was measured in arbitrary units (AU) at baseline and 30 minutes after each manipulation, using Retinal Vessel Analyzer. Systemic and pulmonary hemodynamic parameters were also measured.

Results Mean baseline retinal arteriolar diameter was 231.0±38.1 AU. Thirty minutes after initiation of 20‐ppm NO inhalation, this diameter had increased only by 3.2±3.5% compared to baseline (p>0.05), to 237.9±36.5 AU. Thirty minutes after initiation of 40‐ppm NO inhalation, this diameter had increased by 7.6±4.7% compared to baseline (p<0.05), to 248.3±39.8 AU. Thirty minutes after weaning off the inhaled NO, this diameter had decreased to 232.9±39.1 AU, having returned practically to baseline (p>0.1 compared to baseline). Hemodynamic parameters (mainly cardiac output, blood pressure, and systemic vascular resistance) did not change significantly.

Conclusion In minipigs, NO inhalation at a concentration increased stepwise from 20 to 40 ppm induces a retinal arteriolar vasodilation which is reversed 30 minutes after weaning off the inhaled NO. A potential clinical application of this treatment modality in vascular diseases of the retina needs to be evaluated.
Aquaporin 4 is required to induce retinal angiogenesis in a mouse model of oxygen‐induced retinopathy
Authors: DAL MONTE M , NICCHIA GP , CAMMALLERI M , FRIGERI IA , FORNACIARI I , PISANI F , BAGNOLI P , SVELTO M
Published: August 2014

Purpose Aquaporin 4 (AQP4) is the most abundant water channel in the retina and participates in the formation of blood‐retinal barrier (BRB). In several retinal pathologies accompanied by BRB dysfunction the expression of AQP4 is altered. In the present study, we investigated the effects of AQP4 deletion in the vascular retinal response to hypoxia.

Methods We used wild type (WT) and AQP4 knockout (KO) mice. The retinal angiogenic response to hypoxia was studied in a mouse model of oxygen‐induced retinopathy (OIR) using real time RT‐PCR, Western blot, ELISA and immunohistochemistry.

Results In WT mice, retinal levels of AQP4 were increased in response to hypoxia. In OIR mice, the BRB dysfunction was more pronounced in KO than in WT mice. BRB tight junction proteins, occludin, ZO‐1 and JAM‐C, were analyzed and significant alteration was found for JAM‐C in KO mice, indicating a role for this protein in the observed dysfunctions. The formation of neovascular tufts, which are characteristic of OIR, was completely prevented in KO mice, possibly as a result of the decrease in hypoxia‐induced up‐regulation of VEGF mRNA and protein. Unexpectedly, this reduced increase in VEGF levels was paralleled by a dramatic increase in the activity of transcription factors which regulate VEGF expression indicating that in KO retinas mechanisms of VEGF transcription, such as promoter methylation, may be altered.

Conclusion Together, the present results indicate a role for AQP4 in the formation of angiogenic processes in the retina and suggest that inhibiting AQP4 function may be a strategy to reduce pathologic angiogenesis in proliferative retinopathies.
Ocular hypotensive properties of Cornus mas extract and loganic acid
Authors: SZUMNY D , KUCHARSKA AZ , PIORECKI N , SZUMNY A , SOZANSKI T , DZIEWISZEK W , CHLEBDA E , SZELAG A
Published: August 2014

Purpose Ocular hypertension became a serious problem in a population with increasingly longer life expectancy. Although there are available effective and well established drugs each group possess their disadvantages. In European medicine according to Pharmacopoeia (EP) herbal drugs affected on the eye condition are on the margin of a purely chemical treatment. A few of them possess as an active ingredients biologically active group of terpenoids called iridoids. The loganic acid is an active iridoid in Cornelian cherry (Cornus mas) fruits as a main compound of a polar fraction.

Methods We checked on the animal model (New Zealand rabbits) ocular properties of C. cherry polar fraction and loganic acid. The ultra high pressure liquid chromatography (coupled with mass spectrometers) analysis proved the presence of iridoids: loganic acid, cornuside, and pelaronidin, delfinidin galacto‐ and rhamnosides. The intraocular pressure was measured by ICare vet tonometer after 1, 2, 3 and 5 hours of applanation of one drop 50 µl. The intraocular pressure measurements were performed in conscious rabbits, standing calmly on the table, held delicately without head immobilization.

Results A single dose of 0.7% loganic acid extract in vehiculum containing 0,15% sodium hyaluronate administered directly into the conjunctival sac decreased after 60 min the mean value of intraocular pressure (IOP) about 15 %. The fraction’s main compound – loganic acid decreased the IOP for about 23 %. This effect was compared to timolol, used similarly to the investigated compounds.

Conclusion Although the Cornelian cherry as well as loganic acid are not mentioned in EP we proved it’s possible utility in future ocular hypertension therapy.
New non‐invasive technique for dosing eye drops concentration in tears
Authors: GAUTHIER AS , FRIOT M , PRONGUÉ A , ROYER B , DELBOSC B
Published: August 2014

Purpose Introduction The efficacy of tacrolimus ointment and eye drops has been proven in the treatment of immune corneal pathologies and in prevention of high risk corneal graft rejection. We recently developed a new formulation of tacrolimus 0.06% eye drops with a better tolerance than classical formulation. In such context, the concentration of tacrolimus in tears was investigated in the absence of data in human. We thus developed a non‐invasive technique for dosing eye drops concentration in tears. The objective of the study was to assess the feasibility of this assay.

Methods The tears sampling was performed using Schirmer’s paper strips. After collection, the strips were transferred into a solution of acetonitril with internal standard. This solution allows both the preservation of the samples and the extraction of tacrolimus. The tacrolimus was then measured with a LC/MS/MS. The results were normalized with the length of wetting of the paper.

Results Detectable concentrations of tacrolimus were easily observed until 4 hours after instillation. The main issue was ocular irritation in few patients.

Conclusion This method allows to measure tacrolimus concentration in tears using a non‐invasive method for at least 4 hours. The use of Schirmer’s paper strips will facilitate such studies with children. This convenient method will allow us to investigate the behavior of tacrolimus concentrations with time in tears.
Lymphocytic microparticles modulate macrophages function in experimental choroidal neovascularization
Authors: TAHIRI H , OMRI S , CHUN Y , DUHAMEL F , CHEMTOB S , HARDY P
Published: August 2014

Purpose Pathological choroidal neovascularization (CNV) is the major cause of severe vision loss in patients with age‐related macular degeneration (AMD). Inflammation is a key component in AMD, and macrophages play an important role in CNV generation. We have demonstrated that human T‐lymphocyte‐derived microparticles (LMPs) significantly inhibit angiogenesis in several models of ocular neovascularization. In this study, we investigated whether LMPs modulate angiogenic microenvironment by altering macrophages activities

Methods LMPs were produced from apoptotic human T lymphocytes after treated with actinomycin D. The effects of LMPs on cell viability and cell migration were studied in apoptosis assay and migration assay respectively. Cell growth of human retinal microvascular endothelial cells was assessed after cells were co‐cultured with LMPs pre‐treated macrophages. A laser‐induced CNV model was used to determine labelled choroidal flat‐mounts.

Results LMPs dose‐dependently inhibited macrophages cell growth without altering cell death. In addition, LMPs dramatically abrogated VEGF‐induced macrophages migration. LMPs‐pretreated macrophages exhibited strong inhibitory effect on endothelial cell growth and this effect was associated with the increased expression of IL‐12, CD36 and HIF‐1α. In vivo, intravitreal injection of LMPs significantly suppressed laser‐induced CNV and reduced macrophages infiltration at the lesion sites.

Conclusion These results suggest that LMPs are potent antiangiogenic therapeutic agent. In addition to the direct effects on endothelial cells, LMPs may interfere the proangiogenic environment through modulation of macrophages function during pathophysiological conditions.
SD OCT and fundus auto fluorescence findings in Stargardt disease
Authors: EL MATRI L , CHEBIL A , KORT F , CHARFI H , MAMOURI R , HSAIRI A
Published: August 2014

Purpose To analyze macular morphology with SD OCT and Fundus Auto Fluorescence (FAF) in patients with Stargardt disease (STGD) and to correlate between visual acuity (VA) and macular patterns.

Methods Forty eyes with STGD phenotypes, underwent FAF and SD‐OCT imaging. The levels and the distribution of FAF and atrophic lesions were evaluated.

Results Patients were separated in 2 groups: BCVA ≥ 0.05 and BCVA< 0.05.We found 5 patterns in FAF: Homogeneous high AF of the entire retina; Heterogeneous high and low retinal AF with low central AF; Numerous small areas of atrophy in heterogeneous low AF; Large an isolated central retinal atrophy; Central retinal atrophy without foveolar involvement. Six patterns were found in SD‐OCT: Normal foveal depression, regular photoreceptor IS/OS junction with hyper reflectivity of outer nuclear layer; subnormal foveal depression, foveal disorganization and/or loss of IS/OS junction; Absence of foveal depression, loss of the IS/OS junction and the photoreceptors layer; Macular hole aspect; large retinal atrophy with macular layers disorganization; Pseudo‐coloboma image. Foveal thickness was significantly reduced in all patients (Mean = 107.92 µm) excepted in group I with subclinical STGD. There was a statistically significant correlation between FAF pattern and SD‐OCT pattern (p=0.03) and between BCVA and SD‐OCT pattern (p=0.04).

Conclusion Both SD‐OCT and FAF are useful in the management of STGD. Correlation between structure and function should be useful in guiding selection of patients for future therapeutic.
Clinical presentation of a Roma family with autosomal recessive Usher Syndrome
Authors: KOEV K , CHERNINKOVA S , KAMENAROVA K , GEORGIEV R , KANEVA R
Published: August 2014

Purpose Usher Syndrome is a genetic condition involving sensory neural hearing loss and retinitis pigmentosa (RP).RP is a heritable group of genetic diseases that is characterized by degeneration of the retinal pigment epithelium due to loss of photoreceptors, primary rods and secondary cones.

Methods We present 2 familial cases, brother (48 years old) and sister (45 years old), with Usher syndrome. According to family history data their grandmother (the mother of their father) had the same disease.

Results The visual acuity of the brother was pplc of both eyes, while the visual acuity of the sister was 0,1 of both eyes. Fundoscopically we observed osteoclast‐like pigmentations in the posterior pole of the retina and in and around the macula lutea of both cases. In both cases we found narrowed arterioles and diffuse bilateral wax pallor of the papilla.The ERG of the both had micropotentials with lack of flicker response. The FA of both siblings – revealed dense osteoclast‐like pigment in the posterior pole and the macula area. In the case of the sister through Kugel perimetry was established tunnel vision to 10o. Humphrey perimetry showed reduced retinal sensitivity in bilateral central and peripheral zone; concentric narrowing of the visual field only for the sister.In both of the cases audiogram showed high rates of sensory neural bilateral hearing decrease.

Conclusion The presented two cases of Usher syndrome are a significantly rarer form of RP with probable autosomal‐recessive form of inheritance. Blood for DNA analysis was taken.
POFAL Study: «Protection Oculaire Face aux Agressions Lasers», Phase I
Authors: EL CHEHAB H , BEMELMANS A , NOUVEL‐JAILLARD C , NIEPON ML , RENARD JP
Published: August 2014

Purpose Risk of laser beam exposure, particularly to laser "pointers" easily available on open sale or on internet increases every year. Many incidents and accidents have been reported over the last three years in France. The purpose of this study is to try to determine a retinal lesion threshold secondary to such exposures.

Methods A laser system (532nm) with a power and duration control has been developed specifically for this study to achieve exposure. A first phase was performed in pigmented rodents with different combinations of time ‐ power beam exposure. Powers ranged from 0.5 to 4.5mW and durations from 0.1 to 0.35sec. A second phase was performed in non‐human primates (NPH) with blink reflex time (0.25sec) and 1, 2, 3.5 and 4.5mW. Histological analysis of outer layers and immunoassay to assess tissular damage (GFAP) were performed to each phase.

Results A significant correlation between energy and photoreceptor thickness is found in rodents. Histological analysis did not find a structural alteration or combination threshold. Immunoassay confirm tissular damage in inner layers. Photoreceptors alterations are located at foveal zone in NHP. Outer layers thickness is statistically lower when exposure power is greater than 1mW. A significant correlation between energy and photoreceptor thickness is also found only in foveal zone.

Conclusion This study reports systematic tissue damage when power exposures correspond to upper limits of the class II lasers (1mW). This is the first in‐vivo study analyzing exposure effects to low power laser beam or easily accessible. These initial results are used to guide and adapt research on protection systems for people exposed.
Improved analysis of the outer foveal microstructure ‐ OCT imaging of healthy and abnormal retina
Authors: SJÖSTRAND J , NILSSON M , ROSÉN R , POPOVIC Z
Published: August 2014

Purpose To improve visualization and segmentation of the foveal photoreceptors from the level of outer segments to the synapse layer in the inner portion of the outer plexiform layer. Furthermore, to create a normative model of the topography of the outer nuclear layer (ONL) with cone and rod cell bodies and the Henle fiber layer (HFL) with the axons radiating out from the foveal center (FC). An improved separation of ONL and HFL is clinically relevant for the understanding of microstructural changes in abnormal retina.

Methods Selected eyes from 14 normals and 5 young adults with a history of prematurity were imaged using a commercial spectral domain optical coherence tomography (SD‐OCT) system. Centered and displaced SD‐OCT entrance beam positions were used to obtain straight and tilted scans, respectively. Horizontal scans through FC with a distinct light reflex were selected for analysis. Straight and tilted SD‐OCT images were flattened to the RPE layer prior to registration and averaging. Retinal layer thickness was measured manually at FC and three lateral positions along the temporal and nasal hemi‐meridians.

Results We found a close correspondence between layer thickness measurements at the same lateral positions for both straight and tilted scans. However, a discrepancy was found for the tilt‐up paracentral position for tilted scans, where the foveal slope appeared flatter and the thickness of inner retinal layers was lower than in the straight and tilt‐down positions.

Conclusion Improved visualization of HFL/ONL was confirmed in tilted images. Image flattening and registration simplifies measurement of outer foveal layers in normal and abnormal retina.
Unilateral peripapillary intrachoroidal cavitation and optic disc rotation
Authors: DAI Y , JONAS J , LING Z , SUN X
Published: August 2014

Purpose To examine the morphology of the optic nerve head in patients with unilateral peripapillary intrachoroidal cavitations (PICCs).

Methods The hospital‐based observational study included patients with unilateral PICCs. Tomographic images of the parapapillary fundus were taken by enhanced depth imaging mode of optical coherent tomography. The ocular biometric parameters were compared between the affected eyes and the contralateral unaffected eyes.

Results The study population consisted of 30 patients with a mean age of 42.7±13.8 years (range:22‐72 years), mean axial length of 26.7±2.4 mm (range: 22.00‐32.30 mm) and mean refractive error of ‐8.71±5.21 diopters (range: ‐20.50 diopters to +0.50 diopters). In the eyes affected by PICC as compared with the contralateral eyes, the vertical optic disc diameter (P=0.001) and the minimal disc diameter (P=0.03) were significantly shorter, the ratio of minimal to maximal disc diameter was significantly lower (P=0.02), and the angle of disc rotation was significantly higher (P<0.001).

Conclusion In patients with unilateral PICCS, the eyes with PICCs as compared with the contralateral eyes have optic discs which are more spindle‐like configured due to a disc rotation around the vertical axis and around the sagittal axis. In association with the myopic axial elongation in PICC eyes, the findings may suggest that PICCs are associated with an external traction of the optic nerve at its adhesion at the optic nerve head, leading to a rotation of the optic disc into the temporal inferior direction and simultaneously leading to an increased distance between the parapapillary sclera and parapapillary Bruch´s membrane.
Retinal vessel course and retinal nerve fiber bundle trajectories in the human eye
Authors: JANSONIUS NM , QIU K , SCHIEFER J , NEVALAINEN J , PAETZOLD J , SCHIEFER U
Published: August 2014

Purpose To determine the relationship between the retinal vessel course and the retinal nerve fiber bundle (RNFB) trajectories in the human retina.

Methods High‐quality fundus photographs were used, comprising 28 eyes of 28 subjects (Exp Eye Res 2012). Mean (range) refraction was ‐0.4 (‐8.75 to +6.25) D. In total 625 RNFB trajectories were traced. For all individual trajectories, the departure from the previously published RNFB trajectory model (Vision Res 2009) was calculated. Subsequently, we calculated, per subject, a 'mean departure' for the superior‐temporal and inferior‐temporal regions. To quantify the retinal vessel course, we measured the angles between a line connecting the centers of the fovea and the ONH and a line connecting the center of the ONH and the crossing of the superior or inferior temporal artery or vene with a circle around the ONH; circle radius was half the fovea‐ONH distance. This yielded four angles: AAS, AVS, AAI, and AVI. Multiple linear regression analysis was performed for the superior‐temporal and inferior‐temporal regions separately, with mean departure as dependent variable and refraction, ONH inclination, and the vessel angles as independent variables.

Results In the superior‐temporal region, refraction (P=0.017), ONH inclination (P=0.021), and AAS (P<0.001) were significantly associated with mean departure. The explained variance was 0.54. In the inferior‐temporal region, AAI (P=0.037) and AVI (P=0.021) were significantly associated with mean departure. The explained variance was 0.30.

Conclusion The wiring of the human retina displays a considerable variability. The angles at which the vessels leave the ONH explain an important part of this variability.
Comparison of subfoveal choroidal thickness changes following two different doses of intravitreal bevacizumab therapy for branch retinal vein occlusion
Authors: LEE S
Published: August 2014

Purpose To investigate the effects of two different doses of intravitreal bevacizumab on subfoveal choroidal thickness(SFChT) in patients with branched retinal vein occlusion.

Methods An interventional, retrospective study of patients that were treated with intravitreal bevacizumab injection and had completed 12 months of follow‐up. The study included 16 eyes (16 patients) in the group 1 (1.25mg dose bevacizumb) and 15 eyes (15 patients) in the group 2 (2.5mg dose bevacizumab). Complete ophthalmic examination, fluorescein angiography, and enhanced depth imaging from spectral domain optical coherence tomography(SD‐OCT) were performed at baseline, and during the follow‐up visits.

Results In the group 1, the mean central retinal thickness(CRT) decreased from 553.0±199.8 µm before, 277.0±56.5 µm at 6 months, and 287.1±40.3 µm at 12 months(P<0.05). The average BCVA were 0.90 ± 0.66, 0.23 ± 0.13, and 0.20 ± 0.16 logMAR, respectively. In the group 2, the mean CRT decreased from 515.0±129.3 µm before, and 286.5±85.2 µm at 6 months, and 309.6±69.3 µm at 12 months(P<0.05). The average BCVA were 0.50 ± 0.22, 0.30 ± 0.15, and 0.26 ± 0.14 logMAR, respectively. The SFChT decreased from 269.0 µm (165‐431) to 259.5 µm (149‐413) in the group 1 and from 322.6 µm (212‐483) to 315.1 µm (199‐514) in the group 2. There was no significant difference regarding the CRT change and SFChT between groups (p = 0.48, p = 0.22).

Conclusion The SFChT did not change significantly after intravitreal bevacizumab injection in two groups. There were no statistically significant differences between the two dose groups with regard to CRT, SFChT, and change in visual acuity.
Correlation between hiperreflective foci in patients with macular edema secondary to retinal vein occlusion, and visual outcomes after an intravitreal dexamethasone implant injection
Authors: ALMENARA MICHELENA C , ASCASO FJ , LAVILLA L , CRISTOBAL J , ZABADANI K , CARAMELLO C , MARTINEZ M , HERRERA L , ESTEBAN O
Published: August 2014

Purpose To investigate the relationship between the presence of macular hyperreflective dots (HRD) detected by spectral‐domain optical coherence tomography (SD‐OCT) and visual outcomes in eyes with macular edema secondary to retinal vein occlusion (RVO), following treatment with intravitreal dexamethasone implant.

Methods Retrospective observational study of 16 consecutive cases of RVO‐associated macular edema treated with Ozurdex®. The correlation between best corrected visual acuity (BCVA) (logMAR), central macular thickness (CMT) and the presence of HRD in SD‐OCT before the treatment and two months postoperatively was determined.

Results CMT decreased significantly after treatment (553±131 μm vs 300±67 μm, p <0.0001). Although there was a visual acuity improvement in seven of the 16 eyes (43.7%), there were no significant differences in BCVA between before and following treatment (0.61±0.28 vs 0,59±0.31, p> 0.05). Numerous HRD were detected in 11 eyes (68.8%), disappearing in eight of them (72.7%) after corticosteroid intravitreal therapy. Two months following treatment, logMAR BCVA was significantly worse in the eyes with numerous HRD (0.90±0.17) than in those with few or absent HRD (0.52 ±0.29) (p = 0.045, independent Student t test).

Conclusion Disappearance of HRD following intravitreal dexamethasone therapy and the consequent improvement in visual function would support the hypothesis that hiperreflective foci could represent inflammatory cells. Nevertheless, the presence of HRD in SD‐OCT was not able to predict BCVA after intravitreal Ozurdex®.
Why should we systematically screen sleep apnea syndrome in RVO patients?
Authors: RUSSO A , DOT C
Published: August 2014

Purpose Sleep apnea syndrome (SAS ) has recently been identified as an independent cardiovascular risk factor ,involved in numerous diseases The aim of our study is to evaluate the prevalence and physiopathologic links of SAS in patients with retinal vein occlusion (RVO).

Methods Prospective study including 35 patients. Each patient had a simplified screening questionary, and an ambulatory respiratory nocturnal events measurement using the device RU‐sleeping© (Philips Respironics,Inc.).Ventilatory polysomnography (VPS), reference method, is associated in all cases.

Results Mean age of patients was 73.6 year, the sex ratio of 1.4 and CRVO as many as BRVO. Glaucoma was found in 31% of patients, hypertension in 52%. Signs of SAS were noted in 95% of patients. The prevalence of severe SAS detected by RU‐sleeping© is 84%, it is significantly higher than that of the population over 60 years (25%) (p <0.001). Preliminary results of VPS are very interesting : they found a strong linear correlation between initial macular thickness evalued by SD OCT(590 +/‐ 170μm ) and results of Apnea‐Hypopnea Index (r=0.88, p=0.004), Arousal Index (r=0.74, p=0.035) and Oxygen Desaturation Index (r=0.58, p=0.027) . Side effects of SAS could explain the occurrence of RVO. RVO could be a consequence of a slow‐down of blood flow circulation secondary to hypoxemia, elevated nocturnal intracranial pressure and rheologic variations in SAS. Arousals cause an additional acute increase in arterial blood pressure and heart rate.

Conclusion The results of this preliminary study show a high prevalence of severe SAS in the RVO population. The benefit of early ventilation on prognosis post‐RVO is still unknown. RU‐sleeping© is a simple medical device, which seems interesting for screening SAS ambulatory.
A new model for studying diameter regulation of porcine retinal arterioles and capillaries in vitro
Authors: JENSEN PS , BEK T
Published: August 2014

Purpose Studies of diameter regulation in retinal arterioles in vitro have mostly been performed on larger vessels, but evidence suggests that perturbations in the retinal microcirculation may also play a role in the development of vision threatening retinal diseases. Therefore, the purpose of the present study was to develop an in vitro technique for studying diameter regulation in both larger and smaller vessels.

Methods A special tissue chamber was developed for mounting, cannulating and perfusing porcine hemiretinas while controlling temperature, pH and oxygen saturation. The chamber was mounted in a flourescens microscope, and the effect on the diameter of larger arterioles, pre‐capillary arterioles and capillaries was studied after intravascular and extravascular addition of the thromboxane analogue U46619 and lactate (n=6 for each variable) and NMDA (preliminary).

Results In all vessel calibers the thromboxane analogue U46619 induced a significant contraction after extraluminal application (p<0.02), but not after intraluminal (p>0.13). Lactate had no effect on the diameter of non‐precontracted vessels (p>0.21), but in pre‐contracted vessels lactate relaxed the vessel diameter.

Conclusion The response to vasoactive compounds is different after intraluminal and extraluminal application, and the diameter response of vasoactive compounds is different in larger and smaller retinal vessels. The dilating effect of lactate depends on the state of contraction of the retinal vessel.
Retinal vessel oxygen saturation in diabetic patients with and without cardiovascular disease and its association with renal function
Authors: HEITMAR R , BLANN A
Published: August 2014

Purpose To explore the association of renal function and retinal vessel oxygen saturation in patients suffering from diabetes and cardiovascular disease.

Methods We examined three groups of patients (1: Diabetics, 2: Diabetics with cardiovascular disease and 3: patients suffering from cardiovascular disease without diabetes). All patients Intraocular Pressure, Systemic Blood Pressure and Dual Wavelength Retinal Vessel Oxygen Saturation (arterial and venous vessel saturation and a‐v saturation difference) and Retinal Vessel Calibers were measured following phlebotomy to determine their HbA1c levels. Markers of renal function (ceratinine, eGfr and uACR) were measured in all patients.

Results All three groups were age matched (1: 63 (10)yrs; 2: 64 (9)yrs and 3:65 (10)yrs). Unsurprisingly HbA1c was significantly different between groups (p<0.001), while Intraocular Pressure and Systemic Blood Pressure variables were comparable. While arterial and venous oxygen saturation were comparable between groups, the cardiovascular group had the lowest venous saturation, resulting in the highest a‐v values but this was not statistically significant. Markers of renal function showed a statistically significant correlation with a‐v saturation values in patients suffering from both: diabetes and cardiovascular disease (eGfR and a‐v‐saturation: r=0.65, p=0.001) but not in those suffering from cardiovascular disease alone (r=0.36, p=0.063).

Conclusion Retinal vessel oxygen saturation parameters appear to be associated with renal function in patients suffering from both diabetes and cardiovascular disease.