bluuebunny/crossref_metadata_2025 huggingface dataset:
Intravitreal aflibercept (IVT‐AFL) for macular edema secondary to CRVO: Results of COPERNICUS and GALILEO studies
Authors: CREUZOT C
Published: November 2013

Purpose Evaluate efficacy and safety of IVT‐AFL for treatment of macular edema due to CRVO.

Methods Patients randomized to IVT‐AFL 2‐mg (IVT‐AFL 2q4) or sham monthly for 24 weeks. COPERNICUS: all patients received IVT‐AFL PRN from week 24‐100 (IVT‐AFL 2q4PRN and shamIVT‐AFL PRN). GALILEO: IVT‐AFL PRN was administered to IVT‐AFL group from week 24‐76 and sham group from week 52‐76.

Results Proportion of IVT‐AFL 2q4PRN and shamIVT‐AFL PRN patients gaining ≥15 letters was 56.1% vs 12.3% and 49.1% vs 23.3%, respectively, at week 24 and 100 (COPERNICUS) and 60.2% vs 22.1% and 57.3% vs 29.4%, respectively, at week 24 and 76 (GALILEO; all P<0.01). Mean change in BCVA was +17.3 vs ‐4.0 (P<0.0001) and +13.0 vs +1.5 ETDRS letters (P=0.007) at week 24 and 100 (COPERNICUS) and +18.0 vs +3.3 (P<0.001) and +13.7 vs +6.2 letters (P=0.007) at week 24 and 76 (GALILEO) in IVT‐AFL 2q4PRN and shamIVT‐AFL PRN groups, respectively. Mean reduction from baseline CRT was 457.2 vs 144.8 µm (P<0.001) and 390.0 vs 343.3 µm at week 24 and 100 in COPERNICUS and 448.6 vs 169.3 µm (P<0.0001) and 389.4 vs 306.4 µm at week 24 and 76 in GALILEO in IVT‐AFL 2q4PRN and shamIVT‐AFL PRN groups, respectively. Most frequent ocular SAEs in IVT‐AFL 2q4PRN group were cataract (COPERNICUS) and macular edema (GALILEO). APTC ATEs occurred only in COPERNICUS (2 (1.8%) IVT‐AFL, 2 (2.7%) sham).

Conclusion IVT‐AFL treatment resulted in early, sustained VA gains. Maintenance of VA gains with an extended treatment interval after initial monthly dosing depended on monthly monitoring. Long‐term fixed dosing regimens may be a better treatment paradigm.

Commercial interest
Biomaterials in ophthalmic applications ‐ IOL´s and keratoprosthesis
Authors: STORSBERG J , SCHMIDT C , DUNCKER G , SCHRAGE N , SEL S
Published: November 2013

Biomaterials can be regarded as synthetic or non‐living native materials used in therapeutic approaches. This direct contact with body tissue manifests itself in a wide spectrum of chemical, physical and biochemical interactions. In ophthalmology, biomaterials find their application in the development of intraocular lenses (IOL´s) and keratoprosthesis. The chemical nature of these materials encompasses the full spectrum of physico‐chemical properties of matter, e.g. hydrophilic and hydrophobic poly(meth)acrylates, silicones and fluorinated polymers. Concordantly, the intended use and functionality of the implant necessitates the strict selection of the desired chemical and physical characteristics of the materials to be used, if not the de‐novo creation of suitable substances. In addition, modification of surfaces or the creation of gradual changes in material properties by co‐polymerizations or alternative means of tailoring peculiar aspects of the device may be required to achieve reasonable or functional substitution of the diseased tissue, all the while maintaining ease of the device’s usage by the caring physician and, above all, uncompromised patient’s safety in the intended use of the device throughout its lifecycle.
Immunomodulatory effects of gene therapy in composite corneal grafts
Authors: PASTAK M , SINGER BB , SCHWARTZKOPFF J , SABAN D , CZUGALA M , DANA R , STEUHL KP , ERGüN S , FUCHSLUGER TA
Published: November 2013

Corneal allografts overexpressing anti‐apoptotic protein p35 in BALB/c mice have shown significantly reduced delayed‐type hypersensitivity. However, the precise mechanisms responsible for altered immune response have been unclear. Based on previous data, we hypothesized that expression of p35 in corneal epithelium reduces the priming of T lymphocytes in draining lymph nodes after transplantation. In our results, mixed lymphocyte reaction with C57BL/6 splenocytes revealed statistically decreased frequency of CD4+ T cells in allograft group treated with p35 compared to other allogeneic groups. These findings provide new immunological insights on priming of T cells modified by genetically treated composite allograft to improve transplant survival.
Current available platforms for femtosecond laser cataract surgery
Authors: ALVAREZ DE TOLEDO J , BARRAQUER RI , NAGY Z
Published: November 2013

Different femtosecond laser platforms are nowadays available. Main differences as the particular approaches in anterior segment imaging techniques to focus the laser pulses precisely, interface designs to efficiently and safely dock the patient´s eye and software options in each platform will be presented and discussed.
Proven advantages of femtosecond laser cataract surgery
Authors: NAGY Z
Published: November 2013

Results with femtosecond laser cataract surgery especially with premium lenses (multifocal and accomodative lenses) will be presented. In peer‐reviewed articles was shown the superior results with better posterior chamber lens position, less PCO formation, more favorable results with postoperative higher order aberrations and vision quality will be discussed. The method also useful after ocular trauma, in eyes with loose zonules, in PEX syndrome, in white tumescent cataract and possibly in pediatric cataract. These result will be presented during the course.
Filamentary keratitis epidemiology
Authors: PRONKIN I , MAYCHUK D , VASILJEVA O
Published: November 2013

Purpose To analyze concomitant pathology contributing to filamentary keratitis.

Methods We examined 38 patients (76 eyes) with filamentary keratitis. All of them were consulted by co‐specialists (internist, endocrinologist, reumatologist) with the object to reveal concomitant diseases. The treatment regimen included keratoprotectors, artificial tears, 0,1% dexamethasone, 0,05% cyclosporine. Besides, in case of decompensated concomitant disease patients were treated by appropriate specialist. Among investigative methods were: biomicroscopy, Shirmer test – 1, TBUT‐test. Follow‐up period was 3‐5 months.

Results Among concomitant pathology we revealed:  Thyroid gland disfunction (hypothireosis) – 34,2 %  Rheumatoid arthritis – 21,1 %  Sjögren's Syndrome – 2,6 %  Diabetes mellitus of 2nd type – 7,9 %  Combination of rheumatoid arthritis and thyroid gland dysfunction (nodes against a background of euthyreosis) – 10,5 %  Combination of diabetes mellitus of 2nd type and thyroid gland dysfunction – 13,2 %  Neither endocrine nor rheumatoid diseases revealed – 10,5 %. Among them 1 patient after previous PRK. Shirmer test – 1 results were variable and no appropriateness with treatment regimen was found. TBUT‐test data before treatment were low (6‐9 sec.) with an increase up to 9‐11 sec. after the treatment.

Conclusion 89,5 % of patients had endocrine pathology or rheumatoid diseases or their combination. With this in view, we may consider filamentary keratitis not as a form of severe dry eye syndrome, but as a separate dystrophic corneal disorder with dry eye as its symptom.
Quercetin counteracts the cellular damage caused by HNE and inhibits inflammation in ARPE‐19 cells
Authors: HYTTI M , PIIPPO N , SALMINEN A , KAARNIRANTA K , KAUPPINEN A
Published: November 2013

Purpose Age‐related macular degeneration(AMD) is the leading cause of blindness in the western world. And despite extensive research many questions about disease progression and formation still remain unanswered. One of the driving factors of AMD is a chronic inflammatory process, stimulated by life‐long exposure to light and oxidative stress. In the current study we try to evaluate the anti‐inflammatory properties of Quercetin, a plant derived polyphenol, and to determine the pathways by which it inhibits inflammation.

Methods Cultured ARPE‐19 cells were treated with the lipid peroxidation endproduct 4‐Hydroxynonenal (HNE) to induce an inflammatory response. Quercetin was added 1 hour after stimulation with HNE to assess its power to suppress an already activated inflammatory response. The effects of the treatment on intracellular inflammation were measured with ELISA and quantitative Real‐Time PCR. Cell viability was assessed using the lactate dehydrogenase (LDH)‐assay.

Results Our results show that Quercetin decreased the levels of the pro‐inflammatory cytokines MCP‐1 and IL‐8. It also protected the cells from HNE‐induced toxicity, as was evidenced by a decrease in LDH levels. Quercetin lowered the levels of mitogen‐activated protein kinase (MAP) p38 and of phospho‐CREB but did not affect the levels of NF‐κB or the DNA binding efficacy of its subunit p65.

Conclusion Our results show that Quercetin can reduce the inflammatory response in retinal pigment epithelial cells by down regulating the MAPK pathway and decreasing the phosphorylation of CREB. Furthermore it is able to protect cells from death induced by oxidative stress. Quercetin may, therefore, be a valuable tool in the therapy of inflammation in AMD.
In vivo toxicity evaluation of mannitol included in freezed dry PEA‐III microparticles
Authors: ROJAS B , DE HOZ R , SALAZAR JJ , RAMíREZ AI , GALLEGO BI , TRIVIñO A , ANDRéS‐GUERRERO V , HERRERO‐VANRELL R , RAMíREZ JM
Published: November 2013

Purpose To analyze short term toxicity of the mannitol included (3,375 µg; 0,225%) in an unilateral single intravitreal (ITV) injection (1.5µl) of freezed dry polyester amide (PEA) microparticles (“MPs”).

Methods SD rats were divided into: G1: ITV Mannitol plus BSS; G2: ITV BSS; G3: Aged‐matched control. Clinical examination and animal sacrifice were performed 24 hours, 3 and 7 days post‐injection (PI). Tissue sections were processed for H&E and immunofluorescence with antibodies against GFAP, Iba‐1 and MHC class II.

Results No clinical signs of inflammation were observed at any time point of the study. H&E: The conjunctiva in G1 and G2 had an inflammatory infiltrate that peaked at 24 hours and decreased by day 3. On day 7, tissues looked as aged‐matched control. In both groups, some inflammatory cells were found in the vitreous 24h and 3 days PI, the latter being more intense in G1. Immunostaining: the reactivity of astrocytes and Müller cells in G1 was higher than in G2 up to day 3. In day 7 PI, there was a mild and sectorial reaction of Müller cells in G1. Microglia in G1 and G2 showed morphological signs of activation 24h and 3 days PI, the reaction being stronger in G1. On day 7 PI: i) all microglia in G2 and the microglia in the outer retina in G1 looked like control; ii) the microglia in the inner retina showed signs of activation in G1. No MHC‐II upregulation was found in either group.

Conclusion Intravitreal injection of 1.5µL of mannitol (3,375 µg; 0,225%) induces changes in the glial cells of SD rat retina that should be taken into account in biocompatibility assays after intravitreal injections of mannitol freezed dry microparticles.
Assessment of polyesteramide of PEA Microparticles for in vivo intraocular injections
Authors: DE HOZ R , ROJAS B , RAMíREZ AI , SALAZAR JJ , GALLEGO BI , TRIVIñO A , ANDRéS‐GUERRERO V , HERRERO‐VANRELL R , MIHOV G , DIAS A , ZONG M , RAMíREZ JM
Published: November 2013

Purpose To analyze polyesteramide (PEA) microparticles (“MPs”) interaction with reagents used in histological analysis and their compatibility with the steps required for ocular injection.

Methods Unloaded‐ and dye‐loaded (Chromoionophore II) PEA III MPs suspended in PBS/mannitol were: i) analyzed under light and fluorescence optic microscopy; ii) exposed to reagents, solutions and processes required to perform histological procedures; iii) released through different needle gauges and quantified in a Neubauer chamber. Rat eyes were divided into two groups: intravitreal injection (n= 20) and subtenon/subconjuntival injection (n=24). After sacrifice, tissues were processed as retinal whole‐mount and cryosections.

Results i) PEA III MPs were stable when contacted with distilled water, PBS, 4% PF and 2% glutaraldehyde; ii) PEA III MPs lost shape or dissolved when in contact with Xylene, EtOH or acetone; iii) freezing at ‐20ºC and heating at 60ºC does not impact particles re‐dispersion, shape and polydispersity; iv) no significant differences in MPs number released through different needle gauges (25G, 27G, 30G, 32G) were found; v) in unstained tissues, MPs preserved their morphological characteristics and coalesced into depots.

Conclusion MPs: i) are compatible with some of the steps required for routine histological processing. ii) can be released through needle gauges used in human clinical setting; iii) the injection should be done during the 30 minutes following suspension preparation.
Aquaporin expression in the human retinal pigmented epithelial cell line ARPE‐19
Authors: SALIK D , MOTULSKY E , PERRET J , CASPERS L , DELPORTE C , WILLERMAIN F
Published: November 2013

Purpose Aquaporins (AQPs) are a family of transmembrane channel proteins permeable to water. They are likely to play an essential role in the outer blood retinal barrier allowing passive water transport through the retinal pigmented epithelium (RPE). The identification of AQPs expressed in the RPE could contribute to a better understanding of the development of macular edema in several eye diseases such as diabetic retinopathy. However, the type of AQPs expressed by the RPE is currently a subject of controversy.

Methods We investigated the expression of AQPs in the human RPE cell line ARPE‐19, a model of human RPE. First, AQPs mRNA expression was determined by quantitative real‐time PCR (qRT‐PCR). Furthermore, protein expression was analyzed by both immunofluorescence (IF) and Western blot (WB).

Results The mRNA of AQP1, AQP4, AQP6 and AQP11 were expressed in ARPE‐19 cells. However, the expression of AQP3, AQP4, AQP6, AQP7, AQP8, AQP9, AQP11 and AQP12 were found by IF. Finally, the expression of AQP4 and AQP6 was found by WB.

Conclusion In conclusion, several AQPs were detected both at the mRNA and at the protein level in ARPE‐19 cells and may account for water movement in those cells.
Effect of systemic hyperoxia on retinal oxygen saturation
Authors: TOLD R , PALKOVITS S , BOLTZ A , NAPORA KJ , SCHMIDL D , GARHöFER G , SCHMETTERER L
Published: November 2013

Purpose Several groups have reported that 100% oxygen breathing caused an increase in retinal venous oxygen saturation. In the present study we set out to study the effects of 100% oxygen breathing on retinal blood flow and retinal oxygen saturation to gain more insight into the regulation of retinal oxygenation.

Methods 30 healthy volunteers were included into the present study. The effect of 100% oxygen breathing on retinal blood velocities was performed using laser Doppler velocimetry (LDV). Retinal vessel diameters were measured with the Dynamic Vessel Analyzer (DVA, Imedos, Germany). Retinal oxygen saturation was evaluated in retinal arteries and retinal veins using spectroscopy also employing the DVA. The effect of 100% oxygen breathing on systemic oxygen tension was evaluated based on arterialized blood samples drawn from the earlobe.

Results Breathing 100% oxygen caused systemic hyperoxia as evidenced from a pronounced increase in systemic oxygen tension (p < 0.001). Oxygen saturation increased in both retinal arteries and retinal veins (p < 0.05 each) but the effect in veins was more pronounced. As expected we observed a decrease in retinal vessel diameters, retinal blood velocities as well as in retinal blood flow (p < 0.001 each).

Conclusion The results are compatible with the idea that increased venous oxygen saturation during 100% oxygen breathing is due to a pronounced decrease in retinal blood flow. In addition, our data indicate unchanged retinal oxygen extraction during hyperoxia.
IL18 does not reduce choroidal neovascularization and causes retinal dysfunction in mice
Authors: YASUMA T , HIRANO Y , KIM Y , YASUMA R , FOWLER B , CARVALHO A , GELFAND B , AMBATI J
Published: November 2013

Purpose It was reported that intravitreous administration anti‐mouse IL18 antibody increases the size of laser‐induced choroidal neovascularization (CNV) lesions in mice (Doyle et al. Nat Med 2012). IL‐18 administration was therefore proposed as a potential therapeutic for CNV, although this hypothesis was never directly tested. Here, we determined the effect of IL‐18 injection on laser CNV in mice, and also show for the first time that IL‐18 is toxic to retinal function.

Methods Laser photocoagulations were performed to perforate Bruch’s membrane followed by intravitreous injections of recombinant IL‐18 (rIL‐18) or PBS, and the eyes were collected and analyzed on the day 7 after laser treatment. Laser‐induced CNV lesions stained with isolectin B4 were imaged by a confocal microscope system (Leica). Mice receiving rIL‐18 or PBS were subjected to electroretinography 7 days after sub‐retinal injection. RPE flat mounts of rIL‐18 or PBS treated wild type, Fas‐/‐, and FasL‐/‐ mice were stained for intercellular junctions.

Results Average CNV volume was not different in eyes treated with recombinant IL‐18 compared to vehicle treated. Wild‐type mice receiving rIL‐18 had RPE degeneration, but the degeneration did not occur in Fas or FasL knockout mice. We also injected plasmids coding pro‐IL‐18 and mature IL‐18, and found mature IL‐18 didn't change CNV volume but caused degeneration. Wild type mice receiving rIL‐18 injections showed lower amplitude in electroretinography compared to vehicle injected eyes.

Conclusion IL‐18 injections did not reduce CNV. Also, IL‐18 administration induced RPE degeneration via a Fas/Fas ligand‐dependent pathway.
Ocular and systemic distribution of MRZ‐99030 in pigmented mouse, rat, rabbit and non‐human primate by quantitative tissue analysis
Authors: STRUBLE C , PRESCOTT E , KLEIN KU , WEGENER N
Published: November 2013

Purpose The ocular tissue distribution and systemic pharmacokinetics of MRZ‐99030 was determined after single or repeated topical ocular dose regimens of MRZ‐99030 to pigmented mice, rats, rabbits, and non‐human primates. MRZ‐99030, an amyloid‐β aggregation modulator, is currently under development for the treatment of glaucoma and AMD, which are the leading causes of blindness and represent diseases with high unmet medical need.

Methods Dutch Belted rabbits, Cynomolgus monkeys, Dark Agouti rats, and C57/BL6 mice received single or repeated bilateral topical ocular doses of MRZ‐99030. Ocular tissues and plasma were collected up to 24h after dosing and analyzed for MRZ‐99030 by liquid chromatography‐mass spectrometry (LC‐MS).

Results MRZ‐99030 was readily absorbed into ocular tissues for all species with highest concentrations observed in the cornea and conjunctiva. MRZ‐99030 was also found in the ocular tissues of the posterior segment (choroid with RPE and retina) at all time points. Pharmacokinetics show MRZ‐99030 in all tissues and systemically, with elimination half‐lives that indicate somewhat sustained concentrations in melanin containing tissues. Concentrations in ocular tissues, in particular for the retina, increase with an increase in dose level (mouse and rat) and dose frequency (all species).

Conclusion The results show that MRZ‐99030 is absorbed into the ocular tissues in all species following topical administration and is readily distributed to the posterior segment of the eye, including the retina. Therefore, this finding strongly supports that MRZ‐99030 is able to modulate the Aß aggregation in the target tissue of glaucoma and AMD.
Late results of sclera reconstructive surgery aimed at preventing the progression of myopic macular dystrophies
Authors: MARKOSSIAN G , TARUTTA E , IOMDINA E , KRUZHKOVA G
Published: November 2013

Purpose To assess the long‐term efficiency of scleroplasty performed using a simplified technique of buckling the posterior pole in patients with congenital myopia complicated by macular dystrophy and posterior staphyloma of the sclera

Methods The surgery was performed according to Snyder–Thompson technique in which the buckle made of a biologically active synthetic graft was sutured using a simplified technique of its localization at the posterior pole. 42 surgeries were administered to 34 patients aged 13–43 with myopia of –11.5 to –31.0 D. The shape and stage of staphyloma was determined by ultrasound scanning or with an ophthalmoscope. The follow‐up period reached 3‐8 yrs (4.2±1.3 yrs).

Results Next day after surgery, flattening of the staphyloma can be seen on B‐scan. The axial length becomes 1.0‐2.0 mm shorter, the acoustic density of the posterior pole of the sclera increases by 5.3 dB, visual acuity shows a 0.1‐0.3 growth, while the refraction is 1.5‐2.5 D lower. The late follow‐up results (6‐8 years) demonstrated myopia stabilization in 90.2% of cases. Myopia progression rate turned out to be half as slow as prior to the surgery, and B‐scan showed a sustainable flattening of the staphyloma. Over the whole observation period, no new pathological processes emerged in the macular area, while no existing pathological processes showed progression

Conclusion Scleroplastic surgery combined with posterior pole bucking with a biologically active synthetic graft should be recommended for the treatment of high complicated myopia, the prevention of staphyloma progression, myopic macular dystrophies and vitreomacular traction syndrome.
Evaluation of choroidal thickness depending on the stage of diabetic retinopathy by SD‐OCT
Authors: CHAKER N , MGHAIETH F , DALLELI F , CHEBIL A , BOURAOUI R , MRABET A , EL MATRI L
Published: November 2013

Purpose To evaluate the choroidal thickness in diabetes and study its variation with different stages of diabetic retinopathy (DR).

Methods Retrospective study of 155 eyes of 83 diabetic patients treated between June 2011 and October 2012. All patients benefited from a complete ophthalmologic examination, laboratory tests conventional A‐scan ultrasonography,choroidal and retinal tomography

Results The mean age patients was 57,54 with. There was not diabetic retinopathy DR(‐) in 36,77% of cases. There was a minimal noproliferative diabetic retinopathy NPDR in 17,41%, moderate NPDR in 15%, moderate preproliferative PPDR in 5,8%, severe PPDR in 11,6%, moderate PDR in 6,45%, severe PDR 4,51% and 2,58% in complicated PDR. The tomographic study objectified a thinner choroid in diabetic patients, with mean choroidal thickness (MCT=263+30µm) and subfoveal thickness (SFVCT=261.4+33.8µm). In the group with RD (+), choroid thickness (p=0,04), significantly decreased compared to DR (‐) group, but not correlate with the severity of DR. There was, however, a statistically significant difference between the different stages of DR for the following variables: HBA1C, visual acuity and near VA (p<10‐3). The SD‐OCT has objectified a macular retinal thickening which increased significantly with the severity of DR (p<10‐3). Moreover, the choroidal thickness varied little between the various stages of DR. We found a statistically significant correlation between SFVCT: duration of hypertension, the rate group. While the MCT was significantly correlated with ser

Conclusion SD‐OCT now possible to explore the choroid, measure its thickness and assess its variation with the DR stages
Intravitreal ranibizumab following bevacizumab for macular edema due to retinal vein occlusion
Authors: DURIEUX P , LABALETTE P
Published: November 2013

Purpose Macular edema is the main cause of visual impairment secondary to retinal vein occlusions (RVO). Current treatment is based on intravitreal injections of corticosteroids or VEGF inhibitors. Bevacizumab was first used in the eye on an off‐label basis, whereas ranibizumab was approved in this indication in January 2012 in France. Our work’s objective was to analyse the becoming of patients who received bevacizumab then ranibizumab successively in management of RVO.

Methods This study includes the patients treated effectively with intravitreal bevacizumab for macular edema due to RVO and next treated with intravitreal ranibizumab. We included 9 patients presented with a central retinal vein occlusion (CRVO) and 6 patients with a branch retinal vein occlusion (BRVO). Ophthalmological examination performed after intravitreal injections consists in logMAR visual acuity and central macular thickness measurement by OCT.

Results Intravitreal injections of anti‐VEGF allowed an improvement of the visual acuity and a reduction of the central macular thickness. Final visual acuity was better after treatment with ranibizumab than after bevacizumab in patients presenting with CRVO ( the average gain of visual acuity was 0.30 logMAR). No infectious complication was noted.

Conclusion The therapeutic transition from bevacizumab to ranibizumab stabilizes both visual acuity improvement and decrease of macular thickness even in long time treated patients, despite vision impairment produced by old edema, worsening cataract, or apparition of retinal ischemia areas. In this short series of patients, replacement of bevacizumab by ranibizumab didn’t have negative impact on visual results despite treatment was continued on a longer time course.
Optic disk changes in retinal vein occlusion and correlated factors
Authors: SOO GEUN JOE , SUNG KR , LEE KS , LEE JR , CHAE JB
Published: November 2013

Purpose To evaluate optic disk changes in retinal vein occlusion (RVO) patients and to find risk factors related to increasing cup to disk ratio (C/D ratio)

Methods We used data collected in Korean RVO survey. It was retrospective, cross‐sectional, nation wide and multicentral study. Data of RVO patients were collected from 41 clinical sites which joined in Korean RVO survey from April 2010 to December 2011. Patients’ whole follow up data at base line, 3‐month, 6‐month, 9‐month and 12‐month were collected and analyzed. Among the data, we used fundus photographs (FDP), fluosrecein angiogram (FA) and medical record at base line, 6‐month and 12‐month. C/D ratio was analyzed by three glaucoma specialists. FDP and FA findings including disk hemorrhage, disk edema, non‐perfusion area, disk leak etc and medical records including intraocular pressure (IOP), intravitreal injection of bevacizumab (IVB), steroid therapy etc were analyzed for correlation to C/D ratio increasing.

Results Among enrolled 557 patients, 127 patients met the inclusion criteria. 57 patients were branch retinal vein occlusion (BRVO) and 73 patients were central retinal vein occlusion (CRVO). C/D ratio increased from 0.45 at base line to 0.52 at 12‐month (p<0.001; paired T‐test). Non‐perfusion area, disk edema, disk hemorrhage and disk leak at base line and IOP at 12‐month showed correlation to increase of C/D ratio (p=0.021, p=0.001, p<0.001, p=0.001, p=0.016 respectively). But IVB and steroid use were not related to increased C/D ratio. Detailed subgroup analysis (CRVO, BRVO) will be appeared on the presentation.

Conclusion Eyes with RVO showed increasing C/D ratio. Base line perfusion status and disk damage had correlations to increase of C/D ratio. .

Commercial interest
Retinal tubulations in geographic atrophy associated with age‐related macular degeneration
Authors: RUIZ MORENO JM , LUGO FL , RUIZ‐MEDRANO J , MONTERO JA , DONATE J
Published: November 2013

Purpose To describe the presence of retinal tubulations at the boundaries and within areas of retinal atrophy in patients with geographic atrophy (GA) associated with age‐related macular degeneration (AMD) by spectral‐domain optical coherence tomography (SD‐OCT).

Methods 82 consecutive patients, 50 years or older with GA associated with AMD were examined between January 2012 and July 2012. Patients were evaluated by SD‐OCT and fundus autofluorescence (FAF). Patients with single or multiple and well‐defined areas of atrophy in whom retinal layers could be visualized were included. FAF was performed at the same time that OCT (Spectralis, Heidelberg Eng). Three acquisition protocols were performed: high‐resolution horizontal B‐scan for foveal study and two macular cubes to evaluate the whole macular surface (19 horizontal and 19 vertical B‐scans centred on the fovea). Main Outcomes Measures: Presence of spherules/tubulations within the atrophic area in patients with GA associated with AMD.

Results 50/82 patients with GA presented with single or multiple areas of atrophy with identifiable retinal layers. Clearly visible and slightly hyper/hyporeflective round, rosette‐like, spherule‐shaped structures were localized in the outer nuclear layer (ONL). These structures occasionally contacted the external limiting membrane. They were adjacent to the margin between preserved retina and atrophic area and within the atrophic area. In these cases, uniformly hypereflective, hyporeflective and isoreflective spherules surrounded by hyperreflective halo that might correspond with retinal tubulation were present in the same eye.

Conclusion Retinal tubulations can be observed in the ONL in patients with GA associated with AMD.
Retinal arteriolar diameter response to flicker light provocation ‐ A useful marker for risk stratification in cardiovascular disease?
Authors: HEITMAR R , BLANN A , SUMMERS AJ
Published: November 2013

Purpose To to evaluate the benefit of bilinear and linear fitting to characterize the retinal vessel dilation to flicker light stimulation for the purpose of risk stratification in cardiovascular disease.

Methods Methods Forty‐five patients (15 with coronary artery disease (CAD), 15 with Diabetes Mellitus (DM) and 15 with CAD and DM) all underwent contact tonometry, digital blood pressure measurement, fundus photography, retinal vessel oximetry, static retinal vessel analysis and continous retinal diameter assessment using the retinal vessel analyser (and flicker light provocation). In addition we measured blood glucose (HbA1c) and keratinin levels in DM patients.

Results Results With increased severity of cardiovascular disease a more linear reaction profile of retinal arteriolar diameter to flicker light provocation can be observed.

Conclusion Absolute values of vessel dilation provide only limited information on the state of retinal arteriolar dilatory response to flicker light. The approach of bilinear fitting takes into account the immediate response to flicker light provocation as well as the maintained dilatory capacity during prolonged stimulation. Individuals with cardiovascular disease however show a largely linear reaction profile indicating an impairment of the initial rapid dilatory response as usually observed in healty individuals.
Ocular morpho‐functional analysis: Comparison between prematurely‐born and born at term children
Authors: SPALLONE L , LOMBARDO S , RUBERTO G , BIANCHI PE , TINELLI C , GUAGLIANO R
Published: November 2013

Purpose To evaluate the differences in ocular morpho‐functional parameters between preterm and born at term children

Methods 50 eyes of 25 prematurely‐born children (gestational age ≤34 weeks and birth weight ≤ 1495g) were compared to 40 eyes of 20 children born at term. The age at examination was 6‐8 years old. In preterm group 18 eyes had retinopathy of prematurity (ROP): 8 were affected by mild ROP (stage 1‐2) and 10 by severe ROP (stage 2‐3), treated with laser photocoagulation. The children were submitted to a complete ophthalmic evaluation including ETDRS visual acuity (VA), contrast sensitivity (CS), pattern visual evoked potential (pVEP), retinal nerve fiber layer thickness (RNFL, disc area) and central macular thickness (CMT) measured by spectral domain optical coherence tomography (SD‐OCT)

Results No statistically significant differences were found in functional or structural data between prematurely‐born and born at term children except higher values for disc area in preterm. Conversely many statistically significant differences (VA, CS, P100 amplitude, disc area and CMT) emerged between control and preterm group affected by ROP, especially in severe ROP

Conclusion Many differences in ocular morpho‐functional parameters are pointed out between full term and preterm children affected by ROP. The most important dissimilarities are in stage 3. Maybe it can be correlated with treatment’s damage or due to incomplete development of optic pathways. Because the principal differences are in functional parameters (VA, CS, VEP), without significant morphological changes, we hypothesize that impairment of vision in severe ROP is due not only to retinopathy of prematurity but also to brain damage.
Definition of a normative basis for peripapillary nerve fibers thickness in childhood with sd‐oct
Authors: FACON G , DEFOORT‐DHELLEMMES S , LABALETTE P , ROULAND JF
Published: November 2013

Purpose Since its inception, optical coherence tomography (OCT) has radically changed our way to practice ophthalmology. Yet, the analysis of databases of various machines has no value for patients under 18 years old. In this work we define a normative basis of the thickness of peripapillary nerve fibers in children with SD‐OCT.

Methods We randomly selected 99 children (192 eyes) aged from 2 to 17 years. They were found to be healthy subjects with no history of eye disease and normal visual acuity. A study of the optic nerve head was conducted on Cirrus HD OCT. Two scans were performed in both eye to judge the good reproducibility of the measurement. We divided the population into three age groups (Group 1: 3‐7 years / Group 2: 7‐12 / Group 3: 12‐18 years) before setting the average thickness of each quadrant.

Results Group 1 included 10 patients (19 eyes). The results reflected an overall thickness of 100μm +/‐ 8 to the following distribution: temp: 77μm +/‐8 / Upper: 130 μm +/‐20 / nasal: 66μm +/ ‐10 / lower: 131μm +/‐12. Group 2 included 39 patients (74 eyes). The results reflected an overall thickness of 99μm +/‐ 8 to the following distribution: temp: 72μm +/‐9 / Upper: 126 μm + / ‐16 / nasal: 70μm +/‐13 / lower: 128μm +/‐16. Group 3 included 50 patients (99 eyes). The results reflected an overall thickness of 97μm +/‐ 11 for the following distribution: temp: 63 μm +/‐14 / Upper: 125μm +/‐16 / nasal: 72μm +/‐15 / lower: 128 +/‐19.

Conclusion The definition of a normative database in children is essential on OCT because it's integrated into the daily practice of the ophthalmologist. We define RFNL in children under 18 years old and find a very slight change over time, mainly in the temporal quadrant.
Functional vision of young adults with type i diabetes since childhood
Authors: SIISKONEN M , JäRVINEN K , HAUTALA N , FALCK A
Published: November 2013

Purpose To evaluate vision of young adults with type 1 diabetes (T1D) since childhood.

Methods During 1989‐90 the prevalence of diabetic retinopathy (DR) was evaluated in a population‐based cohort of 5‐16‐year‐old children with T1D living in the catch‐area of the Northern Ostrobothnia Hospital District, Finland. These 216 individuals were contacted 18 years later and evaluated for best corrected visual acuity (BCVA) LogMar, contrast sensitivity (CS) and stage of retinopathy. The CS test was performed using Vistech Chart at five spatial frequencies, 1.5, 3.0, 6.0, 12.0 and 18.0 cycles per degree (cpd). Retinopathy was diagnosed from fundus photographs, and data on past laser treatment and vitreoretinal surgery were also collected.

Results 106 patiens took part in the study. There were 65 males (61%) and 41 females (39%) aged 30±3 years. The duration of diabetes was 23±4 years. Two of the subjects were blind in the right eye. The CS was evaluated of 210 eyes of 106 patients. It was normal in all cpds studied in 93 of 210 eyes, or 39 of 106 patients, and abnormal in one or several cpds in 117 eyes. Abnormality was most likely to be found at cpd 6.0; this was the case in 37% of the eyes. BCVA was 0.1 (LogMar) or better in 189/210 eyes. 34 patients had proliferative DR (PDR). CS was impaired in 30/34 (88%) of patients with PDR and 37/72 (51%) without PDR (p<0.001).

Conclusion The majority of young adults with T1D had good BCVA. However, CS was outside normal range in more than one half, and particularly in patients with PDR.
Change in the antioxidative capacity of extraocular muscles in patients with exotropia
Authors: JUNG S
Published: November 2013

Purpose We compared the oxidative stress and antioxidant capacities of the medial rectus muscles (MRMs) of control subjects and those with exotropia.

Methods A total of 40 MRMs from patients with exotropia and 40 MRMs from normal donor eyes (controls) were assessed. The mRNA levels of neuronal nitric oxide synthase (nNOS) and superoxide dismutase (SOD) were compared between the two groups using semi‐quantitative reverse transcription‐polymerase chain reaction. In addition, SOD1, SOD2, and lipofuscin levels were compared between the exotropic and control groups.

Results nNOS mRNA level was significantly higher in the exotropic group than in the control group (p < 0.001). Western blot analysis revealed that SOD1 and SOD2 expression levels were higher in the control group than in the exotropic group (p < 0.05). The relative lipofuscin fluorescence intensity was higher in the exotropic group than in the control group (p < 0.001).

Conclusion The MRMs of patients with exotropia had a redox imbalance status. Further study is needed to investigate whether this imbalance in antioxidant capacity is present in the extraocular muscles of other patients with strabismus.
Optic disc drusen and peripapillary subretinal neovascular membranes in children
Authors: BENNAI D , BENZERROUG M , BENHAMANA A , BREMOND‐GIGNAC D , MILAZZO S
Published: November 2013

Purpose Choroidal neovascular membranes are a rare cause of decreased vision in children with optic disc drusen. It can cause central vision loss by subfoveal progression of the choroidal neovascularization, serous macular detachment, or submacular hemorrhage.

Methods We report two cases of optic nerve head drusen in childhood. A 6 year‐old girl and a 12 year‐old boy were both refered to our hospital for optic disc edema with unilateral visual loss

Results Fundus examination showed pseudopapillary edema in the two cases. A pediatric check‐up with neurologic and cardiovascular exams and CT scan were performed. B‐Scan ultrasonography showed the presence of the optic nerve head drusen in both eyes but wasn’t identified on CT scan in the two cases. In our cases, optic disc drusen causes peripapillary haemorrhages proceeding from the same mechanism with a juxtapapillary choroidal neovascularization. Because of the location of the hemorrhage only monitoring was recommended. Partial spontaneous visual acuity improvement in 6 months was observed with regression of haemorrhage.

Conclusion Optic nerve head drusen are calciﬁed deposits arising from the prelaminar portion of the optic nerve, they have a reported prevalence of 0.4% in children. Although usually benign, their presence can sometimes be associated with serious ocular conditions and cause amblyopia. They have been reported to cause myriad local vascular complications, including central retinal artery and vein occlusion and peripapillary choroidal neovascularization.
Accuracy of fluorescein angiography (FA) based diagnosis for retinopathy of prematurity: Expert versus non expert graders evaluation
Authors: GUAGLIANO R , BARILLA D , BERTONE C , MAFFIA A , PERITI F , SPALLONE L , ANSELMETTI G , GIACOSA E , TINELLI C , BIANCHI PE
Published: November 2013

Purpose To evaluate accuracy and inter‐rater reliability of RetCam fundus images and digital camera fluorescein angiography (FA) images in acute retinopathy of prematurity (ROP) by comparing diagnoses given by trainee ophthalmologists with those provided by expert ophthalmologists.

Methods We conducted a multicentre retrospective observational study of diagnostic data from 60 eyes of 30 premature infants (average gestational age was 27 weeks, average birth weight 803 g) with classical ROP, stage II evaluated by RetCam 3 (Clarity, Pleasanton, CA) and fluorescein angiography. A staging grid with ocular fundus divided into 3 concentric zones and into 24 of 15° sectors centred around optic papilla was superimposed on 360° retina photomontages (Photoshop) acquired from RetCam and FA images. Non‐expert agreement with expert diagnoses was measured for each sector by means of Cohen’s kappa (Fleiss, 1981).

Results A high degree of concordance was found.Inter‐rater agreement expert versus non‐expert interpretations was really greater for fluorangiographic images than for RetCam ones with 0.61< k <1 for 58,5% of RetCam examined sectors and for 89,9% of FA examined sectors.

Conclusion FA images appear to be really clearer to interpret than RetCam images also by non‐expert ophthalmologists. Our result confirme than FA is very good examination technique with a high degree of reliability, even where trainee pratitioners are involved. ROP management can be improved by entrusting diagnostic responsibilities to trainee ophthalmologists, in order to extend access to correct diagnoses, recognition of threshold lesions and prompt treatment.
Mesenchymal stem cells as an alternative source of stem cells for ocular surface regeneration
Authors: HOLAN V , JAVORKOVA E , TROSAN P , KRULOVA M , ZAJICOVA A
Published: November 2013

Purpose To test the therapeutic potential of mesenchymal stem cells (MSCs) to replace limbal stem cells (LSCs) for the reconstruction of the heavily damaged ocular surface in an experimental mouse model.

Methods MSCs were isolated from the bone marrow of BALB/c mice and expanded in vitro. Their phenotypic markers, differentiation potential, immunoregulatory properties and ability to transdifferentiate into corneal epithelial cells were characterized. These in vitro expanded MSCs were transferred, using nanofiber scaffolds, onto the damaged ocular surface and their therapetic potential was evaluated.

Results MSCs can be expanded in vitro and retain their differentiation potential. When they were cultured in the presence of an extract from a damaged cornea or in the supernatant from cultured corneal cells, MSCs expressed cytokeratin CK12, a marker of corneal epithelial cells. In addition, MSCs displayed strong immunosuppressive properties in vitro and in vivo. After their transfer onto the damaged ocular surface, they supported corneal epithelial healing and inhibited the local inflammatory reaction. The therapeutic potential of MSCs was proven by the rapid regeneration of the ocular surface in the presence of MSCs and by an attenuation of the expression of proinflammatory cytokine genes after the injury.

Conclusion MSCs, which can be obtained relatively easily from bone marrow or adipose tissue, have the potential to replace LSCs for the reconstruction of the heavily damaged ocular surface.
High doses of fatty acids for treating severe dry eye disease
Authors: GEORGIOU T , NICOLAOU D , NEOKLEOUS A , MICHAEL S , IKONOMU C
Published: November 2013

Purpose To evaluate the effect of high doses EPA/DHA for the treatment of severe dry eye disease not responding to current treatments.

Methods 60 eyes (30 patients) with severe dry eyes not responding to current treatments were treated with 5g/day of EPA/DHA. Visual acuity, corneal fluorescein staining, tear break up time (TBUT) and subjective symptoms were noted.

Results 70% of patients used more than 5 treatment approaches before starting EPA/DHA. 83% of patients started with severe corneal fluorescein staining and 17% had moderate staining. At 3 months 44% had no staining and 55% had mild staining. TBUT improved from mean 1.78sec to 4.40sec at 3 months. There was substantial improvement (>50%) on subjective symptoms at 6 weeks of treatment.

Conclusion High doses of fatty acids can be used to improve the signs and symptoms of patients with severe dry eye disease not responding to current treatments.
Corneal nerve structure and function in patients with non‐Sjögren dry eye
Authors: LABBE A , LIANG Q , XU L , BAUDOUIN C , SUN X
Published: November 2013

Purpose To evaluate the relationship between the in vivo morphology of subbasal corneal nerves and clinical parameters in patients with non‐Sjögren dry eye disease (NSDD).

Methods Forty‐three patients with NSDD and 14 healthy age‐ and gender‐matched control subjects were included. Each patient underwent an evaluation of ocular surface disease symptoms using the Ocular Surface Disease Index (OSDI), tear film break‐up time (TBUT), corneal and conjunctival staining (Oxford scale), the Schirmer test, corneal sensation testing using the Cochet‐Bonnet esthesiometer and corneal subbasal nerve analysis with IVCM. One eye of each subject was included in the study.

Results Corneal sensitivity was significantly lower in the dry eye group as compared to the control group (P=0.001). Corneal subbasal nerves showed significant changes in dry eye patients as compared to normal subjects: lower density (P<0.001), increased tortuosity (P<0.001), number of beadings (P<0.001) and width (P=0.014). In patients with dry eye, corneal subbasal nerve density was correlated to age (r=−0.335, P=0.028), the Oxford scale (r=−0.562, P<0.001) and central corneal sensitivity (r=0.305, P=0.047). The maximum length of nerve fibers within a frame (MaxL) was correlated to the OSDI (r=−0.332, P=0.030) and the Oxford scale (r=−0.321, P=0.036). In multivariate analysis corneal subbasal nerve density remained correlated to the Oxford score (P<0.001). The Oxford score was also correlated to central corneal sensitivity (r=−0.317, P=0.039).

Conclusion NSDD patients presented significant alterations of subbasal corneal nerve structure and function. In NSDD, subbasal nerve alterations were correlated to ocular surface tissue damage.
The usefulness of corneal confocal microscopy to assessing and monitoring changes associated with hematopoietic diseases
Authors: WOJCIK L , WYLEGALA E , SMEDOWSKI A
Published: November 2013

Purpose Evaluation of corneal confocal microscopy in vivo to assess and monitor changes in the course of hematopoietic proliferative diseases.

Methods In 3 patients (2 males and 1 female) examined because of suspicion of an unknown keratopathy we performed the following: basic slit lamp examination, corneal scans using Scheimpflug camera (Pentacam, Oculus) and corneal confocal microscopy in vivo (Rostock Cornea module, Heidelberg Engineering Retina tomograph III). All patients were sent to hematology consult.

Results On a slit lamp examination we described macroscopic, polymorphic deposits of crystals, located in the full thickness of corneal stroma. In the image from Scheimpflug camera ‐ diffusive crystals causing increased hyperreflexive stroma. The corneal confocal microscopy images showed polymorphic crystalline deposits within the corneal stroma reaching the level of the endothelium from Bowmann membrane. After exclusion of hypercholesterolemia and cystinosis, patients were referred to the hematology consultation, where the following hematopoietic diseases were diagnosed: multiple myeloma, monoclonal gammopathy, light chain disease.

Conclusion Corneal confocal microscopy is a useful tool for the detection and differentiation of the etiology of crystalline keratopathy. Performed at the appropriate stage can help in the early detection of disorders of the hematopoietic system.