bluuebunny/crossref_metadata_2025 huggingface dataset:
Enzymatic vitreolysis
Authors: LE MER Y
Published: August 2014

One year after the official approval of ocriplasmin in the indication of symptomatic vitreo‐macular adhesion, the results and potential complications of enzymatic vitreolysis in « real life » are better understood. The best candidates for intravitreal injections seem to be the younger phakic patients with a symptomatic, focal and isolated (i.e. without associated epiretinal membrane) vitreous traction. The vast majority of traction release occurs before the end of the first week after injection. Ocriplasmin allow to close 40% of the small macular holes with vitreous traction, thus avoiding surgery with intraocular tamponade. The rate of complications is low but a specific one raises some concerns. A few cases of visual impairment, most of the time transitory even if long lasting, have been reported with modifications on OCT and ERG. An enzymatic cleavage of intraretinal laminin is a biologically plausible mechanism. Although rare, the potential complications of ocriplasmin have to be well known to avoid any unjustified risk in its clinical use. The better indications are now defined and to keep a good benefit/risk ratio, it would not be justified to take any chance by using enzymatic vitreolysis in the less favorable cases.

Commercial interest
Orphan drug for acanthamoeba keratitis (ODAK) project: validation of an acanthamoeba polyphaga keratitis model
Authors: GUEUDRY J , RAZAKANDRAINIBE R , HUMBERT C , AIFA A , FRANCOIS A , LE GOFF L , FAVENNEC L , MURAINE M
Published: August 2014

Purpose Acanthamoeba keratitis is a sight‐threatening infectious disease.The ODAK project (Orphan Drug for Acanthamoeba Keratitis) is a European research project, the objective of which is to assess safety and efficacy of PHMB (polyhexamethylene biguanide) eyedrops to provide the basis for marketing authorisation. The aim of our study is to develop a rat model of Acanthamoeba polyphaga keratitis suitable for this project.

Methods Sprague‐Dawley rats were injected in the left cornea stromal layer with Acanthamoeba polyphaga. A subconjunctival injection of 0.57 mg long‐acting betamethasone was administred and clinical examination was performed weekly. One rat was injected with culture media as sham. Corneal scrapings were performed for bacterial and parasitological cultures and real‐time PCR analyses. Paraffin‐embedded corneas were analysed after hematoxylin‐eosin and Schiff periodic acid staining.

Results Clinical infections were observed in 7/9 rats (78%). Trophozoites and/or cysts were detected in axenic culture after 1 month in 7/9 rats (78%). Acanthamoeba polyphaga DNA was detected in 7/9 rats (78%) by real‐time PCR. No clinical or microbiologic infection was detected in sham. Histological studies detected trophozoites and/or cysts only in 3/9 rats.

Conclusion In this study, a rat model of Acanthamoeba polyphaga keratitis was obtained with good correlation between clinical findings, culture and/or PCR findings. This model was found suitable for assessment of PHMB in animals. The research leading to these results has received funding from the European Union Seventh Framework Programme ([FP7/2007‐2013] under grant agreement n° 305661.
Rho‐associated kinase inhibition prevents pathological neovascularization after corneal trauma
Authors: SIJNAVE D , VAN BERGEN T , VANDEWALLE E , STALMANS I
Published: August 2014

Purpose The aim of this study was to investigate the effect of AMA0526, a selective and locally acting ROCK inhibitor on endothelial cells in vitro and in vivo by using a mouse corneal neovascularization (NV) model.

Methods In vitro, the effect of AMA0526 (0.1; 1 and 10 µM) on endothelial cell proliferation and FBS‐stimulated migration was investigated. A mouse corneal micropocket (MCM) model was used to study the in vivo effect of the ROCK inhibitor on corneal NV. A bFGF pellet was implanted in both eyes and topical administration was applied once daily using AMA0526 (0.1%) in one eye and vehicle (PEG/H2O) in the contralateral eye. Outcome was investigated by analysing vessel length, clock hours and NV area 7 days post implantation. Histological outcome was evaluated by immunohistochemical staining for inflammation (CD45) and angiogenesis (CD31).

Results HBMEC and HUVEC proliferation was significantly inhibited in a dose‐dependent manner by ROCK inhibition. AMA0526 (1 and 10 µM) also induced significant reduction of FBS‐stimulated endothelial cell migration, respectively by 29% and 40%. In the MCM model, AMA0526 treatment significantly reduced NV area by 28% and vessel length by 28%, as compared to vehicle treated. These effects were associated with a decreased infiltration of inflammatory cells (P<0.05; 32% reduction) and a reduced blood vessel density (P<0.05; 40% reduction) at day 7.

Conclusion AMA0526 inhibits endothelial cell proliferation and migration in vitro and is efficacious in reducing corneal NV after bFGF micropocket implantation. These results indicate that ROCK inhibition by AMA0526 may have therapeutic value for the treatment of pathological corneal NV.
3D reconstruction of corneal endothelial cell shape: new insight in structure‐function relationships
Authors: HE Z , BERNARD A , DEFOE D , PISELLI S , ACQUART S , FOREST F , DUMOLLARD JM , PEOC'H M , GAIN P , THURET G
Published: August 2014

Purpose Corneal endothelial cells (CECs) support the pump‐leak theory explaining the maintenance of corneal transparency. CEC are highly polarized with a pole facing aqueous humor having an hexagonal shape bordered by apical tight‐junctions that control permeability. The interdigitated shape of basolateral membranes, described in the late 70’s, are much less known although they bear most of the pumping sites. Aim: to revisit the shape of CEC with modern microscopy and 3D reconstruction.

Methods Optimized methods of immunolocalization (fixation and antigen retrieval) were applied on flat mounted whole cornea (fresh or after organ culture). The subcellular structures were distinguished by visualizing apical pole with actin, myosin and ZO‐1; lateral membranes with NCAM (CD56), connexion 43, vimentin and tubulin, and the basal pole with integrin. Stacks of high magnification images were acquired with a confocal microscope with a 150nm pitch. 3D reconstruction was performed with imageJ using convolve and Gaussian blur filters, and a model was defined.

Results A 3D map of all markers was obtained. In particular, CD56 perfectly outlined the basolateral membranes of CEC. The 3D model highlighted the dramatic increase in membrane surface due to basolateral expansions.

Conclusion CD56 staining pattern and especially the presence of numerous interdigitations should be considered as a hallmark for functional CEC and their study should therefore be integrated in quality controls of CEC production for regenerative medicine processes. Modifications of this 3D structure should also be studied in endothelial diseases. Grant: IFRESIS, St‐ETIENNE METROPOLE
The Boston type 1 keratoprosthesis and endophthalmitis: a systematic review
Authors: COLE ST , AVADHANAM VS , LIU CSC
Published: August 2014

Substituting the natural cornea is no easy task. Researchers have shaped and honed methods for over 200 years, seeking the ultimate surrogate. Today the Boston type 1 keratoprosthesis is the world’s most commonly used artificial cornea. Advances in both surgical technique and postoperative management have drastically reduced the prevalence of endophthalmitis. The authors conducted a systematic review of endophthalmitis arising from the Boston type 1 technique. Medline, Embase, Google Scholar and The Cochrane Library were systematically searched alongside grey literature sources for relevant studies. Many methods are currently employed to reduce complications including vancomycin prophylaxis and the use of bandage contact lenses. The results will be presented with a view to collate the research conducted to date.
Gene expression in conjunctival melanoma cell lines treated with the histone deacetylase (HDAC) inhibitor valproic acid (VPA)
Authors: MUNOZ‐ERAZO L , MADIGAN M , CONWAY RM
Published: August 2014

Purpose To investigate the differential regulation of genes in conjunctival melanoma cell lines (CRMM1 and CM2005.1) treated with valproic acid (VPA), a class I and II histone deacetylase (HDAC) inhibitor.

Methods Based on previous viability assays, cell lines were treated with VPA (CRMM1: 3mM, CM2005.1: 5mM). At 24 and 72 h post‐treatment, RNA was extracted and processed for RT‐PCR using defined gene‐array microfluidic cards. Gene functions chosen for investigation related to HDACs, cell cycle (cyclins e.g. CCND2, CCNA1) cell death (caspases), melanocyte function (PAX6), increased susceptibility to malignant transformation (BAP1, GNAQ) and DNA damage (GADD45A).

Results Upregulation of HDACs 1,2,3,4 6, SIRT2 and GADD45A occurred in CRMM1 cells by 24h but only after 24h for CM2005.1. Both CRMM1 and CM2005.1 showed increased CCND2 after VPA treatment, albeit higher in CM2005.1 (>700‐fold by 72h, compared to 22‐fold in CRMM1). CCNA1 was increased at 24 and 72 h in CRMM1 (>200 fold 24h). For CM2005.1 cells, CCNA1 was initially downregulated and upregulated by 72h (~30‐fold).

Conclusion The delayed increase in GADD45A (DNA damage gene) in CM2005.1 cells compared with CRMM1 cells, is consistent with our toxicity assays showing CRMM1 more responsive to VPA than CM2005.1. The differences of CCND2 and CCNA1 fold‐changes (which are partially regulated by HDACs) between the two cell lines, may explain their dissimilar responses to VPA. Funding – NFMRI
Periorbital necrotizing fasciitis in a 69 year old patient. Medical management and use of hyperbaric oxygen as further adjunctive therapy
Authors: PORTALIOU DM , KOUROUPAKI A , KABANAROU S , KARVELA I , FERETIS E , XIROU T
Published: August 2014

Purpose To report a case of periorbital necrotizing fasciitis in a 69 year old patient that was successfully managed with the use of intravenous antibiotics and surgical debridement. In addition to the usual treatment modalities, Hyperbaric Oxygen (HBO) was used as further adjunctive therapy

Methods A 69 year old male presented with profound swelling over the right eye and right side of forehead. On admission the physicians made the diagnosis of septic shock. Patient had no history of alcohol abuse, insect bite, infection, recent penetrating injury, blunt trauma, face surgery or known immunosuppression conditions such as diabetes mellitus. Orbital CT showed a predominantly preseptal soft‐tissue swelling consistent with the diagnosis of periorbital necrotizing fasciitis

Results Patient started on empiric treatment with broad‐spectrum intravenous antibiotics that modified according to blood culture results few days later. Surgical debridement and microbiologic evaluation of the necrotic tissue were performed. Streptococcus pyogenes and Staphylococcus aureus were isolated from tissue samples. Patient was further treated with twenty sessions of Hyperbaric Oxygen Therapy. Complete resolution of the infection occurred six weeks after initial diagnosis.

Conclusion Treatment of periorbital necrotizing fasciitis with intravenous antibiotics and surgical debridement can be further enhanced with Hyperbaric Oxygen sessions with promising results.
Role of Azithromycin in the treatment of children meibomian gland disease
Authors: LAZREG S , BENALI ABDELLAH M
Published: August 2014

Purpose To determine the usefulness of azitromycin eye drops in the treatment of moderate to severe meibomian gland disease (MGD) in children;

Methods Prospective study conducted on 78 children with MGD. At the first examination, all patients already experienced various ophthalmological treatments without any success leading us to test azithromycin eye drops, a macrolide family with anti‐inflammatory properties. The treatment consisted on azithromycin twice a day during 5 days repeated each month for 3 months associated with Dexamethasone eye drops (6 drops a day during one week, the firs month) and daily eyelid hygiene (manual or warm glasses) during the all the treatment course.The follow‐up visits were performed on D7, D30, D60 and D90 with slit lamp examination and photography

Results 78 children were included, 76.4% had severe corneal complications (neovascularization, ulcers, phlyctenular keratitis). After the first week of treatment, a marked improvement in symptoms was observed in all children probably due to the effect of dexametasone drops, At D60; we observed improvement in corneal signs in 76.8% of cases with a significant decrease of corneal neovessels and phlyctenular. Associated with azithromycin eye drops, warm glasses showed a better efficacy than manual technic. In 5 cases, in spite of more than 3 months treatment with azithromycin, the results were no conclusive;

Conclusion Azithromycin associated with eyelid hygiene is a very effective in treatment in children with MGD; furthermore, its ease of use, its very good efficacy and the absence of side effects, makes this therapy a good alternative and choice in this disease,
Common supranuclear eye movement disorders
Authors: BORRUAT F
Published: August 2014

Supranuclear disorders of eye movement result from a relative deafferentiation of oculomotor nuclei (III, IV, VI) in the presence of intact nuclei, cranial nerves and extraocular muscles. In supranuclear oculomotility disorders there is often a dissociation of eye movements (for example, gaze palsy with preserved vestibulo‐ocular reflex, or saccadic palsy with preserved pursuit). This presentation will discuss the most important supranuclear disorders, including internuclear ophthalmoplegia, dorsal mesencephalic syndrome, skew deviation, and progressive supranuclear palsy. At the end of the session, participants should be able to recognize and provide a differential diagnosis for the aforementioned supranuclear disorders.
Serous retinal detachment associated with diabetic macular edema over the course of Ranibizumab treatment
Authors: QU L , FAJNKUCHEN F , CHAINE G , GIOCANTI‐AUREGAN A
Published: August 2014

Purpose Diabetic macular edema (DME) is frequently associated with subretinal detachment (SRD). SRD does not seem associated with a change of spontaneous evolution of DME. But we do not know wether SRD has an impact on DME resolution under intravitreal injections (IVT) of Ranibizumab. The purpose of our study was to describe the course of DME treated by Ranibizumab with or without SRD over 6 months.

Methods We retrospectively enrolled patients treated by ranibizumab for DME with central foveal thickness (CFT) > 300 µm between November 2012 and November 2013. Group 1 was DME with SRD and group 2 was DME without SRD. We measured manually SRD on a SD‐OCT (OPKO). We studied best corrected visual acuity (BCVA), BCVA variation from baseline, CFT with or without SRD on OCT and the total number of IVT over 6 months.

Results 48 eyes with DME of 40 patients were included. 23 eyes (47,9 %) had SRD at baseline (group 1) and 25 eyes (41 %) did not (group 2). At baseline, BCVA in decimal was 0,19 (40,3 letters in ETDRS) in group 1 and 0,25 (51,3 letters ETDRS) in group 2 (p<0,05). CFT was 666µm and SRD was 215µm in group 1 and 528µm in group 2. After 6 months, mean change of BCVA was + 0,21 in decimal (+ 20,9 letters in ETDRS) in group 1, and + 0,17 in decimal (+ 7,8 letters ETDRS) in group 2 (p < 0,05). The final CFT was 327µm in group 1 (‐ 339 µm) and 379 µm (‐ 147µm) in group 2. Group 1 received 4,3 IVT over 6 months against 4,2 IVT in group 2.

Conclusion DME with SRD had a thicker CFT and a lower BCVA at baseline than DME without SRD in our case series. DME with SRD seemed to have the best results under ranibizumab regarding BCVA, and CFT after treatment.SRD associated with DME seems to be a good functiona
Improved outcome after primary vitrectomy in diabetic patients treated with simvastatin
Authors: LOUKOVAARA S , SAHANNE S , TUUMINEN R
Published: August 2014

Purpose Simvastatin treatment may reduce intravitreal levels of potent vasoactive, angiogenic, and fibroproliferative factors. Here, we evaluated the effect of preoperative simvastatin treatment on the outcome of primary vitrectomy in diabetic patients.

Methods Prospective, observational case control study of type 1 and 2 adult diabetic patients admitted for primary vitrectomy in management of sight‐threatening forms of diabetic retinopathy (DR). A 1‐month best corrected visual acuity (BCVA) gain and cumulative 12‐month re‐vitrectomy frequency of 192 diabetic patients, 79 on simvastatin treatment and 113 without any statin medication.

Results Diabetic patients with simvastatin treatment had a better 1‐month BCVA improvement than did those without statin treatment (p=0.009). Subgroup analysis revealed that diabetics on simvastatin had better post‐operative BCVA improvement when preoperative status included partial or panretinal laser photocoagulation (p=0.042 and p=0.049) and anti‐VEGF therapy (p=0.011). Moreover, diabetics pre‐operatively with macular edema (p=0.009), vitreous hemorrhage (p<0.001), proliferative retinopathy (p<0.001), or tractional retinal detachment (p=0.010) had better BCVA recovery, if receiving simvastatin. Our 12‐month follow‐up revealed that the frequency of revitrectomies (p<0.001) and re‐revitrectomies (p=0.016) were lower in diabetics on simvastatin treatment.

Conclusion These data provide novel insight into the potential clinical benefit for patients with sight‐threatening DR undergoing vitrectomy treated with simvastatin.
Pronostic factors and complications of vitrectomy in patients with advanced diabetic retinopathy
Authors: AJAMIL RODANES S , MANZANAS LEAL L , LÓPEZ GÁLVEZ MI
Published: August 2014

Purpose The aim of this study is to present the results of pars plana vitrectomy in patients with advanced disease and to identify preoperative risk factors and postoperative visual outcome.

Methods The study was carried out at the University Hospital in Valladolid (Spain) with data from patients throughout two years.

Results Retrospective chart review of patients who underwent posterior plas plana vitrectomy (PPV) during 2010‐2011 for non‐clearing vitreous haemorrhage (NCVH), tractional retinal detachment (TDR) or diabetic edema with vitreomacular traction (TME) and followed for at least 6 months.The primary outcome measure was the best corrected visual acuity (BCVA) at the end of the follow‐up period and its correlation with preoperative risk factors.The secondary outcomes were postoperative complications and the influence of the status of the external retina in the ocular coherence tomography (OCT). 58 patients underwent PPV for advanced retinal disease. NCVH was the most frequent surgical indication in 32 patients and 21 of them had gone through laser previously. Mean preoparative BCVA was 1.96 ± 1.13 logarithm of minimum angle of resolution (logMAR) units and it improved.TDR was the indication in 10 patients. Only 50% of them had laser and all of them suffered from long term disease. There was not significant improvement in the BCVA and 3 patients developed neovascular glaucoma. Ind

Conclusion Preoperative BCVA, long term disease, the lack of laser treatment and the external retina seem to be some of the most important risk factors in these patients.
Lens and visual development
Authors: LÖFGREN S
Published: August 2014

The visual development is dependent on a number of factors, such as eye media transparency, refraction, eye growth, environmental light input and visual image input. The lens plays an important role for the visual development. The lecture will cover lens growth and development, in connection to visual development in children. Form changing lens disease and light absorbing disease in or around the lens can be amblyogenic, although in many cases the situation can be resolved with refractive treatment or lens removal. Unfortunately the postoperative or treatment efficiency on visual development is not always perfect. Besides the above diseases there is also the question about indirect effects of aphakia or intraocular lens on eye and visual development. Further, some words on emmetropization related to lens structure and function. Pillar‐stone papers will be presented to serve as backbone for newer data.
Biocompatibility and functionality of a tissue‐engineered stroma transplanted in the living animal
Authors: BRUNETTE I , BOULZE PANKERT M , GOYER B , ZAGUIA F , BAREILLE M , PERRON MC , LIU X , DOUGLAS CAMERON J , PROULX S
Published: August 2014

Corneal tissue shortage has become a major concern worldwide, which has motivated the search for alternative solutions to eye bank human eyes for corneal transplantation. Biocompatibility and functionality of stromal lamellar grafts tissue‐engineered in vitro from corneal stromal cells using self‐assembly approach, without the addition of exogenous material or scaffold, and transplanted in vivo in the cornea of an experimental model open the way to a new therapeutic modality for the rehabilitation of diseased corneas.
KPro Biomaterials
Authors: AVADHANAM VS , INGLAVE G , SANDEMAN S , LIU CSC
Published: August 2014

Research into keratoprosthessis(KPro) is at least 200 years old. In the early days, when corneal pathology was recognised as a specific cause for blindness, its treatment involved a replacement of the diseased cornea with artificial materials. Afterwards cadaveric corneal transplantation has proven to be more successful than prosthetic corneal substitutes. However, the need for keratoprostheses is still present. Scores of KPro devices have been proposed and many biomaterials have been investigated. Only 2 devices, the osteo‐odonto‐keratoprosthesis (OOKP) and Boston type1 KPro, have proven to be viable in the longer term although complications do occur. A true artificial cornea in form and function is still a fantasy and may not be clinically feasible. Since corneal involvement can be secondary to ocular surface disease, a universal KPro that cures every type of corneal blindness may not be a pragmatic solution. Development of biomaterials may be tailored towards KPros designed specifically for different ocular pathology rather than towards a ‘one size fit for all’ device. Translation of laboratory work into clinical practice for KPro development will require better concordance between clinicians and scientists.
Anterior ischemic optic neuropathy following selective intra‐arterial chemotherapy for unilateral retinoblastoma
Authors: DE FRANCESCO S , MENICACCI F , BORRI M , HADJISTILIANOU T
Published: August 2014

Purpose To describe anterior ischemic optic neuropathy (AION) observed in a child treated with selective intra‐arterial chemotherapy (SIAC) for relapse in unilateral retinoblastoma.

Methods Charts and retcam images of patient were reviewed, and procedures data were collected. The ophthalmoscopic features at diagnosis suggested for a malignant transformation of a retinoma/retinocytoma. Fluorangiographic and MRI findings were evaluated.

Results AION spontaneously resolved within 4 weeks.

Conclusion AION could be a possible transient side effect of repeated intra‐arterial chemotherapy.
Genetic analysis of an orbital metastasis from a primary hepatic neuroendocrine carcinoma
Authors: HEEGAARD S , VON HOLSTEIN S , PRAUSE J , STENMAN G
Published: August 2014

Purpose To give an overview of neuroendocrine carcinoma metastases to the eye region.

Methods Critical review of the present literature demonstrated by a patient case.

Results A 71‐year‐old female with a known history of primary hepatic neuroendocrine carcinoma, presented with a visual defect, proptosis and restricted eye movements of the right eye. Biopsies from the orbit and from the primary hepatic neuroendocrine carcinoma showed similar morphological and immunohistochemical features and high‐resolution, array‐based comparative genomic hybridization demonstrated loss of one copy each of chromosomes 3 and 18, and gain of 1q both in the primary hepatic neuroendocrine carcinoma and in the orbital tumour. The orbital mass was diagnosed as a metastasis from the primary hepatic neuroendocrine carcinoma.

Conclusion Primary hepatic neuroendocrine tumours are very rare, and the orbit is an extremely rare location for a neuroendocrine carcinoma metastasis. This is the first reported case of an orbital metastasis with origin from a primary hepatic neuroendocrine carcinoma.
Suspicious choroidal mass – an interdisciplinary challenge
Authors: GRAEFF E , GRIESHABER M , MEYER P
Published: August 2014

Purpose To highlight the importance of interdisciplinary work up based on a patient with presumed choroidal metastatic of unknown primary tumor.

Methods Clinical‐pathological case report.

Results A 57 year old woman was referred to our clinic because of a progressive vision loss in her right eye for seven days. Loss of vision field and light flashes followed 3 days later. General medical history was inconspicuous and last general check‐up including gynaecologic examination performed by general practitioner was apparently normal. At first presentation, a yellowish choroidal mass in the inferior part of fundus was found clinically. Further diagnostic exams like ultrasound, OCT, fluorescence angiography and MRI of the orbit were suspicious for a choroidal metastasis of unknown primary tumor. An immediate interdisciplinary work‐up with gynaecologists and oncologist was performed; histology of a punch biopsy of the left mammae confirmed the suspected finding of a multiple low differentiated invasive growing ductal carcinoma. Furthermore, metastasis of the lung and axillary lymph nodes were found. Because of the multiple metastases, a combined chemotherapy and radiation therapy was initiated.

Conclusion Choroidal mass is indicative for metastasis which requires immediate interdisciplinary work‐up even in the absence of a positive medical history. Since biopsy of the choroidal mass should not be performed, the diagnosis was made by the biopsy of the primary tumor, showing a metastasized aggressive breast tumor. Thanks to efficient interdisciplinary work up, local and systemic therapy saved vision in her right eye and best palliative care was offered.
Brillouin spectroscopy and lens refilling
Authors: STACHS O
Published: August 2014

The confocal Brillouin spectroscopy is an innovative measurement method that allows the non‐invasive determination of the rheological properties of materials. Its application in ophthalmology can offer the possibility to determine in‐vivo the biomechanical properties of transparent biological tissue such as the crystalline lens. This seems to be a promising approach concerning current presbyopia research. Due to the spatially resolved detection of the viscoelastic lens properties, a better understanding of the natural aging process of the lens and the influences of different lens opacities on the stiffness is expected. From the obtained spectral data the relative protein levels, the relative refractive index profile and the relative density profile within the lens tissue can be derived. A measurement set‐up for confocal Brillouin microscopy based on spectral analysis of spontaneous Brillouin scattering signals by using a high‐resolution dispersive device is presented. In‐vitro and in‐vivo test results on native and artificial lenses are presented and evaluated concerning their rheological significance.
Mechatronic system to restore accommodation
Authors: GUTHOFF RF
Published: August 2014

The Artificial Accommodation system is a mechatronic approach to restoring accommodation. It consists of an autonomous device that will be implanted into the capsular bag of the eye similar to implantation of intraocular lenses today. The device measures accommodation demand and accordingly adjusts its refractive power by means of an integrated active optical element. Realization of this far reaching vision requires development of the respective subsystems, their integration into a small hermetic and biocompatible housing and adapted surgical procedures. Development of subsystems is well under way and first integration steps are being taken starting from macro scale down to target size. In this talk, the concept of the overall system is described and the results obtained for the different subsystems are discussed.
The AkkoLens Lumina accommodative intraocular lens
Authors: ROMBACH M
Published: August 2014

The AkkoLens Lumina accommodating intraocular lens is located within the ciliary muscle which drives the lens directly; it is not in the capsular bag which has no further role after the implantation. The Lumina is designed to provide ~4D of accommodative power using small movements requiring little force. The Lumina is implanted with a standard butterfly cartridge through a 2.8mm incision making the surgery suture‐free. In ongoing clinical trials, the Lumina has been placed in ~65 eyes with phenomenal results; patients see near, intermediate and far with all the data confirming this. The visual acuity and contrast sensitivity of the Lumina are comparable to the high‐quality monofocal IOL used as the control lens.
Posterior hyaloid findings as visualized by SD OCT
Authors: KRASTEL H , HOFMANN F , BAIER D , KAHLERT CHR , KUZNIAR A , HARDER B , JONAS J
Published: August 2014

Purpose To direct attention to the structures of the posterior hyaloid as visualized by SD OCT, and to improve understanding of vitreo‐retinal biomechanics.

Methods Findings were collected from a Wetzlar study cohort of subjects who gave their informed consent to gather experience in vitreal SD OCT. In addition, OCT images were worked up retrospectively from the Mannheim pool of recordings. Exams were performed by the RS 3000 SD OCT (Nidek) or by the Spectralis SD OCT (Heidelberg engineering). Images underwent a modified processing to favour the visualization of vitreous structures.

Results Observations range from a completely attached and homogeneous hyaloid with regular foveal profile at the age of 75, to premacular vitreal bursae and intravitreal lacunae, regions of low and high density within an apparently disintegrating hyaloid, intravitreal condensates and supposed cell aggregations. Various patterns of holes within the posterior limitating vitreal membrane appeared in connection with vitreo‐retinal and vitreo‐papillar traction of a partially detached vitreous

Conclusion OCT visualization of vitreous structures contributes to our understanding of vitreal degradation and vitreo ‐ retinal interaction.

Commercial interest
Apoptosis and proliferation in diabetic eyes
Authors: STEWART EA , SAKER S , AMOAKU WM
Published: August 2014

Purpose Diabetic retinopathy (DR) is the most common cause of visual loss in the working population and the incidence of diabetes is increasing. In addition, 80% of diabetic patients will show some form of retinopathy after 15 years, even with good glycaemic control. The mechanism of diabetic retinopathy is still not fully understood although hyperglycaemia is the main determinant. Diabetes appears to have contradictory effects on vasculature, causing reduced angiogenesis or increased angiogenesis at different vascular sites.

Methods The effect of high glucose (HG) on in vitro proliferation, apoptosis and angiogenesis of retinal endothelial cells was investigated using relevant assays. Real time PCR was used to quantify signalling responses to high glucose through gene expression of key signalling molecules such as HIF and expression of VEGF.

Results HG conditions reduced the proliferation of retinal endothelial cells but no increase in apoptosis was detected, and increased VEGF prevented this response. Gene expression of HIF was increased with HG and that of VEGF decreased dependent on glucose concentration and exposure time.

Conclusion Contrary to other research in this area we found that apoptosis may not play the major role in the early phase of DR, and that reduced endothelial cell proliferation precedes apoptosis. Angiogenic signalling induced by hyperglycaemia is complex and requires further elucidation.

Commercial interest
CL1R2 antibody, as well as Bevacizumab, promotes the regression of pathologic retinal neovascularisation in Vldlr knockout mice
Authors: SOLER V , HAMID S , TOLOU C , TRICOIRE C , DAUSSION MA , LE BOUTEILLER P , CASSAGNE M , CALVAS P , MALECAZE F , GALIACY S
Published: August 2014

Purpose Very low‐density lipoprotein receptor mutant mice (Vldlr(‐/‐)) demonstrate retinal neovascularisation. Monoclonal antibody CL1‐R2 recognizes human membrane receptor CD160, which is expressed on activated endothelial cells of neovessels but not in vessels of healthy tissues. In this study, we evaluated the therapeutic potential of CL1R2 antibody in Vldlr(‐/‐) mice as a model for exudative age‐related macular degeneration and macular telangiectasia.

Methods Thirty Vldlr(‐/‐) mice benefitted at postnatal day (P) 42 from retinal angiography. Mice population was then divided in three groups (ten mice per group). According to the groups, mice underwent intravitreal injection of CL1‐R2 or Bevacizumab or control antibody. At P56, mice benefitted from angiography and were sacrificed.

Results At P42, Vldlr(‐/‐) retinas presented with neovascular lesions. At P56, we observed decrease of neovascular lesions in eyes treated with CL1R2 antibody and with bevacizumab. This decrease of neovascular lesions was not observed in control mice.

Conclusion CL1R2 antibody, as well as Bevacizumab, promotes the regression of pathologic retinal neovascularization in the Vldlr knockout mouse. As CL1R2 is an activator of NK cells, our result suggest that the activation of NK cells inhibits the development of Vldlr(‐/‐) mice retinal neovascularisation.
Study of endothelial progenitor cells in young diabetic patients with type 1 diabetes mellitus
Authors: TSILIMBARIS M , SIMANTIRAKI D , KAPSALA Z , TSIKA C , PONTIKOGLOU C , MAMOULAKIS D , PAPADAKI H
Published: August 2014

Purpose Purpose: To evaluate the presence of Endothelial Progenitor Cells (EPCs) in the peripheral blood of young patients with Diabetes Mellitus Type I (T1DM).

Methods Blood samples were collected and analyzed from 23 individuals: 15 patients with DM (mean DM duration‐years: 13 (range:3‐31)), mean age‐years: 26(9‐45) and 8 controls without DM mean age‐years: 32 (range:10‐41). The presence of Diabetic Retinopathy (DR) was documented with slit lamp examination and fluorescence angiography, according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) criteria. The EPCs were detected with flow cytometry using the following primary antibodies: anti‐CD34, anti‐CD45, anti‐CD133 and anti‐hVEGFR2.

Results Progenitor EPCs, defined as CD45‐/CD34+/CD133+/VEGFR2+ cells, were detected in 10/23 samples (mean%: 0.00069, SEM:0.000261). 7/15 patients had EPCs detected in the periphery blood (mean%: 0.000899, SEM:0.000384) . EPCs were detected in all 5 patients with PDR (mean%: 0.000998, SEM:0.000206). Also, 1/5 patients with NPDR (0.0035%) and 1/5 patients without clinically proven DR (0.005%) had detectable EPCs. Finally, circulating EPCs were identified in 3/8 individuals of the control group (mean%: 0.000299, SEM:0.000169).

Conclusion CD45‐/CD34+/CD133+/hVEGFR2+ EPCs were detected in the peripheral blood of non diabetic persons and diabetic patients with or without evidence of DR. The clarification of the presence of EPCs in the peripheral blood early in the disease course could potentially offer significant information about the pathophysiology of diabetic microangiopathy.
Diabetic retinopathy and estimated cerebrospinal fluid pressure. The Beijing eye study 2011
Authors: JONAS J , WANG N , XU L , XU JIE , WANG Y , YOU Q
Published: August 2014

Purpose We tested the hypothesis whether prevalence and severity of diabetic retinopathy are associated with cerebrospinal fluid pressure (CSFP)

Methods The population‐based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.69.8 years. Based on a previous study with lumbar cerebrospinal fluid pressure (CSFP) measurements, CSFP was calculated as CSFP[mmHg]=0.44xBody Mass Index[kg/m2]+0.16 Diastolic Blood Pressure[mmHg]–0.18xAge[Years]‐1.91.

Results In binary regression analysis, presence of diabetic retinopathy was significantly associated with higher levels of HbA1c (P<0.001), higher blood concentration of glucose (P<0.001), longer known duration of diabetes mellitus (P<0.001), higher systolic blood pressure (P<0.001;), lower diastolic blood pressure (P<0.001), and higher CSFP (P=0.002). Severity of diabetic retinopathy was significantly associated with higher HbA1c value (P<0.001), higher blood concentration of glucose (), longer known duration of diabetes mellitus (P<0.001), lower level of education (P=0.001), lower diastolic blood pressure (P=0.002), higher systolic blood pressure (P=0.006), and higher CSFP (P=0.006).

Conclusion Higher prevalence and severity of diabetic retinopathy were associated with higher estimated CSFP after adjusting for systemic parameters. Higher CSFP through a higher retinal vein pressure may lead to more marked retinal venous congestion and vascular leakage in diabetic retinae.
Hyperosmolar stress induces TonEBP activation in human retinal pigmented epithelial cells
Authors: LIBERT S , WILLERMAIN F , SALIK D , DELPORTE C
Published: August 2014

Purpose Macular edema, a frequently encountered complication of diabetic retinopathy (DR), results from alterations of the blood retinal barrier (BRB) and leads to modifications of the retinal pigmented epithelium (RPE) functions. Osmolar changes of the surrounding medium could be responsible for some modifications of the RPE functions leading to a disturbance of the retinal homeostasis.

Methods To study the modification and stability of the key hyperosmolar response factor Tonicity Enhancer Binding Protein’s (TonEBP) expression in ARPE‐19 cells, derived from human RPE, were submitted to hyperosmolar stress of increasing concentration and for various times.

Results In response to hyperosmolar stimulation of ARPE‐19 cells, a dose‐dependent increase in TonEBP mRNA and protein levels, as well as TonEBP nuclear translocation, were observed. Moreover, the mRNA levels of Aldose Reductase (AR) and Sodium‐dependent Taurine Transporter (TauT), two TonEBP target genes required for increasing the intracellular ionic force, increased in a delayed manner following hyperosmolar stimulation. Additionally, SB203580, a p38 protein kinase inhibitor, but not its inactive analogue SB202474, inhibited TonEBP nuclear translocation in ARPE‐19 cells submitted to hyperosmolar stimulation.

Conclusion In ARPE‐19 cells submitted to hyperosmolar stress, TonEBP expression is induced, and its nuclear translocation stimulated through a mechanism involving p38 protein kinase activation. It is likely that TonEBP nuclear translocation mediates the increase of AR and TauT expression induced by hyperosmolar stress and plays a role in RPE cells osmoadaptation.
Postoperative endophthalmitis
Authors: BARRAQUER R
Published: August 2014

Abstract not provided
The problem of bacterial resistance in medicine and in ophthalmology
Authors: GRZYBOWSKI A
Published: August 2014

In 2013 US Centers for Disease Control and Prevention released its first ever report on antibiotic resistance and pointed that antimicrobial resistance is one of the most serious health threats nowdays. The same year report on global risks by the World Economic Forum argued that “the greatest risk … to human health comes in the form of antibiotic‐resistant bacteria”. Although it is mainly caused by agricultural use of antibiotics, the other factors include overuse of antibiotics for systemic infections, inappropriate durations of treatment, prophylactic use of antibiotics, use of subtherapeutic dosages of antibiotics by non‐compliant patients, and misuse of antibiotics for non‐bacterial infections. The most common use of antibiotic in ophthalmology include conjunctivities, intravitreal injections and post‐cataract endophthalmitis prophylaxis. There is increasing number of evidance that their use should be re‐considered and often limited or eliminated. Finally, limiting the use of antibiotics is consistent with both ethics of rationing and ethics of waste avoidance.
The evidence: the intraoperative antibiotic
Authors: BARRY P
Published: August 2014

The evidence on which the " ESCRS Guidelines on Endophthalmitis prophylaxis following cataract surgery (2013) " is based will be presented. This comprises studies from Sweden, Spain, France, South Africa, Asia, North America and Japan showing a reduction in infection rates reducing by factors of 3 ‐ 22 fold when the intracameral route was introduced. Risks and relative contraindications will also be discussed.
The evidence: pre‐operative and post‐operative antibiotics
Authors: GRZYBOWSKI A
Published: August 2014

Postoperative endophthalmitis is an ophthalmic surgeon’s most serious complication, as it is related with a high risk of visual loss. As such, many strategies are employed to minimize this possibility including preoperative, intraoperative and postoperative strategies. Although most surgeons can justify their approach, there is a paucity of prospective studies, which can serve as true evidence. The purpose of this paper is to review the literature on the subject of pre‐operative and post‐operative antibiotics used for prevention of postoperative endophthalmitis and to determine the effectiveness of these measures.
FRO 2014: Can Xiaflex® improve glaucoma surgery outcome?
Authors: VAN DE VELDE S , STALMANS I
Published: August 2014

Failure of glaucoma filtration surgery due to excessive post operative wound healing is still a major problem in the treatment of glaucoma. With this project we want to examine if Xiaflex® is able to reduce fibrosis after glaucoma filtration surgery and in this way may improve surgical outcome.
FRO 2014: Proteomic analysis of posterior capsular plaques and capsules in developmental cataracts
Authors: VAN LOOVEREN J
Published: August 2014

When operating children with developmental cataract surgeons are often confronted with an opaque plaque adhering to the inside of the posterior capsule. In a previous study using immunohistochemical analysis we were able to demonstrate that these posterior capsular plaques can contain collagen type II, a type of collagen which was never demonstrated in a human lens before. We also exposed the strong adherence of the anterior hyaloid membrane (containing collagen type II) to the center of the posterior lens capsule indicating a dysgenesis of Berger’s space in these specific cataract cases. The purpose of this study is to increase knowledge of the biochemical composition of these posterior capsular plaques and capsules in developmental cataract by using proteomic approaches. We believe these insights will be beneficial to understand cataract formation in these children and ultimately will improve the surgical outcome of cataract surgery in these particular cases with generally worse prognosis.
FRO 2014: Exploring the role of a novel disease gene EML4 in autosomal recessive retinitis pigmentosa
Authors: VAN SCHIL K , LEROY BP , DE BAERE E
Published: August 2014

Whole exome sequencing (WES) in a patient with autosomal recessive retinitis pigmentosa (arRP) revealed a missense mutation in the Echinoderm Microtubule associated protein Like 4 (EML4) gene, affecting a highly conserved amino acid residue. The protein has been shown to be essential for microtubule formation and stabilization, and to interact with ARL6, which has been previously linked to recessive Bardet‐Biedl syndrome. The major aim of this project is to assess the contribution of the EML4 gene to the arRP phenotype observed in this patient and in additional patients with overlapping retinal dystrophies (RDs).
Predictive value of color Doppler imaging of central retinal artery in outcome of corneal graft
Authors: AMAOUCHE N , KOSKAS P , FADLALLAH A , COCHEREAU I , BERGES O , GABISON E
Published: August 2014

Purpose To assess the value of color Doppler imaging (CDI) of the Central Retinal Artery (CRA) in predicting visual acuity post corneal graft procedures.

Methods Forty‐seven eyes of 47 patients with severe corneal disease that require corneal graft were included in a retrospective cohort study. At baseline, CDI were performed for all eyes and hemodynamic parameters of the CRA were measured: Resistive Index (RI) and peak systolic velocity (PSV). All eyes underwent B mode Echography: Analysis of vitreo‐ retinal morphology, macula, and papilla. Inclusion criteria were the following: Corneal graft for any etiology, Best Corrected visual acuity (BCVA) less than 0.8 Log MAR, and no correct visualization of the fundus at preoperative clinical examination.

Results 2 DALK (Depth Anterior Lamellar Keratoplasty), 2 DSEAK (Descemet stripping automated endothelial keratoplasty) and 43 PK (Penetrating Keratoplasty) were performed. After 12 mouths of follow‐up: 41.5% of eyes (Group A) had visual acuity improvement (BCVA equal or superior to 2 lines Log MAR scale compared to baseline) and 58.5 % of eyes (Group B)had no improvement. The mean (SD) PSV was 15.00 ± 8.72 in group A and 11.04 ± 5.39 in the group B with significative difference (p=0.032). The mean (SD) RI was 0.68 ± 0.11 in group A and 0.67 ± 0.06 in the group B with no significative statistical difference (p=0.864). However a Pearson correlation test showed a significative negative correlation between RI and BCVA (p=0.046).

Conclusion In eyes with opaque cornea, the RI and PSV of the CRA may reliably predict prognosis in corneal graft. Discovering bad CDI parameters in advance allows avoiding post‐operative disappointments.
Big bubble deep anterior lamellar keratoplasty from the perspective of the novel predescemetic corneal layer
Authors: GOWEIDA M
Published: August 2014

Purpose To evaluate the intraoperative findings and complications during big bubble deep anterior lamellar keratoplasty (DALK) based on the newly described predescemetic (Dua layer).

Methods A retrospective review of medical records and surgical videos of a series of patients who underwent DALK using the big bubble technique from September 2009 to March 2014.

Results One hundred and thirty four eyes were enrolled in this study. Type 1 bubble was achieved in 56 eyes (41.8%) while in 14 eyes (10.4%) type 2 bubble was formed, 2 eyes (1.5%) had mixed bubble. Failure of formation of the big bubble occurred in 62 eyes (46.3%). All eyes with type 1 bubble were completed as DALK with microperforation in 4 eyes. All eyes with type 2 bubble were converted to PKP due to large perforation except 2 eyes were successfully completed as DALK with microperforation in one eye and intact DM in the other.

Conclusion Type 2 bubbles are very likely to perforate during removal of the overlying stroma, factors leading to the formation of the thin walled type 2 bubbles should be studied and better strategies to avoid perforation should be adapted.