bluuebunny/crossref_metadata_2025 huggingface dataset:
Deficiency in the expression of Vps13C is associated with altered retinal and lens development in mice
Authors: Amarie O. , Rathkolb B. , Fuchs H. , Gailus‐Durner V. , Hrabě de Angelis M. , Graw J.
Published: September 2017

While performing genotyping screening in the German Mouse Clinic we identified the Vps13C mouse mutant with eye phenotype where the homozygous mutant mice show signs of neurodegeneration, indicated by a reduction in the total retinal thickness, additionally the retinal blood vessels showed a pattern with structural alteration. Eye histology revealed the display of lipid‐like droplets in the retinal layers and in the anterior lens matrix. VPS 13C is a member of the VPS13 family of vacuolar protein sorting‐associated proteins highly conserved throughout eukaryotic evolution. While mutations in VPS13A and VPS13B cause the genetic diseases chorea‐acanthocytosis (ChAc) and Cohen syndrome, respectively, VSP13C is reported to be associated with Parkinsons disease and late onset Alzheimer's disease (LOAD). Moreover VPS13C has recently been found to be involved in the protein degradation through the ubiquitin being closely associated with lipid droplets and lysosomes. Human diseases are caused by the dysregulated accumulation of ubiquitinated protein aggregates, including neurodegenerative disorders. We believe Vps13c could open novel avenues for uncovering new treatments of metabolic and neurodegenerative disorders.
Human case
Authors: Hamel C. , Bocquet B. , Manes G. , Meunier I.
Published: September 2017

We will present two cases of early onset, possibly congenital, retinal dystrophies, in children, who do not have Leber congenital amaurosis. Visual acuity is decreased, and the fundus shows serpentine like images, most visible in infrared. OCT evidences abnormal retinal structure. ERG has been performed. Molecular genetics is undergoing.
Role of taurine in cone death
Authors: Picaud S. , Trouillet A. , Hadj‐Saïd W. , Dubus E. , García‐Ayuso D. , Sahel J. , El‐Amraoui A. , Petit C.
Published: September 2017

Cone photoreceptors degenerate in a number of retinal diseases leading thereby to blindness or low vision as in age‐related macular degeneration or retinal dystrophies. However, mechanisms leading to cone photoreceptor death remain enigmatic. In the 70s, taurine depletion was shown to lead to complete photoreceptor degeneration. We have investigated the relative cone/rod sensitivity to taurine depletion and the effect of taurine supplementation on cone degeneration in a model of Usher syndrome type 1. Using a taurine transporter blocker, we have shown that taurine depletion induces a cone degeneration prior to the rod loss. This cone degeneration affect both blue and green cones throughout the retina. To investigate whether taurine could provide an interesting neuroprotective agent in retinal diseases, we supplemented a mouse model of Usher syndrome type 1 with taurine. This taurine supplementation prevented the cone photoreceptor degeneration and the associated retinal gliosis. These studies demonstrate that taurine is an essential antioxidant for cone photoreceptor survival. Its supplementation could slow down the degenerative process of cone photoreceptors as in our in animal models of Usher syndrome type 1.
The role of p62/SQSTM1 in IL‐1β‐mediated cytokine production in retinal pigment epithelial cells
Authors: Kauppinen A. , Korhonen E. , Piippo N. , Hytti M. , Kaarniranta K.
Published: September 2017

Purpose

p62/SQSTM1 is a selective autophagy substrate being added to ubiquitinated proteins directed to lysosomal degradation. Its levels increase inside the retinal pigment epithelial (RPE) cells when proteasomal activity and autophagic clearance decline during aging. p62/SQSTM1 can also contribute to the activation of pro‐inflammatory nuclear factor kappa B (NF‐κB) or mitogen‐activated protein kinase (MAPK) pathways. According to our previous studies, reduced intracellular clearance promotes the NLRP3 inflammasome‐mediated release of IL‐1β, which subsequently stimulates RPE cells to produce other pro‐inflammatory mediators, such as IL‐8. In the present study, we have investigated, whether increased levels of p62/SQSTM1 play a role in the IL‐1β‐induced response.

Methods

Upregulation of p62/SQSTM1 was induced by bafilomycin A1 or the over‐expression vector, or prevented by p62/SQSTM1‐specific small interfering RNA (siRNA) transfection. Thereafter, the cells were exposed to IL‐1β. The release of IL‐6 and IL‐8 were detected using the enzyme‐linked immunosorbent assay (ELISA) method. In addition, the autophagy markers p62/SQSTM1 and LC3 were determined using the western blot technique.

Results

IL‐1β resulted in low IL‐6 and high IL‐8 production in human RPE cells. p62/SQSTM1 and its absence were verified but they did not affect the cytokine profiles.

Conclusions

Our data suggest that p62/SQSTM1 does not play a role in the IL‐1β‐induced production of pro‐inflammatory cytokines in human RPE cells.
National diabetic retina screening programme: identifying non‐diabetic eye disease
Authors: Murphy R. , Keegan D.
Published: September 2017

Purpose

The Irish Diabetic RetinaScreen Service offers Nationwide screening to all diabetics over the age of 12. It is internationally unique given the integrated nature of its screening and treatment arms. It is now well established, demonstrating impressive uptake with considerable clinical impact. The aim of this study is to explore the significant and increasing number of referrals from the Diabetic RetinaScreen Service with non‐diabetic eye disease. We determine the individual contributions of pathology sub‐groups and their respective outcomes.

Methods

We retrospectively examined a 12‐month referral assessment database from the Mater Misericordiae University Hospital treatment center from January 2016 to 2017. Non‐diabetic eye disease referrals were identified and analysed with respect to their frequency of referral and outcome.

Results

One thousand nine hundred and ninety‐three patients seen in the MMUH during the 12‐month period were included in the study. Diabetic eye disease referrals comprised 1250/1993 (63%) referrals, with 743/1993 (37%) referred for assessment of non‐diabetic eye disease. Substantial pathology sub‐groups included retinal artery and vein occlusions; Arterial emboli; Cataract; Glaucoma; Age Related Macular Degeneration; and Pigmented retinal lesions. We discuss the relative contribution from each pathology and the subsequent assessment outcomes.

Conclusions

Several non‐diabetic, sight threatening ocular pathologies, which are often asymptomatic in their early course, are being identified and referred for appropriate treatment. The referral volume is increasing. Quantifying this promotes a more informed discussion on increased service demands, helping predict its practical and financial impact, and influencing strategies on future service provisions.
Macular changes in patients with multiple sclerosis – A texture analysis of optical coherence tomography data
Authors: Bernardes R. , Silva G. , Batista S. , Sousa L. , Castelo Branco M.
Published: September 2017

Purpose

In this work, a novel approach is used to assess macular changes in patients diagnosed with multiple sclerosis. The vast majority of the studies, if not all, do use the capacity of the optical coherence tomography (OCT) to detect changes along the optical path to identify the different retinal layers and the detection of these to measure the thickness of the retina and the different layers. In particular, the measurement of the retinal nerve fibre layer (NFL) has played a fundamental role in related studies. In this work, we computed a fundus image for the NLF, the ganglion cell layer (GCL), the inner plexiform layer, the inner nuclear layer, the outer plexiform layer and the out nuclear layer and analysed the texture of these fundus images to find their relative differences to the healthy control group.

Methods

A total of 152 eye scans, from 38 healthy controls (age (m/sd): 36.3/9.2 years) and 39 multiple sclerosis patients (age (m/sd): 38.8/7.3 years) were performed by the Cirrus HD‐OCT (Carl Zeiss Meditec, Dublin, CA, USA) and exported to be segmented by the OCT Explorer (Retinal Image Analysis Lab, Iowa Institute for Biomedical Imaging, Iowa City, IA, USA). The segmentation was further analysed and corrected when necessary.

Results

Each of these images was analysed using first and second order statistics. A support vector machine (SVM) classification process was used to assess the capacity to discriminate between healthy controls and patients to find that the layer presenting the highest difference between the control and the patient group is, surprisingly, the GCL, with over 10% in classification accuracy compared to the NFL layer.

Conclusions

This finding points to the need for further analysis of retinal changes beyond that of the thickness measurement and only in the nerve fiber layer.
Ophthalmoscopic and video OCT methods to detect spontaneous venous pulsation in individuals with apparently normal intracranial pressure: the rebirth of the SVP?
Authors: Jenkins K.S. , Layton C.J. , Adams M.K.M.
Published: September 2017

Purpose

To compare the efficiency of high magnification binocular indirect ophthalmoscopy and direct ophthalmoscopy in detecting the spontaneous venous pulsation (SVP) at the optic nerve head, and to demonstrate the utility of video optical coherence in detecting the phenomenon in patients with normal intracranial pressure.

Methods

The SVP of the right eye of 54 consecutive clinic patients presenting without neuro‐ophthalmic symptoms and with BMIs under 30 were dilated and examined by one ophthalmologist using a 66D handheld Volk lens, then examined by a second blinded ophthalmologist using direct ophthalmoscopy. Immediately the patient was assessed by a third blinded ophthalmologist via vOCT for the presence or absence of SVP.

Results

The population included 20 males and 34 females and were corrected for VA (M 0.127 LogMAR, SD 0.22, SE 0.036), IOP(M 16.5 SD 4.02 SE 0.558), phakia, age (M 68.3, SD 15.15, SE 2.062), C:D ratio (M 0.48 V 0.58 H, SD 0.19 V 0.18 H, SE 0.035 V and 0.033 H), BP (M 136/79, SD 17.71 Sys 12.04 Dia, SE 2.410 Sys, 1.639 Dia) and weight (M 75.48, SD 15.92, SE 2.486). SVPs were detected in 32 of 54 patients using direct ophthalmoscopy, and in 33 of 54 patients using a 66D lens and slit lamp. The ophthalmologists using direct ophthalmoscope and the 66D lens agreed in 49 of 54 cases, giving an inter‐rater reliability of 91%. All patients were found to have SVP on vOCT.

Conclusions

Ophthalmoscopically‐assessed SVP has a high inter‐observer agreement in normal subjects. However, 26% of patients with apparently normal ICP had no ophthalmoscopically detectable SVP. Conversely, SVP was detectable in all patients with apparently normal ICP by vOCT, suggesting it may be a more useful clinical assessment than ophthalmoscopically assessed SVP‐detection.
Outcomes and endpoints in glaucoma
Authors: Cordeiro M.F.
Published: September 2017

Clinical trials in glaucoma have historically relied in IOP. However, the emergence of neuroprotection in glaucoma ghas lead to a need for new measures of trial success. Several potential outcomes exist including autoimmune and genetic biomarkers, brain and retina imaging, clinical signatures of RGC disease and structural and functional endpoints. These will be covered in this talk including DARC – detection of apoptosing cells.
Misunderstanding laboratory evaluation
Authors: Neri P. , Pirani V. , Cesari C.
Published: September 2017

Intraocular inflammations always represent a diagnostic challenge for ophthalmologists. It is often tough to make a precise etiological diagnosis in certain subsets that very often appear atypical. Recently, several advances in the investigations for uveitis have been introduced. Such scientific achievements have significantly helped uveitis specialists in the management of such clinical conditions. Although the approach to laboratory diagnosis of uveitis should be directed by the history, patient's symptoms and signs, and clinical examination, very often the ophthalmologist can be confused if such method is not rigorously followed. The matching of clinical pattern and the tests should be always considered in order to reach the goal of a correct interpretation. This review summarizes various modalities of laboratory investigations and their role in the diagnosis of uveitis, furthermore paying attention to the most common mistakes in their interpretation.
Mistaking infection for inflammation
Authors: Albini T.
Published: September 2017

Among the first steps in diagnosing any patient with uveitis is to identify infection. Common infections that may masquerade as autoimmune disease include herpes simplex virus, varicella zoster virus or cytomegalovirus (CMV) anterior uveitis, chronic post‐surgical endophthalmitis, endogenous endophthalmitis, acute retinal necrosis, CMV retinitis in immunocopme patients, syphilis, atypical toxoplasmosis and tuberculosis. Patient history and clinical exam can often make the diagnosis. The utility of diagnostic tests such as treponemal tests, quantiferon testing, Mantoux skin test, and toxoplasmosis serology will be covered. Case series of polymerase chain reaction (PCR) testing of anterior chamber and/or vitreous aspirate for anterior segment and posterior segment uveitis will be reviewed, with an emphasis on demonstrated clinical utility. More invasive biopsy such as vitreous biopsy via pars plana vitrectomy or chorioretinal biopsy may be necessary in some settings. Appropriate treatment and criteria for treating specific infections will be covered. Cases of polymicrobial infection will be reviewed as well. Emphasis will be placed on distinguishing infection from autoimmune disease.
Fear of the correct treatment dose
Authors: Lowder C.
Published: September 2017

• Fear of the correct treatment dose

O Underdosing valacyclovir

o Underdosing immunosuppressive therapy

Uveitis can occur in all age‐groups and often has devastating effects on vision. The visual loss can have a variety of causes including cataract formation, vitritis, optic nerve damage and macular edema. In patients with active inflammatory disease resulting in reduced vision, corticosteroids are a very important part of the management, and uveitis specialists have learnt a long time ago that their use should be optimized. Even if serious side effects are associated with chronic use of systemic steroids, the correct full‐dose should be employed. The concept of optimizing the treatment by using the correct dose, then lower it to the minimum effective dose that controls inflammation, should be applied as well to the second step of uveitis treatment, immunomodulatory agent. Tailored treatments must also be extended to infectious uveitis, for which there is a low level of awareness of recommended guidelines to control the diseases. A perfect example is anti‐viral treatment in cases on herpes uveitis, which should be tailored when the causing herpes virus is identified.
Gene therapy strategies for hypoxia‐inducible angiogenesis in ocular neovascularization
Authors: ANDRE H. , Hertzman M. , Kristiansson A. , Svensson E. , Alatar S. , Ruononen J. , Lu Y. , Kvanta A.
Published: September 2017

Purpose

Our previous results have associated HIF expression in RPE cells to CNV progression, and we have shown that gene transfer of prolyl hydroxylase domain (PHD)2 in the mouse model of nAMD resulted in mitigation of HIF‐mediated angiogenesis. Here, we investigate the function of hypoxia‐regulated molecular elements in modulating the expression of transgenes in retinal pigment epithelium (RPE) cells, with putative use in gene therapy strategies for the treatment of nAMD.

Methods

Hypoxia‐mediated RPE‐specific expression vectors were generated using the minimum mouse Rpe65 promoter (pRpe65), while hypoxia‐mediated expression was achieved using hypoxia‐response elements (HRE) and oxygen‐dependent degradation peptides (ODP). Hypoxia‐dependent regulation of transgenes in ARPE‐19 cells was determined by green fluorescence protein (GFP) expression. Expression pattern analyses of transgenes in response to hypoxia and reoxygenation were assayed by western blot and RT‐PCR.

Results

Use of pRpe65 resulted in RPE‐specific expression of GFP. Hypoxia‐enhanced expression of GFP was achieved with HRE‐driven pRpe65, and GFP expression patterns were regulated at the transcriptional level. Fusion of ODP to GFP resulted in hypoxia‐mediated expression, under pRpe65 regulation, and GFP protein expression was subject to hypoxia‐dependent protein expression.

Conclusions

Our data shows that transgenes can be expressed specifically in RPE cells and be regulated by hypoxia, both by transcriptional and post‐translational regulation, limiting the therapeutic gene expression to pathologic hypoxic RPE cells. These results may have implications for the clinical treatment of ocular vascular pathologies, such as nAMD, particularly regarding the use of gene therapy to negatively regulate neoangiogenesis.
What is the meaning of autofluorescence in retinal diseases?
Authors: Kaarniranta K.
Published: September 2017

The fluorophore is fluorescent chemical compound that absorbs light energy of a specific wavelength and re‐emits light at a longer wavelength. The absorbed wavelengths, energy transfer efficiency, and time before emission depend on both the fluorophore structure and its chemical environment, as the molecule in its excited state interacts with surrounding molecules. Excitation energies range from ultraviolet through the visible spectrum, and emission energies may continue from visible light into the near infrared region. Recently, fundus autofluorescence (FAF) imaging has got more role in retinal diagnosis. FAF imaging is a quick and non‐invasive method. It provides information also from inside of the cells (RPE cells). For example lysosomal lipofuscin is highly autofluorescent compound. FAF is useful for monitoring disease progression, estimate age of lesions or severity level. However, FAF imaging is unspecific and observations must be combined with other diagnostic methods. In this course we discuss benefits and limitations of FAF in retinal diseases.
Histological analysis with OCT
Authors: Paterno J.
Published: September 2017

Each distinct retinal layer is visible on the optical coherence tomography (OCT). In clinic, the OCT has been part of diagnostics of retinal disease over 25 years, and due the technical advances, state‐of‐the‐art OCT technique provides an impressive non‐invasive tool for evaluating retinal anatomy in vivo, corresponding well to histological studies. This talk will discuss the current use and future of OCT in retinal disease research and disease models.
OCT‐A: guided treatment of diabetic retinopathy
Authors: Coscas G. , Lupidi M. , Coscas F.
Published: September 2017

Diabetic retinopathy (DR) is the leading cause of blindness in working‐age individuals in the developed world, affecting approximately 75% of patients with diabetes mellitus after 15 years. One of the early changes in diabetic eyes is loss of pericytes and proliferation of endothelial cells leading to the development of microaneurysms. Pericyte loss impairs the blood–retinal barrier, thereby leading to venous dilation and beading. The gold standard to screen for DR is dilated biomicroscopic fundus examination, where microaneurysms in the posterior pole are typically the first sign on ophthalmoscopy. Although fluorescein angiography is more sensitive than examination to detect early DR, it is invasive, costly, and time consuming, and therefore, is not appropriate as a screening test for DR. Optical coherence tomography angiography (OCT‐A) is a fast, noninvasive imaging technique that uses motion contrast to create OCT‐angiograms by comparing the decorrelation signal among sequential OCT B‐scans. Optical coherence tomography angiography may be a valuable screening tool for DR, useful as a clinical trial endpoint, and efficient in guiding early treatment decisions in the future.
Irradiation induced retinopathy: OCT‐A in the management and treatment
Authors: Zografos L.
Published: September 2017

Irradiation induced maculopathy is a major complication of conservative management of intraocular tumors. Risk factors include an irradiation dose of more than 20 Gy with proton beam or Gy with brachytherapy and co‐existing diabetes and high blood pressure. In irradiation induced maculopathy, we observe a disruption of the inner B/R barrier, a disruption of the outer B/R barrier and a progressive vaso‐occlusive microangiopathy. In a prospective trial, based on more than 150 cases of irradiation induced maculopathy, examined with fluoresceine angiography, OCT‐angiography, B‐mode OCT and OCT “en face”, the status of the deep capillary plexus in OCT‐A had the best correlation with the residual visual acuity. Intravitreal anti‐VEGF applied in cases with disrupted deep capillary plexus contribute to the maintain of the visual function and reduced the progressive perifoveal capillary loss.
Pars plana & ciliary sulcus drainage tubes
Authors: Bloom P.
Published: September 2017

Primary glaucoma surgeries, whether minimally invasive or trabeculectomy, are usually effective in lowering intra‐ocular pressure. However, in a proportion of cases the initial procedure is ineffective or the procedure fails; in this eventuality, comprehensive glaucoma specialists need to be skilled in a number or other surgical strategies.

Glaucoma drainage devices (‘tubes’) have long been used in complex or advanced cases, and are increasingly being used earlier on in the glaucoma treatment paradigm. In this part of the symposium, consideration will be given to instances where drainage tubes inserted into the anterior chamber are unlikely to be effective or have a high risk of failure. In such situations, there may be advantages for the drainage tube to be implanted through the posterior limbus or the pars plana.

Consideration will be given to the indications, techniques, advantages and complications of posterior tube implantation. Clinical case scenarios will be described using anterior segment photography and video presentations, so that skills and knowledge will be transferred effectively; this will allow assimilation of these techniques into the clinical practice of glaucoma specialist participants.
Ocular angiography: dual FA/ICGA scoring of posterior uveitis
Authors: Herbort C.P.
Published: September 2017

In the recent past uveitis has become an exact clinical science thanks, among others, to the availability of performing imaging methods. The SUN process (standardization of uveitis nomenclature) should have been the forum where these new imaging modalities should have been integrated. However SUN did just the opposite, perpetuating old and obsolete measurement methods. For the evaluation of posterior uveitis they recommended the more than 30 year old vitreous haze scoring system comparing vitreous haze to a set of 4 pictures with increasing grades of vitreous haze, recommending it as the gold standard and main outcome measure for clinical trials on new treatments in posterior uveitis. This method is subjective and has a scale of only 4 grades, improper to reach statistical significance even in cases with pronounced vitritis. Dual FA/ICGA angiography allows scoring of both retinal and choroidal inflammation with scales of respectively 40 for each. Such a numbered measurement modality is by far more adequate to measure posterior uveitis as it scores both the retinal and choroidal inflammation in entities that mostly have limited vitreitis. Several studies will illustrate the central role of FA/ICGA in monitoring posterior uveitis.
Tips and tricks in grossing & processing specimens
Authors: Moulin A.
Published: September 2017

This course will review the modalities to address the specimens for optimal histopathological processing and establishment of a correct diagnosis. It will cover orbital, palpebral, conjunctival and intraocular biopsies as well as larger resections. The course will be illustrated by clinicopathologic correlations from routine specimens.
Overview of adult and paediatric orbital pathology
Authors: Heegaard S.
Published: September 2017

An update of the most important orbital diseases both for adults and for children will be presented.Diagnostic hallmarks for the most important diseases will be shown and correlated to the clinical features.
Comparative ocular pathology and animal models used in eye research
Authors: Heegaard S.
Published: September 2017

This lecture dealing with comparative eye pathology will present various interesting animal eyes seen from a basic anatomical point of view but also seen as a potential animal eye model used for research. Anatomical differences in different animal eyes will be presented and nature's way of solving different eye problems is discussed.
Is macular pigment spatial profile a clinical biomarker in children of AMD parents?
Authors: Richer S. , Huntjens B. , Pratt S. , Rutledge G. , Perry B. , Novil S. , Pratt G.
Published: September 2017

A central dip in macular pigment (MP) has shown to be more prevalent with age, in AMD patients, and in smokers. We investigated clinical and genetic biomarkers in non‐smoking children of AMD parents (n = 131) over 40 years of age without AMD pathology in relation to their MP spatial profile. MP peak and volume were obtained with ARIS (Visual Pathways, Inc, Prescott, AZ USA) while spatial profiles for both eyes were classified visually and objectively. We explored risk factors including serum carotenoids and in‐vivo skin carotenoids, and cardiovascular biomarkers including omega‐3 fatty acids EPA and DHA, methylenetetrahydrofolate reductase C677T and A1298C in this well‐nourished Caucasian study group. Objectively, a central dip appeared more prevalent in children of AMD patients (41%) when compared to a healthy population. Those with central dip showed increased mean MP peak and volume, decreased serum L, Z, EPA and DHA, and decreased skin carotenoids in comparison to no dip. Identifying biomarkers in children genetically susceptible to AMD and introducing lifestyle changes such as nutrient repletion could provide invaluable advice to those associated with increased risk of AMD.
The importance of the polarity proteins CRB in the differentiation process of the RPE cells
Authors: Lillo C. , Paniagua A.E. , Segurado A. , Fernandez‐Dolón J. , Valle V. , Albertos H. , Velasco A.
Published: September 2017

Apicobasal polarity is essential for epithelial cell function, and it is determined by the expression of three polarity protein complexes: Scribble, Par and Crumbs. Both the Par and the Crumbs complex, promote apical membrane identity. Crumbs complex is composed by PALS1, PATJ and the Crumbs homologs (CRB) proteins. We have recently described the expression of one of the Crumbs proteins, CRB2, in the retinal pigment epithelial (RPE) cells. To better understand this process, we have studied the role of CRB2 in human RPE cells during differentiation in vitro and in the mouse retina in vivo. To achieve this goal, we analyzed the temporal sequence of the establishment of the polarity proteins during human fetal RPE cells polarization and knocking‐down CRB2, we analyzed the establishment of junctional complexes and features involved in the acquisition of polarization compared to the control RPE cultures. We demonstrate that, in differentiating RPE cells, CRB2 functions, as the sole CRB protein, in the formation of the junctional complex and apicobasal polarity. Additionally, the absence of the CRB2 protein from these cells results in a delay in the formation of cell‐cell junctions and in an increase in cell proliferation in RPE cells.
Interventions to increase attendance for diabetic retinopathy screening: a systematic review and meta‐analysis
Authors: Lawrenson J.G. , Graham‐Rowe E. , Lorencatto F. , Bunce C. , Burr J.M. , Francis J.J. , Rice S. , Aluko P. , Vale L. , Peto T. , Presseau J. , Ivers N.M. , Grimshaw J.
Published: September 2017

Purpose

Study objectives were to: 1) determine the effectiveness of interventions to improve diabetic retinopathy screening (DRS) attendance; 2) specify intervention content in terms of behaviour change techniques (BCTs); 3) determine whether interventions that included particular BCTs were more effective in increasing attendance.

Methods

We searched the Cochrane Library, MEDLINE, EMBASE and clinical trials registers to February 2017 for randomised controlled trials (RCTs) that were designed to improve attendance for DRS or were evaluating general quality improvement (QI) strategies for diabetes care and reported the effect of the intervention on DRS attendance. We did not use any date or language restrictions in the searches. We identified and categorised component BCTs using an established BCT Taxonomy (BCTTv1).

Results

We included 66 RCTs. QI interventions were multifaceted and targeted patients, healthcare professionals (HCPs) or healthcare systems. Overall, DRS attendance increased by 12% (risk difference (RD) 0.12 [95% CI 0.10‐0.14]) compared with usual care, with substantial heterogeneity in effect size. Both DRS‐targeted and general QI interventions were effective, particularly where baseline DRS attendance was low. All frequently identified BCTs were associated with significant improvements in attendance. Higher effect estimates were observed in sub‐group analyses for the BCTs ‘goal setting (outcome)’ (0.26 [0.16‐0.36]) and ‘feedback on outcomes of behaviour’ (RD 0.22 [0.15‐0.29]) in interventions targeting patients, and ‘restructuring the social environment’ (RD 0.19 [0.12‐0.26]) and ‘credible source’ (RD 0.16 [0.08‐0.24]) in interventions targeting HCPs.

Conclusions

RCT evidence indicates that QI interventions incorporating specific BCT components are associated with meaningful improvements in DRS attendance compared to usual care.
Cost‐effectiveness of intravitreal therapy with both anti‐VEGF and Dexamethasone implant in patients with Diabetic Macular Edema
Authors: D'amico Ricci G. , Bouzios D. , Boscia F. , Lupino M. , Pinna A.
Published: September 2017

Purpose

The aim of this study was to evaluate the cost‐effectiveness of intravitreal therapy (IVT) with both anti‐VEGF and Dexamethasone implant in patients with Diabetic Macular Edema (DME) during two years’ follow‐up.

Methods

A retrospective review of 191 patients (382 eyes) with type I and II diabetes and DME was performed. Pre‐IVT and final best correct visual acuity (BCVA), central macular thickness (CMT), intraocular pressure (IOP), number and type of IVT,number of examinations, and fluorescein angiography were assessed. Based on surgery procedure other than IVT, patients were divided into 5 groups. To avoid bias, we analysed only patients who had undergone cataract surgery before (group 1) or during enrolment (group 2).

Results

41 eyes from Group 1 and 48 eyes from group 2 were evaluated. Median BCVA ranged between 20/80 and 20/63 Snellen (P = 0.008) in Group 1 and from 20/63 to 20/40 Snellen (P = 0.0035) in Group 2, while improvement up to 1 Snellen line was observed in 58.5 and 68.75% of eyes in Group 1 and 2, respectively.In terms of median CMT, a statistically reduction (P = 0.0007) was found in Group 2 (‐85 μm), whereas no statistical differences were found in Group 1. The two groups showed no statistically significant difference in median IOP. The estimated cost per eye was €7803 in Group 1 and €8988 Group 2, whereas the mean cost per patient was €15190 and €16580 in Group 1 and 2, respectively. Analysis between groups did not show any statistical difference in the considered parameters.

Conclusions

In this study, despite the high treatment cost, vision improvement in DME patients undergoing IVT was disappointing. Our results emphasise the need for a better understanding of the cost‐effectiveness of DME treatment
Fluorescence lifetime imaging ophthalmoscopy
Authors: Dysli C. , Wolf S. , Zinkernagel M.S.
Published: September 2017

Fluorescence Lifetime Imaging Ophthalmoscopy (FLIO) allows in vivo measurement of autofluorescence lifetimes of natural retinal fluorophores upon laser excitation. Beyond fluorescence intensity, lifetimes provide further information about the metabolic state of the retina as they are dependent on micro environmental factors.

Fluorescence lifetimes were investigated in healthy retinae and compared with retinal diseases such as retinal artery occlusion, geographic atrophy due to age related macular degeneration, central serous chorioretinopathy, Stargardt disease, and choroideremia.

Retinal autofluorescence lifetimes feature disease specific patterns. They allow identifying differences within retinal deposits and changes of local or systemic metabolic conditions over time. Thereby, FLIO provides a promising tool for investigation of retinal metabolic changes. Especially neurodegenerative diseases associated with intracellular deposits shall be further investigated. As FLIO is a non invasive imaging technique which is easy to apply it might qualify as a screening technique for early detection of retinal changes also in neurodegenerative diseases.
What makes ocular surface anatomy attractive for a scleral lens?
Authors: Knop E.
Published: September 2017

The ocular surface consists of the moist mucosal organs at the anterior eye surface. They are a continuous anatomical unit from the lacrimal gland over conjunctiva & cornea into the lacrimal drainage system. Joined by the flow of tears and governed by regulatory systems, e.g. nerves, hormones & immune system ‐ thus they also form a functional unit as a constant moist chamber (for details please see: WWW.OSCB‐BERLIN.ORG). The main function is to provide the environment for vision by the entrance of light and its refraction.

“MOISTURE is KEY” because it keeps the cornea transparent and establishes the pre‐ocular tear film as main refraction unit. At the same time the moist chamber is highly endangered in our humid environment.

SCLERAL CONTACT LENSES are large contact lenses that rest on the sclera and vault over the cornea by providing a pool underneath, with the patient′s own tears including all factors for nutrition & regulation. Sclerals are thus a unique medical tool to restore both essential functions when the ocular surface and particularly the cornea is altered: constant moisture and a homogeneous refraction interface. In addition they shield the cornea against the chronic mechanical forces in eye movements and blinking.
Two photon microscopic findings of sonoporation‐assisted enhancement of corneal penetration of fluoroquinolone antibiotics
Authors: Lee J.A. , Jeong H. , Kim J.Y. , Tchah H. , Kim K.H. , Kim M.J.
Published: September 2017

Purpose

To investigate the sonoporation‐assisted enhancement of corneal penetration of fluoroquinolone antibiotics.

Methods

Enucleated mouse corneas were imaged by two‐photon microscopy to observe normal corneal structure ex vivo. For estimation of the threshold of corneal epithelial damage, sonoporation was applied with different intensities (1.5, 2.0 and 3.0 W/cm2) for 5 minutes on each cornea. Gatifloxacin and besifloxacin were applied on each cornea and the depth of drug penetration was observed with two‐photon microscopy. After sonoporation (1.5 and 1.7 W/cm2, respectively) was applied with fluoroquinolone eyedrops, we compared the aspects of drug penetration in sonoporated cornea with those in normal cornea. In vivo two photon microscopy imaging was conducted with gatifloxacin application.

Results

Normal cornea observed with two‐photon microscopy showed regular arrangement of epithelial cells without any damaged cells. Threshold intensity of sonoporation that can damage some epithelial cells without significant structural destruction was determined as 1.5~2.0 W/cm2. When gatifloxacin was applied on normal cornea, gatifloxacin fluorescence was observed only on surface of corneal epithelium. After sonoporation, whole epithelium showed increased gatifloxacin and besifloxacin fluorescence. But the penetration depth and the extent of Besifloxacin were less than those of gatifloxacin, due to its own molecular structure. The threshold intensity was revealed as 1.3 W/cm2 in vivo. In vivo corneal penetration of gatifloxacin enhanced after sonoporation, and this result was comparable with that of ex vivo.

Conclusions

We observed the enhancement of corneal penetration of fluoroquinolone antibiotics after sonoporation was done on mouse cornea ex vivo as well as in vivo. Besifloxacin showed poor penetration compared with gatifloxacin even after sonoporation.
Nevus, melanocytoma and melanoma: differential diagnosis
Authors: Shields C.
Published: September 2017

A major analysis on 3680 cases of iris tumors revealed two main types of tumors including solid (79%) and cystic (21%). The most common solid mass was the melanocytic tumor, which included nevus (60%), melanocytoma (3%), and melanoma (26%).

Iris nevus is benign. This tumor tends to occur in the inferior portion of the iris. In an analysis of 1611 consecutive eyes with iris nevus, growth into melanoma was documented in 4% at 10 year followup. Statistical analysis for nevus at greatest risk for growth can be remembered by the lettering ABCDEF representing Age (< 40 years), Blood (hyphema), Clock hour inferior, Diffuse configuration, Ectropion, Feathery margins.

Iris melanocytoma is benign and appears as a dark brown mass, occasionally with iris and angle seeding. This tumor carries 1% risk for transformation into melanoma.

Iris melanoma is malignant and represents 4% of all uveal melanomas. This tumor exhibits slow growth. An analysis of 317 eyes with iris melanoma documented risk for metastasis at 10 years in 9%. Factors predictive of metastasis included extraocular extension and secondary glaucoma.

Differentiation and understanding the behavior of these three similar‐appearing tumors is important in their management.
Circumscribed irido‐ciliary melanoma: surgery versus irradiation
Authors: Desjardins L. , Cassoux N. , LumbrosoLeRouic L. , Dendale R.
Published: September 2017

Iris tumors include congenital benign cyst, naevi, melanocytomas malignant melanomas, benign adenoma,leiomyomas, metastatic tumors, iris location of leukemia or lymphomas and histiocytic proliferations like iris xanthogranuloma.

Patients with metastatic disease rarely develop a bilateral diffuse melanocytic uveal proliferation (BDUMP) which can cause retinal detachment and blindness.

The diagnosis of an iris tumor is made by careful medical history, slit lamp examination, UBM ultrasonography and OCT of the iris.

In rare instances fine needle aspiration biopsy can be useful but follow up is often the more important test to differentiate stable naevus versus malignant melanoma of the iris.

Treatment can be a simple observation for naevi or melanocytoma..Surgery is still the best option for adenomas and leiomyomas. Metastatic disease can be treated by chemotherapy and external beam radiation. Xanthogranulomas of the iris usually respond well to steroids. For melanoma of the iris a lot of centers do not use surgery and prefer radiotherapy most often proton beam radiotherapy. Results of proton beam therapy of iris melanoma will be presented.
In vitro modeling of aniridia‐related PAX6 haploinsufficiency by the use of CRISPR/Cas9 on limbal epithelial cells
Authors: Roux L. , Concordet J.P. , Ferrigno O. , Aberdam D.
Published: September 2017

Purpose

Haploinsufficiency of PAX6 in humans is the main cause of congenital aniridia, a rare eye disease characterized by iris hypoplasia and reduced visual acuity. Patients have also progressive disorders including cataract, glaucoma and corneal abnormalities making their condition very challenging to manage. Aniridia‐related keratopathy (ARK), caused by a combination of factors including limbal stem‐cell deficiency, impaired healing response, abnormal differentiation, and infiltration of conjunctival cells onto the corneal surface, affects up to 95% of patients. It usually begins in the first decade of life resulting in recurrent corneal erosions, sub‐epithelial fibrosis with corneal decompensation and opacification. Unfortunately, current treatment options for aniridia patients are currently limited. Although animal models partially recapitulate this disease, there is no in vitro cellular model of AKT needed for drug/therapeutic tools screening and validation.

Methods

We used genome editing (CRISPR/Cas9 technology) to introduce a nonsense mutation into one allele of the PAX6 gene in TERT‐immortalized limbal cells, which remain identical to primary limbal cells able to differentiate into corneal cells upon calcium raise at confluency.

Results

A resulting mutated clone, expressing half of the amount of PAX6 protein and thus representative of haploinsufficiency, was further characterized. Sequencing analysis showed that no off‐target mutations were induced. The mutated cells displayed reduced cell proliferation and cell migration but enhanced cell adhesion. Known PAX6 targets expression was also reduced. Remarkably, addition of recombinant PAX6 protein was able to activate endogenous PAX6 gene and, as a consequence, rescue partially the phenotype.

Conclusions

Our in vitro model will be powerful to identify drugs that could rescue the corneal defect.
Association between the retinal vascular network, cardiovascular history and risk factors in the elderly
Authors: Arnould L. , Binquet C. , Guenancia C. , Kawasaki R. , Daien V. , Bron A. , Creuzot‐Garcher C.
Published: September 2017

Purpose

To identify patterns summarizing the retinal vascular network in the elderly and to investigate the relationship of these vascular patterns with cardiovascular history.

Methods

We conducted a population‐based study, the Montrachet study (Maculopathy Optic Nerve nuTRition neurovAsCular and HEarT diseases), in participants older than 75 years. History of cardiovascular disease and a score‐based estimation of their 10‐year risk of cardiovascular mortality (Heart SCORE) were collected. Retinal vascular network analysis was performed by means of Singapore “I” Vessel Assessment (SIVA) software. Principal component analysis was used to condense the information contained in the high number of variables provided and to identify independent retinal vascular patterns.

Results

Overall, 1069 photographs (1069 participants) were reviewed with SIVA software. The mean age was 80.0 ± 3.8 years. We extracted three vascular patterns summarizing 41.3% of the vascular information. The most clinically relevant pattern, Sparse vascular network, accounted for 17.4% of the total variance. It corresponded to a lower density in the vascular network and higher variability in vessel width. Diabetic participants with hypoglycemic treatment had a sparser vascular network pattern than subjects without such treatment (Odds ratio, [OR], 1.68; 95% CI, 1.04–2.72; P = 0.04). Participants without history of cardiovascular disease who had a sparser vascular network were associated with a higher Heart SCORE (OR, 1.76; 95% CI, 1.08–2.25; P = 0.02).

Conclusions

Three vascular patterns were identified. The Sparse vascular network pattern was associated with being a higher risk profile for cardiovascular mortality risk at 10 years.
X‐linked juvenile retinoschisis: different mutations – same phenotype
Authors: Strupaite R. , Ambrozaitytė L. , Cimbalistienė L. , Ašoklis R. , Utkus A.
Published: September 2017

Purpose

To describe the phenotype‐genotype correlation of three X‐linked retinoschisis (XLRS) cases in juveniles with different novel mutations from Lithuanian population.

Methods

Based on clinical symptoms and family history, a preliminary diagnosis of XLRS was established in three adolescent male patients. Comprehensive ophthalmological examinations, including best‐corrected visual acuity (BCVA), slit‐lamp, fundus examination, spectral domain optical coherent tomography (SD‐OCT) and full‐field electroretinography, were performed. RS1 (NM_000330.3) gene coding exons Sanger sequencing was performed.

Results

At the time of ophtalmic and genetic counselling the patients were 9, 12 and 17 years old. The patients demonstrated macular retinoschisis and typical cyst‐like cavities on SD‐OCT images with logMAR BCVA ranging from 0.5 to 0.2. The mean central foveal thickness was 569.7 μm. Two of the three patients presented with peripheral retinoschisis. Flash‐ERG demonstrated a reduced b/a ratio (<1.0) in all patients. RS1 c.599G>T (p.R200L) mutation was detected in one case, in silico analysis showing to be pathogenic. HGMD involves three other different mutations at the same position supporting the pathogenicity of the identified variant. c.(92_97)insC (p.W33 fs) mutation was identified for another proband, in silico analysis indicating the variant is possibly damaging. The third case was identified with a pathogenic mutation c.422C>G (p.R141H), HGMD CM981753.

Conclusions

These are the first cases of XLRS in the Lithuanian population confirmed by molecular genotyping. Although clinical expression of XLRS is highly variable presented patients had a different genotype but similar phenotypic traits. Functional analysis would be of benefit to characterise the identified variants on the effect of retinoschisin expression.
Non‐surgical treatment of idiopathic macular hole (IMH)
Authors: Xirou T.
Published: September 2017

Ocriplasmin and Pneumatic vitreolysis are the two non surgical treatment options for the management of IMHs. While closure of IMH after vitrectomy has a success rate very high, it is challenging the option of managing IMHs without the necessity of a surgical procedure. Cost‐effectiveness and safety profile are the main parameters to be considered in these relative new non surgical treatment options, mainly proposed for IMHs less than 400 μm in diameter with vitreomacular traction.
Why the eye? Current understanding on the pathogenesis of ocular toxicities
Authors: Neri P. , Nicolai M. , Bisceglia P.
Published: September 2017

The increased use of several different pharmaceutical agents has provided a positive impact to patients benefits. On the other hand, the ophthalmologist is seeing more patients with ocular side effects secondary to such agents. In particular, ocular toxicity induced by cancer chemotherapy, biologic agents and immunesuppressive drugs includes a broad spectrum of disorders, which reflect the peculiar physiological, anatomical and biochemical characteristics of the eye. The progresses achieved by the science in understanding ocular biostructure has allowed a better knowledge on ocular side effects. This achievement assists the ophthalmologist and other specialists to recognize them early and intervene before severe visual impairment occurs. A prompt intervention for the treatment‐related toxicities may also provide the opportunity for a minimization or resolution of an expected side effect. Therefore, ophthalmologist should examine patients for any therapy that can present potential ocular side effects, according to the type of used drug. The biostructure and pathophysiology of potential toxicity of different drugs will be reviewed.