bluuebunny/crossref_metadata_2025 huggingface dataset:
Bilateral quantification of vascular density in diabetic patients using optical coherence tomography angiography
Authors: Czako C. , Ecsedy M. , Récsán Z. , Szepessy Z. , Resch M. , Borbándy Á. , Tátrai E. , Sándor G. , Horváth H. , Zsolt Nagy Z. , Kovács I.
Published: September 2017

Purpose

To measure capillary vessel density (VD) using optical coherence tomography angiography (OCT‐A) in both eyes of diabetic patients and to evaluate its correlation with systemic risk factors.

Methods

A total of 103 eyes of 61 diabetic patients underwent OCT‐A imaging (RTVue‐XR Avanti; Optovue, Fremont, CA, USA). The control group included 92 eyes of 46 individuals without diabetes mellitus. In diabetic patients the duration of diabetes, insulin therapy, blood pressure, HbA1C, dyslipidemia and the presence of diabetic retinopathy was recorded. VD was examined in the central macula with a radius of 3 mm. The effect of risk factors on VD was assessed bilaterally using multivariable regression analysis.

Results

Vessel density was significantly decreased in diabetic patients compared to controls (47.26 vs. 50.88%; p < 0.001). In control subjects, VD significantly decreased with age (r = −0.54; p < 0.001), while in diabetic patients VD was associated only with the duration of diabetes among the risk factors (r = ‐0.15/year, p = 0.03). VD was also significantly decreased in diabetic patients without clinically detectable diabetic retinopathy compared to control subjects (48.19 vs. 50.88%, p < 0.001). Between‐eye difference in VD were significantly higher in diabetic patients with retinopathy (4.46±2.95%) and without retinopathy (4.19 ± 2.40%) in comparison to the controls (2.74 ± 2.24%; p = 0.02 for both comparisons).

Conclusions

Significantly decreased retinal vessel density and increased between‐eye asymmetry can be measured in diabetic patients compared to control subjects even before the presence of clinically detectable diabetic retinopathy. While in control subjects vessel density decrease with aging, in diabetic patients both vessel density and between‐eye asymmetry are significantly associated with the duration of diabetes.
Differential diagnosis of cystoid macular edema by optic disc thickness in optical coherence tomography
Authors: Cardigos J. , Crisostomo S. , Basilio A. , Costa L. , Carvalho B. , Vieira L. , Flores R.
Published: September 2017

Purpose

The differential diagnosis between Irvine‐Gass Syndrome (IGS) and Diabetic Macular Edema (DME) is currently established by angiography, which is an invasive and time‐consuming tool. The aim of this study is to evaluate differences in optic disc's nerve fiber layer thickness (RNFL) in patients with macular edema associated with IGS and Diabetes Mellitus (DM).

Methods

Retrospective case control study of 28 eyes of 28 patients with macular edema divided into 2 groups. Group 1 included 14 eyes with IGS diagnosed by clinical and angiographic criteria and group 2 included 14 eyes with cystoid diabetic macular edema (DME) without previous ocular surgery. A control group (group 3) of 14 eyes of 14 healthy patients paired by age and gender were also included. Ophthalmologic examinations included visual acuity (VA) measurements, slit‐lamp examination, Goldmann applanation tonometry, Spectral‐Domain Optic Coherence Tomography (SD‐OCT) and fluorescein angiography.

Results

Forty two patients (21 females and 21 males), with a mean age of 66.57 ± 10.80 years were included in this study. Optic disc nasal and temporal RNFL thicknesses as well as central macular thickness were significantly higher in group 1 and 2 compared with control group (p < 0.05). Nasal RNFL thickness was higher in IGS than in patients with DME (p < 0.001). To detect IGS (Group 1), comparative to DME (Group 2), using Nasal RNFL thickness, the area under the curve was 0.842 p < 0.002. A cut‐off criterion of 82.50 μm resulted in 92.9% sensitivity and 71.4% specificity.

Conclusions

Optic disc SD‐ OCT imaging might be a useful diagnostic tool to differentiate IGS from DME.
Intraconal hybrid neurofibroma ‐ schwannoma of the orbit
Authors: Verhelst E. , Lauwers N. , Siozopoulou V. , de Keizer R.W.J. , De Groot V.
Published: September 2017

Purpose

Among peripheral nerve sheet tumors, an orbital hybrid neurofibroma‐schwannoma has been described twice. We describe a third case of orbital tumor with features of both a neurofibroma and a schwannoma.

Methods

Case report. A 39 year old man presents with diplopia and decreased vision (0.6) in the left eye. He has a proptosis of 7 mm, with mechanical restriction of elevation and horizontal eye movements. MRI shows a well‐defined lesion (2,5 x 1,9 x 2,3 cm) in the superotemporal intraconal space, displacing the globe, optic nerve and superior and lateral rectus muscles. The tumor demonstrates heterogeneous contrast enhancement, and is diagnosed as a probable cavernous hemangioma. Through a transconjunctival approach a red‐blueish lesion was found with a thin capsule and without lateral adhesions. The tumor could be extracted in 2 parts and consisted of a yellow/white coherent soft mass.

Results

Patient had complete recovery of visual acuity, and only diplopia in extreme lateral gaze. The pathology revealed a tumor composed of small spindle cells arranged in fascicles. The cells showed no atypia and there was no mitotic activity. There were also less cellular areas with a myxoid component. At places we could recognize a fibrous capsule surrounding the tumor. The tumor cells were strongly and diffuse positive with S100. In a few enclosed axons there was focal reactivity with neurofilament. The image is that of a neural tumor with features of both a neurofibroma and a Schwannoma.

Conclusions

This is the third reported orbital hybrid neurofibroma‐schwannoma. Although this type of tumor elsewhere in the body is often associated with schwannomatosis and neurofibromatosis, our patient did not show signs of systemic involvement.
The advantages of serological tests of blood and tears for the diagnosis and the follow up of corneal rickettsiosis
Authors: Benabderrahim K. , Feki J. , Khairallah M.
Published: September 2017

Purpose

Serological tests were rarely performed in the first intention in the diagnosis of corneal rickettsiosis in patients from an endemic area. The purpose is to elucidate the advantages of serological tests for rickettsiosis in the atypical cases of corneal infections

Methods

Case series study included 03 patients. immunofluorescent‐antibody tests were performed to detect rickettsiosis in the blood and in the tears

Results

2 patients with atypical disciform keratitis, 1 patient with panuveitis with corneal involvement. Rickettsiosis was suspected because of skin palpebral lesions in 2 patients and in chronic uveitis in the 3rd patients. Serological tests were positive in the blood and in the tears. Treatment with tetracyclin was effective in the three cases without use of corticotherapy. In the follow up, good evolution of corneal signs and negative serological tests were noted.

Conclusions

Rickettsiosis should be considered in the etiology of atypical cases of corneal infection and serological blood and tear testing should be performed firstly in patients from an endemic area.
Retinal vasculitis
Authors: Bodaghi B.
Published: September 2017

Nearly all etiologies of intermediate, posterior or panuveitis may be associated with retinal vasculitis. The clinical analysis of different inflammatory markers is the first step for diagnostic orientation and further work‐up. Different cases will be discussed in an interactive manner in order to highlight the vascular type of involvement, associated vitreous inflammation, macular edema, retinal or choroidal lesions such as granuloma or ischemia. A systemic autoimmune, autoinflammatory or infectious disease have also to be taken into consideration. Therapeutic options remain significantly large, ranging from close monitoring to corticosteroids, different types of immunosuppressors, biolgics, antimicrobials, anti‐VEGFs, laser photocoagulation and rarely vitrectomy. Prognosis is variable based on etiology, diagnostic delay and therapeutic efficacy.
Human case
Authors: Sergouniotis P. , Ellingford J. , Hall G. , Ramsden S. , Biswas S. , Ashworth J. , Black G.
Published: September 2017

Inherited eye disease cases will be presented with an emphasis on conditions with readily recognisable features that aid precise diagnosis. Cases of monogenic disorders mimicking common, multifactorial disease will also be shown. The value of genomic testing will be highlighted and the role of investigations to exclude/identify extraocular involvement will be discussed.
The supportive role of interferon‐γ in retinal differentiation of mesenchymal stem cells
Authors: Hermankova B. , Kossl J. , Javorkova E. , Bohacova P. , Hajkova M. , Zajicova A. , Krulova M. , Holan V.
Published: September 2017

Purpose

Retinal disorders represent a serious health problem causing a decreased quality of vision or even blindness. There are currently no effective treatment protocols for these disorders. The promising approach for the treatment of retinal disorders is stem cell‐based therapy. Mesenchymal stem cells (MSCs) are a perspective candidate due to their possibility to migrate to the site of injury, differentiate into multiple cell types and produce a number of trophic factors. In this study we analysed the potential of murine bone marrow‐derived MSCs to differentiate into cells expressing retinal markers and tested the possibility to express neurotrophic factors by differentiated MSCs.

Methods

Flow cytometry was use to characterize the phenotypic markers of murine MSCs isolated from bone marrow. The retinal extract were prepared by homogenization of posterior segments of the mouse eyes and the supernatants were prepared by stimulation of spleen cells with Concanavalin A. MSCs were cultured with retinal extract and supernatants simulating the environment of retinal damaged for 7 days. The expression of genes for retinal markers and growth factors by MSCs was detected using real‐time PCR.

Results

MSCs cultured with retinal extract and supernatant differentiated to the cells expressing retinal cell markers. To identify a supportive molecule in the supernatant from activated spleen cells, MSCs were cultured with retinal extract in the presence of various T‐cell cytokines. The expression of retinal markers was enhanced only in the presence of IFN‐γ, and the supportive role of spleen cell supernatants was abrogated with the neutralization antibody anti‐IFN‐γ.

Conclusions

The results show the supportive role of IFN‐γ in differentiation of MSCs to the cells expressing retinal cell markers and the enhanced ability of differentiated cells to express growth factors.
Forgetting malignancies
Authors: Sen H.N.
Published: September 2017

Masquerade syndromes are a rare group of neoplastic or non‐neoplastic disorders that present as uveitis. Approximately 40% of all uveitis cases remain idiopathic despite exhaustive clinical and laboratory investigations. The consequence of missing a malignant masquerade syndrome can be devastating. Among uveitis patients older than 60 years, malignancy constitutes 1.5‐5% of all cases. Among uveitis patients of all ages malignant masquerade syndromes constitute only 2‐3% of cases in tertiary uveitis centers. There are some distinguishing characteristics between uveitis patients and neoplastic masquerade patients: patients with neoplastic masquerade often present at an older age, have unilateral disease and posterior segment involvement and are more likely to be Caucasian. Diagnosis of malignancies in the eye can be difficult but important and clinical features at presentation can help raise suspicion. Early diagnosis and intervention not only saves vision and improve quality of life but it can also be life‐saving.
Plasmalogens and cell‐cell communication between retinal glial cells
Authors: Bron A. , Mazzocco J. , Leclere L. , Fenech C. , Grall S. , Buteau B. , Gregoire S. , Creuzot‐Garcher C. , Leloup C. , Bretillon L. , Fioramonti X. , Acar N.
Published: September 2017

Purpose

Plasmalogens are glycerophospholipids containing a vinyl‐ether bond at sn‐1 position of their glycerol backbone and polyunsaturated fatty acids (PUFAs) at sn‐2. We have previously shown that plasmalogens are involved in the regulation of perinatal retinal vascular development and particularly in astrocyte template formation (Saab et al, PLoSONE 2012 9(6):e101076). Since retinal Müller cells and astrocytes can communicate through calcium waves and connexin 43‐rich gap junctions, the aim of our study was to determine whether a reduction of plasmalogen levels affects communication between retinal glial cells.

Methods

Primary Müller cells and astrocyte were isolated from retinas of 9‐days old and cerebral cortex from 21‐days old Wistar rats, respectively. SiRNA against DHAPA‐AT ‐the key enzyme of plasmalogen biosynthesis‐ were used to decrease plasmalogen content of Müller cells before they were co‐cultured with naïve astrocytes. Calcium waves initiated in Müller cells by topical application of ATP were monitored by Fura‐2 calcium imaging. Expression levels of cellular proteins involved in calcium metabolism, including connexin 43, were evaluated by proteomics and Western‐blotting in reponse to Si RNA treatment.

Results

Treating Müller cells with SiRNA against DHAP‐AT led to a reduction of plasmalogen content of about 60% and to a remodelling of PUFA distribution in cell membranes. The expression of connexion 43 was reduced by more than 50% in Müller cells treated with SiRNA. This was associated with an alteration of calcium waves originating from Müller cells as well as a slowed propagation to neighbouring astrocytes.

Conclusions

These data suggest that membrane plasmalogens content influences cell‐to‐cell communication between retinal Müller cells and astrocytes. Altered coupling between these cells might be one of the factors influencing perinatal vascular development.
Modulation of the rod outer segment aerobic metabolism diminishes the production of radicals due to light absorption
Authors: Panfoli I. , Calzia D. , Degan P. , Caicci F. , Manni L. , Traverso C.E.
Published: September 2017

Purpose

Oxidative stress is a primary risk factor for inflammatory and degenerative retinopathies. Irradiation with blue light of eye explants was shown to cause an oxidative stress, higher in the rod outer segment (OS) than in the inner limb, ultimately impairing the extra‐mitochondrial aerobic metabolism of the OS. Here, to establish a correlation between the energy metabolism and phototransduction, the aerobic metabolism of purified bovine rod OS was assayed in function of exposure to either ambient or dim light.

Methods

Isolated bovine rod OS, purified by Fycoll/sucrose gradient were utilized. Production of Reactive Oxygen Intermediates (ROI) was evaluated by citofluorimetry, with dihydrorhodamine 123 (DHR) probe; ATP synthesis and oxygen consumption were assayed by luminometry or oximetry, respectively. When necessary, isolated OS were preincubated with 30 μM Resveratrol, for 15 min, or 5 mM Metformin, for 2 h.

Results

Upon exposure to ambient light for 1 h, a significant increase in oxygen consumption as well as ATP synthetic ability by rod OS was observed, along with a consistent ROI production, with respect to dim light, i.e. the physiological rod conditions. Pretreatment with resveratrol, inhibitor of F1Fo‐ATP synthase, or metformin, inhibitor of the respiratory complex I, significantly diminished the ROI production in vitro.

Conclusions

Data show for the first time the relationship between light and the rod OS metabolism. A production of ROI by the OS in vitro was also observed, positively correlating to light exposure. A beneficial effect of metformin and resveratrol was found, as modulators of ROI production, consistently with their inhibitory action on the complexes I and V of respiration, respectively. Data shed new light on the prevention of the cone loss secondary to rod damage due to oxidative stress.
Tube surgery in scarry eyes!
Authors: Ahmed F.
Published: September 2017

The use of glaucoma drainage devices (GDD) has been a vital advancement in the management of patients with refractory glaucoma. However, GDD implantation can be difficult‐ due to either the disease pathology or scarring from previous surgery.

The aim of this presentation will be to show examples of implanting GDD in eyes in which conventional GDD surgery is difficult.

The second part of the presentation will be looking at approaches on how to manage eyes with uncontrolled intra‐ocular pressure even after glaucoma drainage device implantation.
Ocular fluid analysis to pin down the cause of inflammation
Authors: Neri P. , Gorgoni F. , Pirani V. , Pelliccioni P. , Nicolai M.
Published: September 2017

The accuracy for the diagnosis of inflammatory eye diseases is a crucial step for an appropriate treatment strategy and their management in general. In most of the cases, non‐invasive techniques, such as fluorescein angiography, indocyanine green angiography and optical coherence tomography, can lead to a correct diagnosis. In addition, blood tests and neuro‐imaging can be strongly contributory. However, it has been estimated that in 8% of cases with uveitis, approximately, the clinical presentation can be atypical and, moreover, systemic medical evaluation might be non‐conclusive. In order to minimize such ambiguities, diagnostic sampling of ocular fluids can help in determining the etiology of the disease, and can provide sufficient evidences for the treatment management. The diagnostic tests for atypical or uncertain uveitis subsets include: anterior chamber tap, vitreous biopsy and chorioretinal biopsy. This lecture will focus on the indications, techniques, reliability and limitations of vitreous biopsy for ocular inflammatory or pseudo‐inflammatory diseases.
New biomaterials and ocular drug delivery
Authors: Sheardown H. , Muirhead B. , Zhang J.
Published: September 2017

The need for new methods of delivering pharmacologically active agents to the eye has never been greater with the growing incidence of ocular disorders. Polymeric drug delivery methods show great promise for enhancing drug residence time as well as convenience for the patient. This talk will focus on three novel polymer based drug delivery systems developed in our labs. A mucoadhesive micelle system has been developed using acceptable polymers and has been shown to enhance the on eye residence time and the delivery of cyclosporine A in the treatment of dry eye disease. A transparent, in situ gelling injectable system has been examined to enhance the delivery of various drugs for treating diseases of the back of the eye. Finally, a Vitamin E based system is injectable, gelling upon exposure to aqueous conditions will be described. The potential of these systems as well as their limitations will be discussed and next steps in their development with a goal of creating a clinically viable drug delivery system will be described.
Overview of conjunctival and eyelid tumours
Authors: Van Ginderdeuren R.
Published: September 2017

In this part of the course an overview will be given of the most common and most important conjunctiva and eyelid tumours (basal cell carcinoma, squamous cell carcinoma, sebaceous cell carcinoma, malignant melanoma). For each disease clinical‐pathologic correlations will be emphasized. Typical and atypical characteristics will be shown.

In most cases the clinician finds the correct diagnosis, but even then it is important to investigate the section margins and the degree or details of the tumour. In rare cases a surprise in diagnosis is found and some important examples of these will be given, with also the useful consequences on the clinical follow‐up of these patients.

Correct diagnosis can also be useful in non‐malignant processes and examples will be given.

A short overview will be given of newer techniques and diagnostic possibilities.
A review of the nature & role of pre‐receptoral, wavelength‐selective, ocular filters in vertebrates
Authors: Douglas R.
Published: September 2017

Such filters are widespread in all vertebrates groups, most notably fish. Several species have pigmented corneas, whose density may alter with illumination. Filters within lenses are common, occurring in animals that inhabit well‐lit environments as well as the deep‐sea. Pigmented humours are rare but have been reported in a few species. Various layers within the retina also contain pigments, including the primate macular pigment, that absorb short wavelength light and the inner segments of many animals, such as birds, contain coloured oil droplets.

While many of these filters are various carotenoids, other substances such as mycosporine‐like amino acids, are common. The variety of filtering pigments indicates pigmentation has evolved independently on a number of occasions; a clear testament to its importance.

Most pigments serve to reduce short wavelength light and have a variety of functions including; protection of the eye by removing the most damaging photons, acting as antioxidants, and improving image quality by reducing scatter. In deep‐sea fish they enhance the visibility of bioluminescence and in animals with oil droplets they refine the spectral properties of photoreceptors.
A review of motion photometry in the assessment of macular pigment distribution profiles obtained over two decades; applications and insights
Authors: Robson A. , Moreland J.
Published: September 2017

This presentation will review the use of a Moreland anomaloscope, modified for motion photometry, in the assessment of macular pigment (MP) over the last 20 years. Early studies examined the influence of MP on chromatic visual evoked potentials and highlighted the limitations of monitor‐based methods of MP quantification, involving the use of carotenoid solutions to simulate MP. Detailed examinations using motion photometry characterised a wide range of MP distribution profiles and revealed a lack of correlation between peak optical density at the fovea and computations of the total complement of MP within the central 15 degrees, corroborated using 2‐wavelength fundus autofluorescence measurements. Motion photometry assessments in individuals with widely different MP distribution profiles demonstrated a high degree of stability over periods of up to 19 years, pertinent to studies that aim to monitor MP in disease or modify MP through dietary supplementation.
A genome‐wide association study suggests that the NADPH Oxidase 4 (NOX4) gene is associated with severe diabetic retinopathy in a Scottish diabetic population
Authors: Meng W. , Hebert H. , Palmer C.
Published: September 2017

Diabetic retinopathy is one of the devastating eye complications in patients with diabetes. The purpose of this study is to investigate the genetic contributors of severe diabetic retinopathy using a Scottish diabetic population through a genome‐wide association approach. In the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) datasets, cases of severe diabetic retinopathy were defined as type 2 diabetic patients who were ever graded as having severe background retinopathy (Level R3) or proliferative retinopathy (Level R4) in at least one eye according to the Scottish Diabetic Retinopathy Grading Scheme or who were once treated by laser photocoagulation. Controls were diabetic individuals whose longitudinal retinopathy screening records were either normal (Level R0) or only with mild background retinopathy (Level R1) in both eyes. 560 cases of type 2 diabetes with severe diabetic retinopathy and 4,106 controls were identified in the GoDARTS cohort. We revealed that rs3913535 in the NADPH Oxidase 4 (NOX4) gene reached a p value of 4.05 × 10−9. This genome‐wide association study of severe diabetic retinopathy suggests that the NOX4 gene might play a role in retinopathy.
A systematic review of the associations between dietary intake and diabetic retinopathy
Authors: Wong M. , Man R. , Gupta P. , Fenwick E. , Li L.J. , Lamoureux E.
Published: September 2017

Purpose

The evidence linking diet with diabetic retinopathy (DR) is growing, but DR‐specific dietary guidelines are still lacking. We conducted a comprehensive systematic assessment of the association between dietary intake and DR, and determined key areas for further research.

Methods

PubMed, Embase, Medline, and the Cochrane Central register of controlled trials were systematically searched for papers published between Jan 1967 and Jan 2017 according to standardized criteria. Interventional and observational studies, investigating nutrient intake, food and beverage consumption, and dietary patterns, were included. Data extraction was performed through a standardized extraction form, and study quality was evaluated using a modified Newcastle‐Ottawa scale for observational studies, and the Cochrane collaboration tool for interventional studies.

Results

Of 4265 titles initially identified, 31 studies (3 interventional, 9 cohort, 4 case‐control, 15 cross‐sectional) were retained. The evidence suggests the intake of dietary fibre, oily fish, and a Mediterranean diet to be protective of DR. Conversely, higher caloric intake was associated with higher DR risk. No significant associations of DR with carbohydrate, vitamin D and sodium intake were found. The association between DR and antioxidants, fatty acids, proteins, alcohol, and other popular beverages such as tea and coffee remains equivocal.

Conclusions

Diet is a crucial aspect of DR management, with dietary components including dietary fibre, oily fish, and a Mediterranean diet being protective of DR, and a high caloric intake associated with greater DR risk. However, further cohort studies to untangle the effects of other key dietary components on DR, such as antioxidants, fatty acids, proteins, alcohol and popular beverages, are needed in order to better inform clinical guidelines.
Topical betamethasone sodium phosphate, tetracycline hydrochloride and nonsteroidal anti‐inflammatory drugs in the treatment of diabetic macular edema: a case report
Authors: D'Amico Ricci G. , Bouzios D. , Boscia F. , Pinna A.
Published: September 2017

Purpose

To report a case of clinically significant diabetic macula edema (DME) cured only with topical Betamethasone Sodium Phosphate, Tetracycline Hydrochloride and nonsteroidal anti‐inflammatory drugs.

Methods

A 44‐year‐old type I diabetic woman was referred to our Unit after a partial tarsorrhaphy procedure for exposure keratopathy in her left eye. OCT examination of her right eye revealed a clinically significant DME with important visual loss (Central Macular Thickness [CMT] 716 μm, Best Correct Visual Acuity [BCVA] 20/100 Snellen). The patient refused the suggested intravitreal therapy (Ranibizumab injections with PRN protocol). Topical treatment with Betamethasone Sodium Phosphate, Naphazoline Nitrate, Tetracycline Hydrochloride (Alfaflor®, Alfa Intest, Italy) and Diclofenac (Voltaren Oftabak®, Thea, France) eye‐drops 4 times/day was started.

Results

In the following 10 months, right CMT decreased to 335 μm and right BCVA increased to 20/25 Snellen. However, OCT scans still showed some intraretinal cysts. Topical Diclofenac was then replaced with Bromfenac (Yellox®, Bausch & Lomb, Italy) eye‐drops 2 times/day. After 4 months’ treatment, right BCVA was 20/20 Snellen and OCT scans showed a normal CMT. This treatment was continued and there was no recurrence of DME in the next 11 months of follow‐up. No adverse events were noted.

Conclusions

Topical Betamethasone Sodium Phosphate and Tetracycline Hydrochloride, together with nonsteroidal anti‐inflammatory eye‐drops, might be an effective alternative for the treatment of newly diagnosed DME in patients not suitable for intravitreal therapy. Future case‐control studies are necessary to confirm these results.
AD in the eye
Authors: Davis B. , Ravindra N. , Guo L. , Cordeiro M.F.
Published: September 2017

Alzheimer's Disease (AD) is the most common form of dementia, however, diagnosis of this condition typically occurs late in the disease process and can only be confirmed post‐mortem. Late diagnosis of AD is problematic as considerable damage to the brain has already occurred by the time symptoms present. Timely diagnosis would therefore serve to create a window of opportunity for novel therapeutics designed to slow or prevent AD progression. The retina presents the only portion of the CNS that can presently be readily and non‐invasively imaged at the single cell resolution owing to the optically transparent nature of the eye. Visual defects have long been reported in AD patients and there are growing reports that histopathological changes in the brain can also be observed in the retina. This talk outlines recent developments in our understanding of potential retinal manifestations of AD with a view to using these findings to develop novel retinal based diagnostics.
Chronic exposure to TNFα impairs RPE barrier and immunosuppressive functions
Authors: Touhami S. , Beguier F. , Augustin S. , Reichman S. , Goureau O. , Nandrot E. , Guillonneau X. , Bodaghi B. , Sennlaub F.
Published: September 2017

Purpose

The retinal pigment epithelium (RPE) is a monolayer of pigmented cells with important roles in the outer blood‐retinal barrier and subretinal immune suppression. Failure of RPE functions and inflammation have both been hypothesized to play a role in the pathophysiology of age related macular degeneration (AMD). We here investigated the long‐term effects of TNFα on RPE morphology and function in vitro.

Methods

Primary porcine RPE cells were cultivated until confluence, then recombinant TNFα was added daily in the culture medium (at 0.8, 4, 20 or 100 ng/ml=C1,C2,C3 and C4) for 10 days. RPE cell morphology and gene expression, barrier, phagocytosis and immunosuppressive functions were assessed.

Results

Cell morphology and gene expression:TNFα (i) decreased cell number (3653.6,3428,3227,2791 and 2020 cells/mm2 respectively for control,C1,C2,C3 and C4, all p < 0.01); (ii) increased cell size (+5.3,+12.6,+13.9 and +9.5% of control for C1,C2,C3 and C4, all p < 0.05); (iii) increased the % of multinucleated cells (5.7,7.7,9.4,9.9 and 15.9% of multinucleated cells for control,C1,C2,C3 and C4, all p < 0.05); (iv) and decreased OTX2 (a major RPE gene) expression (‐11.1, ‐19.7, ‐52 and ‐82.9% of control for C1,C2,C3 and C4, all p < 0.05). Barrier function: Stimulation by TNFα (i) disturbed Zonula Occludens 1 cellular distribution and actin F distribution and (ii) significantly decreased RPE transepithelial resistance in a dose‐dependent manner (‐70, ‐88.5 and ‐90.8% of control for C2,C3 and C4, p < 0.05). Immunossupressive function: 10 day pre‐stimulation with ‐TNFα significantly decreased RPE capacity to induce monocyte death after 24 h of co‐culture (p < 0.05).

Conclusions

Chronic exposure to TNFα deteriorates major RPE functions that are essential to visual function and might play a key role in the pathophysiology of AMD.
Imaging endpoints in clinical trials
Authors: Garhofer G.
Published: September 2017

Clinical drug trials usually rely on primary endpoints that are well‐described direct measures of patient benefit or are closely related to clinical outcomes such as visual field testing. However, there is a lack of short‐term, easy to measure, highly reproducible endpoints predictive for visual acuity outcomes that would qualify as sufficiently predictive variables for patients′ benefit in clinical trials. This of special importance for the follow up of slowly developing diseases, which requires long‐term studies with large sample sizes. The rapid progression in the development of in‐vivo imaging techniques offers now new and exiting possibilities to assess human anatomic or physiologic information in unprecedented high resolution. Thus, the use of these new imaging techniques such as optical coherence tomography as possible endpoints in clinical phase III trials has been widely and controversially discussed. This talk aims to summarize the potential and limitations of modern imaging techniques to serve as surrogate parameters to substitute for clinical endpoints in ocular drug development.
Ultrawidefield OCT
Authors: KOLB J.P. , Klee J. , Klein T. , Kufner C. , Wieser W. , Neubauer A. , Huber R.
Published: September 2017

Retinal wide‐field imaging plays an increasingly important role for the diagnosis of various types or pathologies, some of which start or prevalently appear in the periphery. Despite the great value of wide field fundus cameras and scanning laser ophthalmoscopes for diagnosis and documentation, these devices only acquire 2‐dimensional data in form of en face projections. However, cross‐sectional imaging with optical coherence tomography (OCT) can provide a wealth of additional information. To cover a wide area of the retina of 100° or more of viewing angle, 5 – 10 million OCT scans are required. Current commercially available OCT technology is not able to capture such large data sets and the acquisition time would be prohibitively long.

We recently developed retinal Megahertz OCT (MHz‐OCT), an OCT system that can acquire more than 1 million depth scans per second. It can achieve the high speed by using a new type of swept laser source: the Fourier Domain Mode Locked (FDML) laser. This high speed enables us to acquire a densely sampled 3‐dimensional OCT data set in the non‐mydriatic eye, covering an area of up to 100° angle on the human retina. Technology development and diagnostic potential of such devices will be discussed.
Rostock Cornea Module 2.0 – a versatile extension for anterior segment imaging
Authors: Stachs O. , Sperlich K. , Bohn S. , Stolz H. , Guthoff R.
Published: September 2017

Purpose

In vivo corneal confocal laser scanning microscopy became a valuable tool for studying corneal morphology in health and disease. Enabling the optical dissection of the corneal architecture, this technique offers non‐invasive in vivo imaging at a cellular level being important for current research. Presently there is only one device available without undergoing technological changes in the last years. We are presenting new Rostock Cornea Module developments for anterior segment imaging using up to date confocal scanning laser technology.

Methods

We redesigned the RCM in a modular way. It is possible to use different microscope objectives for user defined requirements as well as to choose between contact and non‐contact application. Since the focal adjustment inside the cornea is often fiddly, we incorporated a fast piezo stage for closed‐loop focus control and adjustment. Further topics addressed: modular setup, extended field of view, reduction of eye movement and compression artifacts as well as software based noise reduction technologies.

Results

We tested the new RCM in combination with a Spectralis platform, offering a resolution of 1536 by 1536 pixel. Performing contact measurements, we get similar results compared to the well‐known RCM‐HRT combination, but with a higher resolution and wider field of view. In non‐contact measurements, the reflection on the cornea surface is very prominent and limits imaging of epithelial structures. We could achieve high resolution stromal imaging of e.g. keratocytes nuclei and stromal nerves.

Conclusions

The RCM 2.0 concept is a versatile extension for visualization corneal structures at a cellular level enabling instant focal plane shifts. Further improvements, wavelength adaption and dedicated customizations are subject of current research.
Simulation in flight safety ‐ what can we learn from the airline industry?
Authors: Dow I.
Published: September 2017

In this presentation I will look at the evolution of aircraft simulators since 1910, how they are currently used to deliver type and recurrent pilot training and, finally, give consideration to their impact on the safety of commercial flight since 1946.
The Royal College of Ophthalmologists and surgical training evolution in the UK
Authors: Spencer F.
Published: September 2017

The Royal College of Ophthalmologists (RCOphth) sets the curriculum and standards for surgical training in the UK; this receives approval from the General Medical Council. The evolution of surgical training will be presented.

A microsurgical skills course, in simulation, prior to commencing live surgery has been mandatory for more than 7 years. A new strategy to increase simulation in all surgical subspecialties was initiated in 2014. This included the development of a curriculum for simulation with recommendations and resources published since 2015.

Increasing availability of inexpensive options for simulation has allowed this to be available in all UK regions and to be considered mandatory in the required surgical competencies in the curriculum.

Recent developments have included the introduction of Entrustable Professional Activities, or EPAs, to demonstrate the ability to manage an entire surgical list, demonstrating planning, teamwork and communication in addition to surgical technique. This also highlights the importance of considering simulation in communication skills or immersive simulation techniques.
Traditional immunesuppressive therapy: is there something we should know further?
Authors: Pichi F.
Published: September 2017

The cornerstone of management of ocular inflammatory disease historically has been corticosteroids, which are invaluable in the immediate control of inflammation; however, corticosteroids are inappropriate for long‐term use as they are associated with a wide array of toxic side effects. As we continue to learn more about the various etiologies and elucidate the basic science pathways and mechanisms of action that cause intraocular inflammation, new therapeutic approaches have evolved. They include employment of immunomodulatory agents (corticosteroid‐sparing therapies) that have expanded our treatment options for these vision‐threatening diseases. These pharmacologics provide therapy for ocular and systemic inflammation in an individualized, patient‐tailored, stepladder approach with the ultimate goal of durable, corticosteroid‐free remission.
The role of electrophysiology
Authors: Holder G.
Published: September 2017

Purpose

To demonstrate the role of electrophysiological assessment in the investigation and management of the patient with photophobia, or whose vision is worse under bright lighting conditions.

Methods

Standardised (ISCEV standard) techniques for electrophysiological assessment will be described, as will any necessary non‐standard protocol additions.

Results

Selected cases will be used to illustrate the value of the objective data provided by electrophysiology. The electrophysiological data will be discussed in association with the results of relevant imaging modalities.

Conclusion

Electrophysiological assessment provides objective functional data important to the diagnosis and management of this group of patients.
LHON: A look into nuclear and environmental factors; What is “sufficient”?
Authors: Sadun A. , Ross‐Cisneros F. , Tian J. , Anderson K. , Irvine A. , Karanjia R. , La Morgia C. , McManus M. , Wallace D. , Carelli V.
Published: September 2017

Purpose

In Leber's Hereditary Optic Neuropathy (LHON) mutations of the mtDNA, are necessary but not sufficient for visual loss. We studied nuclear/environmental interactions in patients and in the Wallace LHON mouse model, to consider what is “sufficient”. The LHON mutation causes a modest decrease in ATP production, but a large increase in ROS production. Nuclear genetic and environmental factors may play upon these factors

Methods

We noted in the data of Kirkman et al (Brain 2009) that heavy smoking mitigated visual loss by delaying disease onset. We reproduced these peculiar results (Carelli et al, Brain 2013). We also studied the ND6 mutant Wallace mouse model of LHON. 30 mice of 12 groups were sacrificed at 23 months including ND6 mutant vs ND6 wildtype and nicotinamide nucleotide transhydrogenase‐NNT +/+ vs ‐/‐ (NNT deletion), under different environments of air and smoke. 10 experiments compared the axonal nerve fiber spectrums.

Results

In our patient pedigrees, heavy smoking also mitigated visual loss, but we saw in this, the existence of two subtypes of LHON. Type I, with an abrupt and severe loss of vision in the teens, was characterized by severe losses of both structure and function. Type II occured decades later with a more insidious onset, with less structural than functional loss. Type II patients were more likely to smoke. In the mice, we found the predominant loss of small fibers in NNT −/− mice carrying the ND6 mutation which were exposed to smoke.

Conclusions

Both nuclear modifiers and environmental factors in combination with LHON mutations can lead to vision loss. NNT is a transhydrogenase that couples hydride transfer from NAD(H) to NADP(+) and proton translocation across the inner mitochondrial membrane. NNT is potentially an important nuclear modifying gene for LHON.
Adaptive optics retinal imaging in patients with GNAT2 mutations
Authors: Georgiou M. , Kalitzeos A. , Michaelides M.
Published: September 2017

Purpose

To investigate the retinal structure in three subjects, from two pedigrees, with molecularly confirmed GNAT2 gene mutations with heterogeneous phenotype.

Methods

Spectral Domain OCT (SD‐OCT) scans and custom‐built Adaptive Optics Scanning Laser Ophthalmoscope (AOS0LO) sequences were acquired after full ophthalmological examination, ERG and colour vision testing twice, 1‐2 years apart. The foveal outer nuclear layer (ONL) retinal thickness was measured using Bioptigen SD‐OCT; 120 B‐scans were acquired with a 7mm nominal scan width, aligned, registered and averaged in ImageJ. A 5‐pixel wide longitudinal reflectivity profile provided the distance between the internal and external limiting membrane. Peak cone density and inter‐cone spacing were measured at 0.5 degree from the fovea using confocal AOS0LO images. Voronoi analysis was also performed.

Results

Hardy‐Rittler‐Rand plates suggested normal colour vision in one of our subjects. Conversely, the colour vision test for the other two subjects (from the other pedigree) suggested colour blindness. All three subjects had non‐detectable cone ERG. The peak para‐foveal density varied from 30 543 to 50 943 cones/mm2 and was significantly lower than previously reported values for unaffected subjects at 168 162 ± 23 529 cones/mm2 (mean ± SD). Voronoi diagrams revealed the heterogeneity of the cone mosaic with only 44% ‐ 53% of photoreceptors having six neighbouring cells. The ONL thickness was variable and due to the small sample size no conclusion could be drawn.

Conclusions

Microscopic retinal imaging allowed photoreceptor visualisation and quantification. It can play a significant role in a multimodal investigation, including functional and structural measurements for an in depth phenotyping of GNAT2 gene, implicated in achromatopsia and other inherited retinal diseases.
Pathophysiology of macular interface
Authors: Kalemaki M.
Published: September 2017

Purpose

To study the pathophysiology of the vitreomacular interface disorders (epiretinal membrane, macular hole, vitreomacular traction syndrome).

Methods

Retrospective review of published articles concerning the above entities.

Results

Posterior Vitrous Detachement (PVD) variations have been considered to be the initial event leading to vitreomacular interface abnormalities. Depending on the level of PVD (eg schisis, partial or complete), different pathophysiological cataracts may occur involving a number of cells and growth factors at the vitreomacular interface.

Conclusions

The pathophysiology of the vitreomacular interface includes a sequence of events such as cellular migration, proliferation and modulation of the extracellular matrix. The quality and quantity of the involved cells and growth factors vary between different vitromacular interface disorders.
The particularities of corneal infectious diseases in children
Authors: Bremond‐Gignac D.
Published: September 2017

Corneal infections in children can affect subjects of all ages with a high frequency in newborns and infants. In infant, children and teenagers the most common ocular pathogens, that differ from the adult, are Haemophilus Influenzae, Staphylococcus aureus, Streptococcus pneumonia and also Moraxella species. These infections could lead to ulcers and sight‐threatening complications. Infectious keratitis in children is not common but can cause a severe visual impairment if late diagnosed with delayed treatment established or with weak efficacy. In children corneal infections can be difficult to diagnose because the pathology can develop without pain. In addition, the examination may be difficult to perform. Identification of the pathogen must be performed as far as possible. The treatment should be provided earlier and aims to eliminate the bacteria, virus or fungus pathogens. Specific epidemiology of pathogens will be detailed according to age. Risks of visual impairment and amblyopia must be integrated. An update on topical antibiotics and current options will be reviewed with practical aspects, diverse clinical cases and considering quality of life of children and parents.
Inflammatory biomarkers of the tear proteome in anterior segment disease
Authors: Beuerman R. , Zhou L.
Published: September 2017

Ocular surface inflammation is linked to a number of adverse outcomes which vary depending on adjunct factors such as recent surgery or presence of disease. Usually the level of inflammation is thought to be important in the evaluation. However, from a clinical point of view there are limited methods of evaluating inflammation. Proteomics allows the simultaneous accurate quantification of a large number of proteins associated with inflammation using just a few microliters of tears so that individual patients can be evaluated. For example, studies have shown several members of the S100 family of proteins which are contain 2 EF hand calcium binding motifs to be upregulated in dry eye and pterygium. The S100 proteins can bind to RAGE receptors on immune cells to stimulate further inflammation. Other proteins associated with inflammation include various heat shock proteins such as HSPA8, 70 kDa protein. YWHAZ is found which is associated with cell injury and may be directly related to the type of pathology. Thus, using proteomics a more complete picture of the ocular surface inflammation can be developed and used to predict clinical outcomes.
Cornea and lacrimal gland synergy, a corner stone for a healthy vision
Authors: Michon F.
Published: September 2017

A disturbed tear film secretion results in an ocular dryness, which can induce a corneal opacification. Interestingly, few studies have correlated the cornea renewal to the LG secretion. Nonetheless, our preliminary data suggested that LG secretion changes from birth to the eyelid opening, happening two weeks after birth in mouse. We have investigated the transcriptomic signature of the LG and cornea in embryonic, postnatal (eyelid closed) and adult animals. This analysis confirmed that the LG secretes morphogenetic factors (IGF2, HGF, EGF, KGF), while not expressing the receptors. Interestingly, the cornea epithelium expresses the corresponding receptors, but not the ligands. Moreover, the secretion of these factors is peaking prior the eyelid opening, correlating to an intense proliferation in the cornea epithelium. Moreover, the changes of secreted factors shortly after cornea wounding demonstrate a direct regulatory loop between the two organs modulating the tear composition. Our data provide a new research avenue for the development of tear film biomimetic enhancing the corneal healing.
Tips and tricks in open globe injuries (management of intraocular foreign bodies)
Authors: Durukan H.
Published: September 2017

Traumatic open globe injuries with intraocular foreign bodies (IOFBs) may result in severe visual loss depending on a number of factors including elevated risk for endophthalmitis, toxicity to the IOFB material, and postoperative proliferative vitreoretinopathy. Surgical removal of an IOFB is perhaps the most unpredictable surgery, especially in the presence of media haze, requiring intense preoperative workup and patient counseling. There is still significant controversy in the management of IOFBs, particularly the timing and method of surgery. The purpose of this topic is to familiarize clinicians with the recent advances in diagnosis and management of such injuries.