bluuebunny/crossref_metadata_2025 huggingface dataset:
Satellite in transit metastases in a case of loco‐regional metastatic conjunctival melanoma
Authors: Malaise Denis , Matet Alexandre , Beaulaton Clément , Lévy Christine , Lumbroso Livia , Gardrat Sophie , Barnhill Raymond , Cassoux Nathalie
Published: December 2019

Purpose

To report the clinical and histopathological findings of satellite in transit metastases in one case of conjunctival melanoma with cervical and parotid lymph node spreading.

Methods

Case report of a patient initially examined at Institut Curie, Paris, on September 2018, with histopathological analysis, review of the literature and discussion.

Results

A 82 year‐old woman was referred for additional treatment after the removal of a 3mm thick pigmented infiltrating conjunctival melanoma in the temporal bulbar conjunctiva of the left eye. Proton beam irradiation was planned but finally declined by the patient. TEP‐CT was prescribed and revealed cervical and parotid lymph‐node infiltration, treated by external radiotherapy in another radiotherapy center. She was referred again 8 months later for local recurrences in the left conjunctiva. We observed 11 pigmented conjunctival nodules in the temporal and supero‐nasal quadrants. We surgically removed them and proton beam irradiation of the entire invaded area was planned. Histopathological analysis of some conjunctival nodules revealed well‐delimitated subepithelial nodules of melanoma cells. These nodules were extravascular and aligned along microvascular channels, suggesting angiotropism and extravascular migratory metastases.

Conclusion

Angiotropism and extravascular migration seem to be implicated in satellite in transit metastases in conjunctival melanoma. It has to be recognized as according to literature it could be a marker of rapid metastatic disease progression and death of the patient.
Ocular surface evaluation using as‐oct and in vivo confocal microscopy in patients with primary sjögren’s syndrome
Authors: Luís Maria Elisa , Cardigos Joana , Barcelos Filipe , Carvalho Helena , Hipólito Diogo , Crisóstomo Sara , Vaz‐Patto José , Alves Nuno
Published: December 2019

Introduction

Dry eye disease severity is classically obtained through an evaluation of tear film stability and tear production, lid margin disease, ocular surface damage and tear osmolarity. Other parameters for severity classification are know being used for a more accurate follow‐up and managing. The purpose of this study is to evaluate the tear meniscus (TM) and corneal sub‐basal nerve plexus (SBNP) in a population with pSS, using anterior segment optical coherence tomography (AS‐OCT) and in vivo Confocal Microscopy (ivCM).

Material and Methods

Observational cross‐sectional study of 50 patients with pSS and 20 healthy controls. All patients were submitted to Schirmer test I without anaesthesia, tear break‐up time and corneal fluorescein staining evaluation. Anterior segment optical coherence tomography (AS‐OCT) was used for TM height and area analysis. In vivo Confocal Microscopy (IVCM) was performed for corneal SBNP density, length and tortuosity. Differences in pSS ophthalmic features were analyzed according to phenotype profile.

Results

TM height was significantly lower in pSS in contrast to healthy controls (p < 0.001). Corneal SBNP density and length were significantly lower and tortuosity significantly higher in pSS patients (p < 0.001, p = 0.004 and p = 0.001, respectively).

Conclusion

The diagnosis of Primary Sjögren’s Syndrome (pSS) is sometimes challenging, taking into account the clinical heterogeneity and diagnostic criteria fulfillment variability. AS‐OCT and IVCM may be useful in additional evaluation of lachrymal unit dysfunction in pSS.
Validation of a predictive model for retinal vascular resistance and blood flow by means of Laser Speckle Flowgraphy
Authors: Pappelis Konstantinos , Choritz Lars , Jansonius Nomdo
Published: December 2019

Purpose

(1) To mathematically predict retinal vascular resistance and blood flow from minimal input; (2) to validate the model predictions in a healthy population using Laser Speckle Flowgraphy (LSF).

Methods

Fundus photographs, OCT and OCT‐angiography scans, and systolic/diastolic blood pressure (SBP/DBP) and intraocular pressure (IOP) measurements were performed in 32 healthy subjects. Predicted vascular resistance (PVR) was determined from the central retinal artery and vein equivalents, the fractal dimension of the vasculature, and population‐based hematocrit values, according to the Poiseuille law and an adapted version of the fractal model proposed by Takahashi et al. (2009). Predicted blood flow (PBF) was calculated as OPP/PVR, where OPP is the ocular perfusion pressure. For validation, the mean blur rate (MBR; measure of velocity) of large vessels inside the optic disc and waveform parameters (heart rate [HR], flow acceleration index [FAI], skew, acceleration time index, blowout score and time, fluctuation, rising rate, falling rate [FR]) were recorded by means of LSF. Linear models reduced by the Akaike Information Criterion were used to assess the relationship of PVR and PBF with the LSF parameters.

Results

In the reduced multivariable model, PVR was higher with higher DBP (p < 0.001), FAI (p < 0.001), and FR (p = 0.042), as well as with lower skew (p < 0.001), MBR (p = 0.001), and fluctuation (p = 0.103). PBF was higher with higher skew (p < 0.001) and MBR (p = 0.040), as well as with lower FAI (p < 0.001) and HR (p = 0.055). The R2 of the models was 0.83 and 0.58, respectively. PVR correlated with retinal nerve fiber layer thickness (RNFLT), but not with macular volume (r = −0.53, p = 0.002; r = −0.218, p = 0.23). PBF correlated with macular volume, but not with RNFLT (r = 0.382, p = 0.031; r = 0.326, p = 0.068).

Conclusions

PVR can be used as a surrogate of vascular resistance. PBF provided a lesser fit with the LSF parameters and partially describes retinal blood flow.

Reference

Takahashi T, Nagaoka T, Yanagida H, et al. (2009). A mathematical model for the distribution of hemodynamic parameters in the human retinal microvascular network. J Biorheol 23:77‐86
Trabeculectomy: An assessment of the quality and readability of online patient information
Authors: Donnelly Aaron
Published: December 2019

Many patients now refer to the internet as a source of patient information. We wanted to assess the quality and readability of online information pertaining to trabeculectomy. We interrogated 3 popular search engines for the terms “trabeculectomy” and “glaucoma surgery”. We analysed the websites against the EQIP (ensuring quality information to patients) and the Flesch Kincaid reading ease score. We found that the mean quality of puplications was poor with a higher than recommended reading grade. Academic sources had a high quality score compared to sources with a commercial interest. It is importat that we guide patients to high quality sources of information on the internet.
Differences in the retina of patients with confirmed diagnosis of multiple sclerosis versus isolated clinical syndrome
Authors: Viladés Palomar Elisa , Orduna Elvira , Beatriz Cordón , Perez‐Velilla Javier , José Vicente Maria , Jesús Rodrigo‐Sanjuan Maria , Satué Maria , Garcia‐Martin Elena
Published: December 2019

Purpose

To assess the differences in the retina nerve fiber layer (RNFL) and the ganglion cell layer (GCL) in subjects with multiple sclerosis (MS) versus subjects diagnosed as clinically isolated syndrome (CIS).

Methods

58 eyes of healthy controls, 67 eyes of MS patients (<10 years) and 10 eyes of patients diagnosed with CIS (<10 years) were included in the study. Measurements were taken using the Posterior Pole Retinal Thickness Map protocol [shows the thickness of the retina throughout the posterior pole (volumetric examination of 30° × 25° OCT]) with the Heidelberg Spectralis optical coherence tomography (OCT) device. We analyzed the 8x8 grid placed along the fovea symmetrically with the papilla. We analyzed the average thickness of the RNFL and the GCL in the 64 cells obtained.

Results

Both groups, EM and CIS, present a significant thinning of the RNFL (27 and 32 cells respectively) and the GCL (45 and 20 cells respectively) with respect to the healthy controls. On the other hand, there has been a significant thinning of the RNFL in patients with MS (9 cells) versus GCL and a slightly significant thinning of the GCL (3 cells) in MS patients with CIS.

Conclusions

OCT is able to detect significant changes in the retina of patients who do not meet dissemination criteria in time and space for the diagnosis of MS. These CIS patients present a significant thinning of the RNFL and the GCL with respect to healthy controls and there are slightly differences between MS and CIS in the RNFL and the GCL.
The epidemiology of myopia in school children worldwide.
Authors: Grzybowski Andrzej , Kanclerz Piotr , Tsubota Kazuo , Lanca Carla , Saw Seang‐Mei
Published: December 2019

Purpose

Both genetic and environmental factors play a role in the increasing prevalence of myopia. This modern rise mirrors the trend of children spending a considerable amount of time reading, studying or—more recently—being glued to computer and smartphone screens. The aim of this study is to present an update on the current epidemiology and risk factors for myopia in school children in different countries around the world.

Methodology

PubMed and Medline were searched for the following keywords: prevalence, incidence, myopia, refractive error, risk factors, children and visual impairment. English language articles published between Jan 1, 2013 and Nov 30, 2018 were included in the study. Studies were critically reviewed for study methodology and robustness of data. Seventy‐nine studies were included in the review.

Results

Prevalence remains higher in Asia (60%) compared with Europe (40%) using cycloplegic refraction examinations. Studies reporting on non‐cycloplegic measurements show exceptionally high myopia prevalence rates in school children in East Asia (70%–80%) compared with North America (42.2%). Low prevalence under 10% was described in African and South American children. New risk factors, apart from outdoor time and near work exposure, such as dim light, the use of LED lamps for homework, low sleeping hours, reading distance less than 25 cm and living in an urban environment were described in recent studies.

Conclusions

The high rates of myopia prevalence among school children, especially Asian populations, are strongly influenced by particular lifestyle habits. Increase in outdoor time remains the best strategy to prevent myopia onset. Additional epidemiological studies should be carried out on implementation of public health strategies to tackle and avoid myopia onset. High‐risk populations with high myopia prevalence might need a combined approach of increased outdoor time, changes in near distance activities in preschool children and treatment to control myopia progression.
Genotype‐phenotype correlation in a French cohort of aniridia
Authors: Bremond‐Gignac Dominique
Published: December 2019

Congenital aniridia consists in a complex malformation of the eye with congenital absence of iris. Aniridia is a rare panocular disorder affecting, beyond iris, cornea, angle structures, lens and fovea, and possibly associated with other anomalies.This genetic rare disease can cause severe visual impairment occurring from various mechanisms as glaucoma, limbal insufficiency and foveal hypoplasia. PAX6 gene is mainly involved in the disease. We aim to understand the features of patients with congenital aniridia, identifying the characteristics phenotypes of the disease and its associated anomalies. We analyse our patient cohort who underwent a complete ocular examination with ophthalmic exploration and who had genetic molecular analysis. Specific analysis of each ocular feature (as aniridia‐related keratopathy, glaucoma, cataract, foveal hypoplasia, optic nerve hypoplasia and other features) is detailed with early clinical signs that can be observed. An evaluation of risk factors is required for the follow‐up of aniridia patients in order to get a better therapeutic orientation.
Influence of donor size on outcome of DMEK
Authors: Cursiefen Claus
Published: December 2019

Novel strategies to improve outcome after DMEK are discussed. A special focus is placed on the effect of different sizes of donor tissue.
Pattern of RGCs loss in toxic optic neuropathies
Authors: Barboni Piero
Published: December 2019

Toxic optic neuropathies are characterized by bilateral visual loss, papillomacular bundle damage, central or centrocecal scotoma and color vision defect. Multifactor causes play important role in disease manifestation, and nutritional and/or genetic defects (such as mitochondrial DNA mutation) could trigger the disease. Toxic optic neuropathies cause defect to mitochondrial metabolism with consequent damage of retinal ganglion cells with higher energy (ATP) demand. The pattern of RGC and RNFL loss follow a specific pattern characterized by preferential involvement of fibers of papillo‐macular bundle anatomical distribution, the typical feature of mitochondrial diseases.
Part 4: Laser photocoagulation of macroaneurysms: clinical cases in DME
Authors: Dupas Bénédicte
Published: December 2019

Prevalence of capillary telangiectatic capillaries (TelCaps) is estimated to be around 30% of cases in patients with diabetic macular edema (DME). TelCaps may be occult, or barely visible on fundus, because they are frequently associated with haemorrhages, exsudates or because of their transparency. TelCaps can take several appearances: round light red lesion, surrounded by a white ring (corresponding to a thickened wall), or isolated dark red lesions. They can be isolated, or multiple, and are predominant in the macular area. ICG‐angiography allows the detection of the TelCaps, and precise their location compared to larger retinal vessels. Media opacities (such as cataract), or eye movements, or non visualization of TelCaps on fundus, might prevent from efficient photocoagulation. Baseline laser parameters to start with are: spot size 60 µm, spot duration: 50–100 ms, power : 100 mW. Several shots can be performed. If the targeted TelCap is missed, a white burn is visible on the retinal pigmentary epithelium. The TelCaps to close to the fovea (i.e., located <500 µm from the center) should not be treated. We will present several clinical cases to illustrate the photocoagulation technique.
Update on keratoconus diagnosis and treatment
Authors: Modis Laszlo
Published: December 2019

The diagnosis of keratoconus has changed revolutionary during the past years. With the appearance of 3D corneal tomography and OCT devices even subclinical forms of the disease can be detected. Similarly, a wide range of interventions has been introduced in the treatment modalities as well. Earlier, nearly only rigid gas permeable contact lens and penetrating keratoplasty were the solutions. Nowadays, either conventional epithelium‐off or epithelium‐on collagen cross‐linking (CXL) treatment targets the cause of the disease. Intracorneal ring segments, toric IOLs, and keratorefractive procedures are also available sometimes in combination with CXL to treat certain forms of the disease. Surgical treatment shifted to deep anterior lamellar keratoplasty, which preserves the integrity of the globe. Postoperative immune rejection is less frequent, endothelial cell count reduction is less as compared to penetrating keratoplasty. Corneal hydrops, a special form of the disease usually requires conservative treatment and after the healing process surgery can be performed if necessary.
Iatrogenic dry eye disease
Authors: Horwath‐Winter Jutta
Published: December 2019

Dry eye disease (DED) can be caused by a variety of iatrogenic interventions. Major causes of the iatrogenic DED are systemic or topical drugs, contact lens wear, and ophthalmological surgical procedures, including cataract, corneal refractive, lid, glaucoma and vitreoretinal surgery as well as keratoplasty. Furthermore, botulinum toxin injections and cosmetic applications, e.g. eye makeup, eyelash growth, fillers, conjunctival whitening, tattooing, and jewellery/piercing are also considered risk factors for iatrogenic DED. Indirect procedures such as continuous positive airway pressure and radiation treatment as well as non‐ophthalmic conditions (e.g. GvHD) will also be discussed. Appropriate tear film and ocular surface evaluation at pre‐ and post – intervention as well as improved knowledge of pathophysiological mechanisms, therapeutic options and prophylactic measures will contribute to the elucidation of unmet medical needs in patients suffering from still underestimated iatrogenic DED.
Atypical corneal endothelial dystrophy
Authors: Liskova Petra
Published: December 2019

A case with and unusual phenotype of corneal endothelial dystrophy will be presented.
Changes in cell density as an early marker for low dose ionising radiation‐ induced cataractogenesis
Authors: Uwineza Alice
Published: December 2019

Epidemiological data correlates exposure to low dose ionising radiation (IR) and cataractogenesis later in life. Our understanding of the underlying biological mechanisms is still in its early stages as we seek to explore the applicability of the linear no‐threshold model in these low dose and low dose rate exposures. A single layer of epithelial cells (LECs) covers the anterior hemisphere of the lens. Central and peripheral regions (PR) are designated on the basis of position and cell density. The PR is considered the most radiosensitive region of the epithelium. To understand how LECs manage IR‐exposure at low dose levels and rates, mice of various genetic backgrounds were exposed to 0.5, 1 and 2 Gy using Co60 gamma‐rays at dose rates of 0.3 or 0.063 Gy/min. The cell density and cell proliferation of LECs were analysed at specific time points post‐IR. A differential LECs organisational structure and response to IR in the various mice strains was observed in a dose rate and gender dependent manner. Our data indicate that low dose IR‐effects require a relatively long latency period, in line with epidemiological data from longitudinal studies and evidencing the importance of such studies particularly with respect to human health, occupation, environment and unintended exposures. Longitudinal studies are essential to understand IR‐induced cataract. The mechanisms and processes of IR‐induced cataract formation are incomplete at present, but our data call into question the applicability of the linear no‐threshold model at these low dose/dose rate levels.
An update on effects of ionizing radiation exposure on the eye
Authors: Hamada Nobuyuki
Published: December 2019

Over the past half century, the International Commission on Radiological Protection (ICRP) has considered that the lens is the most radiosensitive ocular structure, and has recommended dose limits for the lens to prevent occurrence of vision impairing cataracts (VICs). Epidemiological evidence that doses much lower than previously thought produce cataracts led ICRP to recommend reducing dose threshold for VICs and reducing the equivalent dose limit for the lens in 2011, when only a single threshold of 0.5 Gy was recommended. Based on epidemiological evidence, no dose rate effect was assumed and it was assumed that minor opacities progress into VICs. This contrasts with previously recommended separate thresholds each for different exposure scenarios, and for minor opacities and VICs. The absence of dose rate effect was based on the observed similar thresholds for protracted exposures in Chernobyl cleanup workers and in the Japanese atomic bomb survivors. Progression was assumed predicated on similar risks of cataracts and cataract surgery. Since 2012, there has been mounting epidemiological evidence for cataracts, also for other ocular diseases (e.g., glaucoma, diabetic neuropathy and macular degeneration). This presentation deals with the scientific basis of the ICRP 2011 recommendation, discusses the plausibility of two assumptions considering emerging scientific evidence, and considers radiosensitivity of the lens among ocular structures.
miRNA profile in normal and aniridia conjunctival cells versus severity of aniridia‐associated keratopathy
Authors: Latta Lorenz
Published: December 2019

Patients with congenital aniridia develop aniridia‐associated keratopathy (AAK), most of them exhibiting a similar disease mechanism namely haploinsufficiency of the PAX6 gene. The clinical onset and progression of AAK is quite diverse across patients. MiRNAs may act as regulatory elements affecting AAK progression. In mouse animal models the role of miRNAs controlling corneal vascularization has come into research focus. Interestingly, some of the miRNAs involved in neovascularization of the cornea, such as miR‐204, are regulated by PAX6 expression. The aim of this study was to identify deregulated miRNAs in conjunctival cells of AKK patients compared to unaffected controls, also in context with PAX6 haploinsufficiency. We further attempted to correlate miRNA expression with clinical severity of AKK (Staging ranging from 0 intact limbus, no pannus, clear cornea to 4 – end‐stage, thick, white, opaque vascularized pannus). We analyzed the miRNA expression profile in conjunctival cells of 20 patients with AKK and 20 age and sex matched controls using microarrays. We identified 10 down‐ and 11 upregulated miRNAs, including downregulated miR‐204‐5p and upregulated mir‐375. The latter miRNA has been reported to bind in PAX6 3′ UTR. Two patients showed mir‐204‐5p expression levels similar to healthy controls. These patients had mutations in PAX6 flanking genes likely affecting PAX6 regulatory regions and 0‐1 severity of AAK phenotype. Our results show strong expression changes in miRNA profile of Aniridia patients.
Technique of laser photocoagulation of TelCaps; clinical cases in DME and other diseases
Authors: Delyfer Marie‐Noelle
Published: December 2019

The control of the duration of macular edema is a key‐factor to prevent irreversible neuro‐retinal lesions. Pharmacological studies have demonstrated the interest of early intravitreal treatments (either anti‐VEGF or dexamethasone) to control vascular macular edema, especially in diabetic macular edema and retinal vein occlusions. However, in some cases, pharmacological therapy fails to control retinal exudation, either at once or after a while. The remodeling of the retinal capillary network secondary to chronic vascular disturbances can indeed maintain the exudation. Telangiectatic capillaries is one of modifications of the vascular network that can be involved in persistent or recurrent vascular edema. TelCaps may be identified on the fundus as dark‐reddish round lesions often with white borders. They may be either isolated or gathered in clusters. In some cases, however, TelCaps remain barely visible. ICG‐angiography remains the most efficient imaging mode for TelCaps detection, enabling to precise their number and location towards the fovea. Our presentation will focus on clinical presentations of such TelCaps in vascular diseases: diabetic retinopathy, retinal vein occlusions, Coats’ disease. Both management and outcomes will be discussed.
Posterior uveitis: Vitrectomy on eyes with bag‐in‐the‐lens IOL
Authors: Lytvynchuk Lyubomyr
Published: December 2019

Implication of the bag‐in‐the‐lens IOL implantation into uveitic cataract surgery became an alternative approach that has change the course of postoperative period. The use of bag‐in‐the‐lens IOL in patients with uveitis has certain advantages, including less postoperative inflammatory reaction and decreased risk of posterior synechia. In combined surgery the clear optic IOL area allows for improved visualization during the vitrectomy. However, the uveitic eyes can present with additional challenges which have to be reconsiderd.
Proteomic approach to new drugable targets of retinal neovascularization
Authors: Vähätupa Maria
Published: December 2019

Retinal neovascular diseases such as retinopathy of prematurity (ROP), proliferative diabetic retinopathy (PDR) and retinal vein occlusion (RVO) are major causes of visual impairment in western countries. Oxygen‐induced retinopathy (OIR) model is widely used model for studying these retinopathies. The purpose of our study was to characterize changes in protein levels during OIR model using by a recently developed technique, sequential window acquisition of all theoretical mass spectra (SWATH‐MS) proteomics. Samples from normoxic and OIR animals were collected in three time points; P13, P17 and P42 and analyzed with SWATH‐MS. Immunoblotting and immunohistochemistry from mouse and human PDR samples was used to confirm these results and address their relevance for human neovascular retinopathies. We performed the most extensive proteomic profiling of OIR to date and quantified almost 3000 unique proteins and their expression levels in control and OIR retinas. The methodology used in the study allowed also temporal profiling of OIR proteome. The most prominent group of proteins induced at the early hypoxic phase of OIR were crystallins, while angiogenesis related proteins such as Filamin A and B, Annexin 2 and Myosin 9 were upregulated at the peak of neovascularization. In addition, the upstream regulator analysis identified potentially upregulated enhancers of angiogenesis, among them TGF‐β1. As retinal neovascularization regresses later in OIR, majority of the changes seen in protein expression levels returned to normal at P42, but there was still evidence suggesting that proteins involved in neurotransmission stayed at reduced levels.
Diagnostic and postoperative evaluation: application of new imaging modalities
Authors: Papastefanou Vasilios
Published: December 2019

The diagnosis of epiretinal membranes is clinical following a thorough history and fundus assessment. This lecture focuses however on additional imaging modalities currently available to facilitate the diagnostic and postoperative evaluation. Multicolour fundus imaging or confocal infrared imaging have provided superior ERM detection in comparison to fundus photography in mild cases. Diagnostic evaluation with OCT allows the estimation of retinal deformity due to the membrane, determines the involvement of the fovea and, with en‐face OCT, allows for the estimation of the membrane extent and dynamic development. High resolution OCT allows for the classification of epiretinal membranes to conventional or atypical. Specific retinal features have been identified in symptomatic eyes (macropsia). OCT imaging has allowed the determination of the ERM profile for specific categories of patients as patients with uveitis or concurrent diabetic macular oedema. Imaging following ERM peeling allows the estimation of anatomic and functional outcomes. OCT allows the qualitative and quantitative assessment of central macular thickness or individual retinal layers. Additional retinal features, some of which could have prognostic implications such as features of retrograde maculopathy, can be identified. Pre‐ and postoperative macular vascular circulation can be evaluated with the use of OCT‐A and evaluation of retinal oxygen saturation can be evaluated with the use of retinal oximeter. The features of the FAZ postoperatively have been investigated and have been associated with the degree of visual recovery. The impact of artefacts in this modality need to be taken into account.
Introduction and clinical aspects in Usher syndromes
Authors: Millán José M.
Published: December 2019

Usher syndrome (USH, OMIM 276900, OMIM 276905, OMIM 605472, ORPHA: 886) is the most prevalent deaf‐blindness of genetic origin. It is a recessive inherited disease characterized by sensorineural hearing loss (HL), visual loss due to retinitis pigmentosa (RP), and, in some cases, vestibular dysfunction. Prevalence estimates range from 3.2 to 6.2/100,000. Patients with USH are classified into three clinical subtypes (USH1, USH2, or USH3), based on the severity and progression of hearing impairment and the presence or absence of vestibular dysfunction. Usher syndrome type I (USH1) is the most severe type, characterized by severe to profound congenital sensorineural hearing loss, vestibular dysfunction and prepubertal onset of RP eventually leading to legal blindness. USH2 is characterized by moderate to severe hearing impairment, normal vestibular function and later onset of retinal degeneration. USH3 displays progressive hearing loss, RP and variable vestibular phenotype. In the last years, next generation sequencing (NGS) techniques have revolutionized the world of the molecular genetic diagnosis. NGS has allowed to molecularly characterize a high number of patients, thus permitting to establish some phenotype‐genotype correlations that had been elusive to date.
Neurotrophic keratopathy‐diagnosis and clinical presentations
Authors: Messmer Elisabeth M.
Published: December 2019

Neurotrophic keratopathy is defined as a disease related to alterations in corneal nerves leading to impairment in sensory and trophic function with consequent breakdown of the corneal epithelium, affecting health and integrity of the tear film, epithelium and stroma. It can occur with infections, autoimmune disease, after trauma or ocular surgery, with intracranial neoplasia, in systemic disease and genetic syndromes. It is classified in three stages: mild (epithelial changes without epithelial defect), moderate (epithelial defect) and severe (stromal involvement). Clinical hallmark is reduced or absent corneal sensation. Therefore, corneal sensitivity testing is essential in the diagnosis of neurotrophic keratopathy along with patient history, clinical examination and diagnostic tests such as vital stains and, if possible, in vivo confocal microscopy.
Witelo and his works on optics
Authors: Polak Agnieszka
Published: December 2019

Witelo (1230‐1314) was the first Polish scholar whose scientific achievements influenced European science. He was a mathematician, physicist, astronomer, philosopher and theologian. Witelo studied liberal arts at the University in Paris, canon low, philosophy and scientist at the Universities at Bologna and Padua. He was interested in ancient philosophy of Aristotle and works of Islamic philosopher Averroes. He also studied the seven volume work of Islamic scientist Hasan Ibn al‐Haytham (Alhazen) translated into Latin. Two of Witelo's works have survived to our times. One is “De natura daemonum and de causa primaria poenitentiae”, second “Perspectiva”, published in 1536. This work had a major impact on the development of European science. It consists of 10 books and it is a treatise on optics. In this treatise Witelo collected the knowledge on mathematics, physics and astrology. In the books III and IV the author presented the outline of the eye structure, the mechanism of image formation in the eye and some aspects of psychology and physiology of vision. He wrote about illusions of perception, flat and parabolic mirrors, the problem of refraction of light on the border of centers of diverse optical density and meteorological optics, including the rainbow phenomenon. He was the first in Europe to present the intromission theory of light. The Universities of Oxford and Cambridge had lectures on optics based on both the theory of Alhazen and Witelo. The theory of Witelo was studied by Leonardo da Vinci, Nicolaus Copernicus and Johannes Kepler who wrote the treatise on optics entitled “Ad Vitelonem paralipomena”.
Roles of LIM homeodomain 2 (Lhx2) in the differentiation of mammalian retinal pigmented epithelium
Authors: Ashery‐Padan Ruth
Published: December 2019

Normal vision depends on the retinal pigmented epithelium (RPE), a metabolic cell layer that is vital to the development and function of the adjacent retinal photoreceptors. The aim of this study was to uncover the transcriptional regulatory program and the cis‐regulatory elements required for RPE differentiation and maintenance. Lhx2 is a member of LIM homeodomain (LIM‐HD) protein family; it is a key factor for neural differentiation and is known to be required for early morphogenesis and patterning of the vertebrate eye. To discover the roles of Lhx2 in the differentiation of the mammalian RPE, we conducted functional studies in vivo using conditional mutagenesis in mouse, and knockdown in human RPE derived from embryonic stem cells (hES‐RPE). This was combined with global identification of regulatory regions bound by Lhx2 and a genomic characterization of these sites in the course of RPE differentiation. The results place Lhx2 upstream of a complex regulatory network that controls RPE differentiation, morphology and function in mice and humans.
Small apperture‐IOL for cataract surgery in keratoconus
Authors: Moussa Sarah
Published: December 2019

Due to advancements in treatment of keratoconus the number of keratoplasty procedures has significantly decreased. This development leads to an increase in the number of patients with a therapeutically stable keratoconus developing a cataract. The selection of the best IOL is still a challenge in these cases. A new option for keratoconus patients with cataract might be the IC‐8 IOL (AcuFocus), a small aperture aspheric monofocal lens that follows the same principle as the KAMRA coneal inlay (AcuFocus).
Question it
Authors: Besinis Dimitrios
Published: December 2019

Compliance with medical treatment is one of the most important aspects of every chronic condition. Non‐compliance in glaucoma has been thoroughly investigated and one of the major reasons is patient education. It is true that we are treating an “asymptomatic” disease with medication that potentially cause immediate side effects. Trying to deal with compliance and succeed in the treatment of glaucoma, we should be able to educate our patients about the condition and the importance of IOP control. There are certain questions that can be discussed in every consultation in order to facilitate patient education. Patient forums are also very helpful in the understanding of glaucoma. In this talk I will present certain questions that should be discussed in every consultation and I will also underline the importance of patient forums.
Immunglobulin depositions in different organs in monoclonal gammopathy
Authors: Garderet Laurent
Published: December 2019

Monoclonal immunoglobulins (heavy and/or light chain) can deposit in various organs. The most prominent targeted organs are the kidney, the nerves, the heart, the liver, the gastrointestinal tract but it could also involve the eyes, the skin and it can interact with the hemostasis proteins. This is at the origin of a new concept called monoclonal gammopathy of clinical significance (MGCS). It is challenging to diagnose and even though the B cell clone may be small, it may be important, in some circumstances, to initiate a hematological treatment.
Role of Rho kinase pathway in diabetic retinopathy: from a diabetic rat model to human eye pathology
Authors: Rothschild Pierre‐Raphael
Published: December 2019

Diabetic macular oedema is the main cause of visual loss in diabetic retinopathy, particularly in type 2 diabetic patients. The pathogenic mechanisms are not fully elucidated. Rho/Rock1 pathway is activated in diabetes and is responsible for cellular contraction. ROCK1 activation induces actin cytoskeleton remodeling. We hypothesized that Rho/Rock1 diabetes‐induced activation could contribute to cytoskeleton remodelling especially in retinal vessels subsequently altering retinal perfusion.

Methods

We used 12 months old Goto‐Kakizaki (GK) type 2 diabetic rats. Rho/Rhock1 pathway activation effects on retinal vasculature was analysed and ROCK inhibition by Fasudil administered into the vitreous was tested in rats in vivo on vascular perfusion.

Results

In diabetic rats, activation of ROCK‐1 induces focal vascular constrictions, endoluminal blebbing and subsequent retinal hypoxia. Intraocular injection of fasudil, significantly reduces retinal hypoxia. Diabetes‐induced cell blebbing may contribute to ischemic maculopathy and represent an intervention target.
The retinal venous pressure ‐ A new measurable parameter in glaucoma risk assessment
Authors: Stodtmeister Richard
Published: December 2019

Low ocular perfusion pressure (OPP) is a risk factor for the progression of glaucoma. OPP is calculated as the difference between mean ophthalmic artery pressure and the venous pressure in the eye which is assumed being equal to the intraocular pressure (IOP). Thus lowering IOP lowers the ocular venous pressure and increases the OPP. This view, however, needs a modification because in the past 25 years it has been shown that the retinal venous pressure (RVP) may be considerably higher in approximately one third of glaucoma patients. In an own series of 50 glaucoma patients 16 patients could be identified just because of a lacking spontaneous pulsation of the central retinal vein. These patients had an IOP of 15(4)mmHg (median (interquartile range) and a RVP of 31(12)mmHg. Also other study groups reported on patients with a high RVP despite an inconspicuous IOP. In a long‐term study of 82 months the RVP was strongly predictive for an increased excavation of the optic disc (odds ratio 1.3/mmHg RVP). We hypothesize that the RVP may be a more potent risk factor than the IOP. Until now, the RVP has been measured by the Dynoptor or by contact lens dynamometry. Due to the hesitant acceptance of these measurement techniques a new method has been developed in which the cornea is no longer touched. By including the RVP in glaucoma diagnostics a new parameter may be available for the risk assessment of this disease.
Agonistic autoantibodies in ocular and systemic disease
Authors: Kunze Rudolf
Published: December 2019

Agonistic autoantibodies activate G‐protein coupled receptors (GPCRs) by binding to extracellular loop1 or 2. This mechanism was observed for ß1‐adrenoceptors (AR), the α1‐AR and others. They are pathophysiologically organ‐specific and may be disease‐associated or exacerbating, e.g. in dilated cardiomyopathy (DCM), refractory hypertension or vascular Alzheimer's disease. Additionally, these receptors, in particular ß2‐AR, are located on ocular structures (e.g. ciliary body, trabecular meshwork). As main targets of intraocular pressure (IOP) maintenance might be regulated via ß2‐AR, targets of this AR are in the spotlight of glaucoma research.
AI opportunities and challenges
Authors: Schmetterer Leopold
Published: December 2019

Classical approaches to extract information from medical images include semantic features, defined by human experts, and agonistic features, defined by equations. The concept of machine learning approaches is to use agonistic features, but not based on mathematical description or modeling, but by a black box approach. Principal steps in establishing deep learning based approaches include training of a convolutional neuronal network based on a large dataset, using clinical diagnosis is the gold standard, testing performance in a validation dataset and refining the convolutional neuronal network by adding longitudinal data. In diseases such as diabetic retinopathy the diagnostic performance of such convolutional neural networks is at least as good as the performance of human graders. Up to now artificial intelligence approaches are, however, narrow. They may be superior to humans in performing one task, but they do not address factors that are important for treatment decisions. The present talk will summarize opportunities and challenges in implementing artificial intelligence in healthcare and discuss issues related to reimbursement, liability and patient acceptance.
Genetic landscape of Usher syndromes
Authors: Roux Anne‐Francoise
Published: December 2019

Usher syndrome (USH) refers to recessively inherited disorders that associate hearing loss (HL) and retinitis pigmentosa (RP). Three clinical subtypes are defined with respect to the degree of HL, the age of RP onset and the occurrence of vestibular areflexia. Ten genes, that when mutated lead the development of the disease, have been identified: six (MYO7A, USH1C, CDH23, PCDH15, USH1G and CIB2) are involved in Usher type 1, the most disabling form, three (USH2A, ADGRV1 (GPR98) and WHRN) in Usher type 2, the most frequent form, and one, CLRN1, in Usher type 3. For many years, molecular diagnosis of Usher syndrome was laborious as many of these genes consist of numerous exons (e.g. 49 for MYO7A and 72 for USH2A, the most frequently involved genes). In the last years, implementation of MPS (Massively parallel sequencing) in diagnosis laboratories permits simultaneous sequencing of all the USH genes, thus making molecular studies of Usher patients much easier and faster. Yet, additional tools to search for hidden mutations or to classify the numerous variants of unknown clinical significance are needed in order to offer a proper comprehensive diagnosis. When gene panels include additional genes mimicking USH syndrome, it becomes possible to address subtle differential diagnoses. However, since several USH genes are involved in non‐syndromic HL as well, they can now be screened in patients presenting with apparent non‐syndromic form. Then, the challenge is to provide the most accurate genetic counselling as whether a child carrying two USH1 pathogenic variants will develop Usher syndrome or not. Finally, elucidating the molecular causes of Usher syndrome remains the essential step to build patient cohorts and to develop therapeutic approaches.
Current and future gene‐based therapies for Usher syndromes
Authors: Kalatzis Vasiliki
Published: December 2019

Inherited retinal dystrophies are a group of genetically and clinically heterogeneous disorders characterized by photoreceptor degeneration. One common example is retinitis pigmentosa (RP), which is characterized by impaired night vision and progressively decreasing peripheral vision. Moreover, RP can be present as either an isolated visual defect or in association with extra ocular symptoms. The most common syndromic form is Usher syndrome, which is characterized by RP associated with neurosensory deafness of varying severity. The difficulty of this double handicap demands the development of novel therapies. The advantage of the Usher syndrome group is that each disease is monogenic thus lending themselves to gene‐based therapies. The caveat is that the most common forms are due to mutations in large genes, thus rendering gene replacement challenging. This talk will present an overview of current gene‐based therapies for Usher syndrome as a whole and will concentrate on novel genome‐editing advances for the most prevalent causative gene, USH2A.
Photocoagulation of Telangiectatic capillaries using Navigated Laser
Authors: Pedinielli Alexandre
Published: December 2019

Targeting macular telangiectatic capillaries for laser photocoagulation can be challenging. The aim of this talk is to present laser photocoagulation using a Navigated laser. The first part of the presentation will discuss the modalities of treatment and the second part will talk about the short and the long terms effects in patients with macular edema.
Assessing loss of colour vision in patients with clinical disorders
Authors: Barbur John L. , Rauscher Franziska G.
Published: December 2019

Conventional colour assessment (CA) tests rarely isolate the use of Red/Green (RG) colour signals. The successful completion of a visual task cannot therefore be attributed entirely to the use of RG signals, even in normal trichromats. A good example is the Farnsworth D15 test; when no errors are accepted, 6.3% of normal trichromats fail and 50% of deutans and 41% of protans pass. The use of Yellow/Blue (YB) colour signals as well as rod and cone mediated luminance signals contributes significantly to the outcome of the test.

Patients with diseases of the retina and systemic diseases that affect colour vision vary in the severity of RG and YB loss, from almost normal responses to complete loss of colour vision. These patients also often exhibit reduced rod and cone mediated luminance contrast sensitivity. When acquired loss, as a result of disease, adds to congenital RG deficiency, CA becomes even more challenging. When taken together, these factors account for the large variability and inconsistency of outcome in conventional CA tests.

The recent development of sensitive and specific tests for assessment of RG and YB deficiencies and the establishment of reliable, normal‐age limits have transformed the effectiveness of CA as a clinical tool in the detection and monitoring of diseases such as diabetes, age‐related macular degeneration, glaucoma and a range of other degenerative diseases of the photoreceptors, neural retina and the RPE that often manifest first through a reduction in YB and RG chromatic sensitivity. The latter can range from thresholds that are just above normal age limits to complete loss of colour vision, even when high contrast acuity and other visual functions remain largely unaffected. The loss of colour vision often varies over the retina and in some patients, the loss can be asymmetric and no longer follows the rules of RG and YB chromatic opponency. Such findings have important implications on the processing of chromatic signals.
Assessing the severity of colour vision loss – implications for occupational environments
Authors: Barbur John L. , Rodriguez‐Carmona Marisa , Evans Benjamin
Published: December 2019

Colour is often used in safety‐critical environments to code and signal information. Colour is also used to enhance target ‘conspicuity’ and visual performance in ‘grouping’, segmentation and pop‐out tasks. Colour vision (CV) is not a key requirement in everyday life, but in some safety‐critical jobs, it can be a matter of life and death. The absence of normally functioning chromatic mechanisms leads to reduced chromatic sensitivity and also to changes in the perceived colour of objects. CV is needed in some occupations, but the majority of subjects with congenital colour deficiency (CCD) retain some red / green (RG) CV. When the latter is combined with normal, yellow / blue (YB) colour signals, many CCD subjects are able to carry out suprathreshold, colour‐related tasks as well as normal trichromats. Since severity of loss in congenital deficiency extends from almost normal to complete absence of CV, it is important to determine accurately severity of CV loss. Empirical studies carried out in some occupations established the degree of CV loss that can be classed as ‘safe’. This led to the establishment of minimum requirements that can be enforced. In addition to safety, the overall aim is to ensure that all subjects with anomalous trichromatic colour vision who can perform the safety‐critical, colour tasks in a given job as well as normal trichromats pass and do not end up being discriminated against unfairly on the basis of their CCD. Until very recently, it has not been possible to achieve this aim, simply because many existing CV tests lack sensitivity and / or specificity and also fail to quantify reliably the severity of CV loss. Improved understanding of CV and the recent development of sensitive and specific CV tests have transformed traditional colour assessment (Br Med Bull. 2017;122 (1):51–77). Results will be presented to show how a single colour assessment test can be used to establish the applicant’s class of CV and to quantify the severity of loss.