AUTOMATED DETECTION OF VITRITIS USING ULTRAWIDE-FIELD FUNDUS PHOTOGRAPHS AND DEEP LEARNING.

BACKGROUND/PURPOSE: Evaluate the performance of a deep learning algorithm for the automated detection and grading of vitritis on ultrawide-field imaging. METHODS: Cross-sectional noninterventional study. Ultrawide-field fundus retinophotographs of uveitis patients were used. Vitreous haze was defined according to the six steps of the Standardization of Uveitis Nomenclature classification. The deep learning framework TensorFlow and the DenseNet121 convolutional neural network were used to perform the classification task. The best fitted model was tested in a validation study. RESULTS: One thousand one hundred eighty-one images were included. The performance of the model for the detection of vitritis was good with a sensitivity of 91%, a specificity of 89%, an accuracy of 0.90, and an area under the receiver operating characteristics curve of 0.97. When used on an external set of images, the accuracy for the detection of vitritis was 0.78. The accuracy to classify vitritis in one of the six Standardization of Uveitis Nomenclature grades was limited (0.61) but improved to 0.75 when the grades were grouped into three categories. When accepting an error of one grade, the accuracy for the six-class classification increased to 0.90, suggesting the need for a larger sample to improve the model performances. CONCLUSION: A new deep learning model based on ultrawide-field fundus imaging that produces an efficient tool for the detection of vitritis was described. The performance of the model for the grading into three categories of increasing vitritis severity was acceptable. The performance for the six-class grading of vitritis was limited but can probably be improved with a larger set of images.

Ophthalmic Emergency Visits in the Wake of the COVID 19 Pandemic: Our Experience at a Tertiary Hospital in Israel.

BACKGROUND: In response to the coronavirus disease-2019 (COVID-19) pandemic, routine clinical visits to the ophthalmic emergency department (OED) were deferred, while emergency cases continued to be seen. OBJECTIVES: To assess the consequences of the COVID-19 pandemic for ophthalmic emergencies. METHODS: A retrospective chart analysis of patients who presented to the OED during the peak of the COVID-19 pandemic was conducted. The proportions of traumatic, non-traumatic-urgent, and non-traumatic-non-urgent presentations in 2020 were compared to those of the same time period in 2019. Duration of chief complains and best-corrected visual acuity were also assessed. RESULTS: There were 144 OED visits in 2020 compared to 327 OED visits during the same 3-week-period in 2019. Lower mean age of OED patients was present in 2020. Logarithmic expression (LogMAR) best corrected visual acuity (BVCA) was similar in both years. In 2020 there was a reduction in traumatic, non-traumatic-urgent, and non-traumatic-non-urgent cases compared to 2019 (15.4% reduction, P = 0.038; 57.6% reduction, P = 0.002; 74.6% reduction, P = 0.005, respectively). There was a higher proportion of same-day presentations at commencement of symptoms in 2020 compared with 2019 (52.8% vs. 38.8%, respectively P = 0.006). CONCLUSIONS: During the COVID-19 pandemic, the number of OED visits at a tertiary hospital dropped by more than half. Although the drop in visits was mostly due to decrease in non-traumatic-non-urgent cases, there was also decrease in non-traumatic-urgent presentations with possible important visual consequences. Additional studies should elucidate what happened to these patients.

Ocular Involvement in Hereditary Amyloidosis.

The term amyloidosis describes a group of rare diseases caused by protein conformation abnormalities resulting in extracellular deposition and accumulation of insoluble fibrillar aggregates. So far, 36 amyloid precursor proteins have been identified, and each one is responsible for a specific disease entity. Transthyretin amyloidosis (ATTRv) is one of the most common forms of systemic and ocular amyloidosis, due to the deposition of transthyretin (TTR), which is a transport protein mainly synthesized in the liver but also in the retinal pigment epithelial cells. ATTRv amyloidosis may be misdiagnosed with several other conditions, resulting in a significant diagnostic delay. Gelsolin and keratoepithelin are other proteins that, when mutated, are responsible for a systemic amyloid disease with significant ocular manifestations that not infrequently appear before systemic involvement. The main signs of ocular amyloid deposition are in the cornea, irido-corneal angle and vitreous, causing complications related to vasculopathy and neuropathy at the local level. This review aims at describing the main biochemical, histopathological and clinical features of systemic amyloidosis associated with eye involvement, with particular emphasis on the inherited forms. We discuss currently available treatments, focusing on ocular involvement and specific ophthalmologic management and highlighting the importance of a prompt treatment for the potential sight-threatening complications derived from amyloid deposition in ocular tissues.

New Highlights of Resveratrol: A Review of Properties against Ocular Diseases.

Eye diseases are currently a major public health concern due to the growing number of cases resulting from both an aging of populations and exogenous factors linked to our lifestyles. Thus, many treatments including surgical pharmacological approaches have emerged, and special attention has been paid to prevention, where diet plays a preponderant role. Recently, potential antioxidants such as resveratrol have received much attention as potential tools against various ocular diseases. In this review, we focus on the mechanisms of resveratrol against ocular diseases, in particular age-related macular degeneration, glaucoma, cataract, diabetic retinopathy, and vitreoretinopathy. We analyze, in relation to the different steps of each disease, the resveratrol properties at multiple levels, such as cellular and molecular signaling as well as physiological effects. We show and discuss the relationship to reactive oxygen species, the regulation of inflammatory process, and how resveratrol can prevent ocular diseases through a potential epigenetic action by the activation of sirtuin-1. Lastly, various new forms of resveratrol delivery are emerging at the same time as some clinical trials are raising more questions about the future of resveratrol as a potential tool for prevention or in therapeutic strategies against ocular diseases. More preclinical studies are required to provide further insights into RSV's potential adjuvant activity.

Validity of International Classification of Diseases Codes for Identifying Neuro-Ophthalmic Disease in Large Data Sets: A Systematic Review.

BACKGROUND: Administrative health claims data have been used for research in neuro-ophthalmology, but the validity of International Classification of Diseases (ICD) codes for identifying neuro-ophthalmic conditions is unclear. EVIDENCE ACQUISITION: We performed a systematic literature review to assess the validity of administrative claims data for identifying patients with neuro-ophthalmic disorders. Two reviewers independently reviewed all eligible full-length articles and used a standardized abstraction form to identify ICD code-based definitions for 9 neuro-ophthalmic conditions and their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). A quality assessment of eligible studies was also performed. RESULTS: Eleven articles that met criteria for inclusion are as follows: 3 studies of idiopathic intracranial hypertension (PPV 54%-91% and NPV 74%-85%), 2 studies of giant cell arteritis (sensitivity 30%-96% and PPV 94%), 3 studies of optic neuritis (sensitivity 76%-99%, specificity 83%-100%, PPV 25%-100%, and NPV 98%-100%), 1 study of neuromyelitis optica (sensitivity 60%, specificity 100%, PPV 43%-100%, and NPV 98%-100%), 1 study of ocular motor cranial neuropathies (PPV 98%-99%), and 2 studies of myasthenia gravis (sensitivity 53%-97%, specificity 99%-100%, PPV 5%-90%, and NPV 100%). No studies met eligibility criteria for nonarteritic ischemic optic neuropathy, thyroid eye disease, and blepharospasm. Approximately 45.5% provided only one measure of diagnostic accuracy. Complete information about the validation cohorts, inclusion/exclusion criteria, data collection methods, and expertise of those reviewing charts for diagnostic accuracy was missing in 90.9%, 72.7%, 81.8%, and 36.4% of studies, respectively. CONCLUSIONS: Few studies have reported the validity of ICD codes for neuro-ophthalmic conditions. The range of diagnostic accuracy for some disorders and study quality varied widely. This should be taken into consideration when interpreting studies of neuro-ophthalmic conditions using administrative claims data.

Triaging ophthalmology outpatient referrals with machine learning: A pilot study.

IMPORTANCE: Triaging of outpatient referrals to ophthalmology services is required for the maintenance of patient care and appropriate resource allocation. Machine learning (ML), in particular natural language processing, may be able to assist with the triaging process. BACKGROUND: To determine whether ML can accurately predict triage category based on ophthalmology outpatient referrals. DESIGN: Retrospective cohort study. PARTICIPANTS: The data of 208 participants was included in the project. METHODS: The synopses of consecutive ophthalmology outpatient referrals at a tertiary hospital were extracted along with their triage categorizations. Following pre-processing, ML models were applied to determine how accurately they could predict the likely triage categorization allocated. Data was split into training and testing sets (75%/25% split). ML models were tested on an unseen test set, after development on the training dataset. MAIN OUTCOME MEASURE: Area under the receiver operator curve (AUC) for category one vs non-category one classification. RESULTS: For the main outcome measure, convolutional neural network (CNN) provided the best AUC (0.83) and accuracy on the test set (0.81), with the artificial neural network (AUC 0.81 and accuracy 0.77) being the next best performing model. When the CNN was applied to the classification task of identifying which referrals should be allocated a category one vs category two vs category three priority, a lower accuracy was achieved (0.65). CONCLUSIONS AND RELEVANCE: ML may be able to accurately assist with the triaging of ophthalmology referrals. Future studies with data from multiple centres and larger sample sizes may be beneficial.

Long non-coding RNAs in ocular diseases: new and potential therapeutic targets.

Long non-coding RNAs (lncRNAs) are non-protein coding transcripts containing more than 200 nucleotides. In the past, lncRNAs were considered as 'transcript noise' or 'pseudogenes' and were thus ignored. However, in recent years, lncRNAs have been proven to regulate gene expression at the epigenetic, transcriptional and translational level, and thereby influence cell proliferation, apoptosis, viability, immune response and oxidative stress. Furthermore, increasing evidence points to their involvement in different diseases, including cancer and heart diseases. Recently, lncRNAs were shown to be differentially expressed in ocular tissues and play a significant role in the pathogenesis of ophthalmological disorders such as glaucoma, corneal diseases, cataract, diabetic retinopathy, proliferative vitreoretinopathy and ocular tumors. In this review, we summarize the classification and mechanisms of known lncRNAs, while detailing their biological functions and roles in ocular diseases. Moreover, we provide a concise review of the clinical relevance of lncRNAs as novel, potential therapeutic targets in the treatment of eye diseases.

An ontological foundation for ocular phenotypes and rare eye diseases.

BACKGROUND: The optical accessibility of the eye and technological advances in ophthalmic diagnostics have put ophthalmology at the forefront of data-driven medicine. The focus of this study is rare eye disorders, a group of conditions whose clinical heterogeneity and geographic dispersion make data-driven, evidence-based practice particularly challenging. Inter-institutional collaboration and information sharing is crucial but the lack of standardised terminology poses an important barrier. Ontologies are computational tools that include sets of vocabulary terms arranged in hierarchical structures. They can be used to provide robust terminology standards and to enhance data interoperability. Here, we discuss the development of the ophthalmology-related component of two well-established biomedical ontologies, the Human Phenotype Ontology (HPO; includes signs, symptoms and investigation findings) and the Orphanet Rare Disease Ontology (ORDO; includes rare disease nomenclature/nosology). METHODS: A variety of approaches were used including automated matching to existing resources and extensive manual curation. To achieve the latter, a study group including clinicians, patient representatives and ontology developers from 17 countries was formed. A broad range of terms was discussed and validated during a dedicated workshop attended by 60 members of the group. RESULTS: A comprehensive, structured and well-defined set of terms has been agreed on including 1106 terms relating to ocular phenotypes (HPO) and 1202 terms relating to rare eye disease nomenclature (ORDO). These terms and their relevant annotations can be accessed in http://www.human-phenotype-ontology.org/ and http://www.orpha.net/ ; comments, corrections, suggestions and requests for new terms can be made through these websites. This is an ongoing, community-driven endeavour and both HPO and ORDO are regularly updated. CONCLUSIONS: To our knowledge, this is the first effort of such scale to provide terminology standards for the rare eye disease community. We hope that this work will not only improve coding and standardise information exchange in clinical care and research, but also it will catalyse the transition to an evidence-based precision ophthalmology paradigm.

Ophthalmic manifestations of Gaucher disease: the most common lysosomal storage disorder.

Gaucher disease (GD) results from a deficiency of glucocerebrosidase activity and the subsequent accumulation of the enzyme's metabolites, principally glucosylsphingosine and glucosylceramide. There are three principal forms: Type I, which is the most common, is usually considered non-neuronopathic. Type II, III and IIIc manifest earlier and have neurological sequelae due to markedly reduced enzyme activity. Gaucher's can be associated with ophthalmological sequelae but these have not been systematically reviewed. We therefore performed a comprehensive literature review of all such ophthalmic abnormalities associated with the different types of Gaucher disease. We systematically searched the literature (1950 - present) for functional and structural ocular abnormalities arising in patients with Gaucher disease and found that all subtypes can be associated with ophthalmic abnormalities; these range from recently described intraocular lesions to disease involving the adnexae, peripheral nerves and brain. In summary, Gaucher can affect most parts of the eye. Rarely is it sight-threatening; some but not all manifestations are amenable to treatment, including with enzyme replacement and substrate reduction therapy. Retinal involvement is rare but patients with ocular manifestations should be monitored and treated early to reduce the risk of progression and further complications. As Gaucher disease is also associated with Parkinsons disease and may also confer an increased risk of malignancy (particularly haematological forms and melanoma), any ocular abnormalities should be fully investigated to exclude these potential underlying conditions.

Clinical Registries in Ophthalmology.

TOPIC: Clinical registries in ophthalmology. CLINICAL RELEVANCE: In recent years, advancements in digital technology and increasing use of electronic medical records in health systems have led to the dramatic growth in large clinical data sets. Clinical data registries are organized systems that collect data on patients diagnosed with a disease or condition or who undergo a certain procedure. METHODS: A search of the PUBMED database was conducted in January 2018 for clinical registries in ophthalmology. RESULTS: Ninety-seven clinical eye registries were found, with significant growth in numbers in the last 4 decades. The most common conditions captured were blindness or low vision, corneal transplantation, glaucoma, and cataract surgery. Most registries originate in the European region, North America, and Australia. Nine registries had multinational coverage, whereas 48 were national registries. As the numbers and scope of clinical registries have expanded, valuable observational data have been used to study real-world clinical outcomes in healthcare quality measurement and improvement and to develop new guidelines and standards. Pertinent areas of its use include studying treatments and outcomes in cataract surgery, corneal transplantation, and macular degeneration. CONCLUSIONS: The use of clinical registries for quality improvement and research has grown significantly in the last few decades, and this trend will continue as information technology infrastructures develop.

An Interpretable and Expandable Deep Learning Diagnostic System for Multiple Ocular Diseases: Qualitative Study.

BACKGROUND: Although artificial intelligence performs promisingly in medicine, few automatic disease diagnosis platforms can clearly explain why a specific medical decision is made. OBJECTIVE: We aimed to devise and develop an interpretable and expandable diagnosis framework for automatically diagnosing multiple ocular diseases and providing treatment recommendations for the particular illness of a specific patient. METHODS: As the diagnosis of ocular diseases highly depends on observing medical images, we chose ophthalmic images as research material. All medical images were labeled to 4 types of diseases or normal (total 5 classes); each image was decomposed into different parts according to the anatomical knowledge and then annotated. This process yields the positions and primary information on different anatomical parts and foci observed in medical images, thereby bridging the gap between medical image and diagnostic process. Next, we applied images and the information produced during the annotation process to implement an interpretable and expandable automatic diagnostic framework with deep learning. RESULTS: This diagnosis framework comprises 4 stages. The first stage identifies the type of disease (identification accuracy, 93%). The second stage localizes the anatomical parts and foci of the eye (localization accuracy: images under natural light without fluorescein sodium eye drops, 82%; images under cobalt blue light or natural light with fluorescein sodium eye drops, 90%). The third stage carefully classifies the specific condition of each anatomical part or focus with the result from the second stage (average accuracy for multiple classification problems, 79%-98%). The last stage provides treatment advice according to medical experience and artificial intelligence, which is merely involved with pterygium (accuracy, >95%). Based on this, we developed a telemedical system that can show detailed reasons for a particular diagnosis to doctors and patients to help doctors with medical decision making. This system can carefully analyze medical images and provide treatment advices according to the analysis results and consultation between a doctor and a patient. CONCLUSIONS: The interpretable and expandable medical artificial intelligence platform was successfully built; this system can identify the disease, distinguish different anatomical parts and foci, discern the diagnostic information relevant to the diagnosis of diseases, and provide treatment suggestions. During this process, the whole diagnostic flow becomes clear and understandable to both doctors and their patients. Moreover, other diseases can be seamlessly integrated into this system without any influence on existing modules or diseases. Furthermore, this framework can assist in the clinical training of junior doctors. Owing to the rare high-grade medical resource, it is impossible that everyone receives high-quality professional diagnosis and treatment service. This framework can not only be applied in hospitals with insufficient medical resources to decrease the pressure on experienced doctors but also deployed in remote areas to help doctors diagnose common ocular diseases.

Frequency of ocular diseases among recipients of disability benefits in the metropolitan region of Recife, Brazil / Incapacidade para o trabalho por doenças oculares na população segurada da Previdência Social da região metropolitana do Recife, Brasil: um estudo de frequência

ABSTRACT Purpose: To identify the frequency of ocular diseases among recipients of disability benefits in the metropolitan region of Recife, Brazil. Methods: A review was performed of 217,221 cases of disability benefits granted between 2010 and 2015 by the executive managerial department of the Brazilian National Institute of Social Security (Instituto Nacional do Seguro Social [INSS]) in Recife, which encompasses 14 municipalities of the metropolitan region, including the capital. The frequencies of the identified cases of ocular morbidity were then determined according to their group in the International Classification of Diseases, 10th Revision (ICD-10), their cause, the age, sex, and income of the recipient, and the type and duration of the benefit. Results: Of all disability benefits granted, 5,324 (2.5%) were due to ocular disease, the majority (91.1%) consisting of sick pay. Most of the beneficiaries (64.6%) were males, were 20 to 59 years of age, and 61.2% earned the minimum wage or less. The principal ocular diseases for which sick pay benefits were granted were cataract (24.5%), conjunctivitis (21.1%), and pterygium (8.8%). Blindness and low vision were the principal ocular diseases in cases of accident indemnity and disability retirement. Conclusions: The results highlight the magnitude of the problem of ocular diseases to the social security system, with serious economic and social losses, and emphasize the need for measures aimed at their prevention. Moreover, integration between the national departments of health and social security needs to be improved.

RESUMO Objetivo: Identificar a frequência das doenças oculares entre os segurados com benefícios por incapacidade. Métodos: Estudo retrospectivo de 217.221 benefícios por incapacidade concedidos pelo Instituto Nacional do Seguro Social (INSS) da gerência executiva de Recife, que engloba os 14 municípios da região metropolitana, incluindo a capital, no período de 2010-2015. Os casos de doenças oculares foram avaliados quanto à frequência considerando seu grupo na CID-10. Foi feita ainda uma análise do perfil dos benefícios concedidos por estas doenças com relação à causa, idade, sexo, faixa salarial, espécie e duração do benefício. Resultados Do total dos benefícios concedidos, 5.324 foram decorrentes de doenças oftalmológicas (2,5%) e entre estes, a maioria como auxíliodoença (91,1%). Houve predomínio do sexo masculino (64,6%), faixa etária dos 20 aos 59 anos e valor de até 01 salário mínimo (61,2%). Entre as concessões de auxíliodoença a principal causa foi a catarata (24,5%), seguida pela conjuntivite (21,1%) e pterígio (8,8%). A cegueira e baixa visão foi a principal causa de auxílio-acidente e aposentadoria por invalidez. Conclusões: Os resultados destacam a magnitude do problema das doenças oculares para a Previdência Social, com graves perdas econômicas e sociais, e enfatizam a necessidade de medidas que visem sua prevenção e maior integração entre os serviços de saúde e o INSS (Instituto Nacional do Seguro Social).

Peripapillary choroidal thickness in contralateral eyes after evisceration of diseased eyes / Espessura coroide peripapilar de olhos contralaterais após evisceração do olho doente

ABSTRACT Purpose: To evaluate peripapillary choroidal thickness changes in contralateral eyes of patients who had undergone evisceration of their diseased eyes. Methods: In this retrospective study, peripapillary choroidal thickness parameters in 34 eyes of 34 patients who had undergone diseased-eye evisceration between March 2014 and May 2016 were evaluated using spectral domain optical coherence tomography. The scans were manually delineated to identify the principal surfaces of Bruch's membrane, the Bruch's membrane opening, and the anterior sclera. Peripapillary choroidal thickness was measured between the Bruch's membrane and the anterior sclera at increasing distance away from the Bruch's membrane opening. The mean peripapillary choroidal thickness values in the contralateral eyes of the patients and those of the control group were compared. Results: The mean peripapillary choroidal thickness was higher in the contralateral eyes of the patients compared with that of normal eyes at all distances from the Bruch's membrane opening. Conclusion: Increased peripapillary choroidal thickness was noted in the contralateral eyes of the patients, potentially resulting in a thicker choroid. Although further investigation is required to determine the cause, these findings indicate the presence of a compensatory factor in the contralateral eyes.

RESUMO Objetivo: Avaliar as alterações da espessura coroide peripapilar em olhos contralaterais de pacientes submetidos à evisceração do olho doente. Métodos: Neste estudo retrospectivo, parâmetros da espessura coróide peripapilar de 34 olhos de 34 pacientes submetidos à evisceração, entre março de 2014 e maio de 2016, foram avaliados com tomografia de coerência óptica de domínio espectral. As varreduras foram manualmente delineadas para identificar as principais superfícies da membrana de Bruch, a abertura da membrana de Bruch e a esclera anterior. A espessura coroide peripapilar foi medida entre a membrana de Bruch e a esclera anterior a uma distância crescente da abertura da membrana de Bruch. Compararam-se os valores médios da espessura coroide peripapilar dos olhos contralaterais dos pacientes e do grupo controle. Resultados: A espessura coroide peripapilar média foi mais espessa nos olhos contralaterais dos pacientes, quando comparada com os olhos normais, em todas as distâncias da abertura da membrana de Bruch. Conclusão: O aumento da espessura coroide peripapilar foi notado nos olhos contralaterais dos pacientes. O espessamento da coroide pode ser resultante do distúrbio. Embora seja necessária uma investigação mais aprofundada para determinar a causalidade, esses achados podem apontar para um fator compensatório dos olhos contralaterais.

Peripapillary choroidal thickness in contralateral eyes after evisceration of diseased eyes.

PURPOSE: To evaluate peripapillary choroidal thickness changes in contralateral eyes of patients who had undergone evisceration of their diseased eyes. METHODS: In this retrospective study, peripapillary choroidal thickness parameters in 34 eyes of 34 patients who had undergone diseased-eye evisceration between March 2014 and May 2016 were evaluated using spectral domain optical coherence tomography. The scans were manually delineated to identify the principal surfaces of Bruch's membrane, the Bruch's membrane opening, and the anterior sclera. Peripapillary choroidal thickness was measured between the Bruch's membrane and the anterior sclera at increasing distance away from the Bruch's membrane opening. The mean peripapillary choroidal thickness values in the contralateral eyes of the patients and those of the control group were compared. RESULTS: The mean peripapillary choroidal thickness was higher in the contralateral eyes of the patients compared with that of normal eyes at all distances from the Bruch's membrane opening. CONCLUSION: Increased peripapillary choroidal thickness was noted in the contralateral eyes of the patients, potentially resulting in a thicker choroid. Although further investigation is required to determine the cause, these findings indicate the presence of a compensatory factor in the contralateral eyes.

Frequency of ocular diseases among recipients of disability benefits in the metropolitan region of Recife, Brazil.

PURPOSE: To identify the frequency of ocular diseases among recipients of disability benefits in the metropolitan region of Recife, Brazil. METHODS: A review was performed of 217,221 cases of disability benefits granted between 2010 and 2015 by the executive managerial department of the Brazilian National Institute of Social Security (Instituto Nacional do Seguro Social [INSS]) in Recife, which encompasses 14 municipalities of the metropolitan region, including the capital. The frequencies of the identified cases of ocular morbidity were then determined according to their group in the International Classification of Diseases, 10th Revision (ICD-10), their cause, the age, sex, and income of the recipient, and the type and duration of the benefit. RESULTS: Of all disability benefits granted, 5,324 (2.5%) were due to ocular disease, the majority (91.1%) consisting of sick pay. Most of the beneficiaries (64.6%) were males, were 20 to 59 years of age, and 61.2% earned the minimum wage or less. The principal ocular diseases for which sick pay benefits were granted were cataract (24.5%), conjunctivitis (21.1%), and pterygium (8.8%). Blindness and low vision were the principal ocular diseases in cases of accident indemnity and disability retirement. CONCLUSIONS: The results highlight the magnitude of the problem of ocular diseases to the social security system, with serious economic and social losses, and emphasize the need for measures aimed at their prevention. Moreover, integration between the national departments of health and social security needs to be improved.

[Overview of Congenital Stationary Night Blindness with Predominantly Normal Fundus Appearance]. / Überblick über die kongenitale stationäre Nachtblindheit mit überwiegend normalem Fundus.

Congenital stationary night blindness (CSNB) is a clinically and genetically heterogeneous group of non-progressive retinal disorder with largely normal fundus appearance. The mode of inheritance can be autosomal dominant (adCSNB), autosomal recessive (arCSNB) or X-chromosomal (XLCSNB). Additional ocular signs can be myopia, hyperopia, strabismus, nystagmus and reduced visual acuity. The Riggs and Schubert-Bornschein form of CSNB can be discriminated by electroretinography. While the Riggs form represents a dysfunction of the rods, a signal transmission defect from photoreceptors to bipolar cell is described in patients with the more frequently occurring Schubert-Bornschein form. The Schubert-Bornschein form can be further divided into incomplete (icCSNB) and complete (cCSNB) showing different electroretinograms (ERGs). While patients with cCSNB show a dysfunction of the ON-signaling pathway, patients with icCSNB show a dysfunction of the ON- and OFF-signaling pathways, affecting visual acuity as well. Using classical linkage, candidate gene analyses and more recent next-generation sequencing approaches, to date, mutations in 13 different genes have been associated with this disease. In vitro and in vivo models showed a correlation of the phenotype of patients with the expression, protein localization and function of the respective molecules: genes, mutated in patients with the Riggs form of CSNB have an important role in the rod phototransduction cascade. Genes mutated in patients with icCSNB, code for proteins important for glutamate neurotransmitter release at the synaptic cleft of the photoreceptors. Genes mutated in patients with cCSNB, code for proteins important for glutamate uptake and further signal transmission to the ON-bipolar cells. Preliminary in vivo studies showed that CSNB may be cured by gene therapy. These studies concerning CSNB are important for the precise diagnosis of patients with this disease, but are also helpful in deciphering key molecules essential for signal transmission from photoreceptors to bipolar cells. So far, it is a poorly understood field.

Management of Extraocular Infections.

Extraocular infection is a frequently encountered problem in children including neonates and infants. Prompt recognition of the extraocular disease and management at first contact reduces the ocular morbidity and visual impairment. Delay in administering appropriate therapy and referral to an eye care personnel may result in blindness; sometimes bilateral, due to severe ophthalmia neonatorum. This review is mainly aimed at offering basic, brief information about common extraocular infections prevalent among infants and children living in developing countries as a ready reference to practising pediatricians and neonatologists. Through this review, the pediatricians, as the first contact may feel confident and comfortable in managing ocular infection in pediatric population particularly living in remote rural and tribal region. Literature search was made by retrieving related publications through peer reviewed journals, PUBMED and Cochrane meta-analysis.