Abstract: The disease burden of diabetic retinopathy (DR) is tremendous around the world. While DR is correlated with hemoglobin A1c (HbA1c) and duration of diabetes, genetic differences likely account for variation in susceptibility to DR. DR is a polygenic disorder with demonstrated heritability. However, linkage and admixture analyses, candidate gene association studies, and genome-wide association studies (GWAS) have not identified many loci for DR that can be consistently replicated. Larger, collaborative, multi-ethnic GWAS are needed to identify common variants with small effects. Rigorous defining of controls groups as patients with a long duration of diabetes without DR, and case groups as patients with severe DR will also aid in finding genes associated with DR. Replication in independent cohorts will be key to establishing associated loci for DR. Investigations of mitochondrial DNA and epigenetics in DR are ongoing. Whole exome sequencing presents new opportunities to identify rare variants that might be implicated in DR development. Continued research in the genetic epidemiology of DR is needed, with the potential to elucidate pathogenesis and treatment of an important disease.

Abstract: There are many advantages to understanding the genetics of human disease. Genetic markers can be used to calculate the risk of developing a disease, and elucidation of genetic risk factors can pinpoint the molecular aetiology of disease, which can facilitate the development of targeted therapies. Diabetic retinopathy (DR) is a common complication of diabetes that has a significant impact on quality of life. It has a clear genetic component, but determination of the genetic risk factors has proven difficult. To date, genome-wide studies for DR have been conducted on relatively small patient cohorts compared to other complex eye diseases and replication of genetic findings has been limited. The disease is highly heterogeneous, confounding attempts to classify patients into appropriate groups for genetic analysis and making direct comparisons between studies challenging. Future studies to determine the genetic causes of DR will need to focus on larger sample sizes, detailed phenotyping and appropriate classification of patients. Global co-operation and meta-analyses combining data from multiple studies will be critical to the discovery of genetic risk loci for DR.

Abstract: The Guangzhou Twin Eye Study (GTES) is a population-based study of young twins residing in Guangzhou City. The major aim of GTES is to explore the impact of genes, environmental factors and gene-environment interactions on common eye diseases. From 2006, for more than 1,300 twin pairs, age 7–26 years old, progressive ocular phenotypes, such as refraction, ocular biometrics, weight, and height were collected annually, while non-progressive phenotypes such as parental refraction, corneal thickness, retinal fundus, intraocular pressure and DNA only collected at baseline. In the current study, we summarize the major findings on the etiology of myopia in recent decades.

Abstract: Mononuclear phagocytes (MP) comprise a family of cells that include microglial cells (MC), monocytes, and macrophages. The subretinal space, located between the RPE and the photoreceptor outer segments, is physiologically devoid of MPs and a zone of immune privilege mediated, among others, by immunosuppressive RPE signals. Age-related macular degeneration (AMD) is a highly heritable major cause of blindness, characterized by a breakdown of the subretinal immunosuppressive environment and an accumulation of pathogenic inflammatory MPs. Studies in mice and humans suggest that the AMD-associated APOE2 isoform promotes the breakdown of subretinal immunosuppression and increased MP survival. Of all genetic factors, variants of complement factor H (CFH) are associated with greatest linkage to AMD. Using loss of function genetics and orthologous models of AMD, we provide mechanistic evidence that CFH inhibits the elimination of subretinal MPs. Importantly, the AMD-associated CFH402H isoform markedly increased this inhibitory effect on microglial cells, indicating a causal link to disease etiology. Pharmacological acceleration of resolution of subretinal inflammation might be a powerful tool for controlling inflammation and neurodegeneration in late AMD.

Abstract: The inverted retina is a basic characteristic of the vertebrate eye. This implies that vertebrates must have a common ancestor with an inverted retina. Of the two groups of chordates, cephalochordates have an inverted retina and urochordates a direct retina. Surprisingly, recent genetics studies favor urochordates as the closest ancestor to vertebrates. The evolution of increasingly complex organs such as the eye implies not only tissular but also structural modifications at the organ level. How these configurational modifications give rise to a functional eye at any step is still subject to debate and speculation. Here we propose an orderly sequence of phylogenetic events that closely follows the sequence of developmental eye formation in extant vertebrates. The progressive structural complexity has been clearly recorded during vertebrate development at the period of organogenesis. Matching the chain of increasing eye complexity in Mollusca that leads to the bicameral eye of the octopus and the developmental sequence in vertebrates, we delineate the parallel evolution of the two-chambered eye of vertebrates starting with an early ectodermal eye. This sequence allows for some interesting predictions regarding the eyes of not preserved intermediary species. The clue to understanding the inverted retina of vertebrates and the similarity between the sequence followed by Mollusca and chordates is the notion that the eye in both cases is an ectodermal structure, in contrast to an exclusively (de novo) neuroectodermal origin in the eye of vertebrates. This analysis places cephalochordates as the closest branch to vertebrates contrary to urochordates, claimed as a closer branch by some researchers that base their proposals in a genetic analysis.

Abstract: Pediatric neuro-ophthalmology is a subspecialty within neuro-ophthalmology. Pediatric neuro-ophthalmic diseases must be considered separate from their adult counterparts, due to the distinctive nature of the examination, clinical presentations, and management choices. This manuscript will highlight four common pediatric neuro-ophthalmic disorders by describing common clinical presentations, recommended management, and highlighting recent developments. Diseases discussed include pediatric idiopathic intracranial hypertension (IIH), pseudopapilledema, optic neuritis (ON) and optic pathway gliomas (OPG). The demographics, diagnosis and management of common pediatric neuro-ophthalmic disease require a working knowledge of the current research presented herein. Special attention should be placed on the differences between pediatric and adult entities such that children can be appropriately diagnosed and treated.

Abstract: To describe the current aging population in China and globally, especially as it applies to age-related macular degeneration (AMD). To review the current standards of care for treating both wet (exudative) eAMD and dry (atrophic) aAMD. And to introduce a model for experimentation that is based on the Age-Related Eye Disease Study (AREDS) using eye bank tissue. A literature search that outlines current aging populations, standards of clinical treatment as defined by large, multicenter, randomized clinical trials that present level-I data with a low risk for bias. An experimental model system of AMD is presented that enables scientific analysis of AMD pathogenesis by applying grading criteria from the AREDS to human eye bank eyes. Analysis includes proteomic, cellular, and functional genomics. The standard of care for the treatment of eAMD is currently defined by the use of several anti-vascular endothelial growth (anti-VEGF) agents alone or in combination with photodynamic therapy. Monotherapy treatment intervals may be monthly, as needed, or by using a treat-and-extend (TAE) protocol. There are no proven therapies for aAMD. AMD that is phenotypically defined at AREDS level 3, should be managed with the use of anti-oxidant vitamins, lutein/zeaxanthin and zinc (AREDS-2 formulation). By understanding the multiple etiologies in the pathogenesis of AMD (i.e., oxidative stress, inflammation, and genetics), the use of human eye bank tissues graded according to the Minnesota Grading System (MGS) will enable future insights into the pathogenesis of AMD. Initial AMD management is with lifestyle modification such as avoiding smoking, eating a healthy diet and using appropriate vitamin supplements (AREDS-2). For eAMD, anti-VEGF therapies using either pro re nata (PRN) or TAE protocols are recommended, with photodynamic therapy in appropriate cases. New cellular information will direct future, potential therapies and these will originate from experimental models, such as the proposed eye bank model using the MGS, that leverages the prospective AREDS database.