PURPOSE: Prisms used for field expansion are limited by the optical scotoma at a prism apex (apical scotoma). For a patient with two functioning eyes, fitting prisms unilaterally allows the other eye to compensate for the apical scotoma. A monocular patient's field loss cannot be expanded with a conventional or Fresnel prism because of the apical scotoma. A newly invented optical device, the multiplexing prism (MxP), was developed to overcome the apical scotoma limitation in monocular field expansion. METHODS: A Fresnel-prism-like device with alternating prism and flat elements superimposes shifted and see-through views, thus creating the (monocular) visual confusion required for field expansion and eliminating the apical scotoma. Several implementations are demonstrated and preliminarily evaluated for different monocular conditions with visual field loss. The field expansion of the MxP is compared with the effect of conventional prisms using calculated and measured perimetry. RESULTS: Field expansion without apical scotomas is shown to be effective for monocular patients with hemianopia or constricted peripheral field. The MxPs are shown to increase the nasal field for a patient with only one eye and for patients with bitemporal hemianopia. The MxPs placed at the far temporal field are shown to expand the normal visual field. The ability to control the contrast ratio between the two images is verified. CONCLUSIONS: A novel optical device is demonstrated to have the potential for field expansion technology in a variety of conditions. The devices may be inexpensive and can be constructed in a cosmetically acceptable format.

Genetic associations for keratoconus could be useful for understanding disease pathogenesis and discovering biomarkers for early detection of the disease. We conducted a systematic review and meta-analysis to summarize all reported genetic associations for the disease. We searched in the MEDLINE, Embase, Web of Science, and HuGENET databases for genetic studies of keratoconus published from 1950 to June 2016. The summary odds ratio and 95% confidence intervals of all polymorphisms were estimated using the random-effect model. Among 639 reports that were retrieved, 24 fulfilled required criteria as eligible studies for meta-analysis, involving a total of 53 polymorphisms in 28 genes/loci. Results of our meta-analysis lead to the prioritization of 8 single-nucleotide polymorphisms (SNPs) in 6 genes/loci for keratoconus in Whites. Of them 5 genes/loci were originally detected in genome-wide association studies, including FOXO1 (rs2721051, P = 5.6 × 10(-11)), RXRA-COL5A1 (rs1536482, P = 2.5 × 10(-9)), FNDC3B (rs4894535, P = 1.4 × 10(-8)), IMMP2L (rs757219, P = 6.1 × 10(-7); rs214884, P = 2.3 × 10(-5)), and BANP-ZNF469 (rs9938149, P = 1.3 × 10(-5)). The gene COL4A4 (rs2229813, P = 1.3 × 10(-12); rs2228557, P = 4.5 × 10(-7)) was identified in previous candidate gene studies. We also found SNPs in 10 genes/loci that had a summary P value < 0.05. Sensitivity analysis indicated that the results were robust. Replication studies and understanding the roles of these genes in keratoconus are warranted.

The members of the Management and Therapy Subcommittee undertook an evidence-based review of current dry eye therapies and management options. Management options reviewed in detail included treatments for tear insufficiency and lid abnormalities, as well as anti-inflammatory medications, surgical approaches, dietary modifications, environmental considerations and complementary therapies. Following this extensive review it became clear that many of the treatments available for the management of dry eye disease lack the necessary Level 1 evidence to support their recommendation, often due to a lack of appropriate masking, randomization or controls and in some cases due to issues with selection bias or inadequate sample size. Reflecting on all available evidence, a staged management algorithm was derived that presents a step-wise approach to implementing the various management and therapeutic options according to disease severity. While this exercise indicated that differentiating between aqueous-deficient and evaporative dry eye disease was critical in selecting the most appropriate management strategy, it also highlighted challenges, based on the limited evidence currently available, in predicting relative benefits of specific management options, in managing the two dry eye disease subtypes. Further evidence is required to support the introduction, and continued use, of many of the treatment options currently available to manage dry eye disease, as well as to inform appropriate treatment starting points and understand treatment specificity in relation to dry eye disease subtype.

OBJECTIVE: To examine the efficacy of various disinfection methods for reusable tonometer prisms in eye care and to highlight how disinfectants can damage tonometer tips and cause subsequent patient harm. METHODS: Literature searches were conducted last in October 2016 in the PubMed and the Cochrane Library databases for original research investigations. Reviews, non-English language articles, nonophthalmology articles, surveys, and case reports were excluded. RESULTS: The searches initially yielded 64 unique citations. After exclusion criteria were applied, 10 laboratory studies remained for this review. Nine of the 10 studies used tonometer prisms and 1 used steel discs. The infectious agents covered in this assessment include adenovirus 8 and 19, herpes simplex virus (HSV) 1 and 2, human immunodeficiency virus 1, hepatitis C virus, enterovirus 70, and variant Creutzfeldt-Jakob disease. All 4 studies of adenovirus 8 concluded that after sodium hypochlorite (dilute bleach) disinfection, the virus was undetectable, but only 2 of the 4 studies found that 70% isopropyl alcohol (e.g., alcohol wipes or soaks) eradicated all viable virus. All 3 HSV studies concluded that both sodium hypochlorite and 70% isopropyl alcohol eliminated HSV. Ethanol, 70% isopropyl alcohol, dilute bleach, and mechanical cleaning all lack the ability to remove cellular debris completely, which is necessary to prevent prion transmission. Therefore, single-use tonometer tips or disposable tonometer covers should be considered when treating patients with suspected prion disease. Damage to tonometer prisms can be caused by sodium hypochlorite, 70% isopropyl alcohol, 3% hydrogen peroxide, ethyl alcohol, water immersion, ultraviolet light, and heat exposure. Disinfectants can cause tonometer tips to swell and crack by dissolving the glue that holds the hollow tip together. The tonometer tip cracks can irritate the cornea, harbor microbes, or allow disinfectants to enter the interior of the tonometer tip. CONCLUSIONS: Sodium hypochlorite (dilute bleach) offers effective disinfection against adenovirus and HSV, the viruses commonly associated with nosocomial outbreaks in eye care. Tonometer prisms should be examined regularly for signs of damage.

PURPOSE: To determine sensitivity and specificity of laser-scanning in vivo confocal microscopy (LS-IVCM) for detection of filamentous fungi in patients with microbial keratitis and to evaluate the effect of observer's imaging experience on these parameters. DESIGN: Retrospective reliability study. METHODS: This study included 21 patients with filamentous fungal keratitis and 24 patients with bacterial keratitis (as controls). The etiology of infection was confirmed based on the response to specific therapy regardless of culture results. All patients had undergone full-thickness corneal imaging by a LS-IVCM (Heidelberg Retina Tomograph 3 with Rostock Cornea Module; Heidelberg Engineering, Heidelberg, Germany). The images were evaluated for the presence of fungal filaments by 2 experienced observers and 2 inexperienced observers. All observers were masked to the clinical and microbiologic data. RESULTS: The mean number of images obtained per eye was 917 ± 353. The average sensitivity of LS-IVCM for detecting fungal filaments was 71.4% ± 0% for the experienced observers and 42.9% ± 6.7% for the inexperienced observers. The average specificity was 89.6% ± 3.0% and 87.5% ± 17.7% for these 2 groups of observers, respectively. Although there was a good agreement between the 2 experienced observers (κ = 0.77), the inexperienced observers showed only a moderate interobserver agreement (κ = 0.51). The LS-IVCM sensitivity was higher in patients with fungal infections who had positive culture or longer duration of the disease. CONCLUSIONS: Although LS-IVCM has a high specificity for diagnosing filamentous fungal keratitis, its sensitivity is moderate and highly dependent on the level of the observer's experience and training with this imaging modality.

The National Eye Institute launched the Audacious Goals Initiative (AGI) in 2013 with the aim "to restore vision through the regeneration of neurons and neural connections in the eye and visual system." An AGI Town Hall held at the Association for Research in Vision and Ophthalmology Annual Meeting in 2016 brought together basic, translational, and clinical scientists to address the clinical implications of the AGI, with a particular emphasis on diseases amenable to regenerative medicine and strategies to deal with barriers to progess. An example of such a barrier is that replacement of lost neurons may be insufficient because damage to other neurons and non-neuronal cells is common in retinal and optic nerve disease. Reparative processes such as gliosis and fibrosis also can make it difficult to replenish and regenerate neurons. Other issues include choice of animal models, selecting appropriate endpoints, ethics of informed consent, and regulatory issues. Another area critical to next steps in the AGI is the choice of target diseases and the stage at which early development studies should be focused. For example, an advantage of doing clinical trials in patients with early disease is that supporting cellular and structural constituents are still likely to be present. However, regenerative studies in patients with late disease make it easier to detect the effects of replacement therapy against the background of severe visual loss, whereas it may be harder to detect incremental improvement in visual function in those with early disease and considerable remaining visual function. Achieving the goals of the AGI also requires preclinical advances, new imaging techniques, and optimizing translational issues. The work of the AGI is expected to take at least 10 years but should eventually result in therapies to restore some degree of vision to the blind.

Pathological angiogenesis in the eye is an important feature in the pathophysiology of many vision-threatening diseases, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration, as well as corneal diseases with abnormal angiogenesis. Development of reproducible and reliable animal models of ocular angiogenesis has advanced our understanding of both the normal development and the pathobiology of ocular neovascularization. These models have also proven to be valuable experimental tools with which to easily evaluate potential antiangiogenic therapies beyond eye research. This review summarizes the current available animal models of ocular angiogenesis. Models of retinal and choroidal angiogenesis, including oxygen-induced retinopathy, laser-induced choroidal neovascularization, and transgenic mouse models with deficient or spontaneous retinal/choroidal neovascularization, as well as models with induced corneal angiogenesis, are widely used to investigate the molecular and cellular basis of angiogenic mechanisms. Theoretical concepts and experimental protocols of these models are outlined, as well as their advantages and potential limitations, which may help researchers choose the most suitable models for their investigative work.-Liu, C.-H., Wang, Z., Sun, Y., Chen, J. Animal models of ocular angiogenesis: from development to pathologies.

Cancer stem-like cell (CSC) model has been established to investigate the underlying mechanisms of tumor initiation and progression. The imbalance between acetylation and deacetylation of histone or non-histone proteins, one of the important epigenetic modification processes, is closely associated with a wide variety of diseases including cancer. Acetylation and deacetylation are involved in various stemness-related signal pathways and drive the regulation of self-renewal and differentiation in normal developmental processes. Therefore, it is critical to explore their role in the maintenance of cancer stem-like cell traits. Here, we will review the extensive dysregulations of acetylation found in cancers and summarize their functional roles in sustaining CSC-like properties. Additionally, the use of deacetyltransferase inhibitors as an effective therapeutic strategy against CSCs is also discussed.

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a neurological syndrome characterized by small vessel disease (SVD), stroke, and vascular cognitive impairment and dementia caused by mutations in NOTCH3 No therapies are available for this condition. Loss of mural cells, which encompass pericytes and vascular smooth muscle cells, is a hallmark of CADASIL and other SVDs, including diabetic retinopathy, resulting in vascular instability. Here, we showed that Notch3 signaling is both necessary and sufficient to support mural cell coverage in arteries using genetic rescue in Notch3 knockout mice. Furthermore, we show that systemic administration of an agonist Notch3 antibody prevents mural cell loss and modifies plasma proteins associated with Notch3 activity, including endostatin/collagen 18α1 and Notch3 extracellular domain in mice with the C455R mutation, a CADASIL variant associated with Notch3 loss of function. These findings open opportunities for the treatment of CADASIL and other SVDs by modulating Notch3 signaling.