Vital Dyes in Vitreomacular Surgery

Vital dyes contain complex molecules with chromophores that stain living tissues and have greatly enhanced identification and removal of transparent vitreoretinal tissues during surgery. Several “chromovitrectomy” dyes are frequently used by vitreoretinal specialists, including indocyanine green, trypan blue, brilliant blue G, and triamcinolone acetonide; other dyes are also under investigation. Trypan Blue was approved by the U.S. Food and Drug Administration (FDA) for epiretinal membrane removal, and preservative-free triamcinolone acetonide was approved by the FDA for intraocular use. However, currently available chromovitrectomy dyes have their limitations, and of particular concern for some of them is the possibility for acute and chronic toxicity to the neurosensory retina and retinal pigmented epithelium. The potentially irreversible acute toxicity and other limitations, such as lack of long-term safety profiles, highlight the need for further advancements

Induced pluripotent stem cell-based therapy for age-related macular degeneration

Introduction: In age-related macular degeneration (AMD), stem cells could possibly replace or regenerate disrupted pathologic retinal pigment epithelium (RPE), and produce supportive growth factors and cytokines such as brain-derived neurotrophic factor. Induced pluripotent stem cells (iPSCs)-derived RPE was first subretinally transplanted in a neovascular AMD patient in 2014. Areas covered: Induced PSCs are derived from the introduction of transcription factors to adult cells under specific cell culture conditions, followed by differentiation into RPE cells. Induced PSC-derived RPE cells exhibit ion transport, membrane potential, polarized VEGF secretion and gene expression that is similar to native RPE. Despite having similar in vitro function, morphology, immunostaining and microscopic analysis, it remains to be seen if iPSC-derived RPE can replicate the myriad of in vivo functions, including immunomodulatory effects, of native RPE cells. Historically, adjuvant RPE transplantation during CNV resections were technically difficult and complicated by immune rejection. Autologous iPSCs are hypothesized to reduce the risk of immune rejection, but their production is time-consuming and expensive. Alternatively, allogenic transplantation using human leukocyte antigen (HLA)-matched iPSCs, similar to HLA-matched organ transplantation, is currently being investigated. Expert opinion: Challenges to successful transplantation with iPSCs include surgical technique, a pathologic subretinal microenvironment, possible immune rejection, and complications of immunosuppression

Gene Therapy for Inherited Retinal and Optic Nerve Degenerations

Introduction: The eye is a target for investigational gene therapy due to the monogenic nature of many inherited retinal and optic nerve degenerations (IRD), its accessibility, tight blood-ocular barrier, the ability to non-invasively monitor for functional and anatomic outcomes, as well as its relative immune privileged state.Vectors currently used in IRD clinical trials include adeno-associated virus (AAV), small single-stranded DNA viruses, and lentivirus, RNA viruses of the retrovirus family. Both can transduce non-dividing cells, but AAV are non-integrating, while lentivirus integrate into the host cell genome, and have a larger transgene capacity. Areas covered: This review covers Leber’s congenital amaurosis, choroideremia, retinitis pigmentosa, Usher syndrome, Stargardt disease, Leber’s hereditary optic neuropathy, Achromatopsia, and X-linked retinoschisis. Expert opinion: Despite great potential, gene therapy for IRD raises many questions, including the potential for less invasive intravitreal versus subretinal delivery, efficacy, safety, and longevity of response, as well as acceptance of novel study endpoints by regulatory bodies, patients, clinicians, and payers. Also, ultimate adoption of gene therapy for IRD will require widespread genetic screening to identify and diagnose patients based on genotype instead of phenotype

The acute and chronic effects of intravitreal anti-vascular endothelial growth factor injections on intraocular pressure: A review

The acute and chronic effects of repeated intravitreal antivascular endothelial growth factor (VEGF) injections on intraocular pressure have not been fully characterized, and the development of sustained ocular hypertension could adversely affect patients who are at risk of glaucomatous optic neuropathy. As expected, volume-driven, acute ocular hypertension immediately follows intravitreal injection, but this pressure elevation is generally transient and well tolerated. Several medications have been investigated to limit acute ocular hypertension following anti-VEGF therapy, but the benefits of pretreatment are not conclusive. Chronic, sustained ocular hypertension, distinct from the short-term acute ocular hypertension after each injection, has also been associated with repeated intravitreal anti-VEGF injections. Risk factors for chronic ocular hypertension include the total number of injections, a greater frequency of injection, and preexisting glaucoma. Proposed mechanisms for chronic ocular hypertension include microparticle obstruction, toxic or inflammatory effects on trabecular meshwork, as well as alterations in outflow facility by anti-VEGF agents. Although limiting anti-VEGF therapy could minimize the risk of both acute and chronic ocular hypertension, foregoing anti-VEGF therapy risks progression of various macular diseases with resulting permanent central vision loss. While definitive evidence of damage to the retinal nerve fiber layer is lacking, patients receiving repeated injections should be monitored for ocular hypertension and patients in whom sustained ocular hypertension subsequently developed should be periodically monitored for glaucomatous changes with optic nerve optical coherence tomography and static visual fields

Visual hallucinations in the psychosis spectrum and comparative information from neurodegenerative disorders and eye disease

Much of the research on visual hallucinations (VHs) has been conducted in the context of eye disease and neurodegenerative conditions, but little is known about these phenomena in psychiatric and nonclinical populations. The purpose of this article is to bring together current knowledge regarding VHs in the psychosis phenotype and contrast this data with the literature drawn from neurodegenerative disorders and eye disease. The evidence challenges the traditional views that VHs are atypical or uncommon in psychosis. The weighted mean for VHs is 27% in schizophrenia, 15% in affective psychosis, and 7.3% in the general community. VHs are linked to a more severe psychopathological profile and less favorable outcome in psychosis and neurodegenerative conditions. VHs typically co-occur with auditory hallucinations, suggesting a common etiological cause. VHs in psychosis are also remarkably complex, negative in content, and are interpreted to have personal relevance. The cognitive mechanisms of VHs in psychosis have rarely been investigated, but existing studies point to source-monitoring deficits and distortions in top-down mechanisms, although evidence for visual processing deficits, which feature strongly in the organic literature, is lacking. Brain imaging studies point to the activation of visual cortex during hallucinations on a background of structural and connectivity changes within wider brain networks. The relationship between VHs in psychosis, eye disease, and neurodegeneration remains unclear, although the pattern of similarities and differences described in this review suggests that comparative studies may have potentially important clinical and theoretical implications. © 2014 The Author

American College of Rheumatology Provisional Criteria for Clinically Relevant Improvement in Children and Adolescents With Childhood-Onset Systemic Lupus Erythematosus

10.1002/acr.23834ARTHRITIS CARE & RESEARCH715579-59

Leftward bias in number space is modulated by magical ideation

BACKGROUND: Productive symptoms of schizophrenia and positive-symptom schizotypy have both been related to signs of right-sided hemispatial inattention ("pseudoneglect"). We here set out to explore, in healthy subjects, the relationship between one form of mild schizotypy ("magical ideation"; MI) and asymmetries in number space, which is a bias toward relatively small numbers, reportedly represented to the left of larger numbers. METHODS: Forty right-handed participants filled in the MI scale and performed a number-line bisection (NLB) task and a randomization task (the Mental Dice Task, MDT, requiring randomization of the digits from 1 to 6). RESULTS: We found pseudoneglect in number space, that is, more errors toward small numbers in the NLB task and an overproduction of small digits in the MDT. Individual participants' MI scores were correlated to the size of pseudoneglect in both numerical tasks. CONCLUSIONS: Explicit (NLB) and implicit (MDT) assessments of the exploration of number space may be relevant to studies of the mechanisms underlying the formation of delusional and schizotypal beliefs. We propose that, in healthy subjects, a trait-like imbalance in hemispheric cooperation may not only produce asymmetries in physical and representational space, but also predisposes to develop magical ideas. Specifically, an over-proportional influence of the right hemisphere semantic system (preferentially coding oblique and remote associations) leads to the assumption of connections between randomly associated events