Association of systemic and demographic risk factors with prevalence of retinopathy in US adults with prediabetes.

Background/objectives: To investigate the relative contribution of systemic risk factors to retinopathy in prediabetes using a nationally representative cohort in the US.

Subjects/methods: A group of 2098 participants aged ≥40 years with available HbA1c and gradable retinal images from the National Health and Nutrition Examination Survey 2005-2008 were included in this retrospective cross-sectional analysis. Participants were stratified into control, prediabetes, and diabetes groups based on HbA1c and anti-hyperglycaemic medication use.

Tandem Mass Tag LC-MS/MS of Aqueous Humor From Individuals With Type 2 Diabetes Without Retinopathy Reveals Early Dysregulation of Synaptic Proteins.

Purpose: An early neurodegenerative component of diabetic retinal disease (DRD) that precedes the vascular findings of clinically diagnosed diabetic retinopathy (DR) is increasingly being recognized. However, the relevant molecular mechanisms and biomarkers for early DRD are poorly defined. The purpose of this study was to uncover novel potential mediators of early diabetic retinal neuronal dysfunction through analysis of the aqueous fluid proteome in preclinical DR.

Retinal characteristics in eyes with pathologic myopia among individuals self-identifying as Black.

Objective: Investigate retinal characteristics of pathologic myopia (PM) among patients self-identifying as Black.

Design: Retrospective cohort single-institution retrospective medical record review.

Methods: Adult patients between January 2005 and December 2014 with International Classification of Diseases (ICD) codes consistent with PM and given 5-year follow-up were evaluated.

Retina-sparing suprachoroidal intraocular foreign body resulting in cyclodialysis cleft.

Purpose: Suprachoroidal intraocular foreign bodies (IOFBs) are an exceedingly rare manifestation of ocular trauma. Here we present a unique case of a metallic wire tracking from the cornea through the suprachoroidal space, and remarkably sparing the retina and lens. The patient attained an excellent visual outcome after management of resultant cyclodialysis cleft.

Association of heart rate variability with progression of retinopathy among adults with type 2 diabetes.

Aim: We evaluated the associations of heart rate variability (HRV) with incident vision-threatening retinopathy and retinopathy progression among adults with type 2 diabetes.

Methods: Participants recruited to the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study with HRV measures at baseline were analysed. HRV measures included standard deviation of all normal-to-normal intervals (SDNN) and root mean square of successive differences between normal-to-normal intervals (rMSSD).

Retinal Neurodegeneration in Diabetes: an Emerging Concept in Diabetic Retinopathy.

Purpose Of Review: Diabetic retinopathy (DR), the leading cause of blindness in working-aged adults, remains clinically defined and staged by its vascular manifestations. However, early retinal neurodegeneration may precede vascular pathology, suggesting that this neuronal damage may contribute to disease pathogenesis and represent an independent target for intervention. This review will discuss the evidence and implications for diabetic retinal neurodegeneration.

Nrf2 deficiency decreases NADPH from impaired IDH shuttle and pentose phosphate pathway in retinal pigmented epithelial cells to magnify oxidative stress-induced mitochondrial dysfunction.

The nuclear factor-erythroid 2-related factor-2 (Nrf2), a major antioxidant transcription factor, is decreased in several age-related diseases including age-related macular degeneration (AMD), the most common cause of blindness among the elderly in western society. Since Nrf2's mito-protective response is understudied, we investigated its antioxidant response on mitochondria. Control and Nrf2-deficient retinal pigmented epithelial (RPE) cells were compared after treating with cigarette smoke extract (CSE).

Clinical Outcomes of Secondary Scleral-Sutured Foldable Hydrophilic Acrylic Intraocular Lens Placement by Trainees: A Single-Site Analysis.

Purpose: To evaluate the outcomes of a 4-point scleral-fixated foldable Akreos AO60 intraocular lens (IOL) insertion using Gore-Tex suture performed by trainees under supervision of a single attending surgeon.

Methods: Retrospective chart review for 53 eyes of 50 patients whose surgery was performed by trainees under supervision of a single surgeon between 2015 and 2018 at a tertiary care hospital (Johns Hopkins Wilmer Eye Institute, Baltimore, MD). Indications for surgery, preoperative risk factors, and intraoperative techniques were analyzed.

SYPHILITIC OUTER RETINOPATHY: A MASQUERADING DIAGNOSIS REVEALED AFTER STEROID-INDUCED PROGRESSION TO PANUVEITIS.

Purpose: To report a case of syphilitic outer retinopathy revealed after progression to panuveitis after a course of oral steroids for suspected poison ivy.

Methods: Retrospective case report.

Results: A 44-year-old diabetic man presented with progressive symptoms of nyctalopia and color vision changes associated with outer retinal disruption on macular imaging but minimal evidence of intraocular inflammation on examination.

Post-operative intracranial gas migration with optic nerve infiltration and atrophy following retinal detachment repair.

Purpose: To report a patient with post-operative gas migration into the optic nerve and lateral ventricles after retinal detachment repair.

Observations: A 78-year-old pseudophakic man developed a temporal visual field cut in his non-operative, right eye 3 weeks after repair of a recurrent, shallow, macula-involving retinal detachment with perfluoropropane intraocular gas in the left eye. Visual acuity in the right eye measured 20/40, and static perimetry demonstrated temporal visual field loss that respected the vertical midline.

Sensitivity and Specificity of Potential Diagnostic Features Detected Using Fundus Photography, Optical Coherence Tomography, and Fluorescein Angiography for Polypoidal Choroidal Vasculopathy.

Importance: The use of indocyanine green angiography (ICGA) is a criterion standard for diagnosing polypoidal choroidal vasculopathy (PCV), an endemic and common cause of vision loss in Asian and African individuals that also presents in white individuals. However, the use of ICGA is expensive, invasive, and not always available at clinical centers. Therefore, knowing the value of certain features detected using fundus photography (FP), optical coherence tomography (OCT), and fluorescein angiography (FA) to diagnose PCV without ICGA could assist ophthalmologists to identify PCV when ICGA is not readily available.

Retinal Neurodegeneration as an Early Manifestation of Diabetic Eye Disease and Potential Neuroprotective Therapies.

Purpose Of Review: Diabetic retinopathy (DR) is a major cause of visual impairment and blindness throughout the world. Microvascular changes have long been regarded central to disease pathogenesis. In recent years, however, retinal neurodegeneration is increasingly being hypothesized to occur prior to the vascular changes classically associated with DR and contribute to disease pathogenesis.

Clinical and Ultrastructural Studies of Epiretinal Pigmentary Deposits after Retinectomy with Silicone Oil.

Purpose: Large relaxing retinectomies have become increasingly used in the repair of retinal detachment related to proliferative vitreoretinopathy (PVR). Retinectomies expose the retinal pigment epithelium (RPE) to the vitreous cavity; the direct effects of silicone oil on the RPE are only beginning to be understood.

Design: Retrospective case series.

Stem Cell-Based Therapy for Diseases of the Retinal Pigment Epithelium: From Bench to Bedside.

Age-related macular degeneration (AMD) represents a leading cause of blindness in the elderly, and Stargardt's macular dystrophy (SMD) is the most common form of juvenile-onset macular degeneration. Dry AMD and SMD share an underlying pathophysiology, namely dysfunction and ultimately loss of the retinal pigment epithelium (RPE), suggesting that RPE transplantation may offer a potential treatment strategy for both patient populations. Stem cells have emerged as a promising source of replacement RPE.

Endophthalmitis following intravitreal injection of anti-VEGF agents: long-term outcomes and the identification of unusual micro-organisms.

Background: While the development of targeted molecular therapy to inhibit vascular endothelial growth factor (VEGF) has revolutionized the treatment and visual prognosis of highly prevalent retinal diseases such as diabetic retinopathy and age-related macular degeneration, each intravitreal injection of these agents carries a small risk of endophthalmitis which can be visually devastating. In the absence of specific guidelines, current management of post-injection endophthalmitis is typically extrapolated from data regarding endophthalmitis occurring after cataract surgery despite potential differences in pathogenic organisms and clinical course. Here, we assess the contribution of intravitreal injections of anti-VEGF agents to all cases of endophthalmitis at our tertiary care referral center and characterize the clinical outcomes and microbial pathogens associated with post-injection endophthalmitis in order to inform management of this serious iatrogenic condition.

Nrf2 signaling is impaired in the aging RPE given an oxidative insult.

Age-related macular degeneration (AMD) represents the leading cause of blindness in the elderly, yet no definitive therapy exists for early, dry disease. Several lines of evidence have implicated oxidative stress-induced damage to the retinal pigment epithelium (RPE) in the pathogenesis of AMD, suggesting that the aging RPE may exhibit increased susceptibility to cell damage induced by exogenous stressors. The transcription factor Nrf2 serves as the master regulator of a highly coordinated antioxidant response in virtually all cell types.

SIRT1 activating compounds reduce oxidative stress and prevent cell death in neuronal cells.

Activation of SIRT1, an NAD+-dependent deacetylase, prevents retinal ganglion cell (RGC) loss in optic neuritis, an inflammatory demyelinating optic nerve disease. While SIRT1 deacetylates numerous protein targets, downstream mechanisms of SIRT1 activation mediating this neuroprotective effect are unknown. SIRT1 increases mitochondrial function and reduces oxidative stress in muscle and other cells, and oxidative stress occurs in neuronal degeneration.

Pcif1 modulates Pdx1 protein stability and pancreatic β cell function and survival in mice.

The homeodomain transcription factor pancreatic duodenal homeobox 1 (Pdx1) is a major mediator of insulin transcription and a key regulator of the β cell phenotype. Heterozygous mutations in PDX1 are associated with the development of diabetes in humans. Understanding how Pdx1 expression levels are controlled is therefore of intense interest in the study and treatment of diabetes.

Pdx1 (MODY4) regulates pancreatic beta cell susceptibility to ER stress.

Type 2 diabetes mellitus (T2DM) results from pancreatic beta cell failure in the setting of insulin resistance. Heterozygous mutations in the gene encoding the beta cell transcription factor pancreatic duodenal homeobox 1 (Pdx1) are associated with both T2DM and maturity onset diabetes of the young (MODY4), and low levels of Pdx1 accompany beta cell dysfunction in experimental models of glucotoxicity and diabetes. Here, we find that Pdx1 is required for compensatory beta cell mass expansion in response to diet-induced insulin resistance through its roles in promoting beta cell survival and compensatory hypertrophy.

Minireview: Meeting the demand for insulin: molecular mechanisms of adaptive postnatal beta-cell mass expansion.

Type 2 diabetes results from pancreatic ss-cell failure in the setting of insulin resistance. This model of disease progression has received recent support from the results of genome-wide association studies that identify genes potentially regulating ss-cell growth and function as type 2 diabetes susceptibility loci. Normal ss-cell compensation for an increased insulin demand includes both enhanced insulin-secretory capacity and an expansion of morphological ss-cell mass, due largely to changes in the balance between ss-cell proliferation and apoptosis.

The PDX1 homeodomain transcription factor negatively regulates the pancreatic ductal cell-specific keratin 19 promoter.

Keratin 19 is a member of the cytokeratin family that is critical for maintenance of cellular architecture and organization, especially of epithelia. The pancreas has three distinct cell types, ductal, acinar, and islet, each with different functions. Embryologically, the pancreatic and duodenal homeobox 1 (PDX1) homeodomain protein is critical for the initiation of all pancreatic lineages; however, the later differentiation of the endocrine pancreas is uniquely dependent upon high PDX1 expression, whereas PDX1 is down-regulated in the ductal and acinar cell lineages.

Profile of histone lysine methylation across transcribed mammalian chromatin.

Complex patterns of histone lysine methylation encode distinct functions within chromatin. We previously reported that trimethylation of lysine 9 of histone H3 (H3K9) occurs at both silent heterochromatin and at the transcribed regions of active mammalian genes, suggesting that the extent of histone lysine methylation involved in mammalian gene activation is not completely defined. To identify additional sites of histone methylation that respond to mammalian gene activity, we describe here a comparative assessment of all six known positions of histone lysine methylation and relate them to gene transcription.