Outcomes of Open-Globe Injuries With Associated Retinal Detachment: Experience at an Ocular Trauma Center.

To characterize the clinical features and outcomes of open-globe injuries with associated retinal detachment (RD). A retrospective review was performed. Thirty-six patients with open-globe injuries and subsequent rhegmatogenous RD were analyzed between January 2016 and September 2021.

Response of Diabetic Macular Edema to Anti-VEGF Medications Correlates with Improvement in Macular Vessel Architecture Measured with OCT Angiography.

Purpose: Improvements in best-corrected visual acuity (BCVA) and central subfield thickness (CST) have been well documented after intravitreal injection of anti-VEGF medications in diabetic macular edema (DME); however, their effect on the vasculature of the macula in diabetic retinopathy (DR) remains poorly understood. Our aim was to explore the effect of intravitreal injection of anti-VEGF on parameters of retinal vascular microstructure in DR with OCT angiography (OCTA).

Design: Retrospective study of adult patients with DME that were treated with anti-VEGF intravitreal injections at the University of Illinois at Chicago between 2017 and 2022.

Modulation of Retinal Inflammation Delays Degeneration in a Mouse Model of Geographic Atrophy.

The advanced form of AMD, geographic atrophy, is associated with increased RPE oxidative stress and chronic inflammation. Here we evaluated the effects of delivering an anti-inflammatory viral gene by an AAV-vector in a mouse model of geographic atrophy. We measured changes in retinal function, structure, and morphology over nine months with electroretinography, optical coherence tomography, and fundoscopy, respectively.

Binocular benefit following monocular subretinal AAV injection in a mouse model of autosomal dominant retinitis pigmentosa (adRP).

Autosomal dominant retinitis pigmentosa (adRP) is frequently caused by mutations in RHO, the gene for rhodopsin. In previous experiments in dogs with the T4R mutation in RHO, an AAV2/5 vector expressing an shRNA directed to human and dog RHO mRNA and an shRNA-resistant human RHO cDNA (AAV-RHO820-shRNA820) prevented retinal degeneration for more than eight months following injection. It is crucial, however, to determine if this RNA replacement vector acts in a mutation-independent and species-independent manner.

Occult retinopathy following treatment of Hepatitis C with glecaprevir/pibrentasvir (Mavyret).

Background/purpose: Medication-induced ocular toxicity is an important consideration in the differential diagnosis of unexplained visual disturbance. We present a case of visual disturbance after starting treatment with glecaprevir/pibrentasvir (Mavyret), a therapy for Hepatitis C virus approved by the FDA in 2017.

Methods: A 50-year-old male with no significant ocular history experienced bilateral visual disturbance, including visual field and acuity loss, shortly after initiating treatment with Mavyret for Hepatitis C.

Automated segmentation and analysis of retinal microglia within ImageJ.

Microglia are immune cells of the central nervous system capable of distinct phenotypic changes and migration in response to injury. These changes most notably include the retraction of fine dendritic structures and adoption of a globular, phagocytic morphology. Due to their characteristic responses, microglia frequently act as histological indicators of injury progression.

Sectoral activation of glia in an inducible mouse model of autosomal dominant retinitis pigmentosa.

Retinitis pigmentosa (RP) is a group of blinding disorders caused by diverse mutations, including in rhodopsin (RHO). Effective therapies have yet to be discovered. The I307N Rho mouse is a light-inducible model of autosomal dominant RP.

Corneal Opacification and Spontaneous Recovery following Injection of Healon5 into the Corneal Stroma during Intervention for Postoperative Hypotony.

We report the self-limited nature of corneal opacification after accidental injection of Healon5 into the corneal stroma. A 52-year-old male with a new diagnosis of severe stage, primary open-angle glaucoma underwent successful trabeculectomy OS, which was complicated by ocular hypotony and shallow anterior chamber (AC) on postoperative day 1. Healon5, a hyaluronic acid-containing viscoelastic device, was accidentally introduced into the corneal stroma during attempted injection into the AC.

Expression of a CARD Slows the Retinal Degeneration of a Geographic Atrophy Mouse Model.

Age-related macular degeneration (AMD) has been linked to oxidative damage and para-inflammation, an activation of inflammasome signaling in the retinal pigment epithelium (RPE) and the underlying choriocapillaris. Herein, we tested the efficacy of a gene-delivered caspase-1 inhibitor in controlling the retinal degeneration observed in two models of RPE-choroid oxidative damage. In an acute model of oxidative stress (NaIO3 injection), eyes pre-treated with the sGFP-TatCARD (trans-activator of transcription; caspase activation and recruitment domain) vector demonstrated a recovery of retinal function and partial protection of RPE structure 1 month after damage, in contrast with control-treated eyes.

Co-Delivery of a Short-Hairpin RNA and a shRNA-Resistant Replacement Gene with Adeno-Associated Virus: An Allele-Independent Strategy for Autosomal-Dominant Retinal Disorders.

Recombinant adeno-associated virus (rAAV) has become an important gene delivery vector for the treatment of inherited retinal degenerative diseases. Many of the mutations leading to retinal degeneration are inherited in an autosomal-dominant pattern and can produce toxic gain-of-function and/or dominant-negative effects. Here we describe an allele-independent gene therapy strategy with rAAV to treat autosomal-dominant retinal degenerative diseases.

Clinically Relevant Outcome Measures for the I307N Rhodopsin Mouse: A Model of Inducible Autosomal Dominant Retinitis Pigmentosa.

Purpose: The I307N rhodopsin (Rho) mouse is a light-inducible model of autosomal dominant retinitis pigmentosa (adRP) that may be useful in testing therapies. We investigated the time-course of retinal changes of the I307N Rho mouse with spectral-domain optical coherence tomography (SD-OCT).

Methods: SD-OCT was performed up to day 30 after light damage; electroretinography (ERG) was employed to evaluate photoreceptor function.

Mutation-independent rhodopsin gene therapy by knockdown and replacement with a single AAV vector.

Inherited retinal degenerations are caused by mutations in >250 genes that affect photoreceptor cells or the retinal pigment epithelium and result in vision loss. For autosomal recessive and X-linked retinal degenerations, significant progress has been achieved in the field of gene therapy as evidenced by the growing number of clinical trials and the recent commercialization of the first gene therapy for a form of congenital blindness. However, despite significant efforts to develop a treatment for the most common form of autosomal dominant retinitis pigmentosa (adRP) caused by >150 mutations in the rhodopsin () gene, translation to the clinic has stalled.

A cell penetrating peptide from SOCS-1 prevents ocular damage in experimental autoimmune uveitis.

We describe an immunosuppressive peptide corresponding to the kinase inhibitory region (KIR) of the intracellular checkpoint protein suppressor of cytokine signaling 1 (SOCS-1) that binds to the phospho-tyrosine containing regions of the tyrosine kinases JAK2 and TYK2 and the adaptor protein MAL, and thereby inhibits signaling downstream from these signaling mediators. The peptide, SOCS1-KIR, is thus capable of downregulating overactive JAK/STAT or NF-kB signaling in somatic cells, including those in many compartments of the eye. Attachment of poly-arginine to this peptide (R9-SOCS1-KIR) allows it to penetrate the plasma membrane in aqueous media.

Neuroinflammation in Retinitis Pigmentosa, Diabetic Retinopathy, and Age-Related Macular Degeneration: A Minireview.

The eye is an immuno-privileged organ. However, certain diseases such as uveitis are intrinsically linked to inflammation. In several retinal degenerative diseases, there is a unique damage at the onset of the disease, but evidence suggests that chronic and low-grade inflammatory processes play an important role in their progression.

Acute heart failure with cardiomyocyte atrophy induced in adult mice by ablation of cardiac myosin light chain kinase.

Aims: Under pressure overload, initial adaptive hypertrophy of the heart is followed by cardiomyocyte elongation, reduced contractile force, and failure. The mechanisms governing the transition to failure are not fully understood. Pressure overload reduced cardiac myosin light chain kinase (cMLCK) by ∼80% within 1 week and persists.

HDAC Inhibitors Enhance T-Cell Chemokine Expression and Augment Response to PD-1 Immunotherapy in Lung Adenocarcinoma.

Purpose: A significant limitation of checkpoint blockade immunotherapy is the relatively low response rate (e.g., ∼20% with PD-1 blockade in lung cancer).

Targeting the Nrf2 Signaling Pathway in the Retina With a Gene-Delivered Secretable and Cell-Penetrating Peptide.

Purpose: Oxidative stress has been linked to several ocular diseases, initiating an inflammatory response that increases tissue injury. The Nrf2 transcription factor regulates expression of antioxidant genes and is tightly regulated by Kelch-Like ECH-Associated Protein 1 (Keap-1). We evaluate the antioxidant and anti-inflammatory properties of an adeno-associated virus (AAV) vector delivering an Nrf2-derived peptide that binds Keap-1.

Lung tumor NF-κB signaling promotes T cell-mediated immune surveillance.

NF-κB is constitutively activated in many cancer types and is a potential key mediator of tumor-associated inflammation, tumor growth, and metastasis. We investigated the role of cancer cell NF-κB activity in T cell-mediated antitumor responses. In tumors rendered immunogenic by model antigen expression or following administration of antitumor vaccines, we found that high NF-κB activity leads to tumor rejection and/or growth suppression in mice.

IKKβ-induced inflammation impacts the kinetics but not the magnitude of the immune response to a viral vector.

Microbial adjuvants in vaccines activate key transcription factors, including NF-κB and interferon response factors (IRFs). However, the individual role of these transcription factor pathways in promoting adaptive immunity by adjuvants is not clear. It is widely believed that induction of a strong inflammatory response potentiates an adaptive immune response.