Pathogenic mechanisms of immune checkpoint inhibitor (ICI)-associated retinal and choroidal adverse reactions.

Purpose: To summarize and categorize postulated mechanisms of immune checkpoint inhibitor (ICI)-mediated retinal and choroidal inflammation and discuss resulting implications for evaluation and management of these adverse reactions.

Design: Targeted literature review with interpretation and perspective Methods: We performed a review of selected literature describing immune-mediated retinal and choroidal adverse reactions associated with ICI therapy, synthesizing and categorizing the likely underlying pathogenic mechanisms. Based on these mechanistic categories, we provide perspective on a rational approach to the evaluation of patients with ICI-associated inflammatory disorders of the retina and choroid.

Pyramidal Inflammatory Deposits of the Retinal Pigment Epithelium and Outer Retina in Ocular Syphilis.

Purpose: To evaluate the role of OCT in the diagnosis of uveitis secondary to syphilis.

Design: Consecutive, retrospective case series.

Participants: All patients 18 years of age or older with ocular syphilis from 2 tertiary referral centers.

Ocular Toxoplasmosis after Exposure to Wild Game.

Purpose: To describe eight patients with toxoplasma retinochoroiditis following exposure to wild game.

Methods: Retrospective, multicenter case series.

Results: Eight men, aged 29 to 71 (mean, 56 years), developed toxoplasmic retinochoroiditis after hunting and/or consuming wild game in the United States, including seven deer and one bear.

Novel TMEM98, MFRP, PRSS56 variants in a large United States high hyperopia and nanophthalmos cohort.

Nanophthalmos is a rare condition defined by a small, structurally normal eye with resultant high hyperopia. While six genes have been implicated in this hereditary condition (MFRP, PRSS56, MYRF, TMEM98, CRB1,VMD2/BEST1), the relative contribution of these to nanophthalmos or to less severe high hyperopia (≥ + 5.50 spherical equivalent) has not been fully elucidated.

Incidence and Outcome of Uveitic Glaucoma in Eyes With Intermediate, Posterior, or Panuveitis Followed up to 10 Years After Randomization to Fluocinolone Acetonide Implant or Systemic Therapy.

Purpose: To evaluate long-term risk and outcomes of glaucoma in eyes with intermediate, posterior, and panuveitis managed with systemic or fluocinolone acetonide (0.59 mg, "implant") therapy.

Design: Prospective Follow-up of the Multicenter Uveitis Steroid Treatment (MUST) Clinical Trial Cohort.

Ciliary Body Mass as a Feature of Ocular Sarcoidosis.

Importance: Ocular sarcoidosis may be the primary and only clinical manifestation of sarcoidosis, and irreversible loss of visual acuity may occur from delayed treatment. Thus, early diagnosis is imperative to preserve visual acuity. Establishing the diagnosis of sarcoidosis in cases manifesting only in the eye may require a diagnostic biopsy, which may prove challenging in the absence of available ocular surface, lacrimal gland, and systemic tissue for biopsy.

Technique and Results of Permanent Medial Tarsorrhaphy for Complex Eyelid Malposition.

Purpose: To evaluate the results of permanent medial tarsorrhaphy and to describe the surgical technique.

Methods: Medial tarsorrhaphy was performed on 30 eyelids with symptomatic exposure keratopathy secondary to eyelid malposition. Observational, retrospective review of preoperative and postoperative examination findings was performed.

Expression and regulation of alarmin cytokine IL-1α in human retinal pigment epithelial cells.

Human retinal pigment epithelial (hRPE) cells play important immune-regulatory roles in a variety of retinal pathologic processes, including the production of inflammatory cytokines that are essential mediators of the innate immune response within the ocular microenvironment. The pro-inflammatory "alarmin" cytokine IL-1α has been implicated in both infectious and non-infectious retinal diseases, but its regulation in the retina is poorly understood. The purpose of this study was to elucidate the expression and regulation of IL-1α within hRPE cells.

Distinct CD40L receptors mediate inflammasome activation and secretion of IL-1β and MCP-1 in cultured human retinal pigment epithelial cells.

CD40L signaling occurs in several diseases with inflammatory components, including ocular and retinal diseases. However, it has never been evaluated as a pathogenic mechanism in age-related macular degeneration (AMD) or as an inducer of inflammasome formation in any cell type. mRNA and protein levels of CD40, IL-1β, NALP1, NALP3, caspase-1, and caspase-5 were determined by RT-PCR, qPCR, and Western blot.

Morphological assessment of the retina in uveitis.

Background: The objective of this study is to describe a system for color photograph evaluation in uveitis and report baseline morphologic findings for the Multicenter Uveitis Steroid Treatment (MUST) Trial. Four-hundred seventy-nine eyes of 255 subjects with intermediate, posterior, and panuveitis had stereoscopic color fundus photographs obtained by certified photographers and evaluated by certified graders using standardized procedures to evaluate morphologic characteristics of uveitis. The posterior pole was evaluated for macular edema, vitreoretinal interface abnormalities, and macular pigment disturbance/atrophy; the optic disk was assessed for edema, pallor, or glaucomatous changes.

Cataract Surgery Outcomes in Uveitis: The Multicenter Uveitis Steroid Treatment Trial.

Purpose: To assess the visual outcomes of cataract surgery in eyes that received fluocinolone acetonide implant or systemic therapy with oral corticosteroids and immunosuppression during the Multicenter Uveitis Steroid Treatment (MUST) Trial.

Design: Nested prospective cohort study of patients enrolled in a randomized clinical trial.

Participants: Patients that underwent cataract surgery during the first 2 years of follow-up in the MUST Trial.

Fluorescein angiography versus optical coherence tomography for diagnosis of uveitic macular edema.

Objective: To evaluate agreement between fluorescein angiography (FA) and optical coherence tomography (OCT) results for diagnosis of macular edema in patients with uveitis.

Design: Multicenter cross-sectional study.

Participants: Four hundred seventy-nine eyes with uveitis from 255 patients.

Chronic retinal necrosis: cytomegalovirus necrotizing retinitis associated with panretinal vasculopathy in non-HIV patients.

Purpose: To characterize a unique cytomegalovirus (CMV)-associated retinopathy in patients with limited immune dysfunction.

Methods: Retrospective observational case series. CMV was confirmed as the pathogenic agent via polymerase chain reaction analysis of aqueous or vitreous humor samples or via immunohistochemical analysis of retinal biopsy specimens.

Retinal vasculitis in Toxocara canis neuroretinitis.

Background: The purpose of this case report is to describe clinical and angiographic findings of retinal vasculitis in acute Toxocara canis neuroretinitis associated with systemic infection.

Findings: A 16-year-old male presented with a 1 week history of left eye pain, floaters, and decreased visual acuity. Ocular examination was consistent with neuroretinitis and retinal vasculitis.

IL-8 and MCP Gene Expression and Production by LPS-Stimulated Human Corneal Stromal Cells.

Purpose. To determine time course of effect of lipopolysaccharide (LPS) on production of interleukin-8 (IL-8) and monocyte chemotactic protein (MCP) by cultured human corneal stromal cells. Methods.

Expression and functional roles of caspase-5 in inflammatory responses of human retinal pigment epithelial cells.

Purpose: To investigate the expression, activation, and functional involvement of caspase-5 in human retinal pigment epithelial (hRPE) cells.

Methods: Expression and activation of caspase-5 in primary cultured hRPE cells, telomerase-immortalized hTERT-RPE1 cells (hTERT-RPE1), or both, were measured after stimulation with proinflammatory agents IL-1β, TNF-α, lipopolysaccharide (LPS), interferon-γ, monocyte coculture, adenosine triphosphate (ATP), or endoplasmic reticulum (ER) stress inducers. Immunomodulating agents dexamethasone (Dex), IL-10, and triamcinolone acetonide (TA) were used to antagonize proinflammatory stimulation.

Island pedicle and horizontal advancement cheek flaps for medial canthal reconstruction.

Purpose: To describe the surgical technique for and results of island pedicle cheek flap repair of medial canthal defects.

Methods: We retrospectively reviewed the charts of all patients with medial canthal defects repaired with island pedicle and horizontal advancement cheek flaps from November 2007 and July 2009. Patient demographics, risk factors for poor wound healing, diagnosis, operative findings, technique, and postoperative results were reviewed.

MCP-1-activated monocytes induce apoptosis in human retinal pigment epithelium.

Purpose: The inflammatory response in age-related macular degeneration (AMD) is characterized by mononuclear leukocyte infiltration of the outer blood-retina barrier formed by the retinal pigment epithelium (RPE). A key mechanistic element in AMD progression is RPE dysfunction and apoptotic cell loss. The purpose of this study was to evaluate whether monocyte chemoattractant protein (MCP)-1-activated monocytes induce human RPE apoptosis and whether Ca(2+) and reactive oxygen species (ROS) are involved in this process.

Activation of P2X receptors induces apoptosis in human retinal pigment epithelium.

Purpose: The retinal pigment epithelium (RPE) is considered a primary site of pathology in age-related macular degeneration (AMD), which is the most prevalent form of irreversible blindness worldwide in the elderly population. Extracellular adenosine triphosphate (ATP) acts as a key signaling molecule in numerous cellular processes, including cell death. The purpose of this study was to determine whether extracellular ATP induces apoptosis in cultured human RPE.

Chronic postoperative fungal endophthalmitis caused by trichosporon asahii.

Purpose: To describe a patient with chronic postoperative fungal endophthalmitis caused by Trichosporon asahii.

Methods: A retrospective case report.

Results: An 82-year-old woman was found to have culture-proven T.

Rigid nylon foil-anchored polytetrafluoroetyhlene (Gore-Tex) sheet stenting for conjunctival fornix reconstruction.

Purpose: To describe an operative technique that deepens foreshortened conjunctival fornices by providing a scaffold for epithelialization that opposes contractile forces during wound healing.

Design: Retrospective interventional case series.

Participants: Seventeen patients with anophthalmic sockets containing foreshortened conjunctival fornices.

Dual involvement of caspase-4 in inflammatory and ER stress-induced apoptotic responses in human retinal pigment epithelial cells.

Purpose: To investigate the functional involvement of caspase-4 in human retinal pigment epithelial (hRPE) cells.

Methods: Expression and activation of caspase-4 in hRPE cells were measured after stimulation with proinflammatory agents IL-1beta (2 ng/mL), TNF-alpha (20 ng/mL), lipopolysaccharide (1000 ng/mL), interferon-gamma (500 U/mL), or monocyte coculture in the absence or presence of immunomodulating agent cyclosporine (3 or 30 ng/mL), dexamethasone (10 microM), or IL-10 (100 U/mL) and endoplasmic reticulum (ER) stress inducer thapsigargin (25 nM) or tunicamycin (3 or 10 microM). The onset of ER stress was determined by expression of GRP78.

Detection of retinal metabolic stress resulting from central serous retinopathy.

Purpose: To test whether eyes with central serous retinopathy have elevated retinal flavoprotein fluorescence (FPF) using a novel clinical imaging method.

Methods: Three male patients with unilateral central serous retinopathy were examined for FPF at 535 nm induced by 1-msec flashes of 467 nm light. FPF was captured with an electron multiplying charged-coupled device camera with a 512 x 512 pixel chip.

Association of superoxide anions with retinal pigment epithelial cell apoptosis induced by mononuclear phagocytes.

Purpose: Oxidative stress of the retinal pigment epithelium by reactive oxygen species and monocytic infiltration have been implicated in age-related macular degeneration. The purpose of this study was to determine the role of superoxide anions (O(2)(-)) in mononuclear phagocyte-induced RPE apoptosis.

Methods: Mouse RPE cell cultures were established from wild-type and heterozygous superoxide dismutase 2-knockout (Sod2(+/-)) mice.