NO EFFECT OF REAL-WORLD UNIVERSAL FACE MASKING ON POST-INTRAVITREAL INJECTION ENDOPHTHALMITIS RATE AT A SINGLE TERTIARY ACADEMIC CENTER.

PURPOSE: To determine whether universal masking during COVID-19 altered rate and outcomes of postinjection endophthalmitis. METHODS: Retrospective, single-site, comparative, cohort study. Eyes diagnosed with endophthalmitis within 4 weeks of intravitreal injection at the University of Michigan from August 1, 2012, to November 15, 2022, were identified. Cases were considered "masking" between March 15, 2020, and November 15, 2022. Endophthalmitis rate, visual acuity, and microbial spectrum were investigated. RESULTS: There were 20 postinjection endophthalmitis cases out of 72,194 injections (0.028%; one in 3,571 injections) premasking and 10 of 38,962 with universal masking (0.026%; one in 3,846 injections; odds ratio 0.9; 95% [confidence interval]: 0.4-2.0). Referral from the community was unchanged with 32 cases referred premasking (0.35 cases/month) and 10 cases with masking (0.31 cases/month). Presenting mean the logarithm of the minimum angle of resolution visual acuity with masking of all postinjection endophthalmitis cases trended worse (2.35 ± 0.40) compared with premasking (2.09 ± 0.48; P = 0.05) with light perception visual acuity more common with masking (31.6% vs. 10.9%, P = 0.06). There was no delay in time from procedure to initial treatment ( P = 0.36), no difference in the rate of initial treatment with tap and inject (T/I), and similar positive-culture rates ( P = 0.77) between the cohorts. Visual acuity after 30 days of follow-up was clinically unchanged (∼20/500 vs. 20/400; P = 0.59). CONCLUSION: Universal masking had no effect on postinjection endophthalmitis rate or on the rate of culture-positive cases. Although presenting visual acuity appeared worse with masking, this was not statistically significant, and current treatment paradigms resulted in similar visual outcomes.

Herpes simplex virus dissemination with necrotizing hepatitis following Descemet membrane endothelial keratoplasty.

BACKGROUND: Corneal transplants are the most common type of transplant and increasing in frequency. Donor cornea tissues are a rare source of herpes simplex virus (HSV) transmission and not routinely tested for presence of HSV. Donor graft-to-recipient transmission typically causes graft failure and anterior uveitis, and extra-ocular HSV disease has not been previously reported. We present a case of HSV transmission from donor cornea tissue that nearly cost the corneal transplant recipient his life. CASE REPORT: An elderly immunocompetent man developed an acute illness 10 days after having donor corneal tissue implanted in a Descemet membrane endothelial keratoplasty (DMEK). He was found to have HSV necrotizing hepatitis per liver biopsy, trilineage cytopenia, rhabdomyolysis, acute kidney failure, altered mental status, early-stage hemophagocytic lymphohistiocytosis (HLH), and donor corneal tissue implant infection resulting in graft failure and anterior uveitis. HSV DNA was detected in cerebral spinal fluid, peripheral blood, explanted donor corneal tissue, and anterior chamber fluid (220 million HSV DNA copies per mL). HSV-1 seroconversion denoted a primary HSV infection, and the patient had no other risk factor for HSV acquisition. Early recognition of HSV dissemination prompting treatment with intravenous acyclovir, as well as a short course of HLH-directed therapy, resolved the systemic illness. Vision was restored to near normal by replacement of the infected corneal graft with new donor DMEK tissue in conjunction with intravitreal foscarnet treatment. CONCLUSION: Awareness of the potential risk of donor cornea tissue transmitting HSV and leading to life-threatening HSV disease is paramount to early diagnosis and treatment. The role of donor cornea tissue in HSV transmission and disease merits additional attention and investigation.

Temporally independent association of multiple evanescent white dot syndrome and optic neuritis.

PURPOSE: To describe three patients that developed temporally distinct episodes of optic neuritis and multiple evanescent white dot syndrome (MEWDS). METHODS: We retrospectively reviewed the medical records and imaging studies of three women evaluated at a tertiary referral center for both optic neuritis and MEWDS. RESULTS: Three otherwise healthy women, aged 17, 36, and 41, developed temporally separated episodes of optic neuritis and MEWDS. The time periods between the two events were 3, 48, and 60 months, and in two of the three cases, the optic neuritis event preceded the episode of MEWDS. No patient endorsed prodromal flu-like symptoms prior to developing vision loss. The mean presenting visual acuities were better with the optic neuritis episode (LogMAR 0.360, Snellen 20/46) than with retinal event (LogMAR 0.684, Snellen 20/97). All three patients had improvement in vision, with mean visual acuity of 20/29 (LogMAR 0.165) at last follow-up. One patient later developed idiopathic noninfectious posterior uveitis and another developed multiple sclerosis requiring treatment. CONCLUSION: While a rare association, patients can develop both optic neuritis and MEWDS within the same eye at different time points. It is unknown whether such patients are at even higher risk of developing systemic autoimmune disease than are patients with either MEWDS or optic neuritis alone.

The evolution of an active solitary idiopathic choroiditis (focal scleral nodule): a case report of the natural course and a review of the literature.

BACKGROUND: To describe the clinical course of an active solitary idiopathic choroiditis (focal scleral nodule) that nearly resolved over six weeks without intervention. CASE PRESENTATION: An 18-year-old man presented to the emergency department with headaches and new onset central scotoma in the right eye. Visual acuity was 20/20 in both eyes. Fundus examination revealed an amelanotic choroidal lesion with associated shallow subretinal fluid. It measured 6.1 × 6.3 × 1.4mm on A- and B-scan. Evaluation for systemic inflammatory and infectious diseases was negative. A week later, the lesion remained stable, and a month later, there was improvement of the lesion with a decrease in size on OCT and exam and resolution of the subretinal fluid suggesting that the lesion had become inactive. CONCLUSIONS: Solitary idiopathic choroiditis (Focal scleral nodule) is a rare condition characterized by inflammatory granulomatous reaction. This case report sheds light on the unknown natural course of a solitary idiopathic choroiditis (focal scleral nodule).

Long-term visual outcomes of endophthalmitis and the role of systemic steroids in addition to intravitreal dexamethasone.

BACKGROUND: The purpose of this study was to evaluate the role of systemic steroids in post-procedural endophthalmitis as the role of intravitreal steroids in treatment algorithms of endophthalmitis remain controversial. METHODS: This is a retrospective analysis from a single tertiary referral center of all patients older than 18 years old that developed presumed post-procedure endophthalmitis and were treated at our center from 2009 to 2018. RESULTS: Eighty-three patients were followed after being treated for post-procedural endophthalmitis that either received systemic steroids or did not around the time of diagnosis. Almost 30 % of all patients regained a final visual acuity of 20/40 or better, while 31.2% had poor visual outcomes of count fingers or worse. Non-clearing debris was the most significant long-term complication. Visual improvement plateaued in 67.7% by 1 month after diagnosis and initial treatment in both groups. There was no difference in visual outcomes when comparing the sixteen patients that received systemic steroids and the sixty-seven that did not; however, no enucleation or evisceration was required in patients receiving systemic steroids. Five patients that did not receive systemic steroids required an enucleation or evisceration due to a blind, painful eye. CONCLUSIONS: The use of systemic steroids does not seem to worsen long-term outcomes of endophthalmitis compared to those patients that did not receive them and they may prove beneficial in the most severe cases by reducing the risk of losing the globe altogether.

The First Case of Trypanosoma cruzi-Associated Retinitis in an Immunocompromised Host Diagnosed With Pan-Organism Polymerase Chain Reaction.

We report the first case of Trypanosoma cruzi-associated retinitis diagnosed using 28s ribosomal DNA sequencing. The case highlights the utility of broad-range molecular diagnostics for detecting rare and unsuspected ocular pathogens. Ocular involvement in Chagas disease is also discussed.

Herpesvirus-Associated Lymphadenitis Distorts Fibroblastic Reticular Cell Microarchitecture and Attenuates CD8 T Cell Responses to Neurotropic Infection in Mice Lacking the STING-IFNα/ß Defense Pathways.

Type I IFN (IFN-α/ß)-driven immune responses to acute viral infection are critical to counter replication and prevent dissemination. However, the mechanisms underlying host resistance to HSV type 1 (HSV-1) are incompletely understood. In this study, we show that mice with deficiencies in IFN-α/ß signaling or stimulator of IFN genes (STING) exhibit exacerbated neurovirulence and atypical lymphotropic dissemination of HSV-1 following ocular infection. Synergy between IFN-α/ß signaling and efficacy of early adaptive immune responses to HSV-1 were dissected using bone marrow chimeras and adoptive cell transfer approaches to profile clonal expansion, effector function, and recruitment of HSV-specific CD8(+) T cells. Lymphotropic viral dissemination was commensurate with abrogated CD8(+) T cell responses and pathological alterations of fibroblastic reticular cell networks in the draining lymph nodes. Our results show that resistance to HSV-1 in the trigeminal ganglia during acute infection is conferred in part by STING and IFN-α/ß signaling in both bone marrow-derived and -resident cells, which coalesce to support a robust HSV-1-specific CD8(+) T cell response.

Checkpoint inhibitor-induced uveitis: a case series.

PURPOSE: Checkpoint inhibitors are now a common treatment modality for metastatic cancer. In this manuscript, we describe the clinical features and management of autoimmune non-infectious uveitis induced by this class of drugs. METHODS: Seven patients undergoing checkpoint inhibitor treatment for metastatic cancer from uveitis practices at three tertiary referral centers. RESULTS: All seven patients developed various severities of ocular inflammatory disease while taking checkpoint inhibitors for metastatic disease. CONCLUSIONS: Checkpoint inhibitors may induce autoimmune uveitis. Ocular complaints should prompt an early evaluation by an ophthalmologist.

Microglia and a functional type I IFN pathway are required to counter HSV-1-driven brain lateral ventricle enlargement and encephalitis.

HSV-1 is the leading cause of sporadic viral encephalitis, with mortality rates approaching 30% despite treatment with the antiviral drug of choice, acyclovir. Permanent neurologic deficits are common in patients that survive, but the mechanism leading to this pathology is poorly understood, impeding clinical advancements in treatment to reduce CNS morbidity. Using magnetic resonance imaging and type I IFN receptor-deficient mouse chimeras, we demonstrate HSV-1 gains access to the murine brain stem and subsequently brain ependymal cells, leading to enlargement of the cerebral lateral ventricle and infection of the brain parenchyma. A similar enlargement in the lateral ventricles is found in a subpopulation of herpes simplex encephalitic patients. Associated with encephalitis is an increase in CXCL1 and CXCL10 levels in the cerebral spinal fluid, TNF-α expression in the ependymal region, and the influx of neutrophils of encephalitic mouse brains. Reduction in lateral ventricle enlargement using anti-secretory factor peptide 16 reduces mortality significantly in HSV-1-infected mice without any effect on expression of inflammatory mediators, infiltration of leukocytes, or changes in viral titer. Microglial cells but not infiltrating leukocytes or other resident glial cells or neurons are the principal source of resistance in the CNS during the first 5 d postinfection through a Toll/IL-1R domain-containing adapter inducing IFN-ß-dependent, type I IFN pathway. Our results implicate lateral ventricle enlargement as a major cause of mortality in mice and speculate such an event transpires in a subpopulation of human HSV encephalitic patients.

HSV-1 targets lymphatic vessels in the eye and draining lymph node of mice leading to edema in the absence of a functional type I interferon response.

Herpes simplex virus type-1 (HSV-1) induces new lymphatic vessel growth (lymphangiogenesis) in the cornea via expression of vascular endothelial growth factor by virally infected epithelial cells. Here, we extend this observation to demonstrate the selective targeting of corneal lymphatics by HSV-1 in the absence of functional type I interferon (IFN) pathway. Specifically, we examined the impact of HSV-1 replication on angiogenesis using type I IFN receptor deficient (CD118(-/-)) mice. HSV-1-induced lymphatic and blood vessel growth into the cornea proper was time-dependent in immunocompetent animals. In contrast, there was an initial robust growth of lymphatic vessels into the cornea of HSV-1-infected CD118(-/-)mice, but such vessels disappeared by day 5 postinfection. The loss was selective as blood vessel integrity remained intact. Magnetic resonance imaging and confocal microscopy analysis of the draining lymph nodes of CD118(-/-) mice revealed extensive edema and loss of lymphatics compared with wild-type mice. In addition to a loss of lymphatic vessels in CD118(-/-) mice, HSV-1 infection resulted in epithelial thinning associated with geographic lesions and edema within the cornea, which is consistent with a loss of lymphatic vasculature. These results underscore the key role functional type I IFN pathway plays in the maintenance of structural integrity within the cornea in addition to the anti-viral characteristics often ascribed to the type I IFN cytokine family.

CD8+ T cells suppress viral replication in the cornea but contribute to VEGF-C-induced lymphatic vessel genesis.

HSV-1 is the leading cause of infectious corneal blindness in the industrialized world. CD4(+) T cells are thought to be the major leukocyte population mediating immunity to HSV-1 in the cornea as well as the likely source of immunopathology that reduces visual acuity. However, the role of CD8(+) T cells in immune surveillance of the cornea is unclear. Thus, we sought to evaluate the role of CD8(+) T cells in ocular immunity using transgenic mice in which >98% of CD8(+) T cells are specific for the immunodominant HSV-1 epitope (gBT-I.1). We found a significant reduction in virus, elevation in HSV-specific CD8(+) T cell influx, and more CD8(+) T cells expressing CXCR3 in the cornea of transgenic mice compared with those in the cornea of wild-type controls yet similar acute corneal pathology. However, by day 30 postinfection, wild-type mice had drastically more blood and lymphatic vessel projections into the cornea compared with gBT-I.1 mice, in which only lymphatic vessel growth in response to VEGF-C could be appreciated. Taken together, these results show that CD8(+) T cells are required to eliminate virus more efficiently from the cornea but play a minimal role in immunopathology as a source of VEGF-C.

A Case of Persistent Macular Edema and a Disappearing Tattoo.

PURPOSE: To describe a case of macular edema (ME), uveitis, and a disappearing tattoo. METHODS: A single case report from a tertiary referral center. RESULTS: The patient described in the following case report developed ME 15 years after a recently acquired tattoo on his arm had developed an erythematous rash and subsequently spontaneously disappeared with pathology consistent with a granulomatous process. Chest imaging identified the development of hilar lymphadenopathy that had not been previously noted. CONCLUSIONS: This case represents a unique presentation of the delayed development of sarcoidosis many years after the patient had lost a tattoo to a dermal granulomatous reaction to the tattoo ink.

Diagnosis of primary vitreoretinal lymphoma masquerading infectious retinitis by retinal biopsy.

PURPOSE: To report a case of primary vitreoretinal lymphoma masquerading as infectious retinitis that was diagnosed via a retinal biopsy. OBSERVATIONS: A 72-year-old female patient was referred to our ophthalmology clinic for evaluation of retinitis and vasculitis in the right eye (OD). On examination, best-corrected visual acuities (BCVAs) were hand motions OD and 20/20 in the left eye (OS). Fundus examination revealed optic disc edema and diffuse retinal whitening superior to the superotemporal arcade OD. Given the high suspicion of infectious retinitis, the patient was treated with intravitreal foscarnet, systemic acyclovir, and oral prednisone and underwent a comprehensive uveitis workup, which was unremarkable for viral and autoimmune entities. Given the patient's history of diffuse large B cell lymphoma with cutaneous involvement, vitreoretinal lymphoma was suspected, prompting pars plana vitrectomy with a retinal biopsy. Biopsy and immunohistochemistry results were consistent with B-cell lymphoma, and the patient was treated with high-dose methotrexate and rituximab. At 5-month follow-up, BCVAs were hand motions OD and 20/30 OS, and fundus examination demonstrated disc edema with resolution of retinal whitening OD. She responded well to the treatment with regression of vitreoretinal lymphoma on examination and is being monitored closely for lymphoma recurrence. CONCLUSIONS AND IMPORTANCE: Although uncommon, patients with vitreoretinal lymphoma may masquerade as infectious retinitis, and vitreoretinal lymphoma should be suspected when refractory to antiviral therapy and in the setting of a negative workup for viral etiologies. Vitrectomy with retinal biopsy may be considered to aid the diagnosis of vitreoretinal lymphoma although careful consideration of the risks and benefits is warranted.

Comparison of the host immune response to herpes simplex virus 1 (HSV-1) and HSV-2 at two different mucosal sites.

A study was undertaken to compare the host immune responses to herpes simplex virus 1 (HSV-1) and HSV-2 infection by the ocular or genital route in mice. Titers of HSV-2 from tissue samples were elevated regardless of the route of infection. The elevation in titers of HSV-2, including cell infiltration and cytokine/chemokine levels in the central nervous system relative to those found following HSV-1 infection, was correlative with inflammation. These results underscore a dichotomy between the host immune responses to closely related alphaherpesviruses.

Infectious Eye Diseases and Prevention Control.

Ocular infections are rare but can be unfortunate, vision-threatening conditions that can affect any part of the eye, from the outer tissues including the episcleral, sclera, and cornea to inside the eye such as the anterior chamber, vitreous, optic nerve, and retina [...].

The Host-Pathogen Interplay: A Tale of Two Stories within the Cornea and Posterior Segment.

Ocular infectious diseases are an important cause of potentially preventable vision loss and blindness. In the following manuscript, we will review ocular immunology and the pathogenesis of herpesviruses and Pseudomonas aeruginosa infections of the cornea and posterior segment. We will highlight areas of future research and what is currently known to promote bench-to-bedside discoveries to improve clinical outcomes of these debilitating ocular diseases.

Utility of a nitinol stone extractor for intraocular foreign body removal.

Purpose: To describe the novel application of a urological instrument, the nitinol stone basket, in the removal of a retained intraocular foreign body (IOFB). Observations: This is a retrospective case series describing two eyes of two patients presenting with metallic IOFBs after hammering metal-on-metal. Both patients underwent 23-gauge pars plana vitrectomy (PPV) and successful IOFB extraction using the NCircle® Nitinol Tipless Stone Extractor. There were no intraoperative or post-surgical complications. Both patients demonstrated improvement in vision, with most recent postoperative visual acuities of 20/40 and 20/60. Conclusions and importance: The nitinol stone basket may be considered for removal of IOFBs, particularly larger IOFBs that are difficult to grasp with forceps. Our cases add to the literature showing favorable visual outcomes and few complications in the post-operative period using this technique.

Association of Proton Pump Inhibitor/Histamine-2 Blocker Use and Ocular Toxoplasmosis: Findings from a Large US National Database.

OBJECTIVE: To test the hypothesis that the use of proton pump inhibitors (PPIs) is associated with an increased risk of being diagnosed with toxoplasmic retinochoroiditis. DESIGN: Retrospective, matched case-control study using data from 2000 to 2020. PARTICIPANTS: Patients with ocular toxoplasmosis and controls were matched 5:1 for age, sex, and race, with the eligibility date ± 3 months from the index date of exposed match. Patients aged < 18 years with congenital toxoplasmosis, having < 2 years in the insurance plan before the index date, and without ≥ 1 visit to an eyecare provider before the index date were excluded from the study. METHODS: Patients with ocular toxoplasmosis were identified using the International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes, and PPI use or diseases highly associated with PPIs were identified using national drug codes from an administrative medical claims database. MAIN OUTCOME MEASURES: The primary outcome was defined as having a prescription for a PPI or histamine-2 (H2) blocker. Multivariable logistic regression analyses were performed, controlling for demographic and systemic health variables. RESULTS: A total of 4069 cases and 19 177 controls met the eligibility criteria. Of the 4069 patients with ocular toxoplasmosis, 989 (24.3%) were on PPI/H2 blockers compared with 3763 of 19 177 (19.2%) controls. The adjusted logistic regression model demonstrated 1.28 greater odds of PPI/H2 blocker use in cases of ocular toxoplasmosis than matched controls (95% confidence interval, 1.17-1.40; P < 0.001). CONCLUSIONS: Proton pump inhibitor/H2 blocker exposure was associated with an increased risk of being diagnosed with ocular toxoplasmosis, corroborating findings from a prior case series. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Ophthalmic implications of biological threat agents according to the chemical, biological, radiological, nuclear, and explosives framework.

As technology continues to evolve, the possibility for a wide range of dangers to people, organizations, and countries escalate globally. The United States federal government classifies types of threats with the capability of inflicting mass casualties and societal disruption as Chemical, Biological, Radiological, Nuclear, and Energetics/Explosives (CBRNE). Such incidents encompass accidental and intentional events ranging from weapons of mass destruction and bioterrorism to fires or spills involving hazardous or radiologic material. All of these have the capacity to inflict death or severe physical, neurological, and/or sensorial disabilities if injuries are not diagnosed and treated in a timely manner. Ophthalmic injury can provide important insight into understanding and treating patients impacted by CBRNE agents; however, improper ophthalmic management can result in suboptimal patient outcomes. This review specifically addresses the biological agents the Center for Disease Control and Prevention (CDC) deems to have the greatest capacity for bioterrorism. CBRNE biological agents, encompassing pathogens and organic toxins, are further subdivided into categories A, B, and C according to their national security threat level. In our compendium of these biological agents, we address their respective CDC category, systemic and ophthalmic manifestations, route of transmission and personal protective equipment considerations as well as pertinent vaccination and treatment guidelines.

Loss of the type I interferon pathway increases vulnerability of mice to genital herpes simplex virus 2 infection.

The mouse model of genital herpes relies on medoxyprogesterone treatment of female mice to render the vaginal lumen susceptible to inoculation with herpes simplex virus 2 (HSV-2). In the present study, we report that mice deficient in the A1 chain of the type I interferon receptor (CD118(-/-)) are susceptible to HSV-2 in the absence of medroxyprogesterone preconditioning. In the absence of hormone pretreatment, 2,000 PFU of a clinical isolate of HSV-2 was sufficient to establish a productive infection in the vagina of 75% ± 17% and in the spinal cord of 71% ± 14% of CD118(-/-) mice, whereas the same dose of HSV-2 replicated to detectable levels in only 13% ± 13% of vaginal samples and 0% of spinal cord samples from wild-type mice, as determined at day 5 postinfection. The susceptibility to HSV-2 infection in the CD118(-/-) mice was associated with a significant reduction in the infiltration of HSV-specific cytotoxic T lymphocytes into the vaginal tissue, the local production of gamma interferon (IFN-γ), and the expression of T cell-recruiting chemokines CCL5, CXCL9, and CXCL10. Collectively, the results underscore the significant contribution of type I IFNs in resistance to genital HSV-2 infection.