Case report: CMV retinitis following local and systemic immunosuppression.

We report the case of a 71-year-old man who presented 2 years following renal transplantation with diffuse, unilateral cytomegalovirus retinitis five weeks after receiving an intravitreal dexamethasone implant device for the management of central retinal vein occlusion. Examination of the left eye showed diffuse retinal hemorrhages, attenuated and tortuous retinal vessels, and superior retinal whitening. The patient was successfully treated with serial intravitreal foscarnet injections and oral valganciclovir with disease regression observed by 12 weeks after presentation. The patient's visual acuity and examination remained stable at 9-months follow-up.

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.

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.

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.

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.

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.

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.

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 [...].

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.

An update on immunological and molecular tests and their impact in infectious uveitis.

Early diagnosis of infectious uveitis can lead to prompt initiation of treatment to minimize vision-threatening sequelae. As various infectious etiologies of uveitis share similar clinical features, advancements in polymerase chain reaction (PCR) and metagenomic next-generation sequencing (MDS) have shown significant promise in improving diagnostic capabilities. Various techniques of PCR, including real-time, multiplex, comprehensive, and broad-range, have increased the armamentarium for infectious uveitis diagnosis. Additionally, metagenomic deep sequencing technology has provided a methodology to identify causative pathogens as well as novel etiologies of uveitis. This review discusses the diagnostic tools available for infectious uveitis and highlights the advantages and disadvantages of the techniques.

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.

Ophthalmic Features and Implications of Poxviruses: Lessons from Clinical and Basic Research.

Amidst the ongoing monkeypox outbreak, global awareness has been directed towards the prevention of viral transmission and case management, with the World Health Organization declaring the outbreak a public health emergency of international concern. Monkeypox virus is one of several species in the Orthopoxvirus genus, with other species of the genus including the variola, cowpox, mousepox, camelpox, raccoonpox, skunkpox, and volepox viruses. Although the nomenclature of these species is based on the animal host from which they were originally isolated, transmission from animals to humans has been reported with several species. The progression of disease, following an incubation period, typically consists of a prodromal phase with systemic flu-like symptoms. Various organ systems may be affected in addition to the formation of pathognomonic skin lesions. As monkeypox poses a continued public health concern, the ophthalmic sequelae of monkeypox virus, especially those leading to vision loss, warrant consideration as well. This review provides a comprehensive summary of the ophthalmic implications of poxviruses in clinical and laboratory settings reported in the literature, as well as areas of unmet need and future research.

Type I Interferon Signaling Is Critical During the Innate Immune Response to HSV-1 Retinal Infection.

Purpose: Acute retinal necrosis (ARN) is a herpesvirus infection of the retina with blinding complications. In this study, we sought to create a reproducible mouse model of ARN that mimics human disease to better understand innate immunity within the retina during virus infection. Methods: C57Bl/6J wild type (WT) and type I interferon receptor-deficient (IFNAR-/-) mice were infected with varying amounts of herpes simplex virus type 1 (HSV-1) via subretinal injection. Viral titers, optical coherence tomography (OCT) and fundus photography, the development of encephalitis, and ocular histopathology were scored and compared between groups of WT and IFNAR-/- mice. Results: The retina of WT mice could be readily infected with HSV-1 via subretinal injection resulting in retinal whitening and full-thickness necrosis as determined by in vivo imaging and histopathology. In IFNAR-/- mice, HSV-1-induced retinal pathology was significantly worse when compared with WT mice, and viral titers were significantly elevated within two days after infection and persisted to day 5 after infection within the retina. These results were also observed in the brain where there were significantly higher viral titers and frequency of encephalitis in IFNAR-/- when compared to WT mice. Conclusions: Collectively, these findings show that our new mouse model of ARN mimics human disease and can be used to study innate immunity within the retina. We conclude that type I interferons are critical in containing HSV-1 locally within retinal tissues and prohibiting spread into the brain.

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. METHODS: All patients who were diagnosed with intermediate uveitis, posterior uveitis, or panuveitis secondary to syphilis were included in the study (40 patients representing a total of 62 eyes) to identify important imaging features to aid in diagnosis. Patients underwent confirmatory serologic testing, OCT imaging, and dilated examination by a uveitis specialist. MAIN OUTCOME MEASURE: Hyperreflective retinal lesions on OCT. RESULTS: The mean age of the study population was 42.9 ± 12.16 years. Forty-five percent of the eyes included in this study harbored hyperreflective pyramidal lesions of the outer retina and retinal pigment epithelium on OCT. Fifty-four percent of eyes with these imaging findings did not show a placoid retinal lesion on examination. Sixty-eighty percent of the described outer retinal lesions on OCT resolved after treatment for syphilis. Visual acuity ranged from normal (20/20) to no light perception, with a mean of 20/43 at diagnosis, and improved significantly to a mean visual acuity of 20/26 after treatment (P < 0.05). Vision-threatening complications were seen in less than 5% of eyes and included both treatable and irreversible causes of vision loss, including retinal detachment, cystoid macular edema, and optic neuropathy. CONCLUSIONS: Patients treated for uveitis secondary to syphilis achieve good visual recoveries. Outer retinal lesions seen on OCT are common and can serve as an additional imaging finding of the disease.

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. Five patients developed the disease after eating undercooked game meat, while three developed ocular findings after cleaning hunted animals. Seven patients were healthy prior to exposure. LogMAR visual acuity at presentation was 0.697 ± 0.745, improving to 0.256 ± 0.335 by last follow-up. Disease complications developed in five (62.5%) patients, of which recurrence of retinochoroiditis was the most common. CONCLUSIONS: Contact with wild game is a potential source of primary ocular toxoplasmosis in immunocompetent adults. Hunters and consumers of rare game are at risk of serious ocular disease and appropriate contact precautions and cooking may reduce this complication.

A Review of Ocular Drug Delivery Platforms and Drugs for Infectious and Noninfectious Uveitis: The Past, Present, and Future.

Uveitis refers to a broad group of inflammatory disorders of the eye that often require medical and surgical management to improve or stabilize vision and prevent vision-threatening pathological changes to the eye. Drug delivery to the eye to combat inflammation and subsequent complications from uveitic conditions is complex as there are multiple barriers to absorption limiting availability of the needed drug in the affected tissues. As such, there has been substantial interest in developing new drugs and drug delivery platforms to help reduce intraocular inflammation and its complications. In this review, we discuss the challenges of drug delivery, novel technologies recently approved for uveitis patient care and promising drug delivery platforms for uveitis and sequelae of ocular inflammation.

Posterior scleritis and acute posterior multifocal placoid pigment epitheliopathy: A case of painful chorioretinitis and review of the current literature.

PURPOSE: To describe a patient who developed concurrent acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and posterior scleritis. OBSERVATIONS: We describe a middle-aged woman that developed eye pain and photopsia. She was found to have a "T-sign" on ultrasound of the right eye and multiple, nearly confluent, ill-defined subretinal whitish lesions in both eyes. After an extensive laboratory evaluation and neuroimaging, her photopsia, pain with eye movements, and subretinal lesions began to regress on high dose systemic corticosteroids. CONCLUSIONS AND IMPORTANCE: This is the first reported case of bilateral APMPPE and concurrent posterior scleritis. Our case highlights the importance of performing a full review of systems, specifically eliciting neurological changes, and dilated eye examination in all new uveitis cases.