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Purpose: To provide an overview of pre-selected emerging arboviruses (arthropod-borne viruses) that cause ocular inflammation in humans. Methods: A comprehensive review of the literature published between 1997 and 2023 was conducted in PubMed database. We describe current insights into epidemiology, systemic and ocular manifestations, diagnosis, treatment, and prognosis of arboviral diseases including West Nile fever, Dengue fever, Chikungunya, Rift Valley fever, Zika, and Yellow fever. Results: Arboviruses refer to a group of ribonucleic acid viruses transmitted to humans by the bite of hematophagous arthropods, mainly mosquitoes. They mostly circulate in tropical and subtropical zones and pose important public health challenges worldwide because of rising incidence, expanding geographic range, and occurrence of prominent outbreaks as a result of climate change, travel, and globalization. The clinical signs associated with infection from these arboviruses are often inapparent, mild, or non-specific, but they may include serious, potentially disabling or life-threatening complications. A wide spectrum of ophthalmic manifestations has been described including conjunctival involvement, anterior uveitis, intermediate uveitis, various forms of posterior uveitis, maculopathy, optic neuropathy, and other neuro-ophthalmic manifestations. Diagnosis of arboviral diseases is confirmed with either real time polymerase chain reaction or serology. Management involves supportive care as there are currently no specific antiviral drug options. Corticosteroids are often used for the treatment of associated ocular inflammation. Most patients have a good visual prognosis, but there may be permanent visual impairment due to ocular structural complications in some. Community-based integrated mosquito management programs and personal protection measures against mosquito bites are the best ways to prevent human infection and disease. Conclusion: Emerging arboviral diseases should be considered in the differential diagnosis of ocular inflammatory conditions in patients living in or returning from endemic regions. Early clinical consideration followed by confirmatory testing can limit or prevent unnecessary treatments for non-arboviral causes of ocular inflammation. Prevention of these infections is crucial. [ABSTRACT FROM AUTHOR]

To compare visual outcomes, ocular complications and therapies for patients with scleritis-associated intraocular inflammation (SAI) and patients with isolated scleritis (IS). A total of 52 patients (36 with SAI and 16 with IS) were reviewed. Mean age (standard deviation) at presentation was 48.4 years old (± 15.4) in the SAI group and 53 years old (± 17.1) in the IS group (p =.37). Visual acuity was worse at presentation and last visit for patients with SAI compared to IS (p =.04). Patients in the SAI group developed greater posterior segment complications than in the IS group (p =.002). Scleritis with intraocular inflammation was associated with a higher rate of visual morbidity compared to isolated scleritis. More aggressive management strategies may be needed for patients who present with scleritis associated with inflammation. [ABSTRACT FROM AUTHOR]

The article focuses on the use of molecular diagnostics for identifying infectious uveitis and outlines current practices and future directions. Topics include the limitations of traditional diagnostic methods, the advantages of polymerase chain reaction (PCR) and real-time PCR for detecting specific pathogens, and the potential of next-generation sequencing (NGS) for comprehensive pathogen identification and drug resistance analysis.

Coronavirus disease 2019 (COVID-19) is associated with increased risk of microvascular complications; however, reports of ophthalmic manifestations associated with retinal vascular occlusion associated with COVID-19 are limited. In this report, we describe two middle-aged female patients who were admitted for acute hypoxic respiratory failure secondary to COVID-19-induced pneumonia. Following prolonged intensive care unit admission requiring mechanical ventilation and critical care interventions, both patients reported substantially reduced vision upon regaining consciousness. Dilated funduscopic exam showed multiple blot hemorrhages in all quadrants of the posterior pole, bilateral retinal hemorrhage, macular edema, and retinal vascular tortuosity. Both patients were diagnosed with retinal ischemic events owing to bilateral ophthalmic artery occlusion in the first patient, and bilateral central retinal vein occlusion (CRVO) in the second individual. While uncommon, retinal microvascular complications associated with COVID-19 leading to vision loss require prompt evaluation and referral given their potential long-term impact following acute illness. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We provide an updated review of pre-selected RNA viruses causing ocular inflammation in humans. RNA viruses such as coronaviruses and arboviruses are reviewed elsewhere. A Google Scholar search was conducted to identify recent publications on ocular inflammation caused by the RNA viruses specified here. Human RNA viruses target a wide range of ocular tissues from the anterior to the posterior. Influenza, measles and mumps cause anterior segment manifestations including conjunctivitis and keratitis, while retinitis and optic neuritis may be seen posteriorly. Newcastle disease and RSV cause conjunctivitis, whereas HIV causes characteristic anterior uveitis. Cataracts, microphthalmos, and iris abnormalities are common in congenital Rubella, while Rubella virus is associated with Fuchs uveitis syndrome. Newer technologies make it possible to detect more than one pathogen if present simultaneously. RNA viruses may produce significant ocular morbidity, and care should be taken to investigate ocular symptoms during disease outbreaks. [ABSTRACT FROM AUTHOR]

Introduction: Macular edema, a common complication of uveitis, may result in vision loss. The aim of this analysis was to report integrated phase 3 trial data for triamcinolone acetonide injectable suspension for suprachoroidal use (SCS-TA) in the treatment of macular edema secondary to noninfectious uveitis using strict inclusion criteria. Methods: This analysis included patients with central subfield thickness (CST) ≥ 300 µm and best-corrected visual acuity (BCVA) of ≥ 5 and ≤ 70 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at both screening and baseline who received ≥ 1 study treatment in either PEACHTREE (randomized, double-masked SCS-TA or sham control) or AZALEA (open-label SCS-TA). Patients received SCS-TA 4.0 mg (0.1 ml of 40 mg/ml) or control at baseline and week 12. Results: In the SCS-TA group (n = 95), 47.4% of patients gained ≥ 15 ETDRS letters from baseline to week 24 versus 16.7% of patients in the control group (n = 60; P < 0.001). Mean change in BCVA in the SCS-TA group was 9.6 letters at week 4 and 13.9 letters at week 24. CST also improved rapidly in the SCS-TA group (mean change: − 158.4 µm at week 4), with sustained reduction throughout the study (mean change: − 163.9 µm at week 24 versus − 19.3 µm in the control group; P < 0.001). No treatment-related serious adverse events (AEs) were reported. Incidence of AEs pertaining to elevated intraocular pressure was 12.6% and 15.0% in the SCS-TA and control groups, respectively; incidence of cataract formation/worsening AEs was 7.4% and 6.7%, respectively. Conclusion: In this integrated analysis utilizing strict inclusion criteria, SCS-TA was found effective in the treatment of patients with macular edema associated with noninfectious uveitis and was generally well tolerated. Trial registration: ClinicalTrials.gov identifier: NCT02595398, NCT03097315. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Despite increasing evidence that uveitis is common and consequential in survivors of Ebola virus disease (EVD), the host-pathogen determinants of the clinical phenotype are undefined, including the pathogenetic role of persistent viral antigen, ocular tissue-specific immune responses, and histopathologic characterization. Absent sampling of human intraocular fluids and tissues, these questions might be investigated in animal models of disease; however, challenges intrinsic to the nonhuman primate model and the animal biosafety level 4 setting have historically limited inquiry. In a rhesus monkey survivor of experimental Ebola virus (EBOV) infection, we observed and documented the clinical, virologic, immunologic, and histopathologic features of severe uveitis. Here we show the clinical natural history, resultant ocular pathology, intraocular antigen-specific antibody detection, and persistent intraocular EBOV RNA detected long after clinical resolution. The association of persistent EBOV RNA as a potential driver of severe immunopathology has pathophysiologic implications for understanding, preventing, and mitigating vision-threatening uveitis in EVD survivors. Deep characterization of uveitis in a rhesus monkey confirms Ebola virus RNA persistence is associated with severe immunopathology in the eye, with broader implications for the prevention and treatment of sight-threatening uveitis in human survivors of Ebola virus. [ABSTRACT FROM AUTHOR]

Purpose: To assess hospitalized COVID-19 inpatients for the prevalence of retinopathy and tear film SARS-CoV-2 RNA, and associated risk factors for their detection. Methods: Hospitalized COVID-19 patients underwent dilated ophthalmic examination and fundus photography. Conjunctival swabs were assessed for SARS-CoV-2 RT-PCR via a triple target assay. We assessed the relationships of retinopathy with clinical outcomes, systemic risk factors and laboratory data. Results: The median age was 59.5 years and 29 (48%) were female. Retinopathy associated with COVID-19 was observed in 12 of 60 patients (20%). The median age of patients with COVID-19 retinopathy was 51.5 compared to 62.5 years in individuals without retinopathy (p = 0.01). Median BMI was 34.3 in patients with retinopathy versus 30.9 in those without retinopathy (p = 0.04). Fifteen of 60 patients (25%) tested SARS-CoV-2 RNA-positive in their tear film without a relationship with timing of illness and hospitalization. The N2 gene was particularly sensitive with 18 of 19 eyes (94.7%) showing N2-positivity, including 2 patients with alpha variant-positivity (B.1.1.7). Conclusion: Retinopathy was observed in 20% of patients hospitalized for COVID-19. Patients with retinopathy were more likely to be younger and have higher BMI than hospitalized patients without retinopathy. Tear film SARS-CoV-2 RNA was detected in 25% of patients. The relationship of obesity and age with retinopathy requires further investigation. [ABSTRACT FROM AUTHOR]

To report the cytopathology of vitreous biopsy samples in patients with acute retinal necrosis (ARN) who underwent pars plana vitrectomy (PPV). We also describe two patients with unique clinical courses, cytopathologic findings, and immune response A retrospective review of patients with ARN who developed retinal detachment (RD) and underwent PPV from 22011 to 2019 at the Emory Eye Center was performed to assess cytopathology findings of vitreous biopsy samples. Patient demographics and laboratory testing including aqueous humor PCR for viral pathogens were recorded. Additional clinical details abstracted included intravitreal injections, surgical procedures, and vitreous cytopathological reports including immunohistochemistry findings. Fourteen eyes of 12 patients with RD were reviewed. Ten eyes showed HSV DNA (71%) and 4 demonstrated VZV DNA (29%). All eyes received intravitreal antivirals (i.e. ganciclovir or foscarnet) with a median of 8.5 intravitreal injections per eye. Diagnoses prompting PPV included tractional RD in 14 eyes (100%), rhegmatogenous RD in 8 eyes (57%), vitreous hemorrhage in 4 eyes (29%) and vitreous opacity in 4 (29%). Ophthalmic pathology reports showed lymphocyte populations in 10 eyes (71%) with a CD3 + T-cell predominance in two patients where immunohistochemistry of CD3+ and CD20+ for T- and B-cell populations was performed. Observed immune cell populations included macrophages or histiocytes (11 eyes, 79%) and polymorphonuclear cells in 4 eyes (29%). Initial median VA was 2.5 (IQR 2.0–3.0) and improved to 2.0 (IQR 1.48–3.00, p =.48) at 6-months and 1.8 (IQR 1.2–3.0, p =.45) at 12 months follow-up. Our cohort of ARN patients undergoing PPV show a spectrum of immunologic findings with the majority demonstrating a lymphocytic response. Histiocytes, macrophages, and PMNs were also observed. Cytopathologic and immunologic studies suggest that both innate and adaptive immunity are responsible for the clinical disease findings observed in ARN. The variability of the response to treatment in patients with ARN may reflect patient-to-patient differences in their antigen-specific immune response. Understanding the immunologic response associated with ARN may provide valuable information regarding the dosing and timing of treatment. [ABSTRACT FROM AUTHOR]

Background: Primary vitreoretinal lymphoma (PVRL) is an aggressive lymphoma that may present with protean features and represents a diagnostic challenge. Given that patients with PVRL are at high risk of CNS involvement with a high mortality and morbidity rate, prompt diagnosis is crucial to initiate treatment early in the disease course. A multimodality imaging approach including fundus photography, fundus autofluorescence (FAF), optical coherence tomography (OCT), fluorescein and indocyanine angiography, and electroretinography (ERG) can provide information to establish a diagnosis and provide objective measures for management. We review key findings seen via these imaging modalities in patients with PVRL. Observations: Fundus photography can highlight commonly seen patterns of PVRL including vitritis, subretinal disease, retinal pigment epithelial (RPE) abnormalities, optic nerve edema, retinal detachment, and less typical retinitis-like lesions. FAF can identify characteristic patterns of hyper- and hypoautofluorescent signal abnormalities in the macula. Spectral-domain OCT will demonstrate vitreous cells, RPE nodularity, and hyperreflectivity of the outer retina. The presence of a hyper-reflective band in the subretinal space and infiltrates between the RPE and Bruch's membrane can assist in distinguishing PVRL from choroidal lymphoma. Vertical hyperreflective columns (VHRLs) are another pertinent finding that may represent microinfiltrates of the tumor. OCT has proven to be a particularly useful modality in assessing the progress of treatment in PVRL. Fluorescein angiography can show RPE changes, which include granularity, late staining at the RPE level, and blockage. Indocyanine green angiography (ICGA) primarily shows hypocyanescence, which corresponds to PVRL lesions on fundus photography and may occur secondary to loss of RPE and choriocapillaris. Conclusion: While PVRL remains a challenging disease to diagnose and follow, the use of a multimodality imaging approach may assist in establishing a diagnosis. Because of the anatomic spaces PVRL may affect, fundus photography, OCT, FAF, angiography, and ERG can identify key characteristics of the disease, differentiate PVRL from other diseases, and provide baseline information for targeted systemic and local therapies. Further assessment of anatomic and functional targets will aid our clinical application of multimodal imaging in the management of PVRL. [ABSTRACT FROM AUTHOR]

Purpose To assess the extended efficacy and safety of suprachoroidal triamcinolone acetonide injectable suspension (CLS-TA) among patients with macular oedema (ME) secondary to non-infectious uveitis (NIU). Methods Patients with uveitic ME were treated with suprachoroidal CLS-TA at baseline and week 12 of the Efficacy and Safety of Suprachoroidal CLS-TA for Macular Edema Secondary to Noninfectious Uveitis: Phase 3 Randomized Trial (PEACHTREE) study. Time to rescue was evaluated over 24 additional weeks for MAGNOLIA. Safety data, visual acuity and retinal central subfield thickness (CST) reduction were also evaluated. Of the 53 eligible patients (46 CLS-TA and 7 control), 33 patients were enrolled (28 CLS-TA and 5 control). Results Over the entire 48-week period for PEACHTREE and MAGNOLIA, the median time to rescue therapy was 257 days versus 55.5 days for the CLS-TA and sham-control arms, respectively. Of 28 CLS-TA treated patients who participated in MAGNOLIA, 14 (50%) did not require rescue therapy through approximately 9 months after the second treatment. Among CLS-TA patients not requiring rescue, there was a mean gain of 12.1 letters and mean CST reduction of 174.5 µm at week 48. No serious adverse events related to study treatment were observed. Conclusion Approximately 50% of patients did not require additional treatment for up to 9 months following the last CLS-TA administration. [ABSTRACT FROM AUTHOR]

To present a patient with Rosai-Dorfman Disease (RDD), a histiocytic proliferative disorder typified by lymphadenopathy with rare ocular manifestations, who developed panuveitis that responded to pegylated interferon. Descriptive case report of a patient with RDD with multi-organ involvement including ocular manifestations including bilateral panuveitis with choroidal masses. A 54-year-old African American woman with known systemic RDD of the breast, lung, and gastrointestinal tract presented with panuveitis with choroidal masses in both eyes. Her systemic and ocular disease initially responded well to oral and topical steroid therapy. Later, however, her systemic disease progressed with multiple muscular and bony lesions. Systemic therapy was switched to pegylated interferon, a cytokine with antiviral, antitumor and immunomodulatory activity. After 14 months of therapy with pegylated interferon, the patient's systemic and ocular disease stabilized. Rosai-Dorfman disease may be complicated by panuveitis and choroidal masses that may respond to pegylated interferon with stabilization of systemic and ocular manifestations. A multi-disciplinary approach is essential given the unique diagnostic and management challenges of RDD. [ABSTRACT FROM AUTHOR]

To present a case of refractory systemic lupus erythematosus (SLE)-associated retinal vasculitis that responded to the anti-tumor necrosis factor (TNF)-alpha inhibitor adalimumab as corticosteroid-sparing therapy. Descriptive case report of a patient with SLE with retinal vasculitis complicated by an ischemic retinal vein occlusion and cystoid macular edema. A 30-year-old female patient with a history of SLE presented with retinal vasculitis and an ischemic, branch retinal vein occlusion with macular edema in the left eye. Oral corticosteroid was administered along with mycophenolate mofetil (MMF) as a corticosteroid-sparing agent. Despite MMF therapy, the patient developed an exacerbation of her vasculitis with the involvement of both eyes. Adalimumab was initiated with a resultant resolution of retinal vasculitis as a corticosteroid-sparing strategy with over 2 years of follow-up. Anti-TNF-alpha therapy with adalimumab may be effective as a corticosteroid-sparing agent in select patients with ocular inflammation associated with SLE. [ABSTRACT FROM AUTHOR]

Autoimmuntoxizitäten, die nach der Behandlung mit Krebsimmuntherapien häufig auftreten, sind bei Patienten, die mit BRAF/MEK-Inhibitoren behandelt werden, nicht gut charakterisiert. Neuere Daten deuten darauf hin, dass Autoimmuneffekte mit einem überragenden Ansprechen auf beide Behandlungsmodalitäten verbunden sein können; es gibt jedoch wenig Evidenz, die Mechanismen der immunbedingten Toxizität für Patienten unter BRAF/MEK-Inhibitoren beschreibt. Hier beschreiben wir die Erfahrungen eines 59-jährigen HLA-A2, A29, B27-positiven Mannes mit rezidivierendem/metastasierendem Melanom. Nach Progression unter Checkpoint-Inhibitor-Therapie wurde er mit Dabrafenib/Trametinib, gefolgt von Encorafenib/Binimetinib, behandelt, die gut vertragen wurden und zu einem vollständigen Ansprechen führten. 18 Monate nach der BRAF/MEK-Inhibitor-Therapie und drei Monate nach dem ersten vollständigen Ansprechen entwickelte er eine Reihe plötzlich einsetzender, schwerer Toxizitäten: nämlich bilaterale Panuveitis, Zytopenien, Gelenkschmerzen, Hautausschlag, Hyperkalzämie und interstitielle Nephritis, die zu einem BRAF/MEKi-Abbruch führten. Immunologische Analysen zeigten die Induktion einer peripheren Typ-17-Zytokin-Signatur, die durch hohe IL-23-, IL-6-, IL-10-, IL-17A/F-, IL-113- und IL-21-Zytokine im Plasma gekennzeichnet ist, die dem Ausmaß der Symptome entsprechen. Diese Ergebnisse zeigen einen neuen Fall einer verzögerten autoimmunähnlichen Reaktion auf die BRAF/MEK-Inhibition und weisen auf eine mögliche Rolle der ThiTc17-Aktivierung in ihrer Pathogenese hin, was eine zukünftige klinische und immunologische Charakterisierung rechtfertigt. [ABSTRACT FROM AUTHOR]

Uveitis is a common manifestation of post-Ebola syndrome, associated with persistence of Ebola virus (EBOV; Zaire ebolavirus) inside the eye. The iris and retinal pigment epithelia are key components of the blood-ocular barriers, but have the capacity to act as hosts for microorganisms. We investigated the ability of EBOV to productively infect these cell populations. Donor-matched human iris and retinal pigment epithelial isolates (n = 5) were infected with EBOV at a multiplicity of infection of 1 for up to 72 hours. Parallel cultures were infected with Reston virus (RESTV; Reston ebolavirus) or Zika virus (ZIKV), or held uninfected under the same conditions. Viral transcript expression by RT-qPCR on total cellular RNA, cytoimmunofluorescence, and assays of 50% tissue culture infected dose of culture supernatant showed that both iris and retinal pigment epithelial isolates were permissive to infection, and supported replication and release of EBOV, as well as RESTV and ZIKV. However, in comparison to cells isolated from iris, those from retina demonstrated obvious EBOV-induced cytopathic effect, had higher intracellular EBOV nucleoprotein transcript, expressed intracellular EBOV protein more widely, and released EBOV at higher titer. Comparable results were obtained for isolates infected with RESTV and ZIKV. Consistent with observations of retinal pigment epithelial scars in Ebola survivors, our results suggest that an early event in post-Ebola uveitis is infection of the retinal pigment epithelium. Relative susceptibility of retinal pigment epithelial cells to infection with RESTV and ZIKV, as well as EBOV, implies this phenomenon may relate to a cell-specific attribute, such as high phagocytic activity. [ABSTRACT FROM AUTHOR]

Macular edema due to noninfectious uveitis is a sight-threatening complication that is routinely treated with corticosteroids. Triamcinolone acetonide injectable suspension for suprachoroidal use (Xipere™) is an alternative treatment option for patients with noninfectious uveitis-associated macular edema. This review describes the recently FDA-approved triamcinolone acetonide injectable suspension that can be injected into the suprachoroidal space. This physiological space is between the sclera and choroid. This allows for therapeutic targeting of the retina and choroid. This review highlights published clinical trials for this novel drug preparation. Suprachoroidal administration of triamcinolone acetonide has shown improvement in vision and inflammation in studies with noninfectious uveitis-associated macular edema. This unique delivery method suggests the potential to decrease side effects of anterior segment exposure such as glaucoma and cataract, but head-to-head trials are needed for further study of safety and efficacy. Additionally, there are promising prospective studies underway for utilization of the suprachoroidal space for other diseases including macular degeneration, diabetic macular edema, and ocular tumors. [ABSTRACT FROM AUTHOR]

Purpose To evaluate local and systemic safety of suprachoroidal (SC) triamcinolone acetonide injectable suspension (CLS-TA) injections in subjects with non-infectious uveitis (NIU). Design Open-label, prospective multicentre safety study. Participants Thirty-eight subjects with NIU, with and without macular oedema (MO). Methods Treatment consisted of two suprachoroidal injections of CLS-TA 4 mg, 12 weeks apart. Best-corrected visual acuity (BCVA), adverse event (AE) assessment, ophthalmic examinations and optical coherence tomography (OCT) were conducted every 4 weeks for 24 weeks. Blood samples were analysed for plasma triamcinolone acetonide (TA) concentrations. Main outcome measures The main outcome measure was frequency of AEs. Other endpoints included plasma TA concentrations, change in signs of inflammation, BCVA and retinal central subfield thickness (CST). Results Based on a CST of >300 µm, 20 out of 38 subjects had MO at baseline. Mean intraocular pressure (IOP) was 13.3 mm Hg at baseline and 15.2 mm Hg at week 24 in the study eye. A total of six (15.8%) subjects had an IOP rise >10 mm Hg compared with baseline, in the study eye, and two (5.3%) subjects had IOP >30 mm Hg (maximum 34 mm Hg at week 8 and 38 mm Hg at week 20). Cataract formation AEs were reported in four study eyes; one of which was deemed treatment-related. No serious ocular AEs in the study eye occurred in the study. Quantifiable post-injection TA plasma concentration was <1 ng/mL. Efficacy parameters showed improvement over the 24-week study period. Conclusions Suprachoroidally administered CLS-TA was safe and well tolerated over the 24-week, open-label study in NIU subjects with and without MO. [ABSTRACT FROM AUTHOR]

Autoimmune toxicities, while common following treatment with cancer immunotherapies, are not well-characterized in patients treated with BRAF/MEK inhibitors. Emerging data suggest that autoimmune effects may be linked with superior responses to both treatment modalities; however, there is little evidence describing mechanisms of immune-related toxicity for patients on BRAF/MEK inhibitors. Here we describe the experience of a 59-year-old HLA-A2, A29, B27-positive male with recurrent/metastatic melanoma. After progression on checkpoint inhibitor therapy, he was treated with dabrafenib/trametinib followed by encorafenib/binimetinib, which were well-tolerated and resulted in a complete response. Eighteen months into BRAF/MEK inhibitor therapy, and three months after initially finding a complete response, he developed a series of sudden-onset, severe toxicities: namely, bilateral panuveitis, cytopenias, joint pain, skin rash, hypercalcemia, and interstitial nephritis, which led to BRAF/MEKi cessation. Immunological analyses revealed induction of a peripheral type-17 cytokine signature characterized by high IL-23, IL-6, IL-10, IL-17A/F, IL-1β, and IL-21 among other cytokines in plasma corresponding with the height of symptoms. These findings highlight a novel instance of delayed autoimmune-like reaction to BRAF/MEK inhibition and identify a possible role for Th/Tc17 activation in their pathogenesis thus warranting future clinical and immunological characterization. [ABSTRACT FROM AUTHOR]

Objective: The Effects of Youngsters' Eyesight on Quality of Life (EYE‐Q) questionnaire measures vision‐related functioning (VRF) and vision‐related quality of life (VRQoL) in children with uveitis. Our aim was to revise the alpha version of the EYE‐Q to refine VRF and VRQoL subscales and to assess the validity of the EYE‐Q. Methods: Children with juvenile idiopathic arthritis (JIA), JIA‐associated uveitis, and other noninfectious uveitis were enrolled. Patients and parents completed the EYE‐Q, Pediatric Quality of Life Inventory (overall quality of life), and Childhood Health Assessment Questionnaire (physical functioning). The development site completed the alpha version of the EYE‐Q, and the composite sites completed the beta version. We compared item‐subscale correlations, internal consistency, and construct and discriminant validity among the different versions. Results: Of the 644 patients enrolled, 61.6% completed the alpha version, and 38.4% the beta version of the EYE‐Q. Mean ± SD patient age was 11.1 ± 4.2 years, and 70% were female. Fewer White patients (73.5%) completed the alpha version compared to the beta version (86.2%; P < 0.001). With the exception of patient‐reported VRF, both versions had similar item‐subscale correlations. Version comparisons on scale internal consistencies indicated significant differences for parent‐ and patient‐reported VRF, but each scale had a Cronbach's α of >0.80 beta. When data were combined, the EYE‐Q showed significant differences between JIA‐only and uveitis patients on all parent and patient scores, except for patient‐reported VRF. Conclusion: The EYE‐Q appears to be a valid measure of VRF and VRQoL in pediatric uveitis. Our results suggest it may be used as an outcome measure in multicenter pediatric uveitis studies. [ABSTRACT FROM AUTHOR]

Background: This post hoc analysis compared the efficacy and safety of suprachoroidally administered triamcinolone acetonide (CLS-TA) to other commonly available treatments for non-infectious uveitis. Methods: Results from the PEACHTREE study were compared between subjects randomised to CLS-TA not requiring rescue therapy and those subjects randomised to control, who subsequently required rescue therapy. Endpoints included best corrected visual acuity (BCVA), central subfield thickness (CST), treatment emergent adverse events and intraocular pressure (IOP) related safety findings. Results: In this analysis, there were 83 unrescued CLS-TA subjects and 46 rescued control subjects. At Week 24, 51.9% of the unrescued CLS-TA subjects gained =15 letters in BCVA, compared to 37.0% of the rescued control subjects (p = 0.115). Unrescued CLS-TA subjects showed a mean gain of 15.7 versus 10.9 letters in rescued control subjects (p = 0.080). A significantly greater mean reduction in CST was observed for unrescued CLS-TA subjects versus rescued control subjects (174.0 and 148.5 µm; p = 0.040). Of unrescued CLSTA subjects, 4.9% experienced IOP elevations =30 mm Hg at any visit versus 10.9% of rescued control subjects. Further, use of IOP-lowering medications appeared lower in unrescued CLS-TA subjects versus rescued control subjects (7.2% vs. 13.0%). There were no IOP-lowering surgical interventions in either group. Conclusion: CLS-TA subjects experienced significantly greater reduction in CST and tended towards greater improvement in BCVA, compared with rescued control subjects. Suprachoroidally administered CLS-TA showed a lower incidence of IOP-related safety findings. [ABSTRACT FROM AUTHOR]

Purpose: To describe the visual acuity and anatomic outcomes of intravitreal methotrexate (MTX) for the treatment of primary vitreoretinal lymphoma (PVRL). Methods: Single-center retrospective case series of patients with a diagnosis of PVRL treated with intravitreal MTX. Patient records were reviewed for demographic information, ocular exam findings, and treatment regimens including number of MTX injections. Clinical outcomes recorded included visual acuity (VA), time to partial (PR) or complete response (CR), disease-free survival, time to relapse, and any CNS progression. Results: Ten eyes of 7 patients (4 male, 6 female) were reviewed. The mean age ± standard deviation (SD) was 70 ± 12 years. Five patients had prior or concomitant diagnosis of primary CNS lymphoma with a history of systemic chemotherapy including MTX. Three eyes (30%) exhibited isolated vitreous involvement, four (40%) had subretinal lesions, and three (30%) presented with both vitreous and subretinal disease. Mean initial logMAR VA was 0.38 ± 0.52 (Snellen visual equivalent 20/50), while mean final logMAR VA ± SD was 0.34 ± 0.27 (Snellen visual equivalent 20/40) with a mean follow-up time of 26 months (Range, 3–49 months). Patients received an average of 6 intravitreal MTX injections (Range 1–10) over the course of treatment. Two patients received concomitant systemic chemotherapy. Mean time to either PR or CR was 57 days, and 6 eyes (60%) exhibited regression with no relapse after local treatment. For the 4 eyes that eventually relapsed, the mean time ± SD to first relapse was 193 days ± 155 days, and one eye experienced a second relapse. Two of 3 patients with subretinal disease showed complete regression with extended follow-up of 1 and 4 years following treatment with less than 3 doses of intravitreal MTX. One patient with PVRL developed CNS lymphoma during the study period. VA remained stable overall between the initial treatment visit, 3, 6, and 12-months (P > 0.05 for paired comparisons of VA over time). Conclusions: Intravitreal methotrexate was well-tolerated and led to local disease response in the majority of patients at approximately 2 months after initiation of treatment of intraocular lymphoma. Further studies on the efficacy of intravitreal treatment alone versus combined systemic and intravitreal treatment are warranted. [ABSTRACT FROM AUTHOR]

The article discusses research on relapse and remission in children with chronic noninfectious uveitis (NIU) treated with methotrexate (MTX). It enumerates the patient inclusion criteria for the study and the conditions described to determine relapse of uveitis. Data shows the demographic characteristics of children with uveitis treated with MTX. Results reveal MTX tapering/discontinuation in a number of patients and those with sustained remission after MTX discontinuation.

Background: Intraocular lymphoma accounts for fewer than 1% of intraocular tumors. When the posterior segment is involved, it can be further classified as vitreoretinal or choroidal lymphoma. Vitreoretinal lymphoma (VRL) can rarely masquerade as an infectious retinitis making diagnosis and management challenging. Results: A 73-year-old woman with a history of non-central nervous system (CNS) involving diffuse large B-cell lymphoma (DLBCL) was referred for worsening blurry vision—visual acuity of count figures at 2 ft—in her right eye for 8 months. Dilated fundus examination of the right eye was significant for retinal whitening and dot-blot hemorrhages, which was concerning for a viral retinitis and guided initial management. Secondary intraocular lymphoma was also considered. The retinal disease continued to progress despite intravitreal and systemic antiviral therapy, and a diagnostic vitrectomy was inconclusive. A retinal biopsy was then performed, which showed DLBCL, confirming a diagnosis of secondary VRL. Three subsequent treatments with intravitreal methotrexate led to regression of the VRL. Conclusions: Our case highlights the utility of a retinal biopsy after an inconclusive diagnostic vitrectomy in a challenging scenario of VRL to establish a diagnosis and initiate successful treatment. A multidisciplinary team of providers was essential for diagnosis, comprehensive workup, medical and surgical management of the patient. [ABSTRACT FROM AUTHOR]

Background: Following the West African Ebola virus disease (EVD) outbreak of 2013–2016 and more recent EVD outbreaks in the Democratic Republic of Congo, thousands of EVD survivors are at-risk for sequelae including uveitis, which can lead to unremitting inflammation and vision loss from cataract. Because of the known risk of Ebola virus persistence in ocular fluid and the need to provide vision-restorative, safe cataract surgery, the Ebola Virus Persistence in Ocular Tissues and Fluids (EVICT) Study was implemented in Sierra Leone. During implementation of this multi-national study, challenges included regulatory approvals, mobilization, community engagement, infection prevention and control, and collaboration between multiple disciplines. In this report, we address the multifacted approach to address these challenges and the impact of implementation science research to address an urgent clinical subspecialty need in an outbreak setting. Methodology/Principal findings: Given the patient care need to develop a protocol to evaluate ocular fluid for Ebola virus RNA persistence prior to cataract surgery, as well as protocols to provide reassurance to ophthalmologists caring for EVD survivors with cataracts, the EVICT study was designed and implemented through the work of the Ministry of Health, Sierra Leone National Eye Programme, and international partnerships. The EVICT study showed that all 50 patients who underwent ocular fluid sampling at 19 and 34 months, respectively, tested negative for Ebola virus RNA. Thirty-four patients underwent successful cataract surgery with visual acuity improvement. Here we describe the methodology for study implementation, challenges encountered, and key issues that impacted EVD vision care in the immediate aftermath of the EVD outbreak. Key aspects of the EVICT study included defining the pertinent questions and clinical need, partnership alignment with key stakeholders, community engagement with EVD survivor associations, in-country and international regulatory approvals, study site design for infection prevention and control, and thorough plans for EVD survivor follow-up care and monitoring. Challenges encountered included patient mobilization owing to transportation routes and distance of patients in rural districts. Strong in-country partnerships and multiple international organizations overcame these challenges so that lessons learned could be applied for future EVD outbreaks in West and Central Africa including EVD outbreaks that are ongoing in Guinea and Democratic Republic of Congo. Conclusions/Significance: The EVICT Study showed that cataract surgery with a protocol-driven approach was safe and vision-restorative for EVD survivors, which provided guidance for EVD ophthalmic surgical care. Ophthalmologic care remains a key aspect of the public health response for EVD outbreaks but requires a meticulous, yet partnered approach with international and local in-country partners. Future efforts may build on this framework for clinical care and to improve our understanding of ophthalmic sequelae, develop treatment paradigms for EVD survivors, and strengthen vision health systems in resource-limited settings. [ABSTRACT FROM AUTHOR]

We report a case of varicella zoster virus (VZV)-associated anterior uveitis in a patient with weight loss, arthritis and signs of inflammatory bowel disease. Her clinical course included the development of a thalamic stroke secondary to VZV cerebral vasculopathy. Following antiviral therapy, the patient's neurologic symptoms recovered and her ophthalmic findings improved. [ABSTRACT FROM AUTHOR]

Background: The management of an outbreak of endophthalmitis associated with intravitreal bevacizumab represents a challenging real-time process involving identification of cases, treatment and mitigation measures during the outbreak. We summarize the clinical presentation and management of a cluster of endophthalmitis cases from contaminated bevacizumab, in addition to mathematical probabilistic assessment of the number of cases that define an outbreak. Methods: A retrospective study was conducted to assess the management of an endophthalmitis outbreak after intravitreal bevacizumab (IVB) administration. Demographic data, clinical information, individual patient management and public health reporting measures were reviewed. Outcomes of patients who received prophylactic antibiotics for endophthalmitis prevention were also reviewed. Binomial tail probability calculations were performed to determine the likelihood of clusters of endophthalmitis that could inform when an outbreak was evolving that would warrant more public health notification measures and communication. Results: Forty-five eyes of 42 patients who received IVB from a single batch were reviewed. Four cases of endophthalmitis from Granulicatella adiacens, a nutritionally-variant Streptococcus species, were treated successfully with intravitreal antibiotics ± vitrectomy. Thirty-four of the remaining 41 eyes were treated with prophylactic intravitreal vancomycin with no additional cases of endophthalmitis. Outbreak management also included CDC, ASRS and public health authority notification. Binominal tail probabilities demonstrated the rarity of clusters from a single batch (i.e. ~ 1/10,000 for 2 cases; 1/2 million for 3 cases). However, given the U.S. scale of IVB administration, there is an 87% chance of a cluster ≧ 2 and a 1% chance of a cluster ≧ 3 cases annually, which may guide outbreak management. A process diagram was developed to incorporate patient management and public health measures when an outbreak is suspected. Conclusion: Intravitreal antibiotics and vitrectomy were effective in the individual management of cases of endophthalmitis, and no serious adverse events occurred with prophylactic intravitreal vancomycin for at-risk eyes. Best practices for outbreaks should be evaluated, given their likelihood within the U.S. and the sight-threatening consequences of endophthalmitis. [ABSTRACT FROM AUTHOR]

The purpose of this study was to describe the ocular findings, structural ocular complications, and vision impairment in a cohort of Lassa fever survivors in Kenema, Sierra Leone. A retrospective, uncontrolled, cross-sectional study of 31 Lassa fever survivors (62 eyes) who underwent an ophthalmic evaluation in January 2018 at the Kenema Government Hospital in Kenema, Sierra Leone was performed. Data collection included demographic information, ocular/systemic symptoms, visual acuity (VA), and ophthalmic examination findings. Main outcome measures included anterior and posterior segment ophthalmic manifestations and level of VA impairment in Lassa fever survivors. Anterior segment findings included cataract (18%) and pterygium (2%), while posterior segment manifestations consisted of glaucoma (6%), preretinal hemorrhage (2%), and lattice degeneration (2%). Findings suggestive of prior sequelae of uveitis included chorioretinal scarring (5%), retinal fibrosis (3%), and vitreous opacity (2%). Visual acuity was normal/mildly impaired in 53 eyes (85%), moderately impaired in 6 eyes (10%), and 3 eyes (5%) were considered blind by the World Health Organization (WHO) criteria. Median VA was worse in Lassa fever survivors with ophthalmic disease findings (p<0.0001) for both anterior segment (p<0.0001) and posterior segment disease (p<0.013). Untreated cataract was a significant cause of visual acuity impairment (p<0.0001). Lassa fever survivors in this cohort were found to have cataract and posterior segment findings that potentially represent sequelae of uveitis associated with visual impairment. Future studies are warranted to improve our understanding of the spectrum of ocular disease in this emerging infectious disease of public health consequence. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate potential insights into the pathogenesis of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) using multimodal diagnostic imaging and laboratory evaluation in long-term follow-up. A retrospective, single-center case series was conducted on seven consecutive patients (14 eyes) who were given a diagnosis of APMPPE from March 1, 2011, through June 30, 2019 with at least three months of follow-up. Clinical characteristics (age, symptoms, visual acuity [VA]), laboratory testing including coxsackievirus titers, and multimodal imaging from fundus photography, spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), fluorescein angiography (FA), and indocyanine green angiography (ICG) were analyzed for each patient. The initial median VA was 20/71 and final median VA was 20/22. Coxsackievirus B (CVB) titers were elevated (≥ 1:80) in six of seven patients, with a four-fold increase in convalescent titers seen in two patients suggestive of recent infection. All patients were treated with oral corticosteroids, and five patients underwent corticosteroid-sparing immunomodulatory therapy. Initially, multifocal deep choroidal lesions were observed in the posterior pole corresponding to patches of hypocyanescence on ICG. Overlying retinal pigment epithelium (RPE) disease was observed on FAF, although this finding was not universally observed, suggesting that RPE disease may occur as a sequelae to unchecked choroidal inflammation. SD-OCT architectural changes confirmed outer retina and ellipsoid zone disruption. FA of active lesions showed early hypofluorescence and late hyperfluorescence with surrounding leakage while inactive disease showed areas of staining. Long-term follow-up of multimodal diagnostic imaging in APMPPE revealed that choroidal inflammation likely precedes RPE change and photoreceptor damage. Elevation of coxsackievirus titers with seroconversion may be associated with an infectious trigger in concert with immune-mediated disease in this posterior uveitis syndrome. [ABSTRACT FROM AUTHOR]

A 46-year-old patient with previously documented Ebola virus persistence in his ocular fluid, associated with severe panuveitis, developed a visually significant cataract. A multidisciplinary approach was taken to prevent and control infection. Ebola virus persistence was assessed before and during the operation to provide safe, vision-restorative phacoemulsification surgery. [ABSTRACT FROM AUTHOR]

Background: The cases discussed highlight the atypical presentation and diagnostic dilemmas of toxoplasmosis with fulminant retinal necrosis and the potentially devastating visual outcomes of toxoplasma chorioretinitis following local corticosteroid exposure. Case presentation: We report a series of three patients who presented with toxoplasmosis mimicking severe acute retinal necrosis. Patients were between 59 and 77 years old and had been exposed to local corticosteroids preceding our evaluation. All patients demonstrated diffuse retinal whitening with severe vision loss on presentation. Polymerase chain reaction testing (PCR) was diagnostic in two patients, and histopathologic examination of a vitrectomy specimen was diagnostic in one patient. All cases of retinitis resolved with anti-parasitic medication; however, visual acuity failed to improve in all patients due to disease severity and presentation. Conclusions: Local corticosteroid injection may trigger or exacerbate toxoplasmosis chorioretinitis, leading to fulminant retinal necrosis and severe vision loss. Toxoplasma chorioretinitis should be considered in the differential diagnosis of patients presenting with clinical features of acute retinal necrosis, particularly following local corticosteroid injection regardless of their baseline systemic immune status. Diagnostic vitrectomy may be helpful in patients in whom PCR testing is negative and ocular toxoplasmosis is suspected. [ABSTRACT FROM AUTHOR]

A 64-year-old man with a past medical history of liver transplantation on chronic immunosuppressive therapy presented with gradual worsening of vision over 2 months in his right eye. His recent history of Aspergillus and Nocardia pneumonia with positive bronchoalveolar lavage, in concert with vitritis and subretinal abscess, were concerning for endogenous endophthalmitis. A sputum culture and transbronchial lung biopsy stains grew Nocardia farcinica although aqueous humor sampling was negative. He was treated with four serial amikacin intravitreal injections over the course of 4 weeks. Pars plana vitrectomy for worsening macular traction and subsequent cataract surgery resulted in significant clinical and anatomic improvement of vision to 20/60 and consolidation of the subretinal abscess. [ABSTRACT FROM AUTHOR]