Mimickers of anterior uveitis, scleritis and misdiagnoses- tips and tricks for the cornea specialist.

BACKGROUND: Anterior uveitis, inflammation of the anterior chamber and related structures, is a cohort of diseases that can present to almost any general or sub-specialty Ophthalmology practice. Its features classically involve anterior chamber cell and flare. Below the surface of these two signs exist a panoply of diagnoses. BODY: The purpose of this review is to provide a general framework for diagnoses of anterior uveitis that are often missed as well as non-uveitic pathologies that often mimic anterior uveitis. Diagnostic deviation in either direction can have vision-threatening and rarely life-threatening consequences for patients. Using a comprehensive literature review we have collected a broad spectrum of etiologies of anterior uveitis that are easily missed and non-uveitic pathologies that can masquerade as anterior uveitis. CONCLUSIONS: We present a focused review on specific misdiagnosed anterior uveitis pathologies and some of the conditions that can masquerade as anterior uveitis and scleritis.

Challenges in posterior uveitis-tips and tricks for the retina specialist.

PURPOSE: Posterior uveitis is a common chorioretinal pathology affecting all ages worldwide and is a frequent reason for referral to the retina clinic. The spectrum of etiologies for uveitis is very broad and includes infectious and auto-immune diseases. Inflammation can be confined to the eye or may be a part of systemic disease. A useful outline is therefore proposed to aid in the correct diagnosis of these challenging entities. The situation is further complicated by the fact that many neoplastic conditions resemble features of posterior uveitis; they are known as "masqueraders of uveitis". Here, we summarize different posterior uveitides that present with rare findings, along with masqueraders that can be difficult to distinguish. These conditions pose a diagnostic dilemma resulting in delay in treatment because of diagnostic uncertainty. METHODS: An extensive literature search was performed on the MEDLINE/PUBMED, EBSCO and Cochrane CENTRAL databases from January 1985 to January 2022 for original studies and reviews of predetermined diagnoses that include posterior uveitic entities, panuveitis and masquerade syndromes. RESULTS: We described conditions that can present as mimickers of posterior uveitis (i.e., immune check-points inhibitors and Vogt-Koyanagi-Harada-like uveitis; leukemia and lymphoma associated posterior uveitis), inflammatory conditions that present as mimickers of retinal diseases (i.e., Purtscher-like retinopathy as a presentation of systemic lupus erythematosus; central serous chorioretinopathy masquerading inflammatory exudative retinal detachment), and uveitic conditions with rare and diagnostically challenging etiologies (i.e., paradoxical inflammatory effects of anti-TNF-α; post vaccination uveitis; ocular inflammation after intravitreal injection of antiangiogenic drugs). CONCLUSION: This review of unique posterior uveitis cases highlights the overlapping features of posterior uveitis (paradoxical inflammatory effects of anti -TNF α and uveitis; Purtscher-like retinopathy as a presentation of systemic lupus erythematosus, …) and the nature of retinal conditions (ischemic ocular syndrome, or central retinal vein occlusion, amyloidosis, inherited conditions like retinitis pigmentosa, autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), etc.…) that may mimic them is represented. Careful review of past uveitis history, current medications and recent vaccinations, detailed examination of signs of past or present inflammation, eventually genetic testing and/ or multimodal retinal imaging (like fluorescein angiography, EDI-OCT, OCT-angiography for lupus Purtscher-like retinopathy evaluation, or ICG for central serous retinopathy, or retinal amyloid angiopathy) may aid in correct diagnosis.

Pediatric oral fluorescein angiography: a retrospective review from a single institution.

PURPOSE: To describe our experience with locally developed evidence-based guidelines for oral fluorescein angiography (FA) for retinal imaging in children. METHODS: The medical records of consecutive pediatric patients (≤18 years of age) at University of Pittsburgh Medical Center Children's Hospital Eye Center who underwent oral FA between November 1, 2018, and April 1, 2022, were reviewed retrospectively. Adherence to or deviation from the guidelines was noted at the time of testing. RESULTS: A total of 55 patients aged 3-18 with 79 examinations were included. No patient was excluded from the retrospective case review because of lack of recorded data. The main indications for oral FA included uveitis, retinal vasculopathy, disk pathology, and retinal lesions. Three children had transient side effects, and 1 had delayed urticaria 4 hours after examination. No child had anaphylaxis. One patient had suboptimal imaging due to nonadherence to the guidelines-recommended fasting protocol. All other examinations (78/79), where guidelines were followed, provided images adequate for clinical decision making. CONCLUSIONS: Based on our experience, we recommend that oral FA be considered, especially in children where intravenous access is less well tolerated while awake. Informed consent that includes the possibility of delayed side effects is advisable.

Coagulase-negative staphylococcal endophthalmitis: clinical severity and outcomes based on speciation.

OBJECTIVE: To identify characteristics and visual outcomes of coagulase-negative staphylococcal (CoNS) endophthalmitis in the era after the Endophthalmitis Vitrectomy Study. DESIGN: Single-centre retrospective analysis. PARTICIPANTS: Forty-two samples from 40 patients with documented CoNS endophthalmitis. METHODS: Visual acuity outcomes of CoNS endophthalmitis were assessed in relation to species and type of treatment instituted (i.e., pars plana vitrectomy [PPV] versus vitreous tap and injection of intravitreal antibiotics [T&I]) on 42 samples from 40 patients. RESULTS: Staphylococcus epidermidis was the most prevalent CoNS in our study. Cataract surgery and intravitreal injections were the most common sources for acute CoNS endophthalmitis. Eyes presenting with hand motion or better vision had similar mean final vision after either intravitreal antibiotics or PPV, whereas those with light perception or worse vision at onset had better outcomes after PPV only. Subanalysis showed that patients with S. epidermidis endophthalmitis (n = 39 eyes) had similar visual outcomes with either intravitreal injections or PPV regardless of visual acuity. Hypopyon and vitritis are not always present. CONCLUSIONS: Patients with S. epidermidis endophthalmitis may benefit similarly from either early vitrectomy or intravitreal antibiotic injections regardless of visual acuity. This finding may be a supplement to the complements the management standards set forth by the Endophthalmitis Vitrectomy Study.

Herpes zoster ophthalmicus: frequency and risk factors for developing uncommon ocular manifestations.

OBJECTIVE: To determine the frequency of herpes zoster ophthalmicus (HZO) and assess risk factors for developing uncommon ocular manifestations of laboratory-verified HZO. DESIGN: Retrospective cohort study. METHODS: The frequency of HZO out of all herpes zoster cases was calculated using International Classification of Diseases codes for patients seen at the University of Pittsburgh Medical Center from January 1, 2004 to October 31, 2021. We also collected demographic and clinical data of patients with HZO identified by polymerase chain reaction (PCR) detection of varicella zoster virus from January 1, 2011 to December 31, 2020. RESULTS: The frequency of HZO from 2004 to 2021 in all ages was 4.2% and ranged from 2.7% to 6.7% annually, with a consistent increase of 2.9% from 2012 to 2021. After the live zoster vaccine became available in 2008, the frequency of HZO decreased by 5.1% from 2008 to 2012 in patients aged 60 and older. Among 50 cases of PCR-verified HZO, 62% represented clinically-common ocular manifestations, mostly comprised of 13 cases of keratitis and 10 cases of anterior uveitis. Fifteen cases of acute retinal necrosis (ARN) represented the majority of uncommon HZO manifestations (38%), which were significantly more likely to occur in immunosuppressed patients (unadjusted odds ratio 4.55, 95% confidence interval 1.29-13.83). CONCLUSIONS: The overall frequency of HZO from 2004 to 2021 was 4.2% and has increased annually since 2012. Uncommon ocular manifestations of PCR-verified HZO, mostly comprised of ARN, were more likely to occur in immunosuppressed patients.

Relentless placoid chorioretinitis: A review of four cases in pediatric and young adult patients with a discussion of therapeutic strategies.

Introduction: Relentless placoid chorioretinitis (RPC) is a rare, bilateral disease of the retinal pigment epithelium. The clinical course is prolonged and relapsing. No standard treatment has been established to date. The purpose of this case series is to report four cases of RPC in pediatric and young adult patients in which varying treatments were used, comparing them to previously published cases. Methods: A literature review was conducted to investigate currently published presentations and treatment options for RPC. A multicenter retrospective chart review was also performed on four consecutive patients. These patients were diagnosed with RPC because of new chorioretinitis lesions continuing to appear without or despite therapy for 5-36 months (2 patients), with a clinical course prolonged and relapsing, or because of the atypical location of the multiple lesions (>50) extending from the posterior pole to the equator and mid-peripheral retina (all four patients), which were not consistent with other entities like acute posterior multifocal placoid pigment epitheliopathy and serpiginous choroiditis. Results: All four cases of RPC received oral or IV steroids acutely, and three of these patients were transitioned to a steroid-sparing agent and biologic therapy: anti-TNF alpha or anti-IL-6. Quiescence of the chorioretinitis lesions was obtained after 7 months, 1 month, and 36 months; however, the latter had issues with treatment adherence. Mycophenolate mofetil was insufficient to control the disease in one patient, but tocilizumab and infliximab thereafter were effective after cessation of adalimumab due to side effects. Adalimumab when started the first month after the presentation was effective in controlling the disease in one patient. After the failure of interferon-alpha-2a, one patient displayed long-term control with infliximab. One patient did not require a steroid-sparing agent after oral prednisone taper as there was no evidence of progression or recurrence. Conclusion: This case series adds to the current knowledge regarding potential treatments for RPC, specifically the use of anti-TNF-alpha treatment and anti-IL-6 tocilizumab. In this case study, relapses of RPC were found among patients on mycophenolate mofetil and interferon-alpha-2a, and one case did not relapse on oral steroids without a steroid-sparing agent. Our findings suggest that adalimumab, infliximab, and tocilizumab may be useful medications to obtain quiescence of RPC.

OCT Angiography in Noninfectious Uveitis: A Description of Five Cases and Clinical Applications.

BACKGROUND: Optical coherence tomography angiography (OCTA) is a noninvasive imaging modality used to analyze the retinochoroidal vasculature and detect vascular flow. The resulting images can be segmented to view each vascular plexus individually. While fluorescein angiography is still the gold standard for the diagnosis of posterior uveitis, it has limitations, and can be replaced by OCTA in some cases. METHODS: This case series describes five patients with posterior noninfectious uveitis and their description by OCTA. RESULTS: Cases included lupus retinopathy (n = 1) for which OCTA showed ischemic maculopathy as areas of flow deficit at the superficial and deep capillary plexus; choroidal granulomas (n = 1) with a non-detectable flow signal in the choroid; active punctate inner choroiditis and multifocal choroiditis (n = 1) with OCTA that showed active inflammatory chorioretinal lesions as non-detectable flow signals in choriocapillaris and choroid; dense type 2 inflammatory secondary neovascularization (n = 1) associated with active choroiditis; and acute posterior multifocal placoid pigment epitheliopathy (APMPPE) (n = 1) without flow abnormalities at the superficial and deep retinal plexuses but non-detectable flow at the levels of the choriocapillaris and choroid. CONCLUSIONS: Ophthalmologists can use OCTA to identify inflammatory changes in retinal and choroidal vasculature, aiding in the diagnosis, management, and monitoring of posterior uveitis.

Choroidal Mass in a Patient with Undiagnosed Pulmonary Langerhans' Cell Histiocytosis.

BACKGROUND: Langerhan cell histiocytosis (LCH), although not a common cause, should be kept in the differential diagnosis for a patient that presents with a choroidal mass. CASE PRESENTATION: A 28-year-old female presented with a 4-day history of vision loss and associated pain in her right eye. EXAMINATION AND INVESTIGATIONS: A dilated fundus examination revealed a deep subretinal, orange, mottled lesion with associated serous retinal detachment. Ultrasonography demonstrated a solid mass at the posterior pole. Fluorescein angiography revealed corresponding, small, punctate, hyperfluorescent areas with leakage and pooling in the late phase outlining the subretinal fluid. Optical coherence tomography confirmed the choroidal elevation and subretinal fluid. In addition to starting oral steroids for addressing the patient's acute symptoms, a metastatic workup was ordered due to the lesion's appearance. Diagnosis: Computed tomography (CT) of the chest showed nodular lesions and subsequent lung biopsy was S-100 and CD1a positive, diagnostic of Langerhan's cell histiocytosis (LCH). TREATMENT AND OUTCOME: The patient was treated with six cycles of vinblastine and prednisolone therapy followed with a subsequent taper of steroids. Complete resolution of signs and symptoms was noted. DISCUSSION: A review of all reported cases of ophthalmic LCH with or without choroidal involvement was conducted. Diagnostic and therapeutic approaches described in these reportshave been summarized in the current manuscript. This case highlights the importance of pursuing a systemic workup in patients with uveal mass lesions. LCH should be considered in the differential of every choroidal mass.

Bleb Associated Xen Gel Stent Endophthalmitis: A Case Report and Review of Literature.

PURPOSE: To report a case of a unique late complication of the Xen gel stent, stent-related endophthalmitis was preceded by flattening of the bleb. CASE REPORT: A 63-year-old female was presented with late-onset endophthalmitis preceded by flattening of the bleb two years post-insertion of Xen gel stent. B-scan of the posterior chamber revealed vitritis and hyaloid condensation, with no viral, fungal, or bacterial pathologies identified on anterior chamber tap. The patient's eye responded to injections of intravitreal antibiotics. CONCLUSION: Endophthalmitis can occur as late as 2 years after implantation of glaucoma drainage device implants (GDIs) like the Xen gel stent if bleb flattening or leaking leads to contact of the stent with the conjunctiva. Therefore, in case of blebs getting flat, ophthalmologists should watch them more often. Intravitreal antibiotics may also be effective rather than surgical removal in the case of a non-eroded stent complicated by endophthalmitis.

Atypical Case of MOG Antibody-Associated Optic Neuritis with Roth Spots.

PURPOSE: To report an atypical case of MOG antibody-associated optic neuritis with Roth spots and widespread retinal hemorrhages. CASE REPORT: A 49-year-old woman complained of 1 week history painful visual loss in the left eye. Funduscopy exam showed a severe optic disc edema associated with multiple peripapillar hemorrhages, peripheral retinal hemorrhages and Roth spots in the left eye. Orbit MRI revealed an hyperintensity in the left optic nerve, enhanced with gadolinium. The serum Myelin Oligodendrocyte (MOG) antibodies was found positive. Early intravenous high dose of steroids rapidly improved visual acuity and fundus abnormalities rapidly resolved. CONCLUSION: Retinal hemorrhages can also be detected in case of optic disc edema associated with an optic neuritis, as seen in MOGAD.

Fundus Changes in the Offspring of Mothers With Confirmed Zika Virus Infection During Pregnancy in French Guiana, Guadeloupe, and Martinique, French West Indies.

Importance: Most ocular lesions have been described for children with congenital Zika syndrome. The frequency of finding ocular abnormalities is unknown among children exposed to Zika virus (ZIKV) during pregnancy. This study was conducted on newborns whose mothers were positive for ZIKV, confirmed with reverse-transcription polymerase chain reaction (RT-PCR) testing. Objective: To report ocular fundus manifestations in newborns with congenital ZIKV exposure in French Guiana, Martinique, and Guadeloupe, French West Indies, to assess its prevalence. Risk factors, such as the presence of extraocular fetopathies and the gestational term at infection, were sought. Design, Setting, and Participants: This was a cross-sectional multicentric study, conducted from August 1, 2016, to April 30, 2019, for which data were collected prospectively. The study inception was at the beginning of 2016 from the onset of the ZIKV epidemic in the French West Indies. Newborns whose mothers tested positive (by RT-PCR) for ZIKV during pregnancy were included. Interventions: Fundus examination was performed using widefield retinal imaging after pupil dilation. Infection date, delivery mode, and newborn measurements were collected. Main Outcomes and Measures: Anomalies of the vitreous, choroid, retina, and optic disc. Results: A total of 330 children (mean [SD] age, 68 [IQR, 22-440] days; 170 girls [51.5%]) were included. Eleven children (3.3%) had perivascular retinal hemorrhages, and 3 (0.9%) had lesions compatible with congenital ZIKV infection: 1 child had torpedo maculopathy, 1 child had a chorioretinal scar with iris and lens coloboma, and 1 child had a chorioretinal scar. Retinal hemorrhages were found at childbirth during early screening. Lesions compatible with congenital ZIKV infection were not associated with the presence of extraocular fetopathy. Microcephaly was not associated with lesions compatible with congenital ZIKV infection (odds ratio [OR], 9.1; 95% CI, 0.8-105.3; P = .08), but severe microcephaly was associated with an OR of 81 (95% CI, 5.1-1297.8; P = .002). Conclusions and Relevance: Results of this cross-sectional study suggest that the ocular anomalies found may be associated with ZIKV in 0.9% of the exposed population. Ocular lesions were rare, affected mostly the choroid and retina, and seemed to be associated with choroiditis-related scarring that developed during fetal growth.

NiONP-Induced Oxidative Stress and Mitochondrial Impairment in an In Vitro Pulmonary Vascular Cell Model Mimicking Endothelial Dysfunction.

The development and use of nanomaterials, especially of nickel oxide nanoparticles (NiONPs), is expected to provide many benefits but also has raised concerns about the potential human health risks. Inhaled NPs are known to exert deleterious cardiovascular side effects, including pulmonary hypertension. Consequently, patients with pulmonary hypertension (PH) could be at increased risk for morbidity. The objective of this study was to compare the toxic effects of NiONPs on human pulmonary artery endothelial cells (HPAEC) under physiological and pathological conditions. The study was conducted with an in vitro model mimicking the endothelial dysfunction observed in PH. HPAEC were cultured under physiological (static and normoxic) or pathological (20% cycle stretch and hypoxia) conditions and exposed to NiONPs (0.5-5 µg/cm2) for 4 or 24 h. The following endpoints were studied: (i) ROS production using CM-H2DCF-DA and MitoSOX probes, (ii) nitrite production by the Griess reaction, (iii) IL-6 secretion by ELISA, (iv) calcium signaling with a Fluo-4 AM probe, and (v) mitochondrial dysfunction with TMRM and MitoTracker probes. Our results evidenced that under pathological conditions, ROS and nitrite production, IL-6 secretions, calcium signaling, and mitochondria alterations increased compared to physiological conditions. Human exposure to NiONPs may be associated with adverse effects in vulnerable populations with cardiovascular risks.

Cellular and molecular mechanisms of NiONPs toxicity on eel hepatocytes HEPA-E1: An illustration of the impact of Ni release from mining activity in New Caledonia.

Anthropic activities such as open pit mining, amplify the natural erosion of metals contained in the soils, particularly in New Caledonia, leading to atmospheric emission of nickel oxide nanoparticles (NiONPs). These particles are produced during extraction end up in aquatic ecosystems through deposition or leaching in the rivers. Despite alarming freshwater Ni concentrations, only few studies have focused on the cellular and molecular mechanisms of NiONPs toxicity on aquatic organisms and particularly on eels. Those fish are known to be sensitive to metal contamination, especially their liver, which is a key organ for lipid metabolism, detoxification and reproduction. The objective of this study was to assess in vitro the cytotoxic effects of NiONPs on Anguilla japonica hepatocytes, HEPA-E1. HEPA-E1 were exposed to NiONPs (0.5-5 µg/cm2) for 4 or 24 h. Several endpoints were studied: (i) viability, (ii) ROS production, SOD activity and selected anti-oxidant genes expression, (iii) inflammation, (iv) calcium signalling, (v) mitochondrial function and (vi) apoptosis. The results evidenced that NiONPs induce a decrease of cell viability and an increase in oxidative stress with a significant superoxide anion production. An increase of mitochondrial calcium concentration and a decrease of mitochondrial membrane potential were observed, leading to apoptosis. These results underline the potential toxic impact of NiONPs on eels living in mining areas. Therefore, eel exposure to NiONPs can affect their migration and reproduction in New Caledonia.

Hidden in the Eyes-Recurrence of Systemic Hemopathies Reportedly "In Remission": Six Cases and Review of Literature.

Background and Objectives: Secondary ocular localizations of hematological malignancies are blinding conditions with a poor prognosis, and often result in a delay in the diagnosis. Materials and Methods: We describe a series of rare cases of ocular involvement in six patients with hematological malignancies, reportedly in remission, who presented secondary ocular localizations, challenging to diagnose. Two patients had an acute lymphoblastic leukemia (ALL) and developed either a posterior scleritis or a pseudo-panuveitis with ciliary process infiltration. One patient had iris plasmacytoma and developed an anterior uveitis as a secondary presentation. Two patients had a current systemic diffuse large B-cell lymphoma (DLBCL) and were referred either for intermediate uveitis or for papilledema and vitritis with secondary retinitis. Finally, one patient with an acute myeloid leukemia (AML) presented a conjunctival localization of a myeloid sarcoma. We herein summarize the current knowledge of ophthalmologic manifestations of extramedullary hematopathies. Results: Inflammatory signs were associated with symptomatic infiltrative lesions well displayed in either the iris, the retina, the choroid, or the cavernous sinus, from the admission of the patients in the ophthalmological department. These findings suggest that patients with ALL, AML, systemic DLBCL, and myeloma can present with ophthalmic involvement, even after having been reported as in remission following an effective systemic treatment and/or allograft. Conclusions: Early detection of hidden recurrence in the eyes may permit effective treatment. Furthermore, oncologists and ophthalmologists should be aware of those rare ocular malignant locations when monitoring patient's progression after initial treatment, and close ophthalmologic examinations should be recommended when detecting patient's ocular symptoms after treatment.

Indocyanine Green Angiography Features in Acute Syphilitic Posterior Placoid Chorioretinitis.

PURPOSE: Acute syphilitic posterior placoid chorioretinitis (ASPPC) is a rare clinical manifestation of ocular syphilis. The cause of the placoid lesion is still up for debate but could be caused by an impaired choriocapillaris perfusion. However, less attention has been paid to the hypofluorescence of the plaque on late-phase indocyanine green angiography (ICGA). The aim of this study was to comprehensively analyze multimodal imaging findings in patients with ASPPC and to highlight the value of ICGA for the diagnosis of ASPPC. DESIGN: Retrospective observational case study. METHODS: The medical records of patients with uveitis who consulted our tertiary center between 2012 and December 2015 were reviewed. Patients who were diagnosed with uveitis related to syphilis infection with posterior placoid lesions seen on multimodal imaging were included. We compared the aspect of ASPPC on fundus color photography, blue autofluorescence, fluorescein angiography, optical coherence tomography, and early-, mid- and late-phase ICGA. RESULTS: Fifteen eyes of 12 patients were included in the study. Hypofluorescent plaques were seen on late-phase ICGA in all eyes, corresponding to the placoid lesions visible on blue autofluorescence, while the choriocapillaris filling was normal on fluorescein angiography and ICGA. Within the plaques, optical coherence tomography showed ellipsoid zone disruptions, outer retinal disruptions, and retinal pigment epithelium granulations. CONCLUSION: ASPPC could be caused by retinal pigment epithelium dysfunction secondary to an infectious or inflammatory disorder, characterized by a hypofluorescence visible only on late-phase ICGA, and resulting in photoreceptor disruptions. The RPE impairment was reversible after prompt antibiotic treatment.

Cytokines, chemokines and growth factors profile in human aqueous humor in idiopathic uveitis.

To investigate which cytokines, chemokines and growth factors are involved in the immunopathogenesis of idiopathic uveitis, and whether cytokine profiles are associated with. Serum and aqueous humor (AH) samples of 75 patients with idiopathic uveitis were analyzed by multiplex immunoassay. Infectious controls consisted of 16 patients with ocular toxoplasmosis all confirmed by intraocular fluid analyses. Noninfectious controls consisted of 7 patients with Behçet disease related uveitis and 15 patients with sarcoidosis related uveitis. The control group consisted of AH and serum samples from 47 noninflammatory control patients with age-related cataract. In each sample, 27 immune mediators ± IL-21 and IL-23 were measured. In idiopathic uveitis, 13 of the 29 mediators, including most proinflammatory and vascular mediators such as IL-6, IL-8, IL-12, G-CSF, GM-CSF, MCP-1, IP-10, TNF-α and VEGF, were significantly elevated in the aqueous humor when compared to all controls. Moreover, IL-17, IP-10, and IL-21, were significantly elevated in the serum when compared to all controls. We clustered 4 subgroups of idiopathic uveitis using a statistical analysis of hierarchical unsupervised classification, characterized by the order of magnitude of concentrations of intraocular cytokines. The pathogenesis of idiopathic uveitis is characterized by the presence of predominantly proinflammatory cytokines and chemokines and vascular endothelial growth factor with high expression levels as compared to other causes of uveitis. There are indications for obvious Th-1/ IL21-Th17 pathways but also IL9-Th9 and increased IFN-γ-inducing cytokine (IL12) and IFN-γ-inducible CXC chemokine (IP-10). The combined data suggest that immune mediator expression is different among idiopathic uveitis. This study suggests various clusters among the idiopathic uveitis group rather than one specific uveitis entity.

NiONPs-induced alteration in calcium signaling and mitochondrial function in pulmonary artery endothelial cells involves oxidative stress and TRPV4 channels disruption.

In New Caledonia, anthropic activities, such as mining, increase the natural erosion of soils in nickel mines, which in turn, releases nickel oxide nanoparticles (NiONPs) into the atmosphere. Pulmonary vascular endothelial cells represent one of the primary targets for inhaled nanoparticles. The objective of this in vitro study was to assess the cytotoxic effects of NiONPs on human pulmonary artery endothelial cells (HPAEC). Special attention will be given to the level of oxidative stress and calcium signaling, which are involved in the physiopathology of cardiovascular diseases. HPAEC were exposed to NiONPs (0.5-150 µg/cm2) for 4 or 24 h. The following different endpoints were studied: (i) ROS production using CM-H2DCF-DA probe, electron spin resonance, and MitoSOX probe; the SOD activity was also measured (ii) calcium signaling with Fluo4-AM, Rhod-2, and Fluo4-FF probes; (iii) inflammation by IL-6 production and secretion and, (iv) mitochondrial dysfunction and apoptosis with TMRM and MitoTracker probes, and AnnexinV/PI. Our results have evidenced that NiONPs induced oxidative stress in HPAEC. This was demonstrated by an increase in ROS production and a decrease in SOD activity, the two mechanisms seem to trigger a pro-inflammatory response with IL-6 secretion. In addition, NiONPs exposure altered calcium homeostasis inducing an increased cytosolic calcium concentration ([Ca2+]i) that was significantly reduced by the extracellular calcium chelator EGTA and the TRPV4 inhibitor HC-067047. Interestingly, exposure to NiONPs also altered TRPV4 activity. Finally, HPAEC exposure to NiONPs increased intracellular levels of both ROS and calcium ([Ca2+]m) in mitochondria, leading to mitochondrial dysfunction and HPAEC apoptosis.

Choroidal imaging in uveitis: An update.

An important goal of advancements in ocular imaging algorithms and devices has been to improve the image acquisition and resolution of deeper ocular tissues, namely the choroid and its vasculature that are otherwise inaccessible to direct clinical examination. These advancements have contributed to the understanding of the pathophysiology of a number of ocular inflammatory conditions. We focus on the imaging characteristics of clinical conditions where imaging the choroid has improved or radically changed the understanding of the disease, has helped in differentiation of phenotypically similar but distinct lesions, and where imaging features have proven vital for monitoring disease activity. The last two decades have seen some major developments in ocular imaging relevant to uveitis. The current review addresses both the imaging characteristics and their interpretation on conventional modalities such as fundus photography, fluorescein angiography, indocyanine green angiography, and fundus autofluorescence and the recent additions in the armamentarium including optical coherence tomography (OCT) with enhanced depth imaging, swept-source OCT, and OCT angiography.

NEW OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS ON AN INTRARETINAL VASCULAR PROCESS SECONDARY TO TOXOPLASMA RETINOCHOROIDITIS: 2 CASE REPORTS.

BACKGROUND/PURPOSE: To determine which retinal layer is primarily involved in intraretinal vascular processes associated with Toxoplasma retinochoroiditis using multimodal imaging, including optical coherence tomography angiography (OCTA). METHODS: Toxoplasma retinal lesions were analyzed through multimodal imaging, including color fundus photographs, fluorescein angiography, indocyanine green angiography, spectral-domain OCT, and OCTA. RESULTS: Two patients with atypical features of Toxoplasma retinochoroiditis are described in the acute phase. The first patient presented with a primary episode of acute Toxoplasma retinitis associated with an intraretinal abnormal vascular process that was detected at the acute phase by indocyanine green angiography and was better delineated by OCTA. Seven months later, the intraretinal vascular process had fully resolved on OCTA imaging. The second patient presented with a recurrence of active Toxoplasma retinochoroiditis adjacent to a pre-existing pigmented scar. He had a similar abnormal intraretinal vascular process that was identified on both fluorescein angiography at the early phase and indocyanine green angiography, which was also confirmed by OCTA imaging. CONCLUSION: We report a new finding associated with Toxoplasma chorioretinitis: an abnormal intraretinal vascular process that resolved without anti-vascular endothelial growth factor therapy but after toxoplasmosis treatment alone.