Paediatric non-infectious granulomatous uveitis: a retrospective cohort study.

INTRODUCTION: Paediatric granulomatous uveitis (PGU) is rare. In addition, lack of awareness often leads to delayed diagnosis and poor visual outcome. Identifying the underlying cause and deciding how best to treat each patient is challenging. OBJECTIVES: To evaluate the demographics, aetiologies, complications, treatments, and visual prognosis of paediatric non-infectious granulomatous uveitis. METHODS: Retrospective chart review of non-infectious PGU occurring in children before the age of 16 years recruited from the Paediatric Rheumatology Unit, Bicêtre Hospital, France, from 2001 to 2023. RESULTS: We included 50 patients with 90 affected eyes: 29 with idiopathic uveitis, 15 with sarcoidosis, 5 with juvenile idiopathic arthritis, and one with Vogt-Koyanagi-Harada disease. Median age at diagnosis was 9.8 years (range 7.2-12.5). The sex-ratio M/F was 0.52. The most common features of PGU were: panuveitis (56%), bilateral (84%), and chronic (84%). Sarcoidosis was the most frequent diagnosis after idiopathic disease, particularly in the presence of lymphopenia and hypergammaglobulinemia. Uveomeningitis was present in 12% of cases. Upon diagnosis, ocular complications were present in 68 of 90 eyes (76%) particularly in cases of panuveitis. The most commonly used treatments were systemic corticosteroids (72%) and methotrexate (80%). Twenty-three percent of eyes were in remission at last follow-up, 68% were inactive and 4% remained active. The median duration of follow-up was 5.8 years. CONCLUSION: We report the largest cohort of PGU. PGU were mostly idiopathic and had a high rate of complications. Sarcoid and idiopathic panuveitis are serious illnesses in which disease-modifying therapy should be initiated at diagnosis to improve management.

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.

Switching to subtenon triamcinolone acetonide does not jeopardize the functional and anatomic outcomes of dexamethasone implant treated eyes with diabetic macular edema.

BACKGROUND: Intraocular dexamethasone implant (DEXi) is an efficient treatment for diabetic macular edema (DME). However, it may be unavailable or contraindicated. Triamcinolone acetonide is another corticosteroid that has proved to be safe and effective in treating macular edema complicating various diseases including diabetes. The purpose of this study is to evaluate the outcomes of a switch from DEXi to subtenon triamcinolone acetonide (STTA) and back, in eyes with DME. METHODS: Retrospective study. DME eyes that had been treated with DEXi and switched to STTA between October 2018 and February 2019 (stock shortage of DEXi) were included. The functional and anatomical outcomes of the switch and switch-back were studied. RESULTS: 26 eyes of 17 patients (mean age 67.1 ± 8.2 years) were considered. The mean baseline visual acuity (VA) was 0.35 ± 0.17 decimals remaining stable after DEXi, STTA and switch-back to DEXi. The mean central macular thickness (CMT) was 492.7 ± 32.8 µm initially, decreasing to 294.3 ± 133.4 µm after DEXi, 369.9 ± 182.3 µm after STTA and 297.6 ± 72.0 µm after switching back to DEXi (all p < 0.05 versus baseline). Compared to baseline, the CMT reduction was numerically better after DEXi and switching back to DEXi than after STTA (mean reduction: -200.4 µm, -167.7 µm, and -95.08 µm respectively, p = 0.13). Intraocular pressure was comparable after DEXi and STTA. CONCLUSION: DEXi is the steroid of choice in DME. However, STTA can be a cost-effective alternative when DEXi is unavailable or contraindicated. This study suggests that STTA may be used in the context of a step therapy in DME.

Efficacity and Safety of the Fluocinolone Acetonide Implant in Uveitic Macular Edema: A Real-Life Study from the French Uveitis Network.

PURPOSE: To evaluate the safety and efficacy of the fluocinolone acetonide implant (FAi, Iluvien® Horus pharma, Nice, France) in non-infectious uveitic macular edema (UME) and to approach the predictive factors of treatment response. METHODS: This retrospective, multicenter real-life study included patients with chronic non-infectious UME who received intravitreal FAi after at least two dexamethasone implants (DEXi). RESULTS: Twenty-six eyes from 22 patients (73.1% of females) were included. The mean age was 60.4 ± 16 years. The mean follow-up was 11.4 ± 2 months. The mean baseline best-corrected visual acuity (BCVA) was 0.43 ± 0.36 LogMAR, improving significantly after 1, 3, 6 and 12 months (all p < 0.05 vs. baseline). The mean baseline central macular thickness (CMT) was 429 ± 110 µm, improving significantly after 1, 3, 6 and 12 months (all p < 0.05 vs. baseline). Five eyes (19.2%) developed ocular hypertension during the follow-up, requiring initiation or strengthening of intraocular pressure lowering medication. The majority of eyes (77%) did not require any rescue DEXi during the available 12-month follow-up. The resolution of UME after DEXi seemed to predict the anatomical response after FAi. The baseline presence of a disorganization of the inner retinal layers (DRIL) and hyperreflective foci (HRF) were both associated with a higher likelihood of requiring rescue DEXi injections. CONCLUSION: FAi implantation led to a significant BCVA and CMT improvement with a good safety profile over the 12-month follow-up. Predictive factors of treatment outcomes seem to include the anatomical response to DEXi and the presence of DRIL and HRF at baseline.

AUTOMATED DETECTION OF VITRITIS USING ULTRAWIDE-FIELD FUNDUS PHOTOGRAPHS AND DEEP LEARNING.

BACKGROUND/PURPOSE: Evaluate the performance of a deep learning algorithm for the automated detection and grading of vitritis on ultrawide-field imaging. METHODS: Cross-sectional noninterventional study. Ultrawide-field fundus retinophotographs of uveitis patients were used. Vitreous haze was defined according to the six steps of the Standardization of Uveitis Nomenclature classification. The deep learning framework TensorFlow and the DenseNet121 convolutional neural network were used to perform the classification task. The best fitted model was tested in a validation study. RESULTS: One thousand one hundred eighty-one images were included. The performance of the model for the detection of vitritis was good with a sensitivity of 91%, a specificity of 89%, an accuracy of 0.90, and an area under the receiver operating characteristics curve of 0.97. When used on an external set of images, the accuracy for the detection of vitritis was 0.78. The accuracy to classify vitritis in one of the six Standardization of Uveitis Nomenclature grades was limited (0.61) but improved to 0.75 when the grades were grouped into three categories. When accepting an error of one grade, the accuracy for the six-class classification increased to 0.90, suggesting the need for a larger sample to improve the model performances. CONCLUSION: A new deep learning model based on ultrawide-field fundus imaging that produces an efficient tool for the detection of vitritis was described. The performance of the model for the grading into three categories of increasing vitritis severity was acceptable. The performance for the six-class grading of vitritis was limited but can probably be improved with a larger set of images.

Cerebro-Ocular Toxocariasis Revealed by Bilateral Cystoid Macular Edema.

DESIGN: Case Report Case description: This report describes the case of a female patient diagnosed with oculo-cerebral toxocariasis manifesting initially in the form of isolated bilateral cystoid macular edema. Diagnosis was made by means of positive anterior chamber and lumbar puncture western blots. The unusual presentation, ancillary findings and treatment are discussed. The control of intraocular inflammation that was only partially responsive to steroids was eventually achieved with pegylated interferon alfa-2a. CONCLUSION: Isolated macular edema is a rare presentation of ocular toxocariasis. Interferon alfa-2a may prove useful in case of insufficient control of inflammation.

The Infectious Uveitis Treatment Algorithm Network (TITAN) Report 1-global current practice patterns for the management of Herpes Simplex Virus and Varicella Zoster Virus anterior uveitis.

AIMS: To present current expert practice patterns and to formulate a consensus for the management of HSV and VZV AU by uveitis specialists worldwide. METHODS: A two-round online modified Delphi survey with masking of the study team was conducted. Responses were collected from 76 international uveitis experts from 21 countries. Current practices in the diagnosis and treatment of HSV and VZV AU were identified. A working group (The Infectious Uveitis Treatment Algorithm Network [TITAN]) developed data into consensus guidelines. Consensus is defined as a particular response towards a specific question meeting ≥75% of agreement or IQR ≤ 1 when a Likert scale is used. RESULTS: Unilaterality, increased intraocular pressure (IOP), decreased corneal sensation and diffuse or sectoral iris atrophy are quite specific for HSV or VZV AU from consensus opinion. Sectoral iris atrophy is characteristic of HSV AU. Treatment initiation is highly variable, but most experts preferred valacyclovir owing to simpler dosing. Topical corticosteroids and beta-blockers should be used if necessary. Resolution of inflammation and normalisation of IOP are clinical endpoints. CONCLUSIONS: Consensus was reached on several aspects of diagnosis, choice of initial treatment, and treatment endpoints for HSV and VZV AU. Treatment duration and management of recurrences varied between experts.

The Infectious Uveitis Treatment Algorithm Network (TITAN) Report 2-global current practice patterns for the management of Cytomegalovirus anterior uveitis.

AIMS: To present current practice patterns in the diagnosis and management of Cytomegalovirus anterior uveitis (CMV AU) by uveitis experts worldwide. METHODS: A two-round modified Delphi survey with masking of the study team was performed. Based on experience and expertise, 100 international uveitis specialists from 21 countries were invited to participate in the survey. Variation in the diagnostic approaches and preferred management of CMV AU was captured using an online survey platform. RESULTS: Seventy-five experts completed both surveys. Fifty-five of the 75 experts (73.3%) would always perform diagnostic aqueous tap in suspected CMV AU cases. Consensus was achieved for starting topical antiviral treatment (85% of experts). About half of the experts (48%) would only commence systemic antiviral treatment for severe, prolonged, or atypical presentation. The preferred specific route was ganciclovir gel 0.15% for topical treatment (selected by 70% of experts) and oral valganciclovir for systemic treatment (78% of experts). The majority of experts (77%) would commence treatment with topical corticosteroid four times daily for one to two weeks along with antiviral coverage, with subsequent adjustment depending on the clinical response. Prednisolone acetate 1% was the drug of choice (opted by 70% of experts). Long-term maintenance treatment (up to 12 months) can be considered for chronic course of inflammation (88% of experts) and those with at least 2 episodes of CMV AU within a year (75-88% of experts). CONCLUSIONS: Preferred management practices for CMV AU vary widely. Further research is necessary to refine diagnosis and management and provide higher-level evidence.

Atypical retinopathy in ataxia with vitamin E deficiency: report of a sibship.

Typical retinitis pigmentosa (RP) may not be the only retinal phenotype encountered in ataxia with vitamin E deficiency (AVED). The following short case series describes a novel form of retinopathy in AVED. We describe two patients with AVED belonging to the same consanguineous sibship. Both presented an unusual retinopathy consisting of scattered, multifocal, nummular, hyperautofluorescent atrophic retinal patches. The retinopathy remained stable under vitamin E supplementation. We hypothesize these changes to be the result of arrested AVED-related RP following early supplementation with α-tocopherol acetate.

Pan fibroblast growth factor receptor inhibitor associated retinopathy.

PURPOSE: To report a case of Fibroblast Growth Factor Receptor inhibitor (FGFRi) associated retinopathy in a patient treated with Erdafitinib. CASE REPORT: A patient with a history of non-muscle invasive urothelial carcinoma treated with Erdafitinib developed symptomatic unifocal bilateral serous retinal detachments (SRD) eight weeks after starting this new treatment. Six months after discontinuing the drug, the SRDs resolved and visual acuity recovered to baseline. However, hyper and hypo auto fluorescent lesions were still visible on fundus autofluorescence, suggesting a still ongoing retinal pigment epithelium (RPE) impairment. CONCLUSIONS: Cancer treatments using FGFRi are showing promising results but their ocular toxicity is not well reported nor fully understood. Oncologists should be aware of the potential risks associated with FGFRi and involve ophthalmologists for the follow-up of their patients. The toxicity of FGFRi seems to resolve after drug continuation, but a certain degree of infra clinical RPE impairment may persist. Longer term follow-ups are warranted to further understand the effects of FGFRi on the RPE.

Ocular Toxocariasis in Adult Caucasian Patients: Clinical Presentations and Treatment Outcomes.

PURPOSE: To report the clinical features and treatment outcomes in adult Caucasians with ocular toxocariasis (OT) and investigate their prognosis depending on their serological status. METHODS: Retrospective observational cohort study (2016-2021) including consecutive adults with uveitis and positive western blot (WB) in the aqueous humor or vitreous. The presence of serum antibodies was not necessary for inclusion, allowing to compare the outcomes depending on the serological status. RESULTS: Seventeen eyes of 15 patients were included. Mean age at diagnosis was 51.9 years. Vitreous inflammation was the most frequent sign (100%). Vitreoretinal tractions (41.2%) and chorioretinal granulomas (58.8%) were less prevalent. Atypical features were: spontaneous intravitreal hemorrhage (23.5%), exudative retinal detachment (11.8%), isolated macular edema (17.6%), papillitis (29.4%) and vasculitis (47.1%). Twenty percent of patients had a positive serum serology. Baseline clinical features did not differ statistically depending on the serological status; however, the degree of inflammation was numerically higher in patients with negative serology. Overall, macular thickness, anterior and posterior segment inflammation improved significantly after treatment with oral albendazole, systemic ± local corticosteroids. Vitrectomy (47.1%) was performed in case of persistent vitritis (62.5%), retinal detachment (12.5%) and intravitreous hemorrhage (25%). CONCLUSION: OT has no pathognomonic sign and atypical presentations were not infrequent in this adult Caucasian cohort. Serum antibodies were rarely positive, stressing on the importance of ocular sample analysis, especially in case of atypical features. Serum antibodies may prove useful in forecasting the rapidity of inflammation clearance. Antiparasitic and anti-inflammatory treatment was safe and efficient in most cases.

Gains in the current understanding of managing neovascular AMD with brolucizumab.

BACKGROUND: Unresolved retinal fluid and high injection burden are major challenges for patients with neovascular age-related macular degeneration. Brolucizumab addresses these challenges by providing robust vision gains and superior fluid resolution, with the potential for longer treatment intervals. Brolucizumab has been associated with adverse events of retinal vasculitis and retinal vascular occlusion typically in the presence of intraocular inflammation (IOI). To define the incidence of the adverse events, Novartis convened an external safety review committee, which found a rate of 4.6% for definite or probable IOI, 3.3% for retinal vasculitis, and 2.1% for retinal vascular occlusion in the HAWK and HARRIER trials. Novartis also established a coalition to explore 4 areas regarding the adverse events: root cause, patient characterization, event mitigation and vigilance, and treatment protocols for the adverse events. Based on the coalition findings, a risk mitigation framework was developed. Prior to initiating treatment with brolucizumab, it is important to weigh the potential benefit against risk of adverse events and to consider patient risk factors such as prior history of IOI and/or retinal vascular occlusion. To mitigate the potential for IOI-related adverse events, it is important to conduct a thorough dilated eye examination before each injection and closely monitor patients throughout treatment. Patients should be educated on symptoms of IOI to monitor for. Brolucizumab should not be injected in the presence of active IOI. If an adverse event is identified, prompt and intensive treatment should be considered. CONCLUSION: Progress has been made in understanding how to mitigate IOI-related adverse events following treatment with brolucizumab.

Efficacy and Safety of Low-Intensity Pulsed Ultrasound-Induced Blood-Retinal Barrier Opening in Mice.

Systemic drugs can treat various retinal pathologies such as retinal cancers; however, their ocular diffusion may be limited by the blood-retina barrier (BRB). Sonication corresponds to the use of ultrasound (US) to increase the permeability of cell barriers including in the BRB. The objective was to study the efficacy and safety of sonication using microbubble-assisted low-intensity pulsed US in inducing a transient opening of the BRB. The eyes of C57/BL6J mice were sonicated at different acoustic pressures (0.10 to 0.50 MPa). Efficacy analyses consisted of fluorescein angiography (FA) performed at different timepoints and the size of the leaked molecules was assessed using FITC-marked dextrans. Tolerance was assessed by fundus photographs, optical coherence tomography, immunohistochemistry, RT-qPCR, and electroretinograms. Sonication at 0.15 MPa was the most suitable pressure for transient BRB permeabilization without altering the morphology or function of the retina. It did not increase the expression of inflammation or apoptosis markers in the retina, retinal pigment epithelium, or choroid. The dextran assay suggested that drugs up to 150 kDa in size can cross the BRB. Microbubble-assisted sonication at an optimized acoustic pressure of 0.15 MPa provides a non-invasive method to transiently open the BRB, increasing the retinal diffusion of systemic drugs without inducing any noticeable side-effect.

Pathogenic variants in the NLRP3 LRR domain at position 861 are responsible for a boost-dependent atypical CAPS phenotype.

BACKGROUND: Cryopyrin-associated periodic syndrome (CAPS) is associated with NLRP3 pathogenic variants, mostly located in the NACHT (neuronal apoptosis inhibitor protein, MHC class 2 transcription activator, incompatibility locus protein from Podospora anserina, telomerase-associated protein) domain. Cold-induced urticarial rash is among the main clinical features. However, this study identified a series of 14 patients with pathogenic variants of the Y861 residue (p.Tyr861) of the LRR domain of NLRP3 and minimal prevalence of cold-induced urticarial rash. OBJECTIVES: This study aimed to address a possible genotype/phenotype correlation for patients with CAPS and to investigate at the cellular levels the impact of the Y861C substitution (p.Tyr861Cys) on NLRP3 activation. METHODS: Clinical features of 14 patients with CAPS and heterozygous substitution at position 861 in the LRR domain of NLRP3 were compared to clinical features of 48 patients with CAPS and pathogenic variants outside the LRR domain of NLRP3. IL-1ß secretion by PBMCs and purified monocytes from patients and healthy donors was evaluated following LPS and monosodium urate crystal stimulation. RESULTS: Patients with substitution at position 861 of NLRP3 demonstrated a higher prevalence of sensorineural hearing loss while being less prone to skin urticarial. In contrast to patients with classical CAPS, cells from patients with a pathogenic variant at position 861 required an activation signal to secrete IL-1ß but produced more IL-1ß during the early and late phase of secretion than cells from healthy donors. CONCLUSIONS: Pathogenic variants of Y861 of NLRP3 drive a boost-dependent oversecretion of IL-1ß associated with an atypical CAPS phenotype.

Behçet's Disease Uveitis.

Uveitis in Behçet's disease (BD) is frequent (40% of cases) and is a major cause of morbidity. The age of onset of uveitis is between 20 and 30 years. Ocular involvement includes anterior, posterior, or panuveitis. Uveitis may be the first sign of the disease in 20% of cases or it may appear 2 or 3 years after the first symptoms. Panuveitis is the most common presentation and is more commonly found in men. Bilateralization usually occurs on average 2 years after the first symptoms. The estimated risk of blindness at 5 years is 10-15%. BD uveitis has several ophthalmological features that distinguish it from other uveitis. The main goals in the management of patients are the rapid resolution of intraocular inflammation, the prevention of recurrent attacks, the achievement of complete remission, and the preservation of vision. Biologic therapies have changed the management of intraocular inflammation. The aim of this review is to provide an update to a previous article by our team on pathogenesis, diagnostic approaches, and the therapeutic strategy of BD uveitis.

Posterior Herpetic Uveitis: A Comprehensive Review.

PURPOSE: To report and illustrate the main clinical presentations of posterior herpetic uveitis. METHODS: Narrative review. RESULTS: The ocular manifestations of posterior herpetic uveitis include different clinical presentations. Herpes simplex and varicella zoster can cause acute retinal necrosis, progressive outer retinal necrosis, and non-necrotizing herpetic retinopathies. Cytomegalovirus has been associated with fulminant retinitis with confluent areas of retinal necrosis and retinal hemorrhages, indolent/granular retinitis, and frosted branch angiitis. These diverse clinical presentations are often associated with specific risk factors and different immunological profiles of the host. CONCLUSIONS: Herpetic viruses can cause posterior uveitis, presenting various clinical findings. Specific ocular manifestations and the immunological status of the host can help to differentiate the various herpetic entities before laboratory tests confirm the diagnosis.

Detection and Management of Intraocular Inflammation after Brolucizumab Treatment for Neovascular Age-Related Macular Degeneration.

PURPOSE: To present interim descriptive insights from the OCTOPUS and SWIFT studies on incidence, clinical features, management, and outcomes of intraocular inflammation (IOI), vasculitis, and occlusive vasculitis with brolucizumab treatment (Beovu, Novartis) in patients with neovascular age-related macular degeneration (nAMD) who were anti-VEGF naive or pretreated with anti-VEGFs (ranibizumab or aflibercept). DESIGN: OCTOPUS (NCT04239027) and SWIFT (NCT04264819) studies are prospective phase IIIb single-arm, open-label, multicenter studies assessing brolucizumab. SUBJECTS: Anti-VEGF naive (OCTOPUS) and pretreated (SWIFT) patients with nAMD. METHODS: Interim prespecified analysis on the efficacy end point provided an opportunity to analyze IOI-related safety. Reports of IOI-related adverse events (AEs) were reviewed, and AE images and clinical features and outcomes of each case were analyzed by a review committee. RESULTS: Of 505 brolucizumab-treated eyes/patients with median brolucizumab treatment of 8.8 months, 53 eyes demonstrated at least 1 IOI-related AE. The incidence of overall IOI-related AEs was 10.5%; among these events, the incidence was 7.1% for IOI only without retinal involvement and 3.4% for IOI with retinal involvement (2.0% with vasculitis, 1.4% with vascular occlusion with or without vasculitis). Incidence was similar in naive and pretreated patients. Before the onset of the first IOI-related AE, eyes received a median of 2 brolucizumab injections; 81.1% of IOI-related AEs occurred during the loading phase (median, 25.0 days from the last brolucizumab injection). At AE onset, most frequently reported symptoms were floaters (52.8%) and blurred or decreased vision (37.8%). Of the 86.8% of AEs that were treated, most were treated with topical corticosteroids (75.5%), 28.3% by systemic corticosteroids, and 26.8% by intraocular corticosteroids. No severe vision loss was reported for the 7 nontreated AEs. Overall, the median best-corrected visual acuity (BCVA) change at IOI-related AEs resolution from baseline was 1 letter (range, -74 to +32 letters), and 2 patients with occlusive vasculitis had BCVA loss ≥ 15 letters due to IOI-related AEs. All eyes permanently discontinued brolucizumab after the first IOI-related AE. CONCLUSIONS: This analysis highlights the need for monitoring and education of patients to report any signs of IOI-related events immediately when being treated with brolucizumab. IOI should be treated promptly and intensely with corticosteroids. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.