Corticosteroids for the Management of Uveitic Macular Edema: A Comprehensive Review.

Uveitis, which refers to the inflammation of the uveal tract and surrounding structures in the eye, poses a significant risk of vision impairment, with macular edema (UME) being a prevalent complication. The current statement reviews UME's prevalence, pathogenesis, diagnosis, and management strategies, focusing on the utility of systemic and local corticosteroid therapy. Corticosteroids, with their multifaceted effects on inflammatory pathways, serve as the cornerstone of UME treatment. Various administration routes, including topical, periocular, intraocular, and systemic, are employed based on the anatomical type and severity of inflammation. The efficacy of different corticosteroid formulations, such as difluprednate, triamcinolone acetonide, dexamethasone implant, and fluocinolone acetonide implant, is evaluated through clinical trials and retrospective studies. Additionally, the role of corticosteroid-sparing treatments, including antimetabolites like methotrexate and mycophenolate mofetil, is explored. Emerging techniques, such as suprachoroidal space triamcinolone acetonide administration, offer promising alternatives for managing UME. Through a thorough examination of current evidence, this review provides valuable insights into optimizing the management of UME and improving visual outcomes in patients with uveitis.

ADALIMUMAB DRUG MONITORING AND TREATMENT ADJUSTMENT TO DRUG ANTIBODIES IN NON-INFECTIOUS UVEITIS.

PURPOSE: To explore the incidence of antibodies against adalimumab (AAA) development in non-infectious uveitis (NIU) and to examine the impact of treatment adjustment in non-responders. DESIGN: Retrospective case series. METHODS: SETTING: Single-center study. STUDY POPULATION: Patients with NIU treated with adalimumab OBSERVATION PROCEDURE: Blood samples for adalimumab and AAA were collected and therapeutic adjustments post-monitoring in non-responders were analyzed including changes in injection intervals, addition of conventional disease-modifying antirheumatic drugs (cDMARD), and treatment alterations to biologic DMARD. MAIN OUTCOME MEASURES: Proportion of patients with positive AAA and active uveitis, decrease of AAA at final follow-up by different therapeutic interventions. RESULTS: Of 42 patients who underwent laboratory investigations at 17.9 months after adalimumab initiation, 22 (52.4%) patients who were non-responders demonstrated AAA (1243 ng/mL) with a mean adalimumab trough levels of 3.0 µg/mL, significantly lower than the mean drug levels of patients without AAA (11.8 µg/mL). Fifteen (35.7%) patients were receiving concurrent treatment with a second immunosuppressive agent, but the mean antibody level and the mean adalimumab level were not statistically significantly different from the monotherapy group (P = 0.13 and P = 0.34). Reduction in AAA levels and relapse management was greatest among non-responders who were treated by increasing the adalimumab dose and adding an additional immunosuppressive drug (-3565 ng/mL), followed by patients who were shifted to a different biologic (-1153 ug/mL). CONCLUSIONS: The presence of AAA was detected in 88% of non-responder patients and was associated with undetectable adalimumab drug levels. This underscores immunogenicity as a major cause of loss of response in uveitis patients receiving biotherapies. Increasing the dose of adalimumab injections together with the addition of low-dose cDMARDs was the most effective adjustment in immunized non-responders for whom the adalimumab drug concentration was low.

Ultrasound biomicroscopy qualitative and quantitative signs of phacoantigenic uveitis.

BACKGROUND/OBJECTIVE: To describe the ultrasound biomicroscopy (UBM) diagnostic features in patients suspected of experiencing chronic inflammation due to phacoantigenic uveitis SUBJECTS/METHODS: This single-center study enrolled patients referred to the Uveitis Department of Cleveland Clinic Abu Dhabi for chronic anterior uveitis and traumatic cataract. Patients' demographics, causes and dates of the inciting traumatic event, and ophthalmic findings were recorded. 20-MHz UBM assessment of the status of the anterior capsule and the crystalline lens was performed. Then, cataract surgery was performed using a single technique. Comparison of the anterior capsule and lens status by clinical, UBM, and intraoperative evaluation. RESULTS: Forty eyes with phacoantigenic uveitis were considered. The slit-lamp examination could identify interruption of the anterior capsule in 20% of the eyes and liquefied sinking lens material in 10%. An intra-operative defect in the anterior capsule was documented in 87.5% of eyes. UBM imaging showed anterior capsule irregularity in 63.3% of eyes and confirmed the presence of anterior capsule defects in 47.5% and lens matter herniating into the anterior chamber in 15%. Hypoechogenic lacunae within the cataractous lens were detected in 12.5% of eyes. For UBM, sensitivity and specificity values were 82.86% (95% CI: 66.35-93.44) and 100% (95% CI: 47.82-100), respectively. Positive and negative predictive values for UBM were 100% (95% CI: 88.06-100) and 45.45% (95% CI: 28.69-63.32), respectively. The overall diagnostic accuracy of UBM was 85% [95% CI: 70.16-94.29]. CONCLUSION: Ultrasound Biomicroscopy (UBM) is essential for assessing suspected anterior capsule ruptures in phacoantigenic uveitis cases.

Multimodal Imaging in Retinal Vasculitis.

BACKGROUND: Retinal vasculitis is an inflammatory condition that affects the retinal blood vessels. SUMMARY: It can manifest as an idiopathic disorder or be secondary to various infectious or non-infectious diseases, mimicking syndromes, isolated ocular disorders, or drug-induced reactions. Recognizing its distinctive features is crucial for early diagnosis and accurate treatment. This review aimed to demonstrate the variety of tools available to detect disease activity, assess complications, measure the extent of retinal damage, and guide therapy effectively. KEY MESSAGE: This review article highlights the use of multimodal imaging in the comprehensive evaluation of retinal vasculitis.

An Update on Noninfectious Retinal Vasculitis.

BACKGROUND: Retinal vasculitis (RV) signifies the inflammation of various retinal vessels. Noninfectious RV differs from infectious RV with regard to its pathogenesis and treatment. It can have varied clinical presentations and may be associated with systemic vasculitic diseases. SUMMARY: Noninfectious RV can be caused due to type-III hypersensitivity reactions, increased expression of intracellular adhesion molecules, and genetic susceptibility. Noninfectious RV is primarily classified on the basis of the type of retinal vessels involved. It can be further classified as an occlusive or nonocclusive. RV can be a major association of systemic diseases like Behcet's disease, sarcoidosis and systemic lupus erythematosus. Newer modalities, like ultra-widefield fundus fluorescein angiography, can help in the management of RV. Effective treatment of noninfectious RV requires anti-inflammatory and immunosuppressive therapy. The patients may require treatment with high-dose corticosteroids and biological agents. Anti-vascular endothelial growth factor injections and laser photocoagulation may be indicated to treat the occlusive disease. Prompt treatment may prevent complications like vitreous hemorrhage, neovascular glaucoma, and tractional retinal detachment. The treatment more often requires a multidisciplinary approach. KEY MESSAGES: This review provides a comprehensive update on the various causes of noninfectious RV, including both systemic and isolated ocular conditions. It also details various complications and management strategies for this condition.

Vitreoretinal Interface Cells Correlate In Vivo With Uveitis Activity and Decrease With Anti-Inflammatory Treatment.

Purpose: To highlight the utility of en face swept-source optical coherence tomography angiography (SS-OCTA) in assessing vitreoretinal interface cells (VRICs) of patients with active uveitis and their dynamics. Methods: In this prospective, single-center study, 20 eyes from patients with active uveitis were analyzed using six 6 × 6-mm macular scans at three time points: active inflammation (baseline), clinically improving (T1), and resolved inflammation (T2). VRICs were visualized using 3-µm en face OCT slabs on the inner limiting membrane. The variation of VRIC number, density, and size over time was assessed, and VRIC measurements were compared with clinical grading. Results: At baseline, the VRIC count was significantly higher (552.5 VRICs) than that of the healthy controls (478.2 VRICs), with a density of 15.3 cells/mm2. VRIC number decreased significantly to 394.8 (P = 0.007) at T1, with a density of 10.9 cells/mm2 (P = 0.007). VRIC size reduced from 6.8 µm to 6.3 µm at T1 (P = 0.009) and remained stable at T2 (P = 0.3). Correlation coefficients between inflammatory parameters (anterior chamber cells and National Eye Institute vitreous haze), and VRIC count indicated a positive correlation at baseline (r = 0.53), weakening at T1 (r = 0.36), and becoming negative at T2 (r = -0.24). Conclusions: En face SS-OCTA revealed increased VRIC number and size in active uveitis, likely due to monocyte recruitment. Post-inflammation control, VRIC number, size, and density significantly decreased, returning to normal despite residual anterior chamber cells or vitreous haze. Translational Relevance: Visualization of VRICs by in vivo OCT opens up new opportunities for therapeutic targets.

Unraveling the Complexities of Severe Acute Respiratory Syndrome Coronavirus 2: A Comprehensive Ophthalmic and Systemic Perspective.

The editorial explores the profound implications of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, which emerged in December 2019 and rapidly evolved into a global health crisis. Despite initial focus on respiratory symptoms, the virus revealed significant ocular implications, prompting a reevaluation of the eye's role in its transmission, diagnosis, and systemic effects. The paradoxical nature of SARS-CoV-2-simultaneously novel and familiar within the coronavirus family-has been central to guiding the global medical response, including the swift development of vaccines. The pandemic has intensified research into the eye's susceptibility to viral infections, enhancing our understanding of virus-host interactions and the systemic impacts of viral diseases. The editorial delves into the pathophysiology of SARS-CoV-2, highlighting its potential to trigger autoinflammatory and autoimmune reactions with significant ocular repercussions. It examines the rapid vaccine development and deployment, the associated ocular side effects, and the ongoing research necessary to mitigate these outcomes. As the World Health Organization declared the end of COVID-19 as a public health emergency, the focus has shifted toward understanding the virus's long-term implications, including its effects on ocular health. This work underscores the critical role of interdisciplinary collaboration in addressing the systemic impacts of viral infections. It emphasizes the importance of ophthalmology in the broader context of public health and highlights the need for continued vigilance, research, and adaptation in a postpandemic world. The editorial calls for an integrated approach to health care, emphasizing the lessons learned from the SARS-CoV-2 pandemic to prepare for future health challenges, with a particular focus on the intersection of virology, immunology, and ophthalmology.

The Humira in Ocular Inflammations Taper (HOT) Study.

PURPOSE: To assess factors that impact the risk of relapse in patients with noninfectious uveitis (NIU) who undergo adalimumab tapering after achieving remission. DESIGN: Retrospective study. METHODS: In this multicenter study, patients with NIU were treated with adalimumab and subsequently tapered. Patient demographics, type of NIU, onset and duration of disease, the period of inactivity before tapering adalimumab, and the tapering schedule were collected. The primary outcome measures were independent predictors of the rate of uveitis recurrence after adalimumab tapering. RESULTS: Three hundred twenty-eight patients were included (54.6% female) with a mean age of 34.3 years. The mean time between disease onset and initiation of adalimumab therapy was 35.2 ± 70.1 weeks. Adalimumab tapering was commenced after a mean of 100.8 ± 69.7 weeks of inactivity. Recurrence was observed in 39.6% of patients at a mean of 44.7 ± 61.7 weeks. Patients who experienced recurrence were significantly younger than those without recurrence (mean 29.4 years vs 37.5 years, P = .0005), and the rate of recurrence was significantly higher in younger subjects (hazard ratio [HR] = 0.88 per decade of increasing age, P = .01). The lowest rate of recurrence was among Asian subjects. A faster adalimumab taper was associated with an increased recurrence rate (HR = 1.23 per unit increase in speed, P < .0005). Conversely, a more extended period of remission before tapering was associated with a lower rate of recurrence (HR = 0.97 per 10-weeks longer period of inactivity, P = .04). CONCLUSIONS: When tapering adalimumab, factors that should be considered include patient age, race, and duration of disease remission on adalimumab. A slow tapering schedule is advisable.

Optical coherence tomography angiography in birdshot chorioretinopathy.

PURPOSE: To describe the retinal vascular changes in birdshot chorioretinopathy (BSCR) using optical coherence tomography angiography (OCTA) and to compare them with changes in macular thickness. METHODS: In this multicenter study, patients with a diagnosis of BSCR and a positive HLA-A29 underwent fluorescein angiography, spectral domain optical coherence tomography (SD-OCT), and OCTA. The foveal avascular zone (FAZ) and the area of capillary non-perfusion were manually measured by two examiners in fluorescein angiography (FA) and 3 × 3-mm OCTA images of the superficial retinal layer. These measurements were compared to central retinal thickness. To calculate normal capillary density, we collected data from 22 controls who had OCTA performed on one visit only. RESULTS: A total of 44 eyes with BSCR were enrolled. The mean automated parafoveal superficial capillary density in BSCR eyes was 0.47 ± 0.03. The differences between the foveal capillary density of BSCR patients and healthy subjects were statistically significant (P < 0.001). The mean area of FAZ manually measured on the 3 × 3 mm unsegmented OCTA images was larger in eyes with BSCR (1.34 ± 0.41 mm2; P < 0.0001). Measurement of FAZ area showed good interobserver (κ 0.88) and intraobserver repeatability (κ 0.79) on OCTA images. The intraclass correlation coefficient for FAZ measurements on FA between the two observers was 0.48. The OCT retinal thickness maps of all BSCR eyes demonstrated statistically significant thinning compared to those of control subjects (P < 0.01). CONCLUSION: Our study demonstrates the potential contribution of OCTA as a new non-invasive imaging technology that monitors disease activity in BSCR patients.

Automated quantification of uveitic keratic precipitates by use of anterior segment optical coherence tomography.

BACKGROUND: Evaluation of ocular inflammation via common imaging modalities like optical coherence tomography (OCT) has emphasised cell visualisation, but automated detection of uveitic keratic precipitates (KPs) remains unexplored. METHODS: Anterior segment (AS)-OCT dense volumes of the corneas of patients with uveitic KPs were collected at three timepoints: with active (T0), clinically improving (T1), and resolved (T2) inflammation. At each visit, visual acuity and clinical grading of the anterior chamber cells were assessed. A bespoke algorithm was used to create an en face rendering of the KPs and to calculate their volume and a ratio of the volume of precipitates over the analysed area. The variation of AS-OCT-derived measurements over time was assessed, and compared with clinical grading. RESULTS: Twenty eyes from 20 patients (13 females, mean age 39 years) were studied. At T0, the mean volume of the corneal KPs was 0.1727 mm3 , and it significantly reduced to 0.1111 mm3 (p = 0.03) only at T2. The ratio between the volume of the KPs and the corneal area decreased from T0 (0.007) to T1 (0.006; p = 0.2) and T2 (0.004; p = 0.009). There was a statistically significant correlation between the AC cell count and the AS-OCT volume measurements of the KPs at the three time points. CONCLUSIONS: AS-OCT can image uveitic KPs and through a bespoke algorithm we were able to create an en face rendering allowing us to extrapolate their volume. We found that objective quantification of KPs correlated with inflammatory cell counts in the anterior chamber.

In Vivo Visualization of Macrophage-Like Cells in Patients with Uveitis by Use of En Face Swept Source Optical Coherence Tomography.

AIMS: To detect macrophage-like cells (MLCs) in uveitis patients and describe their characteristics compared to healthy subjects by using en face SS-OCTA. METHODS: Fifteen consecutive patients with "active" uveitis and 11 healthy participants underwent 6 macular scans of 6×6mm using SS-OCTA. The 3µm en face OCT slabs on inner limiting membrane were used to visualize the MLCs. RESULTS: In healthy subjects there was an average of 478.2±149.7 MLCs with a density of 13.28±4.16 cells/mm2. MLCs were larger in patients with "active" uveitis than in controls (891.18±69.46 µm2 vs.885±77.53 µm2). Patients with "active" anterior uveitis had a significantly reduced count and density of MLCs (172±14.68 and 4.77±0.4 cell/mm2) compared to controls, while patients with posterior uveitis had a statistically increased count (546.1±132.4) and area (909.23+/-54.97 µm2) of MLCs compared to controls. CONCLUSIONS: MLCs detected with en face SS-OCTA are increased in number and size in active posterior uveitis eyes compared to controls.

Fundus autofluorescence in uveitis: from pathogenesis to imaging interpretation.

PURPOSE: This review aims to summarize the current fundus autofluorescence (FAF) ailment for diagnosis and follow-up of uveitis. METHODS: A thorough literature search was performed in the PubMed database. RESULTS: FAF maps the retinal pigment epithelium's (RPE) health. Therefore, several posterior infectious and non. This fast, easy-to-perform, noninvasive technique can detect and manage infectious uveitis. CONCLUSIONS: FAF serves to understand pathophysiologic mechanisms of uveitis and is a valuable prognostic indicator of themselves.

Focal Posterior Herpetic Retinitis.

Despite having 20/20 vision, a 17-year-old Emirati female presented with central visual changes in her left eye. These changes were attributed to a dull foveal reflex with pigmentary alterations. Retinal pigment epithelium (RPE) mottling at the macula level, attenuating the ellipsoid zone, and a hyper-reflective line connecting the RPE to the outer nuclear layer was observed through spectral domain optical coherence tomography (SD-OCT) of the left eye. In the presence of negative results from laboratory evaluations, the patient was started on oral prednisolone. The medication induced an increased reflectivity of the inner layers on SD-OCT, which turned into a full-thickness macular retinitis with vitreous inflammation, causing a visual decrease to 20/80. A vitreous tap confirmed a positive result for HSV-1, and the patient was prescribed oral valacyclovir 3 g. This treatment led to a resolution of the retinitis and a restoration of the patient's vision to 20/25.

Multimodal Imaging Study of Patients With Vitamin A Deficiency Retinopathy.

OBJECTIVES: To describe multimodal imaging findings of vitamin A deficiency retinopathy. METHODS: A retrospective study of patients with serum retinol < 0.3 mg/L. Fundus color photos, spectral domain-optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF) were reviewed and, when available, electrophysiological tests were analyzed. RESULTS: Forty-five eyes (63.9 ± 15.7 years) were included. Ultra-widefield fundus photography showed drusen-like deposits (53.3%) and macular retinal pigment epithelium (RPE) mottling (40%). The deposits were hypoautofluorescent, and a perifoveal hyperautofluorescent ring was present in 8.9%. By SD-OCT, the ellipsoid zone had an irregular appearance (100%) and conical deposits anterior to the RPE (33.3%). Electroretinogram (ERG) (66.7%) showed a decrease in b-wave in the scotopic registers, and microperimetry (4.4%) showed decreased foveal sensitivity. After vitamin A supplementation, SD-OCT and FAF showed resolution of all findings. Forty percent of eyes had restoration of the scotopic registers in ERG and improved macular sensitivity by microperimetry (4.4%). CONCLUSIONS: Vitamin A deficiency causes a mild cone dysfunction in addition to the more severe absent rod response. [Ophthalmic Surg Lasers Imaging Retina 2023;54:330-336.].

COVID Vaccine-Associated Uveitis.

PURPOSE: Following the pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2, different vaccines were developed and approved by the main medical authorities under emergency protocol regulations. Although highly effective and well-tolerated in most patients, vaccines can uncommonly cause ocular adverse effects. In this article, the current evidence related to vaccine-associated uveitis is reviewed. METHODS: A literature review of uveitis post various SARS-CoV-2 vaccinations. RESULTS: Uveitis was reported following various forms of vaccinations but was more commonly seen following the Pfizer mRNA vaccine which is the most used vaccination worldwide. In western countries, the most common uveitis is mild anterior uveitis, developing within a week of first or subsequent vaccination with good resolution following appropriate topical steroid therapy in most cases. Posterior uveitis and particularly Vogt-Koyanagi-Harada disease was more prevalent in Asia. Uveitis may develop among known uveitis patients and those with other autoimmune diseases. CONCLUSION: Uveitis following Covid vaccinations is uncommon and has a good prognosis.