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.

Switch to faricimab after initial treatment with aflibercept in eyes with neovascular age-related macular degeneration.

PURPOSE: To investigate the efficacy and outcomes of switching neovascular age-related macular degeneration (nAMD) patients from aflibercept to faricimab, focusing on visual acuity, retinal fluid management, and treatment intervals. The primary aim was to assess the early outcomes in nAMD patients refractory to aflibercept and explore faricimab's potential as a longer-lasting therapeutic alternative. METHODS: A single-center retrospective study was conducted on 50 refractory nAMD patients at Cleveland Clinic Abu Dhabi from September 2022-May 2023. Patients were switched from aflibercept to faricimab, having met specific criteria for refractory nAMD. The study analyzed best-corrected visual acuity (BCVA), central subfield thickness (CST), and fluid changes post-switch, using Optical Coherence Tomography (OCT). RESULTS: After three faricimab injections, significant reductions in CST were observed, with a notable decrease in retinal fluid. The mean BCVA remained stable throughout the study period. Although there was a decrease in the maximum pigment epithelial detachment (PED) height, it was not statistically significant. Treatment intervals post-switch showed that the majority of patients maintained or extended their treatment intervals, with a significant proportion achieving resolution of intraretinal fluid (IRF) and subretinal fluid (SRF). CONCLUSIONS: Switching to faricimab from aflibercept in refractory nAMD patients led to significant improvements in retinal fluid management and CST, with stable BCVA outcomes. Faricimab presents a promising alternative for patients requiring frequent aflibercept injections, potentially offering a more manageable treatment regimen with extended dosing intervals. This study highlights the need for personalized therapeutic strategies in nAMD treatment, though further research is necessary to optimize treatment switches.

Use of Color Channel Optimization in 3D Heads-Up Vitrectomy vs Standard Operating Microscope for Macular Surgeries.

Purpose: To compare the efficacy and safety of color channel optimization with 3-dimensional (3D) heads-up vitrectomy (3D HUD group) vs standard operating microscope vitrectomy (control group) for macular surgery. Methods: This retrospective multicenter comparative study comprised patients having 25-gauge pars plana vitrectomy for macular hole, epiretinal membrane (ERM), or vitreomacular traction. The minimum follow-up was 6 months. Surgeons completed a subjective questionnaire after each case. The main outcome measures were safety related (dye reinjection rate, macular ERM or internal limiting membrane [ILM] peeling time, endoillumination intensity). Other outcome measures included total surgical time, surgical outcomes, and subjective surgeon-related parameters. Results: The study included 74 eyes (36 in 3D HUD group; 38 in control group). There were no statistical differences in baseline parameters between groups. Significantly more eyes in the control group than in the 3D HUD group required dye reinjection (23.7% vs 5.6%; P = .03). Less time was required for ERM and ILM peeling in the 3D HUD group (both P < .01); however, the total surgical time was the same between groups. Eyes in the 3D HUD group required lower endoillumination (P < .001). There were no between-group differences in the rates of complications. Surgeons said depth perception was better in the control group (P < .001), with no differences in comfort or visibility. Conclusions: 3D heads-up-based color channel optimization for macular surgeries is safe and effective. Although it may have safety advantages, it did not affect the visual or anatomic outcomes or total surgical time and did not improve surgeon comfort or visibility.

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.

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.

Switch to faricimab after initial treatment with aflibercept in eyes with diabetic macular edema.

PURPOSE: To assess the effectiveness of a switch to faricimab in individuals affected by DME and previously treated with aflibercept. METHODS: In this retrospective, single-center study, DME patients previously treated with at least 3 injections of aflibercept then switched to faricimab were enrolled. Best corrected visual acuity (BCVA) and central subfield thickness (CST) were recorded at baseline, at the time of the switch and at 6 months follow-up. At transition to faricimab, patients were categorized as "good visual responders" (≥ 5 letters from baseline) or "poor visual responders" (< 5 letters), and as "good anatomical responders" (any reduction in edema compared to baseline) or "poor anatomical responders" (no reduction or worsening of edema). Changes in BCVA and CST were recorded at 6 months after the switch to faricimab. RESULTS: 100 eyes of 100 patients (61 female, 61%) were switched to faricimab after a mean of 6.8 ± 3.3 aflibercept injections. At the 6 months follow-up, only "poor visual responders" (N = 62) demonstrated a meaningful increase in BCVA (Δswitch-6M = + 5 letters; P = 0.007), coupled with a reduction in CST (Δswitch-6M = - 67.9 µm; P = 0.004); participants with "poor anatomical response" upon transitioning exhibited a significant functional gain (Δswitch-6M = + 4.5 letters; p = 0.05) but limited CST enhancements (Δswitch-6M = - 95.1 µm; p = 0.05). CONCLUSIONS: Faricimab shows a positive impact on anatomical and functional metrics in DME cases refractory to aflibercept.

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.

Uveitis-Glaucoma-Hyphema Syndrome Secondary to Implantable Collamer Lens.

Purpose: To report the first case of uveitis-glaucoma-hyphema (UGH) syndrome post implantable collamer lens (ICL).Methods: Case reportResults: A 41-year-old female presented to our clinic complaining of bilateral eye pain and redness for two weeks. Her past medical history was significant for ICL, in both eyes and multiple sclerosis controlled with treatment. She had a long-standing history of bilateral recurrent uveitis and glaucoma. Ultrasound biomicroscopy revealed several sulcus cysts displacing the ICLs haptic into the ciliary body, leading to iris abrasion and uveitis-glaucoma-hyphema syndrome.Conclusion: We present the first published case worldwide about UGH syndrome secondary to ICL. This is an unusual complication, and measures can be taken to avoid it. This provides evidence of the importance of postoperative follow-up by the surgeon and appropriate work-up when such cases are suspected.

Immunomodulatory Treatment Versus Systemic Steroids in Inflammatory Choroidal Neovascularization Secondary to Idiopathic Multifocal Choroiditis.

PURPOSE: To evaluate the influence of immunomodulatory therapy (IMT) on visual and treatment outcomes of inflammatory choroidal neovascularization (iCNV) in patients affected by multifocal choroiditis (MFC), and to compare them to patients treated with steroids as needed. DESIGN: Multicenter retrospective matched cohort study. METHODS: Patients affected by MFC with iCNV were divided into a IMT group and a "steroids as needed" group and matched according to the time between diagnosis and beginning of systemic treatment. Visual acuity (VA), number of anti-vascular endothelial growth factor (VEGF) intravitreal injections, and number of iCNV reactivations during 2 years of follow-up after treatment initiation were compared between the 2 groups. RESULTS: A total of 66 eyes of 58 patients were included, equally divided into the 2 groups. Patients in the IMT group had a lower relative risk (RR) of iCNV reactivation (0.64, P = .04) and of anti-VEGF intravitreal injection retreatment (0.59, P = .02). Relapses of MFC-related inflammation were independently associated with a higher RRs of iCNV reactivation (1.22, P = .003). Final VA was higher in the IMT compared to the steroids as needed group (mean [SD], 69.1 [15.1] vs 77.1 [8.9] letters, P = .01), and IMT was associated with greater VA gains over time (+2.5 letters per year, P = .04). CONCLUSIONS: IMT was associated with better visual and treatment outcomes in MFC complicated by iCNV compared to steroids as needed. The better outcomes of the IMT group and the association between MFC-related inflammation and iCNV reactivations highlight the need for tighter control of inflammation to prevent iCNV relapses and visual loss.

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.

Description of Macrophage-Like Cells in Active Ocular Toxoplasmosis.

Macrophage-like cells (MLC) have a fundamental role in the maintenance of immunosurveillance, response to inflammation and tissue injury in the retina. MLC can be visualized in vivo with conventional en face optical coherence tomography (OCT). The aim of this study is to describe this population of cells in active toxoplasmosis. We present two cases of active toxoplasma retinochoroiditis imaged at 2 time points, where the MLC were threshold after image processing and averaging for removing background and noise. In both patients the MLC collocated with the area of ischemia at the level of the choriocapillaris and retinal vessels.

Herpetic anterior uveitis following COVID-19 vaccines: a case series.

Purpose: To report a case series of herpetic uveitis following COVID-19 vaccinations. Methods: Demographic, clinical and treatment-related data of herpetic anterior uveitis cases was collected at five tertiary eye hospitals between January 2021 and June 2022. A retrospective database review at one of the centers comparing the number of cases of herpetic eye disease before and after the introduction of COVID-19 vaccination was performed as well. Results: Twenty-four patients (9 female, 15 male) with a mean age of 54 years (range 28-83 years) were diagnosed with herpetic uveitis, reporting an onset of symptoms 3-42 days after the first, second or third dose of COVID-19 vaccination. Median time between vaccination and onset of herpetic eye disease was 10 days (mean 12.7 ± 10.15 days) days. The administered vaccines were BNT162b2, mRNA-1273, BBIBP-CorV and Ad26.COV2.S. The cases included 11 HSV, 10 VZV and 1 CMV anterior uveitis, 2 were not further specified. There was an equal number of first episodes (n = 12, 50%) and recurrent episodes (n = 12, 50%). Response to established regimens was generally good. The retrospective database review revealed the exact same incidence of herpetic uveitis during the pandemic and ongoing vaccination compared to prior SARS-CoV-2. Conclusion: This report includes 24 cases of herpetic anterior uveitis in a temporal relationship to various COVID-19 vaccines. This study supports the potential risk of herpetic eye disease following COVID-19 vaccines, but proof of a direct, causal relationship is missing.

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.