Risk factors for emerging intraocular inflammation after intravitreal brolucizumab injection for age-related macular degeneration.

PURPOSE: To analyze the risk factors associated with emerging intraocular inflammation (IOI) after intravitreal brolucizumab injection (IVBr) to treat age-related macular degeneration (AMD). METHODS: This study included 93 eyes of 90 patients. The incidence of emerging IOI was analyzed. The patients were classified into IOI or non-IOI groups, and background clinical characteristics in each group were compared. RESULTS: IOI occurred in 14 eyes of 14 cases (16%; five women, nine men [5:9]; IOI group) after IVBr; contrastingly, no IOI occurred in 76 patients (10 women, 66 men [10:66]; non-IOI group). The mean ages in IOI and non-IOI groups were 79.4 ± 8.1 and 73.8 ± 8.9 years old, respectively, and the average age in the IOI group was significantly higher than that in the non-IOI group (P = 0.0425). In addition, the percentages of females in the IOI and non-IOI groups were 43% and 13%, respectively, and IOI occurred predominantly in females (odds ratio: 4.95, P = 0.0076). Moreover, the prevalence of diabetes in the IOI and non-IOI groups was 64% and 32%, respectively, with a significant difference (odds ratio: 3.90, P = 0.0196). In contrast, the prevalence of hypertension in the IOI and non-IOI groups was 36% and 57%, respectively, with no significant difference (P = 0.15). CONCLUSION: The comparison of clinical profiles of IOI or non-IOI cases in IVBr treatment for AMD suggests that the risk factors for IOI are old age, female sex, and history of diabetes; however, IOI with vasculitis or vascular occlusion in this cohort does not seem to cause severe visual impairment. Further studies are required to investigate potential risk factors for IOI.

Infection with SARS-CoV-2 causes flares in patients with juvenile idiopathic arthritis in remission or inactive disease on medication.

BACKGROUND: Flares of juvenile idiopathic arthritis (JIA) have been described in the context of various infections. Flares of rheumatic diseases in adults have been described following infection with SARS-CoV-2 in several cohorts. So far, the effect of infection with SARS-CoV-2 on the course of JIA is unknown. METHODS: The database of the German Center for Pediatric and Adolescent Rheumatology was searched for patients with confirmed infection with SARS-CoV-2 and subsequent disease flare, admitted from July 2020 until June 2021. cJADAS-27, ESR and C-reactive protein, as well as uveitis activity, medication at the time of flare and treatment of flare was extracted. Patient cases were described individually. RESULTS: Out of 988 patients admitted, five patients with remission off medication (n = 2) or inactive disease on medication (n = 3) were identified, with flare symptoms up to four weeks after infection with SARS-CoV-2. CONCLUSIONS: Flares can occur after infection with SARS-CoV-2 in patients with JIA in remission or inactive disease on medication. Treating physicians need to be aware of this fact, especially when counseling patients with rheumatic diseases about the respective dangers of COVID-19 and vaccination against SARS-CoV-2.

Blau syndrome: a case report from Palestine.

BACKGROUND: This case study documents the first familial case of Blau syndrome (BS) in Palestine characterized with mutation in CARD15/NOD2. CASE PRESENTATION: Eighteen years old female was initially misdiagnosed with Juvenile idiopathic arthritis (JIA). The patient had been on steroids and methotrexate treatment for the last 16 years, but did not respond well to treatment. Initial examination at Saint John of Jerusalem Eye Hospital Group clinic showed bilateral intermediate uveitis with camptodactyly. The patient's sister (aged 19 years) had bilateral intermediate uveitis and camptodactyly. Both eyes of their father had signs of old posterior uveitis. Father's left eye showed 360 degrees posterior synechia, mature cataract with old Keratic precipitates (KPs). He also had camptodactyly. The patient was referred to pediatric rheumatologist to rule out sarcoidosis. Lung CT scan showed bronchiectasis, genetic consultation followed. Complete eye examination, full history, refraction, and Optical coherence tomography (oct) were done. Systemic and topical steroid therapy could not control the ocular inflammation. The family then was referred to a geneticist. Genetic analyses showed that the proband and all three family members had an R334q mutation in the CARD15/Nod2 gene. CONCLUSIONS: BS should be considered in the differential diagnosis of childhood uveitis, especially in low and middle income countries where it is misdiagnosed in many cases, which delay appropriate diagnosis and thus control. Genetic analysis of the CARD15/Nod2 gene is helpful in the diagnosis. Steroids alone are not enough to control the disease, other immunosuppressants and biologics are needed.

Corneal and anterior chamber morphology in patients with noninfectious intraocular inflammation / Morfologia da córnea e da câmara anterior em pacientes com inflamação intraocular não infecciosa

ABSTRACT Purpose: To evaluate the corneal and anterior chamber morphology in phakic eyes with noninfectious intraocular inflammation. Methods: This study included 59 eyes with active uveitis, 62 with inactive uveitis, and 95 healthy eyes. Corneal endothelial cell density, hexagonal cell ratio, coefficient of variation (CV), corneal thickness and volume, maximum keratometry, and anterior chamber volume and depth (ACD) measurements were performed using a specular microscope and Pentacam HR. Results: The mean duration of uveitis was 24.6 ± 40.5 (0-180) months. The mean number of uveitis attacks was 2.8 ± 3.0 (1-20). Coefficient of variation was significantly higher in the active uveitis group compared with inactive uveitis group (p=0.017, Post Hoc Tukey). Anterior segment parameters other than coefficient of variation were not significantly different between active/inactive uveitis and control groups (p>0.05). Multiple linear regression analysis showed that coefficient of variation was greater in active uveitis compared with inactive uveitis after adjusting for the duration of uveitis, type of uveitis, having a rheumatologic disease, and having immunosuppressive treatment (p=0.003). The duration of uveitis and number of attacks were not significantly correlated with ocular parameters (p>0.05, Spearman's correlation). The difference in parameters was not significant based on uveitis type (p>0.05). Conclusions: Coefficient of variation was higher in eyes with active uveitis than that in eyes with inactive uveitis, whereas corneal endothelial cell density and anterior chamber morphology did not significantly differ between active/inactive uveitis and control groups.(AU)

RESUMO Objetivo: Avaliar a morfologia da córnea e da câmara anterior em olhos fácicos com inflamação intraocular não infecciosa. Métodos: Esse estudo incluiu 59 olhos com uveíte ativa, 62 olhos com uveíte inativa e 95 olhos saudáveis. A densidade de células endoteliais da córnea, a proporção de células hexagonais, o coeficiente de variação, o volume e a espessura da córnea, a ceratometria máxima e o volume e profundidade da câmara anterior foram medidos com um microscópio especular e uma Pentacam HR. Resultados: A duração média da uveíte foi de 24,6 ± 40,5 (0-180) meses. O número médio de crises de uveíte foi de 2,8 ± 3,0 (1-20). O coeficiente de variação foi significativamente maior no grupo com uveíte ativa do que no grupo com uveíte inativa (p=0,017, Tukey post-hoc). Não houve diferença significativa nos demais parâmetros do segmento anterior entre os grupos com uveíte ativa, com uveíte inativa e controle (p>0,05). A análise de regressão linear múltipla demonstrou que o coeficiente de variação foi maior na uveíte ativa do que na uveíte inativa, após ajustes para a duração e tipo de uveíte e a presença ou não de doença reumática e de tratamento imunossupressor (p=0,003). A duração da uveíte e o número de crises não demonstraram correlação significativa com os parâmetros oculares (p>0,05, correlação de Spearman). A diferença nos parâmetros não demonstrou correlação significativa com o tipo de uveíte (p>0,05). Conclusões: O coeficiente de variação foi maior nos olhos com uveíte ativa do que naqueles com uveíte inativa, ao passo que a densidade de células endoteliais e a morfologia da câmara anterior não mostraram diferenças significativas entre os grupos com uveíte ativa, com uveíte inativa e controle.(AU)

Immunopathophysiology and clinical impact of uveitis in inflammatory rheumatic diseases: An update.

BACKGROUND: Uveitis is one of the most frequent ophthalmologic manifestations in rheumatology. Uveal inflammation can underlie a systemic inflammatory rheumatic disease (SIRD) in approximately 30% of cases with a significant burden on the quality of life since it represents a cause of blindness in up to 20% of cases in Western countries. METHODS: In this review, we provide a comprehensive overview of the pathophysiology of uveitis associated with SIRDs. According to our literature survey on the epidemiology of uveitis among SIRDs, spondyloarthritides, Behçet's disease and sarcoidosis get the major impact. RESULTS: In Behçet's uveitis, the key players are highly polarized Th1 and Th17 lymphocytes, natural killer T cells and γδ T cells. All contribute to a great destructive inflammatory environment with the most serious visual damage resulting from the involvement of the posterior segment of the eye. In contrast, spondyloarthritides-related uveitis derives from a complex interaction between genetic background and extra-ocular inflammatory mediators originating from enthesitis, arthritis, psoriatic lesions and microbiome pro-inflammatory alterations. In such conditions, the immune infiltration of CD4+ T cells, Th17 and natural killer cells along with pro-inflammatory cytokines, TNF-α among all, leads to intraocular inflammation. Lastly, granuloma formation represents the primary hallmark lesion in sarcoid uveitis. This suggests a profound link between the innate system that mainly recruits activated macrophages and adaptive system involving by Th1, Th17 and Th17.1 cells. CONCLUSIONS: Awareness among rheumatologists of a potential severe ocular involvement generates new insights into targeted therapeutic approaches and personalized treatments for each patient.

Clinical profile and evolution of patients with juvenile-onset Behçet's syndrome over a 25-year period: insights from the AIDA network.

Behçet's syndrome (BS) represents an understudied topic in pediatrics: the main aims of our study were to characterize demographic and clinical features of a cohort of BS patients with juvenile-onset managed in three tertiary referral centers in Italy, evaluate their evolution in the long-term, and detect any potential differences with BS patients having an adult-onset. Medical records of 64 juvenile-onset and 332 adult-onset BS followed-up over a 2-year period were retrospectively analyzed and compared. Mean age ± SD of first symptom-appearance was 10.92 ± 4.34 years with a female-to-male ratio of 1.06:1. Mucocutaneous signs were the most frequent initial manifestations, followed by uveitis. Throughout the disease course, genital aphthae (76.56%) and pseudofolliculitis (40.63%) prevailed among the mucocutaneous signs, while major organ involvement was represented by gastrointestinal and ocular involvement (43.75 and 34.38%, respectively). No significant differences emerged for both mucocutaneous signs and specific major organ involvement between juvenile-onset and adult BS patients. After excluding nonspecific abdominal pain, juvenile-onset BS patients were less frequently characterized by the development of major organ involvement (p = 0.027). Logistic regression detected the juvenile-onset as a variable associated with reduced risk of long-term major organ involvement (OR 0.495 [0.263-0.932], p = 0.029). In our cohort, juvenile-onset BS resembled the clinical spectrum of adult-onset patients. Pediatric patients with a full-blown disease at onset showed a more frequent mucocutaneous involvement. In addition, patients with juvenile-onset seemed to develop less frequently major organ involvement and had an overall less severe disease course.

Visual Dysfunction in Multiple Sclerosis and its Animal Model, Experimental Autoimmune Encephalomyelitis: a Review.

Visual disabilities in central nervous system autoimmune diseases such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are important symptoms. Past studies have focused on neuro-inflammatory changes and demyelination in the white matter of the brain and spinal cord. In MS, neuro-inflammatory lesions have been diagnosed in the visual pathway; the lesions may perturb visual function. Similarly, neuropathological changes in the retina and optic nerves have been found in animals with chronic EAE. Although the retina and optic nerves are immunologically privileged sites via the blood-retina barrier and blood-brain barrier, respectively, inflammation can occur via other routes, such as the uvea (e.g., iris and choroid) and cerebrospinal fluid in the meninges. This review primarily addresses the direct involvement of the blood-retina barrier and the blood-brain barrier in the development of retinitis and optic neuritis in EAE models. Additional routes, including pro-inflammatory mediator-filled choroidal and subarachnoid spaces, are also discussed with respect to their roles in EAE-induced visual disability and as analogues of MS in humans.

The Effect of Adalimumab in Korean Patients with Refractory Noninfectious Uveitis.

We sought to analyze the efficacy of adalimumab in active noninfectious uveitis, and evaluate its efficacy and safety for the management of refractory noninfectious uveitis in Korean patients. A retrospective observational study was conducted. A total of 23 eyes of 14 Korean patients with noninfectious uveitis refractory to conventional treatment, including corticosteroid and immunosuppressive agents, were treated with adalimumab between December 2017 and February 2020. The primary outcomes were vitreous haziness grades, anterior chamber cell grades, and central macular thickness measured prior to injection and at 1, 3, 6, and 12 months after the first adalimumab injection. Among the 23 eyes, 14 eyes (60.9%) were diagnosed with panuveitis and 9 eyes (39.1%) with posterior uveitis [mean follow-up period: 22.3 months (7-27)]. The most common etiologic diagnoses requiring adalimumab injection were Behçet's disease (9 eyes, 39.1%), followed by undifferentiated inflammation (6 eyes, 26.1%), Vogt-Koyanagi-Harada disease (3 eyes, 13.0%), psoriasis (2 eyes, 8.7%), serpiginous chorioretinopathy (2 eyes, 8.7%), and systemic lupus erythematosus (1 eye, 4.3%). At the 1-year follow-up after the first injection, anterior chamber cell grade decreased from 0.5±0.4 to 0.3±0.4, and vitreous haziness grade decreased from 1.1±1.1 to 0.3±0.5 (p<0.05). Central macular thickness improved from 347.2±98.1 µm to 264.3±61.1 µm (p<0.05). Adalimumab injection in patients with refractory noninfectious uveitis decreased the anterior chamber cell grade, vitreous haziness grade, and central macular thickness with no severe side effect. Overall, adalimumab injection may, therefore, be an effective and relatively safe treatment modality for noninfectious uveitis in Korean patients.

Contemporaneous Risk Factors for Visual Acuity in Non-Infectious Uveitis.

INTRODUCTION: We evaluated the associations of clinical and demographic characteristics with visual acuity (VA) with over 5 years in a subspecialty noninfectious uveitis population. METHODS: Retrospective data from 5,530 noninfectious uveitis patients were abstracted by expert reviewers, and contemporaneous associations of VA with demographic and clinical factors were modeled. RESULTS: Patients were a median of 41 years old, 65% female, and 73% white. Eyes diagnosed ≥5 years prior to cohort entry had worse VA (-1.2 lines) than those diagnosed <6 months prior, and eyes with cataract surgery performed prior to entry had worse VA (-5.9 lines) than those performed during follow-up. Vitreous haze (-4.2 lines for 3+ vs quiet), hypotony (-2.5 lines for ≤5 mm Hg vs 6-23 mm Hg), and CNV (-1.8 lines) all were strongly associated with reduced VA. CONCLUSION: Factors associated with reduced VA included well-known structural complications, and lack of subspecialty care during cataract surgery.

A novel mutation in early-onset sarcoidosis/Blau syndrome: an association with Propionibacterium acnes.

BACKGROUND: Early-onset sarcoidosis (EOS) and Blau syndrome (BS) are systemic inflammatory granulomatous diseases without visible pulmonary involvement, and are distinguishable from their sporadic and familial forms. The diseases are characterized by a triad of skin rashes, symmetrical polyarthritis, and recurrent uveitis. The most common morbidity is ocular involvement, which is usually refractory to conventional treatment. A gain-of-function mutation in the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene has been demonstrated in this disease; however, little is known about the relationship between the activation of NOD2 and the pathophysiology of EOS/BS. Here we describe EOS/BS with a novel mutation in the NOD2 gene, as well as detection of Propionibacterium acnes (P. acnes) in the granulomatous inflammation. CASE PRESENTATION: An 8-year-old Japanese girl presented with refractory bilateral granulomatous panuveitis. Although no joint involvement was evident, she exhibited skin lesions on her legs; a skin biopsy revealed granulomatous dermatitis, and P. acnes was detected within the sarcoid granulomas by immunohistochemistry with P. acnes-specific monoclonal (PAB) antibody. Genetic analyses revealed that the patient had a NOD2 heterozygous D512V mutation that was novel and not present in either of her parents. The mutant NOD2 showed a similar activation pattern to EOS/BS, thus confirming her diagnosis. After starting oral prednisolone treatment, she experienced an anterior vitreous opacity relapse despite gradual prednisolone tapering; oral methotrexate was subsequently administered, and the patient responded positively. CONCLUSIONS: We presented a case of EOS/BS with a novel D512V mutation in the NOD2 gene. In refractory granulomatous panuveitis cases without any joint involvement, EOS/BS should be considered as a differential diagnosis; genetic analyses would lead to a definite diagnosis. Moreover, this is the first report of P. acnes demonstrated in granulomas of EOS/BS. Since intracellular P. acnes activates nuclear factor-kappa B in a NOD2-dependent manner, we hypothesized that the mechanism of granuloma formation in EOS/BS may be the result of NOD2 activity in the presence of the ligand muramyl dipeptide, which is a component of P. acnes. These results indicate that recognition of P. acnes through mutant NOD2 is the etiology in this patient with EOS/BS.

Uveitis for the non-ophthalmologist.

The uveitides are a heterogeneous group of diseases characterized by inflammation inside the eye. The uveitides are classified as infectious or non-infectious. The non-infectious uveitides, which are presumed to be immune mediated, can be further divided into those that are associated with a known systemic disease and those that are eye limited,-ie, not associated with a systemic disease. The ophthalmologist identifies the specific uveitic entity by medical history, clinical examination, and ocular imaging, as well as supplemental laboratory testing, if indicated. Treatment of the infectious uveitides is tailored to the particular infectious organism and may include regional and/or systemic medication. First line treatment for non-infectious uveitides is corticosteroids that can be administered topically, as regional injections or surgical implants, or systemically. Systemic immunosuppressive therapy is used in patients with severe disease who cannot tolerate corticosteroids, require chronic corticosteroids at >7.5 mg/day prednisone, or in whom the disease is known to respond better to immunosuppression. Management of many of these diseases is optimized by coordination between the ophthalmologist and rheumatologist or internist.

Clinical Features and Visual Outcome of Uveitis in Japanese Patients Younger than 18 Years.

Purpose: To investigate the clinical features and visual outcome of young Japanese patients with uveitis.Methods: Patients younger than 18 years who presented with uveitis at the University of Tokyo Hospital between 2000 and 2018 were retrospectively reviewed.Results: The study comprised 98 patients whose mean age was 12.3 ± 3.8 years. Anterior uveitis was present in 52.0%, panuveitis in 37.8%, and posterior uveitis in 10.2%. The most common diagnosis was juvenile chronic iridocyclitis (JCI) (29.6%) followed by tubulointerstitial nephritis and uveitis syndrome (4.1%) and neuroretinitis (4.1%). Thirty-nine patients received systemic anti-inflammatory treatment. Among all subjects, 56% presented with ocular complications and 20% underwent ocular surgery. Visual acuity of 20/200 or less was observed in 6.2%. The common causes of decreased vision were hypotony, serous retinal detachment, and pupil disorder.Conclusions: JCI was the most common diagnosis. Hypotony, serous retinal detachment, and pupil disorder can lead to visual loss.

Pediatric Uveitis in a Referral Center in North Part of Turkey.

Purpose: To analyze the demographic characteristics, clinical features, ocular complications, and visual outcome of pediatric patients with uveitis.Methods: Retrospective evaluation of medical records.Results: The study included 156 eyes of 93 patients. Fifty-three patients were female and 40 were male. Mean age at onset of the uveitis was 9.54 ± 4.29 years. The mean follow-up period was 29.88 ± 28.97 months. Anterior uveitis (49.5%) was the most common anatomic type followed by panuveitis (21.5%), intermediate uveitis (18.3%), and posterior uveitis (10.7%). Juvenile idiopathic arthritis (JIA) was the most common leading systemic disease (18.3%) followed by Behçet disease (11.8%). It was detected at least one complication in 53 (34.0%) eyes at presentation. Mean LogMAR visual acuity was found <0.3 in 136 (87.2%) eyes at final examination.Conclusion: The most common localization was the anterior segment and the most common etiologic relationship was JIA. Visual outcome could be satisfactory with early and appropriate treatment.

Clinical findings and outcomes of uveitis associated with multiple sclerosis.

PURPOSE: To describe the clinical findings and outcomes in patients who presented with uveitis associated with multiple sclerosis. METHODS: Retrospective review of 20 patients (38 eyes). RESULTS: The most frequent ocular finding was multifocal elongated retinal perivenous "sheathing" with focal vascular leakage on fundus fluorescein angiography in 29 eyes followed by vitreous snowballs and debris in 26 eyes, anterior chamber inflammation in 15 eyes, mutton-fat keratic precipitates in 14 eyes, posterior synechiae in 13 eyes, cystoid macular edema in 9 eyes, iris nodules in 4 eyes, and optic neuritis in 3 eyes. Patients with cystoid macular edema were treated successfully with systemic corticosteroids combined with mycophenolate mofetil. Ocular complications were cataract in 6 eyes, glaucoma in 2 eyes and vitreous hemorrhage in 1 eye. CONCLUSIONS: Multifocal elongated retinal perivenous "sheathing" with focal vascular leakage on fundus fluorescein angiography is the most frequent finding in uveitis associated with multiple sclerosis.

Visual Acuity Outcome over Time in Non-Infectious Uveitis.

Introduction: We evaluated visual acuity (VA) over 5 years in a subspecialty noninfectious uveitis population.Methods: Retrospective data from 5,530 noninfectious uveitis patients with anterior, intermediate, posterior or panuveitis were abstracted by expert reviewers. Mean VA was calculated using inverse probability of censoring weighting to account for losses to follow-up.Results: Patients were a median of 41 years old, 65% female, and 73% white. Initial mean VA was worse among panuveitis (20/84) than posterior (20/64), intermediate (20/47), and anterior (20/37) uveitides. On average, mean VA improved by 0.62, 0.51, 0.37, and 0.26 logMAR-equivalent lines over 2 years, respectively (each P < .001), then remained stable, except posterior uveitis mean VA worsened to initial levels.Conclusion: Mean VA of uveitic eyes improved and, typically, improvement was sustained under uveitis subspecialty care. Because VA tends to improve under tertiary care, mean VA change appears a better outcome for clinical studies than time-to-loss of VA.

Comparison of Modified Posterior Sub-Tenon's vs. Trans-Septal Triamcinolone Injection for Non-infectious Uveitis.

Purpose: To compare the safety and efficacy of trans-septal vs. modified posterior sub-Tenon's (PST) corticosteroid injections for noninfectious uveitis.Methods: Retrospective comparison of periocular triamcinolone injection by modified PST (n = 36) vs. traditional trans-septal (n = 79) techniques. Safety and efficacy outcomes were analyzed with regression models.Results: There was no significant difference in visual acuity improvement between the groups at 6 months. There were higher rates of vitritis resolution in the modified PST group but this was not statistically significant (85.7% vs 62.9%, p = .07). Intraocular pressure (IOP) elevation rate trended higher with the modified PST injection (21.9% vs 9.0%, p = .06), with no instances of glaucoma surgery in either group. Two modified PST injection patients with refractory IOP rises had IOP normalization after corticosteroid depot removal. One year cataract surgery rates were similar.Conclusion: Modified PST injection offers clinical efficacy but with possibly higher IOP response rate which could be managed with corticosteroid removal.

Intravitreal Steroid Treatment for Uveitis Associated with Dabrafenib and Trametinib for Metastatic Cutaneous Melanoma.

Purpose: To report a case of bilateral retinal inflammation under long-term therapy with dabrafenib/trametinib for metastatic cutaneous melanoma.Methods: Retrospective chart review.Results: A 59-year-old patient with metastatic cutaneous melanoma diagnosed in 2004 under treatment with dabrafenib/trametinib since 2014 presented to our department with intraretinal hemorrhage and extrafoveal macula edema on the right eye and optic disc swelling on the left eye. The patient did not report visual complaints. After cessation of dabrafenib/trametinib and subconjunctival and intravitreal corticosteroid injections, optic disc swelling on the left eye recovered after 6 months. The macula edema on the right eye was treated with one intravitreal anti-VEGF (vascular endothelial growth factor) injection after encroaching upon the fovea 10 months after initial presentation. The final visual acuity was 20/20 on both eyes.Conclusion: Even after years of treatment with low dose dabrafenib/trametinib, ocular toxicity can develop. Such cases can respond well to intravitreal corticosteroids.

Seven-Year Outcomes of Uveitic Macular Edema: The Multicenter Uveitis Steroid Treatment Trial and Follow-up Study Results.

PURPOSE: To evaluate the long-term outcomes of uveitic macular edema (ME). DESIGN: Longitudinal follow-up of a cohort of participants in a randomized clinical trial. PARTICIPANTS: A total of 248 eyes of 177 participants with uveitic ME enrolled in the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study. METHODS: OCT measurements, taken at baseline and annually, were graded by reading center graders masked to clinical data. Macular edema was defined as a center macular thickness (CMT) ≥240 µm on time-domain OCT or time-domain OCT equivalent. Resolution of ME was defined as normalization of macular thickness on OCT. Relapse of ME was defined as increase in macular thickness to ≥240 µm in an eye that previously had resolution. Visual acuity was measured at each visit with logarithmic visual acuity charts. MAIN OUTCOME MEASURES: Resolution and relapse of ME. Visual acuity. RESULTS: Among 227 eyes with ME followed ≥1 year, the cumulative percent of eyes with ME resolving at any point during 7 years was 94% (95% confidence interval [CI], 89-97). Epiretinal membranes on OCT were associated with a lower likelihood of ME resolution (hazard ratio [HR], 0.74; 95% CI, 0.55-1.01; P = 0.05). Among 177 eyes with resolved ME, the cumulative percent with relapse within 7 years was 43% (95% CI, 32-51). Eyes in which ME resolved gained a mean of 6.24 letters (95% CI, 4.40-8.09; P < 0.001) compared with eyes that remained free from ME during the 1-year follow-up intervals, whereas eyes in which ME did not resolve experienced no gain in vision (mean change -1.30 letters; 95% CI, -2.70 to 0.09; P = 0.065), and eyes that developed ME during the year (incident or relapsed) experienced a mean loss of -8.65 letters (95% CI, -11.5 to -5.84, P < 0.001). CONCLUSIONS: Given sufficient time and treatment, nearly all uveitic ME resolves, but episodes of relapse were common. Visual acuity results were better among eyes with resolved ME, suggesting that control of inflammation and resolution of ME might be visually relevant treatment targets.