Purpose To evaluate the efficacy of corticosteroid‐sparing immunomodulatory therapy (IMT) in patients with recurrent and/or sight‐threatening central multifocal choroiditis (MFC). Methods This was a retrospective cohort study in a tertiary uveitis centre including all patients with MFC who have been treated with IMT for at least 12 months. Clinical data and imaging results were collected regarding the period prior to the start of IMT and at 3, 6, 12 and – where available – 24 months after the start of IMT. Main outcome measure was the number of annual recurrences of choroiditis with or without active choroidal neovascularization before and after the start of IMT. Secondary outcomes were the percentage of patients with (steroid‐free) remission and the median time between the start of IMT and (steroid‐free) remission. Results Thirty‐two patients (39 eyes) were included. At the start of IMT, none of the patients were in (steroid‐free) remission. At 24 months, the probability of achieving remission and steroid‐free remission was 88,5% and 50%, respectively. The median time to achieve remission and steroid‐free remission was 21 and 83 weeks, respectively. In 17 patients (20 eyes) with available clinical data and imaging results for ≥ 12 months prior to the start of IMT, the mean number of recurrences/year decreased significantly from 1.40 ± 0.81 at baseline to 0.49 ± 0.47 (p = 0.001) after the start of IMT. Conclusions Preventive therapy with IMT should be considered in patients with recurrent and/or sight‐threatening MFC to decrease the number of recurrences/year and to increase the prospects of achieving either remission or steroid‐free remission.

Purpose To evaluate the efficacy of adalimumab in patients with central multifocal choroiditis (cMFC) refractory to conventional corticosteroid-sparing immunomodulatory agents (IMT). Methods Medical records were reviewed from all patients with cMFC and treated with adalimumab with follow-up of at least 12 months. The study focused on the 12 months prior to and after the start of adalimumab. The imaging results were independently evaluated by two ophthalmologists. The main outcomes were the number of patients without a relapse of disease activity in 12 months after the start of adalimumab and the ability to stop the systemic corticosteroids to evaluate the corticosteroid-sparing effect. Results Twelve patients (18 eyes) were included. In 8/12 (67%) patients no relapse of disease activity was observed in the 12 months after the start of adalimumab. In 9/12 patients the systemic corticosteroid treatment could be stopped and in an additional 2 patients tapered to ≤7,5mg daily. In the 12 months before the start of adalimumab, the patients experienced a median of 3 (range 2–4) relapses of disease activity. Nine patients experienced relapses while treated with a combination of systemic corticosteroids (mean dose 13,6 mg; range 5–25 mg) and IMT. Moreover, 3 patients treated with IMT, experienced relapses after tapering and stopping the systemic corticosteroids. In all eyes (n = 5) with CNV before the start of adalimumab, the intravitreal anti -VEGF injections could be stopped after the start of adalimumab. Conclusions AND IMPORTANCE: Adalimumab may be effective in patients with cMFC refractory to IMT and may be considered as a treatment option in patients with cMFC.

PurposeWe aimed to evaluate the blood cell composition in patients with central multifocal choroiditis (cMFC), a rare form of posterior uveitis predominantly affecting young myopic women.MethodsIn this retrospective observational case-control study, a 104-parameter automated hematocytometry was conducted by the Cell-Dyn Sapphire hematology analyzer for 122 cases and 364 age- and sex-matched controls. Cox proportional regression analysis was used to assess the relation between the blood cell composition and the time between disease onset (first visit) and the start of systemic corticosteroid-sparing immunomodulatory therapy (IMT).ResultsAt a false discovery rate of 5% (Padj), we identified a decrease of blood monocytes in cases with cMFC, which could be attributed to disease activity. Cox proportional hazard analysis including age and sex revealed that increased platelet granularity (measured by mean intermediate angle scatter) was an independent risk factor for treatment with IMT (hazard ratio = 2.3 [95% confidence interval = 1.28 - 4.14], Padj = 0.049). The time between the first presentation and the start of IMT was 0.3 years in the group with an increased platelet granularity and 3.4 years in the group without increased platelet granularity.ConclusionsPatients with cMFC demonstrated a decrease in blood monocytes. Moreover, platelet granularity could potentially be used as a marker for treatment with IMT.

Purpose To evaluate the clinical course of idiopathic multifocal choroiditis (MFC) and punctate inner choroidopathy (PIC) and the efficacy and safety of treatment options during pregnancy. Methods Patients with MFC or PIC and a pregnancy in 2011–2019 from two academic centres were enrolled. For the most recent pregnancy, data on best‐corrected visual acuity (BCVA) before and after pregnancy, relapse rate in pregnancy and postpartum period and obstetric, maternal and neonatal outcomes were collected. Treatment regimens consisted of a wait‐and‐see regime and an immunosuppressive treatment regime with systemic corticosteroids and/or azathioprine, both combined with intravitreal antivascular endothelial growth factor injections when indicated. Results Sixteen women (26 affected eyes) were included. Median Snellen BCVA was 20/19 before pregnancy and 20/18 after delivery. In seven pregnancies a wait‐and‐see regime and in nine pregnancies an immunosuppressive treatment regime was carried out. Fourteen intravitreal anti‐VEGF injections were given in six pregnancies. The relapse rate during pregnancy was 44% and in the postpartum period 31%. Maternal/obstetrical and fetal complications occurred in 31% and 13% of the pregnancies, respectively. Fifteen healthy children were born and one pregnancy ended in a stillbirth in a patient with a complicated obstetrical history. One patient treated with azathioprine developed intrahepatic cholestasis of pregnancy (ICP). Conclusions Among women with MFC and PIC BCVA remained stable during pregnancy despite a relapse rate of 44% in pregnancy. No major maternal, obstetric and fetal complications occurred in pregnant patients treated with systemic corticosteroids, azathioprine or intravitreal anti‐VEGF injections, though one patient developed ICP while treated with azathioprine.

Introduction The aim of this study is to describe the course of disease in patients with idiopathic multifocal choroiditis (MFC) and punctate inner choroidopathy (PIC) and to identify risk factors associated with an increased relapse rate of disease activity. Methods In this prospective observational cohort study, demographical and clinical data were collected concerning the relapses rate of disease activity, the conclusions of the multimodal imaging results, treatment, complications and self-reported quality of life. Disease activity was defined as new inflammatory lesions or active inflammation in pre-existing chorioretinal lesions either with or without active choroidal neovascularization (CNV). Linear regression analysis was performed to identify risk factors associated with an increased relapse rate. Results In total 122 eyes of 82 patients (93% females) were included with a median age (IQR) of 45 (37-54) years. A history of secondary CNV was present in 66% of the eyes. During follow-up the best-corrected visual acuity remained stable despite a median relapse rate (IQR) of 1.0 (0.25-3). Cycles of oral corticosteroids was given in 59% of the patients, 72% were treated at baseline or started treatment during follow-up with a disease-modifying antirheumatic drug (DMARD) and 35% with a biological agent in addition to the DMARD. Both a history of secondary CNV (B=1.2, 95% CI 0.7-1.7, P=3.6×10-5) and high myopia (<-6 diopters) (B=0.6, 95% CI 0.1-1.1, P=0.02) independently increased the relapse rate of disease activity. Discussion/Conclusion A history of secondary CNV and high myopia were associated with an increased relapse rate of disease activity. Moreover, the results of this study emphasize the challenging character of treating patients with MFC/PIC.

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ImportanceIdiopathic multifocal choroiditis (MFC) is poorly understood, thereby hindering optimal treatment and monitoring of patients.ObjectiveTo identify the genes and pathways associated with idiopathic MFC.Design, Setting, and ParticipantsThis was a case-control genome-wide association study (GWAS) and protein study of blood plasma samples conducted from March 2006 to February 2022. This was a multicenter study involving 6 Dutch universities. Participants were grouped into 2 cohorts: cohort 1 consisted of Dutch patients with idiopathic MFC and controls, and cohort 2 consisted of patients with MFC and controls. Plasma samples from patients with idiopathic MFC who had not received treatment were subjected to targeted proteomics. Idiopathic MFC was diagnosed according to the Standardization of Uveitis Nomenclature (SUN) Working Group guidelines for punctate inner choroidopathy and multifocal choroiditis with panuveitis. Data were analyzed from July 2021 to October 2022.Main outcomes and measuresGenetic variants associated with idiopathic MFC and risk variants associated with plasma protein concentrations in patients.ResultsThis study included a total of 4437 participants in cohort 1 (170 [3.8%] Dutch patients with idiopathic MFC and 4267 [96.2%] controls; mean [SD] age, 55 [18] years; 2443 female [55%]) and 1344 participants in cohort 2 (52 [3.9%] patients with MFC and 1292 [96.1%] controls; 737 male [55%]). The primary GWAS association mapped to the CFH gene with genome-wide significance (lead variant the A allele of rs7535263; odds ratio [OR], 0.52; 95% CI, 0.41-0.64; P = 9.3 × 10−9). There was no genome-wide significant association with classical human leukocyte antigen (HLA) alleles (lead classical allele, HLA-A*31:01; P = .002). The association with rs7535263 showed consistent direction of effect in an independent cohort of 52 cases and 1292 control samples (combined meta-analysis OR, 0.58; 95% CI, 0.38-0.77; P = 3.0 × 10−8). In proteomic analysis of 87 patients, the risk allele G of rs7535263 in the CFH gene was strongly associated with increased plasma concentrations of factor H–related (FHR) proteins (eg, FHR-2, likelihood ratio test, adjusted P = 1.1 × 10−3) and proteins involved in platelet activation and the complement cascade.Conclusions and relevanceResults suggest that CFH gene variants increase systemic concentrations of key factors of the complement and coagulation cascades, thereby conferring susceptibility to idiopathic MFC. These findings suggest that the complement and coagulation pathways may be key targets for the treatment of idiopathic MFC.