The efficacy of corticosteroid-sparing immunomodulatory therapy in treating patients with central multifocal choroiditis

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

The efficacy of adalimumab in treating patients with central multifocal choroiditis

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

Exploring Imaging Characteristics Associated With Disease Activity in Idiopathic Multifocal Choroiditis: A Multimodal Imaging Approach

Purpose: To identify characteristics on multimodal imaging (MMI) in idiopathic multifocal choroiditis (MFC) that can identify inflammatory activity and distinguish choroidal neovascularization (CNV) activity from inflammatory activity. Design: Prospective cohort study. Methods: MMI consisted of spectral-domain optical coherence tomography (angiography) (SD-OCT(A)), fundus autofluorescence, fundus photography, infrared imaging, fluorescein angiography (FA), and indocyanine green angiography (ICGA). MMI characteristics obtained during active and inactive disease were compared within the same lesion. Secondly, MMI characteristics were compared between active inflammatory lesions with and without CNV activity. Results: Fifty patients (110 lesions) were included. In 96 lesions without CNV activity, the mean focal choroidal thickness was increased during the active disease (205 µm) compared to the inactive disease (180 µm) (P ≤ .001). Lesions with inflammatory activity typically demonstrated moderately reflective material located in the sub–retinal pigment epithelium (RPE) and/or in the outer retina with disruption of the ellipsoid zone. During the inactive stage of the disease, the material disappeared or became hyperreflective and indistinguishable from the RPE. During the active stage of the disease, the area of hypoperfusion in the choriocapillaris significantly increased as visualized on both ICGA and SD-OCTA. CNV activity in 14 lesions was associated with subretinal material with a mixed reflectivity and hypotransmission of light to the choroid on SD-OCT and leakage on FA. SD-OCTA identified vascular structures in all active CNV lesions and in 24% of lesions without CNV activity (showing old, quiescent CNV membranes). Conclusion: Inflammatory activity in idiopathic MFC was associated with several MMI characteristics, including focally increased choroidal thickness. These characteristics can guide clinicians in the challenging process of the evaluation of disease activity in idiopathic MFC patients

Immunology and Microbiology Clinical Manifestations and Outcome of Syphilitic Uveitis

RESULTS. Mean age was 47 years (range, 27-73 years), 82.4% were male. HIV positivity was found in 28 (35.9%) patients; 13 were newly diagnosed. Most patients had pan (45.9%) or posterior (31.8%) uveitis. On average, logMAR visual acuity (VA) improved significantly from 0.55 at the start of syphilis treatment to 0.34 at 1 month and to 0.27 at 6 months follow-up. Most patients (86.7%) reached disease remission. No differences in efficacy between the various treatment regimens were found. A high logMAR VA at the start of syphilis treatment and a treatment delay of more than 12 weeks were prognostic for a high logMAR VA at 6 months follow-up. Chronicity was not related to any form of treatment, HIV status, or Venereal Disease Research Laboratory test outcome. CONCLUSIONS. In this large cohort of 85 patients with syphilitic uveitis, visual outcomes were favorable in the majority of cases. Visual outcome was dependent on VA at the start of syphilis treatment and treatment delay

Association of Risk Variants in the <i>CFH </i>Gene With Elevated Levels of Coagulation and Complement Factors in Idiopathic Multifocal Choroiditis

Importance: Idiopathic multifocal choroiditis (MFC) is poorly understood, thereby hindering optimal treatment and monitoring of patients. Objective: To identify the genes and pathways associated with idiopathic MFC. Design, Setting, and Participants: This 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 measures: Genetic variants associated with idiopathic MFC and risk variants associated with plasma protein concentrations in patients. Results: This 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 relevance: Results 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.</p

Association of Risk Variants in the CFH Gene With Elevated Levels of Coagulation and Complement Factors in Idiopathic Multifocal Choroiditis

Importance: Idiopathic multifocal choroiditis (MFC) is poorly understood, thereby hindering optimal treatment and monitoring of patients. Objective: To identify the genes and pathways associated with idiopathic MFC. Design, Setting, and Participants: This 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 measures: Genetic variants associated with idiopathic MFC and risk variants associated with plasma protein concentrations in patients. Results: This 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 relevance: Results 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

Risk of Rhegmatogenous Retinal Detachment in Acute Retinal Necrosis With and Without Prophylactic Intervention

Purpose: To study whether preventive laser or preventive vitrectomy is able to lower the risk of rhegmatogenous retinal detachment (RRD) in patients with acute retinal necrosis (ARN). Design: A retrospective, interventional case series. Methods: We performed a retrospective study of 59 patients (63 eyes) with ARN treated in a single tertiary referral center. We analyzed different groups with either no prophylaxis, prophylactic laser, or prophylactic vitrectomy. Main outcome measure was incidence of RRD. Results: Overall incidence of RRD was 44.4%, including 13% at presentation. In a crude analysis, the risk of RRD was highest in 33 patients with prophylactic laser (45.5%), lower in 15 patients with no prophylaxis (26.7%), and lowest in 7 patients with prophylactic vitrectomy (14.3%). Baseline best-corrected visual acuity differed between these groups, but zone and percentage of involved retina did not. In a multivariable model including prophylactic laser and ARN severity, only zone was predictive of RRD. Conclusion: When correcting for severity of disease, we did not observe a reduction in the risk of RRD by prophylactic laser in eyes with ARN. Therefore, prophylactic laser may be abandoned. The role of prophylactic vitrectomy is still unclear, but deserves further investigation

Visual Outcome, Treatment Results, and Prognostic Factors in Patients with Scleritis

<p>Purpose: To analyze the visual outcome, systemic associations, effectiveness of treatment, and predicting features of 104 scleritis patients.</p><p>Design: Retrospective case series.</p><p>Participants: One hundred four patients treated for scleritis at the University Medical Centers of Groningen and Utrecht, The Netherlands.</p><p>Methods: The clinical records of 104 patients diagnosed with scleritis between 1992 and 2011 at the University Medical Centers of Groningen (n = 64) and of Utrecht (n = 40) were analyzed retrospectively.</p><p>Main Outcome Measures: Loss of visual acuity, ocular complications, related systemic disease, type of treatment, time to treatment success, and predictive features.</p><p>Results: Mean age +/- standard deviation (SD) was 51.5 +/- 13.6 years, and 63 (60.6 %) patients were female. Mean follow-up +/- SD was 38.2 +/- 33.8 months. A loss of more than 2 lines of Snellen acuity was observed in 23 patients, 3 of whom had a final visual acuity of no light perception. In general, patients with necrotizing scleritis (n = 15) had a poorer outcome. Ocular complications were observed in 88 (84.6%) patients. Underlying systemic disease was identified in 34 (32.7%) patients. Steroid-sparing immunosuppressive medication was used in 47 patients, 36 of whom were treated with methotrexate (MTX). This treatment was successful in 17 (47.2%) patients over the course of a mean +/- SD of 103.7 +/- 83.7 weeks. Mycophenolate mofetil was the treatment in 10 patients, and in 5 of these patients, treatment success was achieved in a mean +/- SD of 65.3 +/- 37.4 weeks. Treatment with tumor necrosis factor alpha (TNF-alpha) antagonists led to treatment success in a mean +/- SD of 32.6 +/- 21.8 weeks in 5 of the 11 treated patients. Patients with loss of visual acuity or those treated with steroid-sparing immunosuppressive drugs more often had an underlying associated disease, bilateral scleritis, and a longer duration of symptoms at presentation.</p><p>Conclusions: Scleritis is a severe ocular inflammatory disease often associated with ocular complications. In this population, roughly half of the patients were treated with systemic immunosuppressive medication. Mycophenolate mofetil and TNF-alpha antagonists can be used in case of MTX failure. Tumor necrosis factor alpha antagonists seemed to be more effective than MTX. Within this group, an underlying associated disease, bilateral scleritis, and a longer duration of symptoms at presentation were predictive features for a more severe disease course.</p><p>Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2013;120:379-386 (C) 2013 by the American Academy of Ophthalmology.</p>

Potential Predictors of Poor Visual Outcome in Human Leukocyte Antigen-B27-Associated Uveitis

Purpose: To identify potential predictors of permanent vision loss in patients with human leukocyte antigen (HLA)-B27-associated uveitis in a tertiary referral center. Design: Retrospective case-control study. Methods: The charts of 212 patients (338 eyes) with HLA-B27-associated uveitis that visited the University Medical Center Utrecht with a follow-up of at least 6 months were retrospectively studied. Clinical features at presentation and during follow-up were compared to final visual outcome in quiescent state. Eyes with (sub-) normal vision (>20/50) were compared with visually impaired (≤20/50) and blind (≤5/50, or a visual field of 21 mm Hg, hypotony, and panuveitis to be potential predictors at presentation, and the development of secondary glaucoma or hypotony to be predictors of blindness or visual impairment during follow-up. Conclusions: The long-term visual prognosis of HLA-B27-associated uveitis is relatively good, but the true incidence of permanent vision loss is probably still underestimated. Our findings highlight the importance of proper control of intraocular pressure

Prevalence and characteristics of ocular pain in non-infectious uveitis : A quality of life study

Background/aim To survey the frequency, character, severity and impact of ocular pain on quality of life in adult patients with non-infectious uveitis (NIU). Methods This patient-requested cross-sectional survey study describes the results of three self-administered questionnaires (the National Eye Institute Visual Function Questionnaire, the 36-Item Short Form Health Survey (SF-36) and the McGill Pain Questionnaire Dutch Language Version) from 147 patients with NIUs from a university-based tertiary referral centre in Utrecht. Results The mean Visual Function Questionnaire (VFQ) Ocular Pain Score of all patients with NIU was 72 (±24), which is significantly lower than an ocular disease-free reference group (90±15, P<0.0001), indicating more ocular pain. This was true for all types of NIU, regardless of the localisation: although Ocular Pain Scores were lower in patients with anterior uveitis (AU) compared with patients with non-AU (mean 62 (±24) vs 74 (±24), P=0.04), patients with non-AU still scored substantially lower than the reference group that had no ocular history (P<0.0001). Patients with NIU also scored significantly lower on all other VFQ subscales as well as on the SF-36 subscales Role Limitations due to physical problems', 'Vitality', eneral health' and 'Bodily Pain' compared with controls. The VFQ Ocular Pain subscale correlated with other quality of life subscales (both VFQ-25 and SF-36), indicating a relationship between pain and quality of life. Conclusion This study shows that ocular pain is highly prevalent in patients with NIU, regardless of the localisation. Furthermore, ocular pain has an impact on quality of life