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.

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.

The International Vitreoretinal B-Cell Lymphoma Registry: a protocol paper.

INTRODUCTION: Vitreoretinal lymphoma is a rare ocular cancer with high morbidity and mortality despite treatment. Diagnosis by cytopathology is often delayed, and various molecular and image-based investigations have been developed. Diverse treatments are used, but there is a limited medical evidence to differentiate their effectiveness. We designed an international registry that would collect diagnostic, treatment and outcomes data, to establish new evidence for the management of this cancer. METHODS AND ANALYSIS: The International Vitreoretinal B-Cell Lymphoma Registry will accrue data retrospectively for individuals aged 18 years or older, diagnosed with new or recurrent vitreoretinal B-cell lymphoma on or after 1 January 2020. A steering committee of subspecialised ophthalmologists identified 20 key clinical data items that describe patient demographics, tissue involvements, diagnostic testing, ocular and systemic treatments and treatment complications, and visual acuity and survival outcomes. Customised software was designed to permit collection of these data across a single baseline and multiple follow-up forms. The platform collects data without identifiers and at 3 month reporting intervals. Outcomes of the project will include: (1) descriptions of clinical presentations, and diagnostic and therapeutic preferences; (2) associations between clinical presentations, and diagnostics and treatments, and between diagnostics and treatments (assessed by ORs with 95% CIs); and (3) estimations of rates of vision loss, and progression-free and overall survival (assessed by Kaplan-Meier estimates). ETHICS AND DISSEMINATION: The registry has received Australia-wide approval by a national human research ethics committee. Sites located outside Australia are required to seek local human research ethics review. Results generated through the registry will be disseminated primarily by peer-reviewed publications that are expected to inform clinical practice, as well as educational materials.

Central Nervous System Progression in Primary Vitreoretinal Lymphoma with Bilateral and Unilateral Involvement: A Systematic Review and Meta-Analysis.

BACKGROUND: Primary vitreoretinal lymphoma (PVRL) is either unilateral or bilateral at initial presentation. Progression to a central nervous system (CNS) lymphoma is regularly observed and these patients seem to have an inferior survival. Knowledge of the predictive value of laterality for CNS progression may facilitate risk stratification and the development of more effective treatment strategies, and eventually, improve outcomes. The objective of this analysis is to estimate the risk of CNS progression for patients with bilateral versus unilateral involvement of PVRL. METHODS: Systematic literature search for studies on CNS progression in PVRL with bilateral and unilateral involvement according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We assessed the risk of bias and the methodological quality of studies using the Quality in Prognosis Studies (QUIPS) tool. Risk ratios of CNS progression in PVRL with bilateral and unilateral involvement were calculated and combined via a meta-analysis. RESULTS: Twenty-five small-sized (total n = 371 cases) studies were included. The majority of the studies were at medium to high risk of bias. Results suggest no significant difference in CNS progression between bilateral and unilateral PVRL, with a pooled relative risk ratio of 1.12 (95% confidence interval 0.89-1.41). CONCLUSIONS: CNS progression is common in PVRL. From the limited available evidence, there is no significant difference in CNS progression between bilateral and unilateral PVRL.

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.

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.

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.

Clinical Manifestations, Prognosis, and Vaccination Status of Patients With Rubella Virus-Associated Uveitis.

PURPOSE: To assess the clinical and laboratory manifestations and vaccination status of uveitis patients positive for rubella virus (RV) in aqueous humor and investigate its relationship to Fuchs uveitis syndrome (FUS). METHODS: Retrospective study of all uveitis patients, positive for RV in aqueous humor analysis (polymerase chain reaction [PCR] and/or Goldmann-Witmer coefficient [GWC]) between January 2010 and October 2016 at the ophthalmology departments in the Erasmus Medical Center (Rotterdam) and University Medical Center Utrecht. Outcomes of aqueous analyses of FUS patients during this period were assessed. RESULTS: We included 127 patients (144 eyes) positive for RV in aqueous fluid: 23 (20%) by PCR, 120 (97%) by GWC, and 16 (13%) by both. The average age at first presentation was 37 years. Patients typically complained of blurred vision and exhibited a combination of unilateral anterior uveitis, keratic precipitates, vitritis, and absence of posterior synechiae, but the classical FUS was observed in a minority. The main cause of untreatable visual loss was glaucoma. Cystoid macular edema (CME) before intraocular surgery was not encountered. None of the unilateral cases developed involvement of the other eye. None of the patients was vaccinated against RV. All FUS patients, except 2 (5%), were positive for RV. CONCLUSION: RV-associated uveitis and FUS are not exchangeable. Chronic anterior uveitis, vitritis, early development of cataract, and the absence of posterior synechiae and CME characterize RV-associated uveitis. Almost all FUS cases had documented intraocular RV infection, but only some of the patients with RV-associated uveitis presented with FUS.

High-Dimensional Profiling Reveals Heterogeneity of the Th17 Subset and Its Association With Systemic Immunomodulatory Treatment in Non-infectious Uveitis.

Background: Non-infectious uveitis (NIU) is a severe intra ocular inflammation, which frequently requires prompt systemic immunosuppressive therapy (IMT) to halt the development of vision-threatening complications. IMT is considered when NIU cannot be treated with corticosteroids alone, which is unpredictable in advance. Previous studies have linked blood cell subsets to glucocorticoid sensitivity, which suggests that the composition of blood leukocytes may early identify patients that will require IMT. Objective: To map the blood leukocyte composition of NIU and identify cell subsets that stratify patients that required IMT during follow-up. Methods: We performed controlled flow cytometry experiments measuring a total of 37 protein markers in the blood of 30 IMT free patients with active non-infectious anterior, intermediate, and posterior uveitis, and compared these to 15 age and sex matched healthy controls. Results from manual gating were validated by automatic unsupervised gating using FlowSOM. Results: Patients with uveitis displayed lower relative frequencies of Natural Killer cells and higher relative frequencies of memory T cells, in particular the CCR6+ lineages. These results were confirmed by automatic gating by unsupervised clustering using FlowSOM. We observed considerable heterogeneity in memory T cell subsets and abundance of CXCR3-CCR6+ (Th17) cells between the uveitis subtypes. Importantly, regardless of the uveitis subtype, patients that eventually required IMT in the course of the study follow-up exhibited increased CCR6+ T cell abundance before commencing therapy. Conclusion: High-dimensional immunoprofiling in NIU patients shows that clinically distinct forms of human NIU exhibit shared as well as unique immune cell perturbations in the peripheral blood and link CCR6+ T cell abundance to systemic immunomodulatory treatment.

Potential Diagnosis of Vitreoretinal Lymphoma by Detection of MYD88 Mutation in Aqueous Humor With Ultrasensitive Droplet Digital Polymerase Chain Reaction.

Importance: The diagnostic workup of patients suspected of having vitreoretinal lymphoma (VRL) is primarily based on vitreous fluid analysis, including the recently emerging myeloid differentiation primary response gene 88 (MYD88) mutation analysis. Aqueous humor paracentesis is a relatively less invasive and safer procedure than taking vitreous fluid specimens, and aqueous humor-based MYD88 mutation analysis would provide an additional liquid biopsy tool to diagnose and monitor patients with VRL. Objective: To investigate whether the detection of MYD88 L265P by highly sensitive droplet digital polymerase chain reaction (ddPCR) is feasible in the vitreous fluid and aqueous humor of patients with VRL. Design, Setting, and Participants: This cohort study includes aqueous humor and vitreous fluid samples from patients with VRL who were treated at the University Medical Center Utrecht, in Utrecht, the Netherlands, from August 2005 to August 2017. Ocular fluids were randomized and masked before MYD88 L265P analysis, which was performed using an in-house validated ddPCR platform. Patients with uveitis were included as a comparison group. Main Outcomes and Measures: The presence of MYD88 L265P mutation detected by ddPCR in AH and VF. Results: The study included 96 samples from 63 individuals, including 23 patients with VRL (of whom 10 were female and 13 male, with a mean [SD] age of 72 [7.3] years) and 40 individuals with uveitis (of whom 23 were female and 17 male, with a mean [SD] age of 58 [20.9] years). In 17 of 23 patients with VRL (74%), MYD88 L265P was detected; it was not detected in any of the patients with uveitis. It was detectable in both vitreous fluid and aqueous humor samples. In the paired samples, the mutation was detected in 8 of 9 aqueous humor samples (89%) of the MYD88 L265P-positive vitreous fluid samples. In vitreous fluid, the MYD88 ddPCR test showed a sensitivity of 75% (95% CI, 50%-92%) and a positive predictive value of 100%; in aqueous humor, sensitivity was 67% (95% CI, 42%-92%), and positive predictive value was 100%. Specificity was 100% in both fluids. After treatment, the mutation was no longer detectable in any ocular fluids. Conclusions and Relevance: The high concordance between aqueous humor and vitreous fluid samples suggests that use of the easily accessible aqueous humor is nearly as informative as vitreous fluid in the identification of key somatic mutations in patients with VRL. This approach may provide an additional minimally invasive tool for accurate diagnosis, detection of recurrence, and monitoring of treatment.

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', 'General 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.

Diagnosis of Cytomegalovirus Anterior Uveitis in Two European Referral Centers.

PURPOSE: To evaluate diagnostic methods and clinical signs of CMV anterior uveitis (AU), a rarely described entity in Europe. METHODS: We included patients with clinical characteristics of CMV AU and positive PCR and/or Goldmann-Witmer coefficient (GWc) for CMV. RESULTS: We report 21 patients with unilateral uveitis (100%) and signs of Posner-Schlossman syndrome (PSS) (n = 20, 95.2%), Fuchs uveitis syndrome (FUS) (n = 1, 4.7%), and endotheliitis (n = 4, 19,04%). PCR was positive in 15/21 (71.4%) and GWc in 8/9 patients (88.9%) in aqueous for CMV. GWc was the only positive test in 6/9 patients (66,6%). When PCR alone was performed (without GWc) in the first tap, repeated aqueous taps were needed, twice in five cases and thrice in one case. CONCLUSION: Combining PCR and GWc were very helpful to confirm the clinical diagnosis of CMV AU. In case of very high clinical suspicion and negative results, repeated tap seems to be recommended.

No Value for Routine Serologic Screening for Borrelia burgdorferi in Patients With Uveitis in the Netherlands.

PURPOSE: To determine whether routine serologic screening for Borrelia burgdorferi and subsequent aqueous or vitreous humor analysis is useful in patients with uveitis. DESIGN: Cross-sectional study. METHODS: All patients referred to our tertiary uveitis referral clinic in the period of from January 1, 2004 to October 31, 2014, in whom routine serologic screening for Borrelia burgdorferi (IgG as determined by enzyme-linked immunosorbent assay and confirmed by immunoblot) was performed were retrospectively reviewed. In patients with an unclassified uveitis, aqueous and vitreous humor and cerebrospinal fluid were also analyzed. Local antibody production was determined by Goldmann-Witmer coefficient calculation or polymerase chain reaction for B burgdorferi. The seroprevalence of B burgdorferi among patients with uveitis was compared to the general population. RESULTS: Borrelia burgdorferi screening was performed in 1126 uveitis patients (44.3% male, mean age 45.9 ± 19.6 years). The seroprevalence of B burgdorferi among uveitis patients was 3.7% (95% confidence interval 2.6%-4.8%) (n = 42) as compared to 5%-10% in the general Dutch population. Of these 42 patients, 14 (1.2% of all uveitis patients) had an unclassified uveitis, 7 of whom underwent aqueous humor (n = 5) or vitreous humor (n = 2) analysis and cerebrospinal fluid analysis (n = 2). None of the patients had local antibody production in either ocular or cerebrospinal fluid. CONCLUSION: The prevalence of immunoblot-confirmed B burgdorferi IgG seropositivity in our uveitis patients is only slightly lower as compared to the general Dutch population. Intraocular antibody production and DNA was absent in all tested patients. These findings do not support routine serologic examination for Borrelia in uveitis patients.

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 <10 degrees) eyes, using survival analysis. A multivariate Cox proportional hazards analysis was performed to analyze potential predictors for permanent vision loss. RESULTS: Median follow-up was 10.4 years (range, 0.5-44.7 years). During follow-up 226 eyes (66%) experienced vision loss up to 20/50, but most recovered. Twenty patients (9%) became permanently visually impaired or blind in at least 1 eye because of uveitis, after a median of 9.7 years (range, 0-20.9 years). The main cause was secondary glaucoma or related to glaucoma surgery (12/22 eyes, 55%). Survival analysis showed, after adjustment for age and sex, an ocular pressure 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.

Clinical Manifestations and Outcome of Syphilitic Uveitis.

PURPOSE: To analyze visual outcome, effectiveness of various modes of antibiotic treatment, and prognostic factors in patients with serologically proven syphilitic uveitis. METHODS: The clinical records of 85 patients (139 eyes) diagnosed with syphilitic uveitis between 1984 and 2013 at tertiary centers in The Netherlands were retrospectively analyzed. 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.

Long-term visual prognosis of peripheral multifocal chorioretinitis.

PURPOSE: To report on the clinical manifestations, complications, and long-term visual prognosis of patients with peripheral multifocal chorioretinitis and to search for predictors for a lower visual outcome. DESIGN: Retrospective consecutive observational case series. METHODS: setting: Institutional. PATIENT POPULATION: 134 eyes in 69 patients with a minimum follow-up period of 5 years. OBSERVATION PROCEDURE: Clinical characteristics were recorded as well as the visual acuity (VA) at the onset of uveitis; after 1, 5, and 10 years; and at the end of the follow-up period. MAIN OUTCOME MEASURES: Visual acuity, clinical features and complications, required medications and surgeries. RESULTS: The majority of the patients were elderly women with chronic bilateral ocular involvement, who developed multiple ocular complications over time. Systemic sarcoidosis was present in 39% of patients. In addition to peripheral retinal lesions and vitritis, papillitis was present in 95% of cases. The major complications included macular edema (91%), cataract (93%), glaucoma (35%), and optic disc atrophy (25%). The treatment regimens included systemic corticosteroids and/or immunosuppressive drugs in 44% of patients, and 84% of patients required intraocular surgery. One third of the affected eyes developed VA <20/40 at 5-10 years of follow-up. VA at 1 year was the most important predictor of visual outcome at 5 and 10 years (P < .001). CONCLUSIONS: Peripheral multifocal chorioretinitis was associated with a high prevalence of cataract, macular edema, optic disc atrophy, and glaucoma. Despite the chronic course of the disease, multiple complications, and surgical interventions, the majority of patients achieved satisfactory long-term visual acuity.

Treatment strategies in primary vitreoretinal lymphoma: a 17-center European collaborative study.

IMPORTANCE: The best treatment option for primary vitreoretinal lymphoma (PVRL) without signs of central nervous system lymphoma (CNSL) involvement determined on magnetic resonance imaging or in cerebrospinal fluid is unknown. OBJECTIVE: To evaluate the outcomes of treatment regimens used for PVRL in the prevention of subsequent CNSL. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted at 17 referral ophthalmologic centers in Europe. We reviewed clinical, laboratory, and imaging data on 78 patients with PVRL who did not have CNSL on presentation between January 1, 1991, and December 31, 2012, with a focus on the incidence of CNS manifestations during the follow-up period. INTERVENTIONS: The term extensive treatment was used for various combinations of systemic and intrathecal chemotherapy, whole-brain radiotherapy, and peripheral blood stem cell transplantation. Therapy to prevent CNSL included ocular radiotherapy and/or ocular chemotherapy (group A, 31 patients), extensive systemic treatment (group B, 21 patients), and a combination of ocular and extensive treatment (group C, 23 patients); 3 patients did not receive treatment. A total of 40 patients received systemic chemotherapy. MAIN OUTCOMES AND MEASURES: Development of CNSL following the diagnosis of PVRL relative to the use or nonuse of systemic chemotherapy and other treatment regimens. RESULTS: Overall, CNSL developed in 28 of 78 patients (36%) at a median follow-up of 49 months. Specifically, CNSL developed in 10 of 31 (32%) in group A, 9 of 21 (43%) in group B, and 9 of 23 (39%) in group C. The 5-year cumulative survival rate was lower in patients with CNSL (35% [95% CI, 50% to 86%]) than in patients without CNSL (68% [95% CI, 19% to 51%]; P = .003) and was similar among all treatment groups (P = .10). Adverse systemic effects occurred in 9 of 40 (23%) patients receiving systemic chemotherapy; the most common of these effects was acute renal failure. CONCLUSIONS AND RELEVANCE: In the present series of patients with isolated PVRL, the use of systemic chemotherapy was not proven to prevent CNSL and was associated with more severe adverse effects compared with local treatment.

A genome-wide association study identifies a functional ERAP2 haplotype associated with birdshot chorioretinopathy.

Birdshot chorioretinopathy (BSCR) is a rare form of autoimmune uveitis that can lead to severe visual impairment. Intriguingly, >95% of cases carry the HLA-A29 allele, which defines the strongest documented HLA association for a human disease. We have conducted a genome-wide association study in 96 Dutch and 27 Spanish cases, and 398 unrelated Dutch and 380 Spanish controls. Fine-mapping the primary MHC association through high-resolution imputation at classical HLA loci, identified HLA-A*29:02 as the principal MHC association (odds ratio (OR) = 157.5, 95% CI 91.6-272.6, P = 6.6 × 10(-74)). We also identified two novel susceptibility loci at 5q15 near ERAP2 (rs7705093; OR = 2.3, 95% CI 1.7-3.1, for the T allele, P = 8.6 × 10(-8)) and at 14q32.31 in the TECPR2 gene (rs150571175; OR = 6.1, 95% CI 3.2-11.7, for the A allele, P = 3.2 × 10(-8)). The association near ERAP2 was confirmed in an independent British case-control samples (combined meta-analysis P = 1.7 × 10(-9)). Functional analyses revealed that the risk allele of the polymorphism near ERAP2 is strongly associated with high mRNA and protein expression of ERAP2 in B cells. This study further defined an extremely strong MHC risk component in BSCR, and detected evidence for a novel disease mechanism that affects peptide processing in the endoplasmic reticulum.

Clinical manifestations of patients with intraocular inflammation and positive QuantiFERON-TB gold in-tube test in a country nonendemic for tuberculosis.

PURPOSE: To evaluate clinical manifestations of patients with uveitis and scleritis of unknown origin and positive QuantiFERON-TB Gold In-Tube test (quantiferon) in a country not endemic for tuberculosis. DESIGN: Multicenter retrospective cohort study. METHODS: Retrospective review of the clinical, laboratory, and imaging data of 77 patients. Main outcome measures consisted of ocular and systemic features as well as results of laboratory examinations. RESULTS: Out of all, 60 of 71 (85%) were living for at least 6 months in tuberculosis-endemic regions. Location of uveitis was variable; posterior uveitis (29/77; 38%) was the most frequent. Two clinical entities were commonly noted: retinal occlusive vasculitis (21/77; 27%) and serpiginoid choroiditis (11/77; 14%). Antituberculosis treatment was completed in 32 patients; 29 of them (91%) achieved complete remission. Mean quantiferon level was 7.5 U/mL; 71% had values above 2 U/mL and 41% above 10 U/mL. We observed no associations between quantiferon levels and clinical and/or imaging features. Previous tuberculosis infection was diagnosed in 5 of 77 patients (6.5%), while hilar/mediastinal lymphadenopathy was found in 25 of 76 patients (33%). Of these, 12 were consistent with the diagnosis of sarcoidosis, 9 were typical for (prior) tuberculosis, and 4 were compatible with both diagnoses. CONCLUSIONS: Ocular features of patients with idiopathic uveitis and positive quantiferon were diverse, but retinal occlusive vasculitis and serpiginoid choroiditis were common. The quantiferon levels were usually highly elevated and 33% of patients exhibited lymphadenopathy, suggesting frequently the diagnosis of sarcoidosis. Ocular inflammation reacted favorably to antituberculosis treatment, although only a small minority had documented (prior) tuberculosis.