A Rothova

Erasmus MC, Rotterdam, South Holland, Netherlands

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Publications (221)709.66 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Tubulointerstitial nephritis and uveitis (TINU) syndrome is characterized by tubulointerstitial and ocular inflammation. Thus far, the value of noninvasive diagnostic tests is not known.
    Jama Ophthalmology 10/2014; · 3.83 Impact Factor
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    ABSTRACT: Studies of uveitis in children have focused primarily on non-infectious causes. To date, no systematic study of infectious uveitis in children has been conducted. We investigate the prevalence of infectious causes of uveitis in children and explore the diagnostic value of analysing aqueous humour.
    The British journal of ophthalmology. 08/2014;
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    ABSTRACT: Abstract Purpose: To report on clinical manifestations of Purtscher-like retinopathy (PLR) associated with systemic lupus erythematosus (SLE) and visual outcomes. Methods: We performed a retrospective cohort study of 11 patients (21 affected eyes) with PLR in SLE. Results: All patients were treated with systemic corticosteroids ± immunosuppressive agents. Ocular therapy included intravitreal injections with bevacizumab in 18/21 eyes and posterior sub-Tenon injections with triamcinolone acetonide 13/21 eyes. Panretinal photocoagulation (PRP) was performed in 19/21 eyes and pars plana vitrectomy was required in 5/21 eyes. Visual improvement was found at follow-up of 3 and 6 months (p = 0.05). Poor visual outcome was associated with presence of neovascularizations at onset (p = 0.009), development of vitreous hemorrhage during PRP (p = 0.015), and active status of SLE after onset of PLR (p = 0.029). Conclusions: PLR might manifest as a devastating complication of SLE. We recommend treating any systemic activity of SLE and starting an early ocular treatment.
    Ocular immunology and inflammation. 07/2014;
  • Jama Ophthalmology 07/2014; 132(7):896-898. · 3.83 Impact Factor
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    ABSTRACT: 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.
    Human Molecular Genetics 06/2014; · 7.69 Impact Factor
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    ABSTRACT: Abstract Purpose: Previous studies have suggested a link between Q fever and uveitis. We determined whether Coxiella burnetii causes intraocular infection in C. burnetii-seropositive patients with idiopathic uveitis. Methods: From a retrospective observational case series, paired aqueous humor and serum samples from 10 C. burnetii-seropositive patients with idiopathic uveitis were examined for intraocular antibody production by using the Goldmann-Witmer coefficient and by polymerase chain reaction (PCR). Results: Although intraocular IgG against C. burnetii was detected, no intraocular antibody production was observed (low Goldmann Wittmer coefficients). All PCR results were negative. Conclusions: Uveitis due to an intraocular infection with C. burnetii is unlikely.
    Ocular immunology and inflammation. 06/2014;
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    ABSTRACT: To investigate whether recurrence rates of ocular toxoplasmosis are higher during pregnancy among women of childbearing age. Retrospective longitudinal cohort study. We reviewed medical records of all women seen at a university eye clinic (Utrecht, Netherlands) during episodes of active toxoplasmic retinochoroiditis that occurred while the women were of childbearing age (16-42 years). Each woman was sent a questionnaire requesting information regarding all pregnancies and episodes of ocular toxoplasmosis, whether or not episodes were observed at the eye clinic. Conditional fixed-effects Poisson regression was used to model incident rate ratios of recurrence during pregnant versus non-pregnant intervals, adjusted for potential confounders, including age at time of active toxoplasmic retinochoroiditis and interval since last episode of active disease, which are known to influence risk of recurrence. Questionnaires were returned by 50 (58%) of 86 women, 34 of whom had 69 pregnancies during 584 person-years of study. There were 128 episodes of ocular toxoplasmosis during the study period (6 during pregnancy). First episodes of ocular toxoplasmosis occurred between ages 9.6 and 38.5 years. Youngest age at pregnancy was 16.1 years; oldest age at childbirth was 40.9 years. Incident rate ratios for pregnant versus non-pregnant intervals were in the direction of lower recurrence rates during pregnancy, with point estimates of 0.54 and 0.75 under two different approaches, but ratios were not significantly different from the null value (p-values of 0.16 and 0.55). Recurrence rates of ocular toxoplasmosis are likely not higher during pregnancy, in contrast to traditional beliefs.
    American Journal of Ophthalmology 01/2014; · 4.02 Impact Factor
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    ABSTRACT: Birdshot chorioretinopathy (BSCR), a progressive form of non-infectious uveitis, is the strongest HLA-associated disease described to date, with >95% of the patients displaying HLA-A29. Since indirect evidence indicates the involvement of T cells in the etiopathology of the disease, we now isolated, cultured and analyzed the vitreous fluid-infiltrating T cells from two BSCR patients with respect to their phenotype, cytokine profile, clonal distribution and antigen specificity. Phenotypic analyses revealed the predominant presence of both CD4+ and CD8+ T cells in vitreous fluid. Further analyses on short term expanded and cloned T cells suggested that eye-infiltrating T cells generally displayed a Th1 like cytokine profile with secretion of high levels of IFN-γ and TNF-α. In one patient an oligoclonal CD4+ and CD8+ T cell infiltration, with a moderate to strongly skewed TCR Vβ usage was suggestive for an antigen driven infiltration/expansion. Indeed, a number of intraocular CD4+ and CD8+ T cells responded to crude retinal and choroidal lysates. These results, which demonstrate for the first time the existence of eye-antigen-specific T cells in the vitreous fluid of BSCR patients, substantiate the current view on the role of eye-antigen specific T cells in the etiopathology of BSCR.
    Human immunology 01/2014; · 2.55 Impact Factor
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    ABSTRACT: Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease and the most prevalent systemic disorder in children with uveitis. The current prevailing opinion is that JIA is a multifactorial, genetically-predisposed autoimmune disorder that can be influenced by environmental factors and infections; however, the specific pathogenesis of JIA-associated uveitis is not understood, nor has the relationship between the eye and joint inflammation been established. Nevertheless, subtypes of JIA that are associated with uveitis, oligoarthritis, polyarticular rheumatoid factor negative, and psoriatic arthritis appear to have common pathogenicity. We summarizes our current knowledge regarding the pathogenesis of JIA-associated uveitis and discusses the possible role of immune responses and cytokine involvement, genetic associations, and the influence of external triggers in this disease--an association that is supported by data obtained from arthritis research and experimental uveitis models.
    Survey of Ophthalmology 01/2014; · 2.86 Impact Factor
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    ABSTRACT: To evaluate clinical manifestations of patients with uveitis and scleritis of unknown origin and positive QuantiFERON-TB test Gold In-Tube (quantiferon) in a country not endemic for tuberculosis. Multicentre retrospective cohort study. 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. Out of all, 60/71 (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 (n=11/77, 14%). Anti-tuberculosis treatment was completed in 32 patients, 29 (91%) of them 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 5/77 (6.5%) patients, while hilar/mediastinal lymphadenopathy was found in 25/76 (33%) patients. Of these, 12 were consistent with the diagnosis of sarcoidosis, 9 were typical for (prior) tuberculosis and 4 were compatible with both diagnoses. 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 anti-tuberculosis treatment, although only a small minority had documented (prior) tuberculosis.
    American Journal of Ophthalmology 11/2013; · 4.02 Impact Factor
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    ABSTRACT: Purpose: To report on the clinical features and etiology of patients with retinal vasculitis (RV). Materials and Methods: We reviewed medical records of 47 patients (75 affected eyes) diagnosed with RV. Clinical presentations, ocular complications, associated systemic diseases, and treatment regimens were registered. Results: Etiology of RV included infectious causes in 10/47, (21%) while an association with systemic and/or ocular non-infectious disorders was noted in 22/47 (47%). Eales' disease and Behcet's disease represented the most common clinical entities in non-infectious group while tuberculosis-associated RV was diagnosed in 6/10 (60%) among those with infectious disorders. RV was bilateral in 28/47 (60%) patients. Retinal veins were most commonly affected (72%, 34/47). Involvement of arteries was present in 12/47 (25%) and was associated with viral infections and Behcet's disease. Ocular complications developed in 60/75 (80%) eyes. The most common complications were elevated intraocular pressure and/or glaucoma (33/75, 44%). Retinal detachment, vitreous hemorrhage, and cystoid macular edema developed in similar percentages (15%). Conclusions: RV in Thailand manifested mostly in male patients, was typically bilateral and involved mostly veins. Involvement of arteries was observed in patients with viral infections and Behcet's disease. Tuberculosis was the most common infectious cause.
    Indian Journal of Ophthalmology 10/2013; · 1.02 Impact Factor
  • Arthur Menno Braakenburg, Aniki Rothova
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    ABSTRACT: Abstract Purpose: To investigate the ocular and systemic manifestations of retinal vasculitis in HLA-B27-positive patients. Methods: Retrospective noncomparative case series of 9 HLA-B27-positive patients with uveitis and retinal vasculitis. Main outcome measures consisted of ocular and angiographic findings and assessment of any additional systemic disorders. Results: Three male and 6 female HLA-B27-positive patients with a median age of 32 years were diagnosed with retinal vasculitis. Concurrent intraocular inflammation was noted in all patients. All patients suffered from extensive vasculitis of the large retinal veins. Five patients developed retinal vasculitis at the onset of uveitis and the remaining 4 exhibited retinal vasculitis 1-15 years after the onset of uveitis. Vascular occlusions occurred in 4 patients and subsequent neovascularizations developed in 3. Three patients were diagnosed with an HLA-B27-associated systemic disease. Conclusion: Retinal vasculitis may develop in the wake of HLA-B27-associated uveitis and might represent a rare manifestation of HLA-B27-associated disease.
    Ocular immunology and inflammation 10/2013; · 0.72 Impact Factor
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    ABSTRACT: Abstract Purpose: To investigate the prevalence of intraocular infections after allogeneic stem cell transplantation (allo-SCT). Methods: The study design was a single institutional retrospective noncomparative cohort of 135 consecutive patients in 2006 and 2007 who underwent allo-SCT for hematological malignancy. The primary outcome was the development of intraocular infections after allo-SCT and secondary outcome consisted of development of other ocular disorders during follow-up. Results: The most frequent ocular sequel to allo-SCT included ocular graft-versus-host disease (GvHD), which developed in 37/135 patients (27%). Intraocular infection occurred in 1 of 135 patients (0.7%). This patient developed infectious chorioretinitis together with osteomyelitis, endocarditis, and brain abscess with fungus Scedosporium and was successfully treated with a combination of voriconazole, amphotericine B, and surgical interventions. Viral and/or bacterial intraocular infections were not observed at all. Conclusions: Intraocular infections after allo-SCT are currently uncommon due to systematic use of preemptive treatment regimens, frequent controls, and early treatment of systemic infections.
    Ocular immunology and inflammation 10/2013; · 0.72 Impact Factor
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    ABSTRACT: Abstract Purpose: To report on severe HLA B27-associated anterior uveitis complicated by vitritis, hypotony, and serous retinal detachment. Methods: Retrospective case series. Results: Five patients with HLA B27-associated uveitis presented with an acute anterior uveitis complicated by vitritis, hypotony, serous retinal detachment, and ciliochoroidal effusion. Two patients had previously acute anterior uveitis and two suffered from HLA B27-associated systemic disease. Laboratory and imaging examinations did not reveal another cause of uveitis. Despite the aggressive treatment a prolonged and slow recovery followed. Four patients developed macular edema and one additional patient developed a macular pucker. Finally, 3 eyes improved, 2 eyes developed atrophy, and 1 was lost at 4-month follow-up with visual acuity of hand movements. Conclusions: The authors conclude that severe uveitis with a serous retinal detachment might develop in HLA B27-positive patients and may be complicated by protracted hypotony, macular edema, and poor visual outcome.
    Ocular immunology and inflammation 09/2013; · 0.72 Impact Factor
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    ABSTRACT: To report the clinical features of patients with focal chorioretinitis (FCR), as well as toxoplasma serology. We included 25 (4%) consecutive patients with FCR of 593 with uveitis. Controls consisted of 127 patients with posterior and panuveitis and clinical features other than FCR. Results of enzyme-linked immunosorbent assay for anti-Toxoplasma gondii immunoglobulin G (IgG) and IgM, demographic data, and clinical features of patients were registered. Positive anti-T. gondii IgG levels were observed in 21 of 25 patients (84%) with FCR in contrast to 14 of 127 patients (11%) with non-FCR (P < 0.001, Fisher test). The IgG levels >600 IU were found in 19 of 25 patients (76%) with FCR and in none of the patients with non-FCR (P < 0.001). All cases had unilateral involvement. Ocular features consisting of FCR and vitritis were present in all patients, but associated chorioretinal atrophic scars were not commonly seen (7/25 eyes; 28%). Retinal vasculitis was found in 9 of 25 eyes (36%) and affected solely the arteries. The majority of patients with FCR in Thailand exhibit highly positive anti-T. gondii IgG levels suggesting the presence of active systemic infection, which is also consistent with the absence of old scars. The absence of old scars and retinal arteritis were the features distinct from typical ocular toxoplasmosis lesions reported in the European and the U.S. series.
    Retina (Philadelphia, Pa.) 08/2013; · 2.93 Impact Factor
  • Acta ophthalmologica 07/2013; · 2.44 Impact Factor
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    ABSTRACT: PURPOSE: To investigate the presence of biomarkers in aqueous humor (AH) from patients with uveitis associated with juvenile idiopathic arthritis (JIA). METHODS: AH (n=73) and serum (n=105) samples from 116 children were analyzed using Surface Enhanced Laser Desorption/Ionization Time of Flight Mass Spectrometry (SELDI-ToF MS). The samples were divided into the following groups: JIA; silent chronic anterior uveitis (AU) ; other uveitis entities and non-inflammatory controls. Statistical biomarker identification was performed using the SELDI-ToF Biomarker Analysis Cluster Wizard followed by multivariate statistical analysis. Biochemical identification of biomarkers was performed by polyacrylamide gel protein separation, followed by liquid chromatography tandem mass spectrometry. Enzyme-Linked Immuno Sorbent Assay was performed in a number of AH samples representing all four study groups. RESULTS: In the JIA group one AH protein peak at mass/charge (m/z) 13,762 had qualitative and quantitative differences in expression compared to the other uveitis entities and the controls, but not to the group of silent chronic AU. Its quantitative expression in AH of patients with JIA and other silent chronic AU was positively associated with uveitis activity. The protein at m/z 13,762 in AH was identified as transthyretin (TTR). The TTR concentration in AH differed significantly between the study groups (p=0.006) with considerably higher TTR concentrations in JIA and silent chronic AU samples positive for m/z 13,762 than those of the other uveitis and control groups. CONCLUSIONS: TTR is a potential intraocular biomarker of JIA-uveitis. Its role in the pathogenesis of silent chronic AU with and without arthritis needs further investigation.
    Investigative ophthalmology & visual science 04/2013; · 3.43 Impact Factor
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    ABSTRACT: PURPOSE:: To compare the yield of diagnostic pars plana vitrectomy (PPV) with the yield of aqueous analyses in patients with uveitis of unknown cause. METHODS:: Seventy-five consecutive patients (84 eyes) with uveitis involving posterior eye segment who undergo a diagnostic PPV from 2005 through 2009 were retrospectively reviewed. Vitreous specimens were simultaneously analyzed by microbiological culture, flow cytometry, and cytology as well as by polymerase chain reaction and for intraocular antibody production by Goldmann-Witmer coefficient. In 53 eyes, both aqueous and vitreous samples were assessed. The primary outcome measure was the comparison between vitreous and aqueous analyses. RESULTS:: Vitreous analysis was positive in 18 of 84 eyes (21%). Positive results indicated infectious uveitis in 12 of 18 cases (67%) and lymphoma in 6 of 18 (33%) cases. Of the 53 eyes with both aqueous and vitreous samples available, aqueous analysis revealed the diagnosis in 6 of 53 eyes and vitreous in 9 of 53 eyes. Unilateral uveitis (P = 0.022), panuveitis and uveitis posterior (P ≤ 0.001), preoperative immunosuppressive therapy (P = 0.004), and increasing age (P = 0.018) were associated with an increased diagnostic yield of PPV. Overall, 1 year after PPV, median visual acuity improved from 20/200 to 20/80 (Snellen, P ≤ 0.001). Of 18 patients who were on immunosuppressive treatment before PPV, 8 (44%) were able to stop immunosuppressive therapy during 1-year follow-up. The complications of PPV consisted predominantly of cataract development (33/65, 51%). CONCLUSION:: Diagnostic PPV with the analysis of vitreous fluid by multiple laboratories for infectious and malignant disorders was useful in diagnosing uveitis of unknown cause. Previous aqueous analysis was especially valuable for the diagnosis of intraocular infections and may therefore decrease the number of patients who would otherwise undergo an invasive diagnostic PPV. Furthermore, PPV was associated with improved visual acuity and decreased use of immunosuppressive therapy.
    Retina (Philadelphia, Pa.) 04/2013; · 2.93 Impact Factor
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    ABSTRACT: IMPORTANCE Little attention has been paid to clinical features of cytomegalovirus (CMV) infections in individuals without human immunodeficiency virus (HIV). OBJECTIVE To describe the clinical manifestations and comorbidities of patients without HIV infection who have CMV-associated posterior uveitis or panuveitis. DESIGN AND SETTING Retrospective observational case series in an academic research setting. PARTICIPANTS The medical records were reviewed of 18 patients (22 affected eyes) diagnosed as having posterior uveitis or panuveitis who had aqueous positive for CMV by polymerase chain reaction techniques. MAIN OUTCOME MEASURES Demographic data, clinical manifestations, and associated systemic diseases were recorded. RESULTS Ocular features included focal hemorrhagic retinitis (n = 13) and peripheral retinal necrosis (n = 7). Two eyes had no focal retinal lesions but manifested vasculitis and vitritis. All patients exhibited vitreous inflammation. Inflammatory reactions in anterior segments developed in 14 of 22 eyes (64%). Retinal vasculitis was observed in 16 of 22 eyes (73%) and included mostly arteries (in 13 of 16 eyes [81%]). Eleven of 18 patients were taking immunosuppressive medications (5 for hematologic malignant diseases, 4 for systemic autoimmune diseases, and 2 following organ transplants). One additional patient was diagnosed as having non-Hodgkin lymphoma 3 months after the onset of CMV-associated panuveitis, and another patient had primary immunodeficiency disorder. Of the remaining 5 patients, 2 had diabetes mellitus, and 3 had no associated systemic diseases and exhibited no evidence of immune deficiency. CONCLUSIONS AND RELEVANCE Cytomegalovirus-associated infections of posterior eye segments can develop in patients without HIV infection who have compromised immune function of variable severity but may occur also in individuals who have no evidence of immune insufficiency. Cytomegalovirus infections located in posterior eye segments in patients without HIV infection caused intraocular inflammatory reaction in all cases and demonstrated more variable clinical presentation than classic CMV retinitis observed in patients with HIV infection.
    Jama Ophthalmology 03/2013; · 3.83 Impact Factor
  • Article: Reply.
    American Journal of Ophthalmology 03/2013; 155(3):609-10. · 4.02 Impact Factor

Publication Stats

4k Citations
709.66 Total Impact Points

Institutions

  • 2012–2014
    • Erasmus MC
      • Department of Ophthalmology
      Rotterdam, South Holland, Netherlands
  • 1997–2014
    • University Medical Center Utrecht
      • • Department of Ophthalmology
      • • Department of Hematology
      Utrecht, Utrecht, Netherlands
  • 2013
    • Het Oogziekenhuis Rotterdam
      Rotterdam, South Holland, Netherlands
  • 2006–2013
    • Netherlands Institute for Space Research, Utrecht
      Utrecht, Utrecht, Netherlands
    • St. Elisabeth Ziekenhuis Tilburg
      Tilburg, North Brabant, Netherlands
  • 1990–2013
    • VU University Amsterdam
      • Department of Ophthalmology
      Amsterdamo, North Holland, Netherlands
    • University of Groningen
      • Department of Ophthalmology
      Groningen, Province of Groningen, Netherlands
    • Erasmus Universiteit Rotterdam
      • Department of Ophthalmology
      Rotterdam, South Holland, Netherlands
    • Utrecht University
      Utrecht, Utrecht, Netherlands
  • 1988–2013
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Ophthalmology
      Amsterdam, North Holland, Netherlands
  • 2006–2012
    • Chiang Mai University
      • • Department of Medical Technology
      • • Department of Ophthalmology
      Chiang Mai, Chiang Mai Province, Thailand
  • 2009–2011
    • Ljubljana University Medical Centre
      Lubliano, Ljubljana, Slovenia
  • 2008
    • University of California, Los Angeles
      • Department of Ophthalmology
      Los Angeles, CA, United States
  • 1986–1993
    • University of Amsterdam
      Amsterdamo, North Holland, Netherlands