Aniki Rothova

Erasmus MC, Rotterdam, South Holland, Netherlands

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Publications (237)822.58 Total impact

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    ABSTRACT: 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.
    No preview · Article · Feb 2016 · Investigative ophthalmology & visual science
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    ABSTRACT: Purpose: To determine the prevalence of serum antiretinal antibodies (ARAs) among patients with uveitis and establish their clinical relevance. Methods: This prospective study assessed the presence of ARAs by indirect immunofluorescence (IIF) using primate retina in 126 patients with uveitis and 60 healthy controls. Clinical data of uveitis patients were collected from medical charts and included the classification of uveitis, cause of uveitis or its association with systemic disease, stage and activity of uveitis and specific retinal features. Correlations between the presence of specific ARAs and various clinical characteristics were analysed. Results: The presence of ARAs was observed in 49 of 104 (47%) of patients with uveitis and in 10 of 59 (17%) of healthy controls (p < 0.001). Staining of the nuclear layers or the photoreceptors were both more often observed in patients with uveitis compared to healthy controls (p = 0.002 and p = 0.018, respectively). No specific associations were found between the presence of serum ARAs and various clinical characteristics. Conclusion: Serum ARAs were more frequent in patients with uveitis compared to healthy controls, but their clinical role remains elusive. The assessment of intraocular production of specific ARAs may provide further insight into the role of ocular autoantibodies in diverse uveitis entities.
    No preview · Article · Jan 2016 · Acta ophthalmologica
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    ABSTRACT: Background: Sclerotherapy has become the gold standard for the first-line therapy of most venous (VMs) and lymphatic malformations (LMs) of the head and neck. Numerous sclerosing agents are used to treat these low-flow vascular malformations; however, to date, it remains unclear which sclerosing agent is superior in terms of effectiveness and safety. Methods: In a systematic review of the literature (1995-present), we compare the effectiveness and complications of the sclerosing agents most commonly used for cervicocraniofacial VMs and LMs. Results: The literature search yielded 1155 articles, among which 36 (1552 patients) were included in the systematic review. The quality of evidence was low. Pingyangmycin, absolute ethanol, OK-432, ethanolamine oleate, bleomycin, polidocanol, doxycycline, and sodium tetradecyl sulfate (STS) were the most reported sclerosing agents. All agents seem effective, and the mean overall response varies from 71% to 100%. Complications occurred more frequently after ethanol sclerotherapy (18%), compared to other sclerosing agents (0-6%). Cellulitis and ulceration were encountered following sclerotherapy with most sclerosing agents, but skin necrosis was particularly observed after ethanol. Facial nerve paralysis occurred only after OK-432 (0.05%) and ethanol sclerotherapy (6%). Conclusions: This systematic review could not identify a significantly superior sclerosing agent in terms of effectiveness, due to the low quality of the available evidence. Until stronger evidence is available, the difference in complication rates is potentially the deciding factor in the choice between sclerosing agents. As a significantly higher complication rate and more severe local complications were encountered after using absolute ethanol, we cannot recommend this agent for sclerotherapy of cervicofacial vascular malformations.
    Full-text · Article · Nov 2015 · Journal of Plastic Reconstructive & Aesthetic Surgery

  • No preview · Article · Apr 2015 · Acta ophthalmologica

  • No preview · Article · Feb 2015 · Ophthalmology
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    ABSTRACT: Autoimmune retinopathy (AIR) is a rare disorder which may present as a paraneoplastic syndrome. AIR is associated with the presence of anti-retinal antibodies. These antibodies are assumed to cause damage to the retina, resulting in progressive vision loss. A 74-year-old man visited the ophthalmologist with a serious, progressive loss of vision, without any noteworthy abnormalities at routine ophthalmological examination. The electroretinogram was characteristic of loss of photoreceptor function. Anti-retinal antibodies against recoverin were detected in serum. After referral to an internist on account of a suspected diagnosis of paraneoplastic AIR, the patient was diagnosed with a lung carcinoma, confirming the diagnosis of cancer-associated paraneoplastic AIR. An unexplained loss of vision is highly suggestive of paraneoplastic AIR, even in patients without a known malignancy. Laboratory techniques for the detection of the anti-retinal antibody against recoverin have recently been implemented in the Netherlands, facilitating the diagnosis of AIR.
    No preview · Article · Feb 2015 · Nederlands tijdschrift voor geneeskunde
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    ABSTRACT: 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. Retrospective consecutive observational case series METHODS: Setting: institutional Patient population: 134 eyes in 69 patients with a minimum follow-up period of five 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 females 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 intra-ocular surgery. One-third of the affected eyes developed VA < 20/40 at 5-10 years of follow-up. VA at one year was the most important predictor of visual outcome at five and ten years (P = 0.000). 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. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Jan 2015 · American Journal of Ophthalmology
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    Jonas Kuiper · Aniki Rothova · Joke de Boer · Timothy Radstake
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    ABSTRACT: Birdshot chorioretinopathy (BSCR) is a bilateral chronic intraocular inflammation or posterior uveitis that preferentially affects middle-aged Caucasians. BSCR is characterized by distinctive multiple choroidal hypopigmented lesions in combination with retinal vasculitis and vitritis, and the extraordinary feature that virtually all patients are HLA-A29 positive. Its pathophysiology is still poorly understood. BSCR is the strongest documented association between HLA and disease in humans, which makes it an excellent model for studying the underlying immuno-genetic mechanisms of HLA class I-associated diseases. Although the association with HLA-A29 suggests that it is directly involved in the presentation of peptide antigens to T cells, the exact contribution of HLA-A29 to the pathophysiology of BSCR remains enigmatic. This article revisits the HLA-A29 peptidome using insights from recent studies and discusses why HLA-A29 can be considered a canonical antigen presenting molecule. The first genome-wide association study facilitated novel concepts into a disease mechanism beyond HLA-A29 that includes strong genetic predisposition for the ERAP2 gene that affects antigen processing for HLA class I. Furthermore, patients manifest with pro-inflammatory cytokine profiles and pathogenic T cell subsets that are associated with IL-17-linked inflammation. We are beginning to understand that the underlying biology of BSCR comprises various pathologic aspects branched into multiple molecular pathways. We propose to employ Systems Medicine to reveal their dynamic interplay for a holistic view of the immunopathology of this intriguing archetypal HLA class I associated disease. Copyright © 2014. Published by Elsevier Ltd.
    Full-text · Article · Nov 2014 · Progress in Retinal and Eye Research
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    ABSTRACT: 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. To evaluate the outcomes of treatment regimens used for PVRL in the prevention of subsequent CNSL. 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. 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. Development of CNSL following the diagnosis of PVRL relative to the use or nonuse of systemic chemotherapy and other treatment regimens. 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. 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.
    No preview · Article · Nov 2014 · Jama Ophthalmology
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    ABSTRACT: Importance Tubulointerstitial nephritis and uveitis (TINU) syndrome is characterized by tubulointerstitial and ocular inflammation. Thus far, the value of noninvasive diagnostic tests is not known.Objective To determine whether urinary β2-microglobulin (β2M), urinary protein, and serum creatinine have predictive value for detecting TINU syndrome in young patients with uveitis.Design, Setting, and Participants This prospective cohort study was conducted July 2010 through February 2013 at a tertiary care referral center in Utrecht, the Netherlands. Forty-five consecutive new patients with uveitis aged 22 years or younger were enrolled.Exposures Urinary β2M, urinary protein, and serum creatinine were measured prospectively, and the estimated glomerular filtration rate was calculated.Main Outcomes and Measures A post hoc analysis was performed to determine whether urinary β2M, urinary protein, serum creatinine, estimated glomerular filtration rate, and/or pyuria were correlated with definitive and probable cases of TINU syndrome.Results Eighteen of the 45 patients (40%) in our cohort had elevated urinary β2M levels, and 10 patients (22%) had elevated serum creatinine levels. Twenty of 43 patients (47%) had proteinuria. Eight of the 45 patients were diagnosed by a pediatric nephrologist as having renal dysfunction that suggested acute interstitial nephritis. Of these 8 patients, 2 were definitively diagnosed as having TINU syndrome (confirmed by renal biopsy). After excluding other causes of renal dysfunction, the remaining 6 patients with uveitis and renal dysfunction fulfilled the criteria of probable TINU syndrome. The 8 patients with definitive or probable TINU syndrome had higher urinary β2M levels than patients with normal renal function (median β2M, 1.95 mg/L; 95% CI, 1.26-5.16 mg/L vs 0.20 mg/L; 95% CI, 0.19-0.21 mg/L; P < .001; Mann-Whitney U test). Our analysis revealed that the positive predictive value of increased β2M combined with increased serum creatinine was 100% for detecting definitive and/or probable TINU syndrome.Conclusions and Relevance These data suggest that urinary β2M and serum creatinine levels are sensitive and relatively simple diagnostic screening tools for detecting renal dysfunction to diagnose TINU syndrome in young patients with uveitis similar to those evaluated in this study.
    No preview · Article · Oct 2014 · Jama Ophthalmology
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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.
    Full-text · Article · Sep 2014 · Survey of Ophthalmology
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    ABSTRACT: Background/aims 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. Methods Retrospective cohort study in a tertiary referral centre for paediatric uveitis. Medical records of 345 children with uveitis presenting from 1995 through 2010 were reviewed for infectious causes (by serology and aqueous humour analysis). Results A diagnosis of infectious uveitis was established in 60/345 (17%) children. The most prevalent pathogen was Toxoplasma gondii (36/60; 60%), followed by viral infections (18/60; 30%). The most prevalent viral pathogen was varicella-zoster virus (VZV), representing 7/18 (39%) children. Viral causes were less often bilateral than other infectious causes (p=0.04). Specific IgG serum levels determined in 42/60 (70%) patients, were positive in 41/42 (98%). Aqueous humour was analysed for 24/60 (40%) patients and was positive in 18/24 (75%). Conclusions An infectious cause of uveitis was identified in 17% of children with uveitis. T gondii and VZV were the most prevalent pathogens. We recommend analysing the aqueous humour of every child with vision-threatening uveitis of undetermined origin.
    Preview · Article · Aug 2014 · British Journal of Ophthalmology
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    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.
    No preview · Article · Jul 2014 · Ocular Immunology and Inflammation

  • No preview · Article · Jul 2014 · Jama Ophthalmology
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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.
    Full-text · Article · Jun 2014 · Human Molecular Genetics
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    ABSTRACT: Abstract Rubella virus is involved in the pathogenesis of Fuchs heterochromic uveitis and almost all cases in Europe show an active antibody production in the aqueous humor against rubella virus. Herein we report a case of a fully vaccinated patient with common variable immunodeficiency who developed unilateral Fuchs heterochromic uveitis secondary to rubella virus which was proven by intraocular fluid examination. Awareness of rubella associated anterior uveitis should remain also in vaccinated patients, especially those without a fully competent immune system.
    No preview · Article · Jun 2014 · Ocular Immunology and Inflammation
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    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.
    No preview · Article · Jun 2014 · Ocular Immunology and Inflammation
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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.
    Full-text · Article · Jun 2014 · Human immunology
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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.
    No preview · Article · Jan 2014 · American Journal of Ophthalmology
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    ABSTRACT: To determine the cytokine response to ocular lysates of peripheral blood mononuclear cells (PBMCs) from patients with birdshot chorioretinopathy (BSCR). In the PBMCs of 19 patients with BSCR, T cell cytokine production in response to human retina and choroid lysates was analyzed with flow cytometry and compared to the responses against skin lysates. Five patients had active disease and had not yet been treated (naïve to systemic therapy); 14 patients had either immunomodulatory therapy (IMT) or inactive disease (referred as inactive/IMT). The PBMCs of 11 HLA-A29-positive healthy individuals were used as controls. The levels of interleukin-17 (IL-17) in supernatant of cultures stimulated with retina lysate were higher in patients with active BSCR compared to the HLA-A29 positive controls. The levels of other T cell cytokines (IL-10 and interferon-γ [IFN-γ]) in PBMC cultures did not change significantly after stimulation with ocular lysate. The frequency of CD4(+) IL-17(+) (T helper 17 [Th17]) T cells but not of CD4(+) IFN-γ (Th1) T cells was elevated in the PBMCs of patients with active BSCR stimulated by retina lysates compared to skin lysates. Our data demonstrate that PBMCs exhibit an IL-17-mediated immune response to retina lysate in patients with active disease naïve to systemic therapy. This is accompanied by the enrichment of IL-17-producing CD4(+) T cells. These findings support the current concept of chronic Th17-cell mediated inflammation and provide evidence that links the Th17 signatures to ocular-specific immune responses in BSCR.
    Full-text · Article · Dec 2013 · Molecular vision

Publication Stats

6k Citations
822.58 Total Impact Points

Institutions

  • 2012-2016
    • Erasmus MC
      • Department of Ophthalmology
      Rotterdam, South Holland, Netherlands
  • 2014
    • Erasmus University Rotterdam
      Rotterdam, South Holland, Netherlands
  • 2000-2014
    • University Medical Center Utrecht
      • • Department of Ophthalmology
      • • Department of Hematology
      Utrecht, Utrecht, Netherlands
  • 2010
    • Canisius-Wilhelmina Ziekenhuis
      Nymegen, Gelderland, Netherlands
  • 2009
    • Ljubljana University Medical Centre
      Lubliano, Ljubljana, Slovenia
  • 1997-2007
    • Utrecht University
      Utrecht, Utrecht, Netherlands
    • Hong Kong Red Cross Blood Transfusion Service
      Hong Kong, Hong Kong
  • 1995-2007
    • Netherlands Institute for Space Research, Utrecht
      Utrecht, Utrecht, Netherlands
    • Het Oogziekenhuis Rotterdam
      Rotterdam, South Holland, Netherlands
  • 1987-1995
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Ophthalmology
      Amsterdamo, North Holland, Netherlands
  • 1986-1994
    • University of Amsterdam
      Amsterdamo, North Holland, Netherlands