Jeannette Ossewaarde-van Norel

Discrepancies Between Fluorescein Angiography and Optical Coherence Tomography in Macular Edema in Uveitis

PURPOSE To assess the frequency and characteristics of discrepant findings between fluorescein angiography (FA) and optical coherence tomography (OCT) in uveitic macular edema (ME). DESIGN Retrospective cross-sectional study of 112 eyes of 78 patients with uveitic ME on FA, OCT, or both. METHODS ME was graded on OCT and FA of uveitis patients attending the University Medical Center Utrecht. The frequency and severity of discrepant findings were analyzed, and the clinical findings at the time of imaging were assessed. The imaging studies were compared with the clinical characteristics. RESULTS Positive results of both imaging methods (FA+/OCT+) were observed in 61 (54%) of 112 eyes, whereas discrepant results occurred in 51 (46%) of 112 eyes. The FA+/OCT- discrepancy occurred in 34 (30%) of 112 eyes, and the FA-/OCT+ discrepancy occurred in 17 (15%) of 112 eyes. No correlations between the discrepant imaging results and age, gender, duration of uveitis or ME, visual acuity, or cause of uveitis were identified. FA+/OCT- and FA-/OCT+ discrepancies comprised typically mild degrees of ME. The FA+/OCT- discrepancy occurred in 50% of eyes with birdshot chorioretinopathy (7/14), and the FA-/OCT+ discrepancy occurred more often in intermediate uveitis than in other anatomic locations. Although the FA+/OCT+ consistency was noted frequently in active uveitis, the FA-/OCT+ discrepancy was common in eyes with inactive uveitis (8/18; 44% of inactive eyes). CONCLUSIONS Our results emphasize that FA and OCT are complementary investigations, each revealing different aspects of the pathophysiology of uveitic ME.

Development of Macular Edema and Impact on Visual Acuity in Uveitis Associated with Juvenile Idiopathic Arthritis

Abstract Purpose: To investigate the development of macular edema (ME) in relation to the duration of uveitis and visual outcome in uveitis associated with juvenile idiopathic arthritis (JIA). Methods: Sixty-one patients with JIA-uveitis (116 eyes) were investigated by Cirrus OCT for macular thickness. The relation between macular thickness and time interval since onset of uveitis and best corrected visual acuity (BCVA) was analyzed by linear mixed effect models. Results: Duration of follow-up showed significant positive linear relation with central macular thickness. The central macular thickness showed a significant linear relation with BCVA, but not with disease activity. Thirteen patients developed ME (central field thickness >304.4 µm) after a mean time interval of 11.6 years. Thirteen patients had macular thinning after a significant longer interval of uveitis compared to patients with normal or thickened macula. Conclusions: Duration of JIA-uveitis is positively correlated with the development of ME, compromising the visual acuity.

A Disease-Associated MicroRNA Cluster Links Inflammatory Pathways and an Altered Composition of Leukocyte Subsets to Noninfectious Uveitis

Purpose The cause of noninfectious uveitis (NIU) is poorly understood but is considered to be mediated by a complex interplay between genetic, environmental, and-relatively unexplored-epigenetic factors. MicroRNAs (miRNAs) are noncoding small RNAs that are important epigenetic regulators implicated in pathologic signaling. Therefore, we mapped the circulating miRNA-ome of NIU patients and studied miRNA perturbations within the broader context of the immune system. Methods We designed a strategy to robustly identify changes in the miRNA profiles of two independent cohorts totaling 54 untreated patients with active and eye-restricted disease and 26 age-matched controls. High-resolution miRNA-ome data were obtained by TaqMan OpenArray technology and subsequent RT-qPCR. Flow cytometry data, and proteomic data spanning the cellular immune system, were used to map the uveitis-miRNA signature to changes in the composition of specific leukocyte subsets in blood. Results Using stringent selection criteria, we identified and independently validated an miRNA cluster that is associated with NIU. Pathway enrichment analysis for genes targeted by this cluster revealed significant enrichment for the PI3K/Akt, MAPK, FOXO, and VEGF signaling pathways, and photoreceptor development. In addition, unsupervised multidomain analyses linked the presence of the uveitis-associated miRNA cluster to a different composition of leukocyte subsets, more specifically, CD16+CD11c+HLA-DR- cells. Conclusions Together, this study identified a unique miRNA cluster associated with NIU that was related to changes in leukocyte subsets demonstrating systemic changes in epigenetic regulation underlying NIU.

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.