Clinical features of uveitis in elderly patients in central Tokyo (2013-2018).

PURPOSE: To clarify the clinical features of uveitis in elderly patients in central Tokyo. METHODS: We retrospectively identified 1424 patients with uveitis who visited the Uveitis Clinic of the University of Tokyo Hospital between January 2013 and December 2018. The patients were categorized into two groups based on their ages at the time of disease onset: patients aged 65 years or older were included in Group A, whereas those younger than 65 years were included in Group B. The etiological classification of uveitis and its causes were investigated for each group. RESULTS: Group A presented significantly higher rates of infectious uveitis (35.5% vs. 17.8%, p < 0.0001) and masquerade syndromes (17.9% vs. 5.0%, p < 0.0001) than Group B. Furthermore, Group A had significantly higher rates of sarcoidosis (23.1% vs. 9.3%, p < 0.0001), intraocular lymphoma (16.6% vs. 4.6%, p < 0.0001), cytomegalovirus iritis (11.0% vs. 5.6%, p = 0.0043), and cytomegalovirus retinitis (5.2% vs. 1.5%, p = 0.0020) than Group B. CONCLUSION: Our results demonstrate a clear difference in the causative diseases of uveitis between elderly and non-elderly patients. These findings may support ophthalmologists in their diagnostic process for elderly patients with uveitis.

Low-dose radiation induces unstable gene expression in developing human iPSC-derived retinal ganglion organoids.

The effects of low-dose radiation on undifferentiated cells carry important implications. However, the effects on developing retinal cells remain unclear. Here, we analyzed the gene expression characteristics of neuronal organoids containing immature human retinal cells under low-dose radiation and predicted their changes. Developing retinal cells generated from human induced pluripotent stem cells (iPSCs) were irradiated with either 30 or 180 mGy on days 4-5 of development for 24 h. Genome-wide gene expression was observed until day 35. A knowledge-based pathway analysis algorithm revealed fluctuations in Rho signaling and many other pathways. After a month, the levels of an essential transcription factor of eye development, the proportion of paired box 6 (PAX6)-positive cells, and the proportion of retinal ganglion cell (RGC)-specific transcription factor POU class 4 homeobox 2 (POU4F2)-positive cells increased with 30 mGy of irradiation. In contrast, they decreased after 180 mGy of irradiation. Activation of the "development of neurons" pathway after 180 mGy indicated the dedifferentiation and development of other neural cells. Fluctuating effects after low-dose radiation exposure suggest that developing retinal cells employ hormesis and dedifferentiation mechanisms in response to stress.

Ursodeoxycholic Acid Attenuates the Retinal Vascular Abnormalities in Anti-PDGFR-ß Antibody-Induced Pericyte Depletion Mouse Models.

As a clinical manifestations of diabetic retinopathy (DR), pericytes (PCs) loss from the capillary walls is thought to be an initial pathological change responsible for the breakdown of the blood-retinal barrier (BRB). This study was performed to investigate the effects of ursodeoxycholic acid (UDCA) in PC depletion mice by injection of an antibody against platelet-derived growth factor reception-ß (PDGFR-ß clone APB5). To assess the integrity of the retinal vessels, their density, diameters, vessel branching points, and number of acellular capillaries were evaluated. While all types of retinal vessels became enlarged in APB5-induced mice, treatment with UDCA rescued the vasculature; the vessel density, diameter of the veins and capillaries, and vessel branching points were significantly lower in mice treated with UDCA. Although APB5-induced mice displayed progressive exacerbation of retinal edema, whole retinal thickness upon treatment with UDCA was significantly decreased. Additionally, UDCA reduced the expression of F4/80+ macrophages in the APB5-induced retina according to immunofluorescent labeling. UDCA also reduced the increased expression of angiogenic factors and inflammatory mediators (vascular endothelial growth factor, intercellular adhesion molecule-1, and monocyte chemotactic protein-1). These findings suggest that UDCA can be used to prevent the progression of and treat DR.

Analysis of inflammatory mediators in the vitreous humor of eyes with pan-uveitis according to aetiological classification.

Treatment of uveitis is complicated because of its multiple aetiologies and elevation of various inflammatory mediators. To determine the mediators that are elevated in the vitreous humor according to the aetiology of the uveitis, we examined the concentrations of 21 inflammatory cytokines, 7 chemokines, and 5 colony-stimulating/growth factors in vitreous samples from 57 eyes with uveitis associated with intraocular lymphoma (IOL, n = 13), sarcoidosis (n = 15), acute retinal necrosis (ARN, n = 13), or bacterial endophthalmitis (BE, n = 16). Samples from eyes with idiopathic epiretinal membrane (n = 15), which is not associated with uveitis, were examined as controls. Heat map analysis demonstrated that the patterns of inflammatory mediators in the vitreous humor in eyes with uveitis were disease-specific. Pairwise comparisons between the 5 diseases showed specific elevation of interferon-α2 in ARN and interleukin (IL)-6, IL-17A, and granulocyte-colony stimulating factor in BE. Pairwise comparisons between IOL, ARN, and BE revealed that levels of IL-10 in IOL, RANTES (regulated on activation, normal T cell expressed and secreted) in ARN, and IL-22 in BE were significantly higher than those in the other 2 types of uveitis. These mediators are likely to be involved in the immunopathology of specific types of uveitis and may be useful biomarkers.

Retinal vascular inflammatory and occlusive changes in infectious and non-infectious uveitis.

PURPOSE: Retinal vasculitis and occlusive changes are important signs of posterior uveitis and are possible diagnostic markers for uveitis. However, the frequency of arteritis and phlebitis in various uveitis entities, including infectious uveitis (IU) and non-infectious uveitis (NIU), have not been systematically investigated. STUDY DESIGN: Retrospective. METHODS: We investigated the frequency of retinal vascular inflammatory and occlusive changes in patients with IU and NIU. The study included 283 patients with intermediate, posterior, or pan-uveitis who were diagnosed with IU (presumed tuberculous uveitis, acute retinal necrosis, cytomegalovirus retinitis, human T-cell lymphotropic virus type 1-associated uveitis, toxoplasmic retinitis, syphilitic uveitis, rubella virus-associated uveitis, fungal endophthalmitis, and bacterial endophthalmitis) or NIU (sarcoidosis, Behçet's disease, Vogt-Koyanagi-Harada disease, human leukocyte antigen-B27-associated uveitis, systemic lupus erythematosus retinopathy, psoriatic uveitis, rheumatoid arthritis/collagen disease-associated uveitis, multiple sclerosis-associated uveitis, and sympathetic ophthalmia). All patients underwent fluorescein angiography (FA) and color photography examinations of the fundus. Presence of inflammatory and occlusive changes was determined by FA images. RESULTS: Significantly higher positive ratios of phlebitis, vein sheathing, vein occlusion, arteritis, artery sheathing, artery occlusion, and avascular areas were observed in the IU group than in the NIU group (p < 0.05). Notably, the discrepancy between IU and NIU was prominent with regard to retinal arterial changes (arteritis [57.9% vs 11.2%], inflammatory artery sheathing [33.7% vs 0%], and artery occlusion [22.1% vs 3.7%], respectively; p < 0.0001). CONCLUSION: Findings of vasculitis and occlusion, especially in retinal arteries, in FA strongly suggest an infectious origin of active uveitis.