This study indicates that measurement of subfoveal choroidal thickness by EDI-OCT is useful for evaluating the activity of uveitis and the therapeutic efficacy in patients with BD.

Macrophages are involved in low-grade inflammation in diabetes, and play pathogenic roles in proliferative diabetic retinopathy (PDR) by producing proinflammatory cytokines. T cells as well as other cells are also activated by proinflammatory cytokines, and infiltration into the vitreous of patients with PDR has been shown. In this study, we measured helper T (Th) cell-related cytokines in the vitreous of PDR patients to define the characteristics of Th-mediated immune responses associated with PDR. The study group consisted of 25 type 2 diabetic patients (25 eyes) with PDR. The control group consisted of 27 patients with epiretinal membrane (ERM), 26 patients with idiopathic macular hole (MH), and 26 patients with uveitis associated with sarcoidosis. Vitreous fluid was obtained at the beginning of vitrectomy, and centrifuging for cellular removals was not performed. Serum was also collected from PDR patients. IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, soluble sCD40L, and TNFα in the vitreous and serum samples were measured. Both percent detectable and levels of IL-4, IL-6, IL-17A, IL-21, IL-22, and TNFα in the vitreous were significantly higher than those in the serum in PDR patients. Vitreous levels of these cytokines and IL-31 were significantly higher in PDR than in ERM or MH patients. Vitreous levels of IL-4, IL-17A, IL-22, IL-31, and TNFα in PDR patients were also significantly higher than those of sarcoidosis patients. In PDR patients, vitreous IL-17A level correlated significantly with vitreous levels of IL-22 and IL-31, and especially with IL-4 and TNFα. Although it is unclear whether these cytokines play facilitative roles or inhibitory roles for the progression of PDR, the present study indicated that Th2- and Th17-related immune responses are involved in the pathogenesis of PDR.

Inflammation is known to be involved in the progression of diabetic retinopathy. We have recently reported that vitreous levels of IL-4, IL-17A, IL-22, IL-31, and TNFα are higher than the respective serum levels in proliferative diabetic retinopathy (PDR) patients, and that vitreous levels of these cytokines are higher in PDR than in other non-inflammatory vitreoretinal diseases or uveitis associated with sarcoidosis. In the present study, we investigated inflammatory cytokines including Th17 cell-related cytokines in aqueous humor samples obtained from eyes with PDR, and analyzed the association between the aqueous humor and vitreous fluid levels of individual cytokines. The study group consisted of 31 consecutive type 2 diabetic patients with PDR who underwent cataract surgery and vitrectomy for vitreous hemorrhage and/or tractional retinal detachment. Undiluted aqueous humor was collected during cataract surgery, and then vitreous fluid was obtained using a 25G vitreous cutter inserted into the mid-vitreous cavity at the beginning of vitrectomy. IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, soluble CD40 ligand (sCD40L), and TNFα levels in the aqueous humor and vitreous fluid were measured using a beads-array system. Although IL-17A was detected in the aqueous humor of eyes with PDR and the level correlated with IL-17A level in the vitreous fluid, both percent detectable and level of IL-17A in the aqueous humor were significantly lower than those in the vitreous fluid. Vitreous IL-17A level was related significantly to IL-10, IL-22, and TNFα levels in aqueous humor as well as in vitreous fluid, On the other hand, aqueous IL-17A level was not related significantly to aqueous or vitreous levels of IL-10, IL-22 or TNFα level. The present study demonstrated that IL-17A level and detectable rate in the aqueous humor of patients with PDR are markedly lower than those in the vitreous fluid and aqueous IL-17A does not correlate with vitreous levels of other cytokines, and hence should not be used as a surrogate for IL-17A in the vitreous fluid.

OHT in non-granulomatous uveitis was mainly steroid-induced open-angle OHT with some cases of angle-closure OHT caused by pupillary block, while that in granulomatous uveitis was mostly inflammation-induced open-angle OHT with no pupillary block-related angle-closure OHT.

Ocular hypertension (OHT) caused by inflammation or corticosteroid treatment is a common complication of uveitis. Ripasudil hydrochloride hydrate (K-115) is reportedly efficacious for lowering intraocular pressure (IOP). We retrospectively compared the IOP-lowering effect of K-115 for inflammatory and corticosteroid-induced OHT associated with uveitis. Thirty-six consecutive eyes of 27 patients with uveitis-associated OHT (20 and 16 eyes with inflammation- and corticosteroid-induced OHT, respectively) were treated with K-115 with or without other anti-glaucoma agents. In the inflammation-induced OHT, mean IOP and aqueous flare significantly decreased (P < 0.001 and P = 0.035, respectively), changing from 26.4 ± 7.5 mmHg and 28.1 ± 15.0 photon counts per millisecond (pc/ms) at the initial assessment to 17.9 ± 5.4 mmHg and 17.1 ± 10.7 pc/ms at the last visit, respectively. In the corticosteroid-induced OHT, mean IOP significantly decreased (P = 0.0005), changing from 26.7 ± 7.8 mmHg and 18.7 ± 11.2 pc/ms to 18.6 ± 8.8 mmHg and 22.6 ± 15.3 pc/ms, respectively; conversely, aqueous flare remained unchanged. In the inflammation-induced OHT, K-115 was more efficacious in the eyes with higher IOP. Neither remarkable adverse effects nor exacerbation of uveitis were observed in the eyes of either group during the observation period. K-115 decreased IOP in both inflammation- and corticosteroid-induced OHT associated with uveitis and played a synergistic role in reducing ocular inflammation in uveitis treatment.

BackgroundNeovascular age-related macular degeneration (nAMD) is a leading cause of blindness in older people. Low-grade inflammation is well-known as one of the pathogenic mechanisms in nAMD. Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for nAMD, although macula atrophy (MA) developed under anti-VEGF therapy causes irreversible visual function impairment and is recognized as a serious disorder. Here, we show specific expression patterns of aqueous humor (AH) cytokines in nAMD eyes developing MA under intravitreal injection of aflibercept (IVA) as an anti-VEGF antibody and present predictive cytokines as biomarkers for the incidence of MA in nAMD eyes under IVA treatment.MethodsTwenty-eight nAMD patients received three consecutive monthly IVA, followed by a pro re nata regimen for 2 years. AH specimens were collected before first IVA (pre-IVA) and before third IVA (post-IVA). AH cytokine levels, visual acuity (VA), and central retinal thickness (CRT) were measured.ResultsTwo-year incidence of MA was 21.4%. In nAMD eyes developing MA [MA (+) group], pre-IVA levels of monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1β, VEGF and post-IVA level of MCP-1 were higher than those in nAMD eyes without MA [MA (−) group]. In hierarchical cluster analysis, pre-IVA MCP-1 and VEGF were grouped into the same subcluster, as were post-IVA MCP-1 and CRT. In principal component analysis, principal component loading (PCL) of pre-IVA interferon-γ-inducible protein 10 (IP-10) was 0.61, but PCL of post-IVA IP-10 decreased to −0.09. In receiver operating characteristic analysis and Kaplan–Meier curves, pre-IVA MCP-1, MIP-1β, and VEGF and post-IVA interleukin-6, MCP-1, and MIP-1β were detected as predictive factors for MA incidence. In 2-year clinical course, changes of VA in groups with high levels of pre-IVA MIP-1β (over 39.9 pg/ml) and VEGF (over 150.4 pg/ml) were comparable to those in MA (+) group.ConclusionSubstantial loss of IP-10 effects and persistent inflammation contribute to incidence of MA, and screening of AH cytokine levels could be a useful method to predict MA incidence in nAMD eyes under anti-VEGF therapy.

Vitreous opacity (VO) is a common feature of intermediate uveitis, posterior uveitis, and panuveitis. Fundus observation is critical for determining the etiology of uveitis, however, is often interfered with VO. In these clinical settings, vitrectomy contributes to a correct diagnosis and guides alternative management strategies. The purpose of this study was to evaluate the diagnostic yield and surgical outcome of vitrectomy in uveitic patients with VO and compare the visual outcome between infectious and noninfectious uveitis. Forty-five eyes with uveitis-associated VO underwent diagnostic and therapeutic vitrectomy, and etiological diagnosis of uveitis was confirmed in 34 of 45 eyes (75.6%). The diagnoses were infectious uveitis in 13 eyes (28.9%), noninfectious uveitis in 21 eyes (46.7%), and unidentified uveitis in 11 eyes (24.4%). Visual acuity (VA) improvement rates at 6 months after surgery were 69.2%, 76.2%, and 90.9% in the infectious, noninfectious, and unidentified uveitis groups, with no significant difference among 3 groups. Significant decrease in inflammation score after vitrectomy was observed only in the infectious uveitis group. This study demonstrated that diagnostic vitrectomy for inflammatory eyes with VO of unknown etiology was effective in infectious and noninfectious uveitis, and the therapeutic effect of VA improvement was observed in both types of uveitis.

Indocyanine green (ICG) angiography is an indispensable inspection to diagnose and treat for chorioretinal diseases. In this study, we investigated the phototoxicity of ICG on RPE cells at the levels of residual ICG after angiography under ambient light. After incubation of ARPE-19 cells in a colorless medium containing 0 to 10 μg/mL ICG for 24 hours in the dark or under 2000 lx illumination from a fluorescent lamp, cell viability decreased and cell death rate increased in cultures with more than 5.0 μg/mL ICG under illumination. In culture with 10 μg/mL ICG under illumination, morphology of cells changed to be oval and TUNEL- and malondialdehyde-positive cells increased compared to other cultures with ICG in the dark or without ICG under illumination. Furthermore, the level of intracellular reactive oxygen species was also elevated. On the other hand, toxicity of ICG denatured by illumination was not observed. Blocking green to red light overlapping wavelengths of ICG absorbance exhibited decreased cell death rate. The present study indicated that ICG at the estimated intravenous concentrations after ICG angiography induces potential phototoxicity on human RPE cells via oxidative damage under continuous ambient illumination and that the cytotoxicity is reduced by blocking green to red light wavelengths.