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.

Age-related macular degeneration (AMD) is a cause of blindness in people older than 50 years. Accumulating evidence indicates the involvement of systemic and local inflammation in the pathogenesis and progression of AMD. Aflibercept is an anti-vascular endothelial growth factor (VEGF) inhibitor, and intravitreal injection of aflibercept (IVA) is the approved treatments of neovascular AMD (nAMD), but the effect on inflammatory response remains unclear. The aim of our study was to investigate the profiles of inflammatory cytokines in the aqueous humor of nAMD patients before and after initiation of IVA. In nAMD patients, IP-10 level was significantly higher and IL-6 level was significantly lower compared with those of cataract patients as controls. Logistic regression analysis identified IP-10 as a positive factor and IL-6 a negative factor associated with the pathogenesis of nAMD. In addition, IP-10 level correlated positively with the mean thickness of macula in the central 1-mm diameter circle. After initiation of IVA, IP-10 level was further elevated, and correlated negatively with VEGF level. These data suggest that IP-10 plays a critical role as an antiangiogenic factor and at the same time an inflammatory factor in the pathogenesis and pathophysiology of nAMD eyes at onset and after IVA initiation.

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.

Aims To evaluate the prevalence and aetiology of intraocular hypertension (OHT) in granulomatous and non-granulomatous uveitis Methods Medical records of 304 consecutive patients (484 eyes) with uveitis who visited the National Defense Medical Collage Hospital between April 2010 and March 2013 were reviewed retrospectively. OHT irrelevant to glaucomatous changes in optic disc or visual field was investigated. Results OHT was found in 123 eyes (25.4%) of 93 uveitic patients (30.6%); 92% of the eyes had open-angle OHT, 45.6% of which was steroid-induced. The prevalence of OHT was 100% (8/8) in Posner–Schlossman syndrome, 50.0% (10/20) in varicella zoster virus-associated iridocyclitis, 45% (9/20) in scleritis, 34.1% (15/44) in Vogt–Koyanagi–Harada disease, 32.1% (18/56) in Behçet's disease (BD), 23.1% (6/26) in acute anterior uveitis, and 20.2% (19/94) in sarcoidosis. Pupillary block was observed only in non-granulomatous uveitis, but not in granulomatous uveitis. Seventy percent of OHT in granulomatous uveitis cases was inflammation-induced, while 76.7% in non-granulomatous uveitis cases was steroid-induced. Conclusions 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.