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Uveitis is an inflammatory condition that can lead to blindness. It is therefore important to understand the pathophysiology against which to develop targeted therapy. Herein, we tested whether the oxidant-responsive transcription factor Nrf2 is involved in regulating the innate immune response and oxidative damage in the LPS uveitis model. As shown by dihydroethidium staining, intraperitoneally injected LPS increased reactive oxygen species in the retina and iris-ciliary body of Nrf2+/+ and Nrf2-/- mice. After LPS injection, ICAM-1, IL-6, TNF-alpha, COX-2, iNOS, and MCP-1 mRNAs were increased more in the retina and iris-ciliary body of Nrf2-/- than in those of Nrf2+/+ mice. NQO-1 and GCLM, two Nrf2-responsive antioxidant enzymes, had reduced expression in Nrf2+/+ retinas after LPS injection, but no change in expression in Nrf2-/- mice. The number of FITC-Con A-labeled leukocytes adherent to the retinal vascular endothelium increased after LPS treatment in both Nrf2+/+ and Nrf2-/- mice compared to control injections, with more adherent leukocytes in Nrf2-/- than in Nrf2+/+ mice. Pretreatment with the Nrf2 activator 1-(2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl)imidazole increased antioxidant gene expression in the retina, reduced inflammatory mediator expression, and reduced leukocyte adherence to retinal vasculature after LPS treatment in Nrf2+/+ mice, but had no effect on Nrf2-/- mice. Treatment targeting the Nrf2 pathway may be a new therapy for uveitis.

ApoB100 lipoprotein particles have been found to accumulate in Bruch membrane prior to the development of Age-related macular degeneration (AMD). This work was performed to determine whether mice that overexpress apoB100 in the RPE-choroid and liver develop landmarks of early AMD over time. Mice transgenic for a human genomic fragment encoding the full length human ApoB (“ApoB100” mice) and litter-mate control mice were given a normal chow or high fat diet for 12 months. Mice were evaluated for human apoB mRNA expression in the RPE/choroid and liver by RT-qPCR. Phenotypic changes associated with early AMD were evaluated by ultrastructural analysis using transmission electron microscopy. Changes were semi-quantified using linear regression analysis. Both the RPE/choroid and liver of ApoB100 mice expressed both human and mouse ApoB mRNA. Transmission electron microscopy showed ultrastructural changes consistent with early human AMD including loss of basal infoldings and accumulation of cytoplasmic vacuoles in the RPE, and basal laminar deposits containing long spacing collagen and heterogeneous debris in Bruch membrane of ApoB100 mice. In ApoB100 mice given a high fat diet, basal linear-like deposits were identified in 12 month old mice. Linear regression analysis showed that the genotype (human ApoB transgene) was a stronger influencing factor than high fat diet in producing AMD-like lesions used in this study. Human ApoB100 transgenic mice overexpress apoB in RPE and, with time, develop validated phenotypic changes that are seen in early human AMD. The phenotypic changes were aggravated by feeding a high-fat diet. The ApoB100 mouse model could be valuable in determining the role of apoB containing lipoproteins in triggering the onset of early AMD.

To investigate the frequency of residual angle closure after resolution of pupillary blocking by laser peripheral iridotomy and the effects of subsequent cataract surgery to resolve angle closure completely.Retrospective, consecutive, interventional study.Among 70 eyes treated with laser iridotomy, 13 with residual angle closure were treated with cataract surgery.The provocative test of angle closure by prone position in a dark room for 1 hour was performed; increases in tension ofor =8 mmHg, 6 or 7 mmHg, andor =5 mmHg were considered to be positive, suspected positive, and negative, respectively. Configuration of the anterior chamber was examined using ultrasound biomicroscopy (UBM).Intraocular pressure (IOP), response to the dark room prone position test, and morphologic analysis by UBM were evaluated before and 3 months after cataract surgery.Residual angle closure after iridotomy was seen in 27 (38.6%) of 70 eyes; this was confirmed functionally by the dark room prone position test and morphologically by UBM. Eyes with IOP ofor =20 mmHg or with a glaucomatous visual field defect before iridotomy had a significantly higher incidence of residual angle closure after iridotomy than eyes without these findings (P0.05). In all the eyes with residual angle closure after iridotomy, the response to the prone position test became negative after cataract surgery, with significant lowering of IOP (P0.01).Residual angle closure after iridotomy was common, especially in eyes with primary angle closure and poorly controlled IOP or glaucomatous optic neuropathy. Cataract surgery was effective to resolve completely the residual angle closure after iridotomy and lower IOP.

Purpose In eyes with primary angle closure (PAC), we quantitatively evaluated anterior bowing of the iris by means of ultrasound biomicroscopy (UBM). Design Retrospective, observational, and consecutive case series. Methods A total of 203 phakic eyes with PAC that had not undergone any surgical or laser treatment were included. Using UBM, we measured anterior chamber depth (ACD) and iris convexity (IC): the maximum distance from the posterior surface of the iris to the iris plane passing through the pupillary margin of the iris and iris root. Results The average IC was 0.22 ± 0.1 mm, although there was considerable individual variation. The IC value was correlated weakly, albeit significantly, with age ( r = 0.22, P r = −0.57, P Conclusions In eyes with PAC, older age and a more shallow ACD appear to be important causes of increased forward bowing of the iris resulting from pupillary block.

To compare the effect of photodynamic therapy (PDT) and intravitreal ranibizumab in patients with polypoidal choroidal vasculopathy (PCV).Randomized clinical trial.Multicenter.Total of 93 patients with treatment-naïve PCV.Patients were randomized to 2 arms. Patients in the PDT arm underwent a single session of PDT with verteporfin, and patients in the ranibizumab arm received 3 monthly ranibizumab injections at baseline. Additional treatment was performed as needed in each arm.Primary outcome measurement was the proportion of patients gaining or losing more than 0.2 logarithm of minimal angle of resolution (logMAR) units from baseline. Mean change of logMAR and central retinal thickness (CRT) were also evaluated.In the PDT arm (n = 47), 17.0% achieved visual acuity gain, 55.3% had no change, and 27.7% experienced visual acuity loss. The results were 30.4%, 60.9%, and 8.7%, respectively, in the ranibizumab arm (n = 46), significantly better than the PDT arm (P = .039). In the PDT arm, mean CRT improved (366.8 ± 113.6 μm to 289.1 ± 202.3 μm, P.001), but logMAR was unchanged (0.57 ± 0.31 to 0.62 ± 0.40). The ranibizumab arm demonstrated improvement in both CRT (418.9 ± 168.6 μm to 311.2 ± 146.9 μm, P.001) and logMAR (0.48 ± 0.27 to 0.39 ± 0.26, P = .003). Mean change of logMAR was also greater in the ranibizumab arm (P = .011).Intravitreal injection of ranibizumab is more effective than PDT for treatment-naïve PCV.