Several drugs approved for a variety of indications have been shown to exhibit antiangiogenic effects. Our study focuses on the PPARγ ligand rosiglitazone, a compound widely used in the treatment of type 2 diabetes. We demonstrate, for the first time to our knowledge, that PPARγ is highly expressed in tumor endothelium and is activated by rosiglitazone in cultured endothelial cells. Furthermore, we show that rosiglitazone suppresses primary tumor growth and metastasis by both direct and indirect antiangiogenic effects. Rosiglitazone inhibits bovine capillary endothelial cell but not tumor cell proliferation at low doses in vitro and decreases VEGF production by tumor cells. In our in vivo studies, rosiglitazone suppresses angiogenesis in the chick chorioallantoic membrane, in the avascular cornea, and in a variety of primary tumors. These results suggest that PPARγ ligands may be useful in treating angiogenic diseases such as cancer by inhibiting angiogenesis.

Glaucoma is an optic neuropathy accompanied by vision loss which can be mapped by visual field (VF) testing revealing characteristic patterns related to the retinal nerve fibre layer anatomy. While detailed knowledge about these patterns is important to understand the anatomic and genetic aspects of glaucoma, current classification schemes are typically predominantly derived qualitatively. Here, we classify glaucomatous vision loss quantitatively by statistically learning prototypical patterns on the convex hull of the data space. In contrast to component-based approaches, this method emphasizes distinct aspects of the data and provides patterns that are easier to interpret for clinicians. Based on 13 231 reliable Humphrey VFs from a large clinical glaucoma practice, we identify an optimal solution with 17 glaucomatous vision loss prototypes which fit well with previously described qualitative patterns from a large clinical study. We illustrate relations of our patterns to retinal structure by a previously developed mathematical model. In contrast to the qualitative clinical approaches, our results can serve as a framework to quantify the various subtypes of glaucomatous visual field loss.

The aim of this study was to evaluate glaucoma onset and progression after implantation of Boston Keratoprostheses (B-KPro) and the role of glaucoma surgery. Records of patients with B-KPro implantation during 2004 to 2009 were reviewed. Parameters relevant to B-KPro surgery and glaucoma status were recorded. The data were analyzed in 5 groups based on the preoperative diagnosis. One hundred six eyes of 87 patients were included, and the average age was 54 ± 6.7 years. Forty-six percent were female. Eighteen eyes had a B-KPro with a titanium back plate, and the others had a poly(methyl methacrylate) back plate. Thirty-three eyes were pseudophakic, and the rest were left aphakic. The follow-up time was 3.3 ± 1.0 years. Indications for implantation included past infection, congenital glaucoma, trauma, autoimmune diseases, aniridia, burns, and others. Sixty-six percent of the eyes had glaucoma preoperatively, and 26% developed de novo glaucoma afterward. The mean intraocular pressure (by finger palpation) was 16.5 ± 5.7 mm Hg. Reliable visual field tests were only available in 59% of the eyes; hence, the cup-to-disc ratio of the optic nerve head was used as the main outcome measure. In B-KPro-implanted eyes with glaucoma, 65% had undergone glaucoma surgery at some point, and 30% did not show progression. Thirty-one percent of the total cohort had disc pallor with a cup-to-disc ratio of <0.8. Glaucoma in B-KPro remains a challenge, despite aggressive attempts to slow down its progression. Patients with glaucoma before B-KPro implantation should be considered for glaucoma surgery before or simultaneously with B-KPro implantation. The high number of eyes with disc pallor suggests that additional mechanisms other than elevated intraocular pressure may play a role in optic neuropathy.

Purpose: To detect visual field (VF) progression by analyzing spatial pattern changes. Methods: We selected 12,217 eyes from 7360 patients with at least five reliable 24-2 VFs and 5 years of follow-up with an interval of at least 6 months. VFs were decomposed into 16 archetype patterns previously derived by artificial intelligence techniques. Linear regressions were applied to the 16 archetype weights of VF series over time. We defined progression as the decrease rate of the normal archetype or any increase rate of the 15 VF defect archetypes to be outside normal limits. The archetype method was compared with mean deviation (MD) slope, Advanced Glaucoma Intervention Study (AGIS) scoring, Collaborative Initial Glaucoma Treatment Study (CIGTS) scoring, and the permutation of pointwise linear regression (PoPLR), and was validated by a subset of VFs assessed by three glaucoma specialists. Results: In the method development cohort of 11,817 eyes, the archetype method agreed more with MD slope (kappa: 0.37) and PoPLR (0.33) than AGIS (0.12) and CIGTS (0.22). The most frequently progressed patterns included decreased normal pattern (63.7%), and increased nasal steps (16.4%), altitudinal loss (15.9%), superior-peripheral defect (12.1%), paracentral/central defects (10.5%), and near total loss (10.4%). In the clinical validation cohort of 397 eyes with 27.5% of confirmed progression, the agreement (kappa) and accuracy (mean of hit rate and correct rejection rate) of the archetype method (0.51 and 0.77) significantly (P < 0.001 for all) outperformed AGIS (0.06 and 0.52), CIGTS (0.24 and 0.59), MD slope (0.21 and 0.59), and PoPLR (0.26 and 0.60). Conclusions: The archetype method can inform clinicians of VF progression patterns.

Exfoliation syndrome (XFS) is a form of deleterious ocular aging categorized by increased risk for climatic droplet keratopathy,^1,2 age-related cataract,^3-5 late-onset spontaneous intraocular lens subluxation,⁶ elevated intraocular pressure with glaucomatous optic neuropathy,⁷ and retinal vein occlusion.^8,9 The discovery that common variants of LOXL1 are present in 99% of XFS cases represents a significant advance in understanding this condition.¹⁰ However, 80% of control individuals also harbor these variants and the ratio of cases to control individuals with trait-related variants is fairly similar in regions where XFS is hyperendemic¹¹ and regions where the condition is relatively rare.¹² This suggests that other genetic or environmental factors contribute to XFS.