Browsing by Subject "Intraocular Pressure"
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Item Open Access Angiopoietin receptor TEK mutations underlie primary congenital glaucoma with variable expressivity.(The Journal of clinical investigation, 2016-07) Souma, Tomokazu; Tompson, Stuart W; Thomson, Benjamin R; Siggs, Owen M; Kizhatil, Krishnakumar; Yamaguchi, Shinji; Feng, Liang; Limviphuvadh, Vachiranee; Whisenhunt, Kristina N; Maurer-Stroh, Sebastian; Yanovitch, Tammy L; Kalaydjieva, Luba; Azmanov, Dimitar N; Finzi, Simone; Mauri, Lucia; Javadiyan, Shahrbanou; Souzeau, Emmanuelle; Zhou, Tiger; Hewitt, Alex W; Kloss, Bethany; Burdon, Kathryn P; Mackey, David A; Allen, Keri F; Ruddle, Jonathan B; Lim, Sing-Hui; Rozen, Steve; Tran-Viet, Khanh-Nhat; Liu, Xiaorong; John, Simon; Wiggs, Janey L; Pasutto, Francesca; Craig, Jamie E; Jin, Jing; Quaggin, Susan E; Young, Terri LPrimary congenital glaucoma (PCG) is a devastating eye disease and an important cause of childhood blindness worldwide. In PCG, defects in the anterior chamber aqueous humor outflow structures of the eye result in elevated intraocular pressure (IOP); however, the genes and molecular mechanisms involved in the etiology of these defects have not been fully characterized. Previously, we observed PCG-like phenotypes in transgenic mice that lack functional angiopoietin-TEK signaling. Herein, we identified rare TEK variants in 10 of 189 unrelated PCG families and demonstrated that each mutation results in haploinsufficiency due to protein loss of function. Multiple cellular mechanisms were responsible for the loss of protein function resulting from individual TEK variants, including an absence of normal protein production, protein aggregate formation, enhanced proteasomal degradation, altered subcellular localization, and reduced responsiveness to ligand stimulation. Further, in mice, hemizygosity for Tek led to the formation of severely hypomorphic Schlemm's canal and trabecular meshwork, as well as elevated IOP, demonstrating that anterior chamber vascular development is sensitive to Tek gene dosage and the resulting decrease in angiopoietin-TEK signaling. Collectively, these results identify TEK mutations in patients with PCG that likely underlie disease and are transmitted in an autosomal dominant pattern with variable expressivity.Item Open Access Macular Vascular Microcirculation in Eyes With Open-angle Glaucoma Using Different Visual Field Severity Classification Systems.(Journal of glaucoma, 2019-09) Bojikian, Karine D; Nobrega, Priscilla; Wen, Joanne C; Zhang, Qinqin; Mudumbai, Raghu C; Johnstone, Murray A; Wang, Ruikang K; Chen, Philip PPrecis
We found significant differences in macular vascular microcirculation between normal and glaucomatous eyes using optical coherence tomography angiography (OCTA). Macular vascular microcirculation changes also showed significant correlations with visual field (VF) severity classification systems.Purpose
To correlate VF severity defined by different classification systems and macular vascular microcirculation in eyes with glaucoma using OCTA.Patients and methods
Twenty normal and 58 open-angle glaucoma (OAG) eyes were scanned using a swept-source OCTA (Plex Elite 9000) and macular vascular microcirculation was measured by calculating the overall blood flux index (BFI) and vessel area density (VAD) over the entire 6×6 mm area excluding the big retinal vessels. Glaucomatous eyes were staged into severity groups based on 4 VF severity classifications: Hodapp-Parrish-Anderson scale, Glaucoma Severity Staging system, ICD-10 glaucoma staging definitions, and VF mean deviation. Central 10-degree VF mean sensitivity (CMS) was calculated based on 24-2 VF. One-way analysis of variance was used to analyze the differences and correlation between macular vascular microcirculation and other clinical parameters.Results
Glaucomatous eyes had significantly lower ganglion cell and inner plexiform layer BFI and VAD (P<0.0001) compared with normal eyes. In OAG patients, BFI and VAD were significantly higher in mild OAG compared with severe OAG with all VF disease severity classification systems (P<0.001). Glaucoma Severity Staging had the highest correlation with changes in macular vascular microcirculation metrics (r=0.734 for BFI; r=0.647 for VAD) and VF CMS had highest correlation with macular vascular microcirculation metrics (r=0.887 for BFI; r=0.903 for VAD).Conclusion
Macular vascular microcirculation metrics detected by OCTA correlate with disease severity in glaucomatous eyes. VF CMS, calculated from only 12 tested central 10-degree points, correlated best with macular OCTA.