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Elliot Cha, Rui Jin, Haiyan Gong; The Relationship Between Morphological Changes and Reduction of Active Areas of Aqueous Outflow in Eyes with Primary Open Angle Glaucoma. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2291.
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The aim of this study was to identify morphological differences between active and non-active areas of outflow in normal human eyes and to further identify additional structural changes that lead to reductions in active areas of aqueous outflow in primary open angle glaucoma (POAG).
Four POAG and four normal human eyes were perfused for 30 minutes at 15mmHg to establish a stable baseline outflow facility. The anterior chamber of each eye was exchanged (5mL) and perfused with a fixed volume (200µL) of fluorescent microspheres to visualize the outflow patterns. All eyes were perfusion-fixed. Fluorescent tracer distribution in episceral veins (EV) and trabecular meshwork (TM) were imaged and analyzed on a global scale. All eyes were then dissected and further categorized into no, low, and high tracer regions. Distribution of tracer throughout the outflow pathway was imaged and analyzed by confocal microscopy in frontal sections and specific morphological changes associated with each flow type were further analyzed using both light and electron microscopy.
Outflow facility was significantly lower in POAG eyes compared to normal eyes (p< 0.05). Areas of active outflow were segmental in normal eyes and significantly reduced in POAG eyes (p< 0.05). Interestingly, the remaining active flow areas of POAG eyes were predominantly in the nasal quadrant. High and low tracer regions for both normal and POAG eyes showed similar outflow morphology, with a discontinuous basement membrane (BM) along the inner wall endothelium of Schlemm’s canal (SC), open SC, and open spaces between trabecular beams. Regions of normal eyes exhibiting no tracer showed a narrower SC and denser extracellular matrix (ECM) in the TM compared to high tracer regions. Regions devoid of tracer in POAG eyes were associated with a collapsed SC, more continuous and thicker BM along the inner wall of SC, and increased ECM beneath the inner wall and in the TM.
Morphological differences were found that consistently distinguished active and non-active areas of outflow in normal eyes. Having the ability to distinguish these areas has permitted us to identify the features that accompany the reduction of active flow area in POAG. Equally important, these features were not found in remaining active areas of outflow.
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