Morphological And Hydrodynamic Changes Of The Outflow Pathway Following Experimental Intraocular Pressure Variation

Purposes:To determine whether the hydrodynamic and morphological changes with acute intraocular pressure (IOP) elevation are reversible when IOP is returned to normal physiologic pressure using a two-colored tracer technique to label the outflow patterns at two different IOPs within the same enucleated bovine eye.Methods:Twelve enucleated bovine eyes were first perfused at 30 mmHg with red fluorescent microspheres (0.5μm,0.002% v/v). After removing the red tracer, perfusion was continued at 7 mmHg with a green tracer, followed by fixative. In 2 control groups, the eyes were constantly perfused at either 30 mmHg (n=6) or 7 mmHg (n=6) using the same methods. The outflow facility was continuously recorded. Confocal images were taken along the inner wall (IW) of the aqueous plexus (AP) and the percent of the effective filtration length (PEFL) was measured. Light microscopy was performed. The number of herniations into collector channel (CC) ostia and separation between the inner wall and juxtacanalicular connective tissue (JCT) were analyzed.Results:In the experimental group (30-7mmHg), the facility was significantly higher at 7mmHg than that at 30mmHg (p=0.002). This corresponded to a significant increase in the PEFL (p<0.01), which was associated with less collapse of AP, a decreased number of CC ostia exhibiting herniations (p=0.020) and a larger area exhibiting separation between the IW and JCT.Conclusion:A reversible change in the available area for aqueous outflow plays an important role in the regulation of outflow facility following acute experimental variation of IOP, which in turn is regulated by morphological changes. Purpose:To investigate the morphological changes of the outflow pathway induced by acute elevated IOP and their contribution to the decreased outflow facility in enucleated normal human eyes, as well as the reversibility of these structure changes and the possible mechanism while the pressure was reversed to normal level.Methods:Ten human eyes were studied within 24 hours postmortem. As the experimental group, three eyes were perfused from 45mmHg to 7mmHg. The outflow facility was recorded at these two IOP levels. The other six eyes were divided into two groups continuously perfusing only at 45mmHg or 7mmHg as controls.150μl green fluorescent microspheres were then perfused at the last IOP level among all three groups. Corresponding facility was also recorded. After perfusion fixation, anterior segments of the eyes were processed and cut into 4 quadrants. Fluorescent macroscopic Images were taken to exhibit the whole outflow pattern. The same samples were then cut into the frontal sections (3μm) to take the confocal images. The effective filtration lengths labeling by fluorescent microspheres were measured and calculated at least 16 images per eye. Using light microscope, the herniations of SC inner wall were analyzed from at least eight CC ostia per eye, the SC width and collapse were also observed as well.Results:In the experimental group, the outflow facility at 7 mmHg (0.253μl/min/mmHg) was remarkably increased than that at 45 mmHg (0.085μl/min/mmHg, p=0.029). There was no significant difference in the outflow facility between the experimental and control groups at 7 mmHg (0.289μl/min/mmHg p=0.48). Correspondingly, the outflow pattern in the experimental group became more diffused compared to the segmental outflow pattern in control high IOP group, as well as the effective filtration length in the experimental group (36.98%) was reversed to have no significant difference with the control low IOP group (40.16%, p=0.48). Consistent with the hydrodynamic changes, the morphological changes in the experimental group (the SC width and the percentage of CC ostia exhibiting herniations) were also reversed to normal level.Conclusions:Decreasing outflow facility following acute IOP elevation coincides with progressive collapse of SC and an increasing number of herniations into CC ostia. These changes appeared to be reversible when IOP was decreased from 45 mmHg to 7mmHg in normal human eyes. Our data suggest that morphological changes of SC and CC ostia may contribute to the increasing outflow resistance. Purpose:Blockages of collector channel ostias caused by the herniation of Schlemm's canal inner wall are found histologically as a common feature in POAG eyes. This study is to explore the aqueous outflow resistance generation area in POAG patients in vivo.Methods:Nighteen POAG patients (24 eyes) undergoing the Canalostomy during 2004-2007 at Pretoria University were studied. Preoperatively, the paracentesis of the anterior chamber followed by a provocative gonioscope examination was applied to patients to check the blood reflux in Schlemm's canal. After a nonpenetrating dissection technique to expose Schlemm's canal was performed, a flexible microcatheter (iTrack 250A, iScience Interventional) was used to dilate the full circumference of the canal. Fluorescence was then injected into the dilated Schlemm's canal through the microcatheter per quadrant in order to evaluate its outflow pattern from Schlemm's canal to the episclera vein. The number of quadrants exhibiting fluorescence egressed collector channels were further counted.Results:Three types of blood reflux patterns were observed within 24 POAG eyes:good reflux (circumferential blood reflux):N=9; patchy reflux (discontinued blood reflux):N=6 and no reflux:N=9. 62.50% eyes had no circumferential blood reflux into Schlemm's canal. In all 24 POAG eyes, the average quadrants exhibiting fluorescence egressed collector channels was 2.37±0.44. The average quadrants exhibiting fluorescence egressed collector channels in the good reflux, patchy reflux and no reflux groups were 3.67±0.50,2.67±1.21,0.89±0.93 respectively. There was a significant positive correlation between the blood reflux pattern and the average quadrants exhibiting fluorescence egressed collector channels (r=0.808, p<0.01). Conclusions:According to our clinical findings above,, the irreversible blockages of collector channel ostias might exist in the African POAG patients, which was consistent with our previous histological findings.