Biomedical subjects
Publications and source records attributed to R A Moses.
Some prostaglandins, topically applied, are known to lower intraocular pressure; a few have been shown to increase facility of outflow. Iloprost (ZK36374), a stable PGI2 analog, was tested in rabbits for effect on intraocular pressure and facility, but was found totally inactive on either.
From geometrical considerations of the trabecular meshwork, ciliary muscle contraction has been predicted to produce an inward movement of the mesh. Goniophotographs taken under carefully controlled conditions before and after topical administration of pilocarpine showed a change in angle between cornea and mesh that is consistent with the predicted change.
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Model experiments and mathematical analysis of intraocular pressure and blood flow show that as venous pressure is increased there is a rapidly increasing tendency for intraocular veins to collapse. Vein collapse slows blood flow markedly. We propose that the visual field loss in glaucoma secondary to elevated venous pressure is associated with intraocular vein collapse and retardation of intraocular blood flow.
The time-dependent increase in apparent facility of outflow (washout effect) that occurs with prolonged perfusion of the eye has imposed limitations on the study of aqueous humor dynamics. The washout effect in postmortem in situ rabbit eyes, undergoing constant pressure perfusion with a saline perfusate, can be attenuated dramatically by adding to the perfusate the serine protease inhibitor and antifibrinolytic agent epsilon-aminocaproic acid (EACA) at a concentration of 3.8 X 10(-3) molar. Washout curves from 13 pairs of rabbit eyes, plotted as outflow facility versus time, were fitted by linear regression, and their washout slopes calculated. The washout slope of all of the 13 eyes perfused with normal saline + EACA was lower in magnitude (less washout) than the paired control eye in the same animal, perfused with a control perfusate of normal saline + leucine. Wilcoxon signed rank test yielded P less than 0.001. This suggests that a significant component of the washout effect may be mediated by fibrinolytic activity, or by some EACA sensitive component of the aqueous drainage pathway, and that addition of EACA to a saline perfusate may be useful for blunting the washout effect in prolonged perfusion studies.
Pfister and associates have shown that treatment with citrate solution reduces the incidence of stromal ulceration after alkali burn of the cornea. In the course of study of the effect of inhibitors of plasminogen activation on corneal re-epithelialization following alkali burns, we noted that when citrate was used in the medication, the healing process proceeded rapidly for three days; however, the denuded area became abruptly larger on the fourth day, and then resumed healing on the fifth day.
The eyeball proptoses about 0.5 mM and increases in intraocular pressure (IOP) about 2 mmHg with voluntary widening of the lid fissure. The findings probably result from the retraction of the upper lid into the orbit, thus increasing the volume of orbit contents and forcing the eyeball forward. Decrease in IOP with repeated tonometry may result, in part, from decay of the increased pressure induced by lid fissure widening.
Respiration and arterial pulse cause intraocular pressure to cyclically vary around a mean pressure. Both the respiratory and arterial pulse waves approximate sine waves, and we have represented the IOP cycle as the sum of sinusoidal pressure waves. A rapidly acting tonometer may record any portion of the IOP cycle. We have computed the probability that a single pressure measurement will lie within a given interval around mean IOP and the probability that the mean of several such measurements will lie within a given range of mean pressure. The probability that an IOP estimate will lie in a given range of mean IOP decreases as the IOP cycle amplitude increases but increases as the number of tonometric measurements averaged together increases.
A method of analysing fluorescein angiograms that yields a parameter of intraocular blood flow designated as the fluorescein appearance rate is presented. The appearance rate was decreased in those eyes in which intraocular pressure (Pi) was found to be increased. The appearance rate was also decreased in the two cases of "low tension glaucoma" whose angiograms we have analysed. The decrease in appearance rate with increase of Pi is the result of increasing vascular flow resistance due to constriction of veins at their exit from the eye.
The effect of lens depression on resistance to flow through the inner wall of Schlemm's canal, circumferentially along the canal, and through the collector channels was measured in enucleated eyes. In one series of experiments the anterior chamber was perfused while canal pressure was monitored, thus allowing us to estimate inner wall resistance and a combination of canal plus collector-channel resistance. In a second series of experiments the inner canal wall was blocked with oil while the canal was perfused, allowing us to measure both circumferential flow resistance and collector-channel resistance. Lens depression decreased inner canal wall resistance in five of five eyes and decreased circumferential flow plus collector-channel resistance in one of eight eyes. These results suggest that tensing the trabecular mesh increases canal inner wall porosity and opens the canal when it is partially collapsed.
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The concept of the conventional aqueous outflow pathway (through the trabecular meshwork and other components of the canal's inner wall, along Schlemm's canal to collector channels, and out of the eye through the collector channels) was modeled on tubes with leaky walls and a network of electrical resistances. Analysis of these models suggested experiments to test the models and to assess the magnitude of the resistance of portions of the pathway. We found that the well-known increase in outflow resistance with increased intraocular pressure was, in large measure, the result of blockage of the collector channels, probably by the canal's inner wall. A model of the trabecular meshwork predicted that tension on the scleral spur and trabecular mesh would cause the meshwork to arch over Schlemm's canal. We depressed the lens to generate such tension, and found that the resistance of the inner wall of the canal decreased. In one eye, lens depression also decreased resistance to flow in the collector channels and the canal of Schlemm and prompted the suggestion that when secretory inhibitors are used in glaucoma, cyclo-tonic agents should be used simultaneously to relieve canal collapse and blockage of collector channels by inner canal wall.
A tonography device, based on the MacKay-Marg tonometer, has been constructed which will applanate the cornea to a preselected area of 5.0 to 6.0 mm diameter and maintain that applanation area. The pressure decrease with time should resemble the pressure decrease following bolus injection of fluid into the eye. In most cases the pressure decreased in a linear slope, abruptly terminating in a pressure plateau. In most cases, the pressure after 4 min of tonography was lower than preliminary Goldmann applanation pressure.
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We have shown that in the excised eye when oil in the anterior chamber has made the trabecular mesh impermeable, resistance to circumferential flow along the canal increases moderately as transmural pressure is increased. At the same time, resistance to outflow from the canal through the collector channels increases markedly as transmural pressure is increased from low levels to 35 or 40 mm Hg. We have suggested that the usual primary defect in open-angle glaucoma is reduced facility of the inner canal wall and that collapse of the canal with reduction of filtering area and plugging of collector channels is a secondary effect.
The corneoscleral trabecular meshwork is a three-dimensional net of diagonally crossing collagenous fiber invested in endothelium. Tension on the mesh should cause it to tend to bow inward and hold Schlemm's canal open. Inward bowing is restrained by attachment of the outer mesh to the corneosclera, by meridional uveal mesh fibers, and by resistance to mesh element crossing to deformation. A lamella of meshwork is analyzed from a geometrical point of view, and it is found that even were the mesh free to assume an inward bowed hyperboloidal shape, the spur movement required to change mesh configuration from that of a cone frustum to hyperboloid would be only 0.047 mm and not readily recognizable gonioscopically.
The scale reading of the pneumatonograph (PTG) is dependent on the force of application to the cornea. Since this force is relatively greater at low intraocular pressure, the scale is compressed, yielding an overestimate of intraocular pressure in physiologic range. When the PTG is held vertically, the weight of the plunger is added to the gas propulsion force and the compression of the scale is accentuated. When a 10-g plunger load is added, as is advocated for tonography, the scale compression is further accentuated. We conclude that the PTG scale is compressed, the PTG is position-sensitive, and that the PTG is totally unsuited to tonography. The PTG is not an applanation tonometer and should not be confused with applanation tonometers.
Blood may be refluxed into Schlemm's canal in the normal eye by occlusion of recipient veins in a sector of the conjunctiva and episclera. The blood makes the anterior margin of the canal distinct near the midportion of the trabecular mesh at the same place in which it is seen after hypotony. Circumferential flow in segments of the canal is possible when a pressure head exists to promote such flow. Evidence was found that the canal is not partially collapsed in the normal eye.