OUTFLOW II The Retinal Circulation, ctd. We follow the blood stream to the optic disc. There, within a fraction of a millimeter, there occurs a precipitous drop in pressure, from the 12 or 15 or 20 or 25 or whatever the intraocular pressure happens to be, to a very low value, perhaps five or three or twomm Hg. The value of the venous pressure within the optic nerve is unknown, but the distance from the optic nerve to the cavernous sinus is small, and we know that in the sinus the venous pressure is zero or less. Simple algebraic calculation illustrates what goes on. If we define resistance as the quotient of pressure gradient divided by flow, then given a constant volume of flow per unit time, the large pressure gradient indicates a proportionately large resistance to flow. The cause of this increase of resistance, and its fluctuations are readily seen. With the ophthalmoscope, one can observe that on the optic disc the increase in resistance to flow is brought about by the pressure induced collapse of the retinal veins. As its cross section becomes smaller, if the volume flow per unit time is to remain the same, as it must, there will be acceleration of the rate of flow. The vein collapses, of course, from a disparity between intravascular and extravascular, i.e. intraocular pressures. The intravascular pressure is low because of a lack of down- stream resistance. There is literally nothing, no resistance, no friction, no back pressure, to prevent the blood in the retianl vein from draining freely into the veins behind the globe. That is why a segment of vein on the disc collapses, sufficient in length to establish a segment of high resistance to flow which will, in effect maintain the intravascular pressures within the eye at above intraocular pressure. It is this resistance which holds back, as it were, the contents of the venous bed in the retina, and prevents its being expressed by the intraocular pressure. It is instructive now to observe, how this collapsed segment of vein which serves as a reducing valve, responds to changes in the various parameters to which it is subject. Simply by lightly placing a finger over the lateral rectus muscle and making pressure on the sclera, one may increase the intraocular pressure, and observing through the ophthalmoscope at the same time, simultaneously, onenotes that the segment of collapsed being becomes longer, up to a point, and then no additional pressure will cause any additional collapse of the vessel. In other eyes even the initial increase of intraocular pressure brings about no change in the length of the compressed vein. As intraocular pressure is increased, the resistance of the vein will also increase, and, depending on the physical characetristic of the vein wall and on the volume of flow, this increase in resistance will be brought about either by additional compression of that segment of vein which is already collapsed, or by the collapsed of an additional distal length of vein, that is, by lengthening of the total amount of collapsed vein. We observe the same phenomenon to occur spontaneously in those eyes where there is spontaneous pulsation of veins on the disc. There the fluctuation in the length of the collapsed segment is caused by pulsations in the intraocular pressure which are transmitted from pulsatile expansion of the choroid secondary to the pulsation of its own blood supply. The arterial pulse momentarily expands the choroidal vasculature, increasing the intraocular pressure, and it is this pressure increase which is reflected in the pulsation of the retinal vein. Consider also the effects on the length of collapsed vein of variations of retinal arterial flow. When flow through the vein increases, there is some small diminution in the length of the collapsed vein at its distal end. Conversely, as is often the case, when, as from arteriosclerotic obstruction of the feeding vessels, there is a diminution of flow, the length of collapsed vein increased. This relationship becomes obviouis from purely algebraic considerations, inasmuch as the pressure gradient is the product of flow times resistance. If the pressure gradient is to remain the same, then when the flow per minute decreases, the resistance must increase. The resistance will increase either as a result of more complete or of more extensive collapse. Whether the change in resistance comes about as the result of more complete or more extensive collapse will be a function of the elastic properties of the vein. The less pliable, the more sclerotic the vein, the longer will be the segment required to bring about the requisite pressure gradient for any given amount of flow. Similarly, the lower the minute volume of flow, the longer will be the segment required to account for any given pressure gradient. We observe that when the flow diminishes beyond a critical point, for any given value of wall stiffness, a localized reduction in pressure can no longer be achieved. The pressure will then be reduced in the entire venous bed. The entire venous tree will then sustain a pressure reduction as manifested by partial collapse of the vein and the broadening of its profile as described above. These observations in physicology, in addition to their explanatory value for a-v nicking and the increase v/a ration commonly seen in obstructive retinal vascular disease of all kinds, will also shed some light on the possible etiology of glaucomatous disc damage. Observation with the ophthalmosocpe, readily confirmed with fluorescein angiography, reveals that the temporal and nasal poles of the disc, those areas in other words that subserve the macula and the temporal field which are as is well known most resistant to glaucomatous damage, have a venours drainage through small horizonatlly cousing veins which enter the central retinal vein near the center of the disc in the proximity of the lamina cribrosa. The central vein in this area is almost always collapsed and the pressure within it is substantially lower than the intraocular pressure. Equally important is the circumstance that when the intraocular pressure is increased the venous pressure in this central segment of vein is unaffected. It is different with the venous drainage from the upper and lower poles of the optic disc. This drainage feeds into the superior and inferior retinal veins at or near the disc margin, where the retinal veins are not collapsed, distal to the collapsed segments. Therefore this venous drainage must contend with the intraocular pressure. Therefore venous drainage from the upper and lower poles of the disc which show the greatest sensitivity to glaucomatous damage, occurs into a segment of vein at or slightly above the intraocular pressure. At least as important, when the intraocular pressure rises, unless, as is usually not the case, the area of collapse extends to this region, the pressure against which the capillary drainage from the upper and lower poles of the disc must contend, increases with the intraocular pressure. Consider then what might happen to the venous circulation on the disc as the intraocular pressure is increased. The venous drainage from the temporal and nasal portions of the disc is affected not at all, inasmuch as it feeds into a segment of retinal vein which is collapsed, and therefore under lower pressure, and an increase in the intraocular pressure will not be transmitted to it. The venous drainage on the other hand from the upper and lower poles of the disc feeds into branches of the retinal vein which are not usually collapsed either at nromal or at elevated intraocular pressures. This fact means that the venous pressure in these segments is equal to or slightly higher than the prevailing intraocular pressure and, more importantly, that as intraocular pressure rises, the pressure in this segment of vein rises with it. At the upper and lower poles of the disc, as distinct from the temporal and nasal poles, the veins act like funnels which serve to conduct increases in intraocular pressure into the disc substance in just those regions where atrophy and excavation from elevated intraocular pressure are most likely to occur. The Choroidal Circulation Let us make a model of drainage from the choroidal circulation. In Issue No. 11 of the Glaucoma Letter we discussed the venous drainage from the retinal circulation. Inferences that can readily me made from retinoscopic observation alone made it possible for us to give explanations for the phenomena of A-V nicking, of increased V/A ratio in arteriosclerotic and hypertensive vascular disease. Such observations also suggested a possible mechanism for the selective distribution of glaucomatous optic nerve damage, and by extension suggested that it might be impairment of the venous circulation that was responsible for the optic atrophy and excavation in glaucoma rather than impairment of arterial circulation as has hitherto been assumed. In addition, and perhaps not least in importance, reflections on the mechanisms of venous drainage from the retinal circulation forced on us as they were by the simple process of observation, by the need to explain and the desire to understand what is so readily observable, provide us with tools to think about venous drainage in general and give us courage to consider other mechanisms of venous drainage in the eye that are more or less inaccessible to inspection. The outlines of the choroidal circulation are well understood. The choroid is supplied by posterior ciliary arteries perforating the sclera in a circular patter around the optic nerve and by the two long posterior ciliary arteries that course beneath the retina at the temporal and nasal meridians respectively. There are also recurrent arterial branches that perforate the sclera at the sites of the insertions of the recti muscles. All these arteries feed a rich and convoluted capillary bed, whose distinctive character is reflected in a distinctive name: the choriocapillaris. The choriocapillaris then drains into the vortex veins. Our knowledge of this circulation derives largely from anatomic and physiologic studies, since the choroid itself is largely obscured from view on ophthalmoscopy by the intervening pigment epithelium. A few salient observations, however, are possible. The long posterior ciliary artery can usually be seen as it courses forward beneath the retina. The vortex veins are visible, and feeding them, a spoke-like network of broad veins. From its location, we can reliably infer that the entire intra- ocular choroidal circulation is subject to the intraocular pressure. We know, also, that on the outside of the globe, the pressure in the ophthalmic vein into which the vortex circulation drains is relatively much lower than the intravascular pressure of the choriocapillaris. As in the case of the retinal circulation, we infer the existence of a pressure gradient. What can we say about its extent and location? It appears that the outflow from the choroidal circulation via the four vortex veins differs in significant respects from the outflow mechanisms of the retinal veins. The vortex veins take, as is well known, an oblique course through the sclera, and it has long been observed through the sclera, and it has been assumed that with increasing intraocular pressure there is progressive compression of the vortex veins, producing an increased resistance to flow and thereby preventing the pressure-induced collapse of the choriocapillaris. It was assumed that it was the pressure of the sclera on these obliquely coursing veins that created the necessary resistance to prevent the emptying of the choroidal vascular bed. That this hypothesis is probably incorrect is suggested by the results of a recent study. John Battaglioli experimentally determined the compressive modulus of sample of sclera from enucleated human eyes, and found that a vessel running circumferentially within the sclera would not become collapsed, and its resistance would remain relatively unaffected until the intraocular pressure had increased to the vicinity of 50 mm. Hg. For vessels that coursed not tangentially, but relatively more obliquely, this pressure would become correspondingly higher, presumably asymptotically approaching infinity, inasmuch as a vessel running radially through the sclera would as the intraocular pressure increased, not only not be compressed, but it would actually dilate with increasing intraocular pressure. It appears therefore that under physiologic conditions, the scleral tuunnel is not likely to be locus of resistance to vortex vein outflow. The implications of Battaglioli's thesis suggested that it might be worthwhile to take another look at the choroidal circulation, to the extent that this can be studies ophthalmoscopically, obscured as it is by the pigment epithelial barrier. When one looks at the fundus with the ophthalmoscope, or with the slit lamp and the contact lens, one sees the vortex: broad bands of choroidal vein like the curved spokes of a wheel converging onto the exit foramen. On first thought one accepts the profile of these vessels as indicative of a large volume, compatible with the well established vascularity of the choroid. Yet the observation that broad venous profiles in the retinal veins represent not engorged but partially collapsed vessels, raises the question whether or not the breadth of these structures that feed the outflow veins of the choroid might not reflect partial collapse rather than engorgement. This suspicion appears to be confirmed in the occasional situation when, because of atrophy of the retinal pigment epithelium one has an opportunity to study choroidal veins stereoscopically with the slit lamp. One sees than that at least some, and perhaps most of the choroidal veins whose shadows one sees are not cylindrical at all. They are flat ribbons. I have never seen one that dis not appear to be in a state of partial collapse. If this observation is borne out by further studies, it may turn out that unlike the healthy retinal venous vascular bed whose volume remains practically unaffected by changes in the intraocular pressure, the volume of the choroidal venous vasculature may not be similarly stable. For if a choroidal vein is collapsed, it means, in effect that its contents have been partially expressed by the intraocular pressure, and that its volume may be expected to vary inversely with the intraocular pressure. The resulting fluctuation of choroidal volume with intraocular pressure would unavoidably be reflected in fluctuating meridional stresses of the choroid itself and specifically of Bruch's membrane. When the intraocular pressure decreases, the volume of blood in the choroidal veins increases, the inner layers of the choroid are displaced centrally, and the stress induced in them by the intraocular pressure diminishes. On the other hand, if the intraocular pressure increases, then the choroid tends to collapse, and Bruch's membrane is displaced toward the periphery of the globe and it becomes correspondingly stretched. This tension in the choroid is transmitted to the ciliary body to which the choroid is anchored, and through it to the scleral spur. With an increase in intraocular pressure then, the choroid tends to collapse, its inner layers are pushed outward by the intraocular pressure, there is increased meridional stress which makes posterior traction on the scleral spur thereby tending to open the canal of Schlemm and restore the intraocular pressure to amore normal level. Although the existence of such a mechanism is likely, there is insufficient data to permit any conclusion as to its importance, if any, in the control of intraocular pressure. The anatomic relationships at the point where the artery crosses the vein prevent the tangentially oriented collapse of the vein. Such collapse, if it occurred, would require a sharp deflection of the artery, as in B. Instead, radially oriented collapse may occur. Alternatively, stiffness of the artery combined with stiffness of the enveloping fibrous tissue may so impede the collapse of the vein at the crossing as to create a dead space of relatively stagnant blood. Such stagnation explains the branch vein occlusions that begin at A-V crossings. A vein crossing over rather than under the artery will not exhibit A-V nicking because in that location collapse of the vein can and does occur without deflection of the artery. * * * * *

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