Chapter 2
Each of these types illustrate a distinct cause or group of causes. The first type brings us near to what may be the essential nature of glaucoma, impairment of ocular nutrition by the intra-ocular tension, which is generally elevated, but may not be above the usual normal. A special weakness in the nutrition of nerve tissue may be assumed. It would help to explain the cavernous atrophy of the optic nerve associated with simple glaucoma. The second type shows impairment of the regulative mechanism permitting rapid rise of the intra-ocular pressure. In persons of good nerve nutrition and strong recuperative power, it may exist for years without doing permanent damage. But joined to causes of the first type, lowered nutritive activity, it causes rapid and permanent loss of sight. The third group are cases associated with glaucoma only as causes. In eyes with low nutritive power, or subject to exacerbations of increased intra-ocular pressure, uveal inflammations may prove disastrous. The fourth type shows the results of the combination of the causes of the other types; with the elements of acute or slow malignancy added--the impaired circulation and lowered oxidation producing some degree of edema of the tissues that insures a fatal result.
This is no complete presentation of my subject, but a selection of facts bearing on the etiology, to serve as a foundation for the discussion of those practical aspects of glaucoma which are to claim your attention through the papers and remarks of subsequent speakers.
Dr. Edward Jackson's Paper on Etiology and Classification of Glaucoma
Discussion,
FRANCIS LANE, M.D.
Chicago.
Not one of the theories thus far propounded to explain the essential cause of increased intra-ocular tension is satisfactory. Our present day knowledge apparently ceases with a more or less incomplete understanding of the mere circumstance under which increase of tension in general depends.
The question of the source of the normal intra-ocular pressure must first be solved before any discussion of a pathological increase can be engaged in. This question primarily hinges on whether the corneo-sclera is to be regarded as an unelastic capsule with a fixed volume, or as a yielding envelope with an ever changing capacity.
This brings us at once to the consideration of that theory which probably has held our attention for the longest period of time, _i. e._, the volumetric theory. According to it, the normal intra-ocular tension depends on the volume of fluids within the eyeball. Any variation in the quantity of the contents gives rise to a change in the pressure, therefore, the globe has been regarded as "an elastic capsule, whose capacity, form, and internal pressure depend on the balance struck between a constant inflow, or formation of aqueous, and a proportionate outflow or resorption." (Henderson.)
Hill has satisfactorily demonstrated that, under physiological conditions, the hydrostatic pressure within the eye and the skull is identical; it rises and falls simultaneously; it is the same as the cerebral venous pressure; it is constantly varying, depending directly on the general circulation. Upon these findings Henderson based his opinion that the physiological properties of the tunica fibrosa and the skull are identical, realizing at the same time, that the rigidity of the corneo-sclera, because of its fibrous nature, is not as firm as the cranium. In accepting this belief the inference was that the cubic capacity of both coverings is fixed. Applying these conclusions to the eye, it can be said that the pressure of the fixed intra-ocular volume varies with the venous tension within the bulb, which in turn is influenced by the general circulation. Such a conception, while not strictly in accord with recognized physiological teachings, proves that the normal intra-ocular pressure is not a question of volume content, but that it is purely a question of pressure of a fixed volume within an unyielding capsule. Dr. Jackson virtually puts aside the volumetric theory with his statement, that "the balance of intra-ocular pressure is not maintained by the slight distensibility of the sclero-corneal coat." Further discussion on the inadequacy of the volumetric theory need not detain us.
It is well to recall a few anatomical features because of their bearing on the theories herein considered.
1. The angle of the anterior chamber is a true angle and not an annular sinus.
2. The meshwork of the iris angle (ligamentum pectinatum), a cellular structure at birth, undergoes a progressive and physiological fibrosis with early subsequent sclerosis, until finally it becomes a fibrous structure. The individual strands of this meshwork are more than two times as large at advanced age as at birth, consequently the alveoli of the meshwork becomes markedly reduced in size.
3. The spongy nature of this meshwork affords free access of aqueous to the venous sinus of Schlemm, thence by tributaries into the supra-choroidal space and anterior uveal venous system.
4. Fuchs's iris cripts afford direct access of aqueous to the veins of the iris.
Furthermore, two simple principles are taught by physics: Fluids are incompressible and they seek the lowest hydrostatic level. The application of these perfectly obvious principles to the eyeball makes the intra-ocular pressure the same as that within the elastic venous walls, which is the lowest circulating pressure within the bulb.
To summarize: The aqueous has direct access to the anterior uveal venous system; the physiological thickening of the strands of the meshwork of the iris angle supplies a mechanical obstruction between the anterior chamber and the venous sinus of Schlemm; intra-ocular pressure stands at the same level as the intra-venous, consequently, the hydrostatic pressure is the same on both sides of the iris angle meshwork, because the canal of Schlemm is a secondary venous system; lastly, the outflow of aqueous into the venous sinus is by diffusion, not by filtration, because the pressure is the same on both sides of the meshwork.
These facts and deductions have given rise to the present day circulatory theory of intra-ocular pressure, so we now can approach the predisposing and exciting factors which determine glaucoma.
The central fact to be borne in mind is, if the physiological pressure is vascular in origin and nature, the pathological pressure must likewise be derived from the same source.
Sclerosis of the meshwork of the iris angle is the predisposing factor because it hinders free access of aqueous into the venous sinus of Schlemm. Sclerosis alone, however, will not cause glaucoma so long as access to the iris veins can keep the intra-ocular pressure at the intra-venous level, and, too, as long as the exciting cause is absent.
The exciting cause is vascular, maintained and influenced by the general circulatory pressure. A rise of the general vascular tension alone will not cause glaucoma, because any alteration in intra-ocular pressure resulting would be purely a temporary change, easily taken care of by the extensive access of aqueous to the intra-ocular venous system. When these two factors coexist in their varying combinations, pathological increase of pressure results--in short, glaucoma.
Syphilis, rheumatism, gout, auto-intoxication and many other constitutional disorders are well recognized agencies which induce sclerosis in body tissues, so there can be little doubt that these conditions produce pathological sclerosis of the meshwork of the iris angle. Psychic disturbances, congested portal or renal system, hard mental or muscular work, etc., etc., induce increased pressure of the general circulation, and so simultaneously the intra-ocular pressure.
According to the edema theory advanced by Fischer, glaucoma is "essentially an edema of the eyeball, and for its production we must hold responsible the same circumstances which are responsible for a state of edema in any other part of the body." The magnificent experimental work of this investigator has shown that edema is nothing more or less than an increased capacity of the protein colloid tissues for water; that the most important factor leading to this increased hydration capacity is an abnormal production or accumulation of acid content, effected by those agencies which are instrumental in causing sclerosis and an increase of blood pressure.
It seems that both of these theories afford an explanation for many of the secondary pathological manifestations which characterize the intra-ocular tissues during a glaucomatous onset.
Fischer criticizes the Henderson theory on the ground that increased blood pressure alone does not lead to edema--edema is thwarted by high blood pressure. On the other hand, if Fischer believes that sclerosis of the meshwork of the iris angle is a result and not a cause of glaucoma, then it would seem that Henderson has the better of the argument. The physiological changes in this structure, which take place with advancing age, can rightfully be looked upon as a predisposing factor in glaucoma.
Dr. Jackson has presented all other phases of this part of the symposium in such a comprehensive manner that nothing further remains to be said.
Pathology of Glaucoma
BY
JOHN E. WEEKS, M.D.,
New York City.
In reviewing the pathology of glaucoma it seems proper to consider the various structures and tissues of the eye in logical order.
_Lids and Conjunctiva._ "The only change observed in these tissues is a reflex edema, excited apparently by pressure on the ciliary nerves and, probably, irritation of the vaso-motor fibers of the sympathetic."
_Lachrymal Gland._ Hyper secretion due to reflex irritation.
_Cornea._ As has been shown by Priestley Smith, the cornea in glaucomatous eyes is, as a rule, smaller than in non-glaucomatous eyes, the mean of a series of measurements being 11.1 mm. horizontally and 10.3 mm. vertically in glaucomatous and 11.6 mm. horizontally and 11 mm. vertically in non-glaucomatous eyes. In cases of considerable increase of tension, particularly if the onset is sudden, the circulation of lymph in the cornea is interfered with, the anterior layers of the cornea become edematous, the spaces between the lamellae filled with albuminous fluid. Some of this fluid finds its way through Bowman's membrane, apparently by way of the minute channels which permit the passage of small nerve twigs, and enters the epithelial cell layer. The fluid finds its way between the epithelial cells in the deeper layers, apparently being taken into some of the superficial cells by imbibition. Some of the swollen surface cells open spontaneously and discharge their contents, others drop off. The process causes a roughening of the surface of the cornea and produces a faint haziness. There is another form of haziness that develops on sudden rise in tension and completely disappears on subsidence of the tension. This is due, as has been shown by V. Fleischl (Sitzungsberichle d. Weiner Akad. d. Wissensch, 1880) and others, to increased tension on the fibrillae of the cornea, a double refraction being induced. In cases of long continued increase of tension minute permanent vesicles form in the epithelial layers, particularly in the superficial portion. Anaesthesia of the cornea develops, due to pressure on the nerve fibers that are distributed to the epithelium, the compression probably occurring along the course of the long ciliary nerves, from which the corneal nerves are derived, as they pass between the choroid and the unyielding sclera (Collins & Mayou).
In advanced cases of glaucoma after the congestive period has subsided the cornea becomes somewhat condensed, the lymph spaces contracted; a condition of sclerosis obtains. Alteration in the shape of the cornea occurs only rarely in adult life. When it does occur it takes place in corneæ that have suffered from keratitis. The alteration is usually in the form of ectasiæ. In infancy and early youth (buphthalmia) the cornea may become uniformly enlarged and globular. Often, however, the enlargement of the cornea is irregular. Increase in tension may produce fissures in Descemet's membrane. These occur more frequently in the cornea that have suffered a change in shape, as in buphthalmos. Gaps occur in the elastic membrane which become covered by endothelium. Some cloudiness may be seen in the corneal lamellae adjacent to these fissures, in some cases due evidently to the filtration of aqueous humor through defective endothelium. Prolonged high intra-ocular tension may be accompanied, particularly in cases of secondary glaucoma, by vesicular and bullous keratitis.
In acute glaucoma the sclera appears to be edematous and slightly thickened. As the disease progresses the sclera becomes denser than normal. The oblique openings--passages for the venae vorticosae--are said to be narrowed. The openings for the passage of the anterior ciliary vessels are enlarged in many, particularly in advanced cases. Minute herniae at these openings are sometimes present. Dilatation and tortuosity of the anterior ciliary veins are due apparently to excessive flow of blood through them on account of the abnormally small amount carried off by the venae vorticosae. In the stage of degeneration, ectasae of the sclera occur most frequently near the equator of the globe. Spontaneous rupture may take place.
_Anterior Chamber._ The anterior chamber is shallow, as a rule. This is almost without exception in primary glaucoma in adults. In secondary glaucoma in which occlusion of Fontana's spaces occurs as a result of the deposition of fibrin or other inflammatory products the anterior chamber may be of normal depth, or deeper than normal. Very deep anterior chamber may occur in glaucoma, due to retraction of lens and iris following fibrinous or plastic exudation into the vitreous, or when it occurs in congenital glaucoma, due to enlargement of the globe.
_Aqueous Humor._ The aqueous humor, as has been pointed out by Uribe-Troncoso (Pathoginie du Glaucome 1903) contains a greatly increased quantity of albuminoids and inorganic salts in glaucoma. In acute glaucoma the increase of albuminoids (blood proteids) is greater than in chronic glaucoma. The aqueous humor becomes slightly turbid in acute attacks, coagulating more readily than the normal. The plastic principle contained in the aqueous is rarely sufficient to cause adhesion between the margin of the iris and the lens capsule, but the colloid nature of the aqueous, according to Troncoso, lessens its diffusibility and prevents its free passage into the lymph channels. The increase in albuminoids is a consequence of congestion and venous stasis and does not precede the attack.
_Filtration Angle._ The changes that occur in the filtration angle before it is encroached upon by iris tissue are sclerosis of the ligamentum pectinatum in adults to which Henderson (Trans. Ophth. Soc. U.K. Vol. xxviii) has called our attention; the accompanying sclerosis of the other tissues to the inner side of Schlemm's canal; and, in some cases, the deposition of pigmented cells derived from the iris and ciliary processes (Levinsohn) which serve to obstruct the lymph spaces. In many of the cases of acute glaucoma and almost all of the cases of chronic glaucoma of long standing the filtration angle becomes blocked by the advance of the root of the iris.
_Iris._ In acute glaucoma the iris is congested and thickened. It is pushed forward and may lie against the cornea at its periphery. When the attack subsides, the iris falls away from the cornea. Aside from the congestion, the primary changes that take place in the iris are indicative of paresis of the fibers of the motor oculi that supply the sphincter pupillae, and stimulation of the fibers from the sympathetic producing vasomotor spasm. The long diameter of the pupil apparently lies in the direction of the terminal vessels of the two principal branches of each long ciliary artery which form the circulus iridis major, where the vasomotor spasm would have the greatest effect in lessening the blood supply. The haziness of the cornea and slight turbidity of the aqueous contribute greatly to the apparent change in the color of the iris. In cases of simple chronic glaucoma there is but little evidence of edema of the iris. If the iris lies in contact with the sclera and cornea for some time, it becomes adherent (peripheral anterior synechia). As the disease progresses, the stroma of the iris atrophies and contracts. There is very little evidence of small-cell infiltration or the formation of cicatrical tissue. Numerous slits may develop in the iris through which the fundus of the eye may be seen (polycoria). The pigment layer does not atrophy in proportion to the stroma of the iris; by the contraction of the stroma of the pigment layer is doubled upon itself at the pupillary margin, forming a black ring of greater or less width (ectropian uveae). The iris becomes attached to the pectinate ligament and to the endothelium of Descemet's membrane. In a very few cases the closure of the angle is not complete at the apex, a small space remaining comparatively free for a long time. The adhesion of the iris to the pectinaform ligament and cornea is not uniform at all parts of the periphery; it varies in width. Portions of the iris angle may remain open while other parts are closed. Where the iris tissue lies in contact with the cornea, the stroma of the iris almost totally disappears. In some cases the iris becomes totally adherent to the cornea.
_Ciliary Body and Chorioid._ In acute glaucoma there is congestion of the entire uveal tract, the congestion partaking more of a venous stasis than of an active or arterial congestion. The vessels of the ciliary process, which are larger and more tortuous in adults of advanced years than in the young, become enormously distended, causing almost complete obliteration of the perilental space. They press against the root of the iris and the equator of the lens, forcing them forward. There is edema of the ureal tract, apparently from transudation of serum. Many small, and sometimes rather large hemorrhages may occur. There is but little small cell infiltration, indicating almost total absence of what is ordinarily recognized as true inflammation. It is probable that the secretion from the glandular zone of the ciliary body is increased.
On subsidence of the congestion, as after miotics or iridectomy, the tissues may return to very nearly a normal condition. The iris recedes from contact with the ligamentum pectinatum and cornea and the filtration angle is again open. In some cases the iris becomes adherent to the head of the ciliary processes and, when atrophy of the ciliary body occurs, is drawn backward at the base of the iris by the receding tissues. If the hypertension persists or is repeated at varying periods, a slow atrophy of the uveal tract sets in. Eventually the ciliary body becomes very much reduced in thickness, is flattened out, the ciliary processes reduced in size and the blood vessels disappear or are reduced much in caliber. Those that persist possess walls that are much thickened. This is particularly true of hemorrhagic glaucoma.
In advanced absolute glaucoma the chorioid may become reduced to a very thin membrane consisting of connective tissue and pigmented cells, scarcely distinguishable even by moderate powers of the microscope. Atrophy is marked in the vicinity of the venae vorticosae. Czermak and Birnbacher describe proliferation of the endothelium of the large veins with contraction and obliteration of their lumen.
_Optic Nerve and Retina._ In the acute form the retina and optic nerve present the same condition that is present in the vascular tunic; namely, that of venous stasis with the consequent edema. Frequently minute hemorrhages occur in the retina, particularly in violent acute attacks. Cupping of the discs slowly develops, causing more or less stretching of the nerve fibers over the edge of the cup. The gradual diminution of the field of vision is due in greater part to death of peripheral nervous elements of the retina, those parts of the field farthest removed from the large arterial trunks suffering first. The arrangement of the arteries at the disc, passing out as they do from the nasal side, of necessity make the vessels that pass to the temporal part of the retina longest and of less caliber. These vessels and their terminals are first to suffer marked diminution in size; death of the perceptive elements supplied with nutrition by these vessels follows. For this reason the nasal part of the field of vision is more often the first to disappear. In congestive (inflammatory) glaucoma, the typical field of vision shows most marked contraction on the nasal side. The disturbance of the nutrition of the retina accounts in greater part for the various forms of visual field met with.
Death of all of the perceptive elements of the retina eventually occurs. The loss of nutrition is apparently not the whole cause of blindness. Atrophy of the nerve fibers follows death of retinal neurons, but atrophy of some of the nerve fibers may be, and probably is, due to the pressure and traction exerted upon them at the margin of the disc. It is probable that too much importance has been given to this mode of interference with the nerve fibers. However, the change in the position of the lamina cribrosa must exert a deleterious effect, particularly on those fibers which pass through the peripheral meshes, the shape of which must necessarily be much distorted. In glaucoma simplex, which is largely devoid of marked congestive periods (acute attacks), a surprisingly high degree of acuity of vision may exist with a deep excavation and pale nerve. Careful studies of the retinal vessels in glaucoma (Verhoeff Arch. of Ophth. XLII. p. 145; Opin. Soc. Française d'Ophth. 1908) disclose the fact that an increase in the elastic tissue and connective tissue elements occurs in _some cases_, also proliferation of the endothelial cells, which serve to irregularly narrow and, in some instances, obliterate the lumen of the vessel. Arteries and veins are both affected. Hyaline degeneration of the media also occurs. The process is not uniform.
_Glaucomatous Cup._ The excavation of the disc progresses slowly and is due in part to stretching the fibers of the lamina cribrosa pressing this structure outward, and partly to atrophy and disappearance of the nerve tissue and much of the vascular tissues in the nerve head. The displacement backward of the lamina cribrosa may cause that structure to lie behind the outer surface of the sclera. Atrophy and cystic degeneration of the nerve trunk follows destruction of retinal neurons and cupping of the disc. Neuroglia remains in part. Connective tissue elements increase in the optic nerve as the nerve fibers disappear.
_Glaucomatous Ring._ The development of the pale circle which surrounds the disc, particularly in glaucomatous eyes, is due to a very slight recession of the pigment layer of the retina and of the margin of the chorioid at this point with some atrophy, apparently consequent on the beginning retraction of the lamina cribrosa and slightly increased pressure of the nerve fiber layer on the underlying tissues at the margin of the disc. This permits the sclera to show through a very little at this part. In some eyes in which there is a beginning sclero-chorioiditis posterior, the condition is very similar to that presented by the glaucomatous ring.