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.

Field of Vision. The two pathological processes that operate to destroy the function of the retina suffice to produce scotomata in the field of vision of varying shapes. The typical glaucomatous field in the acute cases shows a defect most pronounced to the nasal side. As has been shown by Bjeraum, the blind spot corresponding with the optic disc is enlarged in glaucoma, a relative scotoma often connecting it with the blind nasal portion of the field either above or below the horizontal meridian (Straub). The field in a simple glaucoma is apt to approach concentric limitation; namely, more like the field in simple atrophy. This is consistent with the fact that simple glaucoma in many cases possesses the characteristics of glaucoma plus atrophy of the optic nerve.

Vitreous. During the acute attack, the vitreous may become slightly turbid by transudation of serum from the vessel of the ciliary body and the chorioid and may become filled with fibrin. In some chronic cases in which absolute glaucoma is reached the development of small blood vessels in convoluted loops springing from the vessels of the discs has been observed. Any process that increases the volume of the contents of the vitreous chamber, as hemorrhage, neoplasm, profuse serous or plastic exudation, may by pushing iris and lens forward produce an attack of acute glaucoma.

Buphthalmos. Reis (Graefe's Arch. f. Ophth. V. LX. 1905) states that there is always obliteration of the anterior scleral venous channels (Schlemm's canal) in buphthalmos. Seefelder (Graefe's Arch. V. LXIII. 1906) mentions the abnormal position and abnormal narrowing of Schlemm's canal and the imperfect and insufficient differentiation of the cornea-scleral junction. In all of the cases in which the eye has been examined microscopically obliteration of Schlemm's canal has been reported. This is thought to be a defect in development. Magitot (Ann. d'Oculis CXLVII) suggests that injury to mesoderm which pushes itself between the ectoderm and anterior surface of the lens would account for the failure in development of Schlemm's canal. The changes that occur in the tissues of the eye appear to be largely due to the stretching consequent on the more or less uniform distentions of the globe as a result of hypertension.

Cornea. This portion of the fibrous membrane is enlarged, globous or flattened, irregularly thinned, particularly at the periphery, where it may be as thin as tissue paper, nebulous because of the stretching of its fibers principally, but in some degree (differing in different cases) to edema of the epithelial layer. Fissures occur in Descemet's membrane.

Anterior Chamber. This is very deep in the greater number of cases. However, this rule has many exceptions.

The vascular tunic may be congested in young infants, but atrophy soon develops and may reach an extreme degree. The sclera ordinarily becomes quite thin throughout, but may retain almost a normal thickness at the equator of the globe and posteriorly. Posterior sclera ectasae may develop. The iris, as a rule, hangs free from the cornea, often tremulous because of retraction of the lens beyond the iris plane. In some cases the iris is partly or totally adherent to the posterior surface of the cornea.

The vascular membrane (iris, ciliary body and chorioid) and the retina become atrophic, the atrophy varying in degree in various parts. Detachment of the retina may occur, often preceded by or accompanied by subretinal hemorrhage. The optic disc becomes deeply cupped and the tissues of the optic disc and optic nerve extremely atrophied. The crystalline lens may become cataractous and shrunken. Spontaneous rupture of the suspensory ligament with consequent subluxation of the lens may follow.

Secondary Glaucoma. The pathological conditions that precede secondary glaucoma are many and differ widely. They may be briefly classified as:

1. Those that cause a partial or complete closure of the lymph spaces and Schlemm's canal by cicatrical contraction, as in sclero-keratitis.

2. Those that cause obstruction to the lymph spaces at the filtration angle by the deposition of fibrin or cellular elements, as in iritis, hemorrhage into the anterior chamber, etc.

3. Those that cause obstruction of the filtration angle by advancement of the iris and lens, as occurs when the volume of the contents of the vitreous chamber is increased, as from retinal or chorioidal hemorrhage or neoplasm.

The various changes are so numerous that they need not be described further here. The ultimate changes due to high tension resemble those already described.