Cornea

CORNEA, the horny coat (cornea), represents the anterior, more convex, transparent part of the outer fibrous coat of the eyeball, occupying about 1/6 of its surface area. The boundary between the cornea and the sclera is marked by a shallow groove—sulcus sclerae externus. The cornea is, as it were, placed on the eye like a watch glass and has the shape of a meniscus, since its middle is thinner than its edge. Previous figures for the thickness of the cornea—0.8 mm in the middle and 1.0–1.2 mm at the edges—have recently been disputed based on studies of the cornea with a slit lamp (Koby), and the "actual" thickness of the cornea in the center is determined to be 0.466–0.703 mm, with an average of 0.583 mm. The radius of curvature of the anterior surface of the cornea is on average 7.84 mm (Salzmann), but this figure refers only to the middle, spherically curved third of the cornea, its so-called optical zone, while its peripheral parts are noticeably flattened. Thus, the radii of curvature of the cornea in its peripheral parts gradually increase. Furthermore, the radii in different meridians of the cornea can be different; most often, the radius in the vertical meridian is shorter than the radius in the horizontal meridian, as a result of which the refractive power of the vertical meridian is greater than that of the horizontal one; hence, astigmatism arises. According to some recent measurements of the cornea (Berg), its horizontal meridian shows a fairly uniform curvature, whereas the vertical one gives large irregularities, and at the border of the middle and upper third, one can sometimes note a line corresponding to the position of the edge of the upper eyelid with a normally open palpebral fissure. Berg explains such a curvature of the cornea with a relative myopic setting by the pressure of the eyelid on the eye. The curvature of the posterior surface of the cornea is considered smaller and spherically curved; its radius is about 7.0 mm (Salzmann) – 6.22 mm (Tscherming). When viewed from the front, the cornea appears in its shape to approach an ellipse with a longer horizontal axis—on average 11.6 mm (11.65 mm in men and 11.54 mm in women) and a shorter vertical one—on average by 1 mm. This is explained by the fact that in its posterior layers, the cornea extends further into the sclera at the periphery than in the anterior ones, and the resulting overlapping of the sclera onto the cornea is more pronounced at the top and bottom than at the sides. When viewed from behind, the cornea appears round with a diameter approximately equal to the long diameter of its anterior surface. If a plane is drawn through the outer edge of the cornea, it is called the base of the cornea, and the distance from the middle of this plane to the center of the cornea is called the height of the cornea; on average, it equals 2.6 mm and depends not only on the curvature of the cornea itself but also on its size. It is believed that the cornea completes its growth during the second year of a child's life; in recent years, it has been found that already in the second half of the first year of life, the diameter of the cornea reaches the size of an adult's diameter. Everywhere, except for its edge, the cornea possesses transparency and consists of five layers: 1) epithelium, 2) Bowman's membrane, 3) the proper tissue of the cornea, 4) Descemet's membrane, and 5) endothelium (Fig. 1). 1) The corneal epithelium is multilayered, squamous, with a thickness of 0.04–0.05 mm with 5–6 layers (Fig. 2) (according to some authors, up to 8), embryologically a derivative of the ectodermal layer covering the eye primordium.

The basal layer of the corneal epithelium consists of cylindrical cells with a flat base facing Bowman's membrane and rounded ends facing the next, second layer of cells; the nuclei of the cells are oval, and the protoplasm is in most cases lighter than in the cells of the following layers. Among these light cells, one encounters darker and taller cells with concave lateral surfaces and a nucleus shifted toward the apex; these are cells rising into the

Figure 1. Cross-section of a normal cornea: 1—epithelium; 2—Bowman's membrane; 3—nerve; 4—stroma; 5—Descemet's membrane; 6—endothelium; 7 and 8—corneal corpuscles; 9—lamellae of the ground substance.

Figure 2. Corneal epithelium; various layers of epithelial cells.

following layer of the epithelium, and it is at their expense that the regeneration of the epithelium occurs. In the second layer, consisting of two rows of so-called wing cells, the cells have a polyhedral shape; their planes (on sections) are convex in front and concave behind, and the edges between the concave surfaces are more or less elongated in the form of wings. The diameter of the cells of the second layer is approximately the same in all directions; their protoplasm is darker than in the basal layer. In the third layer, there are 2–3 rows of cells; these cells gradually flatten, and on the surface, they become completely flat and thin, thickening only in the region of the nucleus, but this thickening goes toward the deeper layers, so that the anterior surface of the cornea is smooth. The nuclei of the superficial cells are also flattened and stain more weakly than in the deeper layers, but there are no traces of keratinization in the cells themselves. Among the cells of the corneal epithelium, wandering cells, leukocytes, are often visible on sections, mainly in the basal layer. According to the generally accepted opinion, the connection between the epithelial cells is carried out by means of intercellular bridges in the form of threads, with the spaces between the bridges forming a system of slits or channels filled with fluid, the sources of which are sought in the vessels of the corneal limbus and in its ground tissue (through the pores of Bowman's membrane) (Virchow). Recently, Mans has come forward with a new understanding of the normal connection of epithelial cells with each other. In agreement with Unna's views regarding the skin epithelium, he asserts that a system of fibers passes through all layers of the epithelium, starting from Bowman's membrane and reaching the very top layers of the epithelium. This system forms a densely woven basket of fibers around the cell nuclei, which was previously mistaken for the cell membrane. The fibers have a connection with the connective tissue fibers at the limbus on one side, and on the other, they likely have a connection with Bowman's membrane. The same system of fibers exists in the conjunctival epithelium, and where there is no limiting membrane, it is in direct connection with the subepithelial connective tissue. During inflammatory processes, strong changes appear in the fiber system, especially where Bowman's membrane disappears; here, upon completion of the process, a completely "non-physiological" epithelium can form. 2) Bowman's membrane (lamina elastica anterior, s. membrana Bowmani, s. Reicherti), on which the corneal epithelium is located, is a plate of uniform thickness—0.01–0.016 mm, sharply delimited from the epithelium and indistinctly from the underlying proper tissue of the cornea, merging with the latter (Fig. 1). Structureless upon ordinary examination, Bowman's membrane disintegrates upon maceration into fibrils and is essentially only a modified, condensed, and cell-free anterior layer of the proper tissue of the cornea. On sections of Bowman's membrane, one can see pores intended for the passage of nerve fibers (rami perforantes). Bowman's membrane ends without reaching 1.0–1.5 mm to the edge of the cornea (see below, corneal limbus). As a feature of Bowman's membrane, the good resistance of the cornea to trauma is noted, but, conversely, poor resistance to infectious processes and the absence of the ability to restore its integrity after destruction (Reid). 3) The proper tissue of the cornea (ground substance of the cornea, substantia propria corneae) (Figs. 1 and 2) constitutes the main mass, about 90%, of the entire thickness of the cornea. It has a lamellar structure (Fig. 3); the lamellae, the length of which covers the entire cornea (Virchow), intersect with each other at large angles (about 90°) and intertwine at very small angles of inclination, so that on sections they appear almost parallel to the surface of the cornea; their number, according to Salzmann, is 60–65 (according to other authors, up to 100) and their thickness is about 0.01 mm. Individual lamellae consist of thin fibrils of connective tissue, arranged parallel to each other and glued together by interstitial substance. Adjacent lamellae often, in the anterior layers more often than in the posterior ones, anastomose with each other by strands of fibrils. Usually, only two adjacent lamellae anastomose, but in the anterior layers, there are bundles of fibers that penetrate obliquely or in an arcuate manner through several layers to Bowman's membrane (former name—fibrae arcuatae). In the ground substance of the cornea, a network of elastic fibers is described (Tartuferi, Seefelder, and others) between the lamellae of the cornea; a special accumulation of such fibers is located in front of Descemet's membrane. At the periphery of the cornea, the number of lamellae is greater than in the center. Between the lamellae are located the cells of the cornea, or corneal corpuscles (Fig. 1). These cells have a large flat round or irregular-shaped nucleus with

Figure 3. Corneal corpuscles

Figure 4. Corneal corpuscles lying in different planes.

of the ground substance. [They have] several nucleoli and a slightly granular protoplasm with numerous processes, by means of which the cells anastomose with one another, forming a closed network or syncytium (Figs. 3 and 4). The old view of Recklinghausen regarding the existence between the lamellae of the cornea of a highly branched system of thin canaliculi and fissures intended for the circulation of fluid and the nutrition of the cornea, the so-called system of juice canaliculi and fissures, in which the cells of the cornea are also located, has not been confirmed in the studies of Leber, Kryukov, and others. According to Leber, the injection of the canalicular system along the location of the corneal cells occurs because it is easier to disrupt the connection of the cells with the ground substance of the cornea than the connection of the lamellae with each other; for this same reason, wandering cells are found predominantly between the permanent corneal cells and the ground tissue. A number of other authors, such as Ranvier, Wolfrum, and others, hold the same point of view. The question of the lymphatic vessels of the cornea, which is closely related to this issue, is likewise decided in the negative by the majority. Virchow says that in this regard, 3 questions can be posed to the anatomist: 1) are the fissures that we see in the ground tissue of the cornea entirely filled with cells, 2) is it possible to prove the connection of these fissures with lymphatic vessels, and 3) are signs of a system of pathways with a definite direction noticed in the arrangement of cellular formations; based on his own experience and a review of literary data, he gives a negative answer to all these questions. Later studies with a slit lamp, as well as work with intravital staining of eye tissues, have not introduced new data to this issue. The study of corneal cells from the point of view of the reticulo-endothelial system has shown that 1) in the normal state, corneal cells do not accumulate dyes and therefore do not belong to the cells of the reticulo-endothelial system; 2) in non-penetrating wounds of the cornea and the absence of vessels in it, histiocytes do not take part in wound healing; 3) along with vessels, histiocytes also penetrate into the cornea from the pericorneal tissue; 4) in penetrating wounds of the cornea, and especially in prolapse of the iris, histiocytes invade the cornea from the side of the uveal tract. In addition to permanent cells, a small number of wandering cells—leukocytes—are found in the ground substance of the cornea. According to the latest embryological studies by Seefelder, Fischer, and others, after the formation of the corneal endothelium at the expense of the mesenchyme adjacent to the eyeball, the cornea consists of one single-layered outer layer and one inner layer of epithelium-like cells, which is single-layered in the center and multi-layered at the periphery. Between them are the finest fibrils, which are considered remnants of the anterior vitreous body. It is here that cells from the undifferentiated mesodermal mass from the edge of the optic cup later invade, forming the ground substance of the cornea. Apparently, the conjunctiva of the sclera is also formed later from this same mass. 4) Descemet's membrane (lamina elastica posterior) (Fig. 1) differs sharply from the stroma of the cornea in sections and with ordinary staining, especially when stained for elastic fibers. It is distinguished by its homogeneity, although with special treatment (maceration) it breaks down into separate lamellae. The thickness of Descemet's membrane in the center of the cornea is about 0.006–0.01 mm, and at the edges 0.01–0.02 mm. At the edge of Descemet's membrane, on its inner surface, there are usually warty hemispherical outgrowths; the width of the edge occupied by such outgrowths, as well as the thickness of the entire Descemet's membrane, increases with age. Descemet's membrane easily detaches from the ground tissue of the cornea and folds into pleats, for example, during operations for opening the anterior chamber (cataract extraction, iridectomy, etc.), in wounds of the cornea, its inflammations, iritis, acute glaucoma, hypotonia, and others (Samenhof). According to Reid, Descemet's membrane, in contrast to Bowman's membrane, resists infectious processes in the cornea for a long time, but it is easily damaged by eye injuries and is capable of independent repair. In its development, Descemet's membrane represents a cuticular formation, i.e., a product of the secretion of endothelial cells, and in this respect, it also differs from Bowman's membrane. 5) The corneal endothelium, in the form of a single-row layer of cells 0.004–0.005 mm high, with large nuclei and rich in protoplasm, covers the entire inner surface of Descemet's membrane (Fig. 1), passing at the angle of the anterior chamber onto the surface of the iris. When viewed from the surface, the endothelial cells have, for the most part, a rounded hexagonal shape. Morphologically, the corneal endothelium is similar to epithelium, but embryologically it is of mesenchymal origin—from the cells of the mesenchyme adjacent to the optic cup (Seefelder and others). Recently, Sondermann has spoken in favor of the ectodermal origin of the corneal endothelium; the strongly thickened ectoderm at the apex of the lens vesicle, upon its detachment, is split by strands of connective tissue growing in from behind, with the posterior of the detached cells going to form the endothelium. In in vitro cultures (Matsui), endothelial cells grow in the form of cells of diverse shapes—polyhedral, rod-shaped, sometimes similar to fibroblasts, but in essence by no means identical to them, sometimes round, but all these cells sooner or later assume an epithelium-like arrangement. As has been clarified by clinical observations and experimentally (recently by Skullic and others), the preservation of the endothelium is of very great importance for the normal state of the cornea, and a violation of the integrity of the endothelium leads to a number of disorders, primarily to clouding of the cornea, with the endothelium itself possessing the ability to regenerate by multiplication. The limbus of the cornea represents a transitional region from the cornea to the sclera and conjunctiva; in it, the stroma of the cornea turns into the stroma of the conjunctiva, episclera, and sclera. The inner boundary of the limbus lies where Bowman's membrane ends (see above), and thus the width of the limbus is on average about 1 mm. The width of the limbus can be different in individual people, as well as in different races; thus, Ling established a greater width of the limbus in Chinese compared to Europeans. The structure of the limbus differs from the structure of the cornea. The epithelium of the limbus is thickened, the number of its layers can reach up to 10 or more; the boundary of the epithelium facing the stroma becomes sinuous (and not straight, as on the cornea), and here we see a picture of true papillae. In the basal layer of the epithelium, the cells immediately become smaller, poorer in protoplasm, and with a strongly staining nucleus. This type of cell is retained by the basal layer throughout its further extent on the conjunctiva of the sclera. The cells of the limbal epithelium are often pigmented; this is especially noticeable in dark human races and in darkly colored animals. The stroma of the limbus acquires the appearance of connective tissue, first in the superficial and then in the deeper layers, losing the regular arrangement of layers characteristic of the ground tissue of the cornea. Here, too, appear the vessels of the superficial marginal looped network of the cornea as the terminal branches of the anterior ciliary vessels. Thin arterial vessels form arcuate anastomoses between themselves here, from which thin terminal twigs depart in a meridional direction, quickly bending in the form of loops and passing into venous vessels. In the superficial layers of the limbus, elastic fibers are found, the number of which increases sharply upon transition to the sclera. The limbus serves as the site for numerous surgical interventions on the eyeball. The cornea is abundantly supplied with nerves, the study of which has recently received great assistance in the form of intravital staining of eye tissues with subsequent examination using a slit lamp. The nerves of the cornea originate from the ciliary nerves; from 60 to 80 nerve trunks, both medullated and non-medullated, enter the cornea at the periphery, with thinner trunks lying in front and thicker ones behind. Medullated fibers lose their sheath at a distance of 0.3–0.5 mm from the edge of the cornea. In the ground substance of the cornea, nerve fibers form in its middle and anterior layers, not involving the posterior layers, the "plexus of the ground substance of the cornea" (Virchow). Near Bowman's membrane, a thin reticular plexus is formed—a "closing network," according to Virchow, this is the plexus annularis corneae, from which twigs depart that pierce Bowman's membrane and form a subepithelial plexus; from the latter, twigs depart that break up into fibrils and end in the epithelium with round or pear-shaped button-like thickenings. Under the epithelium at the limbus and under the marginal parts of Bowman's membrane, terminal glomeruli are found, identical to Krause's end bulbs. The old dispute about whether only the sensation of pain exists in the cornea (Frey, Marx, and others) or whether, in addition to it, there is also a sensation of pressure (Nagel, Goldscheider, and others), continues to the present time.

Strughold, summarizing the latest literature on this issue, points out: 1) that the sensation of pain is most strongly developed in the center of the cornea, while its periphery is less sensitive to pain; 2) that the sensation of cold is absent in the center of the cornea and well developed at the periphery; 3) that the sensation of warmth is absent on the cornea and even on the conjunctiva of the sclera; 4) that the question of the sensation of pressure on the cornea, separate from the sensation of pain, remains controversial (Strughold himself is a proponent of a positive resolution to this question). The nutrition of the cornea, like that of the entire eye, is in the closest dependence on the nutrition of the entire organism. Recent years have brought new facts proving the importance of avitaminosis for the nutrition of the eye and the cornea. Experiments on guinea pigs, mice (BellaVia), rats (Yudkin), and clinical observations on humans have proven that a deficiency of vitamin A results in a whole series of changes in the cornea (see Avitaminoses, A-avitaminosis). It has been proven that in children, under such conditions, keratomalacia (see) can develop. In adults, so-called marantic ulcers of the cornea, which develop in poorly nourished patients, especially in severe liver diseases (cirrhosis, cancer), bear some resemblance to the latter; their course is sluggish, but as a result, they can destroy the entire cornea. The nutrition of the cornea itself occurs through diffusion and diosmosis. Through the first pathway, fluid entering from the peripheral blood vessels is distributed into the cornea, since Recklinghausen's old concept of the existence of a system of juice canals has not been confirmed (see above). Through the second pathway, soluble substances from the anterior chamber can enter the cornea, but since there are few such substances there, the process of diosmosis is of less importance for the nutrition of the cornea. Fischer's studies showed that the permeability of the cornea depends on the state of its epithelium and endothelium and that the ground substance of the cornea plays a subordinate role in this regard. A pathologically altered cornea has more complex permeability conditions than a normal cornea. The cornea possesses the ability to allow certain substances to pass only in one direction; for example, sodium chloride penetrates only into the eye, and not back out; oxygen from the air also penetrates into the eye, whereas carbon dioxide penetrates through the cornea from the anterior chamber only outwards. On the other hand, the permeability of the cornea also depends on the concentration of hydrogen ions of the introduced substance. Partly due to the absence of vessels in the cornea, and partly due to the evaporation of tear fluid from the surface of the cornea, its temperature when the palpebral fissure is open is lower than the temperature of the surrounding tissues, and reaches only 30°; when the eyelids are closed, it rises to 35-36°. Due to the low temperature of the cornea, the growth of mold fungi is possible on it, which do not grow on living human skin because the temperature is too high for them (Fuchs). Due to the absence of vessels in the cornea, it does not contain, under normal conditions in its tissue fluid, especially in its central parts, the protective substances characteristic of the normal blood serum of the same organism. With artificial general immunization (vaccination) of the organism, the cornea also participates to a certain extent in general immunity, but the fluid of the anterior chamber still contains significantly fewer immune bodies than blood serum (Yamada et al.), and repeated punctures of the anterior chamber are necessary to promote their increase. With local immunization by injections into the cornea itself or into the anterior chamber (Mutermilch, Yamada, Bursuk, et al.), local immunity increases significantly. With infection through the eye, the development of humoral immunity is significantly inferior to that with the intravenous method of immunization, so the eye is an unsuitable portal of entry for vaccination of the organism (Polev and Mikoelyan, et al.). To obtain the development of immune bodies in the cornea of the other eye during local immunization of the cornea of one eye, it is necessary to subject it to repeated irritations (scarification), but even under these conditions, there will still be fewer immune bodies here than in the primarily immunized eye (Polyak, Bursuk). Experiments on vaccination by introducing the vaccine into the conjunctival sac in the form of drops and ointment are being conducted (Polyak, Chirkovsky, and Dymshits), but in general, the clinical application of immunization through the cornea is still only in the development stage. The cornea of a newborn has some peculiarities compared to the cornea of an adult. According to Merkel and Orr, the cornea of a newborn is more curved at the periphery than in the center, i.e., the opposite of what is observed in an adult. Bowman's membrane of a newborn is the same thickness as that of an adult; on the contrary, Descemet's membrane is more delicate; the proper tissue of the cornea is much richer in nuclei. The main growth of the cornea, as indicated above, falls in the first year of life; as the volume of the cornea increases, the number of nuclei in its stroma decreases, Descemet's membrane reaches its usual thickness; warty growths on its periphery are noted for the first time in the 9th year of life. Later age-related changes in the cornea manifest as arcus senilis (see), some clouding of the periphery of the cornea in old age, a decrease in the transverse size of the cornea, obviously due to clouding of the limbus, and flattening of the cornea, with the vertical meridian flattening more than the horizontal, and inverse astigmatism develops. The cornea normally possesses: a mirror-smooth surface, a spherically convex shape, a definite size, transparency, and sensitivity. These properties of the cornea are what are paid attention to during its examination: by simple inspection, inspection with focal illumination and a simple magnifying glass, a corneal microscope and slit lamp, keratoscope, ophthalmometer, in transmitted light, and finally, the state of its sensitivity (see below). For a more precise examination of the shape of the cornea and its surface, so-called keratoscopes are used, the most common of which is the Placido keratoscope. It is a disk on which concentric white and black rings are depicted and there is a hole in the middle. If such a disk is brightly illuminated and held in a strictly frontal plane at a close distance in front of the eye, while viewing its mirror image on the cornea through the central hole, then in the normal state of the cornea, a sharp image with distinct regular circles will be visible in its center; at the periphery of the cornea, the circles will be somewhat elongated and stretched in the meridional direction. With pathological deviations in the shape of the cornea, the images in the center of the cornea will also be elongated or shortened, and with disturbances of the corneal surface, the contours of the images become blurred and appear saw-toothed. There are modifications of the keratoscope where, instead of a circle, a quadrangular plate with the same lines is taken, or radial stripes are applied instead of circular lines. At the present time, so-called photo-keratoscopes have been proposed by Zeiss, where the obtained image is immediately, so to speak, documented on a corresponding photograph. In the absence of a keratoscope, it is permissible to replace it with the reflection of a window frame image on the cornea, which also yields either regular and distinct or distorted and unclear images of the frame. For further development of keratoscopy, see Ophthalmometer. Changes in the surface of the cornea are most often the result of inflammatory diseases of it, keratitis (see), and are expressed either in depressions of the surface—ulcers, traumatic injuries—or in elevations above the surface of the cornea—inflammatory foci, foreign bodies, prolapse of the iris through a wound opening or perforated ulcer, and finally, so-called keratocele or descemetocele. Under this name, small translucent elevations are described, which sometimes form at the site of corneal ulcers when the ulcer destroys the entire thickness of the cornea up to Descemet's membrane, and the latter, due to its increased resistance, is not destroyed but bulges out in the form of a hernia, filling the ulcer defect and protruding above the surface of the cornea. Along with keratocele, it is necessary to mention partial ectasias of the cornea on the basis of limited ulcers that were previously there, inflammatory (see Keratitis) and degenerative processes (see below). The cornea, having lost its elasticity in a given segment due to the aforementioned processes, partially bulges out. Changes in the size of the cornea occur both in the direction of increase—megalocornea—and in the direction of decrease—microcornea, but it should be noted that between macro- and microcornea, on the one hand, and its normal size, on the other, it is impossible to draw sharp boundaries, because they are connected by a series of imperceptible transitions (Peter), and by the name of the above-mentioned anomalies, only sharp degrees of deviations from the average size are implied. Both conditions are mostly congenital in nature, but a definite type of heredity cannot yet be established (Peter). Microcornea is often one of the signs of general underdevelopment of the eyeball—microphthalmia—and the size of the cornea can be very diverse, down to a small piece of flattened transparent tissue of an irregularly rounded shape. Acquired microcornea represents one of the symptoms of atrophy of the eyeball. Megalocornea, in which the diameter of the cornea can reach 14-16 mm, in most cases occurs in so-called hydrophthalmos, when, due to increased intraocular pressure, not only the cornea is stretched, but also the sclera and the entire eyeball as a whole.

In this case, ruptures of Descemet's membrane are often observed in the form of arcuate lines on the posterior surface of the cornea. Megalocornea also occurs without hydrophthalmos (without stretching of the sclera and without ruptures of Descemet's membrane) with satisfactory vision. This condition is familial in nature. Changes in the size and shape of the cornea also include keratoconus and keratoglobus (see Staphyloma). Among congenital anomalies of the cornea, it is necessary to mention the so-called embryotoxon—a ring-shaped opacity of the corneal margin, somewhat resembling arcus senilis (see), but extending further toward the center and, on the other hand, being in direct connection with the sclera. Apparently, this formation represents the sclera having encroached upon the cornea. This also includes congenital opacities in the central parts of the cornea, the cause of which is considered to be defects in Descemet's membrane and insufficient separation of the pupillary membrane from the corneal primordium, or disorders in the detachment of the lens, or intrauterine inflammation of the eye, or finally, trauma during childbirth (forceps). These anomalies are often observed simultaneously with a whole series of other malformations and are found in a number of members of the same family (Peters). Congenital anomalies of corneal pigmentation, melanosis corneae, have been described, with epithelial and endothelial forms being distinguished; in the former, the pigmentation is associated with the pigmentation of the limbus, which is not uncommon in general, while in the latter, the pigment lies in the center of the cornea in the form of a spot and is considered a remnant of the pupillary membrane. Also belonging to congenital conditions is the benign neoplasm of the cornea—a dermoid, usually located on the periphery of the cornea at the limbus in the form of a dense hemispherical tumor with a smooth surface, on which there are sometimes hairs. Among other benign neoplasms of the cornea, one should note epithelial hyperplasias—epitheliomas, according to Lagrange, and papillomas. Clinically, both appear as pale pink, flat, delicately papillary formations, which usually originate from the corneal limbus. Upon removal, they often recur and are prone to degeneration into carcinomas (Polev, Lurye). Carcinomas of the cornea, which also develop on the limbus, are initially difficult to distinguish from papillomas, but later they acquire a nodular appearance and ulcerate; their growth on the cornea proceeds mainly along the surface, but they can also destroy the cornea, growing into the anterior chamber, as well as into the orbit and adjacent accessory sinuses. Pigmented carcinomas that have developed from a naevus pigmentosus of the limbus are encountered, as well as carcinomas in xeroderma pigmentosum. Finally, cases of sarcoma of the cornea that have developed from the limbus have been described, in the form of flat, smooth (non-papillary) formations, more prone than carcinomas to grow into the eye along the vessels. The treatment for all malignant neoplasms is surgical, followed by cauterization and the use of X-rays and radium. A special group of corneal diseases consists of so-called neurotrophic keratitis, the cause of which is disease of the corneal nerves. This includes: neuroparalytic keratitis, herpes corneae simplex and herpes zoster, keratitis disciformis, recurrent corneal erosions and ulcus rodens (see Keratitis), keratitis superficialis punctata (Fuchs), and filamentous keratitis. In filamentous keratitis, thread-like formations are found on the cornea during symptoms of irritation, one end of which is attached to the cornea, and the other is free. The thread-like strands are formed by the epithelium and often recur. The disease is prolonged, but the prognosis is generally favorable. It is believed that filamentous keratitis is a complication of herpes and recurrent corneal erosions, hence the treatment is the same as for those diseases. Keratitis superficialis punctata, according to the latest views (Hanke), also belongs to neurotrophic corneal conditions. Individuals who have had the flu often contract keratitis superficialis punctata, with symptoms of conjunctivitis developing initially, but without catarrhal discharge, and lasting for several days to a week, and then superficial punctate gray opacities appear on one or both corneas, located either in groups or in lines, mainly in the central parts of the cornea. Ulcerations are observed as an exception; sometimes a decrease in corneal sensitivity and intraocular pressure is observed. The course is prolonged, the prognosis is favorable—the opacities disappear. Treatment is according to general rules. Infections constitute one of the most frequent causes of corneal diseases (see Keratitis). Among infectious inflammations of the cornea, gonorrheal keratitis has a particularly severe course (see Blennorrhea, blennorrhea of the newborn). Among infectious corneal ulcers, it is necessary to note the so-called infectious marginal ulcer of zur Nedden, caused by a special bacillus of zur Nedden—a Gram-negative, straight or slightly curved bacillus, often arranged in the form of diplobacilli and similar to the xerosis bacillus. The infectious ulcer resembles catarrhal ulcers (see Keratitis), but differs from the latter in that it is not accompanied by true symptoms of conjunctivitis. Less frequently, these ulcers are located in the central parts of the cornea. The prognosis is favorable. Syphilis plays a very large role in corneal diseases. On its basis, the following develop here: typical parenchymatous keratitis, deep punctate keratitis of Mauthner, sclerosing keratitis (see Keratitis), K. pustuliformis profunda (Fuchs), gummata of the cornea, and finally, superficial keratitis on the basis of acquired syphilis, sometimes developing in the secondary period as a concomitant phenomenon with lesions of the conjunctiva. K. pustuliformis profunda (Fuchs) begins with symptoms of iritis, and then gray stripes and later yellow purulent infiltrates (as if pustules) of various sizes appear in the deep layers of the cornea. In most cases, there are several infiltrates, less often one large one. The cornea does not ulcerate, there is hypopyon in the anterior chamber, and the deep parts of the eye are also involved in the process. The course is prolonged, the prognosis is grave. A gumma of the cornea is a relatively rare formation in the form of a voluminous infiltrate in the thickness of the cornea, which responds to energetic specific therapy (F. Arkhangelsky). A fairly large section of corneal diseases consists of its degenerative changes or corneal dystrophies. They differ from corneal inflammations: 1) clinically—by the absence of inflammatory symptoms; 2) by the steadily progressive course of the disease; 3) by the pathological-anatomical picture, where degenerative processes are present, rather than phenomena of inflammation. In the study of the etiology of corneal degeneration, despite the multitude of published observations, there is still much that is unclear, and Hanke, in the result of an extensive review of the literature in recent years, comes to the same conclusion. It is believed that the causes of dystrophy are either age, or disorders of the nutrition of the eye, or hereditary malformations. Recently, changes in the nerves supplying the cornea, and the nutritional disorders naturally associated with this, have attracted great attention as an etiological factor. Corneal dystrophies include: 1. Arcus senilis (see). 2. Dystrophia epithelialis corneae (Fuchs), characterized by diffuse superficial opacity of the cornea, mainly in the area of the pupil. The epithelium over the opacity has a matte, swollen appearance and resembles coarse shagreen; in old cases, it is raised in the form of vesicles. These vesicles, as well as delicate dark dots, correspond to small cavities within the epithelium. Corneal sensitivity is lost. Sometimes intraocular pressure increases. The course is prolonged, progressive, leading to a sharp decrease in vision. The disease affects either one or both eyes, usually in elderly people. Changes in the corneal nerves (Fuchs) or disorders of the endocrine glands (Seefelder, Leber) are indicated as the cause. Treatment is unsuccessful. 3. Dystrophia calcarea, calcareous degeneration of the cornea (Axenfeld) with deposits of lime mainly on the periphery of the cornea in the form of shiny opacities. Pathologically-anatomically: deposits of calcium phosphate salts between the lamellae of the cornea, mainly in the deep layers, without any signs of inflammation. Corneal sensitivity is not changed. 4. Dystrophia adiposa, fatty degeneration of the cornea: secondary as a consequence of the breakdown of exudate, hemorrhages, necrotic masses, or primary, where the cornea is infiltrated by fat brought from the body. The disease develops slowly and results in a diffuse, with the exception of the periphery, dense, yellowish-white opacity, the surface of which is uneven, slightly pitted, and has little sensitivity. 5. Dystrophia uratica, the deposition of uric acid crystals in the cornea described by Uhthoff and Chevallereau. 6. Band-shaped opacity of the cornea in the form of a gray band 3–5 mm wide, running across the cornea, slightly below its center. It develops slowly over a number of years, with the ends of the cloudy strip forming first, which then merge with each other. Anatomically: deposition of lime salts and hyaline concretions in Bowman's membrane, disintegration of Bowman's membrane into parts, and the development of connective tissue in its place. Usually the disease develops in blind, degenerated eyes, but in rare cases it can also occur in otherwise healthy eyes. In the latter cases, one can attempt to dissolve the calcium carbonate with eye baths using a 10% solution of neutral ammonium tartrate, or in chronic cases, consider surgical scraping of the opacities. 7 and 8.

Nodular and lattice opacities of the cornea—two closely related diseases—usually begin in young years and last a lifetime, often affecting several members of the same family. On the cornea, predominantly in the pupillary part, in nodular opacity, there is a mass of small, variously shaped grayish opacities, sometimes merging into larger irregular figures; in lattice opacity, along with nodules on the cornea, there are opacities in the form of lines forming a whole network. With a superficial position of the nodules in nodular opacity, a rough coarseness of the corneal surface is obtained. At times, small exacerbations of the processes occur, and the spots gradually increase. The state of corneal sensitivity varies, ranging from normal to almost complete anesthesia. Patho-anatomically, in nodular opacity, deposits of hyaline have been found in the superficial layers, or, according to Fuchs, two substances—one amorphous acidophilic between the epithelium and Bowman's membrane and another granular basophilic, mainly in the corneal tissue. Clinically, as a result of the increase in opacities and the formation of cloudy spots consisting of individual points, a third form of this dystrophy can result—spotted corneal opacity. The etiology of all these dystrophies has not been clarified; recently, the opinion about the trophoneurotic nature of the processes has been especially put forward. 9. Pannus degenerativus sometimes develops in eyes blinded by iridocyclitis, glaucoma, etc., is clinically similar to trachomatous pannus (see Pannus) and represents an indistinct superficial corneal opacity, permeated by superficial and deep vessels. Anatomically, there is a development of connective tissue under the epithelium and in the superficial layers of the cornea. Treatment is unsuccessful. 10. Corneal xerosis—see Xerophthalmia. 11. Keratosis corneae—one of the types of xerosis, in which the cornea appears dull, dry, not wetted by liquids, and its epithelium is thickened and keratinized. Keratosis is observed in trachoma, pemphigus, burns, and with insufficient closure of the cornea by the eyelids. 12. Colloid, hyaline, and amyloid degeneration of corneal scars, especially old ones, is not a rarity. In the degenerated areas, calcareous salts can be deposited. In one and the same scar, substances with different chemical reactions can be present, which suggests that they represent only different stages of one and the same process (Hippel). These degenerated areas can ulcerate, and for the treatment of such ulcers, scraping with a sharp spoon can be used, followed by plastic surgery according to Kuhnt, in case of poor healing. 13. In old people, above a strongly developed arcus senilis, a symmetrical development of a groove or furrow is sometimes observed on both corneas, the peripheral edge of which gradually passes into the corneal limbus, and the inner edge steeply, almost vertically, into the arcus senilis. Small vessels are visible in the furrow, but there are no signs of irritation. This marginal thinning of the cornea, or dystrophia marginalis symmetrica (Fuchs), or peripheral furrow keratitis (Schmidt-Rimpler), can subsequently lead to protrusion of the thinned corneal tissue, to so-called peripheral ectasia, associated, of course, with the development of severe astigmatism. Sometimes the protruded part of the cornea bursts even with minor trauma, with all the consequences of this for the eye. In case of a threatened rupture and after it, conjunctival plastic surgery according to Kuhnt can be recommended. Both after corneal inflammations and especially after ulcers, as well as after the above-mentioned corneal degenerations, cicatricial corneal opacities can remain in the form of a cloud, spot, or leukoma [nubecula, macula, leukoma]. A leukoma fused with the iris (leucoma adhaerens) and protruded under the influence of intraocular pressure is called leucoma ectaticum or staphyloma (see Staphyloma). Corneal injuries are very frequent, and among them the most common—up to 80% of all eye injuries—are: 1. Foreign bodies of the cornea. Regarding foreign bodies of the cornea as an occupational disease and their influence on the decrease in corneal sensitivity—see Vision, occupational diseases of the organ of vision. Oxidizing foreign bodies of the cornea (iron, etc.) irritate the eye more strongly than non-oxidizing ones, which sometimes may not cause any reaction at all. Foreign bodies are removed with a special needle. Foreign bodies deeply embedded in the cornea and chemically inert (gunpowder, coal, etc.) are often not removed at all. If a foreign body is seated only in the corneal epithelium, then after its removal no trace remains; otherwise, at least a pinpoint scar remains. The greatest danger in an injury by a foreign body is primary or secondary infection and the development of a corneal ulcer. To prevent this, the eye is washed with a disinfectant liquid (mercury cyanide, etc.), collargol, optochin, etc., are instilled into the eye, disinfectant ointments are applied, and a bandage is applied. -2. Corneal erosions are very frequent in everyday life and industry (see Keratitis). In the fight against foreign bodies and corneal erosions, the most important thing is, of course, their prevention; for preventive measures, see Foreign bodies. -3. Thermal burns of the cornea can be superficial and deep. In superficial burns (match heads, particles of red-hot coals, small red-hot metal particles, etc.), only clouding of the epithelium is observed, resulting in its regeneration after a few days. In deeper burns, where the tissue of the cornea itself becomes necrotic, scars remain after healing; the scarred, degenerated cornea may subsequently protrude. Treatment of burns—washing with disinfectant liquids, non-irritating ointments, 3-5% Scharlachrot ointment as promoting epithelialization, atropine—according to indications. 4. Chemical burns of the cornea are most often caused by acids and alkalis. In mild acid burns, the epithelium becomes necrotic and the cornea becomes slightly cloudy. With the action of concentrated acids, the corneal tissue also becomes necrotic; the prognosis is usually poor. One should not be misled by seeing a transparent part of the cornea after the rejection of necrotic tissue, because usually in such cases not only the entire cornea perishes, but often the entire eye as well. The same degrees of damage can occur with alkali burns, and here the prognosis must always be cautious, and in more severe cases—poor. Treatment for acid burns—washing with weakly alkaline solutions, best of all a 1/2% solution of caustic potash, or a weak soda solution, or simply an abundant amount of water. For alkali burns—thorough washing with weak acetic acid (1:1,000) or abundantly with water. For lime burns, all its pieces are carefully removed from the surface of the eye and the conjunctiva of the eyelids, and it is abundantly washed with water or, even better, with oil. Further treatment, as in general for burns—indifferent ointments, atropine according to indications. In severe burns, transplantation of mucous membrane from the lip according to Denig is recommended for the burned areas. In burns with heavy metal salts (zinc, lead, silver, copper, mercury, etc.), corneal opacities of varying degrees are formed, depending on the concentration of the solution and the duration of action. Treatment—abundant washing with water. Among burns with organic substances (alcohols, chloroform, essential oils, aniline dyes, etc.), it is necessary to especially note burns with an aniline ink pencil. In mild cases, there is staining of the tissues in the color of the pencil, pitting of the cornea, and its clouding; in severe cases—corneal ulcers and its destruction. Treatment—thorough washing of the eye with water and removal of all residues of the caustic substance; for chemical pencil burns—a solution of tannin in drops. 5. Corneal burns by radiant energy (ultraviolet rays, X-rays and radium rays, voltaic arc during electric welding, etc.). In mild degrees of burn, there are only signs of irritation in the eye, and upon examination with a slit lamp, slight desquamation of the corneal epithelium. In severe burns—infiltration of the entire cornea and tissue disintegration. Subjectively—severe photophobia, sensation of sharp foreign bodies in the conjunctival sac. -6. Under the action of high-voltage electric current, corneal opacity can occur, which disappears after a few days. In case of a lightning strike, opacities of various shapes were noted in the cornea, which also usually resolve. Treatment—protection from light, cold compresses, indifferent ointments, for pain—cocaine. For the prevention of injuries by radiant energy—special glasses made of glass with an admixture of lead. -7. Perforating corneal injuries can be of the most diverse size and shape and are usually accompanied by prolapse of the iris into the wound. Uninfected corneal wounds not complicated by injury to the lens can close very quickly, and in 8-14 days all signs of irritation subside. Infected penetrating wounds can lead to the loss of the entire eye. In small uncomplicated corneal wounds, one can limit oneself to a bandage and atropine. In case of iris prolapse, it must either be repositioned, in fresh cases, or excised; in old cases, cauterization of the prolapsed iris can be performed. Sutures are applied to gaping wounds, or conjunctival plastic surgery according to Kuhnt is performed. -8. In injuries of the eyeball in general and the cornea in particular, the epithelium penetrating into the wound canal can proliferate there, forming cysts. In corneal contusions, corneal opacities, usually milky-white in color, or corneal ruptures (relatively rarely) can occur.

Ruptures can proceed in various directions; if they are very large and the eye is crushed, it is necessary to perform an enucleation. The cornea, especially its limbus, is the site of incision for a wide variety of operations. Among operations on the cornea itself, one should mention paracentesis of the cornea, i.e., an incision of the edge of the cornea with a spear-shaped knife for the purpose of gaining access to the anterior chamber of the eye for the removal of pus, foreign bodies, cataractous masses, etc.

A. Pokrovsky. Mitogenetic radiation of the cornea is at the present time a firmly established fact. The epithelium of the cornea belongs to the number of few sources of mitogenetic radiation described in adult animals. Upon exposure of the cornea of a rabbit's eye to a standard detector of mitogenetic rays (see), in the course of 30 sec. – 1 min., it is possible to detect a clear effect of mitosis induction. Fundamentally coinciding results were obtained for the cornea of the frog and man. For the latter case, a correspondence of the obtained effect with the presence or absence of blood radiation has been shown—a circumstance having great methodological significance, since it facilitates the setup of experiments clarifying the dependence of radiation on the general state of the organism (fatigue, presence of malignant neoplasms, etc.). A number of data, in particular biological spectral analysis, compel one to accept that in the cornea there are sources of radiation of two kinds—a powerful glycolytic radiation, apparently arising secondarily during primary mitogenetic irradiation from the side of the blood vessels passing along the edge of the cornea, and a weaker nucleolytic radiation, primarily arising in the cornea. During a 6-day starvation of the animal (rabbit), the chemism of the corneal radiation changes significantly—instead of glycolytic, a proteolytic radiation appears, taking its origin apparently in the impending self-digestion of the tissues of the organism. A number of works have established the value of the cornea as an excellent detector of mitogenetic radiation.

S. Zalkind.