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Studies on the Morphology and Pathology*
802
EDWARD C. ALBERS AND BERTHA A. KLIEN
showing dissolution rather than hyalinization were found in the deep stromal layers near the dilator muscle (fig.2), while the hyalin vessels, many of them still filled with blood, formed the cores of the floating stromal strands. Thus, the essential pathologic change may not b e sclerosis and hyalinization but an obliterative process. Its basis might be a hemodynamic regulating mechanism by which branches that arise at a more unfavor able angle from the main vascular trunks in a given organ are shut off when circulation is becoming impaired in advanced old age.
S U M M A R Y AND C O N C L U S I O N S
Histologic examination of two eyes with iridoschisis obtained post mortem after a clinical period of observation of five years during which a lens extraction in one of them restored vision to 2 0 / 2 5 , permitted the defi nite statement that neither trauma nor any type of associated ocular disease is the cause of this striking condition. It is in a small way a replica of natural death from the aging process. Christie Clinic. 2615 East 76th Street
(49).
REFERENCES
1. Schmitt, A.: Ablosung des vorderen Irisblattes. Klin. Monatsbl. f. Augenli., 58:214-215, 1922. 2. Drabkin, B.: Spontane Loslosung der vorderen mesodermalen Irisplatte. Klin. Monatsbl. f. Augenh., 71:188-190, 1923. 3. Sander, E.: Erworbene Ablosung des vorderen Irisblattes. Klin. Monatsbl. f. Augenh., 74:729-730; 192S. 4. Vogt, A.: Abgeloste vordere Irisplatte als Senile Veranderung (Senile Irisschiirze). 77:710, 1926. 5. Imre: Quoted by Shoenberg.10 6. Dollfus, A.: Degenerescence irenni d'un type particulier. Bull. Soc. ophtal. Paris., 1927, p. 170. 7. Loewenstein, A., and Foster, J.: Iridoschisis with multiple rupture of the stromal threads. Brit. J. Ophth., 29:277-282, 1945. 8. Loewenstein, A., Foster, J., and Sledge, S. K.: A further case of iridoschisis. Brit. J. Ophth., 32:129134, 1948. 9. Gardner, R. R., and Wier, A. R.: Iridoschisis in a case of chronic primary glaucoma. Brit. I. Ophth., 33:509-511, 1949. 10. Shoenberg, J. J.: Case of detachment of the anterior layers of the iris. Arch. Ophth., 56:538-542, 1927. 11. Linn, J. G., and Linn, J. G., Jr.: Detachment of the anterior layers of the iris, (iridoschisis): Report of a case. Am. J. Ophth., 32 :1700-1702, 1949. 12. Viers, R. R.: Iridoschisis (a case report). Am. J. Ophth., 32:261-262, 1949. 13. McCuIloch, C : Iridoschisis as a cause of glaucoma. Am. J. Ophth., 33:1398-1400, 1950. 14. Haik, G. M., Lyda, W., and Waugh, R. L.: Iridoschisis. Arch. Ophth., 48:40-43, 1952. 15. Klien, B.: The ciliary margin of the dilator muscle of the pupil. Arch. Ophth. 15:985-993, 1936. STUDIES ON T H E MORPHOLOGY AND PATHOLOGY* O F T H E TRABECULAR M E S H W O R K I N T H E H U M A N EYE J.
R O H E N , M.D.,
AND H.-H.
UNGER,
M.D.
Freiburg im Breisgau, Germany Gonioscopy and the etiology of glaucoma have equally kept awake the interest in the trabecular meshwork. Although the older authors preferred sagittal sections, more re cent researchers (Ashton, Brini, and Smith, * From the Institute of Anatomy, University of Mainz, Director: Prof. Dr. A. Dabelow; and from the Department of Ophthalmology, Freiburg im Breisgau, Director: Prof. Dr. W. Wegner.
as well as Busacca, Flocks, K u r u s , Rohen, Unger, Vrabec) have also used flat sections or flat preparations in order to obtain a thor ough knowledge of the structure of the chamber angle. In our opinion the results thus far obtained may be summed up to show that there are three different tissue for mations in the meshwork integrated into a, functional unit:
TRABECULAR MESHWORK OF HUMAN EYE
1. An equatorial, elastic reticulum which represents the mechanical basis of the trabeculae and is able to be expanded, indirectly (Unger, and Rohen, 1957) as well as direct ly, by contraction of the ciliary musclechoroid system since a large portion of the anterior ciliary muscle sinews join not only the cornea and the scleral spur, but also the elastic reticulum of the meshwork proper (Rohen, 1956). 2. A system of endothelial cells which communicates with the corneal endothelium, the endothelium of the iris, and the endo thelium of Schlemm's canal. 3. Light-microscopically homogeneous sub stances enveloping the elastic fibers and form ing flat lamellas (fig. 1). According to Graumann and Rohen (in press) the following details are to be distin guished: (a) a central ground substance la mella, and (b) a superficial subendothelial basement membrane (glass membrane) which communicates with another basement mem brane situated between Descemet's membrane and the corneal endothelium and which has been observed by these authors. Descemet's membrane does not extend to the trabecular meshwork. The pertinent literature was thoroughly re viewed by Ashton, et al. We have recently
803
published and discussed new results concern ing the anatomic and functional structure of the trabecular meshwork (Rohen, 1956, 1957; Unger 1956, 1957) which makes a repetition of our findings in the present study unnecessary. MATERIALS AND METHODS
We examined histologically, with regard to alterations of the corneoscleral trabeculae, the chamber angles of enucleated globes with primary or secondary glaucoma and of eyes without increased intraocular pressure, which had to be enucleated because of tumors or perforating injuries. We used sagittal and flat sections. Stains were hematoxylin-eosin, Azan, van Gieson, Masson-Goldner's trichrome stain, PAS-McManus, toluidine blue, and chrome-hematoxylin-phloxin ac cording to Gomori. Materials were 14 globes without glau coma (five from children from two to six years of age) ; six eyeballs with absolute pri mary glaucoma from persons 20 to 75 years of age; 22 globes with absolute secondary glaucoma, mostly from persons 30 to 83 years of age; making a total of 42 eyes. FINDINGS
1. Two sets of tissue in the region of the
.£>.,%«' • ■ S
Fig. 1 (Rohen and Unger). Tangential frozen section of the trabecular meshwork. Note the elastic reticula and the endothelial cells spread flatly between the oval pores. (X320.)
'*Sf
<«•%,
^*9^M
■*m-i j.
0%
804
J. ROHEN AND H.-H. UNGER
D V$
Fig. 2 (Rohen and Lngcr). Reactions of the trabecular endothelium. Cell desquamations (D), vital stora"» (VS), mitoses (M), and amitoses as well as numerous different nuclear shapes (NS) are visible. (X 1,000.) trabecular meshwork are of special impor tance to the aqueous circulation, namely, en dothelium and basement membrane. A.
ENDOTHELIUM
OF
THE
TRABECULAR
MESHWORK
In the normal eye the endothelium is fixed flatly within the trabecular meshwork (fig.
1 ) . With larger meshes in the reticulum it sometimes happens that pores stay open ( A s h t o n ) . T h e smaller ones, however, are as a rule covered completely by endothelium. Mitoses occur, especially in pathologic reac tions of the eye (inflammations, glaucoma), and so do, evidently, amitoses, which is dis closed by the curious shapes of the nuclei
TRABECULAR MESHWORK OF HUMAN EYE
Etidotkdial cetlx iK fa imer M
80S
Srhkmm'.s Canal
Fig. 3 (Rohen and Unger). (Above) Cross section of Schlemm's canal with adjacent meshwork in case of primary glaucoma with strong endothelial reaction. At the bottom of Schlemm's canal one may observe conglomerations of desquamated endothelial cells. (Below) Flat section of the same trabecular meshwork. Numerous isolated endothelial cells in the meshes of the trabecula may be recognized. ([Above] Azan stain, X350; [below] chrome-hematoxylin-phloxin according to Gomori).
(fig. 2). By these processes the endothelium proliferates considerably and is apparently able to fill the sponge-pore spaces to such an extent as to hamper the aqueous outflow and obliterate the inner wall of Schlemm's canal
("pore tissue," Flocks) (fig. 3). We also found such multiplications of cells in eyes with secondary glaucoma and in those with primary glaucoma. We have demonstrated recently (Rohen
806
J. ROHEN AND H.-H. UNGER
and Unger, 1957) that most probably these cells are capable of vital storage and, there fore, have to be designated as retothelia of the angle (RES of the eye) (fig. 2). The storage of pigment has been known for a long time. With siderosis bulbi we found the well-known selective storage of iron in the endothelial cells of the meshwork. Further studies concerning storage of vital dyes are under way.
Figure 2 shows, however, that under path ologic circumstances (secondary glaucoma, inflammatory reactions) these cells, by pha gocytosis of foreign substances, may increase their load, grow considerably larger, and desquamate. Wre also think that those cells with a storage of bacteria and foreign bodies found in the aqueous by Amsler, Huber, and Verrey, in puncturing the anterior chamber, were the retothelia of the angle.
Schlemm's Canal
meshwork
Schlemm's Canal
thickened basement membrane of the «q Trabeculae
Fig. 4 (Rohen and Unger). (Above) Normal trabecula of a woman aged 49 years. (Below) Patient aged 74 years, suffering from absolute glaucoma. Note extreme thickening of trabecular lamellae.
TRABECULAR MESHWORK OF HUMAN EYE
807
Fig. 5 (Rohen and Unger) Flat sections of the trabecula. (a) Of a healthy, normal eye which had to be removed because of cancer of the sinus of Highmor (taken from a woman 49 years of age), (b) Of a 62-year-old patient with pri mary glaucoma. Strong irregular layers on the trabecular lamellae. (c) Of a patient aged 68 years. Secondary glaucoma. Almost com plete conglutination of the thick ened, hyalinized lamellae. Only a few oval pores are to be seen. Schlemm's canal is not visible here, yet it is still open. (All three fig ures, X350.)
B. G R O U N D SUBSTANCES OF T H E TRABECULAR MESHWORK
The basement membrane of the trabecula is probably in close functional dependence upon the endothelium. It is homogeneous by lightmicroscopy. Stained with P A S , it proves heavily reactive to periodate; however, it is not a metachromotope ( G r a u m a n n and Rohen, in p r e s s ) . These authors found that as to its substance and structure the trabecu lar meshwork is characterized by . . . a central ground substance lamella being lined on both sides by an "endothelial basement
membrane system" specialized in the metabolic process, which is well known in connection with the capillaries. The adjacent membranes in ques tion are directly connected with the basement mem brane of the corneal endothelium. Glycoproteides are part of its building substance. . . . If these findings concerning the existence of a special basement membrane, situated be tween the corneal endothelium and Descemet's membrane and which communicates throughout with the trabecular meshwork, can be further corroborated (as in the case of the corneal epithelium which can be con sidered an established fact [Calmettes and co-workers, Graumann and R o h e n ] ) , the na-
808
T. ROHEN AND H.-H. UNGER
Scklemm's Canal mesktfork.
meshwork
Descemets
Sditewm's Ccuud
Fig. 6 (Rohen and Unger). Elliot trephination. Simple chronic glaucoma with cupping and loss of visual field. Note the thickening of the basement membrane of the trabeculae. (Orcein stain. Enlarged [above] X80; [below] X200.)
ture of this meshwork appears in a different light. It is, then, no longer justified to speak of a scleral meshwork (H. Virchow, 1910) ; rather of a modified corneal tissue or a spe cialized endothelial basement membrane sys tem. Therefore, we were not surprised when, upon observing various pathologic reactions of the trabecula, especially in cases of glau coma or perforating injuries which ended in enucleation, we could prove quantitative and
qualitative alterations (Rohen and Unger, 1957), such as have been observed in other endothelial basement membrane systems of the organism, for example, due to old age, with arteriosclerosis, with follicle atresia in the ovary ( Watzka, 1957), or with atrophy of the seminal tubules (H. Stieve, 1955). 2. Pathologic alterations of the meshwork with glaucoma. Thus we found, for example, in the eye of a woman patient, aged 74
TRABECULAR MESHWORK OF HUMAN EYE
809
Fig. 7 (Rohen and Unger). Flat section of the trabecular system of a child, aged four years, who suf fered from perforating injury of the eye. (Azan; X450.) Note the irregular swellings of the trabecular lamellae (arrows).
years, with simple chronic glaucoma, an enormous thickening of the basement mem brane (not of the central ground substance la mella), which had caused a noticeable nar rowing of the trabecular slits. By applying histochemical stains and magnifying the slides considerably under the microscope, it was discovered that layers had formed on the thickened lamellae, the former showing vari ous histochemical reactions. In most cases the reactivity to periodate decreases as the trabecula thickens. There is no indication of metachromacy. We rarely found this increase of ground substances in the trabecular lamellae to be as heavy as in the case pictured (figs. 4 and 5) ; out of the six eyes with primary glau coma examined, all had undergone changes of the basement membrane. In 22 eyes with secondary glaucoma 14 showed no alterations, eight were altered. There were no alterations of the basement membrane in inflamed globes. Out of 14 eyes with tumors or perforating injuries, there were two cases in which the basement membrane was altered. The trabec ular lamellae thicken by deposition of lightmicroscopically homogeneous substances, a prbcess which may be irregular and stop at different degrees.
In Figure 5-b it can be seen that numerous lamellae have been modified while others are completely unchanged. At first the elastic fibers at the center of the lamellae are still visible, later on (fig. S-c) they are merged in the general process of hyaline consolidation. Even histologic examination of Elliot trephinations, that is, a biopsy of glaucomatous eyes (Unger, 1956) shows an alteration of the basement membrane (fig. 6 ) . It is inter esting to note that, for example, with perfor ating injuries, this thickening of the trabeculae can be seen only occasionally. This causes curious shapes (fig. 7) of nodular, clubshaped swellings which are centered around a fiber lamella. If the chamber angle is already obliterated or made impermeable by goniosynechias, one may observe especially a considerable growth and a large conglutination of the homogene ous substances. At this stage the elastic fibers are very often still well visible, whereas they disappear later on just like the endothelium itself (fig 8 ) . We cannot decide whether it is in the endothelium or in the basement mem brane that the degenerative process sets in. We have seen glaucomatous eyes in which the endothelial cells had enormously multiplied without any structural alterations of the base-
810
J. ROHEN AND H.-H. UNGER
SckUmm's Canal
mesktCork
Irix
Scktemns Canal mesfatorii
Fig. 8 (Rohen and Unger). Two cases of complete obliteration of the trabeculae by increase of the basement membrane and conglutination of lamellae in absolute glaucoma. (Above) (PAS stain according to McManus.) Note the heavily periodate-reactive coloring of the basement membrane. (Below) Cross sections of the elastic fibers still visible. (X212.) ment membrane taking place (fig. 3), and, vice versa, a considerable thickening of the membrane without the endothelium being af fected (fig. 4 ) .
DISCUSSION
We cannot therefore, as yet, make any definite statement as to the causal genesis of these alterations. Hence it would be pointless
TRABECULAR MESHWORK OF HUMAN EYE
811
Cormoscktu
lyaheadae
\Trabeadae
Fig. 9 (Rolien and Unger). Autolytic test. Both figures represent the same eye. (Ahove) Fixed im mediately after enucleation. (Below) After 24 hours storage. Note complete dissolution of basement mem brane by autolysis. (Both pictures X350.) to discuss, at this early stage of our investi gation, the question whether the alterations shown are specifically glaucomatous and whether they are to be considered as primary or secondary processes. More comprehensive investigations have been started upon. The present paper is to give some introductory information and draw the attention to a whole series of ques tions. Teng, Paton, and Katzin have de scribed degenerative changes in the outer most layers of the trabecular meshwork; Franqois, Rabaey, and Neetens, as well as Dvorak-Theobald and Kirk, recently ob served a trabecular hypertrophy in eyes with
glaucoma. It is, however, a well-known fact that the fibers of the meshwork become thicker and "sclerosed" with advancing years or with glaucoma. Henderson speaks of a homogeneous sub stance similar to that composing Descemet's membrane, which is laid down more and more by the covering cells with each advanc ing decade. In some cases of glaucoma, histologically investigated, the meshwork showed a homogeneous structure with no interstices (Greeves, Polya, Sarti, Tartuferi) ; in other ones, the interspaces were replaced by a structureless homogeneous substance (de Vries).
812
J. ROHEN AND H.-H. UNGER
In connection with his description of a chamber-lining "glass-membrane" in glaucomatous eyes Reese thought the endothelium to be capable of its production under certain provocations. This cuticular product of the endothelial cells sometimes is laid down primarily in the interstices of the trabeculae; and the tendency is for the inner la mellae to be affected more than the outer. This may be the cause of the trabecular ob struction. It seems possible that Reese's find ings are similar to ours but the figures in his paper only show that the trabecular area is replaced by homogeneous tissue sparse in nuclei. These alterations are not exactly those which we are trying to describe. Due to the nature of the material used by Teng, Paton, and Katzin (eye-bank eyes) the basement membrane disintegrates com paratively easily and disappears almost com pletely by autolysis. Therefore we have car ried out fixation and autolysis experiments. One result can be seen in Figure 9. After the globe had been kept cool for 24 hours, the basement membrane had diminished to a large extent (fig. 9-b). This fact is another indica tion of the affinity to other basement mem branes in the organism where solubility is ex tremely important for metabolism and perme ability. If one considers the main part of the mesh work as an "endothelial basement mem brane system," the genesis of some symptoms might possibly be interpreted as a conse quence of an alteration of this system, in which process the chemically unstable basic
substance of the meshwork reacts with vari ous effects by various degrees of solubility. SUMMARY
We investigated the structure of the tra becular meshwork and some of its pathologic reactions. It was to be seen that the equato rial elastic reticulum which represents the mechanical basis of the trabeculae changes very little in case of disease, while the endothelium and the "glass membrane" connected with it show characteristic reactions. The endothelium is capable of vital storage and hence ought to be designated as retothelium. The cells are able to increase, multiply, and desquamate, with structural alterations becoming evident. The "glass membrane" is comparable to a basement membrane and can react by an in crease of substance in various cases of glau coma, as well as in globes enucleated because of tumors or perforating injuries. In eyes with absolute glaucoma this process reaches extreme degrees, so that in this way, too, the angle becomes obliterated. This must be dis tinguished from the reactions of a central ground substance lamella which envelops the elastic fibers of the trabeculae. The increase of the resistance to outflow might thus be ex plained morphologically. In agreement with Graumann and Rohen we suppose the exist ence of an "endothelial basement membrane system" for which laws similar to those for the wall of the capillaries may be valid. Schumannstrasse 14.
REFERENCES
Amsler, M., Huber, A., and Verrey, F.: L'humeur aqueuse et ses fonctions. Paris, Masson & Cie., 1955. Ashton, N., Brini, A., and Smith, R.: Brit. J. Ophth., 40:257, 1956. Busacca, A.: Elements de gonioscopie normale, pathologique et experimentale. Sao Paulo, Rossolillo, 1945. Calmettes, Deodati, Planel, and Bee: Etude histologique et histochemique de I'epithelium anterieur de la cornee et de ses basales. Arch. Ophthal., 16:481, 1956. Flocks, M.: Arch. Ophth., 56:708, 1956. Francois, J., Rabaey, M., and Neetens, A.: Arch. Ophth., 55:488, 1956. Graumann, W., and Rohen, J.: Chemohistol. Befunde am menschlichen Auge (Cornea, Sklera, Uvea), Ztschr. mikrosk.-anatomische Forschung, in press. Greeves, R. A.: Proc. Roy. Soc. Med. London, Sect. Ophth., 7:112, 1913/14. Henderson, T.: Ophth. Rec, 17:534, 1908. : Glaucoma, London, Edw. Arnold, 1910, pp. 34-38. Kurus, E.: Vers. d. Vereinigg. Rhein-Main. Augenarzte, Frankfurt/M. 1./2. 12. 1956. Polya: Ungar. Beitrage, 2:319, 1899. (Quoted by de Vries.)
TRABECULAR MESHWORK OF HUMAN EYE
813
Reese, A. B.: Am. J. Ophth., 27:1193, 1944. Rohen, J.: Die funktionelle Gestalt des Auges und seiner Hilfsorgane. Verl. d. Akad. d. Wissensch. u. d. Lit., Mainz. Komm. Wiesbaden, Verlag Franz Steiner, 1953. : Ophthalmologica, 131:51, 1956. : Ber. 60. Zusk. Deutsch. Ophth. Ges. Heidelberg. Munchen, J. F. Bergmann, 1956, p. 50. : Arch. f. Ophth., 158:310, 1957. Rohen, J., and Unger, H. H.: Anat. Anz., 104:287, 1957; 105:93, 1958. Sarti, V.: Bull. sc. med. Bologna, 4:147, 1893. (Quoted by de Vries.) Stieve, H.: Der Einfluss des Nervensystems auf die Geschlechtsorgane. Stuttgart, Thieme, 1955. Tartuferi, F.: Giorn. Acad. med. Torino, 30:624, 1882. Teng, C. C., Paton, R. T., and Katzin, H. M.: Am. J. Ophth., 40:619, 1955. Theobald, G. D., and Kirk, H. Q.: Am. J. Ophth., 41:11, 1956. Unger, H. H.: Klin. Wschr., 34:927, 1956. : Deutsch. Ophth. Ges. Heidelberg, Munchen, J. F. Bergmann, 1956, p. 59. : Klin. Wschr., 35:199, 1957. : Arch. Ophth., 158:509, 1957. : Klin. Monatsbl. f. Augenh., 131:385, 1957. : Klin. Monatsbl. f. Augenh., 131:692, 1957. Unger, H. H., and Rohen, J.. Ber. gi. Zusk. Deutsch. Ophth. Ges. Heidelberg, Munchen, J. F. Berg mann, 1957, p. 256. Virchow, H.: Graefe-Saemisch, Handbuch Augenh., Leipzig, Engelmann, 1910, v. 1, p. 281. Vrabec, F.: Ophthalmologica, 128:359, 1954. : Brit. J. Ophth., 41:20, 1957. de Vries, W. M.: Nederl. Tijdschr. v. Geneesk., 43:1688, 1907. Watzka, M.: D. Ovarium, Handb. mikrosk. Anat. d. Menschen. Bargmann, v. Moellendorf, 1957, Suppl. of VII/1.
NEWER OPTICAL AIDS FOR CHILDREN W I T H LOW VISION* JAMES E. LEBENSOHN,
M.D.
Chicago, Illinois
A major campaign of the National Society for the Prevention of Blindness stresses the theme that all persons, especially children, must be given every opportunity to utilize fully whatever sight they possess. Of the 33.5 million in the school popluation of the United States, 8.5 million require eye care for adequate far and near vision. Sightsaving classes for children with a correctible acuity of only 20/70 to 20/200 have an en rollment of 60,000. These partially seeing children respond well to appropriate methods of visual educa tion. Our recognition of their special educa tional status is due in great part to the late Mrs. Winifred Hathaway whose unique monograph, "The Education and Health of the Partially Seeing Child," published post humously in 1955, is a fitting memorial of a life devoted to this cause. * From the Department of Ophthalmology, North western University Medical School. Read before the International Council for Exceptional Children, Kansas City, Missouri, April 9, 1958.
Approximately five percent of the legally blind in this country, or about 15,000, are under 20 years of age. Of these 60 percent have a little sight, which ranges from vague light perception to 20/200 in the corrected better eye. Amblyopia, or uncorrectible poor vision, is more prevalent in rural than in urban areas; and in Negroes, Mexicans, and Indians than in white children. Among Ne groes the ratio is at least double that in the white population. At present about 60 percent of the ambly opia in children is of prenatal origin. Pre maturity by itself, even when not resulting in retrolental fibroplasia, frequently deter mines amblyopic myopia. Infective diseases account for over 20 percent; accidents for about 10 percent. The danger from accidents cannot be overemphasized; more children from one to 14 years of age die from acci dents than from all known childhood dis eases. Most students with normal intelligence and motivation who have sufficient vision to walk
EDWARD C. ALBERS AND BERTHA A. KLIEN
showing dissolution rather than hyalinization were found in the deep stromal layers near the dilator muscle (fig.2), while the hyalin vessels, many of them still filled with blood, formed the cores of the floating stromal strands. Thus, the essential pathologic change may not b e sclerosis and hyalinization but an obliterative process. Its basis might be a hemodynamic regulating mechanism by which branches that arise at a more unfavor able angle from the main vascular trunks in a given organ are shut off when circulation is becoming impaired in advanced old age.
S U M M A R Y AND C O N C L U S I O N S
Histologic examination of two eyes with iridoschisis obtained post mortem after a clinical period of observation of five years during which a lens extraction in one of them restored vision to 2 0 / 2 5 , permitted the defi nite statement that neither trauma nor any type of associated ocular disease is the cause of this striking condition. It is in a small way a replica of natural death from the aging process. Christie Clinic. 2615 East 76th Street
(49).
REFERENCES
1. Schmitt, A.: Ablosung des vorderen Irisblattes. Klin. Monatsbl. f. Augenli., 58:214-215, 1922. 2. Drabkin, B.: Spontane Loslosung der vorderen mesodermalen Irisplatte. Klin. Monatsbl. f. Augenh., 71:188-190, 1923. 3. Sander, E.: Erworbene Ablosung des vorderen Irisblattes. Klin. Monatsbl. f. Augenh., 74:729-730; 192S. 4. Vogt, A.: Abgeloste vordere Irisplatte als Senile Veranderung (Senile Irisschiirze). 77:710, 1926. 5. Imre: Quoted by Shoenberg.10 6. Dollfus, A.: Degenerescence irenni d'un type particulier. Bull. Soc. ophtal. Paris., 1927, p. 170. 7. Loewenstein, A., and Foster, J.: Iridoschisis with multiple rupture of the stromal threads. Brit. J. Ophth., 29:277-282, 1945. 8. Loewenstein, A., Foster, J., and Sledge, S. K.: A further case of iridoschisis. Brit. J. Ophth., 32:129134, 1948. 9. Gardner, R. R., and Wier, A. R.: Iridoschisis in a case of chronic primary glaucoma. Brit. I. Ophth., 33:509-511, 1949. 10. Shoenberg, J. J.: Case of detachment of the anterior layers of the iris. Arch. Ophth., 56:538-542, 1927. 11. Linn, J. G., and Linn, J. G., Jr.: Detachment of the anterior layers of the iris, (iridoschisis): Report of a case. Am. J. Ophth., 32 :1700-1702, 1949. 12. Viers, R. R.: Iridoschisis (a case report). Am. J. Ophth., 32:261-262, 1949. 13. McCuIloch, C : Iridoschisis as a cause of glaucoma. Am. J. Ophth., 33:1398-1400, 1950. 14. Haik, G. M., Lyda, W., and Waugh, R. L.: Iridoschisis. Arch. Ophth., 48:40-43, 1952. 15. Klien, B.: The ciliary margin of the dilator muscle of the pupil. Arch. Ophth. 15:985-993, 1936. STUDIES ON T H E MORPHOLOGY AND PATHOLOGY* O F T H E TRABECULAR M E S H W O R K I N T H E H U M A N EYE J.
R O H E N , M.D.,
AND H.-H.
UNGER,
M.D.
Freiburg im Breisgau, Germany Gonioscopy and the etiology of glaucoma have equally kept awake the interest in the trabecular meshwork. Although the older authors preferred sagittal sections, more re cent researchers (Ashton, Brini, and Smith, * From the Institute of Anatomy, University of Mainz, Director: Prof. Dr. A. Dabelow; and from the Department of Ophthalmology, Freiburg im Breisgau, Director: Prof. Dr. W. Wegner.
as well as Busacca, Flocks, K u r u s , Rohen, Unger, Vrabec) have also used flat sections or flat preparations in order to obtain a thor ough knowledge of the structure of the chamber angle. In our opinion the results thus far obtained may be summed up to show that there are three different tissue for mations in the meshwork integrated into a, functional unit:
TRABECULAR MESHWORK OF HUMAN EYE
1. An equatorial, elastic reticulum which represents the mechanical basis of the trabeculae and is able to be expanded, indirectly (Unger, and Rohen, 1957) as well as direct ly, by contraction of the ciliary musclechoroid system since a large portion of the anterior ciliary muscle sinews join not only the cornea and the scleral spur, but also the elastic reticulum of the meshwork proper (Rohen, 1956). 2. A system of endothelial cells which communicates with the corneal endothelium, the endothelium of the iris, and the endo thelium of Schlemm's canal. 3. Light-microscopically homogeneous sub stances enveloping the elastic fibers and form ing flat lamellas (fig. 1). According to Graumann and Rohen (in press) the following details are to be distin guished: (a) a central ground substance la mella, and (b) a superficial subendothelial basement membrane (glass membrane) which communicates with another basement mem brane situated between Descemet's membrane and the corneal endothelium and which has been observed by these authors. Descemet's membrane does not extend to the trabecular meshwork. The pertinent literature was thoroughly re viewed by Ashton, et al. We have recently
803
published and discussed new results concern ing the anatomic and functional structure of the trabecular meshwork (Rohen, 1956, 1957; Unger 1956, 1957) which makes a repetition of our findings in the present study unnecessary. MATERIALS AND METHODS
We examined histologically, with regard to alterations of the corneoscleral trabeculae, the chamber angles of enucleated globes with primary or secondary glaucoma and of eyes without increased intraocular pressure, which had to be enucleated because of tumors or perforating injuries. We used sagittal and flat sections. Stains were hematoxylin-eosin, Azan, van Gieson, Masson-Goldner's trichrome stain, PAS-McManus, toluidine blue, and chrome-hematoxylin-phloxin ac cording to Gomori. Materials were 14 globes without glau coma (five from children from two to six years of age) ; six eyeballs with absolute pri mary glaucoma from persons 20 to 75 years of age; 22 globes with absolute secondary glaucoma, mostly from persons 30 to 83 years of age; making a total of 42 eyes. FINDINGS
1. Two sets of tissue in the region of the
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Fig. 1 (Rohen and Unger). Tangential frozen section of the trabecular meshwork. Note the elastic reticula and the endothelial cells spread flatly between the oval pores. (X320.)
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Fig. 2 (Rohen and Lngcr). Reactions of the trabecular endothelium. Cell desquamations (D), vital stora"» (VS), mitoses (M), and amitoses as well as numerous different nuclear shapes (NS) are visible. (X 1,000.) trabecular meshwork are of special impor tance to the aqueous circulation, namely, en dothelium and basement membrane. A.
ENDOTHELIUM
OF
THE
TRABECULAR
MESHWORK
In the normal eye the endothelium is fixed flatly within the trabecular meshwork (fig.
1 ) . With larger meshes in the reticulum it sometimes happens that pores stay open ( A s h t o n ) . T h e smaller ones, however, are as a rule covered completely by endothelium. Mitoses occur, especially in pathologic reac tions of the eye (inflammations, glaucoma), and so do, evidently, amitoses, which is dis closed by the curious shapes of the nuclei
TRABECULAR MESHWORK OF HUMAN EYE
Etidotkdial cetlx iK fa imer M
80S
Srhkmm'.s Canal
Fig. 3 (Rohen and Unger). (Above) Cross section of Schlemm's canal with adjacent meshwork in case of primary glaucoma with strong endothelial reaction. At the bottom of Schlemm's canal one may observe conglomerations of desquamated endothelial cells. (Below) Flat section of the same trabecular meshwork. Numerous isolated endothelial cells in the meshes of the trabecula may be recognized. ([Above] Azan stain, X350; [below] chrome-hematoxylin-phloxin according to Gomori).
(fig. 2). By these processes the endothelium proliferates considerably and is apparently able to fill the sponge-pore spaces to such an extent as to hamper the aqueous outflow and obliterate the inner wall of Schlemm's canal
("pore tissue," Flocks) (fig. 3). We also found such multiplications of cells in eyes with secondary glaucoma and in those with primary glaucoma. We have demonstrated recently (Rohen
806
J. ROHEN AND H.-H. UNGER
and Unger, 1957) that most probably these cells are capable of vital storage and, there fore, have to be designated as retothelia of the angle (RES of the eye) (fig. 2). The storage of pigment has been known for a long time. With siderosis bulbi we found the well-known selective storage of iron in the endothelial cells of the meshwork. Further studies concerning storage of vital dyes are under way.
Figure 2 shows, however, that under path ologic circumstances (secondary glaucoma, inflammatory reactions) these cells, by pha gocytosis of foreign substances, may increase their load, grow considerably larger, and desquamate. Wre also think that those cells with a storage of bacteria and foreign bodies found in the aqueous by Amsler, Huber, and Verrey, in puncturing the anterior chamber, were the retothelia of the angle.
Schlemm's Canal
meshwork
Schlemm's Canal
thickened basement membrane of the «q Trabeculae
Fig. 4 (Rohen and Unger). (Above) Normal trabecula of a woman aged 49 years. (Below) Patient aged 74 years, suffering from absolute glaucoma. Note extreme thickening of trabecular lamellae.
TRABECULAR MESHWORK OF HUMAN EYE
807
Fig. 5 (Rohen and Unger) Flat sections of the trabecula. (a) Of a healthy, normal eye which had to be removed because of cancer of the sinus of Highmor (taken from a woman 49 years of age), (b) Of a 62-year-old patient with pri mary glaucoma. Strong irregular layers on the trabecular lamellae. (c) Of a patient aged 68 years. Secondary glaucoma. Almost com plete conglutination of the thick ened, hyalinized lamellae. Only a few oval pores are to be seen. Schlemm's canal is not visible here, yet it is still open. (All three fig ures, X350.)
B. G R O U N D SUBSTANCES OF T H E TRABECULAR MESHWORK
The basement membrane of the trabecula is probably in close functional dependence upon the endothelium. It is homogeneous by lightmicroscopy. Stained with P A S , it proves heavily reactive to periodate; however, it is not a metachromotope ( G r a u m a n n and Rohen, in p r e s s ) . These authors found that as to its substance and structure the trabecu lar meshwork is characterized by . . . a central ground substance lamella being lined on both sides by an "endothelial basement
membrane system" specialized in the metabolic process, which is well known in connection with the capillaries. The adjacent membranes in ques tion are directly connected with the basement mem brane of the corneal endothelium. Glycoproteides are part of its building substance. . . . If these findings concerning the existence of a special basement membrane, situated be tween the corneal endothelium and Descemet's membrane and which communicates throughout with the trabecular meshwork, can be further corroborated (as in the case of the corneal epithelium which can be con sidered an established fact [Calmettes and co-workers, Graumann and R o h e n ] ) , the na-
808
T. ROHEN AND H.-H. UNGER
Scklemm's Canal mesktfork.
meshwork
Descemets
Sditewm's Ccuud
Fig. 6 (Rohen and Unger). Elliot trephination. Simple chronic glaucoma with cupping and loss of visual field. Note the thickening of the basement membrane of the trabeculae. (Orcein stain. Enlarged [above] X80; [below] X200.)
ture of this meshwork appears in a different light. It is, then, no longer justified to speak of a scleral meshwork (H. Virchow, 1910) ; rather of a modified corneal tissue or a spe cialized endothelial basement membrane sys tem. Therefore, we were not surprised when, upon observing various pathologic reactions of the trabecula, especially in cases of glau coma or perforating injuries which ended in enucleation, we could prove quantitative and
qualitative alterations (Rohen and Unger, 1957), such as have been observed in other endothelial basement membrane systems of the organism, for example, due to old age, with arteriosclerosis, with follicle atresia in the ovary ( Watzka, 1957), or with atrophy of the seminal tubules (H. Stieve, 1955). 2. Pathologic alterations of the meshwork with glaucoma. Thus we found, for example, in the eye of a woman patient, aged 74
TRABECULAR MESHWORK OF HUMAN EYE
809
Fig. 7 (Rohen and Unger). Flat section of the trabecular system of a child, aged four years, who suf fered from perforating injury of the eye. (Azan; X450.) Note the irregular swellings of the trabecular lamellae (arrows).
years, with simple chronic glaucoma, an enormous thickening of the basement mem brane (not of the central ground substance la mella), which had caused a noticeable nar rowing of the trabecular slits. By applying histochemical stains and magnifying the slides considerably under the microscope, it was discovered that layers had formed on the thickened lamellae, the former showing vari ous histochemical reactions. In most cases the reactivity to periodate decreases as the trabecula thickens. There is no indication of metachromacy. We rarely found this increase of ground substances in the trabecular lamellae to be as heavy as in the case pictured (figs. 4 and 5) ; out of the six eyes with primary glau coma examined, all had undergone changes of the basement membrane. In 22 eyes with secondary glaucoma 14 showed no alterations, eight were altered. There were no alterations of the basement membrane in inflamed globes. Out of 14 eyes with tumors or perforating injuries, there were two cases in which the basement membrane was altered. The trabec ular lamellae thicken by deposition of lightmicroscopically homogeneous substances, a prbcess which may be irregular and stop at different degrees.
In Figure 5-b it can be seen that numerous lamellae have been modified while others are completely unchanged. At first the elastic fibers at the center of the lamellae are still visible, later on (fig. S-c) they are merged in the general process of hyaline consolidation. Even histologic examination of Elliot trephinations, that is, a biopsy of glaucomatous eyes (Unger, 1956) shows an alteration of the basement membrane (fig. 6 ) . It is inter esting to note that, for example, with perfor ating injuries, this thickening of the trabeculae can be seen only occasionally. This causes curious shapes (fig. 7) of nodular, clubshaped swellings which are centered around a fiber lamella. If the chamber angle is already obliterated or made impermeable by goniosynechias, one may observe especially a considerable growth and a large conglutination of the homogene ous substances. At this stage the elastic fibers are very often still well visible, whereas they disappear later on just like the endothelium itself (fig 8 ) . We cannot decide whether it is in the endothelium or in the basement mem brane that the degenerative process sets in. We have seen glaucomatous eyes in which the endothelial cells had enormously multiplied without any structural alterations of the base-
810
J. ROHEN AND H.-H. UNGER
SckUmm's Canal
mesktCork
Irix
Scktemns Canal mesfatorii
Fig. 8 (Rohen and Unger). Two cases of complete obliteration of the trabeculae by increase of the basement membrane and conglutination of lamellae in absolute glaucoma. (Above) (PAS stain according to McManus.) Note the heavily periodate-reactive coloring of the basement membrane. (Below) Cross sections of the elastic fibers still visible. (X212.) ment membrane taking place (fig. 3), and, vice versa, a considerable thickening of the membrane without the endothelium being af fected (fig. 4 ) .
DISCUSSION
We cannot therefore, as yet, make any definite statement as to the causal genesis of these alterations. Hence it would be pointless
TRABECULAR MESHWORK OF HUMAN EYE
811
Cormoscktu
lyaheadae
\Trabeadae
Fig. 9 (Rolien and Unger). Autolytic test. Both figures represent the same eye. (Ahove) Fixed im mediately after enucleation. (Below) After 24 hours storage. Note complete dissolution of basement mem brane by autolysis. (Both pictures X350.) to discuss, at this early stage of our investi gation, the question whether the alterations shown are specifically glaucomatous and whether they are to be considered as primary or secondary processes. More comprehensive investigations have been started upon. The present paper is to give some introductory information and draw the attention to a whole series of ques tions. Teng, Paton, and Katzin have de scribed degenerative changes in the outer most layers of the trabecular meshwork; Franqois, Rabaey, and Neetens, as well as Dvorak-Theobald and Kirk, recently ob served a trabecular hypertrophy in eyes with
glaucoma. It is, however, a well-known fact that the fibers of the meshwork become thicker and "sclerosed" with advancing years or with glaucoma. Henderson speaks of a homogeneous sub stance similar to that composing Descemet's membrane, which is laid down more and more by the covering cells with each advanc ing decade. In some cases of glaucoma, histologically investigated, the meshwork showed a homogeneous structure with no interstices (Greeves, Polya, Sarti, Tartuferi) ; in other ones, the interspaces were replaced by a structureless homogeneous substance (de Vries).
812
J. ROHEN AND H.-H. UNGER
In connection with his description of a chamber-lining "glass-membrane" in glaucomatous eyes Reese thought the endothelium to be capable of its production under certain provocations. This cuticular product of the endothelial cells sometimes is laid down primarily in the interstices of the trabeculae; and the tendency is for the inner la mellae to be affected more than the outer. This may be the cause of the trabecular ob struction. It seems possible that Reese's find ings are similar to ours but the figures in his paper only show that the trabecular area is replaced by homogeneous tissue sparse in nuclei. These alterations are not exactly those which we are trying to describe. Due to the nature of the material used by Teng, Paton, and Katzin (eye-bank eyes) the basement membrane disintegrates com paratively easily and disappears almost com pletely by autolysis. Therefore we have car ried out fixation and autolysis experiments. One result can be seen in Figure 9. After the globe had been kept cool for 24 hours, the basement membrane had diminished to a large extent (fig. 9-b). This fact is another indica tion of the affinity to other basement mem branes in the organism where solubility is ex tremely important for metabolism and perme ability. If one considers the main part of the mesh work as an "endothelial basement mem brane system," the genesis of some symptoms might possibly be interpreted as a conse quence of an alteration of this system, in which process the chemically unstable basic
substance of the meshwork reacts with vari ous effects by various degrees of solubility. SUMMARY
We investigated the structure of the tra becular meshwork and some of its pathologic reactions. It was to be seen that the equato rial elastic reticulum which represents the mechanical basis of the trabeculae changes very little in case of disease, while the endothelium and the "glass membrane" connected with it show characteristic reactions. The endothelium is capable of vital storage and hence ought to be designated as retothelium. The cells are able to increase, multiply, and desquamate, with structural alterations becoming evident. The "glass membrane" is comparable to a basement membrane and can react by an in crease of substance in various cases of glau coma, as well as in globes enucleated because of tumors or perforating injuries. In eyes with absolute glaucoma this process reaches extreme degrees, so that in this way, too, the angle becomes obliterated. This must be dis tinguished from the reactions of a central ground substance lamella which envelops the elastic fibers of the trabeculae. The increase of the resistance to outflow might thus be ex plained morphologically. In agreement with Graumann and Rohen we suppose the exist ence of an "endothelial basement membrane system" for which laws similar to those for the wall of the capillaries may be valid. Schumannstrasse 14.
REFERENCES
Amsler, M., Huber, A., and Verrey, F.: L'humeur aqueuse et ses fonctions. Paris, Masson & Cie., 1955. Ashton, N., Brini, A., and Smith, R.: Brit. J. Ophth., 40:257, 1956. Busacca, A.: Elements de gonioscopie normale, pathologique et experimentale. Sao Paulo, Rossolillo, 1945. Calmettes, Deodati, Planel, and Bee: Etude histologique et histochemique de I'epithelium anterieur de la cornee et de ses basales. Arch. Ophthal., 16:481, 1956. Flocks, M.: Arch. Ophth., 56:708, 1956. Francois, J., Rabaey, M., and Neetens, A.: Arch. Ophth., 55:488, 1956. Graumann, W., and Rohen, J.: Chemohistol. Befunde am menschlichen Auge (Cornea, Sklera, Uvea), Ztschr. mikrosk.-anatomische Forschung, in press. Greeves, R. A.: Proc. Roy. Soc. Med. London, Sect. Ophth., 7:112, 1913/14. Henderson, T.: Ophth. Rec, 17:534, 1908. : Glaucoma, London, Edw. Arnold, 1910, pp. 34-38. Kurus, E.: Vers. d. Vereinigg. Rhein-Main. Augenarzte, Frankfurt/M. 1./2. 12. 1956. Polya: Ungar. Beitrage, 2:319, 1899. (Quoted by de Vries.)
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Reese, A. B.: Am. J. Ophth., 27:1193, 1944. Rohen, J.: Die funktionelle Gestalt des Auges und seiner Hilfsorgane. Verl. d. Akad. d. Wissensch. u. d. Lit., Mainz. Komm. Wiesbaden, Verlag Franz Steiner, 1953. : Ophthalmologica, 131:51, 1956. : Ber. 60. Zusk. Deutsch. Ophth. Ges. Heidelberg. Munchen, J. F. Bergmann, 1956, p. 50. : Arch. f. Ophth., 158:310, 1957. Rohen, J., and Unger, H. H.: Anat. Anz., 104:287, 1957; 105:93, 1958. Sarti, V.: Bull. sc. med. Bologna, 4:147, 1893. (Quoted by de Vries.) Stieve, H.: Der Einfluss des Nervensystems auf die Geschlechtsorgane. Stuttgart, Thieme, 1955. Tartuferi, F.: Giorn. Acad. med. Torino, 30:624, 1882. Teng, C. C., Paton, R. T., and Katzin, H. M.: Am. J. Ophth., 40:619, 1955. Theobald, G. D., and Kirk, H. Q.: Am. J. Ophth., 41:11, 1956. Unger, H. H.: Klin. Wschr., 34:927, 1956. : Deutsch. Ophth. Ges. Heidelberg, Munchen, J. F. Bergmann, 1956, p. 59. : Klin. Wschr., 35:199, 1957. : Arch. Ophth., 158:509, 1957. : Klin. Monatsbl. f. Augenh., 131:385, 1957. : Klin. Monatsbl. f. Augenh., 131:692, 1957. Unger, H. H., and Rohen, J.. Ber. gi. Zusk. Deutsch. Ophth. Ges. Heidelberg, Munchen, J. F. Berg mann, 1957, p. 256. Virchow, H.: Graefe-Saemisch, Handbuch Augenh., Leipzig, Engelmann, 1910, v. 1, p. 281. Vrabec, F.: Ophthalmologica, 128:359, 1954. : Brit. J. Ophth., 41:20, 1957. de Vries, W. M.: Nederl. Tijdschr. v. Geneesk., 43:1688, 1907. Watzka, M.: D. Ovarium, Handb. mikrosk. Anat. d. Menschen. Bargmann, v. Moellendorf, 1957, Suppl. of VII/1.
NEWER OPTICAL AIDS FOR CHILDREN W I T H LOW VISION* JAMES E. LEBENSOHN,
M.D.
Chicago, Illinois
A major campaign of the National Society for the Prevention of Blindness stresses the theme that all persons, especially children, must be given every opportunity to utilize fully whatever sight they possess. Of the 33.5 million in the school popluation of the United States, 8.5 million require eye care for adequate far and near vision. Sightsaving classes for children with a correctible acuity of only 20/70 to 20/200 have an en rollment of 60,000. These partially seeing children respond well to appropriate methods of visual educa tion. Our recognition of their special educa tional status is due in great part to the late Mrs. Winifred Hathaway whose unique monograph, "The Education and Health of the Partially Seeing Child," published post humously in 1955, is a fitting memorial of a life devoted to this cause. * From the Department of Ophthalmology, North western University Medical School. Read before the International Council for Exceptional Children, Kansas City, Missouri, April 9, 1958.
Approximately five percent of the legally blind in this country, or about 15,000, are under 20 years of age. Of these 60 percent have a little sight, which ranges from vague light perception to 20/200 in the corrected better eye. Amblyopia, or uncorrectible poor vision, is more prevalent in rural than in urban areas; and in Negroes, Mexicans, and Indians than in white children. Among Ne groes the ratio is at least double that in the white population. At present about 60 percent of the ambly opia in children is of prenatal origin. Pre maturity by itself, even when not resulting in retrolental fibroplasia, frequently deter mines amblyopic myopia. Infective diseases account for over 20 percent; accidents for about 10 percent. The danger from accidents cannot be overemphasized; more children from one to 14 years of age die from acci dents than from all known childhood dis eases. Most students with normal intelligence and motivation who have sufficient vision to walk