BIOPSY O F T H E TRABECULAR MESHWORK* I N 50 CASES OF CHRONIC PRIMARY GLAUCOMA H.-H.
UNGER, M.D.,
AND J. ROHEN,
M.D.
Freiburg im Breisgau, Germany
Tissue disks obtained by Elliot's trephin ing operation may be used as a biopsy ma terial (Unger, 1956, 1957). By this method we examined the trabecular meshwork of more than 50 glaucomatous eyes. With this paper we continue our studies on the morphology and pathology of the trabecular meshwork in the human eye (Rohen and Unger), and on the structure of the inner wall of Schlemm's canal (Unger and Rohen). Fundamental results about the cause of increased resistance to aqueous out flow are still lacking. We have recently demonstrated that, in cases of absolute glaucoma,1- there are two places within the meshwork where morpho logic alterations may originate: 1. On the ground substances (glass mem brane) enveloping the central core of the trabecular beams (enormous thickening of these substances, loss of the usual staining affinity, decrease of reactivity to peroidate, and so forth). 2. On the inner wall of Schlemm's canal (alterations of a degenerative nature, circumscript cellular proliferations). Biopsy material now gives us the oppor tunity to examine early and less progressive glaucomas in tissues which are unchanged by autolysis. We used the same methods for histologie preparation as described in our previous papers. From 150 to 200 sections of each Elliot trephination (corneoscleral disk) were examined, a total of over 10,000
sections. Table l shows the clinical data and the histologie findings. So far we have obtained Elliot's trephinations from 140 eyes; 58 disks contained a small part of Schlemm's canal and the adja cent meshwork; 82 showed only Descemet's membrane and the top of the trabeculae joining the deep corneal lamellae. The latter were unfit for our investigations. Our report refers to 50 patients (24 eyes with chronic congestive glaucoma, 34 eyes with simple glaucoma; eight patients have had operations on both eyes). Out of 20 patients with chronic congestive glaucoma only 10 had glaucomatous atrophy but these 10 were not quite identical with those who had an altered meshwork. Seven had an extensive loss of visual functions. The average age was less than in the cases with simple glaucoma. In contrast to that, 21 out of 34 eyes with simple glaucoma showed glaucomatous atro phy but 25 eyes had an acuity which was better than 5/10. In only one case were heavy histologie alterations combined with nearly normal clinical data. On the other hand, two eyes with progressive glaucoma had an unchanged inner wall of Schlemm's canal and unchanged trabeculae within the trephined region of the filtration angle. Of all those with simple glaucoma only six pa tients (44, 51, 56, 64, 78 and 81 years of age) had an unaltered meshwork. We got the impression that our biopsy re sults may be divided into different phases but we can only give some descriptive ex amples drawn from our research. Each ex ample represents a group of exactly the same or nearly similar alterations: 1. Thickening of the trabecular glass membranes with or without intertrabecular
*From the Department of Ophthalmology, Uni versity of Freiburg im Breisgau, Director: Prof. Dr. W. Wegner, and the Institute of Anatomy, University of Mainz, Director: Prof. Dr. A. Dabelow. t Rohen, J., and Unger, H.-H. : Zur Morphologie und Pathologie der Kammerbucht des Auges. Verl. d. Akad. d. Wissensch. u. d. Lit, Mainz, Verlag Franz Steiner, Wiesbaden, 1959. 37
TABLE 1 CLINICAL DATA AND HISTOLOGIC FINDINGS
V my
V»
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s 3
e
tu
te
ttl
w
ni
U 93 8 34 40 98 89 13 137 50 83 55 58 54 62 107 59 27 30 91 123 136 68 108 94 10 32 135 28 47 129 7 38 87 126 81 128 106 104 118 17 105 141 121 9 36 44 127 113 66 120 122 124 116 117 101 2 84 102
O.H. A.K. L.B. O.R. W.K. E.G. K.T. A.L.
J.O.
F.K. H.K. H.K. M.T. M.T. T.S. M.B. W.S.
w.s. E.F.
J.K. J.K.
A.N. M.M. A.Z. E.M. E.M. S.G. K.S. M.B. H.R. B.H. K.L. M.S. E.S. F.S. L.W. A.R. M.R. E.K. B.S. E.A. E.A. E.M. E.M. H.G. H.G. F.S. L.K. L.L. F.S.
J-T.
S.H. M.K. M.K. K.B. O.S. F.O. A.V.
c? 9 9 9
48 39 54 58 62 61 72 63 71 76 41 41 65 65 46 53 59 59 43 55 55 52 47 60
r 1 r 1 1 r r 1 r r 1 r 1 r 1 r r 1 1 1 r 1 r r
9 9 9 9 9 9 9 9 9 9 9 9 9 o" 9 9 9 o* o" 9 9 c? cf 9 c? V 9 9 9 9 cf 9 o*
44 44 69 64 56 55 61 51 69 63 51 59 64 57 47 59 72 72 54 64 79 79 68 69 61 68 70 77 73 73 81 78 70 76
r 1 r 1 1 1 r 1 r r r r r r 1 r 1 r 1 1 1 r r 1 r 1 r r 1 r r 1 r 1
c? 9 9 cf c? 9
&
9 9 o" 9 9 9 9 9 9 c?
& &
c _g o a tu
Pi
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<
a. CHRONIC
ω c 'S. a 3
1
2
+3
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J3 t/3 u o
2 E
O
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X M
GLAUCOMA
E E H E H H M H H M E E E E E E M E E M M E E E
5/3 5/4p 5/5 5/5 5/4p 5/5p S/7p 5/4 5/5 5/7p 5/4p 5/4 5/5p 5/5 5/5 5/7p 5/10 5/3p 5/15 5/15 5/4 5/20 5/50 1/50
E E H M M M H E E H E H E H E H E E M H M M M M H M H M E E E M E ?
b. SIM PLE GLtIUCOMA 5/4 5/5 5/4 5/5p + 5/5p + 5/4 + 5/4p + 5/4p + 5/5 + 5/5p + 5/4p + + 5/4p + + 5/7p + + 5/4 + + 5/4p + + 5/Sp + + 5/5p + + 5/5 + 5/5p + + 5/7 + + 5/7 + + 5/7 + + 5/7 + + 5/7p + + 5/10p + + 5/10p + + 5/15 + + 5/15 + + 5/7.« + 5/20 + 3/50 + + 1/20 + + 1/50' + + FC. + +
+ + + + + + + + + + + + + + + + + + . + + + + + + + + + + + + +
+ + + + ++ ++ + ++ ++ ++ ++ ++ ++ + +++ +++ +++
+ +
+ + ++ + + + ++ ++ ++ ++ + ++ ++ ++ ++ ++ ++ ++ ++ ++ ++ ++ ++ ++ ++ + ++
+ + +
+ +
+
+
+
+ +
+ +
+ +
4-
+
+
+ + + + + + + + + + +
+
+
+ + + + + + + + + +
+
+ +
+ +
+ + + + + + + + + + + +
+ = blind spot enlarged, Bjerrum skotoma; small narrowing of nasal field. + + =loss of nasal field; Bjerrum scotoma; center spared. 4-++=extensive field loss.
+ + +
+ + + + + + +
+ + +
+
+
+
Fig. 1 (Unger and Rohen). Medium-power view of 10 selected sections through Elliot trephinations, showing different phases of glass-membrane changes with or without intertrabecular adhesions. (Stieve, hematoxylin-eosin. )
C. Sdii.
Φ&ΤΪΪΑ
Fig. 2 (Unger and Rohen). Medium-power view of 10 selected sections through Elliot trephinations, showing changes at the inner wall of Schlemm's canal. Slight multiplication of endothelial cells, excessive tumorlike proliferation and degenerated tissue in compact form. (Stieve, hematoxylin-eosin.)
BIOPSY OF TRABECULAR MESHWORK
41
E.A.
Fig. 3A (Unger and Rohen). Visual fields in Case 105, E. A., 9, aged 72 years, simple glaucoma. adhesions and conglutination of lamellae. If synechias have set in, they are first seen in the vicinity of Schlemm's canal. Then the outermost interstices are narrowed or ob structed (figs. 1, 3B, and 3C). 2. Circumscript proliferations of endothelial cells in the inner wall area of the canal of Schlemm (fig. 2). At least two types of cells can be noted there: a. Cells with plump, pale nuclei which ap pear to be enlarged. These cells are to be found more often with proliferative altera
tions of the inner wall of Schlemm's canal. b. Cells with dark nuclei of various shapes. There were four disks from Elliot trephinings in our material with excessive cir cumscript proliferations (figs. 4B and 4C). 3. Gradual disintegration, hyalinization and loss of the meshwork's normal architec ture, especially in old proliferative zones. Most of the trabeculàe are replaced by ho mogeneous tissues sparse in nuclei (fig. 2,bi opsy 120). These changes are well known to
bi 105
weshwork Fig. 3B (Unger and Rohen). Case 10S. Sagittal section of Elliot disk (left eye).
42
H.-H. UNGER AND J. ROHEN
Fig. 3C (Unger and Rohen). Case 105. High-power view of trabeculae, showing swelling of the glass membrane. The trabecular spaces are in good condition. There is a striking circumscript thickening and a foamy appearance of the inner wall area of Schlemm's canal. (Figures 3B and 3C, Stieve, hematoxylin-eosin.)
us from previous study of absolute glau coma. This succession of findings (1-3) does not attempt to classify the pathologic phases. It is possible that disintegration precedes proliferation and vice versa. This paper is considered to be a preliminary report. It is impossible to state definite correlation between histologie and clinical findings on only 50 cases of glaucoma but when we con sider the evidence in Table 1, it appears that pathologic changes of the meshwork occur more frequently with simple glaucomas than with congestive types and more frequently with older glaucomas than in the early stages. To a much lesser degree, these trabecular findings can be present in normal eyes of
individuals of advanced age (Rohen and Un ger). Histologie examinations of the chamber angle of glaucoma tous eyes have been made by many authors. They investigated enucle ated eyes with absolute glaucoma or tissues from post-mortem material. In a previous paper (Rohen and Unger), we have dis cussed the findings of Tartuferi, Sarti, Polya, de Vries, Henderson, Greeves, Rones, Duke-Elder, Reese, Teng, Paton and Katzin, Theobald and Kirk, François, Rabaey and Neetens, et al. In the meantime new re sults which refer to this subject have been reported by Kornzweig, Rohen and Unger, Kornzweig, Feldstein, and Schneider, Teng, Katzin, and Chi, Flocks, Kurus, et al. We
5/15 Fig. 4A (Unger and Rohen). Visual fields in Case 124, S. H., 9, aged 77 years, simple glaucoma.
BIOPSY OF TRABECULAR MESHWORK
43
bi t24
Fig. 4B (Unger and Rohen). Case 124. Sagittal section of Elliot disk (right eye). think that our findings in a certain degree are similar to those of Flocks (one case of early glaucoma), Kornzweig, et al. (seven cases of early glaucoma), as well as the very im portant findings of Teng et al. (four cases of early glaucoma) as far as we can compare with the excellent figures given in his last paper. We think it is too early to speak about histologie findings of the meshwork as etio-
logic factors of glaucoma. Further careful studies must be made. It is most probable that within the mesh work, the main impediment to aqueous out flow is represented by the inner wall of Schlemm's canal. Therefore, we have a spe cial interest in the pathology of this region. We agree with Vail that the pathologic findings of the trabecular meshwork in cases
J3M8ffCUZ.4*\ Fig. 4C (Unger and Rohen). Case 124. High-power view of Schlemm's canal. Trabecular glass mem branes are slightly thickened. There is a tumorlike proliferation of endothelium in the region of the inner wall. (Figures 4B and 4C, Stieve, hematoxylin-eosin.)
H.-H. UNGER AND J. ROHEN
44
of simple glaucoma are of a degenerative na ture. They may contribute to the increase of resistance to the aqueous circulation, thus making glaucoma worse. CONCLUSION
Fifty-eight corneoscleral disks of Elliot trephinings (from SO patients) have been examined for histologie alterations of the trabecular meshwork with early and less progressive glaucoma (chronical congestive glaucoma: 24 eyes; simple glaucoma: 34 eyes). Especially in progressive cases of simple glaucoma two types of biopsy alterations can be observed:
1. Changes of the glass membrane of the trabeculae, with or without intertrabecular adhesions. 2. Changes of the inner wall of Schlemm's canal with or without circumscript prolifera tion of endothelial cells. Four cases showed an excessive, tumor like increase in the number of cells. In one case the meshwork was replaced by amor phous tissues. These alterations are of a degenerative nature. It is probable that they contribute to the obliteration of the intertrabecular aque ous passages. Schumannstrasse 14.
REFERENCES
Duke-Elder, S. : Textbook of Ophthalmology. St. Louis, Mosby, 1941, v. 3, p. 3341. Flocks, M. : Tr. Am. Acad. Ophth., 1958, p. 556. François, J., Rabaey, M., and Neetens, A. : Arch. Ophth., 55 :488, 1956. Garron, L. K., Fenney, M. L , Hogan, M. J., and McEwen, W. K.: Am. J. Ophth., 46:27,1958. Greeves, R. A. : Proc. Roy. Soc. Med. London, Sect. Ophth., 7 :112, 1913-14. Henderson, T. : Ophth. Ree, 17 :534, 1908. : Glaucoma, London, Arnold, 1910, pp. 34-38. Kornzweig, A. L. : Ophth. ibero-am., 18 :12, 1956. Kornzweig, A. L., Feldstein, M., and Schneider, J. : Am. J. Ophth., 46:311, 1958. Kurus, E. : Klin. Monatsbl. f. Augenh., 132:201, 1958. Polya: Ungar. Beitr. 2:319, 1899. Reese, A. B. : Am. J. Ophth., 27 :1193, 1944. Rohen, J., and Unger, H.-H. : Am. J. Ophth., 46:802, 1958. — : Zur Morphologie und Pathologie der Kammerbucht des Auges. Mainz, Verl. Akad. Wiss. Lit., Wiesbaden, Franz Steiner, 1959. Rones, B.: Am. J. Ophth., 21:239, 1938; 45:189, 1958. Sarti, V. : Boll. se. med. Bologna, 4:147, 1893. Tartuf eri, F. : Giorn. Acad. med. Torino, 30:624, 1882. Teng, C. C, Paton, R. T., and Katzin, H. M. : Am. J. Ophth., 40 :619, 1955. Teng, C. C, Katzin, H. M., and Chi, H. H.: Am. J. Ophth., 43:193, 1957. Theobald, G., and Kirk, H. Q. : Am. J. Ophth, 41:11, 1956. Unger, H.-H. : D. O. G. Heidelberg, 1956, München, Bergmann, 1957, p. 59. — : Arch. Ophth, 158:509, 1957. Unger, H.-H, and Rohen, J.: Am. J. Ophth, 48:204, 1959. Vail, D. : Year-Book of Ophthalmology, Chicago, Year-Book, 1958, p. 288. de Vries, W. M. : Nederl. Tijdschr. v. Geneesk, 43 :1688, 1907.