ACTA OPHTHALMOLOGICA V O L . 42 1964

From the Eye Hospital, University of Helsinki (Head: Prof. S. Vannas, M . D.)

and the Institute of Human Genetics of the Sanzfundet Folkhiilsan

EMBRYOTOXON CORNEAE POSTERIUS I N AN ISOLATED POPULATION")

BY

Henrik Forsius, Aldur Eriksson and Johan Fellman

In 1920, Axenfeld described a narrow, grey-white border on the inner surface of the cornea, adjacent to the limbus, which he had detected in a young man. He called it embryotoxon corneae posterius (ECP). Later, the names peripheral refractile post-corneal rim, dysplasie marginale posterieur and anterior or pro- minent border-ring of Schwalbe were suggested. ECP occurs either as a phy- siologically insignificant anomaly, in which case it is detectable only with the slit-lamp as a narrow margin in one or both eyes, as a rule temporally, or as a more prominent border-ring, which often extends further onto the inner surface of the cornea and occasionally completely surrounds the limbus. I t is then frequently observable with the naked eye and has been described in association with many serious ocular anomalies. The occurrence of ECP in connexion with pathological conditions will be discussed in another paper (Forsius & Eriksson).

Histologically, ECP consists of collagenous tissue. Fritz (1906), who studied a large number of eyes histologically, detected ECP in 20 per cent of his material. Seefelder (1910), however, observed it in a much smaller proportion of histologically investigated eyes. In 1949, Streiff showed that ECP is a visible anterior border-ring of Schwalbe, a finding which was confirmed by Burian, Braley & Allen in 1955. Streiff estimated the frequency of histological- ly observable ECP as 20-30 per cent or more. Burian, Braley & Allen de- tected ECP in 72 out of 600 eyes.

Embryologically, ECP is discernible as early as the 6th foetal week (Gastei- ger 1939, Streiff 1949). In foetuses measuring 91 mm the incidence of ECP is the same as in adults (Burian, Braley PC Allen).

Supported by a grant from the Sigrid Jusklius Stiftelse, Helsingfors, and by grant No. 1582 from the Wenner-Gren Foundation for Anthropological Research, Inc., New York.

") Received September 10th 1963.

42

Gonioscopically, this anterior border-ring of Schwalbe was observed by Koeppe as long ago as 1920. Werner (1932) reported that he had sometimes even seen a double ring. Iris synechiae to this ring are common. The first description of anterior synechiae to ECP detected by gonioscopy was published by Bussaca & Pinticart (1948), who made this observation in a patient with hypoplasia of the iris.

The prominence is sometimes fringed with floating filaments (Gasteiger, Streiff). Occasionally ECP is absent in one eye, while the other has a marked arc with or without changes of the iris (Forsius and Eriksson). ECP often occurs in association with gross errors of refraction (Forsius 1960; Forsius and Eriksson).

ECP without other ocular anomalies was first described biomicroscopically by Graves (1934) and Biozzo 8c Lugli (1935).

In a clinical investigation Streiff estimated the incidence of ECP as 20-30 per cent, and Burian, Braley & Allen as 15 per cent. Later, the latter authors also reported that they had diagnosed ECP histologically in 12 per cent of cases. In an investigation of 700 subjects, performed by Marty in 1957, thz frequency was 18.9 per cent. In 68.2 per cent of the subjects exhibiting ECP. both eyes were involved. The anomaly was never associated with glaucoma or with hypoplasia of the iris. I t was only encountered in conjunction with ordinary senile atrophy of the iris in the higher age groups. Neither Streiff nor Marty detected any sex difference or any definite age bias. Without giving any figures, both these authors stated that ECP occurs more often temporally than nasally.

When ECP is associated with anomalies of the iris, a marked dominant heredity of the trait has been demonstrated by many authors. By contrast, the available data regarding the heredity of uncomplicated ECP are few. Biozzi & Lugli (1935) found the anomaly in two successive generations, and independent of sex. Burian, Braley 8c Allen (1935) too, stated that they had observed a familial concentration. Waardenburg (1961) observed it in a mother and daughter and in a father and daughter. No pedigrees have been published.

MATERIAL

In an extensive investigation of the population in an isolated area in the region of the Aland Islands - the archipelago of Kokar, situated in the Baltic, south-west of the Finnish mainland - a total of 498 subjects were examined with a Haag-Streit slit-lamp for the presence of ECP. The results relating to refraction, corneal radius, arcus senilis, degeneration of the ocular fundus, blood groups, etc., are reported separately. The series is not selected, since our purpose was to examine as many subjects as possible. In winter the population

43

Fig. 1. The frequency of embryotoxon corneae posterius in a t least one eye among 498 sub-

jects. The frequency decreases with age. (z' = 21.6, n = 7, p < 0.01).

of Kokar is about 400, but in summer a large number of persons domiciled in Kokar return there. These non-residents have been included in the series.

RESULTS A N D DfSCUSSlON

Fig. 1 shows that the incidence of ECP decreases with age, although this de- crease is probably only apparent, increasing corneal opacities, arcus senilis and growth of the conjunctiva onto the cornea tending to interfere with the diagnosis of ECP. The frequency is somewhat lower in the youngest age group, but this is attributable to technical difficulties. Since a young child cannot be very accurately examined, mild cases may escape recognition.

In 18 eyes there was an astigmatism of 3 D or more. Ten of these eyes showed an ECP and 2 eyes peripheral corneal opacities.

In order to study the heredity of ECP, a series of families consisting of father, mother and at least one child was subjected to closer analysis. The total number of subjects investigated was 249, and these belonged to 73 different families.

Peripheral opacity of the posterior surface of the cornea was classified into 9 different types, as appears in Fig. 2 and Table 1. Since the distribution was almost identical for men and women, the tables for the two sexes have been combined. A total of 267 eyes out of 498 were free from peripheral opacities of the posterior surface of the cornea.

Of the female eyes, 150 entirely lacked peripheral corneal opacities, 39 exhibited only peripheral cornea! opacities, and 87 eyes out of 276 (31.5 O/o)

had definite ECP. Of the male eyes, 31 showed peripheral corneal opacities, and 74 eyes out

of 222 (33.3'0/0) had definite ECP.

44

Table 1. The occurrence of peripheral opacities on the posterior surface of the cornea, classified into 9 different types, as appears in Fig. 2. The figures for men and women are com- bined, since the distribution was almost identical in the two sexes. R = right eye,

L = left eye.

1 2 3 4 5 6 7 8 9 x 267 8 2 1 19 5

1 1 303

60.84

1 9 2 2 3 1 5 2 2 54 2 10.84

3

2 1 11 1 2 2 19 4 3.82

21 10 1 4 39 7 5

6 1 1 3 1

5 87 17.47

6 1.20

1 2 1 3 2 9 1.81 7

8 1 1 1 1 4

0.80

7 2 2 4 16 3.21

310 44 7 20 75 18 7 2 15 498 62.25 8.83 1.41 4.02 15.06 3.61 1.41 0.40 3.01

T E M P O R A L N A S A L - @@@@@@@@G 1 2 3 4 5 6 7 8 9

Fig. 2. Embryotoxon corneae posterius in the right eye, showing different types of corneal opacity and the classification into types used in the text and tables. The dotted lines indicate weak, non-prominent opacities in the posterior periphery of the cornea. The solid line indicates definite embryotoxon corneae posterius (ECP), i. e., a prominent grey arc. In the left eye the numbering is the reverse of that in the right eye, no. 5 ,

for instance, meaning temporal ECP.

(2*3) (5*3) (6.2) (5+6)

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Table 2. Influence of the father on the occurrence of symptoms in the son.

2 2 - 6.09, p < 0.05.

Father

1 2 - 9

1 16 2 18

v, 2 - 9 17 17 34

33 19 52

s

Table 3. Influence of the mother on the occurrence of symptoms in the son.

,ys N 3.23.

Mother

1 2 - 9

31 27 58

Table 4. Influence of the parents on the occurrence of symptoms in the son.

12 - 6.78, p < 0.01.

Father - Mother

1 2 - 9

18 27 45

In Table 1, the two eyes are compared. As a rule, the occurrence of the same symptom in both eyes is more common than the average frequency suggests, as appears from the fact that the majority of cases are grouped around the diagonal. A comparison of groups 2 and 5 reveals no positive

46

Table 5 . Influence of the father on the occurrence of symptoms in the daughter.

12 N 0.832. - ~ _ _ _

Father

1 2 - 9 I. 3 1 23 5 28 f M 3 2 - 9 24 9 33 CI

47 14 61

Table 6. Influence of the mother on the occurrence of symptoms in the daughter.

x* - 0.044.

Mother

1 2 - 9 k

0 1 14 13 27

23 21 44

37 34 7 1

5 2 - 9

CI

Table 7. Influence of the parents on the occurrence of symptoms in the daughter.

p ff 0.022.

Father - Mother

1 2 - 9

22 35 57

correlation. Thus, a posterior peripheral corneal opacity does not seem to be a milder degree of ECP. ECP occurs much more often temporally than nasally (139 eyes against 50).

In Tables 2-7 the correlation between parents and children can be studied. The eyes are classified into two groups, i. e. one in which ECP is entirely lacking and one exhibiting ECP (peripheral corneal opacities included).

41

Tables 2-4 show that if one of the parents has symptoms of ECP, there is a weak tendency for the sons to show the same symptoms. On the basis of the statistical treatment of the data it may be concluded that the father is probably of greater importance. Tables 5-7 seem 'to indicate that there is no correlation between the occurrence of ECP in the parents, on the one hand, and in the daughters, on the other.

The present study reveals no sex difference in the occurrence of ECP, which confirms the results of Streiff and of Marty. A tendency towards a decreased incidence of ECP in the highest age groups, such as was observed by Marty, is also detectable in the present series, but this is probably only apparent. No explanation for the fact that ECP is much more common temporally than nasally was afforded by this study. ECP is seldom seen in the lower quadrant of the cornea, and very seldom in the upper quadrant. ECP around the whole of the cornea was not seen in any of the subjects examined.

Since the incidence of ECP is the same in men and women, we expected the correlation with parents to be the same for the sons and the daughters. This was not the case, however.

The chamber angle is formed by the interaction of two germ layers, the mesoderm and the ectoderm, which mutually influence each other. As has been shown by Collier and Forsius PC Erjksson, for instance, ECP occurs in conjunction with ocular anomalies of both mesodermal and ectodermal origin. I t seems possible that the development of ECP in healthy eyes, too, is due to both ectodermal and mesodermal causes.

The series includes one family in which both parents exhibit ECP (type 5 ) without any of the three children showing the anomaly in any form. I n several families the parents lack ECP (type I) , while the children exhibit the anomaly to a more or less marked degree. This finding seems to be evidence in favour of recessive heredity. I t should be added that very conspicuous embryotoxon (type 9) was present in 3 children in a family in which one of the parents had a similar type of ECP.

SUMMARY

The incidence of embryotoxon corneae posterius (ECP) was investigated in 498 subjects in an isolated population in the archipelago of Kokar, which forms part of the Aland Islands (Finland). The incidence of ECP was found to be lower with increasing age, except for the youngest age group. No sex dif- ference was discernible.

A series of families consisting of father, mother and at least one chila (249 subjects) was studied more closely. A visible embryotoxon corneae posterius (32.3 O/O) was present in 161 eyes out of 498. ECP was commoner temporally

48

(being observed in 139 eyes) than nasally (50 eyes). A grey, non-prominent opacity of the posterior surface of the cornea does not seem to be identical with a lower degree of ECP. A study of the correlation between the occurrence of ECP in parents and

children showed that if one of the parents, the father in particular, exhibits ECP, there is a significant tendency for the son also to have the anomaly. With regard to the daughters, no significant correlation was demonstrable. No definitive conclusions can be drawn regarding the heredity of ECP.

REFERENCES

Axenfeld, T.: Embryotoxon corneae posterius. Ber. deutsch. ophth. Gesellsch. 1920:

Biozzi, G. und Lugli, L.: Ringformige, periphere Verdichtung in der Gegend der Descemet. Graefes Arch. Ophth. 1935: 134: 287-296.

Burian, H. M., Braley, A . E. and Allen, L.: Visibility of the ring of Schwalbe and the trabecular zone. A. M. A. Arch. Ophth. 1955: 53: 767-782.

Busacca, A . et Pinticart, de W. E.: Etude gonioscopique d’un cas de Embryotoxon corneae posterius. Ophthalmologica 1958: 115: 283-290.

Collier, M.: La dysplasie marginale postkrieure de la cornke dans le cadre des ano- malies squelettiques et ectodermiques. Ann. ocul. 1962: 195: 512-549.

Forsius, H.: On the refractive power of the cornea and embryotoxon corneae posterius in high degrees of hypermetropia. Acta ophth. 1960: 38: 5-15.

Forsius, H. and Eriksson, A.: Embryotoxon corneae posterius in a family with slit- pupil and in cases with other anomalies of the iris. Acta ophth. 1963: 41.

Fritz, W.: Ober Membrana Descementi und das Ligamentum pectinatum iridis bei den Saugetieren und beim Menschen. Sitxungsber. Kaiserl. Akad. Wissenschaft, Wien 1906: 115: 3. Nagels Jahresber. Ophth. 1907: 38: 13-15.

Gasteiger, H.: Ober die klinische Bedeutung des Embryotoxon corneae posterius. Klin. Monatsbl. Augenh. 1939: 10.2: 876.

Graves, B.: Certain clinical features of the normal limbus. Brit. J. Ophth. 1934: 18:

Koeppe, L.: Die Mikroskopie des lebenden Auges. Springer, Berlin 1920. S. 307. Marty, F.: Les courbes de frkquence en fonction de I’age de quelques altkrations con-

gknitales ou skniles frkquentes du segment anthrieur. These, Geneve 1957. No. 2338. Seefelder, R.: Das Verhalten der Kammerbucht des Neugeborenen. In: Graefe-Sae-

misch: Hdb. Augenh. Aufl. 2. Engelmann, Leipzig 1910. Bd. 1. Anhang zu Kapi- tel 11. S. 29-35.

Streiff, E . B.: Dysplasie marginale postkrieure de la cornke (Embryotoxon posterius Axelfeld) dans le cadre des malformations irido-cornkennes. Ophthalmologica 1949:

Waardenburg, P. /. In: Genetics and ophthalmology. Vol. 1. By P. J. Waardenburg, J. Franceschetti and D. Klein. Koninklijke Van Corcum & Co., Assen, The Nether- lands 1961, p. 575.

Werner, S.: Gonioskopische Untersuchungen bei Glaucoma primarium. Acta ophth.

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49 Acta Ophthalmol. 42, I 4