A C T A O P H T H A L M O L O G I C A V O L . 5 1 1 9 7 3

Oulu University Eye Hospital (Head: Professor H . Forsius), Oulu. Finland

PSEUDOEXFOLIATION OF THE LENS CAPSULE AND LIBERATION OF IRIS PIGMENT

BY

U. KRAUSE, J. HELVE and H. FORSIUS

A total of 220 inmates of old people’s homes, all over 60 years of age, were examined for pseudoexfoliation of the lens capsule. The incidence recorded for the age group 60-69 years was 10°/o, 70-79 years 21.3O/o and 80-89 years 32.8 “/a. The intraocular tension of the eyes with pseudo- exfoliation averaged 17.5 mmHg, against an average of 15.4 mmHg in normal eyes. After mydriatics, pigmented floaters were seen in the aqueous humour of 61.5 O / o of the normal eyes, and 83.3 “/o of the eyes with pseudoexfoliation. In these latter eyes, moreover, the pigment liberation was distinctly more marked. The trabecular region of the af- fected eyes was more pigmented than that of the normal eyes. The mechanism by which pseudoexfoliation possibly affects pigment liberation and trabecular pigmentation is discussed.

Key words: pseudoexfoliation - fibrillopathia epitheliocapsularis - pig- mented aqueous floaters - trabecular pigment - frequency - Finland.

Lindberg (1917) was the first to describe pseudoexfoliation of the lens capsule (hereafter called simply pseudoexfoliation). Figures quoted in the literature concerning its geographical incidence among the normal population range from 0.1 O/O (Egypt) to 48 O/O (Russia) (Maghraby 1937, Hoorgina 1929). Aasved (1969) has reviewed the literature on the occurrence of pseudoexfolia- tion up to 1969. Among the more recent authors, Bartholomew (1970) reports that pseudoexfoliation is “by no means uncommon in Southern Bantu”, and Faulkner (1971) found it in 380/0 of Navajo Indians aged 60 years or more.

Received September 7, 1972.

U. Krause, 1. Helve and H . ForAius

Forsius & Luukka (1972) reported pseudoexfoliation among old Skolt Lapps (aged 70-79 years) in northern Finland, quoting an incidence of 30.7 O/O. On the other hand, population studies among the Eskimos in Alaska, Greenland and Canada revealed no cases of pseudoexfoliation.

The wide differences between the incidence figures quoted in the literature may be due to the selection of the material studied, e.g. hospital series or gene- ral population, and the age distribution (Aasved 1969). In a later study, Aasved (197 1) reports that the incidence of pseudoexfoliation in subjects aged 40-49 years is 0 O/O but in those aged over 80 it is 7.6 O/O. If, furthermore, the clinical picture of the disease is not adequately known, and unless particular attention is given to its existence, the incidence figures obtained are erroneous. I t has, in fact, proved necessary to correct earlier, incorrect numerical data for several countries (Aasved 1969).

Vogt (1925), Pillat (1934) and Bard (1935) have described how, in glauco- matous eyes with pseudoexfoliation, mydriasis caused an excessive liberation of pigment floating in the aqueous humour. According to Tarkkanen (1962), the phenomenon can only be noted in eyes with pseudoexfoliation. Mitsui & Takagi (1961) reported that sympathomimetic mydriatics induced pigmented floaters in the aqueous in 4.6 O/O of eyes without any signs of iritis. Kristensen (1965) has said that pigmented floaters are noted in connection with mydriasis in 79 O / o

of the eyes without glaucoma or iritis. The older the patients examined, the more frequent and the more distinct is the phenomenon (Mitsui & Takagi 1961, Kristensen 1965, Aggarwal & Beveridge 1971). The mydriatic-induced pigmented floaters are 1.0-1.5 ,um in diameter. A maximum of floaters appears 1-2 hours after mydriasis, and they disappear from the aqueous humour in 12- 24 hours. The particles are apparently pigment granules from the pigment epithelium cells, according to Mitsui & Takagi (1961). Excessive pigment libe- ration may produce a rise of the intraocular tension in the eyes with open- angle glaucoma, but the mechanism in this case is different from that in the water provocative test (Kristensen 1965, 1968). The chamber angle may often be heavily pigmented in pseudoexfoliation (Petersen 1958, Tarkkanen 1962, Sugar 1966, Herven & Hutchinson 1967). In unilateral pseudoexfoliation, the chamber angle of the affected eye is often more heavily pigmented than that of the fellow eye (Tarkkanen 1962). Mitsui & Takagi (1961) found that in the patient in whom mydriasis produces profuse pigment liberation, the degree of trabecular pigmentation is greater than in persons without this liberation.

The purpose of the present work was to study the incidence of pseudoexfolia- tion among the older age groups in Finland and to analyse the possible cor- relation of the disease to pigment liberation by mydriasis and to the trabecular pigmentation.

40

Pseudoexfoliation and Liberation of Iris Pigment

Material and Methods

The series consisted of 220 persons, 98 men and 122 women. They were selected at random from the Old People’s Homes of the City of Oulu and the sur- rounding communes. The place of birth of the participants was recorded in order to ascertain whether the series could be characterized as an isolate. The mean age of the series was 75.6 years, men 74.7 and women 76.4 years.

Every eye, as far as possible, was examined as follows. First, the number of pigmented floaters in the aqueous humour was estimated using the classification proposed by Mitsui (1943) (Table I). A Haag-Streit 900 slit lamp, with 16-fold magnification, was used; the slit was 2 mm high and the width screw in posi- tion 10 (Kristensen 1968). The intraocular tension was measured with an ap- planation tonometer and the grade of trabecular pigmentation was evaluated according to the principle of Becker 8c Schaeffer (1965), with grade 0 corre- sponding to unpigmented and grade 4 to a very heavily pigmented trabecular meshwork. A mean value of the figures indicating pigmentation a t 12, 3, 6 and 9 o’clock was calculated for each eye for further statistical analysis. Signs of pseudoexfoliation were sought in the pupillary margin, lenticular surface, and the posterior corneal surface. One to two hours after instillation of my- driatics (Phenylephrine 10 O/O and Tropicamide 1 O/O) the intraocular tension was measured, and the number of the pigment floaters present was evaluated using the classification described above. Signs of pseudoexfoliation were again sought using the method described. Only definite findings were recorded as positive.

The scheduled series of examinations could be carried out, almost completely, on 206 patients.

Table I . Scale of pigmented floaters in the aqueous humour (Mitsui 1943).

Grade Number of floaters

0 No floaters. 1 2 3 4 5 6

One or more floaters in the whole aqueous humour. One or more floaters within the range of a single beam. About ten floaters within the range of a single beam. Up to a hundred floaters within the range of a single beam. Hundreds of floaters within the range of a single beam. Innumerable floaters within the range of a single beam.

41

U . Kmuse , J . Helve and H . Forsius

R e s u I ts

The patients' places of birth covered a large area of the central part of the country, and therefore the population examined had no characteristics of an isolate.

The examination after mydriasis revealed 48 patients with pseudoexfoliation. In 18 patients it was bilateral and in 30 unilateral. The total of affected eyes was thus 66. None of the 14 patients to whom no mydriatics could be ad- ministered showed any signs of pseudoexfoliation. The incidence of pseudo- exfoliation of the lens capsule among the 220 subjects examined was 21.8 o / o . The figure for men was 21.40/0 and for women 22.1 O/O. Fig. 1 shows the increase in pseudoexfoliation, among both men and women, in the older age groups: from a mean incidence of 10 O / o among those aged 60-69, it increased to 21.3 O/O among those aged 70-79 and ultimately to 32.8 O/O among patients aged 80-89 years.

The primary diagnosis of pseudoexfoliation was correct for 50 eyes, and after mydriasis the disease was discovered in a further 16 eyes. Mydriasis disproved the assumption of pseudoexfoliation in three eyes. In a total of 19 eyes, which was 4.6 O/O of the eyes examined, an erroneous diagnosis was made before the dilatation of the pupil.

Glaucoma had previously been diagnosed in 30 eyes of 16 patients, and 11 of these eyes were affected with glaucoma capsulare. Prior to the instillation

30 Y 8

0" 20 z a

1 0

r n 8 0 0 17 mean

60-69 70-79 80-89 90-99 Age groups (years1

50 108 61 1 No.of investigated patients

Fig. 1. Incidence of pseudoexfoliation (per cent) in the different age groups.

42

Pseudoexfoliation and Liberation o f Iris Pigment

AGE GROUPS WITHOUT PSEUDOEXFOL.

value MeanMitsui Naof eyes

60- 69 2.46 90

70- 79 2.43 166

80 - 89 1.56 78

90- 99 0 1

Total 2.23 335

WITH PSEUDOEXFOL.

Mean Mitsui eyes value

4.00 6

3.96 30

2.91 24

- -

3.55 60

Fig. 2. Liberation of pigmented floaters into the aqueous humour after mydriatics, graded

according to Mitsui’s scale (1943) in eyes with and without pseudoexfoliation.

of mydriatics the intraocular tension in the eyes with pseudoexfoliation was 17.5 mmHg and in those without pseudoexfoliation 15.4 mmHg. This difference in tension is statistically almost significant. The glaucomatous eyes under treat- ment were excluded from these calculations. Twenty-four subjects had uni- lateral exfoliation without glaucoma. On the average, the tension in the eyes with pseudoexfoliation was 1.4 mmHg higher than in the fellow eye.

The tension change following the instillation of mydriatics averaged + 2.1 mmHg (range + 17 and - 4 mmHg) in eyes with pseudoexfoliation. The cor- responding figures for the eyes without pseudoexfoliation were t 1.1 mmHg (range + 13 and - 7 mmHg). Before the instillation of mydriatics, a pigmented floater was only occasionally noted in the aqueous humour. The mean initial value, according to the Mitsui (1943) classification, was therefore almost Grade 0. After mydriatics the pigment liberation could be graded in 395 eyes. Of the eyes with pseudoexfoliation, pigment liberation was noted in 83.3 O/O,

and in these (60) eyes the Mitsui value averaged 3.55. Of the eyes without pseudoexfoliation, mydriasis induced a pigment liberation in 61.5 O i o , and the mean Mitsui value for the (335) eyes was 2.23. The difference between the Mitsui values was statistically highly significant (Fig. 2). In unilateral pseudo- exfoliation, also, a similar difference was elicited: the mean pigment liberation value in the affected eye was 3.4 and in the fellow eye, respectively, 2.4. These

43

U. Krause, /. Helve and H . Forsius

The grade of pign

WITHOUT PSEUDOEXFOL. No. of eyes

178

156

334

i t (GP) in th,

GP

0.73

0.86

0.79

Fig. 3. trabecular re&

WITH PSEUDOEXFOL. No.Qf eyes

27

27

54

GP

1.79

1.20

1.49

)n estimated according to Becker & Shaffer (1965) in eyes with and without pseudoexfoliation.

figures are based on the results for 24 cases of unilateral pseudoexfoliation. The significance of the difference between the figures has not been statistically analysed.

The present results show, therefore, that the pigment liberation after my- driatics seems to reach its maximum at the age of 60-79 years (Fig. Z), after which the pigmentary dust is less intense. This is true both of the eyes with and without pseudoexfoliation.

The grade of pigmentation of the chamber angle in the normal eyes averaged 0.79 and in the eyes with pseudoexfoliation 1.49. The difference between these figures is statistically significant (Fig. 3) . No similar difference was noted in the cases with unilateral exfoliation.

Discussion

As far as Finland is concerned, the incidence of pseudoexfoliation is known only for two isolates (Forsius & Eriksson 1961, Forsius & Luukka 1973). The present study was an attempt to investigate the incidence of pseudoexfoliation in an unselected normal population, if it is assumed that this can be represented by the inmates of old people’s homes.

The series examined, as a result, contains no age groups under 60. The find- ings reported are not comparable with the incidence figure of 8.60/0 quoted by Forsius & Eriksson (1961), which shows the occurrence of the disease among subjects aged over 40, without any detailed age classification. Aasved’s (1969)

44

Pseudoexfoliation and Liberation of Iris Pigment

materials from Norway, England and Germany are composed of the same age groups as the present series. In every age group, our incidence figures are higher than those for the said three countries. I t may be mentioned for com- parison that in Norway the age group 80-89 years had an incidence of 7.6 O/O

(Aasved 1971), against the respective incidence of 32.8 O/O in Finland. Since Aasved’s and the present studies describe the incidence of pseudoexfoliation among the inmates of old people’s homes, the results, in our opinion, are com- parable, and they must be interpreted as showing that the incidence of pseudo- exfoliation in Finland really is higher than in the countries studied by Aasved. A racial difference may be involved here; the existence of such a difference is suggested by the studies of isolates by Forsius & Luukka (1973).

Pigmented floaters produced by mydriasis were seen in 61.50/0 of the examined eyes without pseudoexfoliation. W e could not substantiate the finding (Tarkkanen 1962) that pigment liberation was to be seen only in eyes with pseudoexfoliation. In the affected eyes the incidence amounted to 83.3 O/O

and, moreover, the aqueous humour contained a highly significantly larger number of pigmented floaters than that of the normal eyes.

It is known that the iris liberates pigment more frequently, the older the subjects are (Mitsui & Takagi 1961, Kristensen 1965, Aggarwal & Beveridge 197 1). According to the present results, the grade of pigment liberation seems to reach its peak between 60 and 79 years of age, after which the number of pigmented floaters would seem to decrease. Since the pigment epithelium of the iris is of neuroretinal origin, it has no regenerative ability. This might explain the present finding.

I t has often been claimed previously that the trabecular region of the eyes with pseudoexfoliation is more heavily pigmented. By statistical methods, the observations have now been proved correct. Mitsui & Takagi (1961) assumed that the pigmented floaters in the aqueous humour are pigment granules from the pigment epithelium cells of the iris, and the application of mydriatics causes a rupturing of degenerated cells. I t does not seem inconceivable that the mechanism gains in strength when the iris moves along the uneven (Busacca 1928) surface of an exfoliating lens. Pseudoexfoliation, in this way, would gradually lead to a heavier than normal pigmentation of the trabecular region, and also to the observed massive pigment liberation in connection with mydriasis.

References

Aasved, H. (1969) The geographical distribution of fibrillopathia epitheliocapsularis, so-called senile exfoliation or pseudoexfoliation of the anterior lens capsule. Acta ophthal. (Kbh.) 47, 792-810.

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U . Krause, J . Helve and H . Forsius

Aasved, If. (1971) Mass screening for fibrillopathia epitheliocapsularis, so-called senile exfoliation or pseudoexfoliation of the anterior lens capsule. Acta ophthal. (Kbh.) 49, 334-343.

Aggarwal, J. L. & Beveridge, B. (1971) Liberation of iris pigment in the anterior chamber. Brit. J . Ophthal. 55, 544-549.

Bard, J. (1935) Fall von Glaucoma capsulare mit Pigmentausschwemmung in die Vor- derkammer. Z. Augenheilk. 85, 261.

Bartholomew, R. S. (1970) Lens displacement associated with pseudocapsular exfolia- tion. Brit. J . Ophthal. 54, 744-750.

Becker, B. & Shaffer, R. N. (1965) Diagnosis and Therapy of the Glaucomas, p. 22. 2nd ed. Mosby, St. Louis.

Busacca, A. (1928) Struktur und Bedeutung der Hautchenniederschlage in der vorderen und hinteren Augenkammer. Albrecht v. Grafe’s Arch. Klin. exp. Ophthal. 119, 135- 176.

Faulkner, H. W. (1971) Pseudo-exfoliation of the lens among the Navajo Indians. Amer. J . Ophthal. 72, 206-208.

Forsius, H. & Eriksson, A. (1961) Ophthalmological studies of a population group in the Aland islands. Acta ophthal. (Kbh.) 39, 318-321.

Forsius, H. & Luukka, H. (1973) Pseudoexfoliation of the anterior lens capsule in Lapps and Eskimos. Canad. J. Ophthal. In press.

Hoorgina, E. (1929) Biomicroscopic investigation of deposits on the anterior lens capsule. Ruskii Ophth. J . Sept., 274-290.

Hsrven, I. & Hutchinson, T. B. (1967) Exfoliation syndrome. Acta ophthal. (Kbh.) 45,

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Kristensen, P. (1968) Pigment liberation test in open-angle glaucoma. Acta ophthal. (Kbh.) 46, 586-599.

Maghraby, A. (1937) Glaucoma capsularis. Bull. ophthal. SOC. Egypt 30, 42-50. Mitsui, Y. (1943) A clinical study of aqueous humor with slitlamp microscopy. Acta

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Sugar, H. S. (1966) Pigmentary glaucoma. Amer. J. Ophthal. 62, 499-507. Tarkkanen, A. (1962) Pseudoexfoliation of the lens capsule. Acta ophthal. (Kbh.),

Suppl. 7 1 . Vogt, A. (1925) Ein neues Spaltlampenbild des Pupillengebietes: Hellblauer Pupillen-

saumfilz mit Hautchenbildung aul der Linsenvorderkapsel. Klin. Mbl. Augenlzeilk. 75, 1-12.

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Author’s address: U. Krause, Oulu University Eye Hospital, Oulu, Finland.

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