A C T A O P H T H A L M O L O G I C A VOL. 5 6 1 9 7 8

The Institute o f Clinical Genetics, University o f Odense (Head: M . Hauge), and

The Eye Department, Kommunehospitalet (the Municipal Hospital), Copenhagen (Heads: P . Brcendstrufi, S . E. Lorentren, M. S . Norn and K . Nerskov)

CORNEAL THICKNESS

I. Age Variation, Sex Difference and Oculornetric Correlations

BY

P. H. ALSBIRK

An oculometric survey was performed in a Greenland Eskimo population, covering 98 "/a of selected age groups. From this sample 839 persons without corneal abnormalities, aged 7-89 years, formed the basis of a central cor- neal thickness (CT) study. A sample of 98 Danes in Greenland was mea- sured for comparison. Using Haag Streit 900 pachymeter No. I, the average of three readings from both eyes was taken to represent the individuals. In Eskimos a Gaussian distribution of CT values was found with mean and SD: 0.518 f 0.032 mm in males and 0.529 & 0.029 mm in females. A significant corneal thinning with age was seen, predominantly in males (0.0007 mm decrease per year). Thus in adults an increasingly significant sex difference was observed (0.019 mm above the age of 40), while boys and girls differed only little (0.005 mm). A subsample with primary angle- closure glaucoma showed an insignificant CT excess. The Danes showed a corresponding thinning with age although not signi- ficant. A highly significant ethnic difference was found, but only in men (Eskimos 0.024 mm below Danes). In a subsample of 325 adult Eskimos oczilometric correlations were studied. Between CT and refractive error (r=+0.12) as well as CT and anterior chamber depth (r = -0.12) just significant correlations were found (P < 0.05). Other relationships showed weaker correlations.

Key words: corneal thickness - population study - agehex variation - Greenland EskimodDanes - primary angle-closure glaucoma - oculo- metry - cross-correlations.

Received October 5, 1977.

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P . H . Alsbirk

A pronounced variability of corneal thickness in a large number of anterior eye disorders is an accepted clinical experience. The optical section of cornea is scrutinized in every day work with the slit lamp. However, extensive popula- tion studies on corneal thickness in normal eyes have not yet been published.

For the last ten years, the central corneal thickness (CT) has been easy to measure using an attachment to the Haag Streit 900 slit lamp. The use of this pachymeter has been described by Lowe (1966), Honegger & Genke (1968), Ehlers & Kruse Hansen (1971), and others. They found it to be the equipment of choice, although a slight modification seems desirable due to a significant side difference inherent in the asymmetry of the method (Mishima & Hedbys 1968; Ehlers & Kruse Hansen 1971).

With the Haag Streit pachymeter, mean values of CT in normal eyes between 0.50 and 0.55 mm have repeatedly been found (cf. Delmarcelle et al. 1976) with standard deviations about 0.03 mm. Most of the limited studies in Caucasians have asserted that no influence of age and sex seems to exist (cf. von Bahr 1948; Lavergne & Kelecom 1962; Martola & Baum 1968; Kruse Hansen 1971). How- ever, a report from North Finland showed a slight decrease of CT with age in Finns, Lapps and Skolts, with a thinner cornea in the last mentioned population (Forsius et al. 1971). Kamiya (1973) also found a gradually thinner cornea with increasing age in a Japanese study.

C T seems to be a fairly unique parameter compared to other ocular dimen- sions, which generally show conspicuous cross-correlations. The few studies available have shown that no correlation exists between CT and other ocular dimensions, e.g. axial length and corneal radius of curvature (Lowe 1969). A similar lack of correlations was found by Ehlers et al. (1975) and Ehlers & Kruse Hansen (1976), also including anterior chamber depth and refractive error.

During a study of primary angle-closure glaucoma in a high risk population (Alsbirk 1976) CT measurements were performed as part of the oculometric survey. The present paper describes the age variation and sex difference ob- served in an unselected group of 839 Greenland Eskimos and in a local sample of Caucasians which has been included for comparison. Oculometric cross- correlations were studied in a subsample.

Material and Method

A total of 931 Umanaq Eskimos formed the basis of the anterior chamber depth survey (Alsbirk 1974a) as well as of the present study. They constituted 98 O!o of the population registered in the town (above the age of seven) and villages (above the age of forty). The material is shown in Table I. For the present analyses, 839 persons with two normal corneae and no anterior chamber deformity were used. Ninety-eight Danes

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CT. I . Age Variation, Oculometric Correlations

Males

7-39 1 40+ I Total Aged:

Females 1 M + F

7-39 1 40+ I Total) Total

Total 250 215 465 253 213 466 931

'' Total for the following CT analyses: 839 persons (10 excluded due to anterior chamber deformity).

living in Umanaq for a shorter period were examined for comparison purposes. The ages ranged from 7-84 and 7-89 years in male and female Eskimos, 8-56 and 7-60 years in male and female Danes (mean ages: cf. Table 111). The term "Eskimo" is used in the wide sense previously described and includes even the few 50°/o hybrids in these age groups (Alsbirk 1974a).

Optical paclaymetry using attachment No. I of Haag Streit slitlamp 900 was per- formed, strictly as recommended by the manufacturers. I made three readings from each eye of each person, using the smaller magnification objective. In an earlier paper, the methodological problems of such a field study have been analysed (Alsbirk 1974b). Computed as the standard deviation the error of a triple reading measurement was found to be 0.007 mm (0.012 mm by a single reading). However, when estimated through a repeated triple reading measurement on another day, the error of measurement was significantly larger: 0.013 mm = 2.5 O/o of the average C T value. Furthermore, an ex- tremely significant side difference was found. Left minus right eye CT averaged +0.019 mm (= D of 839 persons; sI) = 0.018 mm, SI) = 0.0006 mm).

For the present analyses of the interpersonal variation each individual was repre- sented by the average o f left and right eye CT values, given to two decimals.

Oculometric cross-correlations were studied in a subgroup of 325 adults (137 men and 188 women over 15 years), i. e. all Eskimos in whom subjective refraction as well as ultrasonic and optical measurements had been performed (cf. Alsbirk 1977).

97 Acta ophthal. 5G. 1 7

P . H . Alsbirk

0.54 - 0.53-

0.52 -

0.51 -

0.50 - 0.49 -

0.48 -

Na of persons

30 101 A R 1 n

- / / , , , . . , , . . . , I , , , I . I ~ . , , I ,

F i g . 1. Corneal thickness (CT) distributions in 839 Eskimos. The mean values & 3 standard deviations are shown below the histograms. The dots (a) indicate expected Nos. in a

Gaussian distribution.

0.40 0.50 0.60 rnm

mm CT 0.55 4

\ 431 9 t I

t 10 20 30 40 50 60 70 80 AGE

Fig . 2. Corneal thickness mean values (a) in eight age groups, based on 839 Eskimos with no corneal abnormality. Vertical double arrows indicate 95 O/o confidence limits of the

mean values.

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CT. 1. Age Variation, Oculometric Correlations

Table 11. CT mean values (CT) and standard deviations (SCT) in 839 Eskimos, according to sex

and age, with 98 Danes for comparison.

Age group

Eskimos 7-15

16-39 40+

t-test I Males Females

1 1 7 0.533 0.030 94 0.538 0.029 N. S. 118 0.521 0.028 144 0.529 0.028 < 0.025 173 0.505 0.032 193 0.524 0.030 < 0.001

Total 408 0.518 0.032 431 0.529 0.029 < 0.001

Danes Total 53 0.542 0.024 45 0.530 0.032 < 0.05

t-test, P: < 0.001 N. S.

N: No. of persons examined (both eyes).

Results

The CT distributions obtained are shown in Fig. 1. No significant deviations from Gaussian distributions were observed (22 goodness of fit tests: 0.7 < P < 0.8 for men and 0.4 < P < 0.5 for women).

Table I1 and Fig. 2 show the variability according to sex and age. In school children no sex difference was found, while in adults men had thinner corneas than women. The Danes, on the contrary, showed slightly thicker corneas in males, cf. Table 11.

The age variation was evident. It was further gauged by a linear regression study, as no discrepancy from a simple linear relationship was suggested by scattergrams. The parameters obtained are given in Table 111 and illustrated in Fig. 3. Although the study was cross sectional, not longitudinal, a corneal thin- ning with age seems to take place. In men the annual decrease, estimated by the regression coefficient, corresponds to a reduction of 0.033 mm in 50 years, in women less than half (0.014 mm/50 years). The Danes showed a corresponding pattern which was, however, insignificant in the small sample examined.

A highly significant ethnic difference was found but only in males, with Eskimos presenting a lower mean value, cf. Table I1 and Fig. 3.

P. H . Alsbirk

N

Table Ill. Corneal thinning with age. CT linear regression parameters in Eskimos and Danes,

Sex

J

- t d 0.55- t ..>.

--.J 53c X E . Y..

Eskimos 408 M 431 F

Danes 53 M 45 F

- 0.55 1

subdivided by sex

I CVY)

Stand. dev.

7 mm regression coefficient

sy.x mm SI, mm

33.6 0.518 -0.000661) 0.00007 0.029 35.4 0.529 -0.000272) 0.00007 0.029 29.7 0.542 -0.00051 0.00028 0.023 27.2 0.530 -0.00040 0.00048 0.032

by,') and 2) differ significantly from zero and from each other (P < 0.001).

The epidemiologic study of primary angle-closure glaucoma (a. c. 9.) included 24 patients from the Umanaq population (Alsbirk 1975). Out of these 17 were part of the present CT population sample, i. e. all had two normal corneas. On the average their CT values were 0.004 mm above those of the general popu- lation; this excess was far from significant.

I # I , , 1

10 30 50 70 10 30 50 70 AGE Fig. 3.

Corneal thickness in Eskimos (E) and Caucasions (C). Linear regressions are shown with 95 "/o confidence limits (vertical double arrows) at mean ages ( 0 )

and at arbitrary extreme ages.

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C T . 1. Age Variation, Oculometric Correlations

Oculometric cross-correlations. Between C T and other oculometric variables the following correlation coefficients were found: Radius af corneal curvature: r = +0.03; corneal diameter: r = -0.06; anterior chamber depth (as age and sex independent deviation score) : r = -0.12"; lens thickness: +0.08; vitreous body length: -0.06; axial length: -0.05; subjective refractive error: +0.12'.'. As no sex difference in the correlations was found, the pooled values of 325 persons are given. Only two correlations '.' did just exceed the 0.05 level of significance (r = 0.1 l) , i. e. there was a very slight trend towards a thicker cornea in hyper- metropic, shallow chambered eyes. The values given were based on age and sex independent CT values (CTDS units, cf. Alsbirk 1978).

Discussion

The results presented here emerged from a population survey and were based on a larger sample than previous studies of corneal thickness. Corneal pathology was no major part of the survey. However, the slit lamp microscope revealed a high frequency of corneal scarring. Thus 4.8 O / o of male and 1.8 O/O of female corneas showed central macula(e) or leukomata, while about 2 O/O of the eyes showed only paracentral or marginal scarring. Obviously the Eskimo cornea bears a high risk of infectious, phlyctenular and traumatic scarring as clearly demonstrated, e. g. by Wyatt (1973), Forsius & Eriksson (1973) and Clemmesen (1976). Ultraviolet radiation causes frequent snowblindness and seems to account for climatic droplet keratopathy (Freedman 1973).

In the present analyses of normal corneas, a highly significant reduction of CT with increasing age was a major finding. It was more pronounced in Eskimo men, who accordingly showed a thinner cornea than women. Danes living temporarily in Greenland also showed a thinner cornea with age although with the limited number of persons available, this decrease was statistically insigni- ficant.

Only the North Finnish survey and the Japanese study mentioned above have given a similar result. The corneal thinning is probably not a secular trend although longitudinal studies will have to prove this. The findings may suggest an arctic environmental influence upon the human cornea. Especially the extra- ordinary thinning in male Eskimos seems to point to climatic factors. However, larger studies in other ethnic groups are needed. So far no other study published has comprised more than 268 eyes (Donaldson 1966, cf. Delmarcelle et al. 1976). In a recent paper Ehlers et al. (1976) found a thicker cornea in newborns than in children aged 2-14 years, who already showed typical adult average values. The authors suggested that CT is a unique biometric parameter, which is

101

P. H . Alsbirk

maintained constant throughout life. Obviously this statement has to be checked. At least it is not true in an Eskimo population. Corneal thinning with age may be a general trend which has so far escaped observation in the majority of earlier studies.

Discrepancies between various CT studies may be due, not only to small materials, but also to the limited precision of the measurement. For instance the age reduction of CT in Eskimo men (0.033 m d 5 0 years) is small compared to the error of measurement, cf. "method" above. As previously reported, variation from this source constituted 1 7 "/o of the total CT variation observed (Alsbirk 197413). Using the higher magnification objective a greater precision was obtained by Ehlers & Kruse Hansen (1971) (single reading SD: 0.008 mm against 0.012 mm in my hands). A significant interobserver variation was found by Weekers et al. (1971): Three observers obtained the following mean values: 0.467, 0.483 and 0.496 mm by 5 readings of CT in the same 5 persons. Norn (1974) has drawn attention to a probably important source of error. The slit width must either be set to an absolute minimum or, if impossible due to room light conditions, the homologous right edges of the optical block must be used in order to eliminate the slit width from the CT reading. However, in doing so, systematically lower CT readings seem to result. A comparative study of such technical problems is clearly wanted. My survey was carried out in reduced room illumination using the narrowest possible slit. All measurements were made by me and all persons in the present material had both eyes measured and averaged. Thus interobserver variation and side difference problems are not involved in the present analyses. In spite of the fairly coarse measurement, the variations of the material were found to be statistically valid.

Primary angle-closure glaucoma (a. c. g.) was the main topic of the population survey from which this CT study was also derived. Lowe (1969) stated that his 61 a. c. g. patients (mean CT: 0.533 mm, SD = 0.034) and 80 normals (0.517 mm, SD = 0.034) showed no significant difference (t = 0.0395). However, it appears that this conclusion is not correct. The data presented by Lowe implies: t = 3.86, P < 0.001, when d. f. are set to No. of eyes examined minus two (=273) or, what seems statistically more correct: t = 2.77, P < 0.01, when each person is counted only once (d. f . = 139). In a recent per- sonal communication Lowe (1976) confirmed that an erroneous t-test result had un- fortunately been published and agreed, that his a. c. g. sample showed significantly higher CT values than controls. Tomlinson & Leighton (1973) and Cevallo et al. (1976) likewise found a small excess in a. c. g. patients (+0.013) and +0.015 mm respectively). However, the oculometric variations relevant to shallowness of the anterior chamber in a. c. g. are very much larger than these few thousandths of a mm. Lowe (1969) still seems to be right when he considers CT as practically irrelevant to a. c. g . as long as no corneal oedema has developed, especially when the limited precision of CT mea- surements is kept in mind.

In this, as in the few earlier studies, CT was insignificantly correlated with most other oculometric dimensions. A trend towards higher CT values in small hyperopic eyes was only suggested. The influence of environmental and genetic factors upon CT will be analysed in a following paper (Alsbirk 1978).

In conclusion, a corneal thickness (CT) population survey in 839 Eskimos showed a gradual decrease of CT with age. No sex difference was found in

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CT. I . Age Variation, Oculometric Correlations

children, but in adults men had lower CT mean values than women. An ethnic difference was found in men where Eskimos showed a lower CT level than Danes. Oculometric correlations were lacking apart from weak associations between CT, anterior chamber depth and subjective refraction.

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Author’s address: P. H. Alsbirk, M. D., Granholmen 26, DK-2840 Holte, Denmark.

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