- ACTA OPHTHALMOLOGICA SCANDINAVICA 1997

Epidemiology of pseudoexfoliation in the island of Crete (Greece) Vassilios P. Kozobolis1.2, Maria Papatzanakil.2, Ioannis G. Vlachonikolis3, Ioannis G. Pallikaris'-2 and Ioannis G. Tsambarlakis'-2

University of Crete', School of Health Sciences, Division of Medicine, Department of Ophthalmology, Crete, Greece Vardinoyannion Eye Institute of Crete', Heraklion, and University of Crete', School of Health Sciences, Division of Medicine, Department of Social Medicine, Biostatistics Laboratory, Crete, Greece

ABSTRACT. Purpose: To evaluate the pseudoexfoliation (PEX) prevalence in the island of Crete (Greece). Method Organized visits to various villages, to examine a predetermined number of people born and living in these villages, in collaboration with the local birth reg- ister offices. Results: PEX prevalence in Crete, in people aged 40 years and more, was found to be 16.1% (men: 21.3%, women: 12.6% - Prefecture of: Heraklion 11.5%, Chania 13.4%, Lasithi 16.9%, Rethymnon 27%). 28.8% of PEX-patients presented IOP > 21 mmHg. In unilateral PEX-patients, mean IOP of PEX-eyes was found to be 17.82 mmHg versus 15.6 nimHg in fellow eyes. Conclusion: PEX prevalence was higher in men than in women and increases with age, as does bilaterality. A correlation between increased PEX prevalence and high altitude may exist. PEX is a risk factor for the development of IOP dis- turbances which seem to appear earlier in women.

Key words: exfoliation syndrome - epidemiology - intraocular pressure.

Acta Ophthalrnol. Scand. 1997: 75: 726-729

rete is an island in the Mediterranean C and is the southernmost part of Greece. The island has a land mass of 8620 km' and a population of 540 074. This allows the realization of a reliable mass screening study.

Pseudoexfoliation syndrome (PEX) is a pathological condition, first described by Lindberg in 1917, the most character- istic feature being the deposition of grey- white flakes of material on the pupillary borders and on other anterior chamber structures. It is well known that the fre- quency of PEX varies from place to place (Cradle & Sugar 1940, 1947; Sunde 1956; Gifford 1959; Ioannides et al. 1961; Tarkannen 1962). PEX syndrome has been recognized in different ethnic groups such as the Scots, Lapps, Navajo Indians, Australian Aborigines and all major tribes of the South African Bantu

(Bartholomew 1979). The explanation for these differences between various places is related to race, environmental (sunlight), and nutritional factors. Several authors have described the familial oc- currence of pseudoexfoliation syndrome (Gifford 1957; Pohjanpelto & Hurs- kainen 1972; Tarkannen 1965; Aasved 1975). Some authors consider that dif- ferences between various places are due to parameters such as: the selection of population, the age and sex distribution of the selected population, the conditions and the accuracy of examination (Aasved 1 96 9).

The purpose of this study was to inves-' tigate the prevalence of PEX in the Island of Crete, in a randomized sample, and to discover the likely variation of the syn- drome in this territory,

Materials and Methods In 13 different villages - in all (4) prefec- tures of the island of Crete - during the last three years (1993,1994, 1995) an in situ study was accomplished. The villages were randomly selected so that they would represent the geographical dis- tribution of the rural population of Crete. We examined 1.43%0 of the total popula- tion of Crete in different places all over the island using a randomized sample.

We were assisted by the local birth reg- ister office of the relevant village which prepared, under our instructions, a list of a randomized sample based on the age and sex of the patients to be examined. Our aim was to examine people born and living in these villages. It is also noted that there is a low (in fact zero) people mo- bility to the villages. Usually there exists an opposite mobility to the urban areas. The percentages by sex and age of the randomized sample (10-year intervals) were approximately equal to the corre- sponding percentages found in the general population covered by the 1991 census. The age distribution is given in 10-year groups, separately for men and women in Table 1. The sampling fraction in each village was approximately 5%. The attendance varied from 60% on average for the villages of the prefecture of Heraklion to 80% on average for the villages of the prefecture of Chania. The age group with the smallest attendance %as 40-49. The male/female ratio and the age distribution of the sampling frac- tion were selected to be approximately equal to those of the population of the relevant village. A low discrepancy in M/F ratio was observed, however, and it was due to incomplete attendance. A dis-

726

ACTA OPHTHALMOLOGICA SCANDINAVICA 1997 -

Table 1. Distribution of the sample by sex and age. Table 2. Distribution of PEX-patients by sex and age.

Age Investigated Investigated O/O row Investigated YO row people men women

Age Investigated PEX O/O row Investigated PEX '/O row men men men women women women

4 0 - 4 9 23 5 21.7 18 78.3 5 0 - 59 I27 35 27.6 92 72.4 6 0 - 6 9 248 95 38.3 I53 61.7 7 0 - 7 9 298 126 42.3 172 57.7 80 + 81 54 66.7 27 33.3

40 - 49 5 0 0 18 0 0 5 0 - 5 9 35 1 2.9 92 0 0 60 - 69 95 14 14.7 153 12 7.8 7 0 - 7 9 126 27 21.4 172 33 19.2 80 + 54 25 46.3 27 13 48.1

Total 777 315 40.S0/0 462 59.5% Total 315 67 21.3 46 2 58 12.6

crepancy in age distribution was also ob- served in the 40-49 age group only which was underrepresented; this was also due to incomplete attendance.

Our group (the author and two other ophthalmologists) with the Mobil Oph- thalmological Unit, visited the village at a predetermined date. All persons (777) were examined by the first author.

The examination was carried out in the local health centers. The conditions for detecting the syndrome were satisfactory as our Mobil Ophthalmological Unit was fully equipped and facilities were pro- vided in the health centres of the villages, such as a dark examination room and a waiting room. All patients were examined before and after dilating the pupils with Tropicamide 0.5%. A slit-lamp with mag- nification 10 x and 16 x was used. All de- tails of the anterior segment (chamber's angle, iris colour, pupil dilatation, lens opacities, etc.) were recorded strictly ac- cording t o protocol. Patients were con- sidered PEX-positive only when presen- ting pseudoexfoliative deposits on the anterior lens surface and/or on the pupil- lary borders or the typical central disk or the typical peripheral zone after dilating the pupil.

Statistical analysis The prevalences of PEX in strata classi- fied by age, sex and geographical location were analysed by the chi-square test (li- near components of associations were tested by the Mantel-Haenszel test). Average levels of IOP were compared (PEX-patients versus non PEX-patients)

by the usual t-test (Armitage & Berry 1989). The calculations were carried out by the statistical software package SPSS for Windows Release 6.0.

Results The prevalence of PEX syndrome was found to be 16.1% (21.3% men, 12.6% women) (Table 3). PEX prevalence in men was statistically significantly higher than PEX prevalence in women XI(^)= 10.54, p < 0.002 / Mantel-Haens- zel,,,= 10.53, p < 0.002).

The prevalence of PEX appears to in- crease with the progressing of age; and the percentages start from 2.9% in men and 0% in women at the 5th decade of life, increasing to 46.3% in men and 48.1% in women in the 8th decade of life (Table 2). There is a statistically signifi- cant difference in the prevalence of the syndrome between the age groups in our study. In particular, there is a large in- crease with age (x2(.,, = 92.833, p<0.001 / Mantel-Haenszel(,, = 79.424, p < 0.001) and this is consistent for both sexes.

The geographical distribution of PEX per prefecture is as follows (Table 3): 11.5% in the prefecture of Heraklion (medwomen: 15.7%/8%), 13.4% in the prefecture of Chania (men/women: 17.4%/11.2%), 16.9%in the prefecture of Lasithi (medwomen: 31.4'/0/8.2~/0) and 27'/0 in the prefecture of Rethymnon (men/women: 27.1 %/ 26.8%) (Table 3, Fig. 1).

Table 3. Distribution o f PEX-patients by sex and prefecture.

Unilateral and bilateral PEX is as fol- lows: 27.2% (34 of the 125) presented unilateralPEXand 72.8%(91 ofthe 125) bilateral PEX. The bilateral PEX-pa- tients were almost 3 times more as com- pared with unilateral PEX-patients. With progressing of age the percentages of uni- lateral PEX decrease (from 42.3% in the 6th decade of life to 18.4% in the 8th de- cade of life) and the percentages of bilat- eral PEX increase (from 57.7% in the 6th decade of life to 8 1.6% in the 8th decade of life) (Table 4).

The presence of PEX syndrome per age, sex and intraocular pressure (TOP > 21) is presented in Table 5: 28.8% of PEX patients presented IOP > 2 1 mmHg (26.9% in men and 31% in wornen). The non PEX-patients presenting IOP > 2 1 mmHg were 5.4"/0. The PEX population has a 5-fold increased prevalence of IOP over 21 mmHg. The frequency of PEX- patients with IOP > 2 1 mmHg increases - without statistical significance ( x ? ( ~ ) = 4.96, p = 0.174) - with the progressing of age in both sexes. We can also observe in Table 5 , that the establishment of IOP disturbances appeared earlier (6th de- cade of life) in women.

In patients with unilateral PEX, we found that the mean IOP in the affected eye was higher by more than 2.0 mmHg as compared with the fellow eye (17.82 f SE 0.853 mmHg vs 15.61 f SE 0.396 mmHg) (Table 6). This difference be- tween the affected and 'non affected eye' was found to be statistically significant: (t(,,,= 3.19, p < 0.004).

Prefecture Investigated PEX O/O row Investigated PEX O/O row Investigated PEX O/O row people patients men men men women women women

Heraklion 227 26 11.5 102 16 15.7 125 1 0 8 Chania 262 35 13.4 92 16 17.4 170 19 11.2 Lasithi 136 23 16.9 51 16 31.4 85 7 8.2 Rethymnon I52 41 27 70 19 27.1 82 22 26.8

Total 777 125 16.1 315 67 21.3 462 58 12.6

727 -

- ACTA OPHTHALMOLOGICA SCANDINAVICA I997

Fig. 1. Map of Crete and PEX prevalence in the prefectures 0 1 the island.

Discussion In our study a prevalence of 16.1% of PEX in the island of Crete was found. This is lower than in studies in the main- land of Greece: a prevalence of 25% has been recorded by Trantas (1926); in an- other study, a prevalence of 22.3%- 23.4% was recorded by Tragakis et al. (1978), and a prevalence of 20.2% in Epirus (the northwest region of Greece) was found by Stefaniotou (1 990). These studies, however, were not based on a randomized sample.

PEX is age dependent (Tarkannen

Table 4. Distribution of PEX population by age and unilateral and bilateral PEX.

Age PEX Patients Patients Yo

patients with with unilateral bilateral

PEX PEX

40-49 0 o - o - 50-59 1 1 - 0 - 60-69 26 11 42.3 15 57.7 70-79 60 15 25.0 45 75.0 80+ 38 7 18.4 31 81.6

Total 125 34 27.2 91 72.8

Table 5. PEX population and IOP.

1962), and this is also proved in the pres- ent study. The typical clinical signs are manifest after the 5th decade of life. A low prevalence of PEX syndrome was found in the population less than 60 years old: 0.1% in the decade 50-59. We found only one PEX-patient (male) in the 6th decade of life. Our youngest patient with exfoliative features was 53 years old. There are other reports in literature with patients who presented PEX earlier: 31 years by Horven & Hutchinson (1967), 46 years by Tarkannen (1962). PEX syn- drome could be present almost one de- cade earlier in Scots, Lapps, in the Icelan- ders of Husavik, in Australian Aborig- ines. An extreme example is that of some members of the Pondo tribe of the South African Bantu: they presented an in- cidence of 6.4% between 30-39 years of age (Bartholomew 1979).

Concerning the higher percentage found in the prefecture of Rethymnon, the only explanation we could think of is that in this prefecture the mean altitude of the selected villages (mean altitude: 470 m), selected according to the geographi- cal distribution of the rural population in this prefecture, was higher in comparison with the villages of Heraklion (mean alti- tude: 110 m), of Chania and Lasithi (mean

altitude: 70 m). Although the same prep- arations and the same procedures were strictly followed in each prefecture con- cerning the selection of population, the conditions and the accuracy of examin- ation, there was still a variation of PEX prevalence among the prefectures.

The 3/4 of all our PEX-cases pre- sented clinically bilateral PEX. An in- crease of the bilaterality with aging was obvious. This is consistent with the find- ings of Aasved series (1971), Tarkannen (1962) and Forsius (1979) among Fin- nish people, Hiller et al. (1982) in Ameri- cans, Kinoshita (1979) among Japanese people. PEX seems also to be assymetric rather than truly unilateral. The abnor-

Table 6. Unilateral PEX. Mean value of IOP in PEX and non PEX-eyes; standard error in brackets.

Intraocular pressure

Unilateral PEX-eye Non PEX- (mmHg) PEX-eye

patients (mmHg) p < 0.05

34 17.82 15.61 (0.853) (0.396)

Age Population Number and (YO) of PEX Number and (“’0) of PEX Number and (YO). PEX Number and (“/o)

without non PEX population patients PEX population men of PEX men women of PEX women PEX with IOP > 21 with IOP > 21 with IOP > 2 1 with IOP > 21

40 - 49 23 0 (OYO) 0 0 0 0 ” 0 0 50-59 126 7 (5.6%) 1 1 1 ‘ 1 0 0

80 + 43 6 (14%) 38 14 (36.8%) 25 9 (36%) 13 5 (38.5%)

60-69 222 10 (4.5%) 26 5 (19.2%) 14 0 (0%) 12 5 (41.7%) 70-79 238 12 ( 5 % ) 60 16 (26.7%) 27 8 (29.6%) 33 8 (24.2%)

Total 652 35 (5.4) 125 36 (28.8%) 67 18 (26.9%) 58 18 (31%)

728

ACTA OPHTHALMOLOGICA SCANDINAVICA 1997 -

malities of the iris vessels (Vannas 1969; Konstas et al. 1991) precede the clinical features, i.e. an increased quantity of pig- ment may be clinically observed in the anterior segment (Sugar 1984; Konstas & Dutton 1991). For this reason the term ‘clinically unilateral pseudoexfoliation’ is accurately used.

There are conflicting results concern- ing PEX prevalence between the sexes. In the present study the prevalence of PEX in men ( 2 1.3%) was higher in comparison with the prevalence in women ( I 2.6%). This is in contrast to the higher pre- valence in females which was found by Tarkannen (1962), Aasved (1971) and Hiller ( 1 982), but consistent with the pre- valence among females found by Bussaca (1928), Ioannides et al. (1961), Sood (1968) and Bartholomew (1979). Prob- ably climatic conditions provoke a more intense effect in the male population be- cause they spend more of their working time in the country.

The significance of epidemiological studies conducted all over the world, lies primarily in the close association be- tween PEX and abnormalities of IOP and glaucoma. About 20% of PEX-patients present IOP abnormalities (Aasved 1971; Kozart & Yannof 1982; Konstas et al. 1993b). 28.8% of PEX-patients in our study were found with IOP abnor- malities. The difference in IOP abnor- malities between men and women was not found statistically significant. In the present study a S-fold increased pre- valence of IOP abnormalities in PEX-pa- tients in Comparison with non PEX-pa- tients was found. As for the IOP in the pseudoexfoliative population, a non stat- istically significant increase of IOP with age in both sexes was recorded. In this study we noted also an earlier appearance of IOP disturbances in PEX-women in comparison to PEX-men. This probably means that the consequences of PEX in provoking IOP disturbances appeared earlier in women.

T h e close relation between PEX and IOP disturbances, was also proved by checking the mean IOP in the eyes with unilateral PEX. In the affected PEX-eye, the mean IOP was increased more than 2.0 mmHg and this is consistent with pre- vious analogous studies (Aasved 1971; Kozart & Yanoff 1982, Madden & Crow- ley 1982; Sugar 1984; Konstas & Dutton 1991; Stefaniotou et al. 1990).

Conclusion - PEX in the island of Crete seems fairly

common. A correlation between in-

creased PEX prevalence and higher al- titudes may exist.

- PEX prevalence increases with age, as well as bilaterality.

- Men are affected more than women. - PEX is a risk factor for the development

of IOP disturbances which seem to ap- pear earlier in women.

References Aasved H (1969): The geographical distribu-

tion of fibrillopathia epitheliocapsularis so called senile exfoliation or pseudoexfolia- tion of the anterior lens capsule. Acta Oph- thalmol (Copenh) 4 7 792-810.

Aasved H (1971): Mass screening for fibrillo- pathia epitheliocapsularis so called senile exfoliation or pseudoexfoliation of the anterior lens capsule. Acta Ophthalmol (Copenh) 50: 334-343.

Aasved H (19 75): Study of relatives of persons with fibrillopathia epitheliocapsularis (Pseudoexfoliation of the lens capsule). Acta Ophthalmol (Copenh) 53: 879-886.

Armitage P & Berry G (1989): Statistical Methods in Medical Research. 2nd Ed, Ox- ford, Blackwell.

Bartholomew RS (1979): incidence of pseu- doexfoliation in South Africa Negroes and Scots. Trans Ophthalmol Soc UK 90: 299- 301.

Busacca A (1928): Structure und Bedeutung der Hautchenniederslage in der vorderen und hinteren Augenkammer. Albrecht v Graefes Arch Ophthal 19: 135-176.

Forsius H (1979): Prevalence of pseudoexfoli- ation of the lens in Finus, Lapps, Icelanders, Eskimos, and Russians. Trans Ophthalmol

Gifford H (1957): A clinical and pathological study of exfoliation of the lens capsule. Trans Am Ophthalmol Soc 55: 189-216.

Gifford H (1958): A clinical and pathologic ’study of exfoliation of the lens capsule. Am

J Ophthalmol46: 508-524. Grandle HS & Sugar HS (1940): Concerning

the chamber angle 11. Exfoliation of the zo- nular lamella and glaucoma capsulare. Am J Ophthalmol23: 928-997.

Grandle HS & Sugar HS (1947): Glaucoma- capsulare. Am J Ophthalmol30: 12.

Hiller R, Sperduto RD & Krueger DE (1982): Pseudoexfoliation, intraocular pressure, and senile lens changes in a population- based survey. Arch Ophthalmol 100: 1080- 1082.

Horven I & Hutchinson BT (1967): Exfolia- tion syndrome. Acta Ophthalmol (Copenh)

ioannides V, Katsourakis N & Velissaropou- 10s P (1961): Glaucoma capsulare. Ophthal- mologica 142: 160-189.

Kinoshita A (1979): Incidence of pseudoex- foliation in Japan. Jpn J Ophthalmol23: 85- 88.

SOC 99: 296-298.

45: 294-298.

Konstas AGP & Dutton GN (1991): Gonios- copic findings in Greek patients with exfoli- ation glaucoma. Acta Ophthalmol (Co- penh) 69: 281-287.

Konstas AGP, Dimitracoulias N & Konstas PA (1993b): Exfoliation syndrome and open angle glaucoma. Klin Monatsbl Augen- heilkd 202: 259-268.

Kozart DM & Yanoff M (1982): intraocular Pressure Status in 100 consecutive patients with exfoliation syndrome. Ophthalmology (Rochester) X9: 214-218.

Lindberg JG (1917): Clinical investigations in depigmentation of the pupillary border and translucency of the iris. Academic disserta- tion. (Eng translation, 1989). Acta Oph- thalmol (Copenh) Suppl 190.

Madden JG & Crowley MJ (1982): Factors in the Exfoliation Syndrome. Br J Ophthalmol

Pohjanpelto P & Hurskainen L (1972): Studies on relatives of patients with glau- coma simplex and patients with pseudoex- foliation of the lens capsule. Acta Ophthal- mol (Copenh) SO: 255-261.

Sood N (1968): Prevalence of pseudoexfolia- tion of the lens capsule in India. Acta Oph- thalmol (Copenh) 46: 211-214.

Stefaniotou M, Petroutsos G & Psilas K ( 1990): The frequency of pseudoexfoliation in a region o f Greece (Epirus). Acta Oph- thalmol (Copenh) 68: 307-309.

Sugar S (1984): Pigmentary glaucoma and the glaucoma associated with the exfoliation syndrome. Am Acad of Ophthalmol 91:

Sunde OA (1956): On the so called senile ex- foliation of the anterior lens capsule. A clinical and anatomical study. Acta Oph- thalmol (Copenh) 34 (Suppl45).

Tarkannen A (1962): Pseudoexfoliation of the lens capsule. Acta Ophthalmol (Copenh) 40 (Suppl71).

Tarkannen A, Voipito H & Koivusalo P (1965): Family study of pseudoexfoliation and glaucoma. Acta Ophthalmol (Copenh)

Tragakis M, Pollalis S, Gartaganis S & Hatzi- thanasis C (1978): Pseudoexfoliation. Bul- letin of Greek Ophthal SOC 46: 482 491.

Trantas A (1926): Lesions seniles de la cap- sule anterieure du cristalline et du bord puppilaire. Arch Ophthalmol46: 482-491.

Vannas A (1969): Fluorescein angiography of the vessels of the iris in pseudoexfoliation of the lens capsule, capsular glaucoma and some others forms of glaucoma. Acta Oph- thalmol (Copenh) 42 (Suppl 105).

66: 432-437.

306-310.

43: 679-683.

Received on August 8th, 1996.

Corresponding author: Vassilios F! Kozobolis, MD Eye Clinic, Heraklion University Hospital P.O. BOX 1352 Heraklion, Crete 711 10, Greece. Tel: ++ 30 - 81 - 392868. Fax: ++ 30 - 81 - 542094.

I L Y -