Ординатура / Офтальмология / Английские материалы / Progress in Lens and Cataract Research_Hockwin_2002

Introduction

Previous studies have indicated that nuclear lens opacification and cataract are common, in particular in persons aged 65 years and older [1–3]. This has also been found in Iceland, where age has appeared to be the main risk factor [4]. In recent years it has become evident that there might be different risk factors for different types of lens opacification. This together with an increasing awareness among researchers of the importance of not only including advanced visually debilitating cataract but also early lens opacification in epidemiological studies led to the development of systems to type and grade lens opacification [5, 6]. For standardization and improved accuracy of typing and grading of lens opacification, improved photographic documentation has been of great value. For the Reykjavik Eye Study we use the EAS-1000 (Nidek) Scheimpflug camera, the quality and reproducibility of which have been reported elsewhere [7, 8]. The purpose of this study was to examine possible risk factors for nuclear lens opacification analyzing the results of the eye examination and the individual questionnaire from the Reykjavik Eye Study [9–12].

Subjects and Methods

This study was performed at the Department of Ophthalmology in Reykjavik from August to October 1996, in cooperation with the Department of Ophthalmology, Kanazawa Medical University (KMU). After the study had been approved by the Data Protection Commission and the Ethics Committee, a random sample was taken from the national population census. It included 1,700 citizens of Reykjavik that were all 50 years old or older, and thus represented 6.4% of inhabitants in this age group, an equal proportion for all ages and both sexes. 64 persons had died or moved and a further 256 persons could not be located at the address indicated by the population census, mostly because they had not yet informed the census bureau of their moving. It is known that up to 20% of Icelanders change their permanent address within any one year. Thus out of 1,379 persons who were both eligible and could be located 1,045 persons or 78.8% of those 50–79 years old and 51.3% of those 80 years old and older were interviewed and examined. They were all Caucasians.

All subjects in the sample were sent a 26-item questionnaire with a letter explaining the study and informing them that within 2 weeks they would receive a phone call enquiring about their willingness to participate. During this phone call people were given help in filling out the questionnaire, and whatever they were not able to answer through the phone they got assistance with when they came for the examination. We tried to contact each person both during working hours and in the evening and during weekends. The content of the questionnaire has been presented in detail in a previous paper [10]. In short, the study variables were divided into four groups: factors regarded as risk, lifestyle habits, general ageing indices and others, including eye and systemic disease and medication. Most of these variables have been recommended by the World Health Organization (1994) [13]. The questionnaire enquired about the average daytime hours participants spent outdoors from 8 a.m. to 4 p.m.

Fig. 1. Scheimpflug photography of dl nuclear lens opacification grade III and pseudoexfoliation (central shield; peripheral band).

on weekdays, in their 20s to 30s, in their 30s to 40s, in their 40s to 50s and at the present time. The participants were also asked to indicate which hours between 8 a.m. and 4 p.m., they were most likely to spend outdoors since this period should include the most important ultraviolet (UV) hours [13, 14]. For the frequency of food intake we used five categories: ‘very often’ indicating on 4–7 days a week, ‘often’ indicating on 2–3 days a week, ‘occasionally’ indicating 1–2 times a fortnight, ‘rare’ less than once a month and ‘never’.

Each of the 1,045 subjects underwent a thorough ophthalmologic examination that followed a protocol and included slit and retroillumination images of the lens using Scheimpflug photography (Nidek EAS-1000). Having excluded those with an unsatisfactory quality of Scheimpflug photographs, pseudophakia and artificial eyes, 1,983 eyes from 993 subjects were examined for nuclear lens opacification. These included 887 eyes in 444 males and 1,096 eyes in 549 females. The diagnosis and grading of nuclear lens opacification followed the KMU system [7]. Grades I–IV of nuclear opacities in the KMU system roughly correspond to that of the LOCS II system grades I–IV [5]. The present paper only considers nuclear lens opacities and for the risk factor analysis all grades are combined. The final grading and classification for data analysis were all done based on image analysis (fig. 1).

The present study is done by the worse eye and includes all participants with nuclear lens opacification, including those mixed with a nuclear component in one or both eyes. Unconditional logistic regression analysis was applied to calculate the relative risk and 95% confidence interval adjusted for age.

Results

Nuclear lens opacification was found in at least one eye of 206 participants, of whom 188 (91%) had nuclear lens opacification in both eyes. These numbers include pure nuclear lens opacification and mixed opacification with a nuclear component. There was an increase in nuclear opacification with increased age, 8% of subjects aged 50–69 years having these changes compared with 46% of participants aged 70 years and older. This is further emphasized when the relative risk is calculated for age (table 1) indicating that each year

Table 1. Relative risk analysis for age, gender and systemic disease

CVD cardiovascular disease.

Table 2. Relative risk analysis for smoking and alcohol consumption

people get older; after the age of 50, the risk of developing nuclear lens opacification is increased by 23%. Over a 10-year period this translates into an almost 800% increased risk. Because of this, all of the remaining calculations were done by controlling for the effects of increasing age. No significant gender difference was found (table 1), although there may be a trend for a higher prevalence in women.

Furthermore, there was no significant effect of systemic diseases such as diabetes, cardiovascular disease or asthma (table 1). Subjects were divided into four groups according to their smoking habits, when estimating the amount of lifetime smoking. Those considered to have smoked 20 pack/years had for example smoked one pack of cigarettes a day for 20 years or half a pack for 40 years. Group 1 includes those who had smoked less than 20 pack/years, group 2 includes those who had smoked more than 20 pack/years, group 3 includes participants smoking either pipe or cigars and group 4 includes those who had never smoked. Table 2 shows that those who have smoked less than 20 pack/years

Table 3. Relative risk analysis for UV light exposure: daytime hours spent outdoors, weekdays 8 a.m. to 4 p.m.

have a somewhat higher prevalence of nuclear lens opacification as compared with nonsmokers, though this is not statistically significant. However, when comparing nonsmokers with those who have smoked 20 pack/years or more the latter are found to have a 2.5-fold increased risk for developing nuclear lens opacification and the results for pipe and cigar smokers are similar.

The effect of alcohol consumption was also examined by dividing the sample into those who had sometimes used alcohol and those who had always been abstainers. We found that alcohol consumption increased the risk of nuclear lens opacification by 67% (table 2). After having controlled it for both the effect of age and smoking this difference is, however, not statistically significant.

We examined and analyzed outdoor exposure to extrapolate whether UV radiation has an effect on nuclear lens opacification. Participants had indicated in the questionnaire how long they stayed outdoors during the most critical UV hours (8:00–16:00) on weekdays. The sample was divided into three groups: those who had very little or no outdoor exposure during weekdays, those who had some outdoor exposure (0.5–4 h), and finally persons who had a lot of outdoor exposure ( 4 h/day) during these most important UV hours. This information was also analyzed separately for different time points in people’s life. As can be seen in table 3, outdoor exposure had no significant effect on the risk of nuclear lens opacification.

108 persons had pseudoexfoliation in one or both eyes, 2.4, 8.7, 16.7 and 33.3% in their 50s, 60s, 70s and 80 years old and older, respectively.

After having been controlled for age the effect of pseudoexfoliation on nuclear lens opacification was not statistically significant. Other variables tested but not found to be significant risk factors were computer usage, infrared light exposure, iris color, hyperopia, glaucoma and use of antihypertensive medication, cholesterol-lowering drugs, systemic cortical steroids and allopurinol. Neither was frequent consumption of cod-liver oil, fish, vitamins, plant oil, herrings, sardines and shrimps versus ‘rare’ or ‘never’ consumption found to be significant risk factor. After having been controlled for age cortical lens opacification grade II and III did not carry an increased risk of developing nuclear lens opacification (OR 1.133; CI 0.862–1.501).

Discussion

In the Reykjavik Eye Study [11] we found lens opacification to be a remarkably bilateral condition whereby 84% of those with lens opacification were found to have the same type of lens opacification in both eyes and 77% to have the same type and grade in both eyes. Nuclear opacification was found to be binocular in 91% of instances and the remaining 9% mostly had grade I in one eye and no nuclear lens opacification in the other or the lens had been removed in one eye.

Ageing greatly increased the risk of developing nuclear lens opacification. This effect is probably somewhat underestimated in particular in those aged 80 and older, since 27.3% of males and 32.6% of females were either aphakic or pseudophakic in this age group [9]. It seems likely that many of these persons have had opacification of the lens nucleus, which is commonly found in cataract patients scheduled for surgery [2, 15].

The increased risk of nuclear lens opacification in smokers is interesting since we have not found smoking to be a risk factor for cortical lens opacification among the participants of the Reykjavik Eye Study [10]. These results are, however, in agreement with several epidemiological studies where the main effect of cigarette smoking on lens opacification has been on the nuclear rather than cortical lens opacification [16–18]. Subcapsular lens opacification is not considered in this paper since it was found in only 1.9% of participants in the Reykjavik Eye Study [9].

Outdoor exposure was shown to be a risk factor for pure cortical lens opacification in the Reykjavik Eye Study [10] but does not have a significant effect on nuclear lens opacification in the present analysis. This last finding is in an agreement with most major epidemiological studies where outdoor exposure and UV radiation is not found to be a risk factor for nuclear lens opacification [19–21].

In our study there were few heavy drinkers, who were excluded and moderate drinkers were always compared to abstainers. In our analysis we did not differentiate between the different types of alcohol, e.g. spirits, wines and beers. It is, however, known that for the greatest part of the lifetime of the participants beer was not sold in Iceland and spirits were more commonly consumed than wines. The effect of alcohol consumption was shown to be protective against early cortical lens opacification [10], but has a trend towards an increased risk for nuclear lens opacification in the present analysis, though this does not reach statistical significance. In the Edinburgh study moderate alcohol consumption was found to lower the risk of developing cataract; this study did, however, not differentiate different types of cataract [22]. More recent studies from Australia and the United States have, however, not found moderate drinking to be a significant risk factor for nuclear lens opacification [23, 24].

It is also of interest that systemic cortical steroid use, found to increase the risk of cortical lens opacification 3.7-fold in our study of risk factors for cortical lens opacification [10], does not seem to affect the development of nuclear lens opacification. Cortical steroids have, however, mostly been associated with posterior subcapsular lens opacification. Furthermore, most commonly used drugs in the community including antihypertensive medication, cholesterollowering drugs and allopurinol were not associated with nuclear lens opacification in the present study, which is in agreement with the results of the Blue Mountains Eye Study [25]. Iris color and hyperopia as well as a frequent intake of herring, sardines and shrimps and of plant oil versus ‘rare’ or ‘never’ consumption were found to have a protective effect on the development of cortical lens opacification [10] and do not seem to have any effect on the development of nuclear lens opacification. Pseudoexfoliation has been associated with nuclear lens opacification [26, 27]. In the present study this association did, however, not reach statistical significance, neither for nuclear nor cortical lens opacification. After having been controlled for age cortical lens opacification grade II and III do not increase the risk of developing nuclear lens opacification. Our results confirm the results of previous studies and indicate a different etiology for different types of lens opacification.

References

1Italian-American Cataract Study Group: Risk factors for age related cortical, nuclear and posterior sub-capsular cataracts. Am J Epidemiol 1991;133:541–553.

2Klein BE, Klein R, Moss SE: Incident cataract surgery – Beaver Dam Eye Study. Ophthalmology 1997;104:573–580.

3Mitchell P, Cumming RG, Attebo K, Panchabakesan J: Prevalence of cataract in Australia – The Blue Mountain Eye Study. Ophthalmology 1997;104:581–588.

4Jonasson F, Thordarson K: Prevalence of ocular disease and blindness in a rural area in the Eastern Region of Iceland during 1980 through 1984. Acta Ophthalmol Scand 1987;182(suppl): 40– 43.

5Chylack LT, Leske C, McCarthy D, Khu P, Kashiwagi T, Sperduto R: Lens classification system II (LOCS II). Arch Ophthalmol 1989;107:991–997.

6Sasaki K, Sakamoto Y, Shibata T, Emory Y: Multipurpose camera: A new anterior eye segment analysis system. Ophthalmic Res 1990;22(suppl):3–8.

7Sasaki K, Sakamoto Y, Fujisawa K, Kojima M, Shibata T: A new grading system for nuclear cataracts – An alternative to the Japanese Cooperative Cataract Epidemiology Study Group’s grading. Dev Ophthalmol 1997;27:42–49.

8Garrett SKM, Robman LD, McCarthy CA, Thomas AP, McNeil JJ, Taylor HR: Reproducibility of automatic standard digital analysis of lens opacities. Austr NZ J Ophthalmol 1998;26(suppl): 29–31.

9Sasaki H, Jonasson F, Kojima M, Katoh N, Ono M, Takahashi N, Sasaki K: The Reykjavik Eye Study – Prevalence of lens opacification with reference to identical Japanese studies. Ophthalmologica 2000;214:412–420.

10Katoh N, Jonasson F, Sasaki H, Kojima M, Ono M, Takahashi N, Sasaki K: Cortical lens opacification in Iceland. Risk factor analysis – Reykjavik Eye Study. Acta Ophthalmol Scand 2001;79: 154–159.

11Arnarsson A, Jonasson F, Jonsson V, Sasaki H, Stefánsson E, Bjarnadottir G, Hardarson T, Bjarnadottir A, Sasaki K: Age and sex specific prevalence of lens opacification in Iceland, Reykjavik Eye Study. Icel Med J 1999;85:778–786.

12Kawakami Y, Sasaki H, Jonasson F, Sakamoto Y, Kojima M, Takahashi N, Sasaki K, Ono M: Eigenschaft und Häufigkeit kortikaler Linsentrübung im Frühstadium (Reykjavik Eye Study Group). Klin Monatsbl Augenheilkd 2001;218:78–84.

13World Health Organization: Report on the Informal Consultation for Research Developments on Solar UV-Radiation and Cataractogenesis. Geneva, WHO, 1994, WHO/PBL/94.43.

14Sliney DH: Epidemiological studies of sunlight and cataract: The critical factor of ultraviolet exposure geometry. Ophthalmic Epidemiol 1994;1:107–119.

15Adamsons I, Munoz B, Enger C, Taylor HR: Prevalence of lens opacities in surgical and general populations. Arch Ophthalmol 1991;109:993–997.

16Flaye DE, Sullivan KN, Culliniam TR, Silver JH, Whitelocke RAF: Cataracts and cigarette smoking. Eye 1989;3:379–384.

17West S, Munoz B, Emmet EA, Taylor HR: Cigarette smoking and risk of nuclear cataracts. Arch Ophthalmol 1989;107:1166–1169.

18Hiller R, Sperduto RD, Podgar MJ, Wilson PW, Ferris FL, Colton T, D’Agostino RB, Roseman MJ, Stockman ME, Milton RC: Cigarette smoking and the risk of development of lens opacities. The Framingham Studies. Arch Ophthalmol 1997;115:1113–1118.

19Taylor HR, West SK, Rosenthal FS, Munoz B, Newland HS, Abbey H, Emmett EA: Effect of ultraviolet radiation on cataract formation. N Engl J Med 1988;319:1429–1433.

20Cruickshanks KJ, Klein BE, Klein R: Ultraviolet light exposure and lens opacities: The Beaver Dam Eye Study. Am J Public Health 1992;82:1658–1662.

21Leske MC, Chylack LT, Wu SY: The Lens Opacities Case-Control Study. Risk factors for cataract. Arch Ophthalmol 1991;109:244–251.

22Clayton RM, Cuthbert J, Duffy J, Seth J, Phillips CI, Bartholomew RS, Read JM: Some risk factors associated with cataract in S.E. Scotland. A pilot study. Trans Ophthalmol Soc UK 1982; 102:331–336.

23Cumming RG, Mitchell P: Alcohol, smoking and cataracts: The Blue Mountain Eye Study. Arch Ophthalmol 1997;115:1296–1303.

24Ritter LL, Klein BE, Klein R, Mares-Perlaman JA: Alcohol use and lens opacities in the Beaver Dam Eye Study. Arch Ophthalmol 1993;111:113–117.

25Cumming RG, Mitchell P: Medications and cataract – The Blue Mountains Eye Study. Ophthalmology 1998;105:1751–1758.

26Seland JH, Chylack LT Jr: Cataract in the exfoliation syndrome (fibrillopathia epithelocapsularis). Trans Ophthalmol Soc UK 1982;102:375–379.

27Hietanen J, Kivelä T, Vesti E, Tarkkanen A: Exfoliation syndrome in patients scheduled for cataract surgery. Acta Ophthalmol (Copenh) 1992;70:440–446.

Fridbert Jonasson, Department of Ophthalmology, University Hospital, IS–101 Reykjavik (Iceland)

Tel. 354 560 2066, Fax 354 560 2062, E-Mail fridbert@landspitali.is

Table 1. Classification of UV spectrum and absorption by the cornea and aqueous [3]

but it is also important to develop primary prevention strategies for age-related cataract. The aim of this paper is to review the epidemiologic evidence linking ultraviolet (UV) radiation and cataract. Given the near universal exposure of the population to sunlight and UV, even if there is only a moderate increased risk of cataract due to ocular UV exposure, many cases of cataract could be due to UV exposure.

When considering whether an environmental risk factor, such as UV exposure, is causally linked to an outcome, such as cataract, researchers must be aware of the epidemiologic criteria for causality for non-communicable diseases [2]. Causal inference in epidemiology includes consideration of the following concepts: biological plausibility of the observed association, strength of the association, specificity of the association, experimental evidence, temporal sequence of events, dose-response relationship, and consistency of the observed association. We will now review each of these concepts in relation to the potential causal relationship between UV exposure and cataract in humans.

Biological Plausibility of the Observed Association

A statistically significant association does not provide enough evidence to determine causality; biological plausibility is also required. A review of the UV spectrum and the absorption of UV radiation through the ocular media provides the basis for the biologically plausible association between UV and cataract (table 1) [3]. Virtually no UV-C is available in the normal situations because it is completely absorbed by the ozone layer. Any UV-C that is encountered is absorbed by the cornea and causes acute photokeratitis. Arc welders encounter UV-C and therefore need protective covering for their eyes. Both UV-A and