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

Table 2. Prevalence of lens opacities of all types by gender and age

*p 0.05; **p 0.01.

participants in their 50s, 60s and 70s and of Amami participants in their 50s and 60s was pure cortical. In Amami, the nuclear and mixed types of opacities were seen more frequently than in Noto.

Prevalence of the Three Main Types of Lens Opacities by Age (table 4) Although the prevalence of grades 1–3 cortical opacity was almost the same

in all the groups, that of grade 2 and above was significantly lower in Icelanders than in the others. The prevalence of nuclear opacity and subcapsular opacity was the highest in Singapore followed by Amami. Although the prevalence of cortical opacity was highest in all age groups in the Noto and Icelandic subjects, nuclear opacity was more common after 60 and 80 in Singapore and Amami, respectively.

Prevalence of Nuclear Opacity by Gender

The prevalence of nuclear opacity by gender is shown in table 5. In none of the groups, was any significant difference seen between males and females.

Table 3. Prevalence of four different types of lens opacities by age and extent

Table 4. Prevalence of three main types of lens opacities by age

Table 5. Prevalence of nuclear opacity by age and gender

Distribution of Nuclear Opacity by Age

Figure 1a and b shows the prevalence of nuclear opacity in participants with lens opacification by age. This type of opacity was most frequently seen in Singapore followed by Amami in all age groups. In the 60s age group, the distribution of grades 1–3 and grades 2–3 nuclear opacity in Singapore was about 7.0 and 14.4 times higher than Noto, 1.9 and 2.7 times higher than Amami and 4.6 and 8.2 times higher than Iceland, respectively.

Discussion

The results of our studies suggest that the prevalence of nuclear opacity is extremely high in Singapore followed by Amami. The main type of lens opacity was nuclear in the Singapore group and cortical in the Noto and Icelandic group. The characteristic lens opacity in Amami was in between the above two groups.

When comparing the prevalence of cataracts of all types with grades 2 and 3 opacities, Singaporean participants in their 60s roughly corresponded with those of Noto and Amami in their 70s and those of Iceland in their 80s. These results suggest that the progression of cataract in the Chinese Singaporeans might

Fig. 1. Distribution of nuclear opacity in the subpopulation with lens opacity by age: grade 1–3 (a) and grade 2–3 (b).

be faster than that of the Japanese residents and that of Icelanders might be the slowest among the four groups.

When comparing the prevalence of the three main types of lens opacities, the grade 1–3 cortical opacity was almost the same in the four climatically different regions except that the cortical opacity of grade 2 and above was lower in Icelanders than in the other three groups. Nuclear opacity was highest in Singapore followed by Amami. Although the prevalence of subcapsular opacity was lower than that of the other types of opacity, the prevalence increased rapidly in Singaporeans in their 70s. This type of opacity was quite low in Icelandic subjects in all age groups. When comparing the three main types of grade 2 and above in all the groups, the prevalence of cortical opacity in their 50s was similar to that of nuclear opacity in their 60s and subcapsular opacity in their 70s (table 4).

Although no difference between males and females was seen in the prevalence of nuclear opacity, the prevalence of lens opacities of all types was significantly higher in females than males, in Noto subjects in their 50s, 60s and 70s and in Icelandic subjects in their 70s. As the prevalence of cortical opacity was significantly higher in females in Noto (data not shown) and Iceland [14], the difference seen in all the types came from the prevalence difference of cortical opacity. From the above results, the risk of visual impairment might be higher in females in the places where the main type of opacity is cortical and there might be no difference between tropical and subtropical areas where the main type is nuclear.

Our results showed that, before the prevalence exceeded 50% of the subjects, that of nuclear opacity increased 2.1–5.4 times per decade. This result suggests that once nuclear opacity starts in a population, it increases rapidly with ageing. In Singapore, 22% of the participants developed nuclear opacity in their 50s and the prevalence reached 68% in their 60s. Our results show that the high prevalence of nuclear opacity at a young age is an important indication for a very high prevalence of it after age 60.

The main purpose of this study was to ascertain the characteristic presence of nuclear cataracts in residents of the tropics and subtropics, and indeed the Singapore and Amami groups have an unusually high prevalence of this type of opacity. We found the same phenomenon in our epidemiological study in Sumatra, Indonesia [18] where the prevalence of nuclear opacity was extremely high. Furthermore, we have done epidemiological studies in three climatically different places in Japan: Hokkaido in the north, Noto in the central area and Okinawa in the south [11]. We have also found that the prevalence of nuclear opacity in the population of Okinawa was significantly higher than that of the other two places. The results of all the studies we have done indicate that the subjects of tropical and subtropical areas are at a high risk for developing nuclear opacity at an early age. We speculated on a possible reason such as race, lifestyle, solar UV and environmental temperature. Regarding race, West et al. [4] found that Caucasians were significantly more likely to have nuclear opacity than African Americans. However, since there was a significant difference in the prevalence of nuclear opacity between the two groups of subjects in Amami and Noto Japan, some other factor must also influence the development of nuclear opacity. The common factors of the living conditions in Singapore, Sumatra, Okinawa and Amami appear to be high UV exposure and high ambient temperature. There have been few studies on the appearance of cataracts that focused on the effect of high environmental temperature on the degree and prevalence of nuclear opacities [19]. Kojima [20] reported that the light scattering intensity in the nuclear part was significantly higher in the rats with a higher ambient temperature than in those with normal temperature. This result indicated the correlation between the high ambient temperature and nuclear opacity.

The effect of high temperature on cataract formation needs further investigation. Regarding the correlation between UV exposure and nuclear opacity, although Wong et al. [21] reported that a higher grade of nuclear cataract tended to be more common in subjects with the most sun exposure, most of the studies have denied this [8, 22–24]. Although no significant correlation was seen between the period of time spent outdoors and nuclear opacity in our studies (data not shown), further investigations should be made.

References

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12Sasaki H, Asano K, Kojima M, Sakamoto Y, Kasuga T, Nagata M, Takahashi N, Sasaki K, Ono M, Katoh N: Epidemiological survey of ocular diseases in K Island; Prevalence of cataract and pterygium. J Jpn Ophthalmol Soc 1999;103:556–563.

13Sasaki H, Shui YB, Kojima M, Chew SJ, Ono M, Katoh N, Cheng HM, Takahashi N, Sasaki K: Characteristics of cataracts in the Chinese Singaporean. J Epidemiol 2001;11:16–23.

14Sasaki 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.

15Katoh N, Sasaki K, Obazawa H: Japanese Cooperative Cataract Epidemiology Study Group: Interview form applied to a cataract epidemiologic study. Dev Ophthalmol 1991;21:108–114.

16Sasaki K, Shibata T, Obazawa H, et al: Classification system for cataracts. Application by the Japanese Cooperative Cataract Epidemiology Study Group. Ophthalmic Res 1990;22(suppl 1): 46–50.

17Sasaki 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 system. Dev Ophthalmol 1997;27:42–49.

18Sasaki K, Zainuddin J, Fujisawa K, Kojima M, Sakamoto Y: Cataract epidemiology study in West Sumatra. Dev Ophthalmol 1989;17:26–32.

19Miranda MN: Environmental temperature and senile cataract. Trans Am Ophthalmol Soc 1980; 78:255–264.

20Kojima M, Okuno T, Miyakoshi M, Sasaki K: Effect of environmental temperature on cataract progression in diabetic rats. J Eye 2000;17:555–558.

21Wong L, Ho SC, Coggon D, Cruddas AM, Hwang CH, Ho CP, Robertshaw AM, MacDonald DM: Sunlight exposure, antioxidant status, and cataract in Hong Kong fishermen. J Epidemiol Community Health 1993;47:46–49.

22Taylor 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.

23Cruickshanks KJ, Klein BEK, Klein R: Ultraviolet light exposure and lens opacities: The Beaver Dam Eye Study. Am J Public Health 1992;82:1658–1662.

24Delcourt C, Carriere I, Ponton-Sanchez A, Lacroux A, Covacho MJ, Papoz L: Light exposure and the risk of cortical, nuclear, and posterior subcapsular cataracts: The Pathologies Oculaires Liées à I’Age (POLA) study. Arch Ophthalmol 2000;118:385–392.

Hiroshi Sasaki, MD, Department of Ophthalmology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 8920-0293 (Japan)

Tel. 81 76 286 2211, Fax 81 76 286 1010, E-Mail sasakimy@aioros.ocn.ne.jp

Current safety standards for the avoidance of cataract after exposure of the eye to UVR [12] are based on an experimental qualitative determination of the toxicity of UVR to the lens [10] and a comparison with environmental exposure of the human eye and skin to provide an adequate margin of safety. The toxicity estimation in the latter experiment was based on the assumption that the occurrence of cataract after an exposure to UVR is a binary response event. Classically, the ED50 strategy [13] is used for toxicity estimation for binary response events.

It has, however, been shown with quantitative measurement of cataract that the dose-response function for UVR-induced cataract is continuous [14]. Therefore, it was attempted here to develop a strategy for toxicity estimation for continuous dose-response functions.

Materials and Methods

Cataract was induced experimentally in rats with UVR-300 nm. Thereafter, a strategy for the estimation of the maximum tolerable dose (MTD) for the avoidance of cataract was developed.

UVR Exposure

Six-week-old Sprague-Dawley rats were anesthetized with an intraperitoneal injection of xylazine (14 mg/kg) and ketamine (94 mg/kg) 10 min prior to exposure. Both eyes were dilated with tropicamide (5 mg/ml) 5 min prior to exposure. The rats were unilaterally exposed to UVR-300 nm (T-max: 300 nm, half-width: 5 nm). The UVR-300 nm was generated with a high-pressure mercury arc source filtered with a water filter. The UVR-300 nm was spectrally selected with a double monochromator. The rats were sacrificed after 1 week in order to allow for maximum intensity of light scattering to develop [15, 16]. Both eyes were enucleated. For each eye, the lens was isolated and transferred to a cuvette containing a balanced salt solution (BSS, Alcon, USA). The intensity of forward scattered light was measured [17].

Experimental Design and Statistics

Altogether, 20 rats were divided into five groups of 4 rats each. The rats from the first group were put on the exposure bench, as the rats from all the other groups, but did not receive any UVR. The other groups received 1, 2, 4 or 8 kJ/m2.

The light scattering data obtained were then analyzed with linear regression.

Ethical Approval

The study had been approved by the local ethical committee for experimental animals.

MTD Strategy

If the intensity of forward light scattering is measured in both eyes in normal nonexposed rats with the method cited above [17], the difference of light scattering will be normal distributed around 0 (fig. 1).

The probability of finding a difference of light scattering between the lenses in a rat in the population of rats of 2 above 0 is 2.3%.

Fig. 1. Frequency distribution of a difference of intensity of light scattering in the normal eyes of a rat. The difference of intensity of forward light scattering is approximately normal distributed with a standard deviation, , and the mean 0, N(0, ).

Fig. 2. Dose-response function for UVR-induced cataract close to a dose that induces an insignificant increase of light scattering ( ). Juxtaposed the limit describing 1 standard deviation ( ) more intense light scattering has been drawn (—).

It is known from previous work [14] that the dose-response function, expressed as difference of intensity of forward light scattering between the exposed and contralateral nonexposed eye, for UVR-induced cataract at doses close to the level where no cataract is induced can be simplified to a 2nd order polynomial, omitting the first order term (equation 1).

where ε belongs to a normal distribution, N(0, ). This is illustrated in figure 2.