Incidence of cataract operations in Finnish male smokers unaffected by alpha tocopherol or beta carotene supplements.

OBJECTIVE: To examine the effect of alpha tocopherol and beta carotene supplementation on the incidence of age related cataract extraction. SETTING: The Alpha-tocopherol Beta-carotene (ATBC) Study was a randomised, double blind, placebo controlled, 2 x 2 factorial trial conducted in south western Finland. The cataract surgery study population of 28,934 male smokers 50-69 years of age at the start. INTERVENTION: Random assignment to one of four regimens: alpha tocopherol 50 mg per day, beta carotene 20 mg per day, both alpha tocopherol and beta carotene, or placebo. Follow up continued for five to eight years (median 5.7 years) with a total of 159,199 person years. OUTCOME MEASURE: Cataract extraction, ascertained from the National Hospital Discharge Registry. RESULTS: 425 men had cataract surgery because of senile or presenile cataract during the follow up. Of these, 112 men were in the alpha tocopherol alone group, 112 men in the beta carotene alone group, 96 men in the alpha tocopherol and beta carotene group, and 105 men in the placebo group. When supplementation with alpha tocopherol and with beta carotene were introduced to a Cox proportional hazards model with baseline characteristics (age, education, history of diabetes, body mass index, alcohol consumption, number of cigarettes smoked daily, smoking duration, visual acuity, and total cholesterol), neither alpha tocopherol (relative risk, RR, 0.91, 95% confidence intervals, CI, 0.74, 1.11) nor beta carotene (RR 0.97, 95% CI 0.79, 1.19) supplementation affected the incidence of cataract surgery. CONCLUSION: Supplementation with alpha tocopherol or beta carotene does not affect the incidence of cataract extractions among male smokers.

Six-year supplementation with alpha-tocopherol and beta-carotene and age-related maculopathy.

PURPOSE: Animal research and observational studies in man suggest a protective effect of antioxidant vitamins in the development of age-related maculopathy (ARM). METHODS: The ATBC study, a population-based, controlled clinical trial of alpha-tocopherol and beta carotene to prevent lung cancer, took place in Finland between 1984 and 1993. Over 29,000 smoking males aged 50 to 69 years were randomly assigned to alpha-tocopherol (AT; 50 mg/day), beta-carotene (BC; 20 mg/day), both of these, or placebo. We performed an end-of-trial ophthalmological examination on a random sample of 941 participants aged 65 years or more from two of the fourteen study areas, to discover if the five to eight-year intervention with alpha-tocopherol and/or beta-carotene had been associated with a difference in ARM prevalence. Age-related maculopathy was assessed using colour photographs of the macula. RESULTS: Altogether, 269 cases of ARM were found; there were more cases in the AT group (32%; 75/237), BC group (29%; 68/234), and combined antioxidant group (28%; 73/257) than in the placebo group (25%; 53/213). However, neither substance was significantly associated with the risk of ARM in a logistic regression analysis controlling for possible risk factors. CONCLUSIONS: No beneficial effect of long-term supplementation with alpha-tocopherol or beta-carotene on the occurrence of ARM was detected among smoking males.

Retinal vascular changes following supplementation with alpha-tocopherol or beta-carotene.

PURPOSE: To examine if long-term supplementation with alpha-tocopherol (AT) or beta-carotene (BC) was associated with the prevalence of vascular changes in retinal arterioles. METHODS: An end-of-trial subsample from a double-blind, placebo-controlled clinical trial designed to study the effects of alpha-tocopherol and beta-carotene on lung cancer incidence (ATBC Study). SETTING: Source population of Helsinki and the surrounding province. PARTICIPANTS: 1072 men 50-69 years old and smoking at least 5 cigarettes per day at study entry. INTERVENTIONS: Random allocation to one of four supplementation regimens: 50 mg per day alpha-tocopherol, 20 mg per day beta-carotene, both alpha-tocopherol and beta-carotene, or placebo. Median follow-up time was 6.6 years (range 5.2-8.0 years). MAIN OUTCOME MEASURE: Presence of vascular changes in retinal arterioles as determined from end-of-trial retinal color photographs. RESULTS: Retinal vascular changes were most prevalent in the AT (161 men, 62%), and in the BC (163 men, 62%) groups. The prevalence rate was lowest in the AT plus BC group (161 men, 55%), and slightly higher in the placebo group (145 men, 57%). There was no statistically significant association of either AT (OR 0.9, 95% CI 0.7-1.2) or BC (OR 1.0, 95% CI 0.8-1.3) supplementation with the prevalence of retinal vascular changes after adjusting for major risk factors. CONCLUSIONS: Supplementation with alpha-tocopherol or beta-carotene for a median of 6.6 years does not protect against retinal vascular changes among smoking males.

Long-term supplementation with alpha-tocopherol and beta-carotene and age-related cataract.

PURPOSE: To study if long-term supplementation with alpha-tocopherol or beta-carotene is associated with cataract prevalence and severity. METHODS: An end-of-trial random sample of 1828 participants from the randomized, double-blind, placebo-controlled clinical trial the alpha-tocopherol, beta-carotene cancer prevention study. The alpha-tocopherol, beta-carotene cancer prevention study was originally designed to examine whether supplementation with alpha-tocopherol or beta-carotene would reduce the incidence of lung cancer in male smokers. The participants for this study lived in Helsinki City or Uusimaa province and were at entry to the alpha-tocopherol, beta-carotene cancer prevention study 50 to 69 years old and smoked at least 5 cigarettes per day. They received alpha-tocopherol 50 mg/day, beta-carotene 20 mg/day, a combination of the two, or placebo supplements for 5 to 8 years (median 6.6 years). Outcome measures were: cortical, nuclear, and posterior subcapsular cataract, differentiated and quantified with lens opacity classification system (LOCS II). Lens opacity meter provided a continuous measure of cataract density. RESULTS: Supplementation with alpha-tocopherol or beta-carotene was not associated with the end-of-trial prevalence of nuclear (odds ratio 1.1 and 1.2, respectively), cortical (odds ratio 1.0 and 1.3, respectively), or posterior subcapsular cataract (odds ratio 1.1 and 1.0, respectively) when adjusted for possible confounders in logistic model. Neither did the median lens opacity meter values differ between the supplementation groups, indicating no effect of alpha-tocopherol or beta-carotene on cataract severity. CONCLUSION: Supplementation with alpha-tocopherol or beta-carotene for 5 to 8 years does not influence the cataract prevalence among middle-aged, smoking men.

Heritability of defects of far vision in young adults--a twin study.

A questionnaire to study defects in far vision in the Finnish Twin Cohort Study was sent to 600 twin pairs of 30 and 31 years of age divided equally by gender and zygosity. An excess in female prevalence of defects in far vision was observed (p less than 0.001). Validation of the questionnaire method to assess negative spherical equivalent of refraction was performed by asking the twins to send their last prescription for glasses. Accuracy of the questionnaire method to detect in far vision was tested using a subsample of cases where actual refraction obtained from the prescription for glasses was available. This actual refraction value was compared with the individuals answers to the questions of far vision. Of the subjects 5.5% were false negatives and 1.8% of the individuals were false positives. In 152 pairs one or both twins had a defect in far vision. Under a threshold liability model, the proportion of total (phenotypic) variance in liability attributable to additive genetic effects was 0.91 in this twin data, while no evidence for effects due to dominance was found.

Twin study on cup/disc ratio of the optic nerve head.

Seventeen healthy twin pairs (10 monozygotic and seven dizygotic) from the Finnish Twin Cohort Study were examined to study the impact of heredity v environment in the determination of cup-to-disc area ratio. These twins were free from any known eye disease. The cup/disc ratio was determined using stereo photography and a computer assisted analysis technique. The zygosity of all twin pairs was confirmed with the DNA 'fingerprint' technique. The intrapair correlations were high among monozygotic pairs compared with those among dizygotic twin pairs. The difference of cup/disc area ratios between the right eyes of members of monozygotic twin pairs was statistically significantly smaller than that of dizygotic twin pairs (p < 0.001). The same was true for left eyes (p < 0.01). This result confirms a genetic determination in cup/disc area ratio in normal eyes.

Acute closed angle glaucoma and sunshine.

STUDY OBJECTIVE: The aim was to examine a possible association of amount of sunshine and risk for acute closed angle glaucoma. DESIGN: This was a retrospective analysis of hospital discharge registry data, linked to meteorological data for the same period. SETTING: The study was a national survey using hospital discharge data for the whole of Finland over a 10 year period. PARTICIPANTS: All subjects with the acute closed angle glaucoma diagnosis from the hospital discharge registry were collected for the years 1972 to 1982. A total of 1796 patients were found. MEASUREMENTS AND MAIN RESULTS: Meteorological data from two cities in Finland, Helsinki and Oulu, were collected for the same years from the Finnish Meteorological Institute. A peak incidence of acute closed angle glaucoma was noted whenever the number of hours without sunshine increased. A regression analysis including incidence of acute closed angle glaucoma as a dependent variable, and sex, mean temperature, mean air pressure, mean humidity, total amount of rain per month, and mean sunshine hours as independent variables, was constructed. Sex and sunshine hours best explained the variation in incidence in a covariate model. No other meteorological variate could improve the model fit. CONCLUSIONS: The result confirms that the number of hours without sunshine is positively associated with the incidence of acute closed angle glaucoma, when other meteorological variables are controlled for.

Impact of heredity in myopia.

A series of 109 like-sexed twin pairs in the age group 30-31 years (54 monozygotic and 55 dizygotic) with one or both members of the twins with myopia was found in the Finnish Twin Cohort. The series was based on a random sample of 1,200 twins in one age stratum of the cohort. The twins received a questionnaire on their health status with special reference to eye diseases and symptoms. The refractive status of the twin pairs was ascertained by asking the twins to send their latest prescription for glasses to the authors or the refraction was obtained from the ophthalmologists or opticians of the twins. The mean difference in refraction between the monozygotic twins was 1.19 dptr in the right eyes and 1.15 dptr in the left eyes. The difference between dizygotic pairs was 2.34 dptr in the right eyes and 2.47 dptr in the left eyes. Analysis of variance showed that the difference in refraction between the two eyes of a twin pair was not significant. The mean difference in refraction between the monozygotic twins was significantly lower than that between dizygotic twins (p less than or equal to 0.001). The intrapair variances were doubled among dizygotic twin pairs compared to monozygotic twin pairs in the male group. The intrapair variance in the female group was 4-fold among dizygotic twin pairs as compared to monozygotic twin pairs. Heritability of myopia was 0.58 (0.74 for males and 0.61 for females) when myopia was considered a dichotomous variable. This result suggests that inheritance has a substantial effect on the etiology of myopia.

Astigmatism in 72 twin pairs.

The Finnish Twin Cohort Study was used to compile twin pairs in whom one or both members had astigmatism. Seventy-two pairs of twins (42 monozygotic and 30 dizygotic) were found. Refractive error and astigmatism information was obtained by asking the twins to send their last prescription for glasses to the authors. The correlations between monozygotic twins for astigmatism were not higher than the correlations between dizygotic twins. The differences in the amounts of astigmatism in monozygotic twins was not statistically significantly different than that in dizygotic twins. This suggests that genetic factors do not contribute to astigmatism, leaving environmental causes as major contributors.

Epidemiologic data on adult glaucomas. Data from the Hospital Discharge Registry and the Registry of Right to Free Medication.

The prevalence of glaucoma was studied using material from the Registry of Right to Free Medications, completed by the Social Insurance Institution of Finland in 1985. A total of 31,981 patients (10,022 males and 21,959 females) received free medication for glaucoma in 1985. Total crude glaucoma prevalence in Finland in 1985 was 0.67%, calculated for the total population (all glaucomas) according to data from this registry. The crude prevalence for those of 40 years of age and over, was 1.7% and for those of age 70 years and older, 6.1%. Age adjusted prevalence showed a female excess of cases with a male-female ratio of 1/1.3. The incidence of different types of glaucoma was studied using the Hospital Discharge Registry for the years 1973-1982. For this 10-year period, a total of 48,864 patients with glaucoma and 10,614 glaucoma suspects were found in a compilation based on an International Classification of Diseases (8th edn.) code number. Of all adult glaucomas, 67% were primary glaucomas, while 33% were secondary glaucomas. An increase in the incidence of glaucoma was noted during the 10-year period, especially for the chronic simple and capsular glaucoma groups. Females were at higher risk for chronic simple, acute angle-closure, capsular and chronic angle-closure glaucoma; whereas, males were at greater risk for other types of secondary glaucomas. The patients with secondary glaucoma were the youngest (mean age 53.5 years in males, and 60.3 years in females), while the patients with capsular glaucoma were the oldest (mean age 71.9 years in males, and 72.8 in females).

Closed-angle glaucoma in 20 pairs of twins.

Two pairs of twins with chronic closed-angle glaucoma identified from the Finnish Twin Cohort Study were clinically studied by the author, and 18 other pairs of twins with the disease were ascertained from the Hospital Discharge Registry of Finland. One of the clinically studied pairs was a pair of monozygotic female twins concordant for chronic closed-angle glaucoma and the other was a pair of dizygotic female twins discordant for the disease. Of the pairs of twins ascertained from the registry one was a monozygotic male pair concordant for closed-angle glaucoma. The remaining 17 pairs (12 same-sex dizygotic and 5 monozygotic pairs) were discordant for the disease. The findings support multifactorial inheritance of chronic closed-angle glaucoma.

Heritability estimate for refractive errors--a population-based sample of adult twins.

The population-based Finnish Twin Cohort study was used to establish a heritability estimate for refractive errors especially for myopia. The twin cohort was derived from adult same-sexed twins in Finland. The total number of twins with both members alive in 1984 was 23,570. Of these, 3,676 twin pairs were monozygotic, and 8,109 pairs dizygotic. The sample for the present study was linked from the Finnish Police Force data base in 1984, where information of a person's possession of a driver's license and the obligation to wear glasses for far correction when driving a motor vehicle is recorded. Correlations in liability were estimated according to a multifactorial method of Smith. Falconer's heritability was 0.62 among males and 0.98 among females in the age group 28-29 years. When compared to previous twin studies of myopia, the proband concordance rates were higher for both MZ and DZ twin pairs.

Myopia and stature.

The association of myopia and height, weight and body-mass index was examined by two methods: a case control method and a co-twin control method. One hundred eightyseven myopic (57 males and 130 females) and 603 non-myopic (335 males and 268 females) subjects were studied in the first study. Among males the myopic subjects were taller compared to the non-myopic subjects (P less than 0.05). Among females such difference could not be found. Weight was not statistically significantly different in these two groups in either sex. When the myopic twin partners were compared to the non-myopic co-twins, a statistically significant difference in body mass index could again be noticed among males (P less than 0.01) but not among females. The difference in social class did not explain the previous associations.

Genetic factors in open-angle (simple and capsular) glaucoma. A population-based twin study.

A nationwide record linkage of the Finnish Twin Cohort Study (FTCS) with the Hospital Discharge Registry and the Registry of Rights for Free medication is presented. This study consists of 108 pairs (114 individuals) of twins with chronic open-angle glaucoma. Of the twin pairs 29 were monozygotic (MZ), while 79 pairs were dizygotic (DZ). Three monozygotic and 3 dizygotic pairs were concordant for chronic open-angle glaucoma (OAG), while 26 monozygotic and 76 dizygotic pairs were discordant. Seventy-three twins had chronic simple glaucoma, while 34 twins had capsular glaucoma, and in 7 patients chronic simple glaucoma was noted in one eye and capsular glaucoma in the second eye. The heritability of chronic open angle glaucoma was 13%. The higher O/E-ratio of concordant twin pairs among MZ twins indicates that genetic factors play a role in this disease. The difference is anyhow surprisingly low compared to former estimates of heritability of open angle glaucoma. The steep rise in prevalence in older age groups was confirmed. The age-adjusted prevalence of chronic open-angle glaucoma in this study was 0.63%.

Validity of hospital discharge registry in acute glaucoma.

Validity of hospital discharge registry in Finland was evaluated in acute glaucoma. Hospital records of 172 patients with the diagnosis 370.00 (acute glaucoma) in the registry were collected from different hospitals. The typical findings in acute glaucoma were searched for in patient documents. The diagnosis of acute glaucoma was in agreement in both the registry and in the present investigation in 80.2%. Other recordings validated in patient files (% of agreement in parenthesis) were: date of birth (98.8%), social security number (92.4%), sex (99.4%), hospital code (100%), date of admission (88.4%), date of discharge (90.2%). The type of hospital did not affect the amount of false recordings. The highest percentage of false recordings was noticed in the health care centers. The most common false diagnoses were: simple glaucoma (11 cases), secondary glaucoma (8 cases) and chronic congestive glaucoma (7 cases). The validity assessment is of importance in epidemiologic studies employing discharge registries.

Primary open-angle glaucoma in 2 monozygotic twin pairs.

Two monozygotic twin pairs with primary open-angle glaucoma (POAG) derived from the Finnish Twin Cohort Study were studied. The first female twin pair was concordant, and the second female pair was discordant for primary open-angle glaucoma. The nondiseased member of this second pair showed preglaucomatous signs in the form of ocular hypertension. The clinical study of the patients included a careful ophthalmologic examination, retinal nerve fiber layer (RNFL) photography and optic disc stereophotography. Visual fields were tested with an automated perimeter (Octopus 2000). The small number of twin pairs in the present study does not permit quantitative analysis of heritability, but it is obvious that whenever a clinical diagnosis of primary open-angle glaucoma in a monozygotic twin is made, the co-twin should be carefully examined.

Ophthalmic disease in twins: a nationwide record linkage study of hospital discharges and free medications for 16,067 twin pairs.

Record linkage of the Finnish Twin Cohort Study with the Hospital Discharge Registry and with the Registry of Rights to Free Medication kept by the Social Insurance Institution gave following numbers of twin pairs with an ophthalmic disease (one or both members of the pair had the disease) in each disease category: 98 with glaucoma simplex (5 concordant pairs), 38 with capsular glaucoma (no concordant pairs), 58 with iritis (no concordant pairs) and 149 with strabismus (2 concordant pairs). The number of concordant pairs in each disease category was small, except for glaucoma simplex in which concordant pairs could be broken down by zygosity. The ratio of observed to expected (based on association by chance) was 6.96 for MZ and 1.74 for DZ pairs. This result suggests that genetic factors play some role in the variability of prevalence of simple glaucoma. Main etiologic factors are still to be found in the environment. Data on occurrence of other diseases of ophthalmologic importance is presented.

Incidence of choroidal malignant melanoma in Finland in the years 1973-1980.

Recent reports concerning the incidence of choroidal and ciliary body melanomas have raised a suspicion of an increase of this malignancy in the developed countries. The rapid rise in the incidence of melanoma of the skin is well known. This study covers the incidence of choroidal and ciliary body melanomas in Finland over the years 1973-1980. A total of 382 cases of intraocular malignant tumours were reported to the Finnish Cancer Registry. 285 choroidal and ciliary body melanomas were found. The age-specific incidences showed a steep rise from the age of 30 to the age of 70. The peak incidence was in the age-group 70 and over. There was only one case, a girl 12 of age, in the age-group 15 years and younger. The age adjusted incidences showed no significant increase during the study period. The age-specific incidence showed no significant difference compared to a previous study. Sex, laterality or latitude were not found to be risk factors.