Occupational exposure to low doses of ionizing radiation and cataract development: a systematic literature review and perspectives on future studies.

Ionizing radiation is a well-known but little understood risk factor for lens opacities. Until recently, cataract development was considered to be a deterministic effect occurring at lens doses exceeding a threshold of 5-8 Gy. Substantial uncertainty about the level and the existence of a threshold subsists. The International Commission on Radiation Protection recently revised it to 0.5 Gy. Based on a systematic literature review of epidemiological studies on exposure to low levels of ionizing radiation and the occurrence of lens opacities, a list of criteria for new epidemiological studies was compiled, and a list of potential study populations was reviewed. Among 24 publications finally identified, six report analyses of acute exposures in atomic bomb survivors and Chernobyl liquidators, and the others report analyses of protracted exposures in occupationally, medically or accidentally exposed populations. Three studies investigated a dose threshold: in atomic bomb survivors, the best estimates were 1 Sv (95 % CI <0-0.8 Sv) regarding lensectomies; in survivors exposed as children, 0.6 Sv (90 % CI <0.0-1.2 Sv) for cortical cataract prevalence and 0.7 Sv (90 % CI 0.0-2.8 Sv) for posterior subcapsular cataract; and in Chernobyl liquidators, 0.34 Sv (95 % CI 0.19-0.68 Sv) for stage 1 cataract. Current studies are heterogeneous and inconclusive regarding the dose-response relationship. Protracted exposures and high lens doses occur in several occupational groups, for instance, in physicians performing fluoroscopy-guided interventional procedures, and in accidentally exposed populations. New studies with a good retrospective exposure assessment are feasible and should be initiated.

Radiation dose and cataract surgery incidence in atomic bomb survivors, 1986-2005.

PURPOSE: To examine the incidence of clinically important cataracts in relation to lens radiation doses between 0 and approximately 3 Gy to address risks at relatively low brief doses. MATERIALS AND METHODS: Informed consent was obtained, and human subjects procedures were approved by the ethical committee at the Radiation Effects Research Foundation. Cataract surgery incidence was documented for 6066 atomic bomb survivors during 1986-2005. Sixteen risk factors for cataract, such as smoking, hypertension, and corticosteroid use, were not confounders of the radiation effect on the basis of Cox regression analysis. Radiation dose-response analyses were performed for cataract surgery incidence by using Poisson regression analysis, adjusting for demographic variables and diabetes mellitus, and results were expressed as the excess relative risk (ERR) and the excess absolute risk (EAR) (ie, measures of how much radiation multiplies [ERR] or adds to [EAR] the risk in the unexposed group). RESULTS: Of 6066 atomic bomb survivors, 1028 underwent a first cataract surgery during 1986-2005. The estimated threshold dose was 0.50 Gy (95% confidence interval [CI]: 0.10 Gy, 0.95 Gy) for the ERR model and 0.45 Gy (95% CI: 0.10 Gy, 1.05 Gy) for the EAR model. A linear-quadratic test for upward curvature did not show a significant quadratic effect for either the ERR or EAR model. The linear ERR model for a 70-year-old individual, exposed at age 20 years, showed a 0.32 (95% CI: 0.09, 0.53) [corrected] excess risk at 1 Gy. The ERR was highest for those who were young at exposure. CONCLUSION: These data indicate a radiation effect for vision-impairing cataracts at doses less than 1 Gy. The evidence suggests that dose standards for protection of the eye from brief radiation exposures should be 0.5 Gy or less.

[Cataract: based on A-bomb survivor studies].

Until now, the radiation protection community had assumed that only high doses of 2 Gy or more cause cataracts. However, new data from the atomic-bomb (A-bomb) survivors suggest that the dose threshold for both minor opacities and vision limiting cataracts may be below 1 Gy. Other studies have shown similar results in recent years. In 2011, the International Commission on Radiological Protection (ICRP) revised their guidelines for permissible occupational and medical exposures to the eye.

[Radiation effects on pregnant women, fetuses, and children].

We conducted a review of literature related to radiation effects on pregnant women, fetuses, and children from the perspective of epidemiology, pathology, and radiobiology. During 8-25 weeks post-conception the central nervous system is particularly sensitive to radiation. Fetal doses in excess of 100 mGy can result in some reduction of IQ (intelligence quotient). Fetal doses in the range of 1000 mGy can lead to severe mental retardation and microcephaly, particularly during 8-15 weeks and to a lesser extent 16-25 weeks after conception. Recent studies of cancers and chromosome aberrations indicated less radiosensitivity in prenatally exposed A-bomb survivors compared with postnatally exposed survivors, for which we provide possible hypotheses as an explanation.

Body iron stores and breast cancer risk in female atomic bomb survivors.

Iron can be a potent pro-oxidant and, on this basis, elevated body iron may increase the risk of cancer. Although epidemiological evidence is mixed, there is overall support for this possibility. In addition, because of this same oxidative capacity, body iron levels may alter radiation sensitivity. In the present study, a nested case-control study of breast cancer was conducted in Japanese atomic bomb survivors. Stored serum samples from the Adult Health Study cohort were assayed for ferritin levels and joint statistical analyses were conducted of ferritin and radiation dose on the risk of breast cancer. Serum ferritin is the best feasible indicator of body iron levels in otherwise healthy people. A total of 107 cases and 212 controls were available for analysis. The relative risk (RR) of breast cancer for a 1 log unit increase in ferritin was 1.4 (95% confidence interval 1.1-1.8). This translates to an RR of 1.64 comparing high and low values of the interquartile range among controls (58 and 13.2 ng/mL, respectively). The results support the hypothesis that elevated body iron stores increase the risk of breast cancer. However, the study was inconclusive regarding the question of whether body iron alters radiation-induced breast cancer risk.

Metabolic cardiovascular disease risk factors and their clustering in subclinical hypothyroidism.

OBJECTIVE: A possible association between subclinical hypothyroidism and cardiovascular disease (CVD) has been reported. Monitoring of atomic-bomb survivors for late effects of radiation exposure at the Radiation Effects Research Foundation has provided the opportunity to examine associations between subclinical hypothyroidism and metabolic CVD risk factors. The objective of the study was to evaluate associations between subclinical hypothyroidism and metabolic CVD risk factors, and a cluster of these factors. DESIGN AND PARTICIPANTS: This was a cross-sectional study of 3549 subjects (mean age 70 years; 1221 men and 2328 women) between 2000 and 2003 comprising 306 subjects with subclinical hypothyroidism and 3243 control euthyroid subjects in Japan. MEASUREMENTS: We investigated associations between subclinical hypothyroidism and metabolic CVD risk factors such as hypertension, diabetes mellitus, dyslipidaemia and hyperuricaemia, and a cluster of these factors. RESULTS: Subclinical hypothyroidism was not significantly associated with either hypertension, diabetes mellitus or hyperuricaemia defined by taking into account the use of medications in both men and women, but in men it was associated with dyslipidaemia (P = 0.02). We observed a significantly increased odds ratio (OR) for the presence of three or more metabolic CVD risk factors in men with subclinical hypothyroidism after adjusting for age, body mass index (BMI), and smoking status [OR: 1.83, 95% confidence interval (CI): 1.13-2.94, P = 0.01]. The significant associations remained after an additional adjustment for atomic-bomb radiation dose. CONCLUSIONS: There appears to be a significant increase in a cluster of metabolic CVD risk factors among people with subclinical hypothyroidism.

Thyroid diseases in atomic bomb survivors exposed in utero.

OBJECTIVE: The objective of the study was to evaluate the association of thyroid disease with radiation dose in atomic bomb survivors exposed in utero. DESIGN: This was a cross-sectional study. SETTING: The study was conducted in atomic bomb survivors in Hiroshima and Nagasaki, Japan. PARTICIPANTS: Participants included 328 atomic bomb survivors exposed in utero (mean age 55.2 yr, 162 males) who participated in the thyroid study at the Radiation Effects Research Foundation. Examinations were conducted between March 2000 and February 2003. MAIN OUTCOME MEASURES: The relationships of various thyroid conditions to atomic bomb radiation dose were measured. RESULTS: Among the 319 participants excluding nine participants whose exposure radiation dose was not estimated, the mean maternal uterine radiation dose was 0.256 Gy. We observed no significant dose-response relationship for the prevalence of solid thyroid nodules (odds ratio at 1 Gy, 2.78; 95% confidence interval 0.50-11.80, P = 0.22), but the risk estimate was similar to the estimate for childhood exposures. The prevalence of cysts and autoimmune thyroid diseases was not associated with radiation dose (P > 0.30). We could not evaluate the dose response for malignant tumors or benign nodules due to the small number of cases. CONCLUSIONS: We did not observe a statistically significant linear dose response to radiation for thyroid nodules or autoimmune thyroid diseases 55-58 yr after participants' in utero exposure. However, the risk estimate for solid thyroid nodules was similar for those exposed in utero and those exposed in childhood. Because the study had limited statistical power to detect moderately sized effects, further studies are needed for a definitive conclusion.

Frequency of hemochromatosis gene (HFE) mutations in Russian healthy women and patients with estrogen-dependent cancers.

Possible association between the C282Y and H63D mutations in the HFE gene and estrogen-dependent cancer risk was assessed. Genotyping was performed using PCR amplification followed by digestion of products with specific restrictases. In a population of 260 healthy women (permanent residents of the southwest European Russia), mutant allele frequencies at the C282Y and H63D sites were evaluated as 3.3 and 16.3%, respectively. In patients with breast, ovarian, and endometrial cancer, C282Y frequencies were also low (1.0, 1.3, and 3.8%, respectively), and no cancer risk associated with the C282Y mutation was found. Odds ratios for breast cancer risk associated with the H63D mutation increased significantly with age: 0.5 in women below 48 years old, 1.0 in a range of 48-57 years, and 4.4 in older women (P(trend)=0.002). The latter value was statistically significant (95% CI, 1.4-14.1), indicating that women bearing the H63D mutation may be at an increased breast cancer risk at an age above 57 years. Preliminary results obtained in patients with two other estrogen-dependent malignancies revealed the same tendency to OR increase with age in ovarian cancer patients (P(trend)=0.008), but no age-related OR differences in endometrial cancer patients.

Systolic blood pressure and systolic hypertension in adolescence of atomic bomb survivors exposed in utero.

Annual medical examinations were conducted during adolescence for the in utero clinical study sample subjects exposed prenatally to the atomic bombs in Hiroshima and Nagasaki. Systolic blood pressure and several anthropometric measurements were recorded during these examinations. For 1014 persons exposed in utero, two types of longitudinal analyses were performed, for a total of 7029 observations (6.93 observations per subject) of systolic blood pressure (continuous data) and systolic hypertension (binary data) for persons aged 9 to 19 years. Body mass index (BMI) and/or body weight were considered in the analyses as potential confounders. For the measurements of systolic blood pressure, the common dose effect was 2.09 mmHg per Gy and was significant (P = 0.017). The dose by trimester interaction was suggestive (P = 0.060). A significant radiation dose effect was found in the second trimester (P = 0.001), with an estimated 4.17 mmHg per Gy, but in the first and third trimesters, radiation dose effects were not significant (P > 0.50). For prevalence of systolic hypertension, the radiation dose effect was significant (P = 0.009); the odds ratio at 1 Gy was 2.23 [95% confidence interval (CI): 1.23, 4.04], and the dose by trimester interaction was not significant (P = 0.778). The dose response of systolic hypertension had no dose threshold, with a threshold point estimate of 0 Gy (95% CI: <0.0, 1.1 Gy). The dose response for systolic blood pressure was most pronounced in the second trimester, the most active organogenesis period for the organs relevant to blood pressure.

Postoperative cataract cases among atomic bomb survivors: radiation dose response and threshold.

Recent evidence argues against a high threshold dose for vision-impairing radiation-induced cataractogenesis. We conducted logistic regression analysis to estimate the dose response and used a likelihood profile procedure to determine the best-fitting threshold model among 3761 A-bomb survivors who underwent medical examinations during 2000-2002 for whom radiation dose estimates were available, including 479 postoperative cataract cases. The analyses indicated a statistically significant dose-response increase in the prevalence of postoperative cataracts [odds ratio (OR), 1.39; 95% confidence interval (CI), 1.24-1.55] at 1 Gy, with no indication of upward curvature in the dose response. The dose response was suggestive when the restricted dose range of 0 to 1 Gy was examined. A nonsignificant dose threshold of 0.1 Gy (95% CI, <0-0.8) was found. The prevalence of postoperative cataracts in A-bomb survivors increased significantly with A-bomb radiation dose. The estimate (0.1 Gy) and upper bound (0.8 Gy) of the dose threshold for operative cataract prevalence was much lower than the threshold of 2-5 Gy usually assumed by the radiation protection community and was statistically compatible with no threshold at all.

Thyroid Dysfunction and Autoimmune Thyroid Diseases Among Atomic Bomb Survivors Exposed in Childhood.

Context: The risk of thyroid cancer increases and persists for decades among individuals exposed to ionizing radiation in childhood, although the long-term effects of childhood exposure to medium to low doses of radiation on thyroid dysfunction and autoimmune thyroid diseases have remained unclear. Objective: To evaluate radiation dose responses for the prevalence of thyroid dysfunction and autoimmune thyroid disease among atomic bomb survivors exposed in childhood. Design, Setting, and Participants: Hiroshima and Nagasaki atomic bomb survivors who were younger than 10 years old at exposure underwent thyroid examinations at the Radiation Effects Research Foundation between 2007 and 2011, which was 62 to 66 years after the bombing. Data from 2668 participants (mean age, 68.2 years; 1455 women) with known atomic bomb thyroid radiation doses (mean dose, 0.182 Gy; dose range, 0 to 4.040 Gy) were analyzed. Main Outcome and Measures: Dose-response relationships between atomic bomb radiation dose and the prevalence of hypothyroidism, hyperthyroidism (Graves' disease), and positive for antithyroid antibodies. Results: Prevalences were determined for hypothyroidism (129 cases, 7.8%), hyperthyroidism (32 cases of Graves' disease, 1.2%), and positive for antithyroid antibodies (573 cases, 21.5%). None of these was associated with thyroid radiation dose. Neither thyroid antibody-positive nor -negative hypothyroidism was associated with thyroid radiation dose. Additional analyses using alternative definitions of hypothyroidism and hyperthyroidism found that radiation dose responses were not significant. Conclusions: Radiation effects on thyroid dysfunction and autoimmune thyroid diseases were not observed among atomic bomb survivors exposed in childhood, at 62 to 66 years earlier. The cross-sectional design and survival bias were limitations of this study.

Radiation dose-response relationships for thyroid nodules and autoimmune thyroid diseases in Hiroshima and Nagasaki atomic bomb survivors 55-58 years after radiation exposure.

CONTEXT: Effects of irradiation on thyroid diseases such as thyroid nodules and autoimmune thyroid diseases have not been evaluated among people exposed to radiation more than 50 years in the past. OBJECTIVE: To evaluate the prevalence of thyroid diseases and their radiation-dose responses in atomic bomb survivors. DESIGN, SETTING, AND PARTICIPANTS: Survey study comprising 4091 cohort members (mean age, 70 [SD, 9] years; 1352 men and 2739 women) who participated in the thyroid study at the Radiation Effects Research Foundation. Thyroid examinations were conducted between March 2000 and February 2003. MAIN OUTCOME MEASURES: Prevalence of thyroid diseases, including thyroid nodules (malignant and benign) and autoimmune thyroid diseases, and the dose-response relationship of atomic bomb radiation in each thyroid disease. RESULTS: Thyroid diseases were identified in 1833 (44.8%) of the total participants (436 men [32.2% of men] and 1397 women [51.0% of women]) (P<.001). In 3185 participants, excluding persons exposed in utero, not in the city at the time of the atomic bombings, or with unknown radiation dose, the prevalence of all solid nodules, malignant tumors, benign nodules, and cysts was 14.6%, 2.2%, 4.9%, and 7.7%, respectively. The prevalence of positive thyroid antibodies, antithyroid antibody-positive hypothyroidism, and Graves disease was 28.2%, 3.2%, and 1.2%, respectively. A significant linear dose-response relationship was observed for the prevalence of all solid nodules, malignant tumors, benign nodules, and cysts (P<.001). We estimate that about 28% of all solid nodules, 37% of malignant tumors, 31% of benign nodules, and 25% of cysts are associated with radiation exposure at a mean and median thyroid radiation dose of 0.449 Sv and 0.087 Sv, respectively. No significant dose-response relationship was observed for positive antithyroid antibodies (P = .20), antithyroid antibody-positive hypothyroidism (P = .92), or Graves disease (P = .10). CONCLUSIONS: A significant linear radiation dose response for thyroid nodules, including malignant tumors and benign nodules, exists in atomic bomb survivors. However, there is no significant dose response for autoimmune thyroid diseases.

A reanalysis of atomic-bomb cataract data, 2000-2002: a threshold analysis.

To obtain the best statistical model for a previous study of cataract prevalence in atomic-bomb survivors, we tested the fitness of the threshold model in an updated dataset of the study, utilizing re-diagnosis by a single ophthalmologist, use of the DS02 dosimetry system, and separation of the in utero group. The results suggest that, in 730 atomic-bomb survivors, we cannot conclude thresholds are greater than 0 Sv in cortical cataract and posterior sub-capsular opacity since the lower 90% confidence limits of the thresholds were 0 Sv. Threshold dose point estimates were 0.6 Sv (90% CI, <0.0-1.2 Sv) and 0.7 Sv (90% CI, <0.0-2.8 Sv) for cortical cataract and posterior sub-capsular opacity, respectively. Detailed regression analyses with no threshold model showed that nuclear color and nuclear opacity have no dose responses (p > 0.40). Cortical cataract showed a significant dose effect (p = 0.002), with an odds ratio (OR)/Sv of 1.30 (95% CI, 1.10-1.53) and no dose-effect modifiers. Posterior sub-capsular opacity showed a significant dose effect (p < 0.001), with an OR/Sv of 1.44 at age of exposure of 10 y (95% CI, 1.19-1.73). The dose effect decreased significantly with increasing age at exposure (p = 0.022). No dose response was observed for in utero survivors (p > 0.20).

Exposure to Atomic Bomb Radiation and Age-Related Macular Degeneration in Later Life: The Hiroshima-Nagasaki Atomic Bomb Survivor Study.

PURPOSE: To investigate the association between radiation exposure from the atomic bombings and the prevalence of age-related macular degeneration (AMD) among older residents of Hiroshima and Nagasaki. METHODS: The Adult Health Study is a cohort study of atomic bomb survivors living in Hiroshima and Nagasaki, comprising 2153 participants who underwent examinations with retinal fundus photographs in 2006-2008. The radiation dose to the eye for the analysis was estimated with the revised dosimetry system (DS02). The retinal photographs were graded according to the Wisconsin Age-Related Maculopathy Grading System modified for nonstereoscopic retinal images. Early and late AMD were defined according to the type of lesion detected in the worse eye of the participants. Person-specific data were analyzed by using a logistic regression model to assess the association between radiation dose and AMD. RESULTS: Among the 1824 subjects with gradable retinal images (84.7% of the overall participants), the estimated eye dose was widely distributed, with a mean of 0.45 Gy and standard deviation of 0.74 Gy. The prevalence of early and late AMD was 10.5% and 0.3%, respectively. There were no significant associations between radiation dose and AMD, with each 1-Gy increase in exposure, adjusted odds ratio was 0.93 (95% confidence interval [CI], 0.75-1.15) for early AMD and 0.79 (95% CI, 0.21-2.94) for late AMD. CONCLUSIONS: No significant associations were found between atomic bomb irradiation early in life and the prevalence of early or late AMD later in life among Japanese atomic bomb survivors.

Association of radiation dose with prevalence of thyroid nodules among atomic bomb survivors exposed in childhood (2007-2011).

IMPORTANCE: Few studies have evaluated the association of radiation dose with thyroid nodules among adults exposed to radiation in childhood. OBJECTIVE: To evaluate radiation dose responses on the prevalence of thyroid nodules in atomic bomb survivors exposed in childhood. DESIGN, SETTING, AND PARTICIPANTS: This survey study investigated 3087 Hiroshima and Nagasaki atomic bomb survivors who were younger than 10 years at exposure and participated in the thyroid study of the Adult Health Study at the Radiation Effects Research Foundation. Thyroid examinations including thyroid ultrasonography were conducted between October 2007 and October 2011, and solid nodules underwent fine-needle aspiration biopsy. Data from 2668 participants (86.4% of the total participants; mean age, 68.2 years; 1213 men; and 1455 women) with known atomic bomb thyroid radiation doses (mean dose, 0.182 Gy; median dose, 0.018 Gy; dose range, 0-4.040 Gy) were analyzed. MAIN OUTCOMES AND MEASURES: The prevalence of all thyroid nodules having a diameter of 10 mm or more (consisting of solid nodules [malignant and benign] and cysts), prevalence of small thyroid nodules that were less than 10 mm in diameter detected by ultrasonography, and atomic bomb radiation dose-responses. RESULTS: Thyroid nodules with a diameter of 10 mm or more were identified in 470 participants (17.6%): solid nodules (427 cases [16.0%]), malignant tumors (47 cases [1.8%]), benign nodules (186 cases [7.0%]), and cysts (49 cases [1.8%]), and all were significantly associated with thyroid radiation dose. Excess odds ratios per gray unit were 1.65 (95% CI, 0.89-2.64) for all nodules, 1.72 (95% CI, 0.93-2.75) for solid nodules, 4.40 (95% CI, 1.75-9.97) for malignant tumors, 2.07 (95% CI, 1.16-3.39) for benign nodules, and 1.11 (95% CI, 0.15-3.12) for cysts. The interaction between age at exposure and the dose was significant for the prevalence of all nodules (P = .003) and solid nodules (P < .001), indicating that dose effects were significantly higher with earlier childhood exposure. No interactions were seen for sex, family history of thyroid disease, antithyroid antibodies, or seaweed intake. No dose-response relationships were observed for small (<10-mm diameter) thyroid nodules. CONCLUSIONS AND RELEVANCE: Radiation effects on thyroid nodules exist in atomic bomb survivors 62 to 66 years after their exposure in childhood. However, radiation exposure is not associated with small thyroid nodules.

Improving the efficiency of nested case-control studies of interaction by selecting controls using counter matching on exposure.

BACKGROUND: Studies of the effect of exposure to a risk factor measured in an entire cohort may be augmented by nested case-control subsets to investigate confounding or effect modification by additional factors not practically assessed on all cohort members. We compared three control-selection strategies-matching on exposure, counter matching on exposure, and random sampling-to determine which was most efficient in a situation where exposure is a known, continuous variable and high doses are rare. METHODS: We estimated the power to detect interaction using four control-to-case ratios (1:1, 2:1, 4:1, and 8:1) in a planned case-control study of the joint effect of atomic bomb radiation exposure and serum oestradiol levels on breast cancer. Radiation dose is measured in the entire cohort, but because neither serum oestradiol level nor the true degree of interaction was known, we simulated values of oestradiol and hypothetical levels of oestradiol-radiation interaction. RESULTS: Compared with random sampling, power to detect interaction was similarly higher with either matching or counter matching with two or more controls. CONCLUSIONS: Because counter matching is generally at least as efficient as random sampling, whereas matching on exposure can result in loss of efficiency and precludes estimation of exposure risk, we recommend counter matching for selecting controls in nested case-control studies of the joint effects of multiple risk factors when one is previously measured in the full cohort.

Is the association between smoking and the retinal venular diameter reversible following smoking cessation?

PURPOSE: Wider retinal venular caliber is shown to be associated with an increased risk of stroke, and smoking is associated with a wider retinal venular caliber. However, the impact of smoking cessation on the retinal vessels has not been previously reported. We examined this issue in an adult cohort of atomic bomb survivors. METHODS: In the Adult Health Study of Japanese atomic bomb survivors, 1664 subjects had retinal photographs taken from 2006 to 2008. The central retinal artery and vein equivalents (CRAE and CRVE) were calculated using a semiautomated software program. Multiple surveys have assessed the effects of smoking since 1963. The associations between smoking, the time since cessation, and the retinal vessel caliber were determined using linear mixed effects models. RESULTS: The CRVE was associated with an increased number of cigarettes smoked per day among women after adjusting for potential confounding factors (age, sex, blood pressure, hypertensive medications, white blood cell count, diabetes, body mass index, lipids, and radiation dose). Females who smoked 10 cigarettes per day had a 6.9-µm wider mean CRVE (P = 0.001) than nonsmokers. Females who had stopped smoking for 10 or more years had a mean CRVE similar to those who had never smoked (191.8 vs. 194.4 µm; P = 0.23). These associations were not observed in males or for CRAE. CONCLUSIONS: Wider retinal venular caliber is associated with smoking in Japanese females; however, this association becomes nonsignificant after 10 or more years of smoking cessation, suggesting that the impact of smoking on retinal venular dilation is reversible following long-term smoking cessation.

Radiation Dose Responses, Thresholds, and False Negative Rates in a Series of Cataract Surgery Prevalence Studies among Atomic Bomb Survivors.

In order to find imperfect sensitivity or the false-negative rate of cataract surgery due to latent clinically significant or severe cataract and a dose-response threshold, cataract surgery prevalence data analysis was made for each of the two-year periods from 1986 through 2005 among atomic bomb survivors. Using the latent variable regression model published earlier, cataract prevalence studies allowing for false-negative and/or false-positive rates were conducted in each of the 10 two-year periods during 1986 to 2005. As the best statistical model for prevalence data, a logistic model with a non-negligible false negative rate was selected for analysis. The commonly used naïve logistic analysis resulted in an average odds ratio (OR) at 1 Gy of 1.33 (95%CI: 1.28, 1.38) for cataract surgery with no linear time trend (p = 0.334), and the OR at 1 Gy with the model allowing for sensitivity was 1.48 (95%CI: 1.40, 1.56) for clinically significant or severe cataract with no linear time trend (p = 0.263). Cataract surgery is an imperfect surrogate for clinically significant cataract, and the sensitivity increased from 0.15 to 0.50 during the 20 y with increasing rate of sensitivity per 2-y period of approximately 22%. The dose-response threshold based on a naïve logistic model for cataract surgery ranged from 0.04-1.03 Gy (simple average of 0.41 Gy) with no linear time trend (p = 0.620) in the 10 2-y periods compatible with the no dose response threshold model in all periods.

Glaucoma in atomic bomb survivors.

Radiation has been associated with increases in noncancerous diseases. An effect of low-dose radiation on the prevalence of clinically detected glaucoma has not been previously reported. We therefore investigated the prevalence of glaucoma in A-bomb survivors and its possible association with radiation dose. A total of 1,589 people who participated in the clinical examination program for A-bomb survivors at the Radiation Effects Research Foundation (RERF) between October 2006 and September 2008 and who had reconstructed radiation doses, were recruited into this cross-sectional screening study. The prevalence of glaucoma and its dose-response relationship to A-bomb radiation were measured. Each subject underwent an initial screening consisting of an interview and ophthalmological examination. Questionable cases with any indication of ocular disease, including glaucoma, were referred to local hospitals for more comprehensive evaluation. A diagnosis of glaucoma was made based on specific optic disc appearance, perimetric results and other ocular findings. Of 1,589 eligible people, we detected 284 (17.9%) cases of glaucoma overall, including 36 (2.3%) cases of primary open-angle glaucoma with intraocular pressure levels greater than 21 mmHg, 226 (14.2%) cases of normal-tension glaucoma and 25 (1.6%) cases of primary angle-closure glaucoma. Seven glaucoma risk factors were examined as potential confounders but only two needed to be included in the final model. Binary regression using a generalized estimating equation method, with adjustment for gender, age, city, cataract surgery or diabetes mellitus, revealed an odds ratio at 1 Gy of 1.31 (95% confidence interval 1.11-1.53, P = 0.001) in the case of normal-tension glaucoma, but no association for other types of glaucoma. The prevalence of normal-tension glaucoma may increase with A-bomb radiation dose, but uncertainties associated with nonparticipation (59% participation) suggest caution in the interpretation of these results until they are confirmed by other studies.

UV radiation may explain intercity difference for cataract in A-bomb survivors.

Accurate assessment of risk factors is important for the evaluation of radiation-induced ocular lens damage. Our previous study identified a significant city difference between Hiroshima and Nagasaki atomic-bomb survivors in terms of cataract prevalence, prompting further analysis. This study analyzed the sites of lens opacities and used model fitting that incorporated the variable impact of UV on the eye, based on the hypothesis that the city difference in the prevalence of cataract was due to differences in UV radiation between the two cities. The results suggested that cataracts among Nagasaki residents were more frequently located at the inferior nasal portion of the lens compared to cataracts in Hiroshima residents, with no ionizing radiation-specific localization observed. Based on the angles of incidence, UV was suggested as a possible cause of the city difference. We therefore analyzed models of city differences in terms of UVA and UVB levels. The UVB model provided a better fit than the UVA model, suggesting that UVB might account for the city difference. The current study implicated the geographic location of the subject, the investigation period, and outdoor activities as potentially important surrogate factors for UVB influence in radiation-induced cataract. In addition, the superior temporal portion of the lens seemed the most suitable for evaluating the effects of ionizing radiation because of the lesser amount of UVB interference at that site.