Cataracts among Chernobyl clean-up workers: implications regarding permissible eye exposures

The eyes of a prospective cohort of 8,607 Chernobyl clean-up workers (liquidators) were assessed for cataract at 12 and 14 years after exposure. The prevalence of strictly age-related cataracts was low, as expected (only 3.9% had nuclear cataracts at either examination), since 90% of the cohort was younger than 55 years of age at first examination. However, posterior subcapsular or cortical cataracts characteristic of radiation exposure were present in 25% of the subjects. The data for Stage 1 cataracts, and specifically for posterior subcapsular cataracts, revealed a significant dose response. When various cataract end points were analyzed for dose thresholds, the confidence intervals all excluded values greater than 700 mGy. Linear-quadratic dose-response models yielded mostly linear associations, with weak evidence of upward curvature. The findings do not support the ICRP 60 risk guideline assumption of a 5-Gy threshold for "detectable opacities" from protracted exposures but rather point to a dose-effect threshold of under 1 Gy. Thus, given that cataract is the dose-limiting ocular pathology in current eye risk guidelines, revision of the allowable exposure of the human visual system to ionizing radiation should be considered.     

Elevated Frequency of Cataracts in Birds from Chernobyl

Background

Radiation cataracts develop as a consequence of the effects of ionizing radiation on the development of the lens of the eye with an opaque lens reducing or eliminating the ability to see. Therefore, we would expect cataracts to be associated with reduced fitness in free-living animals.

Methodology/Principal Findings

We investigated the incidence of lens opacities typical of cataracts in more than 1100 free-living birds in the Chernobyl region in relation to background radiation. The incidence of cataracts increased with level of background radiation both in analyses based on a dichotomous score and in analyses of continuous scores of intensity of cataracts. The odds ratio per unit change in the regressor was 0.722 (95% CI 0.648, 0.804), which was less than odds ratios from investigations of radiation cataracts in humans. The relatively small odds ratio may be due to increased mortality in birds with cataracts. We found a stronger negative relationship between bird abundance and background radiation when the frequency of cataracts was higher, but also a direct effect of radiation on abundance, suggesting that radiation indirectly affects abundance negatively through an increase in the frequency of cataracts in bird populations, but also through direct effects of radiation on other diseases, food abundance and interactions with other species. There was no increase in incidence of cataracts with increasing age, suggesting that yearlings and older individuals were similarly affected as is typical of radiation cataract.

Conclusions/Significance

These findings suggest that cataracts are an under-estimated cause of morbidity in free-living birds and, by inference, other vertebrates in areas contaminated with radioactive materials.     

10-Year Overview of the Hospital-Based Prevalence and Treatment of Congenital Cataracts: The CCPMOH Experience

A review of 6 years of hospitalization charts from Zhongshan Ophthalmic Center (ZOC) revealed that congenital cataracts (CC) accounted for 2.39% of all cataract in-patient cases and that the age at surgery was decreasing before the establishment of the Childhood Cataract Program of the Chinese Ministry of Health (CCPMOH) in December 2010. We aimed to investigate data from the 4 years (January 2011 to December 2014) following the establishment of the CCPMOH, compared, and combined with data from the previous study period (January 2005 to December 2010) to generate a 10-year overview of the hospital-based prevalence and treatment of CC. In the 4-year period after CCPMOH establishment, the prevalence of CC was 2.01% in all hospitalizations, and was 2.78% in all cataract in-patients. Most of the eligible CC in-patients (71%) lived in south China. The ratio of boys to girls was 1.42:1. Nearly 2/3 of the patients underwent cataract extraction with primary intraocular lens (IOL) implantation at a mean age of 78.40±51.45 months, and cataract extraction surgeries without IOL implantation were performed in the remaining 1/3 of patients at a mean age of 10.03±15.92 months. After CCPMOH establishment, an increased incidence of CC was revealed, and the CC in-patients were younger than the patients in the previous period. The 10-year overview (2421 CC in-patients from 206630 hospitalizations) revealed upward trends in both the number and the prevalence of CC and a further reduction in age at surgery. In conclusion, the data from 4-year period after CCPMOH establishment and the 10-year overview showed upward trends in the hospital-based prevalence of CC cases and a further reduction in age at surgery, likely reflecting the effects of the CCPMOH establishment and providing useful information for further CC studies and a valuable foundation for the prevention and treatment of this cause of childhood blindness.     

Visual evoked potentials to structured stimuli in children with cataracts

EPs elicited by diffuse light flashes and check patterns, were studied in children and juveniles with congenital and traumatic cataract, during different periods and various durations of deprivation, as well as in a control group of children and juveniles with normal vision. Specific age characteristics were found in the EPs to check patterns in seven years-old children. In children with congenital cataracts significant changes in the shape and amplitude-temporal EP parameters were recorded. In children with traumatic cataracts, presumably developed after the end of the sensitive period, the changes in EPs were much less pronounced. The obtained data are discussed from the point of view of the duration of the sensitive period of the formation of the visual function in humans and of informative value of different EP components.     

Red blood cell galactokinase activity and presenile cataracts

Red blood cell galactokinase activity was measured in 70 patients with cataracts to assess a possible correlation between galactokinase activity levels and risk of cataract development. Among all, 15 patients developed cataracts during the first year of life, 25 patients under the age of 50 and 30 later in life. No cases of total or partial galactokinase deficiency were found. These results, taken together with the absence of cataracts in 9 patients with partial galactokinase deficiency render less certain the cause and effect relationship between partial galactokinase deficiency and the appearance of cataracts.     

Cataract Development in Atlantic Salmon (Salmo salar L) in Fresh Water

Irreversible bilateral cataracts were diagnosed by slit-lamp biomicroscopy in 178 of 200 farm-raised Atlantic salmon (Salmo salar L) fed a standard diet over a five-month period. Initial changes were anterior polar opacities, progressing to involve both the anterior and posterior cortex before changes in the lens nucleus were seen. The lens changes were recorded and given scores according to the severity of the cataracts. At each of 3 samplings, after 2, 4 and 5 months, 200 fish were measured, weighed and examined by slit-lamp biomicroscopy. At all 3 samplings, there was a significant correlation between body length and both cataract incidence and cataract severity. There was also a significant correlation between body weight and cataract incidence and severity for the 2 last samplings. There was a significant correlation between K-factor as a measure of the shape of the fish, and both cataract incidence and severity, at all 3 samplings. Evaluation of specific growth rate in the periods between the examinations showed that the rapidly-growing fish were most susceptible to cataract formation. After cataract developed, however, the growth rate slowed. Follow-up examination of severely affected fish 3 months after transfer to sea water showed a normal cortical zone in the periphery of the lens in 24 out of 28 fish.     

Epidemiological studies of cataract risk at low to moderate radiation doses: (not) seeing is believing

The prevailing belief for some decades has been that human radiation-related cataract occurs only after relatively high doses; for instance, the ICRP estimates that brief exposures of at least 0.5-2 Sv are required to cause detectable lens opacities and 5 Sv for vision-impairing cataracts. For protracted exposures, the ICRP estimates the corresponding dose thresholds as 5 Sv and 8 Sv, respectively. However, several studies, especially in the last decade, indicate that radiation-associated opacities occur at much lower doses. Several studies suggest that medical or environmental radiation exposure to the lens confers risk of opacities at doses well under 1 Sv. Among Japanese A-bomb survivors, risks for cataracts necessitating lens surgery were seen at doses under 1 Gy. The confidence interval on the A-bomb dose threshold for cataract surgery prevalence indicated that the data are compatible with a dose threshold ranging from none up to only 0.8 Gy, similar to the dose threshold for minor opacities seen among Chernobyl clean-up workers with primarily protracted exposures. Findings from various studies indicate that radiation risk estimates are probably not due to confounding by other cataract risk factors and that risk is seen after both childhood and adult exposures. The recent data are instigating reassessments of guidelines by various radiation protection bodies regarding permissible levels of radiation to the eye. Among the future epidemiological research directions, the most important research need is for adequate studies of vision-impairing cataract after protracted radiation exposure.     

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.     

The induction by 224Ra of myeloid leukaemia and osteosarcoma in male CBA mice

Radium-224 was injected into 12-week-old male CBA mice in the range 2-64 kBq per mouse either as a single injection or as eight injections spaced at 3.5 day intervals over 4 weeks. Small but significant yields of myeloid leukaemia or osteosarcoma were obtained in all but the control groups. An effect of mode of administration (single or multiple injections) could not be demonstrated but the combined results showed: a maximum yield of myeloid leukaemia in the region 8-16 kBq 224Ra; a greater yield of osteosarcoma than myeloid leukaemia at 64 kBq 224 Ra injected.     

Dietary prevention of cataracts in the pink-eyed RCS rat

The American Institute of Nutrition purified ingredient diet (AIN-76) prevented occurrence of mature cataracts associated with hereditary retinal degeneration in pink-eyed, tan-hooded Royal College of Surgeons (RCS) rats. Rats fed a natural ingredient open formula NIH diet or a closed formula commercial diet had a cataract incidence of 27-29% by 3 to 12 months of age. In contrast, only 1 of 50 rats fed the AIN diet developed a mature cataract in one year. When the NIH diet and the commercial diet were pelleted with 25% of ground sunflower kernels, rats fed these diets had a delay in onset and a reduced incidence of mature cataracts to 18% and 5%, respectively. No mature cataracts occurred in rats fed the AIN diet supplemented with 25% sunflower kernels. All diets were fed to the parental generation as well as the progeny (experimental group). The rats were reared at a low level of illumination (1-3 footcandles inside the cage) to minimize effects of light. Prevention of mature cataracts by the AIN purified diet suggests that diets permitting cataracts to occur may have a constituent at a concentration innocuous for normal rats but beyond the homeostatic control of the RCS rat. Posterior subcapsular cataracts of RCS rats are a model for cataracts associated with human hereditary retinal degenerations, such as retinitis pigmentosa and gyrate atrophy. Manipulation of dietary ingredients allowed by the use of the AIN diet may permit identification of nutrients, nutrient interactions of toxic factors involved in cataractogenesis and its prevention.     

Effect of estrogen on radiation-induced cataractogenesis

Cataractogenesis is a widely reported late effect that is observed in patients receiving total-body irradiation (TBI) prior to bone marrow transplantation or radiotherapy for ocular or head and neck cancers. Recent studies indicate that estrogens may protect against age-related and drug-induced cataracts. Moreover, other reports suggest that estrogen possesses antioxidant properties. Since the effect of estrogen on radiation cataractogenesis is unknown, we wished to determine whether estrogen modulates radiation-induced opacification of the lens. Intact or ovariectomized Sprague-Dawley rats were treated with either 17-beta-estradiol or an empty silastic capsule. The right orbit was then irradiated with either 10 or 15 Gy of (60)Co gamma rays using a Leksell Gamma Knife, and lenses were examined at various times postirradiation with a slit lamp or evaluated for light transmission. We found that for ovariectomized rats irradiated with 15 Gy, the lens opacity and the incidence of cataract formation in the estradiol-treated group were significantly increased compared to the control group at the end of the 25-week period of observation. Cataract incidence was also high in irradiated eyes of ovary-intact animals at 25 weeks postirradiation but was greatly reduced in the ovariectomized control group, with less than half of irradiated eyes showing evidence of cataractogenesis. Thus, after irradiation with 15 Gy of gamma rays, estrogen increased the incidence of cataract formation. We also observed that although the incidence of cataract formation in rats irradiated with 10 Gy and receiving continuous estrogen treatment was not altered compared to rats in the control group that did not receive estrogen, the latent period for posterior subcapsular cataract formation decreased and the severity of the anterior cataract increased. Taken together, our data suggest that estrogen accelerates progression of radiation-induced opacification.     

Bone cancer risk in mice exposed to 224Ra: protraction effects from promotion

This paper analyzes data for the osteosarcoma incidence in life-time experiments of (224)Ra injected mice with respect to the importance of initiating and promoting action of ionizing high LET-radiation. This was done with the biologically motivated two step clonal expansion (TSCE) model of tumor induction. Experimentally derived osteosarcoma incidence in 1,194 mice following exposure to (224)Ra with different total radiation doses and different fractionation patterns were analyzed together with incidence data from 1,710 unirradiated control animals. Effects of radiation on the initiating event and on the clonal expansion rate, i.e. on promotion were found to be necessary to explain the observed patterns with this model. The data show a distinct inverse protraction effect at high doses, whereas at lower doses this effect becomes insignificant. Such a behavior is well reproduced in the proposed model: At dose rates above 6 mGy/day a longer exposure produces higher ERR per dose, while for lower rates the reverse is the case. The TSCE model permits the deduction of several kinetic parameters of a postulated two-step bone tumorigenesis process. Mean exposure rates of 0.13 mGy/day are found to double the baseline initiation rate. At rates above 100 mGy/day, the initiation rate decreases. The clonal expansion rate is doubled at 8 mGy/day, and it levels out at rates beyond 100 mGy/day.     

226Ra induced bone-cancers: the effects of a delayed Na-alginate treatment

At the present time no unequivocal evidence exists which shows that a reduction in the body-burden of a radionuclide by decorporative treatment results in a proportional decrease in the risk of long-term radiation effects. We have investigated the effectiveness of the daily administration of Na-alginate via the diet in removing 226Ra from the skeleton and in reducing the number of late effects such as osteosarcomas. The animals used were male C57Bl mice which had been injected with one of three different amounts of 226Ra (4.4, 10.7 or 24.8 kBq) four days prior to the onset of the decorporative treatment. The results showed that although this treatment was able to produce a substantial reduction in the 226Ra content of the mice it did not reduce the incidence of osteosarcoma. These results question the effectiveness of decorporation procedures initiated at longer times after contamination.     

Diabetic cataract of the musk shrew (Suncus murinus, Insectivora) exhibiting spontaneous non-insulin dependent diabetes mellitus (NIDDM).

The EDS colony, developed as a new laboratory colony of the musk shrew, is characterized by a high incidence of early-onset spontaneous non-insulin dependent diabetes mellitus (NIDDM). In this colony, a few diabetic shrews exhibited a cataract at 1 month after the onset of diabetes, and all diabetic shrews had bilateral cataracts at 5 months after the onset of diabetes. In contrast, cataractous animals were never observed among non-diabetic shrews. These results suggest that the cataract in the EDS colony is a diabetic complication.     

Nutrient intake and cataract extraction in women: a prospective study.

OBJECTIVE--To examine prospectively the association between dietary intake of vitamins C and E, carotene, and riboflavin and cataract extraction in women. DESIGN--Prospective cohort study beginning in 1980 with eight years of follow up. SETTING--11 states of the United States. PARTICIPANTS--Female registered nurses who were 45 to 67 years of age. 50,828 women were included in 1980 and others were added as they became 45 years of age. MAIN OUTCOME MEASURE--Incidence of extraction of senile cataracts. RESULTS--493 cataracts were extracted during 470,302 person years of follow up. Intake of carotene and vitamin A was inversely associated with cataract: in multivariate analyses, women in the highest fifth of total vitamin A intake (excluding supplements) had a 39% lower risk of cataract relative to women in the lowest fifth (relative risk 0.61; 95% confidence interval 0.45 to 0.81). Neither riboflavin nor dietary vitamins E or C were associated with cataract in a multivariate analysis. Among specific food items spinach (rather than carrots, the greatest source of beta carotene) was most consistently associated with a lower relative risk. The risk of cataract was 45% lower among women who used vitamin C supplements for 10 or more years(relative risk 0.55 (0.32 to 0.96)), but no association was noted for multivitamin intake. CONCLUSION--Dietary carotenoids, although not necessarily beta carotene, and long term vitamin C supplementation may decrease the risk of cataracts severe enough to require extraction.     

Therapy of ankylosing spondylitis with 224Ra-radium chloride: dosimetry and risk considerations

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease which reduces the quality of life and leads to disability in approximately one-third of the patients. The spectrum of therapeutic modalities is limited. The renaissance of the use of (224)Ra-radium chloride for AS treatment, however, gives rise to concern which should result in the reconsideration of (224)Ra dosimetry and in the discussion of the risks associated with this treatment. The present study introduces new dosimetric calculations for alpha and beta/gamma rays performed according to the model proposed by the International Commission on Radiological Protection (ICRP). After a treatment schedule of 10 intravenous injections, each with 1 MBq of (224)Ra, the absorbed doses were calculated to be highest on the bone surface of the patient (4.4 Gy) with a resulting effective dose of 2.5 Sv.     

雷珠单抗与阿柏西普玻璃体腔注射治疗渗出性年龄相关性黄斑变性的疗效观察

目的:探究雷珠单抗与阿柏西普玻璃体腔注射治疗渗出性年龄相关性黄斑变性的临床疗效与安全性。方法:选取2015年5月～2018年5月我院收治的渗出性年龄相关性黄斑变性患者98例(98眼),采用随机数字表法将患者分为两组,A组玻璃体腔内缓慢注射0.05 m L(0.5 mg)雷珠单抗注射液,B组玻璃体腔内缓慢注射0.05 m L(2 mg)阿柏西普注射液。比较两组患者的视力改善情况、眼动脉血流动力学、黄斑中心凹视网膜厚度及不良反应的发生情况。结果:治疗前两组患者的视力比较无统计学差异(P0.05),治疗后,B组视力显著高于A组(P0.05);。两组患者治疗前后眼动脉血流动力学相关指标比较均无统计学差异(P0.05)。;两组患者治疗后的黄斑中心凹视网膜厚度均显著降低,且治疗3个月B组治疗3个月显著低于A组(P0.05);B组患者注射药物后结膜下大出血发生率显著低于A组(P0.05)。结论:阿柏西普可显著改善渗出性年龄相关性黄斑变性患者的视力,且安全性高,可能与其可显著改善患者的黄斑中心凹视网膜厚度有关,且不良反应发生率低,安全性好。     

微切口超声乳化联合小梁切除术治疗白内障合并青光眼的疗效观察

目的:探讨微切口超声乳化联合小梁切除术治疗白内障合并青光眼的临床疗效。方法:选取2013年1月到2014年1月我院收治的白内障合并青光眼患者100例,按照随机数字表法将患者分为研究组和对照组,每组50例,对照组给予常规超声乳化联合小梁切除术进行治疗,研究组给予微切口超声乳化联合小梁切除术治疗,比较两组术前、术后裸眼视力、散光、眼压,并比较两组术后并发症。结果:两组术后裸眼视力、散光和眼压均较术前明显好转,与术前比较差异具有统计学意义(P0.05),且研究组术后裸眼视力、散光和眼压均优于对照组,两组比较差异具有统计学意义(P0.05);研究组术后并发症发生率显著低于对照组,两组比较差异具有统计学意义(P0.05)。结论:微切口超声乳化联合小梁切除术治疗白内障合并青光眼疗效确切,且术后并发症较少。     

Therapeutic Effect of α-Emitting 224Ra-Labeled Calcium Carbonate Microparticles in Mice with Intraperitoneal Ovarian Cancer

BACKGROUND: Ovarian cancer patients with chemotherapy-resistant residual microscopic disease in the peritoneal cavity have a considerable need for new treatment options. Alpha-emitting radionuclides injected intraperitoneally may be an attractive therapeutic option in this situation as they are highly cytotoxic, while their short range in tissues can spare surrounding radiosensitive organs in the abdomen. Herein we evaluate the therapeutic efficacy of a novel α-emitting compound specifically designed for intracavitary radiation therapy. METHODS: The α-emitter ²²⁴Ra was absorbed on calcium carbonate microparticles. Immunodeficient, athymic nude mice with human ovarian cancer cells growing intraperitoneally were treated with different activity levels of ²²⁴Ra-microparticles. Tumor growth, survival, and tolerance of the treatment were assessed. Two tumor models based on the cell lines, ES-2 and SKOV3-luc, with different growth patterns were studied. RESULTS: In both models, intraperitoneal treatment with ²²⁴Ra-microparticles gave significant antitumor effect with either considerably reduced tumor volume or a survival benefit. An advantageous discovery was that only a few kilobecquerels per mouse were needed to yield therapeutic effects. The treatment was well tolerated up to a dose of 1000 kBq/kg with no signs of acute or subacute toxicity observed. CONCLUSIONS: Intraperitoneal α-therapy with ²²⁴Ra-microparticles demonstrated a significant potential for treatment of peritoneal micrometastases in ovarian carcinoma.     

Increased content of zinc and iron in human cataractous lenses

The purpose of the study was to examine the zinc and iron content of human lenses in different types of cataract and to investigate the possible influence of diabetes on the zinc and iron content of the lens. Iron and zinc of 57 human lenses (28 corticonuclear cataracts and 29 mature cataracts with a mean age of 70.6±16.1 and 74.7±11.1 yr, 41 nondiabetics and 16 diabetics) were determined by atomic absorption spectroscopy. The zinc content of human lenses was significantly increased in mature cataracts compared to corticonuclear cataracts (0.51±0.33 vs 0.32±0.20 μmol/g dry mass, p=0.012). The iron content of mature cataracts was also higher than in corticonuclear cataracts (0.11±0.09 vs 0.07±0.05 μmol/g dry mass, p=0.071). Furthermore, a significant increase of the lens zinc content could be observed with increasing lens coloration (light brown 0.33±0.17 vs dark brown 0.52±0.35 μmol/g dry mass, p=0.032). Diabetic patients seem to have both increased zinc and iron contents in the lens compared to nondiabetic subjects (zinc: 0.45±0.42 vs 0.40±0.22 μmol/g dry mass; iron: 0.12±0.10 vs 0.08±0.05 μmol/g dry mass). These data suggest a possible influence of the lens zinc and iron content on the development of lens opacification. Especially advanced forms of cataract and dark brown colored lenses show significantly increased zinc and iron content.