Article

Individual response of the ocular lens to ionizing radiation

If you want to read the PDF, try requesting it from the authors.

Abstract

Purpose: Cataract (opacification of the ocular lens) is a typical tissue reaction (deterministic effect) following ionizing radiation exposure, for which prevention dose limits have been recommended in the radiation protection system. Manifestations of radiation cataracts can vary among individuals, but such potential individual responses remain uncharacterized. Here we review relevant literature and discuss implications for radiation protection. This review assesses evidence for significant modification of radiation-induced cataractogenesis by age at exposure, sex and genetic factors based on current scientific literature. Conclusions: In addition to obvious physical factors (e.g. dose, dose rate, radiation quality, irradiation volume), potential factors modifying individual responses for radiation cataracts include sex, age and genetics, with comorbidity and coexposures also having important roles. There are indications and preliminary data identifying such potential modifiers of radiation cataract incidence or risk, although no firm conclusions can yet be drawn. Further studies and a consensus on the evidence are needed to gain deeper insights into factors determining individual responses regarding radiation cataracts and the implications for radiation protection.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Identification of factors that modify individual responses of the lens to radiation exposure (e.g. sex, age, genetics, comorbidity and coexposure) warrants further studies (Barnard and Hamada 2022). There has also been a growing interest in radiation effects on ocular structures other than the lens (Hamada et al. 2020;Ainsbury et al. 2021;Little et al. 2021). ...
Article
In April 2011, the International Commission on Radiological Protection recommended reducing the occupational equivalent dose limit for the lens. Such a new occupational lens dose limit has thus far been implemented in many countries, and there are extensive discussions toward its regulatory implementation in other countries. In Japan, discussions in the Japan Health Physics Society (JHPS) began in April 2013 and in Radiation Council in July 2017, and the new occupational lens dose limit was implemented into regulation in April 2021. To share our experience, we have published a series of papers summarizing situations in Japan: the first paper based on information available by early 2017, and the second paper by early 2019. This paper (our third paper of this series) aims to review updated information available by mid-2022, such as regarding regulatory implementation of the new occupational lens dose limit, recent discussions by relevant ministries based on the opinion from the council, establishment process of safety and health management systems, the JHPS guidelines on lens dose monitoring and radiation safety, voluntary countermeasures of the licensees, development of lens dose calibration method, and recent studies on exposure of the lens in nuclear workers and biological effect on the lens.
... Individual sensitivity to radiation varies and is correlated with genetic factors and lifestyle (De Stefano et al. 2021). Although the contribution of genetic predisposition to radiation sensitivity or radiation resistance in cancer is well accepted, the knowledge in the area of the radiation-induced non-cancer effect is not yet very well developed (Foray et al. 2016;Rajaraman et al. 2018;Barnard and Hamada 2022). The background status of the biosystem (from cell to tissue) at the time of irradiation may also impact the biological effect of radiation exposure. ...
Article
Full-text available
Background: Epidemiological studies have indicated that exposure of the heart to doses of ionizing radiation as low as 0.5 Gy increases the risk of cardiac morbidity and mortality with a latency period of decades. The damaging effects of radiation to myocardial and endothelial structures and functions have been confirmed radiobiologically at high dose, but much less is known at low dose. Integration of radiation biology and epidemiology data is a recommended approach to improve the radiation risk assessment process. The adverse outcome pathway (AOP) framework offers a comprehensive tool to compile and translate mechanistic information into pathological endpoints which may be relevant for risk assessment at the different levels of a biological system. Omics technologies enable the generation of large volumes of biological data at various levels of complexity, from molecular pathways to functional organisms. Given the quality and quantity of available data across levels of biology, omics data can be attractive sources of information for use within the AOP framework. It is anticipated that radiation omics studies could improve our understanding of the molecular mechanisms behind the adverse effects of radiation on the cardiovascular system. In this review, we explored the available omics studies on radiation-induced cardiovascular disease (CVD) and their applicability to the proposed AOP for CVD. Results: The results of 80 omics studies published on radiation-induced CVD over the past 20 years have been discussed in the context of the AOP of CVD proposed by Chauhan et al. Most of the available omics data on radiation-induced CVD are from proteomics, transcriptomics, and metabolomics, whereas few datasets were available from epigenomics and multi-omics. The omics data presented here show great promise in providing information for several key events of the proposed AOP of CVD, particularly oxidative stress, alterations of energy metabolism, extracellular matrix and vascular remodeling. Conclusions: The omics data presented here shows promise to inform the various levels of the proposed AOP of CVD. However, the data highlight the urgent need of designing omics studies to address the knowledge gap concerning different radiation scenarios, time after exposure and experimental models. This review presents the evidence to build a qualitative omics-informed AOP and provides views on the potential benefits and challenges in using omics data to assess risk-related outcomes.
... A significantly increased risk of the cataract surgery as a function of radiation dose has hitherto been reported only in LSS [159], where the effect of acute exposure could have been indeed significant. Of note, the reports [152,153] on "a clear and significant increased ERR/Sv in females compared to males" among MPA workers were designated as "the most striking study observing sex effects relating to radiationinduced cataract incidence" [160]. The sex differences can be attributed to a gender-related attitude in the Russian healthcare. ...
Article
Full-text available
This article is a narrative review. The systematic approach is hardly applicable if more and less reliable data are intermingled due to bias, conflicts of interest, political and economical motives. The motives to overestimate Chernobyl consequences included financing, international help and cooperation. Certain writers exaggerating medical and ecological consequences of anthropogenic increase in the radiation background contribute to a strangulation of atomic energy. This is in the interests of fossil fuel producers. Nuclear power has returned to the agenda because of the concerns about energy demand and climate changes. Health burdens are the greatest for power stations based on coal and oil. The burdens are lower for natural gas and still lower for atomic energy. The same ranking applies to the greenhouse gas emissions and hence probably for the climate change. Among limitations of epidemiological studies are the dose-dependent selection and self-selection. It can be reasonably assumed that people knowing their higher doses would be more motivated to undergo medical checkups being at the same time given more attention. Therefore, diagnostics is on the average more efficient in people with higher doses. In this connection the literature on the post-Chernobyl thyroid and renal cancer, urinary bladder, cataracts and other lesions is reviewed here. Results of some Chernobyl-related studies should be re-interpreted, taking into account that many cancers found by the screening during the first decade after the accident, or brought from non-contaminated areas and recorded as Chernobyl victims, were in fact advanced neglected malignancies. The misinterpretation of such tumors as aggressive radiogenic cancers should not mislead towards overtreatment. Examples of the overtreatment are reviewed here. Ionizing radiation is a known carcinogen but there is no evidence of carcinogenicity below a certain level. Apparently, living organisms have adapted to the natural radiation background. The background has been decreasing during the time of life existence. The screening effect and increased attention of exposed people to their own health will probably result in new reports on the enhanced cancer and other health risks in areas with an elevated natural or anthropogenic radiation background. This will prove no causality. A promising approach to the research of dose-response relationships are lifelong animal experiments.
Article
Full-text available
Background: There is accumulating evidence of excess risk of cancer in various populations exposed at acute doses below several tens of mSv or doses received over a protracted period. There is also evidence that relative risks are generally higher after radiation exposures in utero or in childhood. Methods and Findings: We reviewed and summarised evidence from 89 studies of cancer following medical diagnostic exposure in utero or in childhood, in which no direct estimates of radiation dose are available. In all of the populations studied exposure was to sparsely ionising radiation (X-rays). Several of the early studies of in utero exposure exhibit modest but statistically significant excess risks of several types of childhood cancer. There is a highly significant (p<0.0005) negative trend of odds ratio with calendar period of study, so that more recent studies tend to exhibit reduced excess risk. There is no significant inter-study heterogeneity (p>0.3). In relation to postnatal exposure there are significant excess risks of leukaemia, brain and solid cancers, with indications of variations in risk by cancer type (p=0.07) and type of exposure (p=0.02), with fluoroscopy and computed tomography scans associated with the highest excess risk. However, there is highly significant inter-study heterogeneity (p<0.01) for all cancer endpoints and all but one type of exposure, although no significant risk trend with calendar period of study. Conclusions: Overall, this large body of data relating to medical diagnostic radiation exposure in utero provides support for an associated excess risk of childhood cancer. However, the pronounced heterogeneity in studies of postnatal diagnostic exposure, the implied uncertainty as to the meaning of summary measures, and the distinct possibilities of bias, substantially reduce the strength of the evidence from the associations we observe between radiation imaging in childhood and the subsequent risk of cancer being causally related to radiation exposure.
Article
Full-text available
Secondary glaucoma is a typical normal tissue complication following radiation therapy involving ocular radiation exposure at high fractionated dose (several tens of Gy). In contrast, recent studies in acutely exposed Japanese atomic bomb survivors showed a significantly increased risk for normal-tension glaucoma (NTG, a subtype of primary open-angle glaucoma) at much lower dose, but such information is not available in any other cohorts. We therefore set out to evaluate the incidence of risk for primary glaucoma and its subtypes in a Russian cohort of Mayak Production Association nuclear workers who received chronic radiation exposure over many years. Of these, we found a significantly increased relative risk (RR) of NTG incidence (RR=1.88 95% confidence intervals (CI): 1.01, 3.51; P=0.047) in workers exposed to gamma rays at cumulative brain absorbed dose above >1 Gy. We observed the linear relationship between NTG incidence and brain absorbed gamma dose with an excess relative risk per unit brain absorbed dose of 0.53 (95% CI: 0.01, 1.68; P <0.05), but not for any other subtypes nor for total primary glaucoma. Such elevated risk of radiogenic NTG incidence, if confirmed in other cohorts, has significant implications for normal tissue complications in radiotherapy patients receiving ocular radiation exposure, and for ocular radiation protection in radiation workers.
Article
Full-text available
The lens of the eye is one of the most radiosensitive tissues. Although the exact mechanism of radiation-induced cataract development remains unknown, altered proliferation, migration, and adhesion have been proposed as factors. Lens epithelial cells were exposed to X-rays (0.1–2 Gy) and radiation effects were examined after 12 h and 7 day. Proliferation was quantified using an MTT assay, migration was measured using a Boyden chamber and wound-healing assay, and adhesion was assessed on three extracellular matrices. Transcriptional changes were also examined using RT-qPCR for a panel of genes related to these processes. In general, a nonlinear radiation response was observed, with the greatest effects occurring at a dose of 0.25 Gy. At this dose, a reduction in proliferation occurred 12 h post irradiation (82.06 ± 2.66%), followed by an increase at 7 day (116.16 ± 3.64%). Cell migration was increased at 0.25 Gy, with rates 121.66 ± 6.49% and 232.78 ± 22.22% greater than controls at 12 h and 7 day respectively. Cell adhesion was consistently reduced above doses of 0.25 Gy. Transcriptional alterations were identified at these same doses in multiple genes related to proliferation, migration, and adhesion. Overall, this research began to elucidate the functional changes that occur in lens cells following radiation exposure, thereby providing a better mechanistic understanding of radiation-induced cataract development.
Article
Full-text available
Background: The detrimental health effects associated with the receipt of moderate (0.1–1 Gy) and high (>1 Gy) acute doses of sparsely ionising radiation are well established from human epidemiological studies. There is accumulating direct evidence of excess risk of cancer in a number of populations exposed at lower acute doses or doses received over a protracted period. There is evidence that relative risks are generally higher after radiation exposures in utero or in childhood. Methods and findings: We reviewed and summarised evidence from 60 studies of cancer or benign neoplasms following low- or moderate-level exposure in utero or in childhood from medical and environmental sources. In most of the populations studied the exposure was predominantly to sparsely ionising radiation, such as X-rays and gamma-rays. There were significant (p < 0.001) excess risks for all cancers, and particularly large excess relative risks were observed for brain/CNS tumours, thyroid cancer (including nodules) and leukaemia. Conclusions: Overall, the totality of this large body of data relating to in utero and childhood exposure provides support for the existence of excess cancer and benign neoplasm risk associated with radiation doses < 0.1 Gy, and for certain groups exposed to natural background radiation, to fallout and medical X-rays in utero, at about 0.02 Gy.
Article
Full-text available
Recent epidemiological and experimental animal data, as well as reanalyses of data previously accumulated, indicate that the lens of the eye is more radiosensitive than was previously thought. This has resulted in a reduction of the occupational lens dose limit within the European Union countries, Japan and elsewhere. This Commentary introduces the work done by the LDLensRad Consortium contained within this Focus Issue, towards advancement of understanding of the mechanisms of low dose radiation cataract.
Article
Full-text available
Cataract is the leading cause of visual impairment which can result in blindness. Cataract formation has been associated with radiation exposure; however, the mechanistic understanding of this phenomenon is still lacking. The goal of this study was to investigate mechanisms of cataract induction in isolated lens epithelial cells (LEC) exposed to ionizing radiation. Human LECs from different genetic backgrounds (SV40 immortalized HLE-B3 and primary HLEC cells) were exposed to varying doses of 137Cs gamma rays (0, 0.1, 0.25 and 0.5 Gy), at low (0.065 Gy/min) and higher (0.3 Gy/min) dose rates. Different assays were used to measure LEC response for, e.g., viability, oxidative stress, DNA damage studies, senescence and changes to telomere length/telomerase activity at two time points (1 h and 24 h, or 24 h and 15 days, depending on the type of assay and expected response time). The viability of cells decreased in a dose-dependent manner within 24 h of irradiation. Measurement of reactive oxygen species showed an increase at 1 h postirradiation, which was alleviated within 24 h. This was consistent with DNA damage results showing high DNA damage after 1 h postirradiation which reduced significantly (but not completely) within 24 h. Induction of senescence was also observed 15 days postirradiation, but this was not attributed to telomere erosion or telomerase activity reduction. Overall, these findings provide a mechanistic understanding of low-dose radiation-induced cataractogenesis which will ultimately help to inform judgements on the magnitude of risk and improve existing radiation protection procedures.
Article
Full-text available
Recent epidemiological findings and reanalysis of historical data suggest lens opacities resulting from ionizing radiation exposures are likely induced at lower doses than previously thought. These observations have led to ICRP recommendations for a reduction in the occupational dose limits for the eye lens, as well as subsequent implementation in EU member states. The EU CONCERT LDLensRad project was initiated to further understand the effects of ionizing radiation on the lens and identify the mechanism(s) involved in radiation-induced cataract, as well as the impact of dose and dose-rate. Here, we present the results of a long-term study of changes to lens opacity in male and female adult mice from a variety of different genetic (radiosensitive or radioresistant) backgrounds, including mutant strains Ercc2 and Ptch1, which were assumed to be susceptible to radiation-induced lens opacities. Mice received 0.5, 1 and 2 Gy 60Co gamma-ray irradiation at dose rates of 0.063 and 0.3 Gy min–1. Scheimpflug imaging was used to quantify lens opacification as an early indicator of cataract, with monthly observations taken post-irradiation for an 18-month period in all strains apart from 129S2, which were observed for 12 months. Opacification of the lens was found to increase with time post-irradiation (with age) for most mouse models, with ionizing radiation exposure increasing opacities further. Sex, dose, dose rate and genetic background were all found to be significant contributors to opacification; however, significant interactions were identified, which meant that the impact of these factors was strain dependent. Mean lens density increased with higher dose and dose rate in the presence of Ercc2 and Ptch1 mutations. This project was the first to focus on low (<1 Gy) dose, multiple dose rate, sex and strain effects in lens opacification, and clearly demonstrates the importance of these experimental factors in radiobiological investigations on the lens. The results provide insight into the effects of ionizing radiation on the lens as well as the need for further work in this area to underpin appropriate radiation protection legislation and guidance.
Article
Full-text available
One harmful long-term effect of ionizing radiation is cataract development. Recent studies have been focused on elucidating the mechanistic pathways involved in this pathogenesis. Since accumulating evidence has established a role of microRNAs in ocular diseases, including cataract, the goal of this work was to determine the microRNA signature of the mouse lens, at short time periods postirradiation, to understand the mechanisms related to radio-induced cataractogenesis. To evaluate the differences in the microRNA profiles, 10-week-old Patched1 heterozygous (Ptch1+/-) mice, bred onto two different genetic backgrounds (CD1 and C57Bl/6J), received whole-body 2 Gy g-ray irradiation, and 24 h later lenses were collected. Next-generation sequencing and bioinformatics analysis revealed that genetic background markedly influenced the list of the deregulated microRNAs and the mainly predicted perturbed biological functions of 2 Gy irradiated Ptch1+/- mouse lenses. We identified a subset of microRNAs with a contra-regulated expression between strains, with a key role in regulating Toll-like receptor (TLR)-signaling pathways. Furthermore, a detailed analysis of miRNome data showed a completely different DNA damage response in mouse lenses 24 h postirradiation, mainly mediated by a marked upregulation of p53 signaling in Ptch1+/-/C57Bl/6J lenses that was not detected on a CD1 background. We propose a strict interplay between p53 and TLR signaling in Ptch1+/-/C57Bl/6J lenses shortly after irradiation that could explain both the resistance of this strain to developing lens opacities and the susceptibility of CD1 background to radiation-induced cataractogenesis through activation of epithelial-mesenchymal transition.
Article
Full-text available
Ionizing radiation is widely known to induce various kinds of lens cataracts, of which posterior subcapsular cataracts (PSCs) have the highest prevalence. Despite some studies regarding the epidemiology and biology of radiation-induced PSCs, the mechanism underscoring the formation of this type of lesions and their dose dependency remain uncertain. Within the current study, our team investigated the in vivo characteristics of PSCs in B6C3F1 mice (F1-hybrids of BL6 × C3H) that received 0.5-2 Gy γ-ray irradiation after postnatal day 70. For purposes of assessing lenticular damages, spectral domain optical coherence tomography was utilized, and the visual acuity of the mice was measured to analyze their levels of visual impairment, and histological sections were then prepared in to characterize in vivo phenotypes. Three varying in vivo phenotype anterior and posterior lesions were thus revealed and correlated with the applied doses to understand their marginal influence on the visual acuity of the studied mice. Histological data indicated no significantly increased odds ratios for PSCs below a dose of 1 Gy at the end of the observation time. Furthermore, our team demonstrated that when the frequencies of the posterior and anterior lesions were calculated at early time points, their responses were in accordance with a deterministic model, whereas at later time points, their responses were better described via a stochastic model. The current study will aid in honing the current understanding of radiation-induced cataract formation and contributes greatly to addressing the fundamental questions of lens dose response within the field of radiation biology.
Article
Full-text available
Accumulating evidence suggests that ionizing radiation (IR)-induced cataract may be associated with oxidative stress. Nuclear factor erythroid 2-related factor 2 (Nrf2) serves as a master regulator of the antioxidant defense system against oxidative stress. The present study aimed to investigate the effects of different doses of neutron radiation on the Nrf2-reegulated antioxidant defense system in rat lens and assess the status of oxidative stress. A total of 24 SD rats were randomly divided into the following four groups: i) Control group; iis) 0.4 Sv group; iii) 1.2 Sv group; and iv) 3.6 Sv group. The rats were sacrificed 7 days after radiation and lenses were dissected for histological, biochemical (malondialdehyde, glutathione and superoxide dismutase) and western blot (Nrf2, glutamate-cysteine ligase catalytic subunit and heme oxygenase 1) analyses. The morphological features of the lenses remained intact in the 0.4 Sv, 1.2 Sv and control groups, whilst the lenses in the 3.6 Sv group exhibited injuries. Results from the TUNEL assay demonstrated apparent apoptosis in lens epithelial cells following 3.6 Sv neutron radiation whereas sparse apoptosis was observed following 0.4 Sv and 1.2 Sv radiation. Malondialdehyde levels were reduced in the 0.4 Sv and 1.2 Sv groups but increased in the 3.6 Sv group, compared with those in the control group. Conversely, glutathione expression and the activity of superoxide dismutase were higher in the 0.4 Sv and 1.2 Sv groups, but lower in the 3.6 Sv group, compared with those in the control group. In addition, the total and nuclear protein levels of Nrf2 were increased following neutron radiation compared with those in the control group, though the Nrf2 protein levels decreased in the 3.6 Sv group compared with those in the 1.2 Sv group. The levels of glutamate-cysteine ligase catalytic subunit and heme oxygenase 1, downstream antioxidant enzymes of Nrf2, demonstrated the same profile as that in Nrf2. Taken together, the results of the present study suggest that neutron radiation affects Nrf2-regulated antioxidant systems in a two-stage process. Namely, the induction phase for low-dose radiation and regression phase for high-dose radiation. Therefore, it was hypothesized that activation and enhancement of the Nrf2-regulated antioxidant system may be useful in preventing or delaying IR-induced cataract, which may be extended even for other diseases associated with oxidative stress.
Article
Full-text available
The current framework of radiological protection of occupational exposed medical workers reduced the eye-lens equivalent dose limit from 150 to 20 mSv per year requiring an accurate dosimetric evaluation and an increase understanding of radiation induced effects on Lens cells considering the typical scenario of occupational exposed medical operators. Indeed, it is widely accepted that genomic damage of Lens epithelial cells (LEC) is a key mechanism of cataractogenesis. However, the relationship between apoptosis and cataractogenesis is still controversial. In this study biological and physical data are combined to improve the understanding of radiation induced effects on LEC. To characterize the occupational exposure of medical workers during angiographic procedures an INNOVA 4100 (General Electric Healthcare) equipment was used (scenario A). Additional experiments were conducted using a research tube (scenario B). For both scenarios, the frequencies of binucleated cells, micronuclei, p21-positive cells were assessed with different doses and dose rates. A Monte-Carlo study was conducted using a model for the photon generation with the X-ray tubes and with the Petri dishes considering the two different scenarios (A and B) to reproduce the experimental conditions and validate the irradiation setups to the cells. The simulation results have been tallied using the Monte Carlo code MCNP6. The spectral characteristics of the different X-ray beams have been estimated. All irradiated samples showed frequencies of micronuclei and p21-positive cells higher than the unirradiated controls. Differences in frequencies increased with the delivered dose measured with Gafchromic films XR-RV3. The spectrum incident on eye lens and Petri, as estimated with MCNP6, was in good agreement in the scenario A (confirming the experimental setup), while the mean energy spectrum was higher in the scenario B. Nevertheless, the response of LEC seemed mainly related to the measured absorbed dose. No effects on viability were detected. Our results support the hypothesis that apoptosis is not responsible for cataract induced by low doses of X-ray (i.e. 25 mGy) while the induction of transient p21 may interfere with the disassembly of the nuclear envelop in differentiating LEC, leading to cataract formation. Further studies are needed to better clarify the relationship we suggested between DNA damage, transient p21 induction and the inability of LEC enucleation.
Article
Full-text available
The aim of the study was to evaluate the risk and threshold doses of lens opacity among residents exposed to low-dose radiation. Residents aged ≥45 years were recruited from a high natural background radiation (HNBR) area in Yangjiang City and a control area selected from nearby Enping City. Lens opacities (LOPs) were classified according to the Lens Opacities Classification System (LOCS) III system. Face-to-face interviews were conducted to collect information on lifestyles, migration and medical history. Life-time cumulative doses were estimated using gender, age, occupancy factors and environmental radiation doses received indoors and outdoors. Logistic regression analyses were conducted to estimate the dose response and determine thresholds. In the HNBR area, among 479 study participants, 101 (21.1%), 245(51.1%) and 23 cases (4.8%), respectively, of cortical, nuclear and posterior subcapsular (PSC) LOPs were found. In the control area, those types of LOPs were identified among 58 cases (12.6%), 206 cases (51.2%) and 6 cases (1.3%) of 462 examinees, respectively. Cumulative eye lens dose was estimated to be 189.5 ± 36.5 mGy in the HNBR area. Logistic analyses gave odds ratios at 100 mGy of 1.26 [95% confidence interval (CI) 1.00-1.60], 0.81 (95% CI 0.64-1.01) and 1.73 (95% CI 1.05-2.85) for cortical, nuclear and PSC LOPs, respectively. For cortical LOPs, a logistic analysis with a threshold dose gave a threshold estimate of 140 mGy (90% CI 110-160 mGy). The results indicated that population exposed to life-time, low-dose-rate environmental radiation was at an elevated risk of cortical and PSC LOPs. A statistically significant threshold dose was obtained for cortical LOPs and no threshold dose for PSC LOPs.
Article
Full-text available
Purpose: Since the exact development of posterior subcapsular cataracts (PSCs) is poorly understood, we review various risk factors and propose a two-stage etiology for PSCs. Methods: The biological mechanisms associated with age-related cataracts (primarily nuclear cataracts, cortical cataracts and PSCs) were reviewed in relation to selected risk factors that induce PSCs (including atopy, diabetes, hypoparathyroidism, myopia, retinitis, solar radiation, steroid use, uveitis, vitrectomy and ionizing radiation). We particularly focused on ionizing radiation, as this is known to be a risk factor specific to PSCs. Based on an analysis of the reviewed material, we propose a detailed explanation of the etiology of PSCs. Conclusions: Lens epithelial cells (LECs) and lens fiber cells are normally hypoxic and therefore very sensitive to changes in oxidative stress, as quantified by the radiation oxygen effect. We hypothesize that the development of PSC opacities is a two-stage process. Stage I, early in life, is driven by risk factors that promote oxidative stress and ion-pump disruption, harming lens fibers and causing aberrant LECs to proliferate and ectopically migrate as Wedl cells (perhaps by processes associated with an epithelial to mesenchymal transition) to the posterior pole region. After a latent period, in Stage II, the development of PSCs advances mainly due to chronic inflammation and other premature aging-related mechanisms that promote mature vacuolar or plaque PSC. This two-stage hypothesis of PSC etiology accounts for risk factors, such as aging, diabetes and ionizing radiation, which directly affects LECs and the lens. In addition, these risk factors can damage other ocular regions, such as the retina and vitreous, that also indirectly contribute to the development of PSCs. It is possible that the incidence of PSCs may be reduced by reversing the effects of Stage I through various means, including ocular antioxidants.
Article
Full-text available
In 2011, the International Commission on Radiological Protection (ICRP) recommended reducing the occupational equivalent dose limit for the lens of the eye from 150 mSv/year to 20 mSv/year, averaged over five years, with no single year exceeding 50 mSv. With this recommendation, several important assumptions were made, such as lack of dose rate effect, classification of cataracts as a tissue reaction with a dose threshold at 0.5 Gy, and progression of minor opacities into vision-impairing cataracts. However, although new dose thresholds and occupational dose limits have been set for radiation-induced cataract, ICRP clearly states that the recommendations are chiefly based on epidemiological evidence because there are a very small number of studies that provide explicit biological and mechanistic evidence at doses under 2 Gy. Since the release of the 2011 ICRP statement, the Multidisciplinary European Low Dose Initiative (MELODI) supported in April 2019 a scientific workshop that aimed to review epidemiological, clinical and biological evidence for radiation-induced cataracts. The purpose of this article is to present and discuss recent related epidemiological and clinical studies, ophthalmic examination techniques, biological and mechanistic knowledge, and to identify research gaps, towards the implementation of a research strategy for future studies on radiation-induced lens opacities. The authors recommend particularly to study the effect of ionizing radiation on the lens in the context of the wider, systemic effects, including in the retina, brain and other organs, and as such cataract is recommended to be studied as part of larger scale programs focused on multiple radiation health effects.
Article
Full-text available
Purpose: This review discusses recent developments in our understanding of biological and physiological mechanisms underlying radiation cataractogenesis. The areas discussed include effects of low-dose exposures to the lens including potential relevance of non-targeted effects, the development of new personal-protective equipment (PPE) and standards in clinical and nuclear settings motivated by the updated ICRP recommendations to mitigate exposures to the lens of the eye. The review also looks at evidence from the field linking cataracts in birds and mammals to low dose exposures. Conclusions: The review suggests that there is evidence that cataractogenesis is not a tissue reaction (deterministic effect) but rather is a low dose effect which shows a saturable dose response relationship similar to that seen for non-targeted effects in general. The review concludes that new research is needed to determine the dose response relationship in environmental studies where field data are contradictory and lab studies confined to rodent models for human exposure studies
Article
Full-text available
Cataract is one of the major morbidities in the US population and it has long been appreciated that high and acutely delivered radiation doses of 1 Gy or more can induce cataract. Some more recent studies, in particular of the US Radiologic Technologists, have suggested that cataract may be induced by much lower chronically delivered doses of ionizing radiation. It is well recognized that dosimetric measurement error can alter substantially the shape of radiation dose-response relationship and hence the derived study risk estimates, and can also inflate the variance of the estimates. In the present study we evaluate the impact of uncertainties in eye-lens absorbed doses on the estimated risk of cataract in the US Radiologic Technologists Monte Carlo Dosimetry System, using both absolute and relative risk models. Among 11,345 cases we show that the inflation in the standard error for the excess relative risk (ERR) is generally modest, at most about 20% of the unadjusted standard error, depending on the model used for the baseline risk. The largest adjustment results from use of relative risk models, so that the ERR/Gy and its 95% confidence intervals (CI) change from 1.085 (0.645, 1.525) to 1.085 (0.558, 1.612) after adjustment. However, the inflation in the standard error of the excess absolute risk (EAR) coefficient is generally minimal, at most about 0.04% of the standard error.
Article
Full-text available
Tissue reactions and stochastic effects after exposure to ionising radiation are variable between individuals but the factors and mechanisms governing individual responses are not well understood. Individual responses can be measured at different levels of biological organization and using different endpoints following varying doses of radiation, including: cancers, non-cancer diseases and mortality in the whole organism; normal tissue reactions after exposures; and, cellular endpoints such as chromosomal damage and molecular alterations. There is no doubt that many factors influence the responses of people to radiation to different degrees. In addition to the obvious general factors of radiation quality, dose, dose rate and the tissue (sub)volume irradiated, recognized and potential determining factors include age, sex, life style (e.g., smoking, diet, possibly body mass index), environmental factors, genetics and epigenetics, stochastic distribution of cellular events, and systemic comorbidities such as diabetes or viral infections. Genetic factors are commonly thought to be a substantial contributor to individual response to radiation. Apart from a small number of rare monogenic diseases such as ataxia telangiectasia, the inheritance of an abnormally responsive phenotype among a population of healthy individuals does not follow a classical Mendelian inheritance pattern. Rather it is considered to be a multi-factorial, complex trait.
Article
Full-text available
Retinoblastoma represents 3% of cancers in children under fifteen years of age. The standard paediatric treatment for saving the affected eye is supraselective intra-arterial chemotherapy performed in interventional rooms. In order to address the radiation toxicity due to the angiography, the aim of this study was to determine the typical dose value corresponding to the procedure, estimate the paediatric patients’ eye lens dose and study the relationship between dose indicators and dose to the lens. An automatic dose management software was installed in two interventional rooms to obtain the distribution of the dose indicators kerma-area product and reference-point air kerma, getting a typical value 16 Gy·cm2 and 130 mGy, respectively (n = 35). The eye lens dose estimates were obtained with photoluminescent dosimeters placed on the patient’s eyelids. In the left eye, the entrance surface air kerma was 44.23 ± 2.66 mGy, and 12.72 ± 0.89 mGy in the right eye (n = 10). There was a positive correlation between dose to the lens per procedure and dose indicators, with R2 > 0.65 for both eyes. Based on this information, the threshold for the onset of radiation-induce cataracts (500 mGy) will be exceeded if the treatment is performed for more than 8 sessions.
Article
Full-text available
Objective: to describe the clinical types of cataracts in the remote period after acute radiation sickness (ARS). Materials and methods: Twenty four - thirty three years after the emergency exposure, a complete ophthalmolog- ic examination of 53 reconvalescents of ARS conducted. The average age of patients at the time of the examination was (64.6 ± 1.2) years, the average radiation dose of the examined patients was (2.39 ± 0.17) Gy. Ophthalmologic examination included visometry with and without correction, tonometry, autorefractokeratometry, biomicroscopy on a slit lamp, retroillumination photography (infrared and color) of a lens. To evaluate the results of surveys used statistical methods: calculation of average values of quantitative indicators, estimation of probability difference by Student's method. Results: In 10 patients (17 eyes) of the 53 reconvalescents of ARS in the remote period after irradiation artifakia after surgical treatment was recognized. In all other patients, changes in the transparency of the lens were detect- ed, and most patients had combined changes. Radiation cataract with it's characteristic clinical picture was detect- ed in 32 people, and in one more case, it's first signs were recorded. But 14 reconvalescents of ARS in the remote period after irradiation had not radiation cataract. Conclusions: Radiation cataract has not been detected in 14 reconvalescents of ARS in the remote period after irra- diation; the radiation doses of these patients significantly exceeds the threshold levels. Therefore, the absence of it's signs in the remote period in individuals exposed to doses above 2 Gy may indicate that this well-known radia- tion-induced effect is stochastic. Further analysis of the clinical features of the len's pathology in the reconvales- cents of ARS is promising for the study of the mechanism of damage to the lens in this category of victims of the Chornobyl accident.
Article
Full-text available
Objectives Previous analyses of cataract in radiation-exposed populations have assessed relative risk; radiogenic excess additive risk (EAR), arguably of more public health importance, has not been estimated. Previous analysis of a large prospective cohort of US radiologic technologists (USRT) quantified excess relative risk of cataract in relation to occupational radiation dose. We aim to assess EARs of cataract. Methods We estimated EARs of cataract/cataract surgery in the USRT cohort using generalised additive models in relation to occupational radiation exposure, and assessed risk modification by a priori-selected cataract risk factors (diabetes, body mass index, smoking, race, sex, birth-year, ultraviolet B (UVB) radiation exposure). Results There were 11 345 cataract diagnoses and 5440 of cataract surgery during 832 462 and 888 402 person-years of follow-up, respectively. Cumulative occupational radiation exposure was associated with self-reported cataract, but not with cataract surgery, with EAR/10 ⁴ person-year Gy=94 (95% CI: 47 to 143, p<0.001) and EAR/10 ⁴ person-year Gy=13 (95% CI: <0 to 57, p=0.551), respectively. There was marked (p<0.001) variation of EAR by age and by diabetes status, with risk higher among persons ≥75 years and diabetics. There were indications of elevated risk among those with higher UVB radiation (p=0.045), whites (p=0.056) and among those with higher levels of cigarette smoking (p=0.062). Elevated additive risk was observed for estimated occupational radiation eye-lens doses <100 mGy (p=0.004) with no dose–response curvature (p=0.903). Conclusions The elevated additive risks associated with low-dose radiation, if confirmed elsewhere, have important public health and clinical implications for radiation workers as well as regulatory measures.
Article
Full-text available
The International Commission on Radiological Protection (ICRP) has considered for over sixty years that the lens of the eye is among the most radiosensitive tissues, and has recommended dose limits for the lens to prevent occurrence of vision impairing cataracts (VICs). Epidemiological evidence that doses much lower than previously thought produce cataracts led ICRP to recommend reducing dose threshold for VICs and reducing an occupational equivalent dose limit for the lens in 2011, when only a single threshold of 0.5 Gy was recommended. On the basis of epidemiological evidence, ICRP assumed progression of minor opacities into VICs and no dose rate effect. This contrasts with previously recommended separate thresholds for minor opacities and VICs, and for different exposure scenarios. Progression was assumed based on similar risks of cataracts and cataract surgery in Japanese atomic bomb survivors. The absence of dose rate effect derived from the observed similar thresholds for protracted exposures in Chernobyl cleanup workers and in atomic bomb survivors. Since 2011, there has been an increasing body of epidemiological evidence relating to cataracts and other ocular diseases (i.e., glaucoma and macular degeneration), particularly at low doses and low dose rates. This review paper gives an overview of the scientific basis of the 2011 ICRP recommendation, discusses the plausibility of these two assumptions in the light of emerging scientific evidence, and considers the radiosensitivity of the lens among ocular structures.
Article
Full-text available
Glaucoma is a major cause of visual impairment, and secondary glaucoma manifested as neovascular glaucoma has long been known to occur following high-dose fractionated radiation therapy. In contrast, little is known as to whether ionizing radiation exposure causes primary glaucoma, except that a single study in Japanese atomic bomb survivors has reported a significantly increase risk. Therefore, the effect of lower dose and lower dose rate remains unclear. Here we report that in Russian Mayak Production Association workers occupationally exposed to chronic radiation for prolonged periods, incidence of total primary glaucoma and primary open-angle glaucoma is significantly associated with various non-radiation factors (sex, attained age, and cataract diagnosed prior to glaucoma), but neither with cumulative dose from external γ-rays nor with cumulative neutron dose nor with the unweighted sum of cumulative γ and neutron doses. The present results suggest for the first time that chronic radiation exposure does not cause primary glaucoma, although the analyses need to be made in other cohorts exposed at various dose and dose rate.
Article
Full-text available
Cataracts have long been known, but a biomathematical model is still unavailable for cataratogenesis. There has been a renewed interest in ionizing radiation cataracts because the recent international recommendation of the reduced lens dose limit stimulated the discussion toward its regulatory implementation in various countries. Nevertheless, a relationship between radiation (dose and dose rate) and response (e.g., incidence, onset and progression) remains incompletely understood, raising the need for a risk-predictive mathematical model. We here report for the first time an in silico model for cataractogenesis. First, a simplified cell proliferation model was developed for human lens growth based on stem and progenitor cell proliferation as well as epithelial-fiber cell differentiation. Then, a model for spontaneous cataractogenesis was developed to reproduce the human data on a relationship between age and cataract incidence. Finally, a model for radiation cataractogenesis was developed that can reproduce the human data on a relationship between dose and cataract onset at various ages, which was further applied to estimate cataract incidence following chronic lifetime exposure. The model can serve as the foundation for further development of the risk-predictive model for cataractogenesis along with additional considerations of various biological mechanisms and epidemiological datasets.
Article
Full-text available
The influence of dose rate on radiation cataractogenesis has yet to be extensively studied. One recent epidemiological investigation suggested that protracted radiation exposure increases radiation-induced cataract risk: cumulative doses of radiation mostly <100 mGy received by US radiologic technologists over 5 years were associated with an increased excess hazard ratio for cataract development. However, there are few mechanistic studies to support and explain such observations. Low-dose radiation-induced DNA damage in the epithelial cells of the eye lens (LECs) has been proposed as a possible contributor to cataract formation and thus visual impairment. Here, 53BP1 foci was used as a marker of DNA damage. Unexpectedly, the number of 53BP1 foci that persisted in the mouse lens samples after γ-radiation exposure increased with decreasing dose-rate at 4 and 24 h. The C57BL/6 mice were exposed to 0.5, 1 and 2 Gy ƴ-radiation at 0.063 and 0.3 Gy/min and also 0.5 Gy at 0.014 Gy/min. This contrasts the data we obtained for peripheral blood lymphocytes collected from the same animal groups, which showed the expected reduction of residual 53BP1 foci with reducing dose-rate. These findings highlight the likely importance of dose-rate in low-dose cataract formation and, furthermore, represent the first evidence that LECs process radiation damage differently to blood lymphocytes.
Article
Full-text available
Exposure of the lenses to direct ionizing radiation during computed tomography (CT) examinations predisposes patients to cataract formation and should be avoided when possible. Avoiding such exposure requires positioning and other maneuvers by technologists that can be challenging. Continuous feedback has been shown to sustain quality improvement and can remind and encourage technologists to comply with these methods. Previously, for use cases such as this, cumbersome manual techniques were required for such feedback. Modern deep learning methods utilizing convolutional neural networks (CNNs) can be used to develop models that can detect lenses in CT examinations. These models can then be used to facilitate automatic and continuous feedback to sustain technologist performance for this task, thus contributing to higher quality patient care. This continuous evaluation for quality purposes also surfaces other operational or process-based challenges that can be addressed. Given high-performance characteristics, these models could also be used for other tasks such as population health research.
Article
Full-text available
Abstract We examined the relationship between glaucoma subtype and retinal vascular caliber as markers of ocular circulation. Subjects were Japanese atomic bomb survivors in Hiroshima and Nagasaki. After a screening examination, potential cases were subjected to further definitive examination. The diameters of central retinal artery and vein equivalents (CRAE and CRVE) on digitized retinal photographs were measured using an established method. Generalized linear regression analyses were used to examine the associations among vessel diameters, radiation exposure, and prevalence of glaucoma subtypes among the study subjects. We identified 196 cases of glaucoma (12%) based on optic disc appearance, perimetry results, and other ocular findings. The main subtypes were primary angle-closure glaucoma, primary open-angle glaucoma and normal-tension glaucoma (NTG). NTG was the dominant subtype (78%). NTG was negatively associated with CRAE and CRVE, and positively associated with radiation dose. CRVE was negatively associated with radiation dose and the association was unclear for CRAE. The smaller retinal vessel caliber in NTG patients than in subjects without glaucoma may indicate an association between ocular blood flow and the pathogenesis of NTG. However, significant relationships among vessel calibers, NTG and radiation exposure were not clear.
Article
Full-text available
Based on ongoing research on ionizing radiation thresholds for cataracts, the International Commission on Radiological Protection has proposed new guidelines lowering the annual occupational lens of eye dose limit from 150 mSv to 20 mSv. The International Atomic Energy Agency has operationalized these new guidelines. Subsequently, national/regional radiation protection regulators are reviewing their lens of eye dose limits with an aim of moving towards the proposed new limits, resulting in licensees having to demonstrate compliance. In health care settings, fluoroscopic interventional practices generally have higher lens of eye doses and nuclear medicine settings generally have lower doses. A prospective cohort (n = 19) of nuclear medicine technologists wore dedicated lens of eye dosimeters for a 3 mo period synchronized with their body dosimeter schedules. The lens of eye dosimeters were validated to have a linear response in the anticipated dose ranges. The participants worked in a relatively high-volume nuclear medicine practice, which included general and cardiac, positron emission tomography/computed tomography, radiopharmacy, and cyclotron operations. The annualized dose ranges were 0.0-3.68 mSv (lens of eye) and 0.48-4.72 mSv (whole body). There was a good correlation between lens of eye and body dosimeter readings (R = 0.67). There were no significant differences in lens of eye dose by work type, worker sex, or side on which the dosimeter was worn. The findings should be generalizable to other similar practices, especially in North America, and should be sufficient to demonstrate regulatory compliance in nuclear medicine settings with the proposed new lens of eye dose limits.
Article
Full-text available
In this study, the risk of cataract removal surgery was assessed in a cohort of workers occupationally exposed to ionising radiation over a prolonged period. The study cohort includes 22,377 workers of the Mayak Production Association (about 25% of whom are females) first employed at one of the main facilities in 1948–1982, who were followed up to the end of 2008. Dose estimates used in the study are provided by the Mayak Worker Dosimetry System 2008. The mean cumulative dose from external γ-rays (personal dose equivalent Hp(10)) is 0.54 ± 0.76 Sv for males and 0.44 ± 0.65 Sv for females. The mean cumulative doses from neutrons (personal dose equivalent Hp(10)n) were 0.034 ± 0.080 Sv for males and 0.033 ± 0.092 Sv for females. Relative risks and excess relative risks per unit effective dose were calculated based on maximum likelihood. Among 4,177 workers diagnosed with a verified diagnosis of senile cataract, 701 lens removal surgeries (16.7%) were performed by the end of the follow-up period. The risk of cataract removal surgery was shown to be significantly associated with non-radiation factors such as sex, attained age, smoking, an ocular comorbidity (e.g., glaucoma) and a somatic comorbidity (e.g., diabetes mellitus). There was no significant association of cataract removal surgery with external γ-dose regardless of inclusion of the neutron dose adjustment with either linear or non-linear models. It is concluded that cataract removal surgery rate may not be a highly sensitive and specific indicator that could serve as a surrogate for radiation-related cataracts.
Article
Full-text available
Ionizing radiation (IR) damages DNA and other macromolecules, including proteins and lipids. Most cell types can repair DNA damage and cycle continuously their macromolecules as a mechanism to remove defective proteins and lipids. In those cells that lack nuclei and other organelles, such as lens fiber cells and mammalian erythrocytes, IR-induced damage to macromolecules is retained because they cannot be easily replenished. Whilst the life span for an erythrocyte is several months, the life span of a human lens is decades. There is very limited turnover in lens macromolecules, therefore the aging process greatly impacts lens structure and function over its lifetime. The lens is a tissue where biomolecular longevity, lifelong retention of its components and continued growth are integral to its homeostasis. These characteristics make the lens an excellent model to study the contribution of retained macromolecular damage over time. Epidemiological data have revealed a significant association between exposure to IR, the loss of lens optical function and the formation of cataracts (cataractogenesis) later in life. Lifestyle, genetic and environmental factors all contribute to cataractogenesis due to their effect on the aging process. Cataract is an iconic age-related disease in humans. IR is a recognised cause of cataract and the occupational lens dose limit is reduced from 150 to 20 mGy / year averaged over 5 years (ICRP Publication 118). Understanding the effects of low dose IR on the lens and its role in cataractogenesis is therefore very important. So we redefine “cataractogenic load” as a term to account for the combined lifestyle, genetic and environmental processes that increase biomolecular damage to lens macromolecules. These processes weaken metabolic defenses, increase post-translational protein modifications, and alter the lipid structure and content of the lens. IR exposure is a significant insult to the lens because of free radical generation and the ensuing oxidative stress. We support the concept that damage caused by IR compounds the aging process by increasing the cataractogenic load, hereby accelerating lens aging and its loss of function.
Article
Full-text available
This paper criticizes studies claiming huge radiation effects on wildlife at Chernobyl. There are likely to be subtle effects of radiation on organisms in the "hotspots" at Chernobyl. But it is argued here that studies claiming extensive population damage, and much greater sensitivity of organisms in the field than in the lab are not well supported by scientific evidence.
Article
Full-text available
Background: Posterior subcapsular cataract is a tissue reaction commonly found among professionals exposed to ionizing radiation. Objective: To assess the prevalence of cataract in professionals working in hemodynamics in Brazil. Methods: Professionals exposed to ionizing radiation (group 1, G1) underwent slit lamp examination with a biomicroscope for lens examination and compared with non-exposed subjects (group 2, G2). Ophthalmologic findings were described and classified by opacity degree and localization using the Lens Opacities Classification System III. Both groups answered a questionnaire on work and health conditions to investigate the presence of risk factors for cataract. The level of significance was set at 5% (p < 0.05). Results: A total of 112 volunteers of G1, mean age of 44.95 (±10.23) years, and 88 volunteers of G2, mean age of 48.07 (±12.18) years were evaluated; 75.2% of G1 and 85.2% of G2 were physicians. Statistical analysis between G1 and G2 showed a prevalence of posterior subcapsular cataract of 13% and 2% in G1 and G2, respectively (0.0081). Considering physicians only, 38% of G1 and 15% of G2 had cataract, with the prevalence of posterior subcapsular cataract of 13% and 3%, respectively (p = 0.0176). Among non-physicians, no difference was found in the prevalence of cataract (by types). Conclusions: Cataract was more prevalent in professionals exposed to ionizing radiation, with posterior subcapsular cataract the most frequent finding.
Article
Full-text available
The main effect of ionizing radiation on the eyes is the onset of posterior cortical and subcapsular cataracts. Recent studies have raised questions about the mechanism of ocular damage and the threshold dose for the onset of such effects. Currently, operators may be exposed to ionizing radiation during surgical procedures. It has been estimated that urologists can be exposed to an annual dose close to or above 20 mSv/year. The aim of our study was to evaluate the frequency of cataracts in a group of professional radiological operators to verify their possible association with the radiation dose to the crystalline lens and the tasks performed. The records of 73 health workers exposed to ionizing radiation were reviewed. The average annual dose to the crystalline lens, the number of years of exposure, and the presence of radiation-compatible opacities were assessed for all operators. Lenticular opacities were observed in 16.4% of subjects. The presence of alterations was associated with exposure doses below 10 mSv and > 10 years’ experience in fluoroscopically guided procedures. Based on our results, protection of the crystalline lens against exposure to ionizing radiation by means of goggles is recommended. In addition, examination of the lens via slit lamp examination is recommended for all operators involved in interventional procedures with the current levels of radiation exposure.
Article
Purpose: A population-based case-control study was conducted in Yangjiang and Enping areas in South China to assess whether the risk of lens opacity induced by natural high background radiation exposure is modulated by polymorphisms of ATM and TP53. Materials and methods: A total of 133 cases who were diagnosed with cortical and posterior subcapsular (PSC) opacity were recruited, and 419 healthy controls were selected through counter-matching in terms of radiation status. Genomic DNA from all the participants was genotyped with the Illumina platform for four single nucleotide polymorphisms of ATM (rs189037, rs373759, and rs4585) and TP53 (rs1042522). The cumulative lens dose received during the entire life was estimated based on annual indoor and outdoor radiation doses and gender- and age-specific occupancy factors. Non-conditional logistic regression was performed to calculate odds ratio (OR) and 95% confidence intervals (95% CI). Results: ATM rs189037 and TP53 rs1042522 were significantly related to cortical and PSC opacity. The risk of opacity was higher when individuals carried the A allele of ATM rs189037 and C allele of TP53 rs1042522, compared with GG genotype. ATM rs189037 A allele carriers (AG/AA) and TP53 rs1042522 C allele carriers (CG/CC) combined with a cumulative lens dose of 100 mGy or higher showed statistically significant opacity risks (OR =5.51, 95% CI: 1.47–20.66; OR =2.69, 95% CI: 1.10–6.60). Conclusion: The A allele of ATM rs189037 and C allele of TP53 rs1042522 increase the risk of lens opacity induced by radiation. These polymorphisms in ATM and TP53 might modify the risk of cortical and PSC opacity induced by chronic and prolonged low-dose radiation.
Article
When managed with appropriate radiation protection procedures, ionising radiation is of great benefit to society. Opacification of the lens, and vision impairing cataract, have recently been recognised at potential effects of relatively low dose radiation exposure, on the order of 1 Gy or below. Within the last 10 years, understanding of the effects of low dose ionising radiation on the lens has increased, particularly in terms of DNA damage and responses, and how multiple radiation or other events in the lens might contribute to the overall risk of cataract. However, gaps remain, not least in the understanding of how radiation interacts with other risk factors such as aging, as well as the relative radiosensitivity of the lens compared to tissues of the body. This paper reviews the current literature in the field of low dose radiation cataract, with a particular focus on sensitivity and latency.
Article
High radiation doses to the body may lead to the stochastic/deterministic effects of ionizing radiation on the critical organs as well as causing the cataract in eye lens of the clinical staff in interventional radiology. In this study, the received doses of the eyes, skin and whole body of 38 clinical staff including physicians, residents, nurses and radiotechnologists in cardiac angiography departments in three selected hospitals were assessed using personal dosemeters during two bimonthly dosimetry periods. Moreover, the correlation coefficients among the measured dose components including eye lens dose, skin dose and whole body dose equivalent in both area of under and over their lead-apron were calculated for all these occupational groups. The results show that the occupational annual dose values of the clinical staff are below the annual dose limits recommended by International Commission on Radiation Protection. Furthermore, among the measured dose components, the highest correlation coefficient value was obtained between the eye lens dose and personal dose equivalent measured over the lead apron for all the occupational groups.
Article
As chest x rays involve risks of patients falling, radiologic technologists (technologists) commonly assist patients, and as the assistance takes place near the patients, the eye lenses of the technologists are exposed to radiation. The recommendations of the International Commission on Radiological Protection suggest that the risk of developing cataracts due to lens exposure is high, and this makes it necessary to reduce and minimize the exposure. The present study investigated the positions of technologists assisting patients that will minimize exposure of the eye lens to radiation. The results showed that it is possible to reduce the exposure by assisting from the following positions: 50% at the sides rather than diagonally behind, 10% at the right side of the patient rather than the left and 40% at 250 mm away from the patient. The maximum reduction with radiation protection glasses was 54% with 0.07 mmPb and 72% with 0.88 mmPb.
Article
Epidemiological studies suggest an increased incidence and risk of cataract after low-dose (,2 Gy) ionizing radiation exposures. However, the biological mechanism(s) of this process are not fully understood. DNA damage and repair are thought to have a contributing role in radiation-induced cataractogenesis. Recently we have reported an inverse doserate effect, as well as the low-dose response, of DNA damage and repair in lens epithelial cells (LECs). Here, we present further initial findings from two mutated strains (Ercc2+/– and Ptch1+/–) of mice, both reportedly susceptible to radiationinduced cataract, and their DNA damage and repair response to low-dose and low-dose-rate gamma rays. Our results support the hypothesis that the lens epithelium responds differently to radiation than other tissues, with reported radiation susceptibility to DNA damage not necessarily translating to the LECs. Genetic predisposition and strain(s) of mice have a significant role in radiation-induced cataract susceptibility.
Article
Background: Head and neck cancers are currently the most common types of cancers. 3D-conformal radiation therapy is the most common dose delivery technique for head and neck cancers. Eye Lens is a radio sensitive structure and cataract formation as a visual disorder associated with exposure to ionizing radiation which is documented. Objective: Determining the radiation dose to eye lens during head and neck radiography and estimating the probability of cataract induction are essential. Material and methods: This experimental study was performed on 14 patients with head and neck cancers through experimental study analysis. The maximum opacity of the eyes lens were measured by pentacamTM before radiation therapy. CT data of patients were transmitted to Isogray treatment planning Software, and dose calculations for each patient was performed. At the end of radiation treatment, 3 and 6 months after radiotherapy, the eye lens opacity of the patients was assessed. Results: Overall, 28 lenses were studied. Statistical one sample K- S test proved normality of obtained data. Using repeated measures test, the relation before and 3 months after radiotherapy, as well as the relationship before and 6 months after radiotherapy proved a significant relationship. Conclusion: The opacity caused by radiation in eyes is a non-statistical and linear-quadratic response curve with no threshold. This opacity can also appear within 3 months after completion of radiation therapy.
Article
Purpose The long-term effect of low and moderate doses of ionizing radiation on the lens is still a matter of debate and needs to be evaluated in more detail. Material and Methods We conducted a detailed histological analysis of eyes from B6C3F1 mice cohorts after acute gamma irradiation (⁶⁰Co source; 0.063 Gy/min) at young adult age of 10 weeks with doses of 0.063, 0.125 and 0.5 Gy. Sham irradiated (0 Gy) mice were used as controls. To test for genetic susceptibility heterozygous Ercc2 mutant mice were used and compared to wild type mice of the same strain background. Mice of both sexes were included in all cohorts. Eyes were collected 4 hours, 12, 18 and 24 months after irradiation. For a better understanding of the underlying mechanisms, metabolomics analyses were performed in lenses and plasma samples of the same mouse cohorts at 4 and 12 hours as well as 12, 18 and 24 months after irradiation. For this purpose, a targeted analysis was chosen. Results This analysis revealed histological changes particularly in the posterior part of the lens that rarely can be observed by using Scheimpflug imaging, as we reported previously. We detected a significant increase of posterior subcapsular cataracts 18 and 24 months after irradiation with 0.5 Gy (odds ratio 9.3; 95%-confidence interval 2.1 – 41.3) independent of sex and genotype. Doses below 0.5 Gy (i.e. 0.063 and 0.125 Gy) did not significantly increase the frequency of posterior subcapsular cataracts at any time point. In lenses, we observed a clear effect of sex and aging but not of irradiation or genotype. While metabolomics analyses of plasma from the same mice showed only a sex effect. Conclusions This paper demonstrates a significant radiation-induced increase in the incidence of posterior subcapsular cataracts, which could not be identified using Scheimpflug imaging as the only diagnostic tool.
Article
Ionising radiation interacts with lenses and retinae differently. In human lenses, posterior subcapsular cataracts are the predominant observation, whereas retinae of adults are comparably resistant to even relatively high doses. In this study, we demonstrate the effects of 2 Gy of low linear energy transfer ionising radiation on eyes of B6C3F1 mice aged postnatal day 2. Optical coherence tomography and Scheimpflug imaging were utilised for the first time to monitor murine lenses and retinae in vivo. The visual acuity of the mice was determined and histological analysis was conducted. Our results demonstrated that visual acuity was reduced by as much as 50 % approximately 9 months after irradiation in irradiated mice. Vision impairment was caused by retinal atrophy and inner cortical cataracts. These results help to further our understanding of the risk of ionising radiation for human foeti (∼ 8 mo), which follow the same eye development stages as neonatal mice.
Article
Background Accumulated body of evidence shows that ionizing radiation increases the risk of cataracts. The mechanisms are not clear and the International Commission on Radiological Protection (ICRP) indicates a need for research into understanding the process, particularly at low doses and low dose rates of exposure. Purpose: This study was designed to examine protein-level modifications in a human lens epithelial (HLE) cell-line following radiation exposures. Materials and methods: HLE cell-line was subjected to X-rays at varied doses (0-5 Gy) and dose-rates (1.62 cGy/min and 38.2 cGy/min). Cells were collected 20 h post-exposure, lysed and proteins were clarified following fractionation by a molecular weight cut-off filtration method. Fractionated cellular proteins were enzymatically digested and subjected to mass spectrometry analysis. Results Statistically significant radiation dose-related protein changes compared to the control group, were identified. Heatmap and hierarchical analysis showed distinct cluster of responses that were dose-rate dependant. Pathway analysis mapped the proteins to networks and biological functions related to mitochondrial dysfunction, reactive oxygen species generation, cell death, cancer, organismal injury and amyloidosis. Networks were shown to be centred on the Retinoblastoma 1 (RB1) protein with indirect interactions to TP53, a DNA damage response/repair protein. The directionalities of the dose-responses were shown to be a general downregulation of proteins at high dose rates and an upregulation at the low dose rate. In addition, consistent non-linear excursions were observed at doses <0.5 Gy that peaked at 0.25 Gy. Conclusion Findings from this work suggests that ionizing radiation exposure of the HLE cells initiates processes associated with protein misfolding, oxidative stress and cell death mechanisms and that these responses are dose-rate dependant and can be relevant to cataractogenesis.
Article
Aim: During transcatheter aortic valve implantations (TAVI) and other percutaneous structural procedures, some patients may need close anesthesiological care, thus exposing the anaesthesiologist to X-rays. This work aims to investigate the radiation dose received by anaesthesiologists during these specific procedures in order to improve their radiological protection. Methods: Occupational radiation doses were measured prospectively during percutaneous structural procedures in several health professionals using electronic dosimeters worn over the apron at chest level. Results: A sample of 49 procedures were recorded, where the anaesthesiologists' average dose per procedure resulted 13 times higher than that of interventional cardiologists. The average dose per procedure received over the protection apron during TAVIs by the anaesthesiologist was 0.13 mSv, with a maximum value of 0.69 mSv. Taking these figures as a conservative estimation of the eye lens dose, an anaesthesiologist could participate in around 150 procedures before reaching the regulatory annual dose limit for the lens of the eye in Europe (20 mSv). Conclusions: In those clinical procedures where patients need close anesthesiological care, the anaesthesiologists might receive high radiation doses increasing the risk for cataracts and the risk of stochastic radiation effects. The proper use of occupational dosimeters will help identify these situations. It is recommended to use a mobile shielding barrier to reduce radiation exposure to acceptable levels in these situations.
Article
Astronauts participating in prolonged space missions constitute a population of individuals who are at an increased risk for cataractogenesis due to exposure to densely ionizing charged particles. Using a rat model, we have previously shown that after irradiation of eyes with either low-linear energy transfer (LET) 60Co γ rays or high-LET 56Fe particles, the rate of progression of anterior and posterior subcapsular cataracts was significantly greater in ovariectomized females implanted with 17-β-estradiol (E2) compared to ovariectomized or intact rats. However, our additional low-LET studies indicated that cataractogenesis may be a modifiable late effect, since we have shown that the modulation of cataractogenesis is dependent upon the timing of administration of E2. Interestingly, we found that E2 protected against cataractogenesis induced by low-LET radiation, but only if administered after the exposure; if administered prior to and after irradiation, for the entire period of observation, then E2 enhanced progression and incidence of cataracts. Since most radioprotectors tested to date are unsuccessful in protecting against the effects of high-LET radiation, we wished to determine whether the protection mediated by E2 against radiation cataractogenesis induced by low-LET radiation would also be observed after high-LET irradiation. Female 56-day-old Sprague-Dawley rats were treated with E2 at various times relative to the time of single-eye irradiation with 2 Gy of 56Fe ions. We found that administration of E2 before irradiation and throughout the lifetime of the rat enhanced cataractogenesis compared to ovariectomized animals. The enhancing effect was slightly reduced when estrogen was removed after irradiation. However, in contrast to what we observed after γ-ray irradiation, there was no inhibition of cataractogenesis if E2 was administered only after 56Fe-ion irradiation. We conclude that protection against cataractogenesis by estrogen is dependent upon the type and ionization density of radiation that the lens was exposed to. The lack of inhibition of radiation cataractogenesis in rats that receive E2 treatment after high-LET irradiation may be attributed to the qualitative differences in the types of DNA damage induced with high-LET radiation compared to low-LET radiation or how damage may be modified at the DNA or tissue level after irradiation.
Article
Ionizing radiation exposure to the lens of the eye is a known cause of cataractogenesis. Administrative data from the Ontario Health Insurance Program was used to examine the association between low-dose radiation exposure from head CT scans and cataract extraction surgery for 16 million Ontarians over a 22-year period (1994–2015). Subjects were grouped based on the number of head CT scans they received, and a Cox proportional hazards analysis was used to determine if there was a correlation with cataract surgery. Covariates included in the analysis were age, sex, diabetes, hypertension and prior history of intraocular surgery. To account for the potentially long latency period between radiation exposure and cataract formation, the data were analyzed incorporating a 5- and 10-year lag between head CT scan exposure and cataract surgery. Both the 5- and 10-year lagged models followed a similar trend, where only the first three head CT scans significantly increased the risk of cataract surgery by 3–8%. Individuals receiving four or more head CT scans did not have an increased cataract risk and in several cases the risk was reduced. Overall, no positive dose-response relationship was seen between the number of head CT scans received and the risk of cataract surgery. Due to the nature of the data extracted from medical records, several uncertainties exist in the analysis related to dosimetry, ultraviolet light exposure and smoking status. Nonetheless, these results do not support an association between ionizing radiation from repeated head CT scans and cataract formation.
Article
We assessed the feasibility of an epidemiological study on the risk of radiation-related lens opacities among interventional physicians in Germany. In a regional multi-centre pilot study associated with a European project, we tested the recruitment strategy, a European questionnaire on work history for the latter dosimetry calculation and the endpoint assessment. 263 interventional physicians and 129 non-exposed colleagues were invited. Questionnaires assessed eligibility criteria, risk factors for cataract, and work history relating to occupational exposure to ionising radiation, including details on type and amount of procedures performed, radiation sources, and use of protective equipment. Eye examinations included regular inspection by an ophthalmologist, digital slit lamp images graded according to the lens opacities classification system, and Scheimpflug camera measurements. 46 interventional (17.5%) and 30 non-exposed physicians (23.3%) agreed to participate, of which 42 and 19, respectively, met the inclusion criteria. Table shields and ceiling suspended shields were used as protective equipment by 85% and 78% of the interventional cardiologists, respectively. However, 68% of them never used lead glasses. More, although minor, opacifications were diagnosed among the 17 interventional cardiologists participating in the eye examinations than among the 18 non-exposed (59% versus 28%), mainly nuclear cataracts in interventional cardiologists and cortical cataracts in the non-exposed. Opacification scores calculated from Scheimpflug measurements were higher among the interventional cardiologists, especially in the left eye (56% versus 28%). Challenges of the approach studied include the dissuading time investment related to pupil dilatation for the eye examinations, the reliance on a retrospective work history questionnaire to gather exposure-relevant information for dose reconstructions and its length, resulting in a low participation rate. Dosimetry data are bound to get better when the prospective lens dose monitoring as foreseen by 2013 European Directives is implemented and doses are recorded.
Article
Objectives: Interventional cardiologists (ICs) are occupationally exposed to low or moderate doses of ionizing radiation from repeated exposures. It is not clear whether these occupational conditions may affect their eye lens. Therefore, the risk of radiation-induced cataract in the cohort of Polish interventional cardiologists is analyzed in this paper. Material and methods: The study group consisted of 69 interventional cardiologists and 78 control individuals occupationally unexposed to ionizing radiation. The eye lens opacities were examined using a slit camera and evaluated with Lens Opacities Grading System III. Cumulative eye lens doses were estimated retrospectively using a questionnaire including data on occupational history. Results: The average cumulative dose to the left and right eye lens of the ICs was 224 mSv and 85 mSv, respectively. Nuclear opalescence and nuclear color opacities in the most exposed left eye were found in 38% of the ICS for both types, and in 47% and 42% of the controls, respectively. Cortical opacities were found in 25% of the ICS and 29% of the controls. Posterior subcapsular opacities were rare: about 7% in the ICs group and 6% in the control group. Overall, there was some, but statistically insignificant, increase in the risk for opacity in the ICs group, relative to the control group, after adjusting for the subjects' age, gender, smoking status and medical exposure (adjusted OR = 1.47, 95% CI: 0.62-3.59 for the pooled "any-eye any-type" opacity). There was also no evidence for an increased opacity risk with an increase in the dose. Conclusions: The study found no statistically significant evidence against the hypothesis that the risk of cataract in the group of the ICs occupationally exposed to low doses of ionizing radiation is the same as in the control group. Nevertheless, the adverse effect of ionizing radiation still cannot be excluded due to a relatively small study sample size.
Article
Cataracts are the leading cause of blindness and visual disability worldwide. Of the known contributing factors to this condition, ionising radiation is considered the primary concern in a radiological context given the particular radiosensitivity of the lens of the eye. In light of the substantially increased application of computed tomography in brain imaging, an investigation of the relevent literature is warranted to assess thresholds, lens radiation doses and dose reduction techniques in respect to the cataractogenic risk of such examinations. The value and very existence of a lens dose threshold is debatable given different considerations of radiation dose, latency, opacity classifications and historical sample populations, though ICRP guidelines suggest a threshold of 0.5 Gy. Documented CT‐specific radiation doses to the eye following scans of the brain are highly variable between studies (2–130 mGy), primarily owing to discrepancies in scanning technique. These findings, when coupled with the relative ambiguity of known threshold values, present difficulties in assessing the overall risk of cataracts following serial CT examinations to the head. In the absence of definitive risk evaluations, a cautionary approach is advised. The implementation of gantry tilt along the supraorbital margin is recommended as standard practice on account of its highly effective radiation dose reduction outcomes. Organ‐based tube modulation and reductions in tube current may also be considered beneficial. Bismuth eye shielding is only advised where gantry tilting is unachievable, and in such cases, ensure careful adherence to appropriate shield placement and infection control measures.
Article
The 11 March 2011 Fukushima nuclear accident in Japan resulted in widespread radioactive contamination within the 20 km evacuation zone. Japanese field mice (Apodemus speciosus) living within the contaminated region received radiation doses from external environmental contamination as well as internally deposited radionuclides. Cataract formation in the lens of eyes of these mice is a possible deterministic effect of ionizing radiation; however, determination of actual doses is difficult. Since no dose conversion factors currently exist for the lens of the eyes of Japanese field mice, lens dose conversion factors were created using a Monte Carlo N-Particle simulation and compared to the International Commission on Radiological Protection Publication 108 reference rat whole-body dose conversion factors. Monte Carlo N-Particle simulations included doses to the lens of the eyes from external sources (received while both above and below ground), as well as doses from internal contamination. Although the Publication 108 reference rat is almost twice the average mass of the Japanese field mouse, all dose conversion factor calculations using Monte Carlo N-Particle methods were within approximately 37% of the Publication 108 values for the reference rat.
Article
Purpose: The International Commission on Radiological Protection (ICRP) recently recommended reducing the occupational equivalent dose limit for the lens of the eye. Based primarily on a review of epidemiological data, the absorbed dose threshold is now considered to be 0.5 Gy independent of dose-rate and severity of opacifiction, reduced from the previous threshold of 2 Gy. However, direct mechanistic evidence to support an understanding of the underlying molecular mechanisms of damage is still lacking. To this end, we explored the effects of a broad dose-range of ionizing radiation exposure on gene expression changes in a human lens epithelial (HLE) cell-line in order to better understand the shape of the dose-response relationship and identify transcriptional thresholds of effects. Methods: HLE cells were exposed to doses of 0, 0.01, 0.05, 0.25, 0.5, 2, and 5 Gy of X-ray radiation at two dose rates (1.62 cGy/min and 38.2 cGy/min). Cell culture lysates were collected 20 h post-exposure and analysed using whole-genome RNA-sequencing. Pathways and dose-thresholds of biological effects were identified using benchmark dose (BMD) modeling. Results: Transcriptional responses were minimal at doses less than 2 Gy. At higher doses there were a significant number of differentially expressed genes (DEGs) (p ≤ 0.05, fold change ≥ |1.5|) at both dose rates, with 1308 DEGs for the low dose rate (LDR) and 840 DEGs for the high dose rate (HDR) exposure. Dose-response modeling showed that a number of genes exhibited non-linear bi-phasic responses, which was verified by digital droplet PCR. BMD analysis showed the majority of the pathways responded at BMD median values in the dose range of 1.5-2.5 Gy, with the lowest BMD median value being 0.6 Gy for the HDR exposure. The minimum pathway BMD median value for LDR exposure, however, was 2.5 Gy. Although the LDR and HDR exposures shared pathways involved in extracellular matrix reorganization and collagen production with BMD median value of 2.9 Gy, HDR exposures were more effective in activating pathways associated with DNA damage response, apoptosis, and cell cycling relative to LDR exposure. Conclusion: Overall, the results suggest that radiation induces complex non-linear transcriptional dose-response relationships that are dose-rate dependent. Pathways shared between the two dose rates may be important contributors to radiation-induced cataractogenesis. BMD analysis suggests that the majority of pathways are activated above 0.6 Gy, which supports current ICRP identified dose thresholds for deterministic effects to the lens of the eye of 0.5 Gy.