Engaging citizens living in vulnerable circumstances in research: a narrative review using a systematic search.

Although public engagement in research is increasingly popular, the involvement of citizens living in vulnerable circumstances is rarely realized. This narrative review aims to describe and critically analyse concerns and corresponding strategies, tools, and methods that could support the inclusion of these citizens in health research. The 40 studies that are included were thematically analysed using the socioecological model. Concerns originate most often on the intrapersonal level of the socioecological model, but concerns were also identified at institutional, community, and policy levels. It is thought-provoking that there is a lack of attention for the research and policy structure in which engagement practices are designed, implemented and evaluated. More research is needed to explore how these cultures could be changed in a way that promotes rather than restrains the engagement of citizens living in vulnerable circumstances in research and policymaking.

Unfortunately, citizens living in vulnerable circumstances are seldom engaged in research or policymaking. Think of, citizens living in poverty, those with an ethnic minority background or citizens with mental health issues are often excluded. Their involvement is, however, crucial to prevent growing (health) inequalities. To support the engagement of people living in vulnerable circumstances we conducted a literature review. We looked for strategies, tools, and methods that could support the inclusion of these citizens in research or policymaking. In total, 40 studies were identified and analysed. The main finding is that strategies tools, and methods are always context depended. Researchers should always ask: What works for whom in which context? We, therefore, stress the importance of close collaboration with experienced owners and community based organisations from the start. Also, more attention should be paid to how engagement practices are designed, implemented and evaluated. Think of, strict deadlines which limit the time to build trust. Or low budgets that limit the options to create the right preconditions, think of recruitment and data collection in multiple languages. To make sure that not only the 'usual suspects' but also citizens living in vulnerable circumstance will be engaged attention is needed from advocacy groups, research funders and researchers. All these actors need to reflect more often on the question what they can do to change the current research and policymaking culture in such a way that it will support the engagement of citizens living in vulnerable circumstances.

Research and innovation as a catalyst for food system transformation.

BACKGROUND: Food systems are associated with severe and persistent problems worldwide. Governance approaches aiming to foster sustainable transformation of food systems face several challenges due to the complex nature of food systems. SCOPE AND APPROACH: In this commentary we argue that addressing these governance challenges requires the development and adoption of novel research and innovation (R&I) approaches that will provide evidence to inform food system transformation and will serve as catalysts for change. We first elaborate on the complexity of food systems (transformation) and stress the need to move beyond traditional linear R&I approaches to be able to respond to persistent problems that affect food systems. Though integrated transdisciplinary approaches are promising, current R&I systems do not sufficiently support such endeavors. As such, we argue, we need strategies that trigger a double transformation - of food systems and of their R&I systems. KEY FINDINGS AND CONCLUSIONS: Seizing the opportunities to transform R&I systems has implications for how research is done - pointing to the need for competence development among researchers, policy makers and society in general - and requires specific governance interventions that stimulate a systemic approach. Such interventions should foster transdisciplinary and transformative research agendas that stimulate portfolios of projects that will reinforce one another, and stimulate innovative experiments to shape conditions for systemic change. In short, a thorough rethinking of the role of R&I as well as how it is funded is a crucial step towards the development of the integrative policies that are necessary to engender systemic change - in the food system and beyond.

Empowering Patients and Health Professionals to Address Sexual Health in the Context of Anorectal Malformations and Hirschsprung's Disease.

The aim of this study is to develop a tool that is aligned with patients' and health professionals' needs to address sexual health in the context of anorectal malformations and Hirschsprung's disease. A multiphased participatory action-research was conducted. First, an inventory of needs was made through interviews (11 patients, 11 professionals), three online focus groups (4 patients, 20 professionals), and a questionnaire (38 patients). Subsequently, four cocreation sessions with in total four patients and nine professionals were organized to translate the needs into a tool (in the form of a website). The websites' functionality was assessed via a questionnaire (n = 34). The website, directed to patients, their parents, and professionals, stimulates awareness, fills knowledge gaps, and shows possibilities for support. The website is expected to change restrictive attitudes toward sexual health and improve the legitimization of the topic needed for the allocation of resources and sexologists' involvement in current care pathways.

Motivation of university and non-university stakeholders to change medical education in Vietnam.

BACKGROUND: Both university and non-university stakeholders should be involved in the process of curriculum development in medical schools, because all are concerned with the competencies of the graduates. That may be difficult unless appropriate strategies are used to motivate each stakeholder. From 1999 to 2006, eight medical schools in Vietnam worked together to change the curriculum and teaching for general medical students to make it more community oriented. This paper describes the factors that motivated the different stakeholders to participate in curriculum change and teaching in Vietnamese medical schools and the activities to address those factors and have sustainable contributions from all relevant stakeholders. METHODS: Case study analysis of contributions to the change process, using reports, interviews, focus group discussions and surveys and based on Herzberg's Motivation Theory to analyze involvement of different stakeholders. RESULTS: Different stakeholders were motivated by selected activities, such as providing opportunities for non-university stakeholders to share their opinions, organizing interactions among university stakeholders, stimulating both bottom-up and top-down inputs, focusing on learning from each other, and emphasizing self-motivation factors. CONCLUSION: The Herzberg Motivation theory helped to identify suitable approaches to ensure that teaching topics, materials and assessment methods more closely reflected the health care needs of the community. Other medical schools undertaking a reform process may learn from this experience.

The Farmer Life School: experience from an innovative approach to HIV education among farmers in South Africa.

The Farmer Life School (FLS) is an innovative approach to integrating HIV education into life skills and technical training for farmers. This study aims to gain insight into the strengths and weaknesses of this relatively new approach, through the implementation of an adapted version in South Africa. The results are presented of a pilot with three groups of community gardeners, predominantly women, attending weekly sessions. Impact was assessed in terms of three key elements: participation, learning, and empowerment. Data were collected through extensive session reports, follow-up interviews, and reflection exercises with facilitators and participating groups and individuals. The results suggest that a group-based discovery learning approach such as the FLS has great potential to improve food security and wellbeing, while allowing participants to explore issues around HIV/AIDS. However, the analysis also shows that HIV/AIDS-related illness and death, and the factors that drive the epidemic and its impact, undermine farmers' ability to participate, the safety and trust required for learning, and the empowerment process. Participatory approaches such as the FLS require a thorough understanding of and adaptation to the context.

Understanding Diversity in Impact and Responses among HIV/AIDS-Affected Households: the Case of Msinga; South Africa

To gain a more comprehensive understanding of the impact of HIV and AIDS on rural households in Msinga; South Africa; the sustainable livelihoods framework was adapted. An ethnographic perspective was employed to examine: 1) the impact of HIV/AIDS-related illnesses on people's mind and spirit (the internal environment); and 2) the influence of institutional structures and processes (the external environment); in order to better understand 3) the actions taken by individuals and households in response to HIV and AIDS. Members of three support groups at a local drop-in centre were consulted about the impact of HIV and AIDS on their lives through focus groups; a questionnaire and in-depth interviews. The study shows that the psychosocial impact and associated coping strategies; as well as prevailing gender-based power relations and exclusion from social- exchange networks - which are not (readily) available factors in the sustainable livelihoods framework - affect people's lives in different ways and depend on the specific situation of the individual or household concerned. The study confirms the need to restore a household's resource base and to address psychosocial issues. However; the variation in impact to different households requires a diversified and holistic programme of development interventions

The Farmer Life School: experience from an innovative approach to HIV education among farmers in South Africa

The Farmer Life School (FLS) is an innovative approach to integrating HIV education into life skills and technical training for farmers. This study aims to gain insight into the strengths and weaknesses of this relatively new approach; through the implementation of an adapted version in South Africa. The results are presented of a pilot with three groups of community gardeners; predominantly women; attending weekly sessions. Impact was assessed in terms of three key elements: participation; learning; and empowerment. Data were collected through extensive session reports; follow-up interviews; and reflection exercises with facilitators and participating groups and individuals. The results suggest that a group-based discovery learning approach such as the FLS has great potential to improve food security and wellbeing; while allowing participants to explore issues around HIV/AIDS. However; the analysis also shows that HIV/AIDS-related illness and death; and the factors that drive the epidemic and its impact; undermine farmers' ability to participate; the safety and trust required for learning; and the empowerment process. Participatory approaches such as the FLS require a thoroughunderstanding of and adaptation to the context

Dose inhomogeneities for photons and neutrons near interfaces.

Perturbations of charged particle equilibrium (CPE) at interfaces of materials of different atomic composition can lead to considerable differences in the energy deposition by photons and neutrons. Specific examples of these interface perturbations are encountered during irradiation of body cavities and soft tissue adjacent to bone or metallic implants and irradiation of cells in monolayer on the bottom of culture dishes. Another example is the build-up of CPE at air-tissue interfaces, referred to in radiotherapy as the skin sparing effect. For photon irradiation excess production of secondary electrons in high-Z materials, such as glass, bone or gold, will induce appreciably higher doses and decreased cell survival compared to the equilibrium situation. The energy dissipation of fast neutrons in biological materials occurs through recoil protons, heavy recoil nuclei and products of nuclear reactions. Owing to the large contribution from recoil protons to the neutron kerma, the hydrogen content of the biological material mainly determines the energy deposition. For neutron irradiation of cells in monolayer, CPE can be established or deliberately avoided by mounting tissue-equivalent plastic or carbon discs in front of the cells, respectively. This approach makes it possible to distinguish the biological effects of the low- and high-LET radiation components.

Patient and staff dose during CT guided biopsy, drainage and coagulation.

Patient and staff dose during CT guided coagulation of osteoid osteoma, tissue biopsy and abscess drainage were evaluated retrospectively on a conventional CT scanner and prospectively on a scanner equipped with fluoroscopic CT. The computed tomography dose index (CTDI) and the individual dose equivalent, i.e. the penetrating dose for workers at a depth of 10 mm tissue, were measured. Evaluation of CTDI enabled effective dose and maximum skin entrance doses for the patient to be determined. Doses were assessed for 96 CT guided interventions, including 16 drainages with average effective doses of 13.5 mSv and 9.3 mSv for the conventional CT scanner and the scanner with spiral CT fluoroscopy, respectively, 49 biopsies (effective doses of 8 mSv and 6.1 mSv, respectively), and 31 coagulations of osteoid osteoma (effective doses of 2.1 mSv and 0.8 mSv, respectively). Effective doses to patients were in the same range as those observed for regular diagnostic CT examinations. Entrance skin doses were well below the 2 Gy threshold for deterministic skin effects on the CT scanner equipped with fluoroscopic function (0.03-0.33 Gy), whilst skin doses on the conventional scanner were considerably higher (0.09-1.61 Gy). This is mainly owing to the fact that on the conventional scanner mAs was rarely reduced for scans evaluating needle position whereas low mAs per rotation was selected on the scanner with the fluoroscopy option. The maximum dose to a worker measured outside the lead apron was 28 microSv for one single procedure. The mean dose per procedure was below 10 microSv for radiologists and below 1 microSv for radiographers. Correcting for attenuation of the lead apron, the doses to workers are very low.

Protocol for X-ray dosimetry in radiobiology.

PURPOSE: To harmonize X-ray dosimetry in radiobiology to allow a direct comparison of radiobiological studies performed at institutes cooperating within the framework of the European Late Effects Project Group (EULEP). MATERIALS AND METHODS: The 1985 EULEP protocol for X-ray dosimetry and exposure arrangements employed for studies of late somatic effects in mammals required serious revision, e.g. due to the replacement of calibration of dosemeters in terms of exposure by calibration in terms of air kerma free-in-air. An action group established by EULEP and the European Radiation Dosimetry Group (EURADOS) updated the 1985 protocol. RESULTS: The new EULEP-EURADOS protocol for X-ray dosimetry in radiobiology including the code of practice for irradiation of small animals and related dosimetry. The present protocol includes the changes in calibration procedures and dosimetric concepts for irradiation with medium energy X-rays since 1985. Accuracy and precision are replaced by the concept of combined (standard) uncertainty. The revised supplements provide more detailed background information. New appendices contain definitions of general terms used for measurements and mathematical expressions of the relative variances. CONCLUSION: Adherence to the present protocol will result in improved dosimetry and facilitates the comparison of results of radiobiological experiments obtained at different institutes.

Apoptosis is present in the primate macula at all ages.

BACKGROUND: It has become increasingly clear that apoptosis is a main event in photoreceptor cell death in a variety of retinal degenerations. We investigated the role of apoptosis in the physiologically aging primate macula. METHODS: Twenty maculae of rhesus monkeys, aged 6-34 years, were investigated. Apoptosis was determined in formalin-fixed, paraffin-embedded eyes using the TUNEL (TdT-mediated dUTP-biotin nick end labeling) method and quantitatively analyzed. Morphology of TUNEL-positive cells was studied by confocal laser microscopy and transmission electron microscopy. The thickness of the outer nuclear layer (ONL) was determined by image analysis. Furthermore, expression of apoptosis-regulating proteins Bcl-x, Fas and Fas Ligand was studied by immunohistochemistry. RESULTS: TUNEL-positive nuclei showed apoptotic features on confocal laser microscopy. They were scattered and sparsely found in the macula, most frequently in the ONL. The thickness of the ONL decreased with increasing age. Apoptosis was found equally distributed at all ages, although in the two oldest maculae up to 13 times more apoptosis was found. Expression of Bcl-x, Fas and Fas Ligand was equal at all ages. CONCLUSION: Our findings indicate that apoptosis in the primate macula occurs at all ages at similar rates, possibly increasing in the oldest age group, and may account for the decreasing thickness of the primate macula with age.

Long-term effects of total-body irradiation on the kidney of Rhesus monkeys.

PURPOSE: To investigate the long-term effects of total-body irradiation (TBI) on kidneys in non-human primates. METHODS AND MATERIALS: The kidneys of Rhesus monkeys were histologically examined at 6-8 years after TBI with low single doses of 4.5-8.5Gy or two fractions of 5.4Gy. The kidneys of age-matched non-irradiated monkeys served as controls. Irradiation was performed on adult monkeys aged about 3 years; 6-8 years later animals were sacrificed and the kidneys removed and processed for histology. A semi-quantitative scoring system was used to evaluate overall histological damage. Glomerular changes were also morphometrically analysed according to previously published criteria. In selected dose groups (pro)thrombotic and inflammatory changes were investigated by immunostaining cryosections with antibodies against von Willebrand factor (vWF), leukocytes and macrophages. RESULTS: Histological changes were generally mild and only seen in kidneys irradiated with doses higher than 7 Gy. Glomerular changes were characterized by increased mesangial matrix and capillary dilatation. Tubulo-interstitial changes included hypercellularity, fibrosis and mild tubular atrophy. The mean glomerular area expressing vWF protein in the irradiated kidneys was not different from that in the age-matched controls. Numbers of infiltrating leukocytes were not significantly different between irradiated kidneys and controls. However, slightly increased numbers of macrophages were present in the renal cortex after irradiation. CONCLUSIONS: Renal damage after TBI of Rhesus monkeys with single doses of 4.5-8.5 Gy or two fractions of 5.4 Gy was mild, even after follow-up times of 6-8 years.

The effects of fractionated gamma irradiation on induction of mammary carcinoma in normal and estrogen-treated rats.

The effects of dose fractionation on induction of mammary carcinoma were studied in normal and estrogen-treated female rats of the inbred WAG/Rij strain. Groups of 40 animals received total-body doses of 1 or 2 Gy of (137)Cs gamma radiation, administered in fractions of 2.5, 10 or 40 mGy with intervals of 12 h, or in fractions of 10 mGy with intervals of 2, 5 or 24 h. The irradiations were started at the age of 8 weeks. Estrogen treatment was accomplished by implantation of a pellet containing estrogen at the age of 6 weeks. All mammary tumors were resected and classified histologically as carcinoma or fibroadenoma. The age-specific incidence of mammary carcinoma was compared with that in control groups of unirradiated normal or estrogen-treated rats and was expressed as excess normalized risk, using lifetime statistical analysis with both parametric and nonparametric methods. The data were also compared to the results of single-dose experiments reported in previous papers. Fractionated irradiation increased the risk of mammary cancer in both normal and estrogen-treated rats compared to the corresponding unirradiated control group. The excess normalized risk per unit of total dose was approximately equal with or without estrogen treatment. Without estrogen treatment, the effects of the single-dose and fractionated irradiations were approximately equal. In estrogen-treated animals, however, single-dose irradiation was up to 15 times more carcinogenic than the fractionated exposures. This fractionation effect appeared to vanish for total doses below approximately 0.3 Gy. With estrogen treatment, the excess normalized risk was significantly higher for dose fractions of 40 mGy than for fractions of 10 mGy. The risk was also markedly higher for fractionation intervals of 2 or 5 h than for intervals of 12 or 24 h. The results of these experiments show that the effects of dose fractionation on the induction of mammary carcinoma may depend on hormonal status, the total dose delivered, the dose per fraction, and the fractionation interval.

The carcinogenic risk of high dose total body irradiation in non-human primates.

PURPOSE: High dose total body irradiation (TBI) in combination with chemotherapy, followed by rescue with bone marrow transplantation (BMT), is increasingly used for the treatment of haematological malignancies. With the increasing success of this treatment and its current introduction for treating refractory autoimmune diseases the risk of radiation carcinogenesis is of growing concern. Studies on tumour induction in non-human primates are of relevance in this context since the response of this species to radiation does not differ much from that in man. MATERIALS AND METHODS: Since the early sixties, studies have been performed on acute effects in Rhesus monkeys and the protective action of bone marrow transplantation after irradiation with X-rays (average total body dose 6.8 Gy) and fission neutrons (average dose 3.4 Gy). Of those monkeys, which were irradiated and reconstituted with autologous bone marrow, 20 animals in the X-irradiated group and nine animals in the neutron group survived more than 3 years. A group of 21 non-irradiated Rhesus monkeys of a comparable age distribution served as controls. All animals were regularly screened for the occurrence of neoplasms. Complete necropsies were performed after natural death or euthanasia. RESULTS: At post-irradiation intervals of 4-21 years an appreciable number of tumours was observed. In the neutron irradiated group eight out of nine animals died with one or more malignant tumours. In the X-irradiated group this fraction was 10 out of 20. The tumours in the control group, in seven out of the 21 animals, appeared at much older age compared with those in the irradiated cohorts. The histogenesis of the tumours was diverse with a preponderance of renal carcinoma, sarcomas among which osteosarcomas, and malignant glomus tumours in the irradiated groups. CONCLUSIONS: When corrected for competing risks, the carcinogenic risk of TBI in the Rhesus monkeys is similar to that derived from the studies of the Japanese atomic bomb survivors. The increase of the risk by a factor of 8, observed in the monkeys, indicates that patients are likely to develop malignancies more frequently and much earlier in life after TBI than non-exposed individuals. This finding underlines the necessity of regular screening of long-term surviving patients subjected to TBI and BMT.

Aspects of fetal thyroid dose following iodine-131 administration during early stages of pregnancy in patients suffering from benign thyroid disorders.

Detrimental effects on the thyroid of the developing fetus as a result of iodine-131 treatment for thyrotoxicosis of the mother in the first trimester of pregnancy are discussed. Dose estimations under typical clinical circumstances yield a fetal thyroid dose of 100- 450 Sv. This dose may increase considerably if the blood concentration of (131)I in the mother remains high. Under such circumstances there may be fetal thyroid dysfunction, which can lead to severe abnormalities.

Effects of total-body irradiation on growth, thyroid and pituitary gland in rhesus monkeys.

PURPOSE: To investigate the effect of total-body irradiation (TBI) on growth, thyroid and pituitary gland in primates. METHODS AND MATERIALS: Thirty-seven rhesus monkeys (mean age 3.1+/-0.6 years) received either a low-dose (4-6 Gy) TBI (n = 26) or high-dose (7-12 Gy) TBI (n = 11) and were sacrificed together with 8 age-matched controls after a post-irradiation interval of 5.9+/-1.5 years. Anthropometric data were collected: thyroid and pituitary glands were examined; serum levels of thyroid stimulating hormone (TSH), free thyroxin (FT4), insulin-like growth factor-I (IGF-I) and its binding protein-3 (IGFBP-3) were measured. RESULTS: Decrease in final height due to irradiation could not be demonstrated. There was a dose-dependent decrease in body weight, ponderal index, skinfold thickness and thyroid weight. The latter was not accompanied by elevation of TSH or decrease in FT4. Structural changes in the thyroid gland were found in 50% of the irradiated animals. Levels of IGF-I and IGFBP-3 did not differ between the dose groups, but the high-dose group had a lower IGF-1/IGFBP-3 ratio. CONCLUSION: Total body irradiation had a negative effect on body fat. There was no evidence of (compensated) hypothyroidism, but dose-dependent decrease in thyroid weight and changes in follicular structure suggest some effect of TBI on the thyroid gland. The decreased IGF-I/IGFBP-3 ratio in the high-dose group can indicate that the somatotrophic axis was mildly affected by TBI. These results show that TBI can have an effect on the physical build and thyroid gland of primates even in the absence of cytostatic agents or immunosuppressive drugs.

Colour at edges and colour spreading in McCollough effects.

Broerse and O'Shea [(1995) Vision Research, 35, 207-226] proposed that the subjective colours in McCollough effects (MEs) consist of two components: edge colours appearing along the edges of contours, and spread colours radiating from edge colours into adjacent uncontoured regions of test patterns. This proposal was examined in five experiments. First, we demonstrated that fine coloured lines located immediately adjacent to the edges of otherwise achromatic square-wave gratings (i.e. colour-fringed gratings) are sufficient to induce MEs comparable in strength to MEs induced with desaturated versions of traditional uniformly-coloured gratings (Experiments 1 & 2). We then quantified edge and spread colours while varying light/dark duty cycles (white-bar width) in gratings with colour-fringed edges (Experiment 3), uniformly-coloured gratings (Experiment 4), and in achromatic gratings tinged with ME colours after adaptation to colour-fringed gratings (Experiment 5). Whereas the perceived magnitude of edge colours remained constant in all cases, spread colours remained constant only for uniformly-coloured gratings. For both MEs and gratings with colour-fringed edges, spread colours decreased as a function of increasing duty cycle, confirming that conventional MEs may be simulated by gratings with colour-fringed edges. We propose that edge colours arise as a consequence of neural operations correcting for the eye's chromatic aberration, while spread colours reveal a neural filling-in process operating to achieve colour constancy. In seeking to implement these suggestions, we present a putative framework based on the receptive-field properties of single cells described in contemporary neurophysiological investigations of colour.

Long-term effects of X-irradiation on gastrointestinal function and regulatory peptides in monkeys.

PURPOSE: To investigate the long-term effects of X-irradiation on different aspects of gastrointestinal function in the non-human primate (Macaca mulatta). MATERIALS AND METHODS: Animals were exposed to X-radiation (5 or 6 Gy) or not (sham) and gastrointestinal function was investigated 4-6 years after exposure. Basal and agonist-stimulated short circuit current (Isc) responses were measured in isolated jejunum. Intestinal tissue was taken for histological analysis as well as for determination of mucosal marker enzyme activities and gastrointestinal regulatory peptide levels. Vasoactive intestinal peptide receptor characteristics were determined as well as VIP-stimulated Isc responses. GI peptides were also measured in plasma. RESULTS: Few differences were seen in basal electrical parameters or tissue morphology but there was a tendency for reduced basolateral membrane enzyme activity. VIP-stimulated Isc responses were reduced in irradiated animals as were VIP-stimulated adenylate cyclase responses. Plasma and tissue (ileal and colonic muscle layers) gastrin releasing peptide levels were increased in irradiated animals. In contrast circulating gastrin levels were lower. CONCLUSIONS: Late effects of total-body irradiation on GI function in monkeys showed altered circulating and tissue levels of some GI peptides. In addition the biological effects of vasoactive intestinal peptide were modified.

Somatic effects in nuclear medicine and radiology.

Probable risks for the occurrence of somatic effects due to diagnostic radiology and nuclear medicine are summarised. The biological background of radiation carcinogenesis and epidemiological results are discussed. At the Leiden University Medical Centre the average effective dose per examination due to diagnostic radiology and nuclear medicine amount to 0.95 and 4.4 mSv, respectively. These values correspond well with the average values of 0.82 and 3.0 mSv reported for The Netherlands as a whole. Since radiological examinations are performed at a much larger frequency than nuclear medicine the relative collective dose for the first type of examinations is higher than the latter. Risk for occurency of malignancies are at least one order of magnitude lower than the hypothetical risk due to the background radiation typical of The Netherlands.

Late ophthalmological complications after total body irradiation in non-human primates.

PURPOSE: To investigate the long-term effects of total body irradiation (TBI) on the incidence and time course of ocular complications. MATERIALS AND METHODS: Rhesus monkeys treated with TBI photon doses up to 8.5 Gy and proton doses up to 7.5 Gy were studied at intervals up to 25 years post-irradiation. They were compared with control groups with a similar age distribution. Cataract formation and ocular fundus lesions were scored according to a standardized protocol. Fluorescein angiography and histopathology was performed in selected animals. RESULTS: Cataract formation occurred after a latent period of 3-5 years. Significant cataract induction was observed for photon-doses of 8 and 8.5 Gy and beyond 20 years after proton irradiation. The severity of the lesions represents significant impairment of vision and would require cataract surgery if similar results occurred in human bone marrow transplant patients. Fluorescein angiography demonstrated a normal pattern of retinal vessels in 13 out of 14 animals (93%) from the irradiated group and in eight out of nine animals (89%) from the control group. No additional lesions apart from age-related degenerative changes could be demonstrated. Histological evaluation revealed no radiation-associated vasculopathy. CONCLUSIONS: Radiation alone for doses up to 8.5 Gy of photons does not carry a potential risk for fundus pathology, whereas clinically important cataract induction should be anticipated within 5 years after photon doses of 8.0 and 8.5 Gy and proton doses in excess of 2.5 Gy.