The progress described in this report was presented as a poster at the annual meeting of the Association for Research and Vision in Ophthalmology, on May 3, 2006. The following paragraph contains the abstract of this poster.
POSTER ABSTRACT**:
** PLEASE SEE “RESULTS SECTION” FOR UPDATED FINDINGS WHICH IN SOME CASES DIFFER SIGNIFICANTLY FROM THOSE CITED IN ABSTRACT
Purpose: NASCA is a 5-yr study of the risk factors associated with cataract incidence and progression in US astronauts, military pilots, and ground-based controls (GBC). Risk factors studied include: space radiation exposure, nutrition, UV exposure, and age.
Methods: Areal extent of cortical (C), and posterior subcapsular (P) opacity and density of nuclear (N) opacity were assessed in Nidek EAS 1000 digital lens images. Nuclear color was graded with LOCS III. We used the Harvard Food Frequency Questionnaire (HFFQ). Lens-specific radiation exposures from space, medical sources, aviation training, and isotopes were incorporated. Statistical analyses used space radiation dose-response modeling of baseline prevalence of C, P, and N adjusted for age, nutrition, and solar exposure. Several dose-response models were considered, choosing the most parsimonious ones that described the data. We modeled distribution of log C area opaque as a skew-normal distribution, discrete levels of the area of P opacification with an ordered logit-regression and N density at three loci with beta distributions. In each case we determined the statistical significance of age, space radiation exposure, and 105 nutritional variables on the distribution of each type of opacity.
Results: Complete data from 199 astronauts, 90 pilots, and 95 GBC were available after 1 yr. In our preliminary results baseline prevalences of C, N, and P among astronauts and pilots were significantly lower than in GBCs. For astronauts only, age, radiation and sun exposures were statistically significantly associated with worsening, and a- and ß-carotene with amelioration, of C. For N age was the main explanatory variable for all loci. For astronauts only, space radiation had no effect on pixel density of the central N clear zone or the posterior embryonal nucleus, but it did have a small statistically significant effect (worsening) on the pixel density of the N anterior embryonal nucleus. Lutein had a strong protective effect at each of the three N loci. a- and ß-carotene produced similar results. Age was the only variable statistically significantly associated with extent of P.
Conclusions: Age was significantly associated with severity in C, P, and N. For astronauts only, space radiation and UV exposures were significantly associated with worsening C and with opacification of the anterior embryonal nucleus. a- and ß-carotene and lutein had small beneficial effects on C and N opacification, respectively.
Commercial Relationships: All authors: None.
Support: NASA NAG9-01491.
** PLEASE SEE “RESULTS SECTION” FOR UPDATED FINDINGS WHICH IN SOME CASES DIFFER SIGNIFICANTLY FROM THOSE CITED IN ABSTRACT
NARRATIVE PROGRESS REPORT
PROJECT OBJECTIVES:
1. To determine if exposure to space radiation produces more cortical, posterior subcapsular (PSC), or nuclear opacity in astronauts vs. comparison groups after adjustment for age, solar radiation exposure, and possible nutritional effects. 2. To identify nutritional groups that appear likely to be associated with increased or decreased cortical, PSC, or nuclear opacity.
RECRUITMENT STATISTICS AS OF MARCH 23, 2006:
As of March 23, 3006 we have recruited 222 astronauts (188 male/34 female), 94 military pilots (88 male/6 female), and 99 ground-based controls (79 male/20 female).
METHODS:
We gathered demographic data (age, gender, other) with standardized questionnaires. Ocular data were obtained for all subjects (astronauts and controls) from NASA’s standardized, comprehensive, annual, ocular examination that included best-corrected LogMAR Visual Acuity, and contrast sensitivity function. To estimate space radiation doses to the lens we used space dosimetry, and we made a best estimate of the mission and astronaut-specific lens doses, or lens dose equivalents including the individual contributions from trapped radiation and galactic cosmic rays (GCR). We estimated solar UV exposures from validated demographic data and personal histories. We estimated the color of the lens nucleus with the Lens Opacities Classification System (LOCS III) measure of nuclear color. We gathered nutritional data with the validated Harvard Food Frequency Questionnaire (HFFQ).
We used digital images of the lens obtained with a specialized camera (Nidek EAS 1000 Lens imaging system) to assess the type and severity of lens opacification.
STATISTICAL ANALYSIS:
Our basic statistical objectives were to test if exposure to space radiation produces higher cortical, PSC, or nuclear opacification in astronauts vs. comparison groups after adjustment for age, solar radiation exposure, and possible nutritional effects, and to identify nutritional groups that appear likely to be associated with increased or decreased cortical, PSC or nuclear opacity. In this first year of the study, only one observation per subject was available, so no opacity growth models were considered here. Our dependent variables were maximum image area opaque (OD, OS) one observation per subject for the first year, and our independent (explanatory) variables were: subject group, age, annual solar UV exposure, space radiation exposure, and weekly intake of 105 nutrients. Because the distributions of many of the variables were skewed, we used Skew-normal regression modeling.
1. Analysis of PSC data:
The Maximum PSC opacity (OD, OS) measures were grouped into 5 binned ranges. We used ordered logistic regression model to test for effects of explanatory variables on probability of maximum PSC opacity falling into each of the above bins.
2. Analysis of nuclear cataract data:
We used the log of the maximum pixel density (OD, OS) for three locations (nuclear central clear zone, anterior embryonal and posterior embryonal nuclei) and Beta regression to test for effects of explanatory variables on the mean and variance of the distribution of pixel density at each location.
RESULTS:
Cortical opacity tends to increase with age, and with intake of Omega-3-fatty acids. Cortical opacity tends to be lowered by greater intake of A-vitamins and pro-vitamins. There is increased variation in cortical opacities for older subjects and in those exposed to space radiation. There does not appear to be much evidence supporting more variation in cortical opacities for persons with higher sun exposure. There is considerable skewness in the distribution of log cortical opacities.
Posterior Subcapsular (PSC) Opacity: The only explanatory variable that was significantly associated with PSC opacity was age
Nuclear Cataracts: Increased age was shown to be an overwhelming contributor to density of nuclear cataract at all three measurement loci. No other explanatory variable was found to be significantly associated with pixel density.
CONCLUSIONS:
Cortical Cataracts:
1. Age is the most important predictor of cortical opacification. Populations of older people have a higher mean cortical opacity (P<0.001) and a larger spread of opacities (P = 0.012) than do populations of younger people.
2. Astronauts who have not yet flown and non-astronaut pilots appear to have less mean opacity than the ground-based comparison group (P = 0.10) and more clearly have a tighter distribution of cortical opacities (P = 0.017),
3. The population of astronauts who have been exposed to space radiation (i.e. have flown at least one mission) has a significantly increased variation in opacity relative to the other astronauts and pilots (P = 0.007)
4. Astronauts who have flown do not have a discernable difference in mean opacity from those who have not flown. Within the group of astronauts who have flown, there is no relationship between the total amount of space radiation received and the mean or variance of cortical opacity.
5. Solar radiation exposure had no discernable effect on either the mean or variance of cortical opacity.
6. Nutritional Findings: Larger intake of omega fatty acids appears associated with increased cortical opacity (P = 0.012*). Larger intake of A-vitamins and pro-vitamins appears associated with decreased cortical opacity (P = 0.004*)
PSC and Nuclear Cataracts:
1. Increasing age was significantly associated with increasing opacity. No other significant explanatory variables were found. 2. Although no factors other than age appeared to effect PSC and nuclear cataracts across subjects in this cross-sectional study, there may well be effects of radiation (space and/or solar) on the growth rates of these types of cataracts. This question will be addressed when the longitudinal analysis phase begins after the second year of the study.
MANUSCRIPTS IN PREPARATION:
1. We are preparing a manuscript describing the NASCA methodology and recruitment results after the first year. The paper will also have baseline descriptive data on all of the experimental variables assessed in this project. We expect to complete this manuscript and submit it to Archives of Ophthalmology before July, 2006. 2. We are also preparing a second manuscript describing the results of a cross-sectional analysis of the cataractogenic risks of space radiation for astronauts, pilots, and ground-based controls. We will also present the effect of nutritional variables, age, gender, and annual solar UV exposure on these risks. The results of this analysis are described in the annual report (see earlier sections). We also expect to complete this manuscript and submit it to Archives of Ophthalmology before July, 2006.
3. We are analyzing the relationship between the number of loci in the phenotype of posterior subcapsular cataracts and the dose of space radiation. There are significant findings in this analysis, but we have not yet decided if they will be included in Manuscript 2 (above) or in a separate paper. We will make this decision in the next few weeks.
4. As we move into the longitudinal phase of the NASCA project we expect to be able to assess the relationship between dose of space radiation and measures of cataract incidence (new cases of lens opacification) and progression (of existing opacities) and the effects of age, gender, nutrition, and annual solar UV exposure on these progression rates. The manuscripts for these analyses will probably be cataract-specific (separate papers for cortical, nuclear, and posterior subcapsular cataract).
Respectfully submitted,
Leo T. Chylack, Jr., M.D. Principal Investigator of NASCA Project
|