This article was downloaded by: [North Carolina State University] On: 16 March 2015, At: 05:51 Publisher: Routledge Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Archives of Environmental Health: An International Journal Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/vzeh20
Visual Dysfunction among Former Microelectronics Assembly Workers a
b
c
Donna Mergler Ph.D. , Guy Huel D.Sc. , Rosemarie Bowler Ph.D., M.P.H. , d
Frenette Benoit M. Sc. & James Cone M.D., M. P. H.
e
a
Centre pour l'étude des interactions biologiques entre la santé et l'environnement(CINBIOSE) Université du Québec à Montréal b
French National Institute for Health and Medical Research Unité de recherches épidémiologiques c
Occupational Medicine Clinic San Francisco General Hospital , University of California , San Francisco, California, USA d
Cinbiose , Canada
e
Occupational Medicine Clinic San Francisco General Hospital , San Francisco, USA Published online: 03 Aug 2010.
To cite this article: Donna Mergler Ph.D. , Guy Huel D.Sc. , Rosemarie Bowler Ph.D., M.P.H. , Frenette Benoit M. Sc. & James Cone M.D., M. P. H. (1991) Visual Dysfunction among Former Microelectronics Assembly Workers, Archives of Environmental Health: An International Journal, 46:6, 326-334, DOI: 10.1080/00039896.1991.9934398 To link to this article: http://dx.doi.org/10.1080/00039896.1991.9934398
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Visual Dysfunction among Former
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MicroeI ectronics Assem bly Workers DONNA MERGLER, Ph.D. Centre pour I'&ude des interactions biologiques entre la sant6 et I'environnement (CINBIOSE) Universite du Quebec 51 Montr6al GUY HUEL, D.Q. CINBIOSE and French National Institute for Health and Medical Research Unit6 de recherches Cpidhiologiques ROSEMARIE BOWLER, Ph.D., M.P.H. Occupational Medicine Clinic San Francisco General Hospital University of California San Francisco BENOIT FRENETTE, M.Q. CINBIOSE JAMES CONE, M.D., M.P.H. Occupational Medicine Clinic San Francisco General Hospital ABSTRACT. Although known neurotoxins with potential ophthalmotoxic properties are commonly used in microelectronicsassembly, there has been no systematic study of visual disturbances among past or present workers in this industry. The objective of the present study was to compare visual functions, using a matched-pair design, between former workers from a microelectronics plant and a local reference population. From an initial population of 180 former workers and 157 potential referents, 54 pairs were matched for age (f 3 y), education (f 2 y), sex, ethnic origin, and number of children. Near and far visual acuity, chromatic discrimination, and near contrast sensitivity were assessed monocularly. Paired comparisons (Signed-rank Wilcoxon test) revealed that the former microelectronics workers had significantly lower contrast sensitivity, particularly in the intermediate frequencies, independently of near visual acuity loss. There were no differences for far visual acuity in both eyes. Even though near visual acuity and color vision were compromised among the former workers, the differences were only significant for one eye, as was the prevalence of acquired dyschromatopsia (chi-square for matched pairs, p < .001). These findings suggest a pattern of contrast sensitivity deficits consistent with impairment to foveal and/or neuro-optic pathways among these former microelectronics workers. Exposure to ophthalmotoxic chemicals is proposed as the most probable risk factor.
IN MICROELECTRONICS ASSEMBLY, large quantities of organic solvents are employed in many work processes.'" Some of these substances, e.g., trichloroethylene, xylene, toluene, and methylene chloride, are 326
known neurotoxins that have potential ophthalmic toxicity. In 1955, Grandjean" reported visual disturbances among workers who were exposed to trichloroethylene, which was used as a degreaser in a mechanical Archives of EnvironmentalHealth
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engineering plant. Chronic exposure to trichloroethylene has since been reported to produce (a) double vision, (b) changes in color perception, (c) optic nerve damage, and (d) blindness.','' Xylene, toluene, and methylene chloride have been associated with visual disturbances and, in cases of severe exposures, optic neuropathy or visual h a l l ~ c i n a t i o n s . ~More~'~~'~ over, there is increasing evidence of solvent-related acquired dyschromat~psia.'~-~~ The type and severity of color vision loss appear to reflect the extent of damage to the neuro-optic pathway^.'^ The visual system is particularly vulnerable to toxic substances. Vision disorders and visual sense organ pathology constitute one of the criteria for fixing permissible exposure levels for 33 chemical substances in the United state^.^ Although testing of visual functions is noninvasive and can readily be performed under standard conditions in large-scale screening, few epidemiological studies have focused on visual impairment. Altered integrity of neuro-optic pathways is not necessarily reflected by diminished visual acuity; loss of color vision and contrast sensitivity are early clinical indicators of retinal and/or optic neuropathy, even when visual acuity remains Symptoms of visual disorder were among the reported complaints of microelectronics workers, as noted by health hazard evaluations performed by the United States National Institute for Occupational Health and S a f e t ~ , ~ However, ~-~' there has been no study of visual dysfunction in this industry. The present study was undertaken, as part of an overall assessment of neurophysiological and neuropsychological functions, to assess far and near visual acuity, chromatic discrimination, and contrast sensitivity among a group of former microelectronics workers.
Methods Population. The study population consisted of a selfselected group of workers (n = 180) with suspected work-related illness. They had formerly been employed at the same microelectronics assembly plant in Albuquerque, New Mexico, and more than 100 had received compensation for work-related illnesses. Prior to employment, all workers had been screened with the Titmus Vision TestTMfor near and far visual acuity, color discrimination, and stereo depth. This apparatus is used to assess visual ability required for detailed assembly work. Medical records indicate that all of the workers who were hired had adequate vision on all of the parameters measured. Study design. A matched-pair study design was used to determine the possible relationship between visual functions and work in this industry. The pool of referents was made up of 157 persons who were identified by the former workers and who were contacted by the investigators. Informed consent was obtained, and all participation was voluntary. Workers and referents were paired for variables expected to influence visual functions, such as age, and for a series of variables that reflected socioeconomic and expected NovembedDecember 1991 [Vol. 46 (No. 6 ) ]
health status, e.g., educational level, sex, ethnicity, and size of family. The matching process, illustrated in Figure 1, was similar to that of a previous study dedicated to reproductive outcomes in this population.M A self-administered questionnaire was used to obtain information on sociodemographic data (age, sex, years of education, ethnicity, number of children), previous and current work history, medical history, current use and type of medication, hobbies that entailed neurotoxic exposure, and drinking and smoking habits. From the initial group of former workers and referents, 43 former workers and 49 referents were excluded because of other neurotoxin exposure, diabetes, cataracts, reported current use of certain medication (anxiolytics, antidepressants, hypnotics, anticonvulsants, belladonna, I-dopa, reserpines, alpha-methyl dopa, antihistamines, oral steroids, and beta-blockers), andlor missing demographic information. From the remaining group of 137 former workers and 108 referents, matched pairs were established based on the following: age ( * 3 y), education ( * 2 y), sex, ethnic origin (Hispanic, "anglo," other), and number of children (0-3; 4 or more were considered "4"). This process netted 67 matched pairs, from which 13 pairs were excluded because data were missing for visual functions. Therefore, analysis was conducted on 54 pairs, for whom the sociodemographic characteristics are listed in Table 1. Comparisons indicated that good homogeneity existed for all of the control factors (i.e., age, education level, sex, ethnic origin, and number of children). Although the prevalence of "current" smokers was somewhat higher among the referents, the difference was not significant. Nonetheless, the possible contribution of this factor, as well as alcohol consumption, were analyzed. Exposure. Former workers who were retained through the matching process had been employed for an average of 6.1 3.7 y (range, 1-15 y). The plant, which opened in 1971, contained a complete electronics manufacturing operation that produced switching and transmission equipment for telecommunications. The process began with raw materials and progressed through various stages; components such as crystal fi Iters, inductors, transformers, t hick-fiIm microwave circuits, and single- and double-sided printed circuit boards were manufactured. Most of the departments (i.e., hybrids assembly, ceramics, plastics, components assembly, chip capacitors integrated circuits, thin film, semiconductor components, progressive assembly line, and others) were housed in an open area, which contained one general ventilation system. The printed circuit lab, where metal plating and acid etching were done, and the crystal filters and chip capacitor departments were located in closed rooms that contained separate ventilation systems. A list of the 372 commercial products used during the period of employment and the major chemical ingredients contained in each were obtained from the employer. These chemicals included chlorofluorocarbons (e.g., trichlorotrifluoroethane, dichlorodifluorometh-
*
327
Former microclenronics
Potential referents [ram the region
workcn (n
”‘
- 180)
(n
~
History of neurotoxin
~ v m n ysc t of mcdimion that
Cumnt yse ofmedication that curld a f k t pcrrormancc?
cxposurc?
Diabetes. calaracts?
Diabetes. cawace.?
Missing dcmapphics?
Missing demographics?
~
~
$
~
d l r to match
-
Excluded (n
70)
yes
Excluded
(n = 49)
unable to match
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157)
Ncuraodn c x p u r r Mher than in this plant? could affm prfomwct?
I
-
Edumicm (* 2y)
I
SCX
Ethnic origin Number of children
a
1‘
\ Excluded (11-411
67 matched p a i s
Missing dam on visual hunctions?
Excluded (n = 13 p i n )
54 matched pairs
Fig. 1. Illustration of the matching process.
ane), chlorinated hydrocarbons (e.g., trichloroethylene, methylene chloride, and 1-1-1-trichloroethane, 1-1-2 trichloroethane) glycol ethers, isopropanol, acetone, toluene, xylene, and ethyl alcohol. These solvents were used in the majority of the work processes for cleaning, degreasing, modification of epoxies and resins, as fluxing agents for soldering, rinsing in etching and plating, as thinners, and for diluting (diluents). Transformers and other electronics components were often dipped with bare hands into open degreasing containers. Most workers were involved in several aspects of the operation, and job rotation was determined by both roduction needs and the workers’ residual capabilities.R According to FOX,^' this work was associated with daily symptoms of intoxication, including headache, lightheadness, confusion, fatigue, and irritant dermatitis of the hands. Distribution of the 54 workers within various departments and the major chemicals used in each department are shown in Table 2. The workers in this study had worked in an average of 2.5 departments (range, 1-7). Workers were counted for each of the departments in which they had spent time (Table 2). Measurement of visual functions. All visual functions were examined monocularly, under standardized conditions, while the participants wore current prescription glasses or contact lenses. Test administration was standardized, and testers had no knowledge of the exposure status of the person being tested. Each visual function was tested throughout the study by the same tester. 328
Far visual acuity, tested with a Snellen chart placed 6 m from the subject, and near visual acuity, measured with a National Optical Visual Chart placed 0.40 m in front of the subject, were assessed under constant ambient lighting conditions. Color vision was determined with the Lanthony D-15 desaturated panel (Luneau Ophtalmique), a color arrangement test. This test was conducted in a darkened room, and standard illumination was provided by a “daylight” 1 150-lux fluorescent lamp positioned 30 cm above the caps. Near contrast sensitivity was evaluated with the Vistech grating charts (VCTS 60001, which were placed 0.40 m in front of the subject. Contrast sensitivity threshold was ascertained over 3 successive trials for 5 grating frequencies: 1.2, 3, 6, 12, and 18 cycles/degree. Analysis of vision. Subjects were identified only by numbers distributed randomly; therefore, all scoring was carried out without knowledge of group status. The distance (meters) required for normal visual resolution of 1 min of arc was recorded for far and near visual acuity. Color vision loss was classified into types of acquired dys~hromatopia,~’ and a color confusion index33 was calculated. Simple cap inversions were considered “normal.” Cap displacement of 2 places or more on the hue circle were considered as errors and classified as acquired dyschromatopsia. If errors resulted in hue circle patterns parallel to the deutadprotan (red/green) or tritanltetartan (blue/yellow) axes, dyschromatopsia was classified as Type I and Type Ill, respectively, whereas errors resulting in hue circle lines parallel to both these axes were classified as Type II. No specific axis designated patterns where the hue circle lines were not parallel to any axis. Statistical analysis. The score differences were not distributed normally for most of the visual functions. Thus, nonparametric pair comparisons, using the Signedrank Wilcoxon test, were Qualitative analysis of dyschromatopsia was achieved by comparing (chi-square test for matched pairs [ M ~ N e m a r ]the )~~ frequency of discordant pairs among former microelectronics workers and non-microelectronics workers. Potential confounding by alcohol consumption and smoking was analyzed with multiple regression analysis; for each score, the residual (difference between observed and expected) was added to the mean visual score. Similar analyses were used to correct for near visual acuity to account for possible loss resulting from an under-corrected lens prescription. Possible relationships between departmental exposures and visual deficits were explored. Stepwise regression analysis was performed, with paired differences for visual function as the dependent variable, and time spent in each of the 10 departments as the independent variable. Departments were added, 1-by-1, to the model, and the F statistic for inclusion had to be significant at the 30% level; after a department was added, the method looked at all the departments already included in the model and deleted any department that did not produce an F statistic that was significant at the 5% level. In these analyses, mean values were calculated for right and left eyes. Archives of Environmental Health
I
Table 1.-Distribution
of Age, Sex, Education Levd, Ethnicity, and Smoking and Drinking Habits
Characteristic
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I
Former microelectronics workers
Referents
54 43.2 f 9.6 11.7 1.2 96.3
54 43.3 f 10.6 11.7 1.3 96.3
Number Age Years of education Sex (% women)
*
Ethnic origin (number) Hispanic ”Anglo” Other Number of children None One Two Three Four or more Smoking status (% current smokers) Alcohol consumption (glwk)
Standard deviation of mean differences
Signed rank testp value
0.11 -0.02
2.5 1.2
0.902 0.878
-2.7
37.8
0.728
*
38 14 2
38 14 2
5 6 15 14 14 16.7
5 6 15 14 14 29.6;
12.2
Mean of differences
* 28.9
9.55
* 22.4
*Chi square: 2.55 (nonsignificant).
Table Z.-Portrait
of Main Solvent Exposure by Department
Printing and soldering, (hybrid assemby) (n 18) Chip composition operation, chip assembly (n 5) Soldering and circuitboard 23) cleaning (n Printing and thin-film operations (n 9) Crystal filters (n 10)
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Results Statistics for matched-pair design use the difference between the exposed person (i.e., former microelectronics worker) and his or her referent as the variable that is analyzed. If the two groups perform similarly, the results should be distributed equally around zero; negative differences indicate poorer results among the former microelectronics workers, compared with their matched referents. The mean and standard deviations of the differences between pairs, and the percentile distribution of these differences, are presented in Table 3. In this table are provided the absolute differences in measurements; therefore, for far visual acuity, the 25th percentile (Ql) score indicates that for 25% of the former microelectronics workers, the distance required for normal visual resolution of 1 min of arc at 6 m was 1.7 m less than that of their matched referents, whereas the 75th percentile score (43) indicates that for 25% of the former microelectronics workers, the distance required for normal visual resolution of 1 min of arc at 6 m was 1.4 m more than that of their matched referents. There was no difference in far visual acuity between the two groups (Signed-rank, nonsignificant). Even though near visual acuity and color confusion index were skewed towards poorer scores for the former microelectronics workers, the significance level was just reached for the right eye and left eye, respectively. Near contrast sensitivity was significantly different for all frequencies. Indeed, at most frequencies, 75% of the microelectronics workers manifested poorer contrast sensitivity, compared with their matched referents. When smoking status and alcohol consumption were taken into account, the results were unaltered. A graphic presentation of the reduced mean of differences (mean difference divided by standard deviation) is shown in Figure 2. The most striking differences occurred for contrast sensitivity, particularly above 3 cycles/degree (Fig. 2). Among the 54 former microelectronics workers, included through the pairing process, 24 had received compensation for work-related illness; no differences were observed for the visual scores between those who had and those who had not received compensation (Mann-Whitney, p > .05). Because contrast sensitivity loss, particularly in the higher frequencies, may arise from poorly corrected near visual acuity, scores were reanalyzed with a correction for near visual acuity. Paired differences remained significant for all spatial frequencies, with the exception of 18 cyclesldegree. The distribution of pairs with normal vision and dyschromatopsia (including dyschromatosia with no particular axis, Type II and Type I l l dyschromatopsia) is shown in Table 4. There was concordance for the right eye in 31 pairs; of these, 7 had normal color vision, whereas 24 manifested acquired dyschromatopsia. Eighteen of 23 former microelectronics workers presented profiles of dyschromatopsia, whereas no color vision loss was evident in their paired referents. The situation was inverted in the remaining 5 workers. This difference in discordant pairs was significant for the 330
right eyes, but the difference was not significant for the left eyes. Analysis was likewise conducted for which persons with dyschromatopsia with no particular axis and persons with normal vision were grouped; acquired dyschromatopsia included only those with Type I l l or Type I I color vision loss. There was no difference in the outcome: the number of discordant pairs for right eyes remained highly significant, and differences for left eyes were nonsignificant. Results of the stepwise regression analyses revealed that for contrast sensitivity paired differences at 1.5 cpd and 12 cpd, time spent in the printing and soldering department (hybrid assembly) remained significant (p < .05) at the end of the procedure. There was no change in significance level after near and far visual acuity were taken into account. Contrast sensitivity scores of all subjects who had spent time in the printing and soldering department (35 persons from the total 137 former microelectronics workers, following exclusion) were used to confirm this finding. Significant relationships (p < .05) were observed between contrast sensitivity scores and time spent in this department, at all spatial frequencies, with the exception of 18 cpd; multiple regression analyses were used to account for age and near visual acuity. In order to determine whether this department was solely responsible for the observed matched pair differences, paired analyses were recomputed, and the 18 pairs that included persons who had worked in this department were excluded. N o major change was noted. Discussion Good vision is an obvious requirement for the visually demanding task of assembling tiny microelectronic components. Indeed, all of these workers had undergone extensive visual examinations prior to employment, and medical reports indicated good vision. However, at the time of this study, the former workers from this microelectronics plant had overall poorer visual functions, and most significantly, poorer contrast sensitivity than did a matched local reference population who had never worked in this plant. The pattern of contrast sensitivity loss, which best discriminated between the former electronics workers and referents, was particularly interesting because workerlreferent differences were most marked in the intermediate spatial frequencies. Loss of visual acuity, caused by optical phenomenon, are generally associated with changes in high spatial frequencies of the contrast sensitivity pattern 35,36; loss in intermediate and/or low spatial frequencies samples neural rather than optical effi~iency.~’.~~ Recent recognition of this differential pattern of impairment has lead to widespread clinical use of czntrast sensitivity for detecting retinopathies and optic n e u r ~ p a t h i e s . ~In ’ ~the * ~ absence ~~ of loss of visual acuity, 39,45 diminished contrast sensitivity has been observed in patients with diabetic optic neuropathy or Parkinson‘s disease. A “notch” in intermediate spatial frequencies is one of the characteristic patterns of spatial frequency loss associated with multiple sclerosis (pre- and cortical patch of d e m y e l i n a t i ~ n ) . ~A’ , ~ Archives of Environmental Health
Table 3.-Means of Differences and Percentiles of Differences for 54 Matched Pairs of Former Microelectronics Workem and Non-microelectronicsWorkers
-
SD
P10
Q1
Median
Q3
P90
Signed rank
6.2 8.2
- 6.5
-1.80
- 8.0
-1.7 - 3.0
0 0
1.4 1.3
5.3 5.3
ns. n.s.
- 0.09
0.40
-0.80 - 0.63
-0.25 -0.38
0 0
0.13 0.12
0.38 0.50
ns.
- 0.62 - 0.67
-0.39 -0.29
-0.12
0.10 0.23
0.34
*
0.46
ns.
X
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Far visual acuity Right eye (m) Left eye (m)
- 0.83
Near visual acuity Right eye (m) Left eye (m) Color confusion index Right eye (m) Left eye (rn) Contast sensitivity 1.2 cycleddegree: right eye left eye 3.0 cycleddegree: right eye left eye 6.0 cycleddegree: right eye left eye 12.0 cycleddegree: right eye left eye 18.0 cycleddegree: right eye left eye
-
-
- 0.09
0.40
-0.11 - 0.05
0.42
0.48
- 4.65
12.3 11.4 26.9 26.7 43.1 40.8 37.4 41.3 13.3 16.8
-4.50 -13.6 - 13.2 - 17.1 - 17.0 - 14.8 -18.1 -6.74 - 5.05
- 18 - 18 - 57
-13 - 12 - 25 - 25 - 53 - 42 - 34 - 45 - 16 - 18
- 57 - 65 - 56 -68 -68 - 28 - 23
- 0.08 0 0
-18 -18 - 19 - 24 - 18 - 23 -8 -8
Notes: Negative values indicate less desirable results for microelectronics workers. PI0 10th percentile; Q1 1st quattile, Q3 3rd quartile; P90 90th percentile. ns. *p 4 .05. tp 4 .01. *p < .m1.
-
more general spatial frequency loss, observed among patients with compressive lesions of the anterior visual pathways, seems to reflect a more diffuse disturbance of the optic nerve.42 In the present study, spatial frequency loss occurred over all frequency bands, but was greatest between 3 and 12 cycleddegree, which suggested that impairment was of neural origin. This is further supported by the fact that the pattern remained unchanged when statistical correction was made for near visual acuity. Differences in far visual acuity were not significant for the group of former microelectronics workers and their paired referents, whereas results of near visual acuity and acquired color vision loss were contradictory. Although the differences for the latter parameters were skewed towards poorer performances on the part of the former microelectronics workers, they only reached significance level for one eye, and, surprisingly, these were alternate eyes. These differences in laterality for near visual acuity may simply reflect that the results were just above and below the .05 significance level, whereas the differences in color vision possibly reflet a more complex phenomenon. In this region (a high desert plateau), other factors, such as intense light or high levels of ultraviolet radiation may contribute to dyschromatopsia. The prevalence of acquired color vision loss was very high for both the reference population and the microelectronics workers. Color vision loss, retinal damage, and corneal lenticular changes in response to high ultraviolet stimuli and intense light4’fm have been reported in animal and experimental studies. Novembedkember 1991 [Vol. 46 (No. 6)]
-
-
0 0 0 0 0 0 13
0 0
4
13 0 22 25 42 37 32 43 12 18
*
*
* t
* 8
t t t
**
not significant (p > .05).
The results of this study strongly suggest that factods) associated with the microelectronics assembly process or the environment may affect contrast sensitivity. Two major possibilities should be considered. (1) Impairment resulted from visual demands associated with ergonomic constraints of the type of work performed, and (2) toxic exposure had affected neuro-optic pathways. Although close precision work has been associated with loss of far visual acuity, cause and effect have not been well demon~trated.~’,~~ Axial elongation, extraocular muscle tension, increased intraocular pressure, and increased lens power are all interrelated mechanisms that could alter visual acuity in long-term close ~ o r k . ~ ’ *Prolonged ~ near work can also stress accommodation such that patients with low accommodative amplitude or flexibility will complain of asthenopia or blurred vision.56 In the present study, the absence of workerheferent differences for far visual acuity indicates that observed visual impairment did not result from prolonged close work. There are, however, many arguments that can be proffered to support the hypothesis that the type of visual impairment observed in the present study could result from exposure to chemicals with potential ophthalmotoxic properties. Although few industrial hygiene measurements were made in this plant, reports of acute health effects suggest that the levels were fairly high.3’ Moreover, visual disturbances have been associated with many of the soIvents7~’*used by these former microelectronics workers. Furthermore, many solvents were used, and in most departments multiple ex331
Right e y e
Left eye
near visual a c u i t y
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sensitivity (cycleddegree)
n.s.
K
0
n.1.
K
3.0 6.0
12.0 18.0
1-
0
-3
-2
__I__ -
K
I
.
,
-1
.
'
.
'
++
0.0
.
1
0
Reduced mean of differences
--
0
P10
Q1
rned
*
x
43
P90
Fig. 2. Percentile distribution of reduced mean of differences (mean score divided by standard deviation) for all of the measured visual functions. Negative values indicate poorer performance. Signed rank Wilcoxon text values are indicated: n.s. = p > .05; *p < .05; **p < .01; ***p < ,001.
posures were frequent. Although little is known about the possible synergistic effects of exposure to such a large number of organic solvents, a "cocktail" effect i s possible. Despite obvious limits, e.g., worker rotation from one job to another, work processes changing over time, and manipulation of multiple chemicals, an attempt was made to relate time spent in each department and visual outcomes. One department emerged from these analyses: printing and soldering of hybrid assembly. Among the factors that possibly distinguish this department from others i s the proximity of a heated vapor degreaser that consisted of three 1.2-m x 1.2-m containers filled with organic solvent mixtures. Industrial hygiene reports for this department indicate high levels of 1-1-1 trichloroethane and fluorochlorohydrocarbon mixtures; however, no information was provided on a combined index of exposure to these organic solvents and the others used in the work process. Reports of severe acute intoxication when individuals worked around the heated vapor degreaser3' suggest that organic solvent levels were very high. The observed relationship between contrast sensitivity loss in low and intermediate frequencies, and time spent in hybrid assembly, may reflect a particularly ophthalmotoxic solvent mixture or excessive exposure. This study was performed on a self-selected group of former workers from a particular plant and who had 332
suspected work-related illness. A matched design was used to ascertain whether work in this plant was associated with visual deficits among this particular population. There i s widespread agreement among researchers in quantitative epidemiological methods that a matched-pair design provides an appropriate means of minimizing bias." In this type of analysis, pairing is carried out from two initial pools. The groups that result from the matching process are not random, but paired on a series of potentially confounding variables. Analysis is carried out, not on the differences in means, but on the means of the intrapair differences. Possible bias may have arisen from the choice of the initial referent population, which was not random, but instead consisted of persons identified by the former workers. The former workers may have chosen persons who were particularly healthy. Information about their medical and work history does not support this assumption. Moreover, their visual functions were in a normal range, and as expected, varied with age. Finally, contrary to the former microelectronics workers, no information was available on their visual functions at the time when their "pair" began working. This would tend to bias towards initial and subsequent better performance by the former microelectronics workers. The findings of this study, which demonstrate lowered visual contrast sensitivity among this group of former microelectronics assembly workers, and which are conArchives of Environmental Health
Table 4.-Matched-Pain Analysis of Acquired Dyschromatopsia for Former Microelectronics Workers and Non-microelectronicsWorkers Normal color vision
I
Acquired dyschromatopsia
Non-microelectronicsworkers
L? aJ
*$
Right eyes’ Normal color vision Acquired dyschromatopsia
7 18
5 24
Left eyest Normal color vision Acquired dyxhromatopsia
6 14
7 27
.G E .U m
$5
Eti
82 Lal
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*Chi-square for matched pairs limits: 1.27-1 1.5). tChi-square for matched pairs fidence limits: 0.8-5.0).
-
7.34; p
- 2.33;
sistent with neural rather than ocular changes, cannot be generalized to other populations. Clearly, there is a need for more studies on the visual condition of past and current workers in the microelectronics and allied industries, where the work is visually demanding, and large amounts of different organic solvents are manipulated. Industrial hygiene measures should be taken, and methods should be developed to evaluate multiple chemical exposures and their effects. Conclusions This study, conducted among former microelectronics workers, revealed poorer visual functions, compared with a matched reference group from the same region. The most marked differences were observed for near contrast sensitivity, which suggested foveal vision andlor cortical impairment. These workers performed visually demanding work and had been in contact with a large number of organic solvents, including known neurotoxins, e.g., trichloroethylene, trichloroethane, toluene, and xylene, as well as chlorofluorocarbons. The findings of this study provide evidence of contrast loss among this particular group of former microelectronics assembly workers, consistent with impairment to foveal andlor neuro-optic pathways. Multiple organic solvent exposure is proposed as the most probable risk factor; however, more studies of active and past workers in the microelectronics and allied industries are required to further elucidate this relationship.
********** Funding for this project was obtained from the General Medical Fund of the University of California, San Francisco, and from the Quebec Institute for Research in Occupational Health and Safety. We express our appreciation to the participants in this study and a very supportive community of friends, relatives, and professionals who assisted in carrying out this project. We would also like to thank Ms. S. Legault-Belanger, I. Fortier, and Mr. L. Dallaire, who provided invaluable assistance in the conceptualization, testing, and analysis. Thanks is also offered to Ms. D. Allen, Mr. S. Racine, and Mr. L. Dallaire for their tireless efforts in data entry and proofing. Mrs. J. Guerriero, Ms. D. Alexander, and Dr. S. Fox are thanked for coordinating this project in the field. We also sincerely thank G. Berube, S.
NovembedDecember 1991[Vol. &(No. 6)]
< .001. Odds ratio
- 3.6 [95% - 2.0 (95%
not significant. Odds ratio
confidence con-
Legault-B6langer, and C. Brabant for reviewing this manuscript and for their helpful suggestions. Submitted for publication February 1, 1990; revised; accepted for publication April 17, 1991. Requests for reprints should be sent to: Donna Mergler, Ph.D., CINBIOSE, Department des sciences biologiques, Universite du Quebec A Montreal, CP 8888, succ”A”, Montreal, Quebec, Canada H3C 3P8.
********** References
1 . Cone JE. Health hazards of solvents: state of the art reviews. Occup Med 1986; 1:69-87. 2. Ladou J. Potential occupational hazards in the microelectronics industry. Scand J Work Environ Health 1983; 9:43-48. 3. Ladou J. Health issues in the microelectronics industry: state of the art reviews. Occup Med 1986; 1:1-11. 4. National Institute of Occupational Safety and Health. Hazard evaluation and technical assistance report. Dublin, CA: Western Electric Co., 1973; report no. 72-74-51. 5. Pasquini D, Laird L. Hazards assessment of the electronic component manufacturing industry. NIOSH contract no. 210-80-0058;
1982. 6. Wade R, Williams M. Semiconductor industry study. Task force on the electronics industry. California Department of Industrial Relations, DLSH; 1981. 7. Anger K. Neurobehavioral testing on chemicals: impact on recommended standards. Neurobehav Toxicol Teratol 1984; 6:
147-53. 8. Grant WM. Toxicology of the eye. Springfield, IL: Charles C Thomas, 1986. 9. ODonaghue JL, Ed. Neurotoxicity of industrial and commercial chemicals. Vol I. Baton Rouge, FL: CRC Press, Inc.; 1985. 10. Grandjean E, Munchinger R, Turrian V, Haas PS, Knoepfel HK, Rosenmund H. Investigations into the effects of exposure to trichloroethylene in mechanical engineering. Br J Ind Med 1955;
12:131-42. 1 1 . Department of Labor. Occupational exposure to trichloroethylene. Fed Reg 1975; 40:49032. 12. Channer KS, Stanley S. Persistent visual hallucinations secondary to chronic solvent encephalopathy. J Neurol Neurosurg Psychiat 1983; 46~83-86. 13. Ehyai A, Freeman FR. Progressive optic neuropathy and sensorineural hearing loss due to chronic glue sniffing. J Neurol Neurosurg Psychiat 1983; 46:349-51. 14. Wyse DG. Deliberate inhalation of volatile hydrocarbons: a review. Can Med Assoc J 1973; 108:71-74. 15. Alieva ZA. Reduced acuity of color perception resulting from exposure to styrene and tetrachloroethylene vapours. Gig Trud Prof Zabol 1985; 2:ll-13.
333
Downloaded by [North Carolina State University] at 05:51 16 March 2015
16. Legault-Belanger S, Bachand M, Bedard S, Brabant C, de Grosbois S , Mergler D. Perte de discrimination chromatique chez des travailleurs sournis a une exposition complexe et variable aux solvants organiques. Arch Ma1 Prof 1988; 49475-82. 17. Mergler D, Belanger S, de Grosbois S, Vachon N. Chroma1 focus of acquired chromatic discrimination loss and solvent exposure among printshop workers. Toxicol 1988; 49341-48. 18. Mergler D, Blain L, Lagace JP. Solvent related color vision loss: an indicator of neural damage? Int Arch Occup Environ Health 1987; 59:313-21. 19. Raitta C, Seppalainen AM, Huuskonen MS. n-Hexane maculopathy in industrial workers. Alb v Craef Arch Klin Exp Ophthalmol 1978; 2 0 9 9 - 1 10. 20. Raitta C, Teir E, Jolonen E, Helpio E, Malmstrom S. Impaired color vision discrimination among viscose rayon workers exposed to carbon bisulfide. I &cup med 1981; 23:189-92. 21. Arden GB. Testing contrast sensitivity in clinical practice. Clin Vis Sci 1988; 2:213-34. 22. Bodis-Wollner I. Methodological aspects of contrast sensitivity measurements in the diagnosis of optic neuropathy and maculopathy. Doc Ophthal Proc Ser 1983; 35:225-37. 23. Harmor MF. Contrast sensitivity and retinal disease. Ann Ophthalmol 1981; 13:1069-71. 24. Hyvarinen L, Laurinen P, Rovamo J. Contrast sensitivity function in evaluation of visual impairment due to macular degeneration and optic nerve lesions. Acta Ophthalmol 1983; 61:161-70. 25. Hart WM. Acquired dyschromatopsias. SUN Ophthalmol 1987; 32: 10-3 1. 26. Francois J, Verriest G. La detection a I'aide des tests de Farnsworth des dyschromatopsies acquises dans les degenerescences tapeteretineienne. Ann Ocul (Paris) 1956; 113:381-98. 27. National Institute of Occupational Safety and Health. Hazard evaluation and technical assistance report. Broomfield, CO: FMC Corporation, 1977; Report no. 76-101-376. 28. National Institute of Occupational Safety and Health. Health evaluation and technical assistance report. Kittaning, P A Essex International, 1977; Report no. 77-3-420. 29. National Institute of Occupational Safety and Health. Hazard evaluation and technical assistance report. Grove City, OH: Robertshaw Controls Co., 1977; Report no. TA 76-102. 30. Hue1 G, Mergler D, Bowler R. Evidence of adverse reproductive outcomes among women microelectronics workers. Br J Ind Med 1990; 47:400-04. 31. Fox S. Toxic chemicals and stress: anatomy of an out-of-court settlement for women workers at GTE Lenkurt Electronics Plant. Ph.D. Thesis, University of New Mexico, Albuquerque; 1988. 32. Verriest C. Further studies on acquired deficiency of color discrimination. J Opt Soc Am 1963; 53:185-95. 33. Bowman KJ. A method for quantitative scoring of the FarnsworthMunsell Panel D-15. Ada Ophthalmol 1982; 60907-12. 34. Lehman DL, D'Abrere HJM.In Lehmann EL, Ed. Nonparametrics: statistical methods based on ranks. New York: McCraw-Hill International; and San Francisco, CA: Holden-Day, Inc.; 1975. 35. Owsley C, Sekular R, Siemens D. Contrast sensitivity through adulthood. Vision Res 1983; 23:689-99.
334
36. Campbell FW, Green DG. Optical and retinal factors affecting visual resolution. J Physiol 1965; 181:576-93. 37. Creeves AL, Cole BL, Jacobs RJ. Assessment of contrast sensitivity of patients with macular disease using reduced contrast near visual acuity charts. Ophthalmol Physiol Opt 1988; 8371-77. 38. Cainburg AP. A new contrast sensitivity vision test chart. Am J Optom Physiol Opt 1984; 61:403-07. 39. Regan D, Neima D. Low contrast letter charts as a test of visual function. Am Acad Ophthalmol 1983; 90:1192-1200. 40. Bodis Wollner I. Detection of visual defects using the contrast sensitivity function. Int Ophthalmol Clin 1980; 20135-53. 41. Drucker MD, Savino PI, Sergott RC, Bosley TM, Schatz Nj, Kubilis PS. Low-contrast letter charts to detect subtle neuropathies. Am J Ophthalmol 1988; 105:141-45. 42. Kuppersmith MJ, Siege1 IM, Carr RE. Subtle differences of vision with compressive lesions of the anterior visual field pathway measured by contrast sensitivity. Ophthalmology 1982; 8 7 1140-49. 43. Sokol S, Moskowitz SB. Contrast sensitivity in diabetics with and without background retinopathy. Arch Ophthalmol 1985; 103: 51-54. 44. Wolkstein M, Atkin A, Bodis-Wolner I. Contrast sensitivity in retinal disease. Ophthalmology 1980; 87:1140-49. 45. Bodis-Wollner I, Marx M, Mitra S, et at. Visual dysfunction in Parkinson's disease. Brain 1987; 1101675-98. 46. Regan D, Silver R, Murray TJ. Visual acuity and contrasts in multiple sclerosis: hidden visual loss. Brain 1977; 100:563-79. 47. Regan D, Neima D. Low-contrast letter charts in early diabetic retinopathy Ocular hypertension, glaucoma and Parkinson's disease. Br J Ophthalmol 1984; 68:885-89. 48. Regan D. Low-contrast letter charts and sinewave gratings tests in ophthalmological and neurological disorders. Clin Vision Sci 1988; 2~235-50. 49. Schmidt RE, Zuluch JA. Retinal lesions due to ultraviolet laser exposure. Invest Ophthalmol 1980; 101166-75. 50. Wright AA, Sperling HC, Mills SJ. Researches on a unilaterally blue-blinded rhesus monkey. Vision Res 1987; 27:1551-64. 51. Angle J, Wissman DA. Age, reading, and myopia. Am J Optom Physiol Opt 1978; 55:302-08. 52. Richler A, Bear JC, Refraction, nearwork and education: a population study in Newfoundland. Acta Ophthalmol 1980; 58: 468-78. 53. Young FA. The nature and control of myopia. J Am Optom Assoc 1977; 48~451-57. 54. Sat0 T. Criticism of various accommodogeneous theories on school myopia judging from explanation on emmetropization. Doc Ophthalmol Proc Ser 1981; 28:97-102. 55. Collins CC, Bach-y-Rita P, Loeb DR. lntraocular pressure variation with oculorotary muscle tension. Am J Physiol 1967; 213: 1039-43. 56. Cooper J. Accommodative dysfunction. In: Amos JF, Ed. Diagnosis and management in vision care. Butterworths 1987; 431-54. 57. Kleinbaum DC, Kupper LL, Morgenstern H. Epidemiologic research principles and quantitative methods. Toronto: Lifetime Learning Publications, 1982.
Archives of Envimnrnental Health
Archives of Environmental Health: An International Journal Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/vzeh20
Visual Dysfunction among Former Microelectronics Assembly Workers a
b
c
Donna Mergler Ph.D. , Guy Huel D.Sc. , Rosemarie Bowler Ph.D., M.P.H. , d
Frenette Benoit M. Sc. & James Cone M.D., M. P. H.
e
a
Centre pour l'étude des interactions biologiques entre la santé et l'environnement(CINBIOSE) Université du Québec à Montréal b
French National Institute for Health and Medical Research Unité de recherches épidémiologiques c
Occupational Medicine Clinic San Francisco General Hospital , University of California , San Francisco, California, USA d
Cinbiose , Canada
e
Occupational Medicine Clinic San Francisco General Hospital , San Francisco, USA Published online: 03 Aug 2010.
To cite this article: Donna Mergler Ph.D. , Guy Huel D.Sc. , Rosemarie Bowler Ph.D., M.P.H. , Frenette Benoit M. Sc. & James Cone M.D., M. P. H. (1991) Visual Dysfunction among Former Microelectronics Assembly Workers, Archives of Environmental Health: An International Journal, 46:6, 326-334, DOI: 10.1080/00039896.1991.9934398 To link to this article: http://dx.doi.org/10.1080/00039896.1991.9934398
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Visual Dysfunction among Former
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MicroeI ectronics Assem bly Workers DONNA MERGLER, Ph.D. Centre pour I'&ude des interactions biologiques entre la sant6 et I'environnement (CINBIOSE) Universite du Quebec 51 Montr6al GUY HUEL, D.Q. CINBIOSE and French National Institute for Health and Medical Research Unit6 de recherches Cpidhiologiques ROSEMARIE BOWLER, Ph.D., M.P.H. Occupational Medicine Clinic San Francisco General Hospital University of California San Francisco BENOIT FRENETTE, M.Q. CINBIOSE JAMES CONE, M.D., M.P.H. Occupational Medicine Clinic San Francisco General Hospital ABSTRACT. Although known neurotoxins with potential ophthalmotoxic properties are commonly used in microelectronicsassembly, there has been no systematic study of visual disturbances among past or present workers in this industry. The objective of the present study was to compare visual functions, using a matched-pair design, between former workers from a microelectronics plant and a local reference population. From an initial population of 180 former workers and 157 potential referents, 54 pairs were matched for age (f 3 y), education (f 2 y), sex, ethnic origin, and number of children. Near and far visual acuity, chromatic discrimination, and near contrast sensitivity were assessed monocularly. Paired comparisons (Signed-rank Wilcoxon test) revealed that the former microelectronics workers had significantly lower contrast sensitivity, particularly in the intermediate frequencies, independently of near visual acuity loss. There were no differences for far visual acuity in both eyes. Even though near visual acuity and color vision were compromised among the former workers, the differences were only significant for one eye, as was the prevalence of acquired dyschromatopsia (chi-square for matched pairs, p < .001). These findings suggest a pattern of contrast sensitivity deficits consistent with impairment to foveal and/or neuro-optic pathways among these former microelectronics workers. Exposure to ophthalmotoxic chemicals is proposed as the most probable risk factor.
IN MICROELECTRONICS ASSEMBLY, large quantities of organic solvents are employed in many work processes.'" Some of these substances, e.g., trichloroethylene, xylene, toluene, and methylene chloride, are 326
known neurotoxins that have potential ophthalmic toxicity. In 1955, Grandjean" reported visual disturbances among workers who were exposed to trichloroethylene, which was used as a degreaser in a mechanical Archives of EnvironmentalHealth
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engineering plant. Chronic exposure to trichloroethylene has since been reported to produce (a) double vision, (b) changes in color perception, (c) optic nerve damage, and (d) blindness.','' Xylene, toluene, and methylene chloride have been associated with visual disturbances and, in cases of severe exposures, optic neuropathy or visual h a l l ~ c i n a t i o n s . ~More~'~~'~ over, there is increasing evidence of solvent-related acquired dyschromat~psia.'~-~~ The type and severity of color vision loss appear to reflect the extent of damage to the neuro-optic pathway^.'^ The visual system is particularly vulnerable to toxic substances. Vision disorders and visual sense organ pathology constitute one of the criteria for fixing permissible exposure levels for 33 chemical substances in the United state^.^ Although testing of visual functions is noninvasive and can readily be performed under standard conditions in large-scale screening, few epidemiological studies have focused on visual impairment. Altered integrity of neuro-optic pathways is not necessarily reflected by diminished visual acuity; loss of color vision and contrast sensitivity are early clinical indicators of retinal and/or optic neuropathy, even when visual acuity remains Symptoms of visual disorder were among the reported complaints of microelectronics workers, as noted by health hazard evaluations performed by the United States National Institute for Occupational Health and S a f e t ~ , ~ However, ~-~' there has been no study of visual dysfunction in this industry. The present study was undertaken, as part of an overall assessment of neurophysiological and neuropsychological functions, to assess far and near visual acuity, chromatic discrimination, and contrast sensitivity among a group of former microelectronics workers.
Methods Population. The study population consisted of a selfselected group of workers (n = 180) with suspected work-related illness. They had formerly been employed at the same microelectronics assembly plant in Albuquerque, New Mexico, and more than 100 had received compensation for work-related illnesses. Prior to employment, all workers had been screened with the Titmus Vision TestTMfor near and far visual acuity, color discrimination, and stereo depth. This apparatus is used to assess visual ability required for detailed assembly work. Medical records indicate that all of the workers who were hired had adequate vision on all of the parameters measured. Study design. A matched-pair study design was used to determine the possible relationship between visual functions and work in this industry. The pool of referents was made up of 157 persons who were identified by the former workers and who were contacted by the investigators. Informed consent was obtained, and all participation was voluntary. Workers and referents were paired for variables expected to influence visual functions, such as age, and for a series of variables that reflected socioeconomic and expected NovembedDecember 1991 [Vol. 46 (No. 6 ) ]
health status, e.g., educational level, sex, ethnicity, and size of family. The matching process, illustrated in Figure 1, was similar to that of a previous study dedicated to reproductive outcomes in this population.M A self-administered questionnaire was used to obtain information on sociodemographic data (age, sex, years of education, ethnicity, number of children), previous and current work history, medical history, current use and type of medication, hobbies that entailed neurotoxic exposure, and drinking and smoking habits. From the initial group of former workers and referents, 43 former workers and 49 referents were excluded because of other neurotoxin exposure, diabetes, cataracts, reported current use of certain medication (anxiolytics, antidepressants, hypnotics, anticonvulsants, belladonna, I-dopa, reserpines, alpha-methyl dopa, antihistamines, oral steroids, and beta-blockers), andlor missing demographic information. From the remaining group of 137 former workers and 108 referents, matched pairs were established based on the following: age ( * 3 y), education ( * 2 y), sex, ethnic origin (Hispanic, "anglo," other), and number of children (0-3; 4 or more were considered "4"). This process netted 67 matched pairs, from which 13 pairs were excluded because data were missing for visual functions. Therefore, analysis was conducted on 54 pairs, for whom the sociodemographic characteristics are listed in Table 1. Comparisons indicated that good homogeneity existed for all of the control factors (i.e., age, education level, sex, ethnic origin, and number of children). Although the prevalence of "current" smokers was somewhat higher among the referents, the difference was not significant. Nonetheless, the possible contribution of this factor, as well as alcohol consumption, were analyzed. Exposure. Former workers who were retained through the matching process had been employed for an average of 6.1 3.7 y (range, 1-15 y). The plant, which opened in 1971, contained a complete electronics manufacturing operation that produced switching and transmission equipment for telecommunications. The process began with raw materials and progressed through various stages; components such as crystal fi Iters, inductors, transformers, t hick-fiIm microwave circuits, and single- and double-sided printed circuit boards were manufactured. Most of the departments (i.e., hybrids assembly, ceramics, plastics, components assembly, chip capacitors integrated circuits, thin film, semiconductor components, progressive assembly line, and others) were housed in an open area, which contained one general ventilation system. The printed circuit lab, where metal plating and acid etching were done, and the crystal filters and chip capacitor departments were located in closed rooms that contained separate ventilation systems. A list of the 372 commercial products used during the period of employment and the major chemical ingredients contained in each were obtained from the employer. These chemicals included chlorofluorocarbons (e.g., trichlorotrifluoroethane, dichlorodifluorometh-
*
327
Former microclenronics
Potential referents [ram the region
workcn (n
”‘
- 180)
(n
~
History of neurotoxin
~ v m n ysc t of mcdimion that
Cumnt yse ofmedication that curld a f k t pcrrormancc?
cxposurc?
Diabetes. calaracts?
Diabetes. cawace.?
Missing dcmapphics?
Missing demographics?
~
~
$
~
d l r to match
-
Excluded (n
70)
yes
Excluded
(n = 49)
unable to match
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157)
Ncuraodn c x p u r r Mher than in this plant? could affm prfomwct?
I
-
Edumicm (* 2y)
I
SCX
Ethnic origin Number of children
a
1‘
\ Excluded (11-411
67 matched p a i s
Missing dam on visual hunctions?
Excluded (n = 13 p i n )
54 matched pairs
Fig. 1. Illustration of the matching process.
ane), chlorinated hydrocarbons (e.g., trichloroethylene, methylene chloride, and 1-1-1-trichloroethane, 1-1-2 trichloroethane) glycol ethers, isopropanol, acetone, toluene, xylene, and ethyl alcohol. These solvents were used in the majority of the work processes for cleaning, degreasing, modification of epoxies and resins, as fluxing agents for soldering, rinsing in etching and plating, as thinners, and for diluting (diluents). Transformers and other electronics components were often dipped with bare hands into open degreasing containers. Most workers were involved in several aspects of the operation, and job rotation was determined by both roduction needs and the workers’ residual capabilities.R According to FOX,^' this work was associated with daily symptoms of intoxication, including headache, lightheadness, confusion, fatigue, and irritant dermatitis of the hands. Distribution of the 54 workers within various departments and the major chemicals used in each department are shown in Table 2. The workers in this study had worked in an average of 2.5 departments (range, 1-7). Workers were counted for each of the departments in which they had spent time (Table 2). Measurement of visual functions. All visual functions were examined monocularly, under standardized conditions, while the participants wore current prescription glasses or contact lenses. Test administration was standardized, and testers had no knowledge of the exposure status of the person being tested. Each visual function was tested throughout the study by the same tester. 328
Far visual acuity, tested with a Snellen chart placed 6 m from the subject, and near visual acuity, measured with a National Optical Visual Chart placed 0.40 m in front of the subject, were assessed under constant ambient lighting conditions. Color vision was determined with the Lanthony D-15 desaturated panel (Luneau Ophtalmique), a color arrangement test. This test was conducted in a darkened room, and standard illumination was provided by a “daylight” 1 150-lux fluorescent lamp positioned 30 cm above the caps. Near contrast sensitivity was evaluated with the Vistech grating charts (VCTS 60001, which were placed 0.40 m in front of the subject. Contrast sensitivity threshold was ascertained over 3 successive trials for 5 grating frequencies: 1.2, 3, 6, 12, and 18 cycles/degree. Analysis of vision. Subjects were identified only by numbers distributed randomly; therefore, all scoring was carried out without knowledge of group status. The distance (meters) required for normal visual resolution of 1 min of arc was recorded for far and near visual acuity. Color vision loss was classified into types of acquired dys~hromatopia,~’ and a color confusion index33 was calculated. Simple cap inversions were considered “normal.” Cap displacement of 2 places or more on the hue circle were considered as errors and classified as acquired dyschromatopsia. If errors resulted in hue circle patterns parallel to the deutadprotan (red/green) or tritanltetartan (blue/yellow) axes, dyschromatopsia was classified as Type I and Type Ill, respectively, whereas errors resulting in hue circle lines parallel to both these axes were classified as Type II. No specific axis designated patterns where the hue circle lines were not parallel to any axis. Statistical analysis. The score differences were not distributed normally for most of the visual functions. Thus, nonparametric pair comparisons, using the Signedrank Wilcoxon test, were Qualitative analysis of dyschromatopsia was achieved by comparing (chi-square test for matched pairs [ M ~ N e m a r ]the )~~ frequency of discordant pairs among former microelectronics workers and non-microelectronics workers. Potential confounding by alcohol consumption and smoking was analyzed with multiple regression analysis; for each score, the residual (difference between observed and expected) was added to the mean visual score. Similar analyses were used to correct for near visual acuity to account for possible loss resulting from an under-corrected lens prescription. Possible relationships between departmental exposures and visual deficits were explored. Stepwise regression analysis was performed, with paired differences for visual function as the dependent variable, and time spent in each of the 10 departments as the independent variable. Departments were added, 1-by-1, to the model, and the F statistic for inclusion had to be significant at the 30% level; after a department was added, the method looked at all the departments already included in the model and deleted any department that did not produce an F statistic that was significant at the 5% level. In these analyses, mean values were calculated for right and left eyes. Archives of Environmental Health
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Table 1.-Distribution
of Age, Sex, Education Levd, Ethnicity, and Smoking and Drinking Habits
Characteristic
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I
Former microelectronics workers
Referents
54 43.2 f 9.6 11.7 1.2 96.3
54 43.3 f 10.6 11.7 1.3 96.3
Number Age Years of education Sex (% women)
*
Ethnic origin (number) Hispanic ”Anglo” Other Number of children None One Two Three Four or more Smoking status (% current smokers) Alcohol consumption (glwk)
Standard deviation of mean differences
Signed rank testp value
0.11 -0.02
2.5 1.2
0.902 0.878
-2.7
37.8
0.728
*
38 14 2
38 14 2
5 6 15 14 14 16.7
5 6 15 14 14 29.6;
12.2
Mean of differences
* 28.9
9.55
* 22.4
*Chi square: 2.55 (nonsignificant).
Table Z.-Portrait
of Main Solvent Exposure by Department
Printing and soldering, (hybrid assemby) (n 18) Chip composition operation, chip assembly (n 5) Soldering and circuitboard 23) cleaning (n Printing and thin-film operations (n 9) Crystal filters (n 10)
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Results Statistics for matched-pair design use the difference between the exposed person (i.e., former microelectronics worker) and his or her referent as the variable that is analyzed. If the two groups perform similarly, the results should be distributed equally around zero; negative differences indicate poorer results among the former microelectronics workers, compared with their matched referents. The mean and standard deviations of the differences between pairs, and the percentile distribution of these differences, are presented in Table 3. In this table are provided the absolute differences in measurements; therefore, for far visual acuity, the 25th percentile (Ql) score indicates that for 25% of the former microelectronics workers, the distance required for normal visual resolution of 1 min of arc at 6 m was 1.7 m less than that of their matched referents, whereas the 75th percentile score (43) indicates that for 25% of the former microelectronics workers, the distance required for normal visual resolution of 1 min of arc at 6 m was 1.4 m more than that of their matched referents. There was no difference in far visual acuity between the two groups (Signed-rank, nonsignificant). Even though near visual acuity and color confusion index were skewed towards poorer scores for the former microelectronics workers, the significance level was just reached for the right eye and left eye, respectively. Near contrast sensitivity was significantly different for all frequencies. Indeed, at most frequencies, 75% of the microelectronics workers manifested poorer contrast sensitivity, compared with their matched referents. When smoking status and alcohol consumption were taken into account, the results were unaltered. A graphic presentation of the reduced mean of differences (mean difference divided by standard deviation) is shown in Figure 2. The most striking differences occurred for contrast sensitivity, particularly above 3 cycles/degree (Fig. 2). Among the 54 former microelectronics workers, included through the pairing process, 24 had received compensation for work-related illness; no differences were observed for the visual scores between those who had and those who had not received compensation (Mann-Whitney, p > .05). Because contrast sensitivity loss, particularly in the higher frequencies, may arise from poorly corrected near visual acuity, scores were reanalyzed with a correction for near visual acuity. Paired differences remained significant for all spatial frequencies, with the exception of 18 cyclesldegree. The distribution of pairs with normal vision and dyschromatopsia (including dyschromatosia with no particular axis, Type II and Type I l l dyschromatopsia) is shown in Table 4. There was concordance for the right eye in 31 pairs; of these, 7 had normal color vision, whereas 24 manifested acquired dyschromatopsia. Eighteen of 23 former microelectronics workers presented profiles of dyschromatopsia, whereas no color vision loss was evident in their paired referents. The situation was inverted in the remaining 5 workers. This difference in discordant pairs was significant for the 330
right eyes, but the difference was not significant for the left eyes. Analysis was likewise conducted for which persons with dyschromatopsia with no particular axis and persons with normal vision were grouped; acquired dyschromatopsia included only those with Type I l l or Type I I color vision loss. There was no difference in the outcome: the number of discordant pairs for right eyes remained highly significant, and differences for left eyes were nonsignificant. Results of the stepwise regression analyses revealed that for contrast sensitivity paired differences at 1.5 cpd and 12 cpd, time spent in the printing and soldering department (hybrid assembly) remained significant (p < .05) at the end of the procedure. There was no change in significance level after near and far visual acuity were taken into account. Contrast sensitivity scores of all subjects who had spent time in the printing and soldering department (35 persons from the total 137 former microelectronics workers, following exclusion) were used to confirm this finding. Significant relationships (p < .05) were observed between contrast sensitivity scores and time spent in this department, at all spatial frequencies, with the exception of 18 cpd; multiple regression analyses were used to account for age and near visual acuity. In order to determine whether this department was solely responsible for the observed matched pair differences, paired analyses were recomputed, and the 18 pairs that included persons who had worked in this department were excluded. N o major change was noted. Discussion Good vision is an obvious requirement for the visually demanding task of assembling tiny microelectronic components. Indeed, all of these workers had undergone extensive visual examinations prior to employment, and medical reports indicated good vision. However, at the time of this study, the former workers from this microelectronics plant had overall poorer visual functions, and most significantly, poorer contrast sensitivity than did a matched local reference population who had never worked in this plant. The pattern of contrast sensitivity loss, which best discriminated between the former electronics workers and referents, was particularly interesting because workerlreferent differences were most marked in the intermediate spatial frequencies. Loss of visual acuity, caused by optical phenomenon, are generally associated with changes in high spatial frequencies of the contrast sensitivity pattern 35,36; loss in intermediate and/or low spatial frequencies samples neural rather than optical effi~iency.~’.~~ Recent recognition of this differential pattern of impairment has lead to widespread clinical use of czntrast sensitivity for detecting retinopathies and optic n e u r ~ p a t h i e s . ~In ’ ~the * ~ absence ~~ of loss of visual acuity, 39,45 diminished contrast sensitivity has been observed in patients with diabetic optic neuropathy or Parkinson‘s disease. A “notch” in intermediate spatial frequencies is one of the characteristic patterns of spatial frequency loss associated with multiple sclerosis (pre- and cortical patch of d e m y e l i n a t i ~ n ) . ~A’ , ~ Archives of Environmental Health
Table 3.-Means of Differences and Percentiles of Differences for 54 Matched Pairs of Former Microelectronics Workem and Non-microelectronicsWorkers
-
SD
P10
Q1
Median
Q3
P90
Signed rank
6.2 8.2
- 6.5
-1.80
- 8.0
-1.7 - 3.0
0 0
1.4 1.3
5.3 5.3
ns. n.s.
- 0.09
0.40
-0.80 - 0.63
-0.25 -0.38
0 0
0.13 0.12
0.38 0.50
ns.
- 0.62 - 0.67
-0.39 -0.29
-0.12
0.10 0.23
0.34
*
0.46
ns.
X
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Far visual acuity Right eye (m) Left eye (m)
- 0.83
Near visual acuity Right eye (m) Left eye (m) Color confusion index Right eye (m) Left eye (rn) Contast sensitivity 1.2 cycleddegree: right eye left eye 3.0 cycleddegree: right eye left eye 6.0 cycleddegree: right eye left eye 12.0 cycleddegree: right eye left eye 18.0 cycleddegree: right eye left eye
-
-
- 0.09
0.40
-0.11 - 0.05
0.42
0.48
- 4.65
12.3 11.4 26.9 26.7 43.1 40.8 37.4 41.3 13.3 16.8
-4.50 -13.6 - 13.2 - 17.1 - 17.0 - 14.8 -18.1 -6.74 - 5.05
- 18 - 18 - 57
-13 - 12 - 25 - 25 - 53 - 42 - 34 - 45 - 16 - 18
- 57 - 65 - 56 -68 -68 - 28 - 23
- 0.08 0 0
-18 -18 - 19 - 24 - 18 - 23 -8 -8
Notes: Negative values indicate less desirable results for microelectronics workers. PI0 10th percentile; Q1 1st quattile, Q3 3rd quartile; P90 90th percentile. ns. *p 4 .05. tp 4 .01. *p < .m1.
-
more general spatial frequency loss, observed among patients with compressive lesions of the anterior visual pathways, seems to reflect a more diffuse disturbance of the optic nerve.42 In the present study, spatial frequency loss occurred over all frequency bands, but was greatest between 3 and 12 cycleddegree, which suggested that impairment was of neural origin. This is further supported by the fact that the pattern remained unchanged when statistical correction was made for near visual acuity. Differences in far visual acuity were not significant for the group of former microelectronics workers and their paired referents, whereas results of near visual acuity and acquired color vision loss were contradictory. Although the differences for the latter parameters were skewed towards poorer performances on the part of the former microelectronics workers, they only reached significance level for one eye, and, surprisingly, these were alternate eyes. These differences in laterality for near visual acuity may simply reflect that the results were just above and below the .05 significance level, whereas the differences in color vision possibly reflet a more complex phenomenon. In this region (a high desert plateau), other factors, such as intense light or high levels of ultraviolet radiation may contribute to dyschromatopsia. The prevalence of acquired color vision loss was very high for both the reference population and the microelectronics workers. Color vision loss, retinal damage, and corneal lenticular changes in response to high ultraviolet stimuli and intense light4’fm have been reported in animal and experimental studies. Novembedkember 1991 [Vol. 46 (No. 6)]
-
-
0 0 0 0 0 0 13
0 0
4
13 0 22 25 42 37 32 43 12 18
*
*
* t
* 8
t t t
**
not significant (p > .05).
The results of this study strongly suggest that factods) associated with the microelectronics assembly process or the environment may affect contrast sensitivity. Two major possibilities should be considered. (1) Impairment resulted from visual demands associated with ergonomic constraints of the type of work performed, and (2) toxic exposure had affected neuro-optic pathways. Although close precision work has been associated with loss of far visual acuity, cause and effect have not been well demon~trated.~’,~~ Axial elongation, extraocular muscle tension, increased intraocular pressure, and increased lens power are all interrelated mechanisms that could alter visual acuity in long-term close ~ o r k . ~ ’ *Prolonged ~ near work can also stress accommodation such that patients with low accommodative amplitude or flexibility will complain of asthenopia or blurred vision.56 In the present study, the absence of workerheferent differences for far visual acuity indicates that observed visual impairment did not result from prolonged close work. There are, however, many arguments that can be proffered to support the hypothesis that the type of visual impairment observed in the present study could result from exposure to chemicals with potential ophthalmotoxic properties. Although few industrial hygiene measurements were made in this plant, reports of acute health effects suggest that the levels were fairly high.3’ Moreover, visual disturbances have been associated with many of the soIvents7~’*used by these former microelectronics workers. Furthermore, many solvents were used, and in most departments multiple ex331
Right e y e
Left eye
near visual a c u i t y
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sensitivity (cycleddegree)
n.s.
K
0
n.1.
K
3.0 6.0
12.0 18.0
1-
0
-3
-2
__I__ -
K
I
.
,
-1
.
'
.
'
++
0.0
.
1
0
Reduced mean of differences
--
0
P10
Q1
rned
*
x
43
P90
Fig. 2. Percentile distribution of reduced mean of differences (mean score divided by standard deviation) for all of the measured visual functions. Negative values indicate poorer performance. Signed rank Wilcoxon text values are indicated: n.s. = p > .05; *p < .05; **p < .01; ***p < ,001.
posures were frequent. Although little is known about the possible synergistic effects of exposure to such a large number of organic solvents, a "cocktail" effect i s possible. Despite obvious limits, e.g., worker rotation from one job to another, work processes changing over time, and manipulation of multiple chemicals, an attempt was made to relate time spent in each department and visual outcomes. One department emerged from these analyses: printing and soldering of hybrid assembly. Among the factors that possibly distinguish this department from others i s the proximity of a heated vapor degreaser that consisted of three 1.2-m x 1.2-m containers filled with organic solvent mixtures. Industrial hygiene reports for this department indicate high levels of 1-1-1 trichloroethane and fluorochlorohydrocarbon mixtures; however, no information was provided on a combined index of exposure to these organic solvents and the others used in the work process. Reports of severe acute intoxication when individuals worked around the heated vapor degreaser3' suggest that organic solvent levels were very high. The observed relationship between contrast sensitivity loss in low and intermediate frequencies, and time spent in hybrid assembly, may reflect a particularly ophthalmotoxic solvent mixture or excessive exposure. This study was performed on a self-selected group of former workers from a particular plant and who had 332
suspected work-related illness. A matched design was used to ascertain whether work in this plant was associated with visual deficits among this particular population. There i s widespread agreement among researchers in quantitative epidemiological methods that a matched-pair design provides an appropriate means of minimizing bias." In this type of analysis, pairing is carried out from two initial pools. The groups that result from the matching process are not random, but paired on a series of potentially confounding variables. Analysis is carried out, not on the differences in means, but on the means of the intrapair differences. Possible bias may have arisen from the choice of the initial referent population, which was not random, but instead consisted of persons identified by the former workers. The former workers may have chosen persons who were particularly healthy. Information about their medical and work history does not support this assumption. Moreover, their visual functions were in a normal range, and as expected, varied with age. Finally, contrary to the former microelectronics workers, no information was available on their visual functions at the time when their "pair" began working. This would tend to bias towards initial and subsequent better performance by the former microelectronics workers. The findings of this study, which demonstrate lowered visual contrast sensitivity among this group of former microelectronics assembly workers, and which are conArchives of Environmental Health
Table 4.-Matched-Pain Analysis of Acquired Dyschromatopsia for Former Microelectronics Workers and Non-microelectronicsWorkers Normal color vision
I
Acquired dyschromatopsia
Non-microelectronicsworkers
L? aJ
*$
Right eyes’ Normal color vision Acquired dyschromatopsia
7 18
5 24
Left eyest Normal color vision Acquired dyxhromatopsia
6 14
7 27
.G E .U m
$5
Eti
82 Lal
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*Chi-square for matched pairs limits: 1.27-1 1.5). tChi-square for matched pairs fidence limits: 0.8-5.0).
-
7.34; p
- 2.33;
sistent with neural rather than ocular changes, cannot be generalized to other populations. Clearly, there is a need for more studies on the visual condition of past and current workers in the microelectronics and allied industries, where the work is visually demanding, and large amounts of different organic solvents are manipulated. Industrial hygiene measures should be taken, and methods should be developed to evaluate multiple chemical exposures and their effects. Conclusions This study, conducted among former microelectronics workers, revealed poorer visual functions, compared with a matched reference group from the same region. The most marked differences were observed for near contrast sensitivity, which suggested foveal vision andlor cortical impairment. These workers performed visually demanding work and had been in contact with a large number of organic solvents, including known neurotoxins, e.g., trichloroethylene, trichloroethane, toluene, and xylene, as well as chlorofluorocarbons. The findings of this study provide evidence of contrast loss among this particular group of former microelectronics assembly workers, consistent with impairment to foveal andlor neuro-optic pathways. Multiple organic solvent exposure is proposed as the most probable risk factor; however, more studies of active and past workers in the microelectronics and allied industries are required to further elucidate this relationship.
********** Funding for this project was obtained from the General Medical Fund of the University of California, San Francisco, and from the Quebec Institute for Research in Occupational Health and Safety. We express our appreciation to the participants in this study and a very supportive community of friends, relatives, and professionals who assisted in carrying out this project. We would also like to thank Ms. S. Legault-Belanger, I. Fortier, and Mr. L. Dallaire, who provided invaluable assistance in the conceptualization, testing, and analysis. Thanks is also offered to Ms. D. Allen, Mr. S. Racine, and Mr. L. Dallaire for their tireless efforts in data entry and proofing. Mrs. J. Guerriero, Ms. D. Alexander, and Dr. S. Fox are thanked for coordinating this project in the field. We also sincerely thank G. Berube, S.
NovembedDecember 1991[Vol. &(No. 6)]
< .001. Odds ratio
- 3.6 [95% - 2.0 (95%
not significant. Odds ratio
confidence con-
Legault-B6langer, and C. Brabant for reviewing this manuscript and for their helpful suggestions. Submitted for publication February 1, 1990; revised; accepted for publication April 17, 1991. Requests for reprints should be sent to: Donna Mergler, Ph.D., CINBIOSE, Department des sciences biologiques, Universite du Quebec A Montreal, CP 8888, succ”A”, Montreal, Quebec, Canada H3C 3P8.
********** References
1 . Cone JE. Health hazards of solvents: state of the art reviews. Occup Med 1986; 1:69-87. 2. Ladou J. Potential occupational hazards in the microelectronics industry. Scand J Work Environ Health 1983; 9:43-48. 3. Ladou J. Health issues in the microelectronics industry: state of the art reviews. Occup Med 1986; 1:1-11. 4. National Institute of Occupational Safety and Health. Hazard evaluation and technical assistance report. Dublin, CA: Western Electric Co., 1973; report no. 72-74-51. 5. Pasquini D, Laird L. Hazards assessment of the electronic component manufacturing industry. NIOSH contract no. 210-80-0058;
1982. 6. Wade R, Williams M. Semiconductor industry study. Task force on the electronics industry. California Department of Industrial Relations, DLSH; 1981. 7. Anger K. Neurobehavioral testing on chemicals: impact on recommended standards. Neurobehav Toxicol Teratol 1984; 6:
147-53. 8. Grant WM. Toxicology of the eye. Springfield, IL: Charles C Thomas, 1986. 9. ODonaghue JL, Ed. Neurotoxicity of industrial and commercial chemicals. Vol I. Baton Rouge, FL: CRC Press, Inc.; 1985. 10. Grandjean E, Munchinger R, Turrian V, Haas PS, Knoepfel HK, Rosenmund H. Investigations into the effects of exposure to trichloroethylene in mechanical engineering. Br J Ind Med 1955;
12:131-42. 1 1 . Department of Labor. Occupational exposure to trichloroethylene. Fed Reg 1975; 40:49032. 12. Channer KS, Stanley S. Persistent visual hallucinations secondary to chronic solvent encephalopathy. J Neurol Neurosurg Psychiat 1983; 46~83-86. 13. Ehyai A, Freeman FR. Progressive optic neuropathy and sensorineural hearing loss due to chronic glue sniffing. J Neurol Neurosurg Psychiat 1983; 46:349-51. 14. Wyse DG. Deliberate inhalation of volatile hydrocarbons: a review. Can Med Assoc J 1973; 108:71-74. 15. Alieva ZA. Reduced acuity of color perception resulting from exposure to styrene and tetrachloroethylene vapours. Gig Trud Prof Zabol 1985; 2:ll-13.
333
Downloaded by [North Carolina State University] at 05:51 16 March 2015
16. Legault-Belanger S, Bachand M, Bedard S, Brabant C, de Grosbois S , Mergler D. Perte de discrimination chromatique chez des travailleurs sournis a une exposition complexe et variable aux solvants organiques. Arch Ma1 Prof 1988; 49475-82. 17. Mergler D, Belanger S, de Grosbois S, Vachon N. Chroma1 focus of acquired chromatic discrimination loss and solvent exposure among printshop workers. Toxicol 1988; 49341-48. 18. Mergler D, Blain L, Lagace JP. Solvent related color vision loss: an indicator of neural damage? Int Arch Occup Environ Health 1987; 59:313-21. 19. Raitta C, Seppalainen AM, Huuskonen MS. n-Hexane maculopathy in industrial workers. Alb v Craef Arch Klin Exp Ophthalmol 1978; 2 0 9 9 - 1 10. 20. Raitta C, Teir E, Jolonen E, Helpio E, Malmstrom S. Impaired color vision discrimination among viscose rayon workers exposed to carbon bisulfide. I &cup med 1981; 23:189-92. 21. Arden GB. Testing contrast sensitivity in clinical practice. Clin Vis Sci 1988; 2:213-34. 22. Bodis-Wollner I. Methodological aspects of contrast sensitivity measurements in the diagnosis of optic neuropathy and maculopathy. Doc Ophthal Proc Ser 1983; 35:225-37. 23. Harmor MF. Contrast sensitivity and retinal disease. Ann Ophthalmol 1981; 13:1069-71. 24. Hyvarinen L, Laurinen P, Rovamo J. Contrast sensitivity function in evaluation of visual impairment due to macular degeneration and optic nerve lesions. Acta Ophthalmol 1983; 61:161-70. 25. Hart WM. Acquired dyschromatopsias. SUN Ophthalmol 1987; 32: 10-3 1. 26. Francois J, Verriest G. La detection a I'aide des tests de Farnsworth des dyschromatopsies acquises dans les degenerescences tapeteretineienne. Ann Ocul (Paris) 1956; 113:381-98. 27. National Institute of Occupational Safety and Health. Hazard evaluation and technical assistance report. Broomfield, CO: FMC Corporation, 1977; Report no. 76-101-376. 28. National Institute of Occupational Safety and Health. Health evaluation and technical assistance report. Kittaning, P A Essex International, 1977; Report no. 77-3-420. 29. National Institute of Occupational Safety and Health. Hazard evaluation and technical assistance report. Grove City, OH: Robertshaw Controls Co., 1977; Report no. TA 76-102. 30. Hue1 G, Mergler D, Bowler R. Evidence of adverse reproductive outcomes among women microelectronics workers. Br J Ind Med 1990; 47:400-04. 31. Fox S. Toxic chemicals and stress: anatomy of an out-of-court settlement for women workers at GTE Lenkurt Electronics Plant. Ph.D. Thesis, University of New Mexico, Albuquerque; 1988. 32. Verriest C. Further studies on acquired deficiency of color discrimination. J Opt Soc Am 1963; 53:185-95. 33. Bowman KJ. A method for quantitative scoring of the FarnsworthMunsell Panel D-15. Ada Ophthalmol 1982; 60907-12. 34. Lehman DL, D'Abrere HJM.In Lehmann EL, Ed. Nonparametrics: statistical methods based on ranks. New York: McCraw-Hill International; and San Francisco, CA: Holden-Day, Inc.; 1975. 35. Owsley C, Sekular R, Siemens D. Contrast sensitivity through adulthood. Vision Res 1983; 23:689-99.
334
36. Campbell FW, Green DG. Optical and retinal factors affecting visual resolution. J Physiol 1965; 181:576-93. 37. Creeves AL, Cole BL, Jacobs RJ. Assessment of contrast sensitivity of patients with macular disease using reduced contrast near visual acuity charts. Ophthalmol Physiol Opt 1988; 8371-77. 38. Cainburg AP. A new contrast sensitivity vision test chart. Am J Optom Physiol Opt 1984; 61:403-07. 39. Regan D, Neima D. Low contrast letter charts as a test of visual function. Am Acad Ophthalmol 1983; 90:1192-1200. 40. Bodis Wollner I. Detection of visual defects using the contrast sensitivity function. Int Ophthalmol Clin 1980; 20135-53. 41. Drucker MD, Savino PI, Sergott RC, Bosley TM, Schatz Nj, Kubilis PS. Low-contrast letter charts to detect subtle neuropathies. Am J Ophthalmol 1988; 105:141-45. 42. Kuppersmith MJ, Siege1 IM, Carr RE. Subtle differences of vision with compressive lesions of the anterior visual field pathway measured by contrast sensitivity. Ophthalmology 1982; 8 7 1140-49. 43. Sokol S, Moskowitz SB. Contrast sensitivity in diabetics with and without background retinopathy. Arch Ophthalmol 1985; 103: 51-54. 44. Wolkstein M, Atkin A, Bodis-Wolner I. Contrast sensitivity in retinal disease. Ophthalmology 1980; 87:1140-49. 45. Bodis-Wollner I, Marx M, Mitra S, et at. Visual dysfunction in Parkinson's disease. Brain 1987; 1101675-98. 46. Regan D, Silver R, Murray TJ. Visual acuity and contrasts in multiple sclerosis: hidden visual loss. Brain 1977; 100:563-79. 47. Regan D, Neima D. Low-contrast letter charts in early diabetic retinopathy Ocular hypertension, glaucoma and Parkinson's disease. Br J Ophthalmol 1984; 68:885-89. 48. Regan D. Low-contrast letter charts and sinewave gratings tests in ophthalmological and neurological disorders. Clin Vision Sci 1988; 2~235-50. 49. Schmidt RE, Zuluch JA. Retinal lesions due to ultraviolet laser exposure. Invest Ophthalmol 1980; 101166-75. 50. Wright AA, Sperling HC, Mills SJ. Researches on a unilaterally blue-blinded rhesus monkey. Vision Res 1987; 27:1551-64. 51. Angle J, Wissman DA. Age, reading, and myopia. Am J Optom Physiol Opt 1978; 55:302-08. 52. Richler A, Bear JC, Refraction, nearwork and education: a population study in Newfoundland. Acta Ophthalmol 1980; 58: 468-78. 53. Young FA. The nature and control of myopia. J Am Optom Assoc 1977; 48~451-57. 54. Sat0 T. Criticism of various accommodogeneous theories on school myopia judging from explanation on emmetropization. Doc Ophthalmol Proc Ser 1981; 28:97-102. 55. Collins CC, Bach-y-Rita P, Loeb DR. lntraocular pressure variation with oculorotary muscle tension. Am J Physiol 1967; 213: 1039-43. 56. Cooper J. Accommodative dysfunction. In: Amos JF, Ed. Diagnosis and management in vision care. Butterworths 1987; 431-54. 57. Kleinbaum DC, Kupper LL, Morgenstern H. Epidemiologic research principles and quantitative methods. Toronto: Lifetime Learning Publications, 1982.
Archives of Envimnrnental Health
