Tonic Accommodation, Age, and Refractive Error in

Tonic Accommodation, Age, and Refractive Error in Children Karla Zadnik,1 Donald 0. Mutti,1'2 H. S. Kim,5 Lisa A. Jones,4 Pei-Hua Qiu,4 and Melvin L Moeschberget5 An association between tonic accommodation, the resting accommodative position of the eye in the absence of a visually compelling stimulus, and refractive error has been reported in adults and children. In general, myopes have the lowest (or least myopic) levels of tonic accommodation. The purpose in assessing tonic accommodation was to evaluate it as a predictor of onset of myopia. PURPOSE.

Tonic accommodation was measured in children enrolled in the Orinda Longitudinal Study of Myopia using an infrared autorefractor (model R-l; Canon, Lake Success, NY) while children viewed an empty litfieldor a darkfieldwith afixationspot projected in Maxwellian view. Children aged 6 to 15 years were measured from 1991 through 1994 (n = 714, 766, 771, and 790 during the 4 years, successively). Autorefraction provided refractive error and tonic accommodation data, and videophakometry measured crystalline lens curvatures.

METHODS.

RESULTS. Comparison

of the two methods for measuring tonic accommodation shows a significant effect of age across all years of testing, with the lit empty-field test condition yielding higher levels of tonic accommodation compared with the dark-field test condition in children aged 6 through 11 years. For data collected in 1994, mean (±SD) tonic accommodation values for the lit empty-field condition were significantly lower in myopes, intermediate in emmetropes, and highest in hyperopes (1.02 ± 1.18 D, 1.92 ± 1.59 D, and 2.25 ± 1.78 D, respectively; Kruskal-Wallis test, P < 0.001; between-group testing shows each group is different from the other two). Age, refractive error, and Gullstrand lens power were significant terms in a multiple regression model of tonic accommodation (R2 = 0.18 for 1994 data). Lower levels of tonic accommodation for children entering the study in thefirstor third grades were not associated with an increased risk of the onset of myopia, whether measured in the lit empty-field test condition (relative risk = 0.90; 95% confidence interval = 0.75, 1.08), or the dark-field test condition (relative risk = 0.83; 95% confidence interval = 0.60, 1.14). This is the first study to document an association between age and tonic accommodation. The known association between tonic accommodation and refractive error was confirmed and it was shown that an ocular component, Gullstrand lens power, also contributed to the tonic accommodation level. There does not seem to be an increased risk of onset of juvenile myopia associated with tonic accommodation. (Invest Ophthalmol Vis Set. 1999;40:1050-1060)

CONCLUSIONS.

T

onic accommodation is the resting position of the accommodative system in the absence of compelling visual stimuli. It is generally reported to have a range of 0.50 D to 4.00 D, with a mean of approximately 1.50 D in adults.1 Tonic accommodation and its adaptation (how it changes after active accommodation) have attracted considerable interest in recent years as a putative risk factor for myopia2'3 and have been studied widely as a function of refractive error. 45 In early studies, it was shown that emmetropes had significantly higher (i.e., more myopic) values of tonic accomFrom the 'College of Optometry; the 'College of Medicine and Public Health, Division of Epidemiology and Biometrics; and the ''Biostatistics Program, The Ohio State University, Columbus; and the 2 School of Optometry, University of California, Berkeley. Supported by Grant EY08893 from the National Institutes of Health, Bethesda, Maryland. Submitted for publication February 3, 1998; revised November 30, 1998; accepted January 20, 1999. Proprietary interest category: N. Reprint requests: Karla Zadnik, The Ohio State University College of Optometry, 338 West Tenth Avenue, Columbus, OH 43210-1240.

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modation than did high myopes.6 Later, distinctions were drawn within the subgroup of myopia, and hyperopes were examined. Juvenile-onset myopes and emmetropes had similar tonic accommodation values, whereas hyperopes had higher tonic accommodation values, and adult-onset myopes had lower tonic accommodation values.7 Similar relations have been shown in children, with tonic accommodation values progressing from highest in hyperopes, to intermediate in emmetropes, to lowest in juvenile-onset myopes.8'9 Shifts in tonic accommodation of brief duration have been shown during and after near-work tasks, and these short-term shifts seem to vary by refractive error category. Sustained visual work at near increased tonic accommodation immediately after the task (i.e., tonic accommodation shifted in the myopic direction) in those with adult-onset myopia, whereas hyperopes showed decreases in tonic accommodation. Little change in tonic accommodation was exhibited by juvenile-onset myopes and emmetropes after sustained near work.10 In one study, all children increased in tonic accommodation after playing video games, with juvenile-onset myopes showing the Investigative Ophthalmology & Visual Science, May 1999, Vol. 40, No. 6 Copyright © Association for Research in Vision and Ophthalmology

Tonic Accommodation and Refractive Error

IOVS, May 1999, Vol. 40, No. 6

greatest increase.9 Tonic accommodation has been shown to increase during tasks involving cognitive demand as well.11'12 Tonic accommodation has been measured in many ways. With all methods, the goal is to measure the resting state of accommodation under open-loop conditions. The method varies by laboratory and investigator, and individual laboratories have generally adopted a favored method. The methods used include measurement with the Badal helium-neon laser optometer while viewing laser-produced speckles on a rotating cylindrical drum, 113 infrared optometry while the subject views a dark field 6 ' 4 "' 7 or a lit empty field,17 autorefraction while the subject views a dark field,7'9"'3 and dynamic (Nott) retinoscopy while the subject views the retinoscopic beam'3 or a difference of Gaussian target.818 Tonic accommodation has been reported to be more myopic by approximately 0.50 D when measured in a lighted empty field compared with that measured in the dark.'9 In a subsequent study, investigators using procedures similar to those in the present study found no significant differences between resting measures of pretask tonic accommodation in empty-field conditions and in darkness.17 Three studies comparing methods in adults have been published, one comparing subjective and objective methods in the form of helium-neon laser optometry, infrared optometry, and near (dynamic) retinoscopy13; one comparing adaptation of tonic accommodation with infrared autorefraction while viewing either a dark or lit empty field17; and one comparing dynamic retinoscopy viewing either a difference of Gaussian target or the retinoscope beam.20 In the first study, results were similar for all three measurement methods, although near retinoscopy showed less variability across subjects.13 In the second study, tonic accommodation levels were not affected by whether the subjects viewed a dark field or lit empty field while tonic accommodation was measured with an infrared autorefractor.l7 In the third, the results show that tonic accommodation measured in the dark differs from tonic accommodation measured under other conditions for a variety of reasons.20 To date, different test conditions and measurement methods for tonic accommodation in children have not been compared. The relation between tonic accommodation and the ocular components has not been explored beyond that reported for refractive error. For example, the possibility that a person's or a refractive error group's tonic accommodation levels may be a consequence of crystalline lens shape and power has not been considered previously. Correlation coefficients between refractive error and tonic accommodation have ranged from 0.6l,2 to 0.48,6 to 0.24.7 In two studies, investigators have performed regression analysis on tonic accommodation versus refractive error,8'9 but none has made comparisons with any of the anatomic ocular components. Our purpose in measuring tonic accommodation in the Orinda Longitudinal Study of Myopia (OLSM) from 1991 through 1994 included several objectives. First, we wanted to compare measurement methods in school-aged children. Second, we wanted to verify the previously reported relation between tonic accommodation and refractive error in our OLSM sample. Third, we wanted to determine the associations, if any, between tonic accommodation and the ocular components, especially those relating to the crystalline lens. Finally, we wanted to evaluate tonic accommodation as a risk factor for the onset of myopia in children.

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1. Children Enrolled in the Orinda Longitudinal Study of Myopia, 1991 through 1994

TABLE

Year Tested

Age*

1991

1992

1993

6 7 8

48 100 83

43 139

9

94

10 11 12 13 14 15

89 72 81 90 52

49 130 100 76 90 90 84

Total

57

95

112 124 122

77 82

92 69 81 84

790

115

5

52 2

86 75 56 3

714

766

771

93

1994

49 0

Children represented in this table had both lit empty-field and dark-field measures of tonic accommodation at each measurement occasion. * By age rounded to the nearest year.

METHODS

Subjects The study design and entire sample for the OLSM have been described previously.21 All children enrolled in the Orinda Union School District in grades 1,3, and 6 in fall 1989 or fall 1990; in grades 1 or 6 in fall 1991; or in grade 1 in fall 1992, 1993, or 1994 were eligible for this phase of the study. Parents gave consent for their children's participation after all study procedures were explained in accordance with the tenets of the Declaration of Helsinki. The subjects from the OLSM represented in this report are all children measured from 1991 through 1994 for whom we have tonic accommodation measures for fixation of the empty lit field and the dark field, as described later (n = 714, 766, 771, and 790 in the 4 years, successively). All children measured from 1991 through 1994 in the OLSM are included. Children enrolled in or before 1991 had the potential to be represented in the data set four times, children enrolled in 1992 were represented in the data set three times, children enrolled in 1993 were represented in the data set twice, and children enrolled in 1994 were represented in the data set once. Age at the time of testing was rounded to the nearest year (e.g., 14.6 through 154 years was coded as 15 years for the purposes of data analysis). The number of subjects in each age group for children measured in each of the 4 years is shown in Table 1.

Measurement Refractive error was measured by noncycloplegic autorefraction (model R-l; Canon, Lake Success, NY; no longer manufactured). Subjects had the left eye occluded by an eye patch while viewing the 6/9 (20/30) equivalent row of letters on a reduced Snellen card through a +4.00 D Badal lens. Subjective refraction techniques were simulated in this apparatus by moving the letter target along a track away from the subject to relax accommodation, as though plus lenses were being added. Readings were recorded at the point at which the target was clear, and any movement to relax accommodation further resulted in the subject's reporting blur. At least 10 readings

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were taken on the right eye. Spurious values were eliminated according to a previously described protocol.21 We measured the right eye's ocular components and refractive error in the subject sample as described previously in detail.21 Specifically, we used the autorefractor to measure refractive error, the photokeratoscope (KERA; Fremont, CA; no longer manufactured) to measure corneal power, video phakometry to measure crystalline lens curvatures,22 and an ultrasound scanning unit (model 820 A-scan; Humphrey, San Leandro, CA) to measure the eye's axial dimensions, anterior chamber depth, crystalline lens thickness, and vitreous chamber depth.23 Although measurement of the various components was divided among three examiners, each examiner measured the same components on each subject at each annual session. Topical agents were used to induce corneal anesthesia (0.5% proparacaine), pupillary mydriasis, and cycloplegia (two drops of 1.0% tropicamide administered 5 minutes apart). Noncycloplegic refractive error, corneal power, and tonic accommodation were measured before drop instillation. Cycloplegic refractive error, crystalline lens curvatures, and axial dimensions were all measured beginning 25 minutes after the first drop of tropicamide. We have previously documented the effectiveness of tropicamide as a cycloplegic agent in a comparable sample of children.24'25 All measurements were conducted without examiner knowledge of the child's visual activity profile or parental history of myopia. For the purposes of refractive error classification, children were categorized on the basis of the right eye's cycloplegic autorefraction in the vertical and horizontal meridians (average of 10 readings)26 as follows: Myopes were defined as having at least —0.75 D of myopia in the vertical and horizontal meridians, hyperopes had at least +1.00 D of hyperopia in the vertical and horizontal meridians, and emmetropes represented the rest of the sample.

Measurement of Tonic Accommodation Lit Empty Field. A translucent plate of polypropylene was placed over the examiner's side of the mirror housing on the autorefractor. Edges of the housing were obscured by a second polypropylene plate placed on the patient's side of the mirror housing. This plate contained a rectangular aperture (30 mm X 95 mm). The edges of this aperture were further obscured by strips of translucent cellophane tape on each edge, making a final aperture size of 25 mm X 75 mm (20° X 56°). Testing took place in a converted 34-ft mobile home trailer parked out of doors. The autorefractor was located in a room lit by natural light from one window. Lighting conditions were therefore variable depending on the time of day and weather conditions (50-100 candela[cd]/m2). Supplemental illumination from a fluorescent fixture was directed at the polypropylene plate during late afternoon testing times or overcast conditions. Children were instructed to look toward the middle of the plate as though they were looking out a window to keep their fixation centered in the autorefractor. The left eye was occluded by an eye patch. The examiner held up a finger in the middle of the plate to direct fixation. Once the child showed that he or she understood where to look, the finger was removed, and readings were taken. Some young children were unable to maintain steady fixation in the absence of stimuli. To obtain data from all the younger subjects, children in first and second grades fixated a

IOVS, May 1999, Vol. 40, No. 6 15% contrast smudge consisting of a circle 8 mm in diameter (5°) drawn on a piece of translucent cellophane tape and attached to the plate on the examiner's side. The polypropylene plates and autorefractor mirror were regularly cleaned of dust and other particles. Dark Field with Fixation Light. We also measured tonic accommodation in modified darkness. Room lights remained on while the subject wore a pair of custom sunglasses containing an opaque lens over the left eye and a Wratten 89B infrared filter over the right eye. This filter transmits only wavelengths longer than 680 nm. The autorefractor possesses sufficient sensitivity to infrared light to make measurements through this filter. Room lighting was visible around the edges of the sunglasses. The infrared illumination lights on the autorefractor were covered by a removable mask to create a dark field centrally. Steady fixation in darkness was made possible by projecting a red spot in Maxwellian view in the middle of the darkfield.Thisfixationspot was produced by placing a 0.5 mm diameter pinhole illuminated by an incandescent source at the focal point of a +6.25 D lens. A second +6.25 D lens imaged this pinhole in the pupillary plane of the right eye of each subject. The pinhole was frosted with translucent tape to obscure any detail of the filament of the light source. The lateral extent of the fixation spot was restricted by placing a 3 mm aperture 20 mm from the pinhole. At least 10 autorefractor readings were recorded in the right eye by each method by the same examiner. The order of measurement was determined by a random number table. New sequences were used for each year of testing. The data were "scrubbed" by identifying sphere values on the autorefractor printout for a subject that differed from his or her median value by at least 5.00 D. High initial values were discarded if readings decreased by 3-00 D or more. Readings were also discarded if accompanied by a cylinder axis differing significantly from the mode axis (e.g., by 80°). Readings were not discarded if variation in tonic accommodation occurred randomly within a set of readings, as opposed to systematically decreasing from a high initial value. The mean sphere from the lit empty-field and dark-field conditions was subtracted from the mean sphere from the noncycloplegic autorefraction to yield the values of tonic accommodation used in the following analyses.

Statistical Methods The data set collected from the OLSM was analyzed crosssectionally and longitudinally in separate analyses to examine the factors associated with tonic accommodation. The outcome variables were tonic accommodation measured by the empty-field method and by the dark-field method, as described earlier. The explanatory variables were age, cycloplegic refractive error, and other ocular components: corneal power, anterior chamber depth, lens thickness, Gullstrand lens power, calculated equivalent lens power, lens equivalent refractive index, calculated lens spherical volume,27 vitreous chamber depth, and axial length. First, the cross-sectional analysis was performed for data collected in 1991, 1992, 1993, and 1994. Analysis of variance was used to determine whether tonic accommodation was different among refractive error groups (myope, emmetrope, and hyperope) and whether it was related to age. Second, if data were not approximately normally distributed, then the nonparametric Kruskal-Wallis one-way analysis of variance was used. Groups were further compared by Wilcoxon rank sum tests if the Kruskal-Wallis test was

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Tonic Accommodation and Refractive Error

1991

1053

1992

3.50

7

8

9 Age

1011121314 (years)

0.50 6

-I

7

8

1-

9 Age

1011121314 (years)

1994

1993 3.50

6

7

8

9 Age

1011121314 (years)

6

7

8 9 1011121314 Age (years)

FIGURE 1. A plot of tonic accommodation as a function of age for both viewing conditions, lit empty field (dashed line) and darkfield(solid line), as a function of the children's age for each of the 4 years of testing.

significant. Multiple regression with a stepwise selection procedure was used to select statistically significant explanatory variables. Because children of the same age across the 4 years were not the same children, the data were independent by age across test years. The independence of cross-sectional data allowed data across the 4 years to be combined by age. Third, the repeated measure design was used with longitudinal data measured in children who entered into OLSM only in school grades 1,3, and 6 to determine the cohort and/or time effects for tonic accommodation. The statistical analysis software program (Statistical Analysis System; SAS, Cary, NC) was used for cross-sectional data analysis,28 and another procedure (BMDP5V; BMDP, Berkeley, CA) was used for the repeated measures analysis because of its capability for handling missing values.29 Relative risks for the occurrence of myopia were obtained from a proportional hazards time-to-event analysis.30 In the present study, the time variable was the length of time the children were under observation, and either they became myopic or the study concluded without their becoming myopic. This model customarily assumes that the hazards (or risks) for various levels of a factor are proportional. The assumption of proportional hazards was verified. All children in this analysis were nonmyopic at enrollment. Time to myopia was modeled using tonic accommodation under each test condition as covariates. Analyses were completed separately for children en-

rolled in the study during the first, third, or sixth grades, and for all children who were tested in the third grade, regardless of their grade at entry. (This included children enrolled in first grade who were eventually tested during third grade.)

RESULTS

The tonic accommodation values for both viewing conditions, lit empty field and darkfieldwith fixation light, as a function of the children's age are shown in Figure 1 (cross-sectional data). Across all 4 years when these data were collected in the same children, it is evident that the lit empty-field condition yielded significantly higher tonic accommodation values in younger children compared with the dark-field test condition. This difference is therefore unlikely to be caused by a cohort effect of children tested in any 1 year. The differences disappear between ages 9 and 14 years. These differences are again evident in Figure 2A, in which the data are collapsed across test years (cross-sectional data). It is apparent from Figure 2B that the 95% confidence intervals for the difference between the tonic accommodation data for the lit empty-field and the darkfield test conditions do not include 0 through age 11 years, indicating statistically significant differences between results of the two test conditions through that age.

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3.50

0.00 8

9 Age

8

B

9 Age

10

1112

13

14

15

(years)

1011 1213 (years)

14

15

FIGURE 2. A plot of tonic accommodation versus age (A) for all data collected from 1991 through 1994 under the lit empty-field test condition and the dark-field test conditions. The difference in tonic accommodation (B) under the two test conditions as a function of age, with the 95% confidence interval depicted for each age group.

As an estimate of the repeatability of the tonic accommodation measurement techniques, we randomly selected 50 children tested in both 1990 and 1991 whose refractive error categories had not changed between testing occasions. Given that their tonic accommodation would be expected to change slightly with increasing age (Fig. 1), we found an interoccasion mean difference in the lit empty-field measurement of 0.03 ± 1.39 D and an interoccasion mean difference in the dark-field with fixation light measurement of —0.07 ± 1.54 D. Although these values did not represent a high degree of repeatability (95% limits of agreement of ±2.72 D and ±3.02 D, respectively) of this obviously "noisy" measure in children, the previously reported relation between tonic accommodation and refractive error was still evident (Fig. 3), an indication of the measurement method's robustness and validity. The relation between refractive error and tonic accommodation across age groups is represented in Figure 3 (crosssectional data). In all age groups, myopes showed the lowest

value of tonic accommodation, with emmetropes and hyperopes in general showing higher values of tonic accommodation. The data for tonic accommodation under both viewing conditions are shown in Table 2 by refractive error group for all 4 years of data (cross-sectional data). The relation between refractive error and tonic accommodation was evident with both measurement methods across the years of the study. For the lit empty-field test condition, the levels of tonic accommodation were different among the refractive error groups (Kruskal-Wallis test; P < 0.001). Myopes had the lowest levels of tonic accommodation, emmetropes the intermediate levels, and hyperopes the highest levels (Wilcoxon rank sum test: myopes compared with emmetropes, P < 0.001; myopes compared with hyperopes, P < 0.001; and emmetropes compared with hyperopes, P < 0.023). For the dark-field test condition, the levels of tonic accommodation were also different among the refractive error groups (Kruskal-Wallis test, P < 0.001). However, only the myopes were different; the emmetropes and hyperopes were statistically equivalent (Wilcoxon rank sum test: myopes compared with emmetropes, P < 0.001; myopes compared with hyperopes, P < 0.001; and emmetropes compared with hyperopes, P = 0.765). The results of multiple, stepwise regressions to determine the effect of age, refractive error, and the ocular components on tonic accommodation under the lit empty-field and the dark-field viewing conditions are shown in Tables 3 and 4 (cross-sectional data). All variables in Tables 3 and 4 represent those that were screened as significant at P = 0.15 level by a stepwise multiple regression selection method. For tonic accommodation under the lit empty-field viewing condition (Table 3), age, refractive error, and Gullstrand lens power were represented in the models of all 4 years' data. Calculated lens power contributed minimally to the model in 2 years, as did corneal power in 1 year. Anterior chamber depth, lens thickness, and lens spherical volume all entered the model in only 1 year, 1994. For tonic accommodation under the dark-field viewing condition (Table 4), the picture was much less consistent across years. Gullstrand lens power was significant across all 4 years, refractive error was significant in 3 of the 4 years' data sets, and age was significant in 2 of the 4 years. Axial length, corneal power, and corneal curvature entered the model in a statistically significant way in only 1 year each. Overall, the R2 values across years for tonic accommodation with the darkfield viewing condition were lower than those for tonic accommodation with the lit empty-field viewing condition, indicating that, in general, much less of the variability in the former could be explained by age, refractive error, and the ocular components. Thus, in Table 5 we have chosen to highlight tonic accommodation with the lit empty-field viewing condition. Across the years, multiple regression analyses on tonic accommodation with the lit empty-field viewing condition show that the important and consistent predictor variables were age, refractive error, and Gullstrand lens power. The results of multiple regression modeling on tonic accommodation with only these three variables in the model are shown. In an attempt to exploit the statistical power of longitudinal analyses and the ability to construct independent age samples from longitudinal data, repeated measures analyses for children entered into OLSM in school grades 1,3, and 6 were

IOVS, May 1999, Vol. 40, No. 6

Tonic Accommodation and Refractive Error 1992

1991

12

12 ,

10

10

0

8

0 •

°

•

•

6 •

o

•

•

f

(0

•

.II• ill ••;•: si* •

•

-2 •

8

0

f

2

-4

.
=12

1993

M E H Age>=12

1994

12

10-

•Iro 6 A

! 8

< y

\

2 n•

I °

ii si

if

-2

3 144 35

11 172 27

(Number of subjects) 10 140 9 45 162 13

3 134 32

11 205 30

o (Number of subjects) 13 131 17 33 174 7

M E H Age 6-7

M E H Age 8-9

M E H Age10-11

M E H Age 6-7

M E H Age 8-9

M E H Age10-11

M E H Age>= 12

M E H Age >= 12

FIGURE 3. Box plots for tonic accommodation under the lit empty-field viewing condition as a function of age and refractive error for each test year. The open box represents the median value; the upper and lower ends of the filled rectangles the 75th and 25th percentiles, respectively; and the upper and lower filled circles the 100th and zero percentiles, respectively, after excluding outliers. The open circles represent outlying values differing from the nearest value by at least 1.00 D.

performed (Table 6). In each analysis, there was a significant interaction term between the cohort enrolled in 1989 and the initial measurement time, which was controlled for in the

TABLE

Year

analysis. Changes in refractive error, Gullstrand lens power, and crystalline lens refractive index were all significant in modeling the change in tonic accommodation in children

2. Tonic Accommodation by Refractive Error Group for Data Collected in 1991 through 1994 Refractive Error Group

Number of Subjects

Tonic Accommodation with Lit, Empty Field

Tonic Accommodation with Dark Field

1991

Myopes Emmetropes Hyperopes

71 568 75

1.05 ± 0.76 2.13 ± 1.71 2.26 ± 1.92

1992

Myopes Emmetropes Hyperopes

78 605 83

1.20 ± 1.29 2.13 ± 1.69 2.40 ± 2.27

0.94 ± 0.83 1.70 ± 1.50 1.77 ± 1.83 1.00 ± 1.40 1.71 ± 1.58 2.06 ± 2.09

1993

Myopes Emmetropes Hyperopes

69 618 84

1.10 ± 0.99 2.15 ± 1.74 2.21 ± 1.83

0.93 ± 1.06 1.75 ± 1.61 1.41 ± 1.55

1994

Myopes Emmetropes Hyperopes

60 644 86

0.79 ± 0.78 1.92 ± 1.59 2.46 ± 1.88

1.07 ± 1.43 1.70 ± 1.63 1.63 ± 1.63

Tonic accommodation under both viewing conditions is significantly lower in myopes and is different across refractive error groups under the lit empty-field condition for all years of the study. Data are means ± SD in diopters.

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TABLE 3. Multiple Stepwise Regression Results for Tonic Accommodation Measured under the Lit Empty-Field Viewing Condition Year 1991

Variable Age

Refractive error Gullstrand lens power 1992

Age

Gullstrand lens power Corneal power Refractive error Calculated lens power 1993

Age

Gullstrand lens power Refractive error Calculated lens power 1994

Age

Refractive error Gullstrand lens power Anterior chamber depth Lens thickness Lens spherical volume

Coefficient

Partial R2

P

-0.130 0.210 0.139

0.075 0.0001 0.026 0.0001 0.013 0.0012 Adjusted R2 = 0.109

-0.183 0.287 -0.119 0.111 -0.058

0.106 0.028 0.011 0.007 0.002 Adjusted R2 =

0.0001 0.0001 0.0019 0.0149 0.1488 0.148

-0.148 0.211 0.112 -0.066

0.096 0.018 0.006 0.004 Adjusted/?2 =

0.0001 0.0001 0.0251 0.0660 0.121

-0.225 0.145 0.069 -0.414 -6.128 0.070

0.158 0.016 0.008 0.003 0.004 0.003 Adjusted/?2 =

0.0001 0.0001 0.0074 0.1119 0.0521 0.0839 0.184

All variables included in this table represent those that were "screened" as significant at P < 0.15.

enrolled as first graders. Only refractive error and Gullstrand lens power were significant in those enrolled as third graders; and only refractive error, Gullstrand lens power, and anterior chamber depth are significant in those enrolled as sixth graders. These results confirm those of the cross-sectional analyses in that the terms that emerge most consistently as explanatory of tonic accommodation, although they explain a very small

portion of its variance, are Gullstrand lens power and cycloplegic refractive error. Despite the association between a child's current refractive error and tonic accommodation, it does not seem to be a statistically significant risk factor for the future onset of myopia. Relative risks for tonic accommodation by both methods were calculated from a proportional hazards time-to-event

TABLE 4. Multiple Stepwise Regression Results for Tonic Accommodation Measured under the Dark-Field with Fixation Light Viewing Condition Partial R2

Year

Variable

Coefficient

1991

Axial length Corneal power Gullstrand lens power

-0.335 -0.092 0.087

0.037 0.0001 0.008 0.0157 0.005 0.0613 Adjusted R2 = 0.046

1992

Gullstrand lens power Refractive error Corneal power

0.214 0.134 -0.062 -0.059

1993

Gullstrand lens power Refractive error Calculated lens power

0.240 0.115 -0.067

0.050 0.0001 0.019 0.0001 0.007 0.0196 0.003 0.1072 Adjusted i?2 = 0.073 0.046 0.0001 0.008 0.0099 0.005 0.0547 Adjusted i?2 = 0.056

1994

Age

-0.072 0.107 0.084

Age

Gullstrand lens power Refractive error

P

0.023 0.0001 0.007 0.0156 0.004 0.0651 2 Adjusted i? = 0.0297

All variables included in this table represent those that were "screened" as significant at P < 0.15-

Tonic Accommodation and Refractive Error

IOVS, May 1999, Vol. 40, No. 6

1057

TABLE 5. Tonic Accommodation under the Lit Empty-Field Viewing Condition

Modeled across Years with Multiple Regression Models Containing Only Age, Refractive Error, and Gullstrand Lens Power Partial R2

Year

Variable

Coefficient

1991

Age Refractive error Gullstrand lens power

-0.130 0.210 0.139

0.032 0.0001 0.024 0.0001 0.015 0.0013 Adjusted R2 = 0.110

1992

Age Refractive error Gullstrand lens power

-0.173 0.124 0.211

0.054 0.0001 0.010 0.0052 0.030 0.0001 Adjusted R2 = 0.139

1993

Age Refractive error Gullstrand lens power

-0.153 0.106 0.161

0.038 0.0001 0.008 0.0148 0.021 0.0001 Adjusted R2 = 0.118

1994

Age Refractive error Gullstrand lens power

-0.232 0.162 0.161

0.109 0.0001 0.020 0.0001 0.010 0.0060 Adjusted/?2 = 0.177

analysis30 with the onset of myopia (at least —0.75 D in both principal meridians) as the event. The time variable is the length of time until each child either became myopic or the study concluded without the child becoming myopic, for children enrolling in OLSM in the first, third, or sixth grades, or for children enrolling in the first or third grades, with third grade data serving as the baseline (Table 7; longitudinal data). The relative risks for tonic accommodation were not statistically significant, regardless of grade at enrollment or measurement method used.

DISCUSSION These results showing tonic accommodation under two viewing conditions in school-aged children represent the largest data set ever assembled of tonic accommodation in any age group. We found an age-related difference between tonic accommodation measurements made under the two viewing conditions: a lit empty field and a dark field with fixation light. We also found the first association reported between increas-

P

ing age and less myopic levels of tonic accommodation. We confirmed the frequently reported association between tonic accommodation and refractive error,4 " y regardless of viewing condition. When ocular components were included with refractive error in a regression analysis, we also found a comparably modest but significant association between Gullstrand lens power and tonic accommodation. Studies of tonic accommodation provide support for accommodative theories of refractive error development.31 Along with the development of animal models of myopia, the tonic accommodation studies of the 1980s are in large part responsible for the renaissance of interest in the study of human myopia that the field currently enjoys. To date, the interpretation of tonic accommodation data has been that the variability in tonic accommodation and its adaptation reflects the differences in autonomic balance in the eye and therefore may play a role in the causation of refractive error. A theory connecting autonomic status and tonic accommodation describes tonic accommodation as the balance point between the sympathetic and parasympathetic components of accommodation.32

TABLE 6. Unbalanced Repeated Measures Multiple Regressions of Cohort Number (1991 through 1994), Time of Measurement, Refractive Error, and the Ocular Components on Tonic Accommodation Measured Under the Lit Empty-Field Test Condition Grade at Enrollment

Number of Subjects

1

430

3

6

Variable

Coefficient

SE

P

Refractive error Gullstrand lens power Lens refractive index

0.157 0.150 20.488

0.053 0.044 7.102

0.0030 0.0007 0.0039

182

Refractive error Gullstrand lens power

0.113 0.156

0.056 0.049

0.0450 0.0003

256

Anterior chamber depth Refractive error Gullstrand lens power

-0.645 0.092 0.092

0.299 0.047 0.047

0.0307 0.0477 0.0491

1058 TABLE

Zadnik et al.

7. Relative-Risk Tonic Accommodation and Onset of Juvenile Myopia for Children Enrolled in the OLSM

Grade Enrolled 1 1

3 6 6 1 or 3 1 or 3

IOVS, May 1999, Vol. 40, No. 6

Tonic Accommodation Test Condition

Number of Subjects

Lit empty field Dark field Lit empty field Lit empty field Dark field Lit empty field Dark field

491 174 217 70 558 384

667

Relative Risk 0.82(0.66, 0.95 (0.73, 0.81 (0.62, 0.72(0.48, 0.48(0.17, 0.90(0.75, 0.83(0.60,

1.01) 1.24) 1.04) 1.08) 1.35) 1.08) 1.14)

P

0.058 0.725 0.096 0.111 0.164 0.268 0.250

The grade in the table represents the grade at enrollment. All prevalent myopes were excluded from this analysis, and incident cases of myopia developed after the subject enrolled. Incident myopes were defined as those with at least —0.75 D of myopia on cycloplegic autorefraction in both meridians. Note: No baseline data are available for tonic accommodation tested under the dark-field test condition for children enrolled in the third grade in either 1989 or 1990. Values in parentheses are 95% confidence intervals.

Further connection between autonomic tone and refraction was proposed by van Alphen,33 who thought that centrally controlled ciliary muscle and choroidal tension could modify the effects of intraocular pressure and thus control refractive development. Little attention has been paid to the question of whether the differences in tonic accommodation by refractive error status are perhaps a consequence of refractive status rather than a cause of differences in refractive status. These data support the interpretation of tonic accommodation as either a concomitant change with or a consequence of refractive error, rather than as a cause. It seems that the relation between Gullstrand lens power and tonic accommodation (Tables 3, 4, 5) supports the idea that a particular crystalline lens anatomy, the flatter radii characteristic of myopia, is associated with a less myopic tonic accommodation level. Whereas van Alphen33 proposed that an increase in ciliary tension, assumed to be reflected in higher values of tonic accommodation, would be protective against the expansion of the eye, we propose that increased ciliary tension resulting from ocular expansion stretches and flattens the crystalline lens, producing lower levels of tonic accommodation. In support of this association of crystalline lens anatomy with tonic accommodation, crystalline lens thinning during the period in which children are susceptible to juvenile-onset myopia has been described.34 Loss in the power of the crystalline lens during the school years is associated with lens curvature flattening and a decrease in lensequivalent index.35 Mechanical forces on the lens resulting from equatorial growth that accompanies axial growth of the eye may explain these results. If these equatorial stretching forces in the larger, myopic eye increase ciliary tension on the crystalline lens, it is entirely conceivable that the lens will assume a less powerful position under open-loop conditions, producing lower tonic accommodation levels. The absence of any significant association between tonic accommodation and the risk of future myopia further supports the view that the lower levels of tonic accommodation seen in myopes are a consequence rather than a cause of juvenile-onset myopia. A report of tonic accommodation levels just before the inception of adult-onset myopia also found that low levels of tonic accommodation accompany, but do not precede, the onset of myopia.36 Another investigator reports high tonic accommodation in emmetropes who become myopes, but the small sample size, use of an inappropriate parametric statistic,

and failure to correct for multiple comparisons make this marginally significant result inconclusive at best.37 The differences between the two test conditions, especially the differences in the younger children, raise the question of which test condition represents "truth." We incorporated the dark-field test condition specifically to avoid some of the proximal effects inherent in the lit empty-field test condition, but inspection of the data in Tables 3 and 4 shows that both conditions explained variability in tonic accommodation by differences in refractive error and Gullstrand lens power. Perhaps the more rigorous, less contaminated dark-field test condition failed to capture important variance occurring with tonic accommodation and age in school-aged children. Studies in small samples of children in which various open-loop conditions are used could help sort out this question. The greater difference in tonic accommodation between methods in the younger subjects could be caused by the fixation smudge used to maintain accurate fixation in the first and second grade children. We think this is unlikely. The 8-year-olds (no smudge condition) were no different from the 6 year-olds (Fig. 2; smudge test condition). In Figure 3, the relation shown between tonic accommodation and refractive error is the same for 6- to 7-year-olds as for any other age group. Both of these points argue against the sudden removal of some contaminating factor after second grade (6- and 7-year-olds) that affected either the absolute value of tonic accommodation, its relation with refractive error, or our ability to evaluate it as a predictive factor for onset of myopia. In addition, the agerelated difference between the lit empty-field and the dark-field with fixation light test conditions persisted well beyond the 6and 7-year-old age groups in which the difference in test condition was not an issue. Accommodative adaptation is another potential confounding factor. Before measurement of tonic accommodation, children were wearing their habitual refractive error correction (or were not). Children are not monitored in the OLSM specifically for compliance with wear of their correction, although we have noted that children wear their glasses more sporadically than eye care practitioners might like to think. Some myopes had their correction on before testing, perhaps all morning. This would represent different numbers of hours depending on whether they were tested as ourfirstor last group of the school day. Others may have put their glasses on just before proceeding to the mobile clinic. Many moderate hyperopes have no

IOVS, May 1999, Vol. 40, No. 6 correction. Thus, the precise level of accommodative stimulus and therefore adaptation before testing is not known. Adaptation effects reported in children virtually eliminate the association between tonic accommodation and refractive error.9 This raises the question of whether the nonsignincance of tonic accommodation as a risk factor for the onset of myopia in children may be the result of adaptation effects. Three arguments may be made against this causal relation. First, obvious adaptation was eliminated when high initial tonic accommodation readings were discarded. Second, prolonged adaptation effects are measured in the laboratory during maintained open-loop conditions—that is, closing the eyes and maintaining a dark environment,9 extinguishing a lit target,3 or maintaining pinholes in Maxwellian view.38 It is not known how periods of closed-loop distance fixation may interrupt adaptation. Ebenholtz3 reported that distance fixation may be more powerful in creating adaptation, thereby reducing tonic accommodation, than near fixation may be in increasing tonic accommodation. The walk from the classroom to the testing session may serve as a "washout" period for adaptation effects. Finally, the finding of an association between tonic accommodation and refractive error by both methods argues against adaptation effects reducing our ability to detect different levels of tonic accommodation in children in whom myopia developed later. In summary, we found an association between tonic accommodation and refractive error. Myopes had the lowest values of tonic accommodation in both test conditions, and hyperopes had the highest values of tonic accommodation in the lit empty-field test condition. Tonic accommodation decreased with increasing age, especially when measured with the lit empty-field test condition. Tonic accommodation measured under the lit empty-field test condition was approximately 0.75 D greater than tonic accommodation measured under the dark-field test condition between the ages of 6 and 11 years. Multiple regression models using age, refractive error, and Gullstrand lens power accounted for little of the variance in tonic accommodation under the lit empty-field test condition and even less in tonic accommodation under the dark-field condition. Gullstrand lens power was the anatomic, ocular component most strongly associated with tonic accommodation. Tonic accommodation by either method failed to predict the onset of juvenile myopia. These data support the concept that tonic accommodation is probably a consequence of developing refractive error, rather than a cause.

Acknowledgment The authors thank Nina E. Friedman and Pamela A. Qualley, University of California, Berkeley School of Optometry, for their assistance, and Mark A. Bullimore, The Ohio State University College of Optometry, for advice.

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