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Corneal and Crystalline Lens Dimensions Before and After Myopia Onset

Mutti, Donald O.*; Mitchell, G. Lynn; Sinnott, Loraine T.; Jones-Jordan, Lisa A.§; Moeschberger, Melvin L.; Cotter, Susan A.; Kleinstein, Robert N.*; Manny, Ruth E.*; Twelker, J. Daniel*; Zadnik, Karla* The CLEERE Study Group

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Optometry and Vision Science: March 2012 - Volume 89 - Issue 3 - p 251-262
doi: 10.1097/OPX.0b013e3182418213
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Abstract

The optical and structural development of the major dioptric components of the eye, the cornea and crystalline lens, has been well documented from infancy through childhood. The cornea displays little difference as a function of age despite its importance as two thirds of the dioptric power of the eye. At 47 to 48 D, average corneal power is greater in infants than in children or adults for a relatively brief period,13 and then by age 3 to 9 months, it reaches values of 43 to 44 D that remain stable throughout childhood.47 The crystalline lens undergoes more substantial age-related changes in several parameters over a longer period of time. The anterior surface radius of curvature averages 7.2 mm in early infancy and then flattens by some 4.5 mm to reach 11 to 12 mm by age 14 years.4,8,9 The posterior surface follows a similar time course, with radii in infancy averaging 4.7 mm, flattening to 6 to 7 mm by age 14 years.4,8,9 Flattening radii of curvature over time contribute to an overall loss in equivalent power of about 18 to 19 D; the average crystalline lens power of 41 D in infancy becomes about 22 to 23 D by age 14 years.46,9 This power loss from flattening radii of curvature is facilitated by an accompanying decrease in the lens equivalent refractive index (IND) for much of infancy and early childhood. An IND of 1.45 in early infancy drops to 1.43 to 1.42 by age 10 years, responsible for nearly one-half the decrease in crystalline lens equivalent power.46 After age 10 years, lens refractive index appears to be stable on average in white and Asian children, continues to decrease in Native Americans, but switches direction to increase in black and Hispanic children.6 Lens thickness also decreases in infancy and early childhood from an average of 3.7 to 4.0 mm in infancy to 3.4 to 3.5 mm at age 10 years.47,10,11 Except for one report in Tibetan children,9 lens thinning reverses direction to become lens thickening after the age of 10 to 13 years in most ethnic groups.6,7,12 The substantial decreases in crystalline lens power that take place with age are counterbalanced by a vitreous chamber depth (VCD), which elongates from 10 to 11 mm at birth to become 16 and 17 mm by age 14 years.57,911

Precise balance between corneal and lenticular refractive power and the length of the eye should result in a stable refractive state. The ocular components that are in balance in emmetropia are obviously out of balance in myopia: the eye is too long for the optical power of the cornea and crystalline lens. Understanding the temporal pattern of how this imbalance develops requires data both before and after the onset of myopia. Numerous studies have documented average values by age for myopic and emmetropic individuals,1317 longitudinal studies have reported change in ocular components as a function of age,5,7,18 but the behavior of the optical ocular components before and after the onset of myopia has not been reported in detail. One longitudinal study compared children at their last emmetropic visit before myopia onset to children who remained emmetropic. The average corneal power of the children who became myopic was about 0.8 D greater, and there were no differences in lens thickness or power compared with those who remained emmetropic19; however, this study provided data at only one point in time before myopia onset. The purpose of this article is to document the temporal development of corneal power and several crystalline lens parameters (thickness, equivalent power, radii of curvature, and refractive index) across the years before, during, and after myopia onset in comparison with age-matched emmetropic values.

METHODS

Subjects were children aged 6 to 14 years participating between 1989 and 2007 in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study, a cohort study of ocular component development and risk factors for the onset of myopia in children of various ethnicities. The CLEERE Study is an extension of the Orinda Longitudinal Study of Myopia, begun in 1989 in the predominantly white community of Orinda, CA. To improve generalizability with respect to ethnicity, four additional clinic sites were added to recruit predominantly black children (Eutaw, AL), Asian children (Irvine, CA), and Hispanic children (Houston, TX). Testing of Native-American children began in Tucson, AZ, in 2000. Each affiliated university's institutional review board (University of California, Berkeley; The Ohio State University; University of Alabama at Birmingham; Southern California College of Optometry; University of Houston; and University of Arizona) approved informed consent documents according to the tenets of the Declaration of Helsinki. Parents provided consent and children assent before the children were examined.

Ethnic group designation was determined after completion of a medical history form by a parent. Parents selected one of the following six ethnic designations: (corresponding to the categories used by the National Institutes of Health as of 1997 when ethnic data were first gathered): American Indian or Alaskan Native; Asian or Pacific Islander; Black or African American not of Hispanic origin; Hispanic; white not of Hispanic origin; other, or unknown. Ethnicity was assigned to the target ethnic group for the given site when parents provided more than one ethnic designation that included the site's targeted ethnicity (1.7% of subjects). If parents provided more than one ethnic designation and neither included the site's targeted designation, ethnicity was assigned to the non-white ethnic designation. Any missing parent-reported ethnicity was filled in from investigator observation (5.7% of subjects). Investigator observation shows excellent agreement with parent-reported ethnicity.20 There were 4929 children enrolled in CLEERE between 1989 and 2007 and 1110 of these were myopic on at least one visit. Of these, 371 children met the myopia criterion (at least −0.75 D in each principal meridian by cycloplegic autorefraction) on the first visit and were not considered further in the analysis. This criterion level for myopia was chosen because it is beyond the measurement error of the autorefractors used to measure refractive error, it is likely to create symptoms of distance blur, and it is typically of a magnitude considered significant and worthy of correction by clinicians. Of the remaining 739, there were seven children with an ethnic designation of other who were excluded, leaving 732 myopic children for analysis (56% female, 23% Asian, 14% black, 29% Hispanic, 9% Native American, and 25% white). There were 596 emmetropic children who were between −0.25 and +1.00 D (exclusive) in each meridian at all study visits by cycloplegic autorefraction (46% female, 9% Asian, 19% black, 18% Hispanic, 17% Native American, and 37% white). The remaining children were either hyperopic, had simple hyperopic or myopic astigmatism, or were mixed astigmats on at least one visit and were not analyzed (n = 3223). Although the number excluded was large, the inclusion criteria were strict so that clearer contrasts might be drawn between two distinct and unambiguous groups.

Trained and certified examiners measured central refractive error using the Canon R-1 auto-refractor (Canon, Lake Success, NY; no longer manufactured) between 1989 and 2000 and using the Grand Seiko WR 5100-K auto-refractor in 2001 to 2007 (Grand Seiko Co., Hiroshima, Japan). Subjects were tested after mydriasis and cycloplegia. When subjects had an iris color of grade 1 or 2,21 testing was done 30 min after 1 drop of proparacaine 0.5% and 2 drops of tropicamide 1%. When subjects had an iris color darker than grade 2, testing was done 30 min after 1 drop of proparacaine 0.5% and 1 drop each of tropicamide 1% and cyclopentolate 1%.22 The protocol for crystalline lens measurement has been described in detail previously.8 Briefly, two pairs of Purkinje images were produced by a collimated dual fiber optic light source reflecting from the anterior and posterior surfaces of the crystalline lens. The separation of each pair of images is proportional to the radius of curvature in air. These radii in air were converted to radii in the eye, including an individual IND, by an iterative process to produce agreement between the measured Purkinje images, the remaining ocular components, and the subject's refractive error. The individual refractive index and lens radii of curvature were used to calculate the equivalent power of the crystalline lens. The Gullstrand-Emsley value for lens refractive index (1.416) was used with the radii of curvature to calculate a Gullstrand-Emsley crystalline lens power (GLP), one that would serve as a composite representing general lens shape. Corneal power was measured using the Alcon Auto-Keratometer (Alcon Systems, St. Louis, MO). Axial ocular dimensions were measured by A-scan ultrasonography (Model 820, Humphrey Instruments, San Leandro, CA), consisting of five readings using a hand-held probe on semi-automatic mode.

Emmetrope Models

Separate growth curves for each ocular component were constructed for emmetropes as a function of age according to the best fitting models defined by the Akaike Information Criterion.23 Gender and ethnicity and the interaction between ethnicity and age, first without VCD and then with VCD, were subsequently included in the models when appropriate using SAS mixed analysis of variance modeling with repeated measures (version 9.1, SAS Institute, Cary, NC).

Age-, Gender-, and Ethnicity-Matched Emmetropic Values

To be included in the “became myopic” group, a subject had to be non-myopic on at least one visit before a myopic visit (myopia defined as at least −0.75 D in each principal meridian). The year the “became myopic” subject first met the myopia criterion was defined as year 0, the year of onset. The first study year before onset was −1, 2 years prior was −2, and so forth out to −5 years before onset. Each study year after onset for a given subject was designated as +1, +2, and so forth out to +5. The age, gender, and ethnicity of each individual “became myopic” subject at each study visit were applied to each component's emmetrope regression equation. This provided an age-, gender-, and ethnicity-matched emmetropic value of each ocular variable for every “became myopic” data point. Results are presented first as the age-, gender-, and ethnicity-matched emmetrope base model values and then are presented with VCD added to the base emmetrope model to account for the estimated effects of the longer became-myopic VCD. In this analysis, the age, gender, ethnicity, and VCD of each individual “became myopic” subject at each study visit was applied to each component's emmetrope regression equation that included a VCD term. These results provided an age-, gender-, ethnicity-, and VCD-matched emmetrope value to compare with became-myopic data. This adjustment is needed because became-myopic eyes will eventually become on the order of 1 mm longer than emmetrope eyes and VCD is correlated with the ocular components being analyzed.15,2427 This adjustment was not applied to data for corneal power because unlike all other components, corneal power showed no significant within-subject longitudinal correlation with VCD (corneal within-subject correlation = −0.07 vs. between-subject correlation = −0.75). All other component variables showed good concordance for between- and within-subject correlations (between-subject range: −0.25 for refractive index to −0.58 for calculated lens power; within-subject range: −0.15 for refractive index to −0.38 for calculated lens power). If an imbalance in more familiar variables such as age or gender were to occur between groups and these variables were also correlated with outcome variables of interest, then statistical adjustment for these imbalanced variables would be a standard treatment of data to make valid comparisons. In this case, the adjustment for VCD allows one to compare the expected value of an ocular component of a myope to that of an emmetrope with the same VCD as the myope.

The value of this statistical adjustment for VCD is illustrated in the following example. Consider two bands that are stretched and appear to lengthen at the same rate. It might be the case that the two bands show similar lengthening because the forces acting on them and their elastic properties are equal. However, it might be the case that their apparent equality conceals a greater force being applied to one in combination with a greater intrinsic resistance. The difference in VCD between emmetropes and became-myopic children is analogous to the difference in stretching force in this example. The purpose of adding VCD to the emmetrope age, gender, and ethnicity base model is to adjust for the influence of various eye sizes, whether the influence is based in stretch or from any source. This procedure removes differences in component values that are merely due to statistically predictable differences in VCD. Putting component values on a equal footing for VCD (equal force applied in this analogy) allows for a more direct comparison of the underlying differences in the behavior (resistance properties in this analogy) of the crystalline lens during the process of becoming myopic. This approach is reminiscent of van Alphen24 use of partial correlation when he described his size factor S and stretch factor P.

Mixed modeling was then used to compare the mean difference between “became myopic” data and these emmetrope base model values as a function of study visit for each ocular variable. Throughout the following text, became myopic refers to the data from children in that category and emmetrope refers to the values estimated from the model derived from emmetropic children's data. The number of became-myopic children at each study visit are given in Table 1 along with the sample average for the spherical component of refractive error [minus cylinder notation where sphere is the most hyperopic (least myopic) meridian]. A significance level of p < 0.01 was used in consideration of the large sample size. This level of adjustment is somewhat arbitrary but represents a compromise between filtering out false positive findings while allowing small differences to reach significance.

TABLE 1
TABLE 1:
Number of became-myopic subjects and average refractive error (spherical component in minus cylinder notation) at each study visit

RESULTS

Fig. 1A displays the average corneal power of became-myopic children compared with emmetropes as a function of years relative to the onset of myopia. No adjustment was made for VCD because corneal power did not show significant within-subject correlation with change in VCD over time. Emmetropes had a consistent average corneal power of about 43.50 D and became-myopic children averaged about 43.75 D across these years. The difference in corneal power between became-myopic children and emmetropes was significant in every year from −5 and +4. Became-myopic children had steeper corneal powers yet this difference was always very small at under 0.25 D with no significant change across visits (Fig. 1B).

FIGURE 1
FIGURE 1:
Corneal power as a function of annual visit relative to the onset of myopia (−5 years before to +5 years after, with onset designated as year 0). (A) Data are shown for became-myopic children ([Black Square]) and emmetropes (○). Error bars are 95% confidence intervals. (B) The difference between became-myopic and emmetrope data unadjusted for VCD. *Significant differences between became-myopic and emmetropic children (i.e., the difference between groups is significant relative to a value of 0).

Fig. 2A displays the average lens thickness of became-myopic children compared with emmetropes as a function of years relative to the onset of myopia. Without adjusting for VCD, became-myopic children had thinner lenses in each year and a larger amount of lens thinning compared with emmetropes, a decrease of about 0.10 mm across years −5 to +5. The impact of adjusting for the correlation between VCD and lens thickness (and each ocular component that follows) can be seen in the differences between the emmetrope results presented with the dashed lines compared with the solid lines. Adjusting for VCD indicates that if emmetropic eyes were as long as the became-myopic eyes, lens thickness of emmetropes would have decreased by about 0.26 mm between years −5 and +5 (Fig. 2A, open symbols, solid line). The pattern of difference in lens thickness was distinct from corneal power. There were no significant differences in lens thickness between became-myopic children and VCD-adjusted emmetropes in years −5 through −2. The first significant year was −1 with much larger and significant differences to follow in years 0 through +5 (Fig. 2B).

FIGURE 2
FIGURE 2:
Lens thickness in the became-myopic and emmetrope groups (A). The dashed lines represent emmetrope values unadjusted for VCD and the solid lines are following adjustment for VCD. Error bars are 95% confidence intervals. The difference in lens thickness between became-myopic children and emmetropes adjusted for VCD are shown in (B). Symbols are as inFig. 1.

Fig. 3A displays the average calculated equivalent crystalline lens power (CLP) of became-myopic children compared with emmetropes. Without adjusting for VCD, became-myopic children had lower average values than emmetropes for CLP by about 0.50 to 0.75 D in every year but −5, +3, and +5. Each group decreased in CLP by 1.0 to 1.25 D across years −5 to +5. Adjusting for VCD indicates that if emmetropic eyes were as long as the became-myopic eyes, the CLP of emmetropes would have decreased by about 4 D between years −5 and +5 (Fig. 3A, open symbols, solid line). The pattern of difference in CLP was similar to that for lens thickness. There were no significant differences in CLP between became-myopic children and VCD-adjusted emmetropes in years −5 through −1. The first significant year was 0 with increasing differences of 1 to 2 D in years 0 through +5 (Fig. 3B).

FIGURE 3
FIGURE 3:
Calculated lens equivalent power in the became-myopic and emmetrope groups (A); difference in calculated lens equivalent power between became-myopic children and emmetropes adjusted for VCD (B). Symbols are as inFig. 1.

Fig. 4A displays the average GLP of became-myopic children compared with emmetropes. Without adjusting for VCD, became-myopic children had lower (flatter) average values than emmetropes for GLP by about 0.3 to 0.6 D in every year but −5. Each group decreased in GLP by about 0.75 D across years −5 to +5. Adjusting for VCD indicates that if emmetropic eyes were as long as the became-myopic eyes, the GLP of emmetropes would have decreased by about 1.75 D between years −5 and +5 (Fig. 4A, open symbols, solid line). The pattern of difference in GLP was again similar to that for lens thickness. There were no significant differences in GLP between became-myopic children and VCD-adjusted emmetropes in years −5 through −2. The first significant year was −1 where GLP was actually lower, flatter in became-myopic children. The difference then changed in sign to become significantly greater, steeper by 0.1 to 0.9 D in years +1 through +5 (Fig. 4B).

FIGURE 4
FIGURE 4:
GLP in the became-myopic and emmetrope groups (A); difference in GLP between became-myopic children and emmetropes adjusted for VCD (B). Symbols are as inFig. 1.

Fig. 5A displays the average crystalline lens IND of became-myopic children compared with emmetropes. With no adjustment for VCD, the IND for became-myopic children tended to remain in a narrow range of ±0.001 whereas IND for emmetropes decreased by about 0.003. As a result, became-myopic children had lower average values than emmetropes for IND by about 0.001 to 0.002 before onset in years −4 and −2, but a higher average value by about 0.001 at onset in year 0. Accounting for VCD indicates that if emmetropic eyes were as long as the became-myopic eyes, the IND of emmetropes would have decreased by about 0.007 between years −5 and +5 (Fig. 5A, open symbols, solid line). The pattern of difference in IND was again similar to that for lens thickness. There were no significant differences in IND between became-myopic children and VCD-adjusted emmetropes in years −5 through −1. The first significant year was in onset year 0 where IND was higher in became-myopic children by about 0.003. The difference was consistent and significant in years +1 through +5 (Fig. 5B).

FIGURE 5
FIGURE 5:
Crystalline lens IND in the became-myopic and emmetrope groups (A); difference in calculated lens IND between became-myopic children and emmetropes adjusted for VCD (B). Symbols are as inFig. 1.

The results in Figs. 2B to 5B suggest that the crystalline lens does not change in the same manner in response to vitreous chamber elongation after myopia onset as it does before onset. The temporal pattern indicates a substantial inhibition of lens thinning, flattening, and power loss either 1 year before or in the year of myopia onset. Cubic multilevel growth curves were fitted for lens thickness unadjusted for VCD as a function of age and refractive error group to explore this behavior, as reported in previous studies (Fig. 6).7,17 The myopic refractive error group was further subdivided into three different ages of onset: ≤10 years, 10 years to ≤ 12 years, and >12 years. The growth curves indicate thinner lenses for myopes then observed in emmetropes at all ages. At their minimum lens thicknesses, the myopia onset age groups were significantly thinner than emmetropes by 0.04 to 0.05 mm (Table 2; p = 0.0003). The age of minimum lens thickness was also significantly later as the age of myopia onset increased. The age of minimum lens thickness was 0.60 years sooner in the earliest onset group and 0.78 years later in the latest onset group compared with the middle onset group (p = 0.01 for each).

FIGURE 6
FIGURE 6:
Cubic multilevel growth curves for lens thickness as a function of age and three age of myopia onset groups (≤10 years, 10 years to ≤12 years, and >12 years). The growth curves for myopes indicate thinner lenses at all ages with later ages of minimum lens thickness the older the age of onset.
TABLE 2
TABLE 2:
Minimum lens thickness and the age when minimum lens thickness is reached as a function of refractive error group and age of onset of myopia

Ethnicity

The differences between values in became-myopic children and age-, gender-, and ethnicity-matched VCD-adjusted emmetropes (Figs. 1B to 5B) are plotted for each ocular component variable as a function of ethnicity in Fig. 7 (no VCD adjustment for corneal power). Corneal power was not different between became-myopic children and emmetropes in any study year for black, Asian-American, or Native American children. The greater corneal power in became-myopic children was only significant in Hispanics before and at onset and in whites at all visits except +4. Ethnic groups tended to follow a similar trajectory of development across the years before and after onset. Similar to the sample as a whole, differences between became-myopic children and emmetropes generally appeared within ±1 year of onset. One exception was black children whose average lens thickness and GLP were not significantly different between became-myopic children and emmetropes in any year. Black became-myopic children also had the greatest differences in IND of any ethnic group. The pattern for black children for CLP and IND was more of a steady increase in differences between became-myopic and emmetrope children rather than more distinct, abrupt before and after myopia onset differences. Another exception was that lens IND was not significantly different between Native American became-myopic and emmetrope children in any study year.

FIGURE 7
FIGURE 7:
Ocular component differences between became-myopic and emmetrope groups as a function of visit relative to the onset of myopia and ethnicity. Error was similar between ethnic groups. Representative error bars (±95% confidence intervals) are included for Asians only for clarity.

Gender

The differences between values in became-myopic children and age-, gender-, and ethnicity-matched VCD-adjusted emmetropes (Figs. 1B to 5B) are plotted for each ocular component variable as a function of gender in Fig. 8 (no VCD adjustment for corneal power). Results for boys and girls follow each other closely with overlapping 95% confidence intervals for most ocular components, this despite girls tending to have smaller eyes and steeper, more powerful optical component values.6 The one exception was lens thickness, where after onset, from visits +1 through +5, the difference in lens thickness between emmetropic and became-myopic girls was significantly greater (with higher positive differences) than the difference between emmetropic and became-myopic boys.

FIGURE 8
FIGURE 8:
Ocular component differences between became-myopic and emmetrope groups as a function of visit relative to the onset of myopia and gender. Error bars are ±95% confidence intervals.

DISCUSSION

Results before myopia onset indicate that the normal development of the crystalline lens is characterized by thinning, flattening, and decreasing power to maintain emmetropia. These correlations, in place since infancy,4 maintain a balance between focal length and an axial length that will increase on average by about 3.0 mm between the ages of 9 months and 9 years.6 This balance is achieved through a decrease in lens power of over 15.0 D and virtually no change in corneal power.4,6 The influence of the cornea also seemed secondary to that of the crystalline lens with respect to myopia onset. The dioptric difference in became-myopic children relative to emmetropes was minor at under 0.25 D. Corneal powers never changed substantially in either group despite continued eye growth. This finding is consistent with the general stability of corneal power in childhood reported in the literature.9,2730 In contrast, the crystalline lens underwent far more change in became-myopic children in lens thickness, CLP, and GLP before myopia onset than after. Following van Alphen ideas,24 we have proposed that this correlation occurs through stretch from the physical connection between the distensible crystalline lens and the growing eye. Evidence for this stretch process can be found in the thinning of the crystalline lens despite its increasing wet weight31 and the lack of a 1:1 relationship between CLP loss and axial growth.4 A relationship closer to 1:1 would indicate that axial growth tracks CLP loss through defocus rather than that the growing eye stretches the crystalline lens. The relationship in infants was found to be about half this 1:1 ratio.4

The behavior of the crystalline lens before and after myopia onset indicates that the previously correlated, compensating response of the crystalline lens is interrupted at myopia onset. Optically, this result is axiomatic; myopia would be impossible if the crystalline lens and axial length always changed in tandem. Yet myopia is almost always thought of first as excessive length. These results suggest that while excessive growth is important, growth only becomes myopic when an independence develops between the anterior segment (crystalline lens) and posterior segment (axial growth). For the sample as a whole, for each ethnic group (with the possible exception of blacks), and for each gender (with girls showing a greater effect for lens thickness), this independence appeared at onset or within a year of onset. The crystalline lens ceased to thin, flatten, and lose power even as the eye continued to grow. It is noteworthy that despite differences in myopia prevalence between ethnicities, there appears to be some consistency in this process for most ethnic groups.

The predictable effects of defocus on ocular growth in animal models suggest that any sudden increase in axial growth that was independent of the crystalline lens might be caused by sudden exposure to defocus.3235 The source of this defocus could be from either accommodative lag at the fovea, peripheral hyperopic defocus from a relatively prolate ocular shape, or a combination of the two factors. One study has reported exposures to increased accommodative lag 2 years before myopia onset.36 In contrast to those findings, myopic subjects in CLEERE showed a greater accommodative lag compared with emmetropes beginning 1 year after the onset of myopia for the sample as a whole or at onset in subjects wearing a refractive correction.37 Exposure to peripheral defocus is perhaps a better match to crystalline lens results in terms of years relative to onset; on average, subjects in CLEERE were first exposed to relative peripheral hyperopia 1 year before onset.38 Despite this general concordance in time between exposure to defocus and myopia onset, neither accommodative lag at the fovea nor relative peripheral hyperopia have been found to be associated with the risk of myopia onset in children or its rate of progression.37,3941 These negative results notwithstanding, it is possible that peripheral defocus could influence the growth of the eye considering that clinical trials of contact lens and spectacle treatments designed to alter peripheral defocus have shown some beneficial preliminary results in slowing myopia progression.4245 These clinical trial results should be interpreted with caution, however, because the effects are small and sometimes only seen in selected subgroups.44 Nonetheless, the lack of a robust association between defocus and human ocular growth argue against sudden exposure to lag or peripheral hyperopia as a cause of myopic eye growth that is uncompensated by the crystalline lens.

This independence between axial growth and the crystalline lens at myopia onset might be due to cessation of peripheral scleral growth. If the ocular periphery did not grow, the lens might be less likely to stretch and therefore to thin, flatten, and lose power. Animal models suggest that central and peripheral development can be independent46; however, the current thinking from primate studies is that peripheral growth may help to regulate foveal refractive error.4749 Evidence from children at 30° in the temporal retinal periphery suggests that the midperiphery grows both before and after myopia onset, although at different rates compared with axial growth.38 More eccentric peripheral retinal loci nearer the equator, however, do show some evidence of a markedly reduced rate of growth after myopia onset. One of the noteworthy features of magnetic resonance imaging data from Atchison et al.50 is the lack of expansion of the far peripheral height and width of the eye as a function of degree of myopia compared with axial lengthening. These results are similar to recent magnetic resonance imaging data from Singaporean Chinese children showing smaller far peripheral widths relative to axial length in myopes, whereas emmetropes had more symmetric globes.51 Physiologic inhibition of equatorial growth appears unlikely as both anterior retinal growth and ocular expansion are stimulated, not inhibited, by form deprivation in chick and primate models.52,53

If a mechanical process such as crystalline lens stretch underlies the maintenance of emmetropia, then interruption of stretch could be responsible for the abrupt independence between anterior and posterior segment development at myopia onset. Myopic eyes might display thinner lenses compared with emmetropes and, if stretch is inhibited near the onset of myopia, children with later ages of myopia onset might display minima in lens thickness at later ages. Both of these predictions are borne out in the data presented in Fig. 6. Some possible sources of mechanical inhibition are external, such as the size of the orbit or extraocular muscle tension. We have argued against external sources based on the lack of monotonicity in the change in relative peripheral refraction mentioned above.38 In addition, there is an acceleration in the rate of change in refractive error, axial length, and relative peripheral refraction at myopia onset that argues against the steady application of an external restricting force near the equator.38 One proposed internal source of equatorial restriction was resistance of the crystalline lens to continued stretch; however, in vitro stretching studies indicate that the crystalline lens has an extensive capacity for stretch.54 In addition, there was no evidence of excess tension on the crystalline lens in myopes; postsaccadic crystalline lens oscillations were unrelated to refractive error.55 Day et al.56 found that mid- and high-frequency microfluctuations during accommodation were increased in late-onset myopes compared with emmetropes, possibly from accommodative plant noise, but poorer neurologic control and increased blur threshold were other possible sources. Therefore no clear line of evidence points to the crystalline lens itself as a source of internal tension.

The ciliary muscle is a potential candidate source of internal equatorial restriction. Although a recent study indicated that there was no correlation between axial length and ciliary muscle thickness,57 the authors argued that the equally thick but longer ciliary muscles found in longer eyes indicates that the ciliary muscle probably adds tissue as the eye grows. This normal ciliary muscle growth may accelerate as eyes become myopic. Another recent study has shown that the ciliary muscle is thicker in myopic children.58 Schultz et al.55 speculated that the increased thickness of the ciliary muscle in myopes suppressed the effect of the arterial pulse on the high frequency component of accommodative microfluctuations. The abnormally thick ciliary muscle for a given axial length in myopia may provide the mechanical restriction that would interfere with the equatorial expansion needed to maintain the correlation between ocular growth and optical compensation by the crystalline lens. Anterior mechanical restriction may limit far peripheral expansion, resulting in the relatively more prolate ocular shapes found in myopic eyes.50,51 Alterations in ciliary muscle might also explain the increase in the response AC/A ratio before the onset of myopia.59,60 Longitudinal observation of the ciliary muscle along with complete ocular biometry before and after the onset of myopia in children would be needed to confirm these speculations.

In summary, the process of becoming myopic appears to be more than just one of excess axial elongation. The myopic eye is certainly elongated relative to the emmetropic eye, but the elongation is accompanied at myopia onset by an abrupt independence between axial growth and longstanding, compensatory optical changes in the crystalline lens likely in place from infancy up to the time of myopia onset. At onset and for at least the following 5 years, VCD-adjusted lens parameters stopped thinning, flattening, and losing power in children who became myopic compared with children who remained emmetropic. The stability of corneal power suggests that it is unrelated to this process. Future studies should seek to determine the source of this departure from correlated growth that characterizes myopia onset.

Donald O. Mutti

The Ohio State University College of Optometry

338 West Tenth Avenue

Columbus, Ohio 43210-1240

e-mail: mutti.2@osu.edu

REFERENCES

1. Inagaki Y. The rapid change of corneal curvature in the neonatal period and infancy. Arch Ophthalmol 1986;104:1026–7.
2. Insler MS, Cooper HD, May SE, Donzis PB. Analysis of corneal thickness and corneal curvature in infants. CLAO J 1987;13:182–4.
3. Blomdahl S. Ultrasonic measurements of the eye in the newborn infant. Acta Ophthalmol 1979;57:1048–56.
4. Mutti DO, Mitchell GL, Jones LA, Friedman NE, Frane SL, Lin WK, Moeschberger ML, Zadnik K. Axial growth and changes in lenticular and corneal power during emmetropization in infants. Invest Ophthalmol Vis Sci 2005;46:3074–80.
5. Jones LA, Mitchell GL, Mutti DO, Hayes JR, Moeschberger ML, Zadnik K. Comparison of ocular component growth curves among refractive error groups in children. Invest Ophthalmol Vis Sci 2005;46:2317–27.
6. Twelker JD, Mitchell GL, Messer DH, Bhakta R, Jones LA, Mutti DO, Cotter SA, Klenstein RN, Manny RE, Zadnik K. Children's ocular components and age, gender, and ethnicity. Optom Vis Sci 2009;86:918–35.
7. Wong HB, Machin D, Tan SB, Wong TY, Saw SM. Ocular component growth curves among Singaporean children with different refractive error status. Invest Ophthalmol Vis Sci 2010;51:1341–7.
8. Mutti DO, Zadnik K, Fusaro RE, Friedman NE, Sholtz RI, Adams AJ. Optical and structural development of the crystalline lens in childhood. Invest Ophthalmol Vis Sci 1998;39:120–33.
9. Garner LF, Yap MK, Kinnear RF, Frith MJ. Ocular dimensions and refraction in Tibetan children. Optom Vis Sci 1995;72:266–71.
10. Luyckx J. [Measurement of the optic components of the eye of the newborn by ultrasonic echography]. Arch Ophtalmol Rev Gen Ophtalmol 1966;26:159–70.
11. Larsen JS. The sagittal growth of the eye. II. Ultrasonic measurement of the axial diameter of the lens and the anterior segment from birth to puberty. Acta Ophthalmol 1971;49:427–40.
12. Lin LL, Shih YF, Tsai CB, Chen CJ, Lee LA, Hung PT, Hou PK. Epidemiologic study of ocular refraction among schoolchildren in Taiwan in 1995. Optom Vis Sci 1999;76:275–81.
13. Sorsby A, Benjamin B, Davey JB, Sheridan M, Tanner JM. Emmetropia and its Aberrations. Medical Research Council, Special Report Series No. 293. London: Her Majesty's Stationery Office; 1957.
14. Garner LF, Yap M, Scott R. Crystalline lens power in myopia. Optom Vis Sci 1992;69:863–5.
15. Scott R, Grosvenor T. Structural model for emmetropic and myopic eyes. Ophthalmic Physiol Opt 1993;13:41–7.
16. McBrien NA, Adams DW. A longitudinal investigation of adult-onset and adult-progression of myopia in an occupational group. Refractive and biometric findings. Invest Ophthalmol Vis Sci 1997;38:321–33.
17. Shih YF, Chiang TH, Lin LL. Lens thickness changes among schoolchildren in Taiwan. Invest Ophthalmol Vis Sci 2009;50:2637–44.
18. Garner LF, Stewart AW, Owens H, Kinnear RF, Frith MJ. The Nepal Longitudinal Study: biometric characteristics of developing eyes. Optom Vis Sci 2006;83:274–80.
19. Goss DA, Jackson TW. Clinical findings before the onset of myopia in youth. I. Ocular optical components. Optom Vis Sci 1995;72:870–8.
20. Jones LA, Mitchell GL, Zadnik K; The CLEERE Study Group. Agreement between parent-reported and clinician-assessed race in the CLEERE Study. Control Clin Trials 2001;22:98S.
21. Seddon JM, Sahagian CR, Glynn RJ, Sperduto RD, Gragoudas ES. Evaluation of an iris color classification system. The Eye Disorders Case-Control Study Group. Invest Ophthalmol Vis Sci 1990;31:1592–8.
22. Kleinstein RN, Mutti DO, Manny RE, Shin JA, Zadnik K. Cycloplegia in African-American children. Optom Vis Sci 1999;76:102–7.
23. Bozdogan H. Model selection and Akaike's Information Criterion (AIC): the general theory and its analytical extensions. Psychometrika 1987;52:345–70.
24. van Alphen GW. On emmetropia and ametropia. Opt Acta (Lond) 1961;142(Suppl):1–92.
25. Wong TY, Foster PJ, Johnson GJ, Klein BE, Seah SK. The relationship between ocular dimensions and refraction with adult stature: the Tanjong Pagar Survey. Invest Ophthalmol Vis Sci 2001;42:1237–42.
26. Olsen T, Arnarsson A, Sasaki H, Sasaki K, Jonasson F. On the ocular refractive components: the Reykjavik Eye Study. Acta Ophthalmol Scand 2007;85:361–6.
27. Ip JM, Huynh SC, Kifley A, Rose KA, Morgan IG, Varma R, Mitchell P. Variation of the contribution from axial length and other oculometric parameters to refraction by age and ethnicity. Invest Ophthalmol Vis Sci 2007;48:4846–53.
28. Garner LF, Kinnear RF, McKellar M, Klinger J, Hovander MS, Grosvenor T. Refraction and its components in Melanesian schoolchildren in Vanuatu. Am J Optom Physiol Opt 1988;65:182–9.
29. Goss DA, Jackson TW. Cross-sectional study of changes in the ocular components in school children. Appl Opt 1993;32:4169–73.
30. Walline JJ, Jones LA, Mutti DO, Zadnik K. A randomized trial of the effects of rigid contact lenses on myopia progression. Arch Ophthalmol 2004;122:1760–6.
31. Bours J, Fodisch HJ. Human fetal lens: wet and dry weight with increasing gestational age. Ophthalmic Res 1986;18:363–8.
32. Schaeffel F, Glasser A, Howland HC. Accommodation, refractive error and eye growth in chickens. Vision Res 1988;28:639–57.
33. Irving EL, Sivak JG, Callender MG. Refractive plasticity of the developing chick eye. Ophthalmic Physiol Opt 1992;12:448–56.
34. Wildsoet C, Wallman J. Choroidal and scleral mechanisms of compensation for spectacle lenses in chicks. Vision Res 1995;35:1175–94.
35. Smith EL III, Hung LF. The role of optical defocus in regulating refractive development in infant monkeys. Vision Res 1999;39:1415–35.
36. Gwiazda J, Thorn F, Held R. Accommodation, accommodative convergence, and response AC/A ratios before and at the onset of myopia in children. Optom Vis Sci 2005;82:273–8.
37. Mutti DO, Mitchell GL, Hayes JR, Jones LA, Moeschberger ML, Cotter SA, Kleinstein RN, Manny RE, Twelker JD, Zadnik K. Accommodative lag before and after the onset of myopia. Invest Ophthalmol Vis Sci 2006;47:837–46.
38. Mutti DO, Hayes JR, Mitchell GL, Jones LA, Moeschberger ML, Cotter SA, Kleinstein RN, Manny RE, Twelker JD, Zadnik K. Refractive error, axial length, and relative peripheral refractive error before and after the onset of myopia. Invest Ophthalmol Vis Sci 2007;48:2510–9.
39. Mutti DO, Sinnott LT, Mitchell GL, Jones-Jordan LA, Moeschberger ML, Cotter SA, Kleinstein RN, Manny RE, Twelker JD, Zadnik K; CLEERE Study Group. Relative peripheral refractive error and the risk of onset and progression of myopia in children. Invest Ophthalmol Vis Sci 2011;52:199–205.
40. Sng CC, Lin XY, Gazzard G, Chang B, Dirani M, Lim L, Selvaraj P, Ian K, Drobe B, Wong TY, Saw SM. Change in peripheral refraction over time in Singapore Chinese children. Invest Ophthalmol Vis Sci 2011;52:7880–7.
41. Berntsen DA, Sinnott LT, Mutti DO, Zadnik K. Accommodative lag and juvenile-onset myopia progression in children wearing refractive correction. Vision Res 2011;51:1039–46.
42. Cho P, Cheung SW, Edwards M. The longitudinal orthokeratology research in children (LORIC) in Hong Kong: a pilot study on refractive changes and myopic control. Curr Eye Res 2005;30:71–80.
43. Walline JJ, Jones LA, Sinnott LT. Corneal reshaping and myopia progression. Br J Ophthalmol 2009;93:1181–5.
44. Sankaridurg P, Donovan L, Varnas S, Ho A, Chen X, Martinez A, Fisher S, Lin Z, Smith EL III, Ge J, Holden B. Spectacle lenses designed to reduce progression of myopia: 12-month results. Optom Vis Sci 2010;87:631–41.
45. Anstice NS, Phillips JR. Effect of dual-focus soft contact lens wear on axial myopia progression in children. Ophthalmology 2011;118:1152–61.
46. Wildsoet CF, Pettigrew JD. Kainic acid-induced eye enlargement in chickens: differential effects on anterior and posterior segments. Invest Ophthalmol Vis Sci 1988;29:311–9.
47. Smith EL III, Hung LF, Huang J. Relative peripheral hyperopic defocus alters central refractive development in infant monkeys. Vision Res 2009;49:2386–92.
48. Smith EL III, Kee CS, Ramamirtham R, Qiao-Grider Y, Hung LF. Peripheral vision can influence eye growth and refractive development in infant monkeys. Invest Ophthalmol Vis Sci 2005;46:3965–72.
49. Smith EL III, Ramamirtham R, Qiao-Grider Y, Hung LF, Huang J, Kee CS, Coats D, Paysse E. Effects of foveal ablation on emmetropization and form-deprivation myopia. Invest Ophthalmol Vis Sci 2007;48:3914–22.
50. Atchison DA, Jones CE, Schmid KL, Pritchard N, Pope JM, Strugnell WE, Riley RA. Eye shape in emmetropia and myopia. Invest Ophthalmol Vis Sci 2004;45:3380–6.
51. Lim LS, Yang X, Gazzard G, Lin X, Sng C, Saw SM, Qiu A. Variations in eye volume, surface area, and shape with refractive error in young children by magnetic resonance imaging analysis. Invest Ophthalmol Vis Sci 2011;52:8878–83.
52. Fischer AJ, Reh TA. Identification of a proliferating marginal zone of retinal progenitors in postnatal chickens. Dev Biol 2000;220:197–210.
53. Tkatchenko AV, Walsh PA, Tkatchenko TV, Gustincich S, Raviola E. Form deprivation modulates retinal neurogenesis in primate experimental myopia. Proc Natl Acad Sci U S A 2006;103:4681–6.
54. Manns F, Parel JM, Denham D, Billotte C, Ziebarth N, Borja D, Fernandez V, Aly M, Arrieta E, Ho A, Holden B. Optomechanical response of human and monkey lenses in a lens stretcher. Invest Ophthalmol Vis Sci 2007;48:3260–8.
55. Schultz KE, Sinnott LT, Mutti DO, Bailey MD. Accommodative fluctuations, lens tension, and ciliary body thickness in children. Optom Vis Sci 2009;86:677–84.
56. Day M, Strang NC, Seidel D, Gray LS, Mallen EA. Refractive group differences in accommodation microfluctuations with changing accommodation stimulus. Ophthalmic Physiol Opt 2006;26:88–96.
57. Sheppard AL, Davies LN. In vivo analysis of ciliary muscle morphologic changes with accommodation and axial ametropia. Invest Ophthalmol Vis Sci 2010;51:6882–9.
58. Bailey MD, Sinnott LT, Mutti DO. Ciliary body thickness and refractive error in children. Invest Ophthalmol Vis Sci 2008;49:4353–60.
59. Gwiazda J, Grice K, Thorn F. Response AC/A ratios are elevated in myopic children. Ophthalmic Physiol Opt 1999;19:173–9.
60. Mutti DO, Jones LA, Moeschberger ML, Zadnik K. AC/A ratio, age, and refractive error in children. Invest Ophthalmol Vis Sci 2000;41:2469–78.
Keywords:

myopia; crystalline lens; cornea; refractive error

© 2012 American Academy of Optometry