Measurement of the ciliary body dimensions is not a routine practice in either clinical vision care or clinical vision research. In fact, this study may be the largest in vivo report of ciliary body dimensions in a pediatric sample. Because advances in biological imaging provided the means to collect these data, we were able to determine whether the ciliary body was thicker in myopic children.
The thickness of the ciliary body was measured at three locations. Thickness at the two most posterior locations (CBT2 and CBT3) correlated negatively with refractive error and positively correlated with axial length. Oliveira et al.
15 found very similar results in adults, with the strongest associations found between CBT2 and refractive error and axial length. The refractive error correlation coefficients in Oliveira et al. were higher than those found in our study (CBT2:
r = −0.64 in adults vs. −0.29 in children). A possible explanation for this difference in the strength of the association is that this was a cross-sectional sample of children who had not yet reached their final, adult refractive error status (i.e., some of the emmetropic children may still become myopic). If one examines the closed circles in
Figure 2 , it is apparent that some of the emmetropic data points are associated with CBT measurements that are similar to those in the myopic eyes. Are the emmetropic children with thick ciliary bodies in this cross-sectional sample prone to developing myopia in the future? The normal variation in CBT in emmetropic eyes is still unknown. The full meaning of these associations among CBT, refractive error, and axial length is also uncertain.
Where does this new association fit within the body of knowledge that describes the etiology of myopia? Is there something about the genetic or environmental factors that cause myopia that also leads to a thicker ciliary body? Can the process that makes the ciliary body thicker and/or the biomechanical effects of the thicker ciliary body itself lead to elongation of the globe? What portion of the ciliary body is thickened: the muscle, the stromal tissue, or both? Why is the tissue thickened? The answer to these questions will not be found in the data presented herein; much further investigation is needed.
Of course, it is possible that this new association has little relevance to myopia. Still, one might begin to speculate on the topic by considering what has been established in the field of myopia research. As discussed in the introduction of this report, the fact that the myopic eye is generally more prolate than the emmetropic eye is supported by several different studies in which different types of technology were used to measure the shape of the globe (ocular biometry and MRI) and different study designs (both cross-sectional and longitudinal).
1 2 3 The etiology of myopia, or the process that leads to this more prolate globe shape, is the element that is uncertain.
The prevailing theory regarding the etiology of juvenile-onset myopia is the hyperopic defocus model
(Fig. 4A) , and it is supported by a substantial body of work in animal models.
12 13 14 19 20 21 22 23 24 There are also human clinical studies demonstrating that children with myopia accommodate less accurately than children who do not have myopia.
25 26 27 If the hyperopic defocus model is an accurate depiction of the etiology of myopia, how would the enlarged ciliary body fit into this model? In the case of differential growth of the axial and transverse regions of the globe,
3 it is difficult to imagine how growth in the posterior pole alone would lead to a thicker ciliary body. In the scenario outlined in
Figure 4A , an abnormality of the ciliary muscle could be the source of accommodative lag (the “?” in
Fig. 4A ), leading to retinal defocus and axial elongation.
The causal relationship of accommodative dysfunction and myopia, the second arrow in
Figure 4A , is still questioned; the debate continues because there are conflicting reports on the temporal relationship between accommodative lag and the onset of myopia. Two smaller studies have found reduced accommodation before myopia onset,
28 29 while the larger, ethnically diverse CLEERE Study reports higher amounts of accommodative lag only after myopia onset.
27 Thus, the existing longitudinal data on myopia’s development in humans do not appear to unequivocally support the hyperopic defocus model
(Fig. 4A) .
In a 1995 publication, Gwiazda et al.
25 state that others have “questioned whether this accommodative abnormality was a cause or effect of myopia. Yet another possibility is that a common factor, as yet unidentified, accounts for both.” As stated earlier, CLEERE Study investigators have proposed that the crystalline lens could lead to a prolate globe shape through an internal, equatorial growth restriction.
1 While initial investigations into an association between crystalline lens tension and refractive error showed no relationship between the two (Bailey MD, et al.
IOVS. 2008;49:ARVO E-Abstract 3579 and manuscript in preparation), a thickened ciliary muscle may also serve as an internal equatorial growth restriction, and the “yet unidentified” factor that would lead to both accommodative lag and axial elongation in myopia
(Fig. 4B) .
The regions of the ciliary body that showed the strongest relationships with refractive error, axial length, and a more prolate globe shape, were the areas of the ciliary body that should primarily consist of ciliary muscle tissue, CBT2 and -3. Conversely, CBT1 would consist of a higher proportion of stromal tissue relative to CBT2 and CBT3. No association between CBT1 and refractive error was found, and weaker associations were found for CBT1 and axial length. Either the stromal tissue varies randomly in thickness at CBT1 and obscures associations between CBT and refractive error, or the quality of the image at this location leads to random error (discussed further later). Nonetheless, for the sake of argument, if one assumes the thickening of the ciliary body is due to a thickening of the ciliary muscle, an explanation of ciliary muscle hypertrophy could be considered. In hypertrophy of smooth muscle organs, the smooth muscle cells become enlarged and contract poorly.
30 A thickened, poorly contracting ciliary muscle could explain the accommodative abnormalities that are a hallmark of juvenile myopia.
The mechanism by which a thickened ciliary muscle would lead to both accommodative abnormalities and axial elongation
independently is not readily apparent. A thickened ciliary muscle does not seem to be a simple consequence of an elongated eye. Based on the choroidal expansion models of van Alphen,
16 one would expect the enlarged myopic globe to have a
thinner ciliary muscle. Perhaps the muscle thins initially, as van Alphen predicted, and then the ciliary body thickens as a later response in the process of myopia’s development. Alternatively, biochemical processes may underlie both muscle thickening and axial elongation simultaneously. The increased activation of MMP-2
31 that is known to lead to scleral remodeling in the tree shrew model of myopia is also expressed by ciliary muscle cells.
32 Increased activation of MMP-2 in the ciliary muscle, however, leads to a thickening of the ciliary body at the identical locations noted in the present study, CBT2 and -3, with the use of prostaglandin analogues.
33 A longitudinal study is necessary, to determine both the temporal relationship between ciliary body thickening and axial elongation and to determine whether van Alphen’s prediction of ciliary muscle thinning occurs at any point in the process. Thus, there are several reasons for continuing to investigate the relationships depicted in
Figure 4A . These data are also cause for investigating whether any changes occur in the ciliary body during experimentally induced myopia. The ciliary body appears to be thicker in human myopia. Is it also thicker in animal models of myopia?
It was impossible to determine with the OCT (Visante; Carl Zeiss Meditec) if the ciliary muscle is longer in myopic eyes than in nonmyopic eyes; the posterior attachment of the zonules was not visible. In globe expansion studies, van Alphen
16 found elongation of the ciliary muscle. If a longer ciliary muscle leads to elongation of the uvea, it could explain the axial elongation observed in myopia. In addition, hypertrophy in other smooth muscle tissues can lead to a process of fibrosis and excessive collagen deposition.
30 In the ciliary muscle, collagen fibers are known to “interweave with each other to form large and compact bundles [running] in a circular direction as the circular muscle.”
34 If hypertrophy of the ciliary muscle results in excessive deposition of collagen running in a circular orientation, the hypertrophic ciliary muscle may serve as an equatorial growth restriction, leading to uncompensated axial elongation.
1 Both of these possibilities are purely speculative and need further investigation.
When considering the implications of the findings of this study, its limitations should also be considered. The most important limitation is that the data were drawn from a clinical sample of convenience and may not be representative of the myopic condition as a whole. Collection of these data should be repeated in a nonclinical sample, in which myopic subjects at all stages of myopia progression can be measured.
One additional limitation of the present study was the repeatability of the CBT measurements and the minor variability in the examiner’s ability to choose the identical pixel coordinates for the scleral spur on repeated attempts. The SD for measurements of CBT at CBT2 for all subjects was 102 μm, but the between-visits coefficient of repeatability for CBT2 was similar in magnitude, 166 μm. In other words, these measurements were not optimally precise, as the variability across subjects was similar to that of the variability associated with repeated measurements. Determination of the ciliary pigmented epithelium boundary for the CBT1 thickness location was challenging because it was not very distinct in the image
(Fig. 1) . (Coincidentally, at the time of writing this report, Carl Zeiss Meditec released a software update for the Visante, version 2.0, that should assist in improving the quality of the images obtained. According to the manufacturer, Version 2.0 is expected to provide enhanced image quality “with image averaging and registration to provide even greater visual detail in anterior segment and corneal images.”)
An automated image analysis method using these new images is in development by the authors. In this program (MatLab; The MathWorks), a mean location for several selections of the scleral spur and an algorithm-derived measurement scheme is used to measure the dimensions of the ciliary body. Still, it is expected that researchers will have to use a mean of several measurements in research involving the ciliary body. There are no distinct landmarks for the alignment of the measurements, and minor rotational changes in eye position can affect the plane in which the image is acquired. An automated measurement method, however, should make the process of measuring the dimensions in multiple images for each subject more feasible.
In summary, this study documents the existence of a thicker ciliary body in children who are myopic compared to children who are not myopic. Further investigation is necessary to determine the meaning of this association, if any. Improvements in the precision of the CBT measurements made with the OCT (Visante; Carl Zeiss Meditec) are also needed.