Crystalline lens and refractive development
Introduction
The refractive status of the eye usually changes throughout life. Children are born with a mean spherical equivalent refraction in the moderate hyperopic range with a Gaussian distribution of refractions, and then move towards mild hyperopia with a narrower, leptokurtic distribution of refractions over the first year or two after birth. After this early stage, some children then progress in a myopic direction through an increased rate of axial elongation which is, at least in part, controlled by environmental exposures (Wallman and Winawer, 2004). This developmental phase may continue into the third decade after birth, when myopia prevalence reaches its maximum. During school years, many hyperopic children come to be emmetropic. After this, there is a slow shift in the hyperopic direction which may continue over several decades. This hyperopic shift with ageing can be disrupted by the formation of cataract which may lead to quite rapid and pronounced myopic shifts. Two early clinical cross-sectional studies which involved cycloplegia with atropine, characterized this change in refraction with age from birth to senescence (Brown, 1938, Slataper, 1950).
This pattern of change appears to be very general but has never been fully characterized with longitudinal data, because the study would inevitably last longer than the working life of most chief investigators and clinicians (except, perhaps, for the case of the 1958 British Cohort; Rahi et al., 2011). Another limitation of the existing literature is that much of the evidence is based on clinical samples, and has generally been measured without cycloplegia (except for the two early clinical studies mentioned above), even though it is generally recognized that the gold standard for measurement of refractive status requires cycloplegia, at least in children. This requirement may continue into adult life, since accommodation is powerful well until the ages of 40–50. As a result, some overestimation of myopia and major underestimation of hyperopia can occur (Fotouhi et al., 2012, Krantz et al., 2010, Morgan et al., 2014).
For this reason, we have chosen to illustrate the typical pattern of change in refractive status with data from the Tehran Eye Study (Hashemi et al., 2003, Hashemi et al., 2004), which involved a cross-sectional study of refraction using cycloplegia over a wide age range, from 5 to over 75 years of age. Three of the major developmental phases can be clearly seen. It should also be noted that while these data are cross-sectional, strong evidence of longitudinal change has been obtained for each of these phases (Fotedar et al., 2008, Gudmundsdottir et al., 2005, Wu et al., 2005, Lee et al., 2002, Saunders, 1986, Jones et al., 2005b, Mutti et al., 2005).
Fig. 1 of the above mentioned Tehran cross-sectional study shows a complex change with age (Hashemi et al., 2003, Hashemi et al., 2004). The conservative cut-off point for myopia or hyperopia at ±1 diopter (spherical equivalent) was chosen because most subjects with that amount of refractive error wear glasses on a permanent basis; a cut-off point of ±0.50 diopters would make the prevalence of refractive error appear much higher in comparison with this more conservative cut-off point. Myopia is rare at age 5 and increases steadily up to age 25 when it reaches its maximum prevalence of 18% (in this study under this cut-off point). Then myopia prevalence remains stable along adulthood up to age 70, when it increases again. In the meantime hyperopia is very frequent (50%) at age 5 and decreases steadily reaching a minimum (10%) at age 25, the same age when myopia reaches its maximum prevalence (possibly the age at which axial elongation stops). From then on the prevalence of hyperopia increases slowly during adult life, reaching a value of 50% at age 70, and from that age it decreases abruptly, by the same time as myopia prevalence increases.
These changes in the prevalence of refractive error in the Tehran Eye Study, if confirmed prospectively in a long prospective study, would mean that subjects are passing from one category to the other. This is seen many times in the clinic. Hyperopic school children become emmetropic during adolescence. Emmetropic children develop myopia during school and university years. Emmetropic young adults develop hyperopia during their 40–50's and cataract patients in their 70's lose their hyperopia or develop myopia (Duke-Elder and Abrams, 1970a, Saunders, 1984).
Section snippets
The ocular biometric components
From a clinical perspective, refractive status is the key parameter, because clinical correction of refractive error, whether with glasses, contact lenses, refractive surgery, or intraocular lenses, is the key to ensuring good visual acuity. However, from a biological perspective, the ocular components of refraction, specifically corneal and lens power, as well as anterior chamber depth, lens thickness and vitreous chamber depth are optically more important, since it is the balance between
Calculation of crystalline lens power
The crystalline lens power cannot be simply measured with a lensmeter since it is inside the eye. The same accounts for corneal power: usually only its anterior radius is measured, for example by a keratometer. The contribution of the posterior corneal power is assumed by an ideal index, which is calculated to obtain the power of the whole cornea only with the measured anterior radius and that ideal index (Olsen, 1986). Recently, using Scheimflug imaging it has been possible to measure the
Studies in preterm and full term infants
Cook et al. (2003) showed prospective changes in the ocular components of refraction in premature children (without retinopathy) from birth to 5 months of age, performing cycloplegic refractions. From the data in their published table (Cook et al., 2003), the crystalline lens power was calculated using Bennett's formula (Bennett, 1988). Fig. 3 shows how the lens power decreases steadily in premature infants from nearly 60 diopters at birth to 45 diopters by 5 months. Mutti et al. (2005)
Nicholas Brown and the lens paradox
The idea that changes in the internal power of the lens could have importance in refractive error began to gain acceptance in the 70's when Nicholas Brown described the “lens paradox” consisting of an increment in lens thickness with a steepening of the surface and internal curvatures of the ageing lens that would produce systematic myopia at adult ages in which hyperopia and presbyopia are the norm (Brown, 1974, Koretz and Handelman, 1988, Brown et al., 1999). He introduced Scheimpflug
The lens during early growth in chickens
Interestingly, the lens also loses power in growing chicken eyes. A recent re-analysis of the chick schematic eye model that was originally developed by Schaeffel and Howland (1988) showed that Bennett's equation could be used for calculation of lens power in chick eyes (Iribarren et al., 2012b, Iribarren et al., 2014a, Iribarren et al., 2014, Iribarren et al., 2014c). As the original data included refraction, biometry and lens radii measurements, the lens power and equivalent index could be
The shape and the power of the lens during childhood
Although there are studies reporting changes in lens thickness in babies and schoolchildren (Larsen, 1971, Jones et al., 2005b, Mutti et al., 2005, Shih et al., 2009, Wong et al., 2010) the literature shows less data on lens equatorial diameter growth as the lens equator is not visible in vivo by slit lamp observation because it is behind the iris, even after pupil dilation. Augusteyn (2010) has recently reviewed the data of lens equatorial growth. Duke-Elder and Abrams (1961) gave values for
Anterior segment growth
The analysis of the anterior segment growth can help understanding lens growth. The anterior segment growth has been measured by the increase in white to white corneal diameter (Ronneburger et al., 2006, Lagrèze and Zobor, 2007) and by the anterior segment distance from the corneal apex to the posterior pole of the lens (anterior segment length) (Larsen, 1971, Dubbelman et al., 2001, Koretz et al., 2004). It is well known that white to white diameter reaches adult values during the first year
Change in lens shape during childhood
How can the lens change from a rounded ellipsoidal shape in babies to a flatter one in adolescence? This change can be seen in Fig. 9, comparing a 3 month lens with a 14 year old lens (based on Mutti's and Zadnik's published data of curvature and thickness, Mutti et al., 1998, Mutti et al., 2005, Zadnik et al., 1995). The internal structure and the growth of the lens can give the clues for this change. As said, the nucleus of children has been shown to be compacted during school years according
The anterior segment in premature children
The growth of the anterior chamber in premature children is interesting. These small eyes of premature infants have shallower anterior chambers, thicker lenses, smaller anterior segment lengths, more steeply curved corneas and more powerful lenses at 3 months than do full-term infants of the same age (Cook et al., 2003, and Fig. 3, Fig. 4, Fig. 7). Some of the eyes of premature infants develop retinopathy as was seen, for example, in the study of the ocular components of a series of 108
The lens power in school years
Three recent prospective studies have reported on the loss of lens power in schoolchildren. These are the Orinda Study (and its extension, the CLEERE study) (Jones et al., 2005b, Twelker et al., 2009), the SCORM Study (Wong et al., 2010, Iribarren et al., 2012a) and a study involving Chinese myopic twins in Guangzhou (Xiang et al., 2012). The Orinda and CLEERE studies included phakometry, so the lens equivalent refractive index could be estimated and, as said, was shown to decrease with age in
Theories for lens thinning during childhood
Sorsby et al. (1957) proposed a coordinated growth of the components of refraction (mainly axial length with corneal and lens powers) to explain the tendency to produce emmetropic eyes in which differences in axial length were compensated by corneal and lens power. He clearly showed that in the emmetropic range, longer eyes had flatter corneas and less powerful lenses (and vice versa) (Sorsby et al., 1957). Then, van Alphen (1961) proposed a model for eye growth that comprised passive and
Change in ocular components at myopia onset
In experimental models of refractive error, during early eye growth, images falling behind the retina in hyperopic eyes (hyperopic defocus) can induce an accelerated rate of axial growth, and vice versa, images falling in front of the retina (myopic defocus) can down-regulate the rate of axial growth (Wallman and Winawer, 2004). Low outdoor exposure to natural ambient light probably produces an acceleration of axial growth by the down-regulation of retinal dopamine activity (French et al., 2013
The lens power loss during university study years
The mentioned SCORM study in Chinese Singaporean school children showed rates of axial length change of +0.10 mm per year in emmetropes, and +0.28 mm per year in myopic eyes, with a change in lens power of −0.29 diopters per year in emmetropes, –0.36 diopters per year in newly developed myopes and −0.25 diopters per year in persistent myopes (Iribarren et al., 2012a). A prospective study of engineering students in Norway (Kinge et al., 1999) showed that during the three-year follow up, the
The lens in adulthood
We have seen that myopic children have lower lens power than emmetropic children, and hyperopic children have higher lens power than their emmetropic peers. This would produce a positive correlation between refraction and lens power, as higher spherical equivalents have higher lens power and vice versa (Iribarren et al., 2012a). This would be in agreement with the fact that longer eyes, usually the myopic ones, have lower lens power, and vice versa, shorter eyes have higher lens power. This can
Longer eyes of taller subjects have lower powered lenses
The advent of ultrasound biometry in the 70's produced two interesting studies. In 1979 Larsen (Larsen, 1979) showed that taller people had longer eyes (and vice versa) for subjects in the emmetropic range. Since then, many population studies have found that taller people have longer eyes with flatter corneas, irrespective of refractive error (Wong et al., 2001a, Saw et al., 2002, Ojaimi et al., 2005, Eysteinsson et al., 2005, Wu et al., 2007, Lee et al., 2009, Nangia et al., 2010). Also in 1979
How can the lens change its power?
How is it possible that the lens changes its power in opposite directions with ageing, first losing power from birth up to age 70 and then gaining power with cataract formation? Can the lens adjust its power to the general growth of the eye? A theory that could explain these changes can only be based on the understanding of both surface and internal structure of the lens.
As we said before, the lens has a gradient of refractive index because new fresh fibers mature and become compacted as they
Is the rate of lens power loss an actively regulated process?
In the classical studies about the correlation of the ocular components with refraction performed by Tron (1940) and Stenstrom (1948) in younger adults, the lens was found to have no correlation with refraction, and thus was not considered important in the development of refractive error. But things might have looked different if those studies would have been performed in children (who have a positive correlation between refraction and lens power, Iribarren et al., 2012a) or in older adults
Conclusions and future directions
A decreased rate of lens growth after birth, accompanied by compaction of the nuclear lens fibers in the first decade of life is probably responsible for lens thinning after birth and during school years up to age 10–12. Lens thinning is accompanied by flattening of lens curvatures because of changes in overall lens shape. These changes involve axial thinning and equatorial growth from birth to puberty. The lens thinning per se, all other things the same, would increase the power of
Acknowledgments
This review was developed during long lasting discussions with Prof. Ian G. Morgan (Australia), to whom I feel grateful. I wish to thank Prof. Akbar Fotouhi (Iran) for the data in Figure 1 of Tehran Eye Study and for the data in Table 5. I also thank Prof. Michiel Dubbelman (Netherlands) for his comments on the manuscript. I also wish to thank Prof. Bob Augusteyn (Australia) for his permission to reproduce Figures 6A & B, and for the friendly discussion about lens growth in his cited papers.
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Percentage of work contributed by each author in the production of the manuscript is as follows: Rafael Iribarren: 100%.