268 N.A. McBrien

goal of any long-term therapy to reduce the permanent vision loss associated with high myopia.

Introduction

Myopia is a common refractive error in which the resultant focal length of the optical components of the eye is incompatible with its overall axial length. In the vast majority of cases of human myopia (>95%), the refractive error develops due to excessive axial eye size, and not through changes in corneal or lens power.1 Indeed, the single structural correlate responsible for this excessive axial eye size in human myopia of either youth-onset or adult-onset is an enlarged vitreous chamber depth.2

Myopia has a high prevalence in the human population, with some degree of myopia present in 20–30% of individuals in North American, European, and Australian populations.3–5 In selected South-East Asian populations the prevalence is reported to be as high 80%.6,7 High degrees of myopia, typically classed as in excess of 6 dioptres (D), are of major concern due to the fact that the incidence of myopia-related pathology, often in the form of chorioretinal degenerations and/or retinal detachments, is significantly increased.8,9 In fact, up to 70% of myopes over 6 D are reported to have sight-threatening ocular pathology.10 Prevalence studies indicate that 12–15% of all myopes have refractive errors over –6 D, resulting in a prevalence of high myopia in the general population of approximately 3%.11 The ocular pathology associated with high myopia is among the leading causes of registered blindness and partial sight in populations of the developed world.12 Given that high myopia is invariably due to increased eye size, the mechanical stresses placed on the retina and choroid during eye movements are greatly increased in larger eyes, implicating the mechanical consequences of increased eye size in the development of chorioretinal pathology.13,14 In conjunction with a pathological weakening of the sclera,15 the above observations demonstrate the importance of the sclera in maintaining eye size.

Postnatal eye growth is constrained by the properties of the outer coat of the eye. The sclera comprises by far the major component of the ocular coat. The sclera is a fibrous shell of collagenous, fibroblast maintained connective tissue, which is continuous with the cornea anteriorly forming

269 Changes to the Sclera in Myopia

an essentially closed shell around the structures of the anterior, equatorial, and posterior eye. Although historically the sclera has been considered a relatively inert tissue in metabolic terms, more recent research has shown it to undergo constant remodelling during eye growth, continuing throughout life, albeit at a lesser degree.16 In common with other specialized connective tissues, the sclera is highly organized, enabling it to perform its roles. A major functional role of the sclera is the protection of the delicate intra-ocular structures. However, the sclera plays important roles in accommodation, by providing a stable base for the contraction of the ciliary muscle, in promoting accurate eye movements, by providing a stable base for extraocular muscle contractions, and in allowing vascular and neural access to adjacent intra-ocular structures. Most importantly from the viewpoint of this chapter, the sclera, through maintenance of stable ocular dimensions, is critical in determining the absolute size of the eye, and thus plays an important role in determining the absolute refractive error of the eye.

Due to the limitations of studies on post-mortem human myopic eyes in elucidating the biological mechanisms underlying myopia development, researchers have developed suitable animal models of the condition. Since the development of the first animal models of myopia in the 1970’s,17 greater understanding of the mechanisms underlying scleral thinning during the development of high myopia has been possible.

The context of this review is focussed on the role of the sclera in myopia development and its implications for understanding and treating the human condition. Therefore, most of the discussion of data from experimental models will concentrate on the well-characterized mammalian models of myopia, namely the tree shrew, marmoset, and monkey, whose scleral structure is known to be similar to human. In particular, as the most detailed studies of the role of the sclera in myopia have been conducted on the tree shrew model, results from this model will feature strongly. The tree shrew is a diurnal mammal, close to the primate line, with a cone-dominated retina and normal lifespan of six to eight years in captivity.18 Despite the fact that its eye is smaller than that of humans (≈8 mm), it has been shown to be a reliable model of scleral changes in myopia in that it has the same scleral structure and undergoes similar changes to those found in human myopes.19