273 Changes to the Sclera in Myopia

juvenile phase), but that they increase in number as eye growth slows and reaches its adult size. Interestingly, unlike the normal transience of these cells in processes like wound healing, the sclera contains a stable population of myofibroblasts.

Structural Changes to the Sclera in Myopia

Scleral pathology in high myopia is a major cause, if not the most significant factor in the chorioretinal damage that results in the permanent vision loss experienced by a substantial proportion of high myopes.

Thinning of the sclera, particularly at the posterior pole of the eye, has long been known to be an important feature of the development of high myopia in humans. One of the most important clinical consequences of such thinning is the formation of posterior staphyloma, a condition in which the thinned sclera becomes ectasic.40 Staphyloma formation occurs almost exclusively in the region of the posterior pole of the eye, and thus can have a catastrophic affect on vision. When compared with the scleral thickness of age-matched emmetropic eyes, high myopes show a greatly reduced thickness (up to 50% thinner) at the posterior pole of the eye, regardless of the presence of staphyloma. Scleral thinning also occurs in the equatorial and anterior regions of highly myopic human eyes, however, these changes are less marked than those encountered around the posterior pole.

Early theories of scleral thinning hypothesized that the existing scleral tissue was redistributed to cover the surface of the eye as the eye enlarged, suggesting that the sclera stretched passively to accommodate the expanding eye.41 However, early histological observations also showed that profound morphological changes, in addition to the thinning, were apparent in the scleral extracellular matrix. For example, scleral collagen fibril morphology was found to be altered, particularly at the posterior pole of highly myopic eyes, with a characteristic shift in the fibril diameter distribution, resulting in an increased number of small diameter collagen fibrils.42 In addition, the appearance of what were reported to be ‘stellate’ shaped fibrils was noted, another scleral feature that is suggestive of pathology as these anomalies were not observed in normal sclerae.42

In further support of observations that the human sclera undergoes active remodelling during myopia development, biochemical assays from highly myopic eyes show markedly reduced amounts of biochemical

274 N.A. McBrien

markers for collagen and glycosaminoglycans, when compared with the sclera of emmetropic eyes.15 Tensile testing of the sclera from highly myopic human eyes has confirmed that the thinned sclera is less resistant to deformation than the sclera of emmetropic eyes.15

The major drawback from studies of post-mortem tissue from highly myopic human eyes stems from the fact that it is impossible to establish cause and effect of the scleral pathology in high myopia. Specifically, it is not possible to say whether the biochemical changes encountered in the sclera of human high myopes occur prior to, thus implicating them in the cause of scleral thinning and stretch, or whether they are a consequence of the scleral thinning. Such questions are more directly addressed in studies utilizing animal models of myopia, and the results of these studies have enabled us to answer many important questions raised from observations of the sclera of humans with high myopia.

Development of structural and ultrastructural scleral changes in myopia

A major feature of scleral thinning in human myopia is that it is largely confined to the posterior pole of the eye (Fig. 1A). Obviously, a major requirement of any appropriate model to elucidate mechanisms in human myopia is that it should demonstrate this regional change.19 The most remarkable feature of this scleral thinning is the fact that it occurs very rapidly in response to the onset of myopia development. Indeed, it has been found that the posterior sclera thins by some 20% over the first 12 days of myopia development in young tree shrews (Fig. 1B). This time period represents the early phase of myopia development, during which some 12 dioptres of relative axial myopia are induced. This reduction in scleral thickness progresses slowly over the next three to eight months, representing the later phase of myopia development, despite the fact that these eyes continue to display evidence of myopia progression (up to 20 dioptres or an increase in axial eye size of ~7%).19

Analysis of the dry weight of the sclera has demonstrated that the cause of scelral thinning in myopia is due to the actual loss of scleral tissue as opposed to passive stretch of the sclera. The rate of loss of scleral tissue corresponds closely with the time course of scleral thickness changes at the posterior pole of the myopic tree shrew eye and demonstrates that poste-

rior scleral tissue is lost rapidly. Significant decreases in scleral dry weight are apparent at the posterior pole (>5%, p < 0.05) after only five days of

275 Changes to the Sclera in Myopia

Figure 1. Thinning of the posterior sclera in mammalian eyes with progressive high myopia.

A. Light micrographs of toluidine blue-stained transverse-sections of the posterior sclera of a highly myopic and fellow control eye of a tree shrew, following eight months of myopia progression. B. Mean posterior scleral thickness in the myopic, fellow control and age-matched normal eyes of tree shrews following 12 days (n = 2 normal and n = 5 myopic) or 6–20 months (n = 4 each group) of myopia progression. Error bars are 1 SEM. **p < 0.01, *p < 0.05 by paired t-test. (Reproduced with permission from McBrien & Gentle 2003, Copyright Elsevier Science Ltd.)

myopia induction in young tree shrews (Figs. 2A and B), representing the initial stages of myopia development.43 This tissue loss continues to occur rapidly over the initial 12 days of myopia development, accounting for 17% reduction of posterior scleral dry weight (Fig. 2B). Over the next three to eight months of myopia progression the continued loss of scleral