277 Changes to the Sclera in Myopia

tissue is less marked (Fig. 2C).19 These studies demonstrate there is a net tissue loss from the whole sclera of up to 7% of dry weight, unequivocally demonstrating that tissue is lost, rather than just re-distributed, during the development of myopia (Fig. 2B). Such a finding highlights the probability that biochemical changes are a precursor to changes in the material properties of the sclera, and ultimately, to myopia development.

In conjunction with the tissue loss observed in the tree shrew model, characteristic changes in collagen fibril diameter are also apparent in the sclera of highly myopic eyes, consistent with the findings in humans and monkeys. However, fibril diameter changes are only detectable a considerable time after the main changes in scleral thickness and tissue loss have occurred. Studies demonstrate that the scleral fibril diameter distribution profiles remain similar in myopic eyes to those in the sclera of normal eyes during the early phases of myopia development (Fig. 3A). This is despite major changes in scleral thickness and dry weight having occurred in those same eyes.19 However, after longer periods of myopia development (three months), a reduction in median collagen fibril diameter is found at the posterior pole of myopic eyes (Fig. 3B). This change is most marked in the outer scleral fiber bundles, which is consistent with the embryological observation that the outer fiber bundles are the last to mature.20 By six to eight months of myopia development there is a highly significant reduction in collagen fibril diameter across the scleral thickness, with the greatest reduction in diameter, around 35% (Fig. 3C), apparent in the outer layers of the sclera.19 As in humans, these changes are mainly localized to the posterior pole of the eye, although changes also occur in equatorial regions of the sclera, however, these are less dramatic. The shift in fibril diameter in myopic eyes results in a reduction in the gradient in fibril diameter across the scleral thickness, and it is interesting to note that this gradient is virtually absent in eyes with longstanding high myopia (Fig. 4).19

Scleral pathology and staphyloma

Data collected during the long-term development of myopia suggests that although the sclera thins rapidly and alters its material properties during the early stages, shifts in collagen fibril diameter are not apparent until later in myopia development. Recent data indicates that a shift in the ratio of type V collagen to type I collagen production during the early stages of myopia development may ultimately contribute to

279 Changes to the Sclera in Myopia

Figure 4. Reduction in the trans-scleral collagen fibril diameter gradient in eyes with progressive myopia. A. Electron micrographs show transverse sections through collagen fibrils in the defined inner, middle, and outer posterior sclera of highly myopic, fellow control and agematched normal eyes of 9–9.5 month-old tree shrews. B. Graphic representation of the transscleral collagen fibril diameter gradient in highly myopic (n = 3), fellow control (n = 3), and age-matched normal (n = 8) eyes of 9–9.5 month-old tree shrews. (Reproduced with permission from McBrien & Gentle 2003, Copyright Elsevier Science Ltd.)

staphyloma development in later life, through the progressive formation of more small diameter collagen fibrils. Furthermore, these changes are more localized to the posterior region of the eye. In humans, identical fibril diameter changes are reported in staphylomatous eyes. It should be