Aside from blue sclerae, other ocular anomalies which may occur associated with keratoconus are subluxated lenses, cataract, aniridia, retinitis pigmentosa, and optic atrophy. Keratoconus has been described in association with various systemic connective tissue disorders, such as Marfan’s syndrome [136, 137], osteogenesis imperfecta [94, 132], and Ehlers– Danlos syndrome; [124, 130, 138, 139].

8.2.1.6 Buphthalmos

The high intraocular pressure of congenital glaucoma produces enlargement and stretching of scleral and corneal collagen fibers before maturation. This leads to a very large eye or buphthalmos with a corneal diameter greater than 10.5 mm at birth or greater than 12 mm at age 1 year [140, 141]. The sclera, usually thin in premature infants and in white newborns, is even thinner at birth and persists like this beyond the first month of infancy; light transmitted through the thinned sclera strikes the uvea and is reflected outward, producing a bluish tinge. After surgical relief of congenital glaucoma, there is no further stretching of scleral fibers; however, the scleral fibers which have become stretched never return to normal.

8.2.1.7 Coloboma

Cystic outpouching of the posteroinferior sclera or scleral ectasia may occur in association with a peripapillary coloboma of the choroid [55, 142]. The normal vessels of the disc pass over bare ectatic sclera or atrophic choroid and then into normal retina.

Occasionally, intrauterine fetal infection, such as toxoplasmosis may secondarily cause focal areas of scleral thinning and ectasia at the sites of intense retinal and choroidal inflammation [55].

8.2.1.8 Myopia

Simple or stationary myopia develops during youth and stops after completion of body growth; this form of myopia is usually of low to moderate severity and is not associated with significant chorioretinal complications. Degenerative or pathologic myopia develops during youth but

progresses steadily throughout life; this form of myopia is usually severe and is associated with significant chorioretinal complications. Degenerative myopia is associated with an enlargement of the axial length of the posterior segment of the globe. The heredity and certain developmental abnormalities play an important role in myopia. Some investigators observed that chickens raised with translucent occluders over their eyes developed eyes with long axial lengths [143]. Monkeys raised with unilateral lid suture or after unilateral opacification of the cornea with polystyrene beads also developed eyes with abnormal axial lengths; [144, 145] this effect could only be demonstrated when the monkeys were raised in light as opposed to dark. The investigators suggested that visual stimulation is necessary for the development of the alterations. However, small periods of normal vision (2 h) can prevent the development of axial elongation [146]. There appears to be an age window of susceptibility during which abnormal axial length can be induced since adult monkeys cannot be made myopic with lid occlusion [144] and monkeys at age 12 months can only be made less myopic [147].

In degenerative myopia, the sclera is thin, particularly in the posterior segment of the globe; [148, 149] posterior scleral thinning may cause posterior pole and equatorial staphylomas as a result of stretching of the fibers. However, rather than a purely mechanical stretch, the increase in axial length in myopic eyes seems also to be due to increased scleral growth during which both the fibrocytes and the extracellular matrix overgrow; there are more DNA, collagen, protein, and proteoglycan synthesis in the myopic sclera [150–152].

8.2.2Scleral Thinning in Acquired Diseases

8.2.2.1 Iron-Deficiency Anemia

Iron-deficiency anemia is the most frequent cause of acquired blue sclerae. There are no data on the body depletion of iron stores needed before blue sclerae develop, but the presence of blue sclerae is a useful guide to iron-deficiency anemia in