Although disease of the sclera is unusual, when it occurs it can rapidly destroy both
the eye and vision. However, normally the sclera provides an opaque protective coat
for the intraocular tissues and a stable support during variations in internal pressure
and eye movements, which would otherwise perturb the visual process through distortion
of the retina and the lens/iris diaphragm. This stability, which is vital for clear
vision is made possible by the organisation and viscoelastic properties of scleral
connective tissue. Microscopically, the sclera displays distinct concentric layers
including, from outside, Tenon's capsule, episclera, the scleral stroma proper and
lamina fusca, melding into underlying choroid. Two sites exhibit specialised structure
and function: the perilimbal trabecular meshwork, through which aqueous filters into
Schlemm's canal, and the lamina cribrosa, which permits axons of the optic nerve to
exit the posterior sclera. Throughout, sclera is densely collagenous, the stroma consisting
of fibrils with various diameters combining into either interlacing fibre bundles
or defined lamellae in outer zones. Scleral fibrils are heterotypic structures made
of collagen types I and III, with small amounts of types V and VI also present. Scleral
elastic fibres are especially abundant in lamina fusca and trabecular meshwork. The
interfibrillar matrix is occupied by small leucine-rich proteoglycans, decorin and
biglycan, containing dermatan and dermatan/chondroitin sulphate glycosaminoglycans,
together with the large proteoglycan, aggrecan, which also carries keratan sulphate
sidechains. Decorin is closely associated with the collagen fibrils at specific binding
sites situated close to the C-terminus of the collagen molecules. Proteoglycans influence
hydration, solute diffusion and fluid movement through the sclera, both from the uvea
and via the trabecular meshwork. As the sclera is avascular, nutrients come from the
choroid and vascular plexi in Tenon's capsule and episclera, where there is an artery
to artery anastomosis in which blood oscillates, rather than flows rapidly. This predisposes
to the development of vasculitis causing a spectrum of inflammatory conditions of
varying intensity which, in the most severe form, necrotising scleritis, may destroy
all of the structural and cellular components of the sclera. Scleral cells become
fibroblastic and the stroma is infiltrated with inflammatory cells dominated by macrophages
and T-lymphocytes. This process resembles, and may be concurrent with, systemic disease
affecting other connective tissues, particularly the synovial joints in rheumatoid
arthritis. Current views support an autoimmune aetiology for scleritis. Whilst the
role of immune complexes and the nature of initial pro-inflammatory antigen(s) remain
unknown, the latter may reside in scleral tissue components which are released or
modified by viral infection, injury or surgical trauma.