The cornea is oval shaped, with a 12.6 mm horizontal and a 11.7 mm vertical diameter [1].

The central cornea is spherical; the peripheral cornea is flatter and thicker than the central portion.

Peripheral corneal asphericity reduces optical blur from spherical aberration [2, 3].

The cornea transmits wavelengths 310–2500 nm with minimal (<1 %) light scattering [5].

The cornea has a higher refractive index than air (1.376 vs. 1.0).

The total corneal/tear film refractive power is 43.1 diopters (D) due to:

The glycosaminoglycan matrix that maintains the regular crystalline arrangement of fibrils

There are three cell types (from surface to basement membrane): superficial, wing, and basal cells [4].

Desmosomes attach basal, wing, and superficial cells to one another [16].

Tight junctions encircle superficial cells [17].

Gap junctions are numerous among basal and wing cells. These allow intercellular communication and coordination for cell differentiation and migration [18].

Basal cells adhere to the basement membrane via hemidesmosomes [15].

Hemidesmosomes connect to anchoring fibrils that pass through Bowman’s layer to the stroma [19].

Corneal epithelium is maintained by a constant cycle of shedding of superficial cells and proliferation of mitotically active basal cells [11].

Basal cells proliferate and migrate superficially and centrally; most proliferate at the limbus (palisades of Vogt) from where there is a centripetal migration of cells.

This is known as the X, Y, Z hypothesis of corneal epithelial maintenance (Fig. 3.2) [21].

A similar pattern of proliferation and migration occurs after epithelial injury [22].

The corneal epithelium acts as a barrier to preserve stromal homeostasis.

The epithelial cell membranes are joined by tight junctions that prevent water and solutes entering from the tear film [17].

An epithelial metabolic pump exists to maintain stromal dehydration (Fig. 3.3):

Bowman’s layer consists of irregular collagen fibrils deep to epithelial basement membrane [27, 28].

It has predominantly type I collagen and is considered a modified superficial layer of stroma [29].

Its function is unknown; it may be involved in stabilizing the corneal epithelium [30, 31].

The stroma is composed of 200–250 highly organized lamellae that run parallel to the corneal surface (Fig. 3.4).

These are bundles of colinear collagen fibrils approximately 2.0 um thick and 9–260 um long [32, 33].

The lamellae lie oblique to one another anteriorly and orthogonally posteriorly.

At the limbus they form an annulus 1.5–2.0 mm in diameter; this maintains corneal curvature [34].

They lie in a ground substance consisting of a proteoglycan matrix [35].

In the central cornea, the fibrils are 31 nm in diameter and regularly spaced at 57 nm apart [32].

The fibrils have a higher refractive index than the proteoglycan matrix (1.41 v 1.37); however, light scattering is minimized by their uniform lattice arrangement (Fig. 3.5) [36, 37].

Proteoglycans consist of core proteins and carbohydrate side chains [39].

The electrostatic forces help maintain the collagen fibril lattice arrangement [40].

Keratocytes are the main stromal cell type [41].

They synthesize fibrillar collagen and the protein core of the proteoglycans.

Although they are sparse and separated, they have long cytoplasmic processes that provide intercellular communication via connecting gap junctions to form a syncytium [42].

They are activated in stromal injury to differentiate into myofibroblasts for wound healing [43].

The stroma has an inherent tendency to imbibe water and to swell, with negatively charged proteoglycans that cause excess Na⁺ to accumulate [44].

Excess hydration can degrade light transmission.

Pre-Descemet’s layer is a well-defined acellular layer located between Descemet’s membrane and the deepest row of stromal keratocytes [45].

It provides a natural strong cleavage plane between Descemet’s membrane and the stroma.

Interdigitated lateral cell membranes are connected by tight junctions and gap junctions [49, 50].

A metabolic pump sets up an osmotic gradient causing fluid to move from the stroma to the aqueous (Fig. 3.6) [25]:

Endothelial cells generally do not replicate; however, a limbal stem cell source has been identified with limited replicative ability in response to injury [56].

Endothelial cell density decreases with age [57, 58].

Newborns have 5500 cells/mm², while adults have 2500–3000 cells/mm².

A minimum of 400–700 cells/mm² is required for normal corneal function; however endothelial decompensation can occur at higher counts [59–61].

Stable endothelium has a uniform size and shape. Stressed or unstable endothelium demonstrates polymegathism (cells of varying size) and pleomorphism (cells of varying shape) [62].

Corneal innervation is essential for epithelial turnover, wound healing, and protection [65, 66].

Corneal nerves are non-myelinated; they respond to mechanical, thermal, and chemical stimuli.

The cornea is innervated by the anterior ciliary nerves, branches of the ophthalmic nerve (V1).

Bare nerves enter limbally in the mid-stroma and run anteriorly and radially toward the center, forming a stromal plexus [67].

Branches perforate Bowman’s layer to form a subepithelial plexus that innervates basal cells [14, 64].

Corneal sensitivity is greater centrally than peripherally; it is greater superiorly than inferiorly.

Sensitivity is affected by age, iris color (blue is most sensitive, brown is least), environment, diabetes, previous corneal surgery, and contact lens wear [68, 69].

Substance P and calcitonin gene–related peptide are involved in pain transmission and modulation of pain and inflammation. They are important epithelial cell trophic factors [14, 65, 67, 70].