CHAPTER 6

Cornea

Topography

The normal cornea is composed of 5 layers: epithelium, Bowman layer, stroma, Descemet membrane, and endothelium (Fig 6-1). See BCSC Section 2, Fundamentals and Principles of Ophthalmology, and Section 8, External Disease and Cornea, for a discussion of the embryology, structure, and physiology of the cornea.

The corneal epithelium is nonkeratinized, stratified squamous, ranging between 5 and 7 cell layers in thickness. The epithelial basement membrane is thin and is best seen with periodic acid–Schiff (PAS) stain. The basement membrane is more easily visualized when it becomes pathologically thickened, such as in anterior basement dystrophy (ie, map-dot-fingerprint dystrophy) or secondary to endothelial decompensation.

The Bowman layer is located immediately beneath the epithelial basement membrane. It is also known as the Bowman “membrane,” but this term may be misleading because this layer is not a true basement membrane; that is, it is not elaborated by the epithelial cells. Rather, it is more properly regarded as the most anterior layer of the stroma. The Bowman layer is acellular and is composed of irregularly arranged collagen fibrils. It is not restored after injury but is replaced by fibroconnective scar tissue.

The corneal stroma makes up 90% of the total corneal thickness. It consists of collagen-producing keratocytes, collagenous lamellae, and proteoglycan ground substance. The elongated collagenous lamellae are regularly arranged in a precise orientation to yield transparency, allowing for the orderly passage of light through the cornea.

The next layer, the Descemet membrane, is the basement membrane elaborated by the corneal endothelium. The production of Descemet membrane begins during fetal development and continues throughout adulthood. The thickness of this membrane may increase further in endothelial disease states. The Descemet membrane (like the epithelial basement membrane) is a true basement membrane, composed primarily of type IV collagen, and is strongly PAS-positive.

The corneal endothelium is composed of a single layer of cells. The cells appear mostly hexagonal en face, such as on confocal microscopy. In a histologic cross-section of the cornea, the endothelial cells have a cuboidal appearance. The primary function of the endothelium is to maintain corneal clarity by pumping water from the corneal stroma. The number of endothelial cells gradually decreases with age, and endothelial cell loss is accelerated in endothelial disease states. Human endothelial cells cannot regenerate; so as the endothelial cell number declines, the remaining cells flatten and elongate to provide coverage of the posterior corneal surface.

Figure 6-1 Normal cornea. A, The cornea is composed of epithelium (Ep), the Bowman layer (B), stroma (S), the Descemet membrane (D), and endothelium (En). B, On higher magnification, PAS stain highlights the epithelial basement membrane (EBM), distinguishing it from the Bowman layer (B). Because of dehydration of the tissue during processing for paraffin embedding, multiple areas of separation (clefts) of the stromal lamellae are evident (arrows). If the stromal clefts are absent, corneal edema or fibrosis is suspected (the former if the cornea is thick, and the latter if thin). This is an example of a meaningful artifact. C, Higher magnification (H&E stain) also delineates Descemet membrane (D) and endothelium (En). The keratocyte nuclei (arrow) are apparent. (Note that PAS stain also highlights Descemet membrane.) (Courtesy of George J.

Harocopos, MD.)

Introduction to Corneal Pathology

Corneal specimens are among the most common specimens seen by the ophthalmic pathologist. In the pathology laboratory, specimens submitted from penetrating keratoplasty are referred to as corneal “buttons.” The most common indications for keratoplasty are listed in Table 6-1 and are discussed later in this chapter. In recent years, alternatives to penetrating surgery have become more widely utilized for certain corneal conditions in which only some of the corneal layers are diseased. For example, if the anterior cornea is diseased but the endothelium is healthy, then deep anterior lamellar keratoplasty (DALK) may be an option. On the other hand, if only the endothelium is diseased, then endokeratoplasty may be an option (eg, Descemet stripping endothelial keratoplasty [DSEK], in which only Descemet membrane and endothelium are removed). Examples of specimens from these