CHAPTER 3 Cornea and Conjunctiva Anatomy and Physiology EMBRYOLOGY The cornea begins to form when the lens cup separates from the surface ectoderm (7–9 mm embryo at about 33 days), consisting of one to two rows of epithelial cells resting on a thin basal lamina with a cluster of mesenchymal cells near the lip of the optic cup just posterior to the corneal basal lamina. During the following week, some of these mesenchymal cells grow centrally between the basal laminae of the lens and corneal epithelia. At about 40 days the epithelium has a basal cuboidal and a superficial squamous cell layer. Posterior to the basal lamina, the mesenchyme has produced a double row of flattened cells, the future endothelium. By 22–24 mm, migrating mesenchymal cells of neural crest origin invade the space between the epithelium and the endothelium from the periphery to form stroma and sclera. At 2 months (about 35 mm), the cornea has an epithelium of outer squamous and basal columnar cells resting on a basal lamina with a stroma of about 15 layers of cells with rapidly developing collagen fibrils, most in the posterior portion. At 3 months, the endothelium of the central area consists of a single row of flattened cells that rest on an interrupted basal lamina, the first indication of a thin Descemet’s membrane. Collagen fibril formation is preceded by a gradual change from the randomly dispersed stellate fibroblasts to spindle-shaped cells with their long axes parallel to the corneal surface beginning in the posterior layers (in contrast, the sclera develops homogeneously, not in layers, as does the cornea). Although the lamellae are superimposed upon one another, each continues to grow by the addition of collagen fibrils from keratoblasts. Bowman’s layer arises rela- tively late during the fifth month, formed by the most anterior fibroblasts of the stroma. Fiber formation is preceded by synthesis of ground substance, and late in the sixth fetal month keratan sulfate is detectable and increases in amount. The early fetal corneal stroma is hydrophilic and translucent rather than transparent, and condensation begins in the posterior stroma until about the time that the most anterior lamellae are formed when corneal transparency reaches adult quality. By the fifth month, nerve endings are distributed in the epithelium. The diameter of the cornea is determined by the size of the retinal cup; if the eye fails to 92 ANATOMY AND PHYSIOLOGY 93 grow to a normal size, the cornea is also dwarfed, but it is qualitatively normal. CONJUNCTIVA Composed of nonkeratinized stratified columnar epithe- lium (keratinization seen as leukoplakia is often a sign of neoplasia). More wing cells are present than in the cornea, thus conjunctival epithelium is 10 to 12 cells in thickness. Goblet cells in the epithelium are important for mucus production (lost with inflammation ¼ dry eye) and more abundant nasally, in the fornix and the caruncle (most goblet cells are about 4 mm from the limbus called the glands of Manz). Melanocytes and Langerhans’ cells are found among basal cells. Substantia propia has collagen type 1 matrix and a normal chronic lymphocytic infiltrate with IgA present (mucosa-associated lymphoid tissue like Waldeyer’s ring in the throat or Peyer’s patches in the gastrointestinal tract). Episcleral vascular plexus: superficial and deep episcleral network. Episcleritis has edema that separates deep and superficial episcleral vessels with retained scleral contour (in contrast, edema from scleritis distorts scleral contour with retained relation between deep and superficial network). Normal flora: Staphylococcus epidermidis, Corynebacterium species, Propionibacterium acnes LIMBAL STEM CELLS Progenitor cells of the corneal epithelium located in the deep basal layers at the pallisades of Vogt. The G1 cell cycle S-gate, which remains closed in normal epithelial cells, is stimulated to open and allows cell mitosis in the stem cells. CARUNCLE Contains epithelium, goblet cells, hair, adipose, and pilose- baceous units. Do not excise; if it contains a pigmented lesion, it is always a nevus. TEAR FILM 7 mm thick, pH 7.4, hyposmolar (302 mOsm/L), 6.5 mL volume, produced 1.2 mL/minute; thus, turnover every 5 minutes. Func- tions to smooth surface of epithelium (which has 0.5 mm elevated microvilli), provides O2 to cornea, and provides IgA, lactoferrin, lysozyme, beta-lysin, complement, trophic proteins, and growth factors. Classically three tear layers are present: Inner mucinous layer with mucopolysaccharides (MPS): carboxylated mucin from holocrine goblet cells, sulfinated mucin from conjunctiva epithelium; 0.02–0.05 mm thick, adherent to glycocalyx. Middle thickaqueous layer from Krause’s and Wolfring glands (basal tear secretion) and lacrimal gland (reflex secretion). Outer oil layer: 0.1 mm thick(about the wavelength of light); there is 15Â greater aqueous evaporation without it, from Zeis’ (holocrine), Moll’s (apocrine sweat glands), and meibomian (holocrine) glands. 94 CORNEA AND CONJUNCTIVA Figure 3–1 The five layers of the cornea in cross section. CORNEA (Fig. 3–1) Derived from surface ectoderm, 500 mm central thick- ness, 800 mm peripheral. It is 11 Â 12 mm anteriorly (a horizontal oval that points toward the LR, due to a more superficial corneoscleral limbus superiorly and inferiorly), but posteriorly it is circular. The cornea is naturally avascular (receives O2 and nutrition from tears and aqueous) and dehydrated (but still 78% water). It has about 40D refractive power (mainly from the air-tear interface). The sensory nerve pathway is from CN V via the gasserian ganglion to V1 nasociliary nerve through the ciliary ganglion without synapse then the long ciliary nerve to the ciliary body, iris, and cornea. Cornea nerves enter the anterior one-third stroma mostly at 3 and 9 o’clockand have nakednerve endings at the epithelium BM. EPITHELIUM 50 mm thick, four to five cellular layers (deep basal columnar cells undergo mitosis to middle wing cells, then superficial squamous cells desquamate) with a true BM (not Bowman’s layer), and arise from stem cells at the limbus. It turns over approximately every 7 days. BM takes several months to reattach firmly if traumatized. BOWMAN’S LAYER Not a membrane but is condensed acellular anterior stroma 15 mm thickcomposed of randomly arranged compact collagen ANATOMY AND PHYSIOLOGY 95 lamellae. Binds certain growth factors (e.g., anti–fibroblast growth factor). Scars when disrupted, does not heal, and is nonrenewable. STROMA 90% of corneal thickness; composed of approximately 250 regularly spaced collagen lamellae that contain 600 A˚ fibrils that extend across the entire cornea. Keratocytes and glycosaminoglycans (keratan sulfate and chondroitin sulfate) are clear because the wavelength of visible light is about 5000 A˚ . Nonrenewable. DESCEMET’S MEMBRANE Basement membrane of endothelium, 10–12 mm thick. Anterior third is the fetal band, and the posterior nonbanded portion continues to grow with age. The posterior may become banded with diseased endothelium (e.g., Fuchs’ dystrophy has banded posterior Desce- met’s membrane in the patient’s teenage years even though guttae is often not present until age 40). Site of guttae and peripheral Hassall-Henle bodies. ENDOTHELIUM From neural crest, nonrenewable cellular monolayer. Controls hydration by pump function (not a good mechanical barrier). Endothelial cells do not multiply: cell density is about 3500 cells/mm2 at birth and decrease gradually throughout life at about 0.6% per year and about a 10% loss per intraocular surgery. Corneal edema develops if cell density drops below 500–1000 cells/mm2; thus, with normal aging we þ þ have about an 80% reserve of endothelial cells. A Na /K /ATPase and þ bicarbonate pump in the lateral membrane pumps Na and bicarbonate into the aqueous. Cells are joined by zonula occludens (closes posterior intercellular space toward the AC) and macula adherens. CORNEAL HYDRATION The epithelium to endothelium ratio to electrolyte diffusion resistance is about 200:1 (i.e., epithelium is a good water barrier). Stromal GAG ground substance (polyanionic charges) is a ‘‘dry sponge’’ and wants to absorb water (swelling pressure ¼ imbibition/oncotic pres- sure þ IOP) balanced by endothelial pump and epithelium evaporation (only 5%). Earliest symptom of corneal edema is morning vision clouding from microcystic epithelium edema from decreased evaporation overnight. Stromal edema and Descemet’s folds occur when corneal thickness reaches about 0.6 mm, and epithelial edema and bullae form when the cornea is about 0.7 mm. Acute glaucoma with increased IOP pushes more water into the cornea, but with a normal endothelium, the stroma can still be dehydrated. Thus, only epithelial edema is seen because high epithe- lium resistance to water causes the excess corneal water to collect subepithelially (microcystic edema) and has greatly decreased VA. In contrast, endothelial damage (e.g., PBK of Fuchs’ dystrophy) has more stromal edema (water displaces orderly collagen) but less decreased VA than epithelial edema. 96 CORNEA AND CONJUNCTIVA Signs and Symptoms BLUE SCLERA (Mnemonic: GNOME-P): Goltz syndrome (focal dermal hypoplasia), Ota’s nevus (oculodermal menlanocytosis), osteogenesis imperfecta type I (decreased type I collagen, autosomal dominant), Marfan syndrome, Ehlers-Danlos syndrome type VI (autosomal recessive; rule out cardiac disease), pseudoxanthoma elasticum (also may have keratoglobus) BLEPHARITIS (Table 3–1) May be anterior (staphylococcus or seborrheic), posterior (meibomian