Study Notes on Cornea, Sclera, and Wound Healing

ANATOMY, PHYSIOLOGY, AND WOUND HEALING

Cornea

The outer fibrous coat of the eye comprises the posterior opaque sclera and the anterior transparent cornea. The anteriormost sclera is covered by the translucent bulbar conjunctiva, with both connected via the fibrous Tenon's capsule. The point where the cornea, sclera, and bulbar conjunctiva merge is termed the limbus. In domestic species, the horizontal diameter of the cornea exceeds that of the vertical diameter, especially noted in large herbivores. The corneal thickness tends to vary among species and regions; in domestic species, it typically measures between 0.5 and 0.8 mm, being thinner in birds, reptiles, and small exotic mammals.

Structure of the Cornea

The cornea consists of four layers:

  • Stratified epithelium and its basement membrane

  • Collagenous stroma

  • Descemet's membrane (basement membrane of the endothelium)

  • Endothelium

The corneal epithelium is stratified, squamous, and nonkeratinized, generally comprising five to seven cell layers in dogs and cats, and approximately 12-15 cell layers in horses. From deep to superficial, the epithelium consists of basal (columnar), intermediate (polyhedral), and surface (squamous) cells, along with the basement membrane. Basal cells attach to the basement membrane via hemidesmosomes. When basal cells divide, daughter cells migrate towards the surface, flatten into wing cells, and gradually lose organelles. The surface squamous cells possess microvillous projections that anchor the deep mucin layer of the precorneal tear film. The corneal epithelial stem cell population primarily resides at the corneoscleral limbus; their continuous mitotic activity draws basal cells centripetally, allowing regeneration and maturation to occur simultaneously from peripheral to central regions and from inner to outer layers.

The corneal stroma, which constitutes 90% of corneal thickness, is made up of keratocytes, collagen, water, glycosaminoglycans, and other vital components of the extracellular matrix. The arrangement of parallel collagen fibrils into lamellae allows for transparency; this organization can be disrupted by edema, glycosaminoglycan alterations, scar tissue formation, or infiltration by cells or foreign materials, resulting in reduced corneal transparency.

Descemet's membrane serves as the basement membrane of the endothelium. Continuous secretion by endothelial cells causes this membrane to thicken with age and be resilient, although it can thin or rupture due to globe stretching or trauma. Descemet's membrane is exposed during full thickness corneal ulcers and does not stain with fluorescein, appearing as a dark, transparent, often bulging "blister" in central corneal ulcers.

The single layer of endothelium lies posteriorly to Descemet's membrane and is primarily responsible for pumping ions from the stroma into the aqueous humor, which helps maintain the corneal stromal dehydration and transparency. Endothelial cells are postmitotic and typically have limited replication capacity, causing a decrease in cell numbers with age. In canines, endothelial cell density is approximately 2800 cells/mm²; decompensation and inability of the endothelium to manage stroma water occurs below 500 to 800 cells/mm².

Factors Affecting Corneal Transparency

Corneal transparency is essential for vision and maintained by several anatomical and physiological features:

  • A smooth optical surface

  • Lack of keratinization

  • Absence of blood vessels

  • Absence of pigmentation

  • Relatively low cell density

  • Maintenance of a dehydrated state

  • Highly organized arrangement of stromal collagen fibrils

Alterations in these states can result in reduced corneal clarity, evident as:

  • Tear dysfunction

  • Epithelial loss (erosion or ulceration)

  • Keratinization

  • Neovascularization or melanosis

  • Lipid, mineral, or other intracellular deposits

  • Corneal edema

  • Scar formation

Normal Corneal Healing

Each corneal layer heals through different mechanisms and rates; understanding these intricacies is crucial for clinical assessment of healing:

Corneal Epithelium

The corneal epithelium exhibits substantial regenerative capacity. Within minutes post-injury, surrounding epithelial cells migrate to cover the defect. After coverage, mitosis restores the multilayered structure, culminating in reestablishment of attachment to the basement membrane via hemidesmosomes. Healing in the corneal epithelium simultaneously occurs both axially from the limbus and superficially where the basal epithelium resides. Full reepithelialization is typically achieved within 4-7 days, but restoration of normal thickness and maturity takes longer, ensuring proper adhesion to the stroma.

Corneal Stroma

Stromal healing can proceed through:

  1. Avascular Healing: Occurs in uncomplicated situations where resting keratocytes convert to collagen-synthesizing fibroblasts, leading to new collagen deposition but irregularity, potentially diminishing transparency.

    • Neutrophils infiltrate the lesion from the tear film and aqueous humor.

    • Activation of immediate keratocytes and migration to synthesize collagen begins.

    • Macrophages later remove debris.

    • Gradual densification of scar tissue occurs.

  2. Vascular Healing: In severe cases with substantial damage, new blood vessels penetrate the corneal stroma to facilitate repair. The processes, however, yield more extensive fibrosis and scar formation.

  3. Corneal nerves tend to regenerate slowly, restoring sensation over time.

Endothelium and Descemet's Membrane

The endothelium is postmitotic with limited regeneration, with neighboring cells covering damaged areas through sliding and hyperplasia. If endothelial density falls below a critical threshold, corneal edema becomes evident. Descemet's membrane, formed by the endothelium, may be impaired in certain conditions, resulting in morphological changes that can lead to further complications.

Effects of Corticosteroids on Corneal Healing

While corticosteroids can limit opacity and manage associated intraocular inflammation, they also have potential drawbacks:

  • Inhibition of epithelial regeneration

  • Reduced infiltration by inflammatory cells

  • Weakened wound strength

  • Increased susceptibility to infection

Topical corticosteroid use is justified under specific conditions:

  1. Control of infection is confirmed.

  2. An epithelial covering exists (no fluorescein retention).

  3. Structural integrity of the cornea remains intact.

  4. The corneal disease is not due to primary infectious agents like feline herpesvirus.

Topical antibiotics are typically co-administered with corticosteroids in therapeutic contexts.

Sclera

The sclera provides a larger portion of the fibrous coat of the eye compared to the cornea and is structured in three layers:

  • The episclera: A fibrous and vascular outer layer connecting Tenon's capsule with the sclera proper.

  • The scleral stroma: Comprising collagenous fibers, fibroblasts without regular spacing contributing to transparency issues.

  • The lamina fusca: A transition zone to the choroid and ciliary body.

Pathologic Responses of the Cornea

Corneal diseases arise from three primary origins:

  1. Exogenous

  2. Extension from other ocular tissues

  3. Endogenous

Exogenous Factors

These factors necessitate penetration through the corneal epithelium, creating an environment where microorganisms can establish residency, especially post-epithelial breach. The corneal epithelium acts as a formidable barrier against pathogenic invasion.