CHAPTER 4

Infectious Diseases of the External Eye: Basic Concepts and Viral Infections

Defense Mechanisms of the External Eye

The external eye contains diverse tissues that are intricately linked to protect against infection. Components of the ocular adnexa—periorbita, eyelids and lashes, lacrimal and meibomian glands— play different but important roles in the production, spread, and drainage of the preocular tear film. The adnexa, along with the bony orbit, also physically protect the sensitive ocular mucosa and cushion the globe. Functional blink (10–15 blinks per minute) prevents desiccation of the ocular surface and promotes tear turnover; during blinking, the meibomian glands express lipid, tears are pumped from the lacrimal gland and spread onto the cornea, and excess tears are directed into the lacrimal puncta. Tear turnover reduces the contact time of microbes and irritants with the ocular surface.

Lymphoid tissues within the conjunctiva, lacrimal glands, and lacrimal drainage tract furnish acquired immune defense. Important tear-soluble macromolecules exert antimicrobial properties:

Tear lysozyme degrades bacterial cell walls, while β-lysin in the tears disrupts bacterial plasma membranes.

Tear lactoferrin inhibits bacterial metabolism and facilitates tear antibody function and complement activation.

Immunoglobulins in the tear film, particularly secretory IgA, mediate antigen-specific immunity at the ocular surface. Components of both the classic and alternative complement pathways are also present.

Meibomian gland–derived lipids reduce evaporation of the tear film, indirectly protecting the corneal epithelium from desiccation.

Mucins inhibit attachment of microbes to ocular surface epithelium.

Cytokines such as epidermal growth factor (EGF), transforming growth factor βs (TGF-βs), and hepatocyte growth factor (HGF) are present in the tears; their role in ocular surface defense is a promising area of basic investigation.

BCSC Section 2, Fundamentals and Principles of Ophthalmology, discusses the biochemistry and metabolism of the tear film and cornea in detail.

The epithelium of the ocular surface forms a tight mechanical barrier against microbial invasion. The healthy cornea has classically been considered devoid of leukocytes, but activated Langerhans cells (antigen-presenting cells that carry antigen to regional lymphatic tissue and facilitate an acquired immune response) and other dendritic cells normally present in the peripheral corneal epithelium can migrate rapidly to the central cornea. Microbial invasion triggers ocular surface epithelial cells to secrete interleukin-1 (IL-1) and other cytokines that boost the local immune response through the enhancement of immune-cell migration, adhesion, and activation. The rapid cycling of epithelial cells aids in the expulsion of microbes. Upon infection, the constitutive cells of the cornea, the keratocytes in particular, augment the inflammatory cascade by secreting proinflammatory cytokines. Lymphocytes and neutrophils are recruited into the cornea from the tear film, the limbal vascular arcades, and the anterior chamber.

Human conjunctiva contains a complete spectrum of immunologically competent cell types. Uninfected conjunctival epithelium possesses CD8+ cytotoxic/suppressor T lymphocytes and Langerhans cells. Conjunctival substantia propria contains CD4+ helper T cells and CD8+ T cells in roughly equal numbers, along with natural killer T cells, mast cells, B lymphocytes, plasma cells, macrophages, and occasional polymorphonuclear leukocytes. The vascular and lymphatic channels of the conjunctiva transport humoral and cellular immune components to and from the eye. During an infection, inflammatory mediators promote vascular dilation, permeability, and diapedesis from conjunctival blood vessels. Hyperplasia of conjunctival lymphoid follicles and painful swelling of draining preauricular lymph nodes accompany conjunctival infection by viruses, Chlamydia, and virulent bacteria such as Neisseria species but are notably absent in newborns, because of their naïve lymphatic systems.

For a more extensive, illustrated discussion of ocular immunology, see BCSC Section 9,

Intraocular Inflammation and Uveitis.

Garreis F, Gottschalt M, Paulsen FP. Antimicrobial peptides as a major part of the innate immune defense at the ocular surface.

Dev Ophthalmol. 2010;45:16–22.

Normal Ocular Flora

Bacterial colonization of the eyelid margin and conjunctiva is normal and can be beneficial by competitively inhibiting pathogenic strains. The spectrum of normal ocular flora varies with the age and geographic locale of the host. In the eye of an infant delivered vaginally, multiple bacterial species predominate, including Staphylococcus aureus, Staphylococcus epidermidis, streptococci, and

Escherichia coli; streptococci and pneumococci predominate during the first 2 decades of life. Although gram-negative bacteria become more commonly isolated over time, S epidermidis and other coagulase-negative staphylococci, S aureus, and diphtheroids remain some of the most common species (Table 4-1). Nonpathogenic colonization of the eyelid margin with Demodex folliculorum and Demodex brevis also becomes more common with age, with these parasites becoming almost ubiquitous. The use of topical antibiotics or corticosteroids for conditions such as ocular surface disease may alter the spectrum of eyelid and conjunctival flora.

Graham JE, Moore JE, Jiru X, et al. Ocular pathogen or commensal: a PCR-based study of surface bacterial flora in normal and dry eyes. Invest Ophthalmol Vis Sci. 2007;48(12):5616–5623.

Kemal M, Sümer Z, Toker MI, Erdoğan H, Topalkara A, Akbulut M. The prevalence of Demodex folliculorum in blepharitis patients and the normal population. Ophthalmic Epidemiol. 2005;12(4):287–290.

Table 4-1