the fornix and may extend posteriorly into the orbit. As a result of its adipose tissue component, a lipodermoid is softer and yellower than a dermoid (Fig 5-2D). Dermal adnexal structures may or may not be present. Lipodermoids, like dermoids, may be associated with Goldenhar syndrome or linear nevus sebaceous syndrome.

Osseous choristomas contain bone. Complex choristomas combine features of multiple types of choristomas, for example, dermoid or lipodermoid plus osseous choristoma (Fig 5-2E). Clinically, they are often indistinguishable from dermoids or lipodermoids. See BCSC Section 6, Pediatric Ophthalmology and Strabismus, and Section 8, External Disease and Cornea.

Hamartomas

Hamartomas, like choristomas, are benign, congenital proliferations; but in contrast to choristomas, they are abnormal overgrowths of mature tissue normally present at that site (hence the derivation from the Greek word for “mistake mass”). In the conjunctiva, the most common variety of hamartoma is a capillary hemangioma, although this hamartoma most often involves the eyelid and may involve the orbit (see Chapter 13). Some consider hemangiomas to be true (acquired) neoplasms.

Inflammations

Because the conjunctiva is an exposed surface, a variety of organisms, allergens, and toxic agents can initiate an inflammatory response known as conjunctivitis. The response can be subdivided according to the time frame of symptoms and signs (acute or chronic); according to the appearance of the conjunctiva (papillary, follicular, or less commonly, granulomatous); or according to etiology (infectious, noninfectious). See BCSC Section 6, Pediatric Ophthalmology and Strabismus, and Section 8, External Disease and Cornea, for additional discussion.

Papillary Versus Follicular Conjunctivitis

Most cases of conjunctivitis may be categorized as either papillary or follicular, according to the macroscopic and microscopic appearance of the conjunctiva (Fig 5-3). Neither type is pathognomonic for a particular disease entity. Papillary conjunctivitis shows a cobblestone arrangement of flattened nodules with central vascular cores (Fig 5-4). It is most commonly associated with an allergic immune response, as in vernal and atopic keratoconjunctivitis, or it is a response to a foreign body such as a contact lens or ocular prosthesis. Papillae coat the tarsal surface of the upper eyelid and may reach large size (giant papillary conjunctivitis). Limbal papillae may occur in vernal keratoconjunctivitis (Horner-Trantas dots). The histologic appearance of papillary conjunctivitis is identical, regardless of the cause: closely packed, flat-topped projections, with numerous eosinophils, lymphocytes, plasma cells, and mast cells in the stroma surrounding a central vascular channel.

Figure 5-3 Schematic representation of papillary and follicular conjunctivitis. A, In papillary conjunctivitis, the conjunctival epithelium (checkered blue) covers fibrovascular cores with blood vessels (red), and the stroma contains eosinophils (pink circles) and lymphocytes and plasma cells (blue circles). B, In follicular conjunctivitis, the conjunctival epithelium covers lymphoid follicles, which have a paler germinal center surrounded by a darker corona (central pale blue surrounded by dark blue), and the surrounding stroma contains lymphocytes and plasma cells (small blue circles). (Courtesy of Patricia Chévez-Barrios,

MD.)

Figure 5-4 Papillary conjunctivitis. A, Clinical appearance. Papillae efface the normal palpebral conjunctival surface and form a confluent cobblestone pattern. B, Low-power photomicrograph exhibits the closely packed, flat-topped papillae with central fibrovascular cores (arrows). The normal meibomian glands (M) of the tarsus are also shown. (Part A courtesy of Harry H. Brown,

MD; part B courtesy of George J. Harocopos, MD.)

Follicular conjunctivitis (Fig 5-5) is seen in a variety of conditions, including inflammation caused by pathogens such as viruses; atypical bacteria; and toxins, including topical medications (glaucoma medications, especially brimonidine, or over-the-counter ophthalmic decongestants). In contrast to papillae, follicles are small, dome-shaped nodules without a prominent central vessel. Accordingly, whereas a papilla clinically appears more red on its surface and more pale at its base, a follicle appears more pale on its surface and more red at its base. Histologically, a lymphoid follicle is situated in the subepithelial region and consists of a germinal center, containing immature, proliferating lymphocytes; and surrounding corona, containing mature lymphocytes and plasma cells. The follicles in follicular conjunctivitis are typically most prominent in the inferior palpebral and forniceal conjunctiva.

Figure 5-5 Follicular conjunctivitis. A, Clinical photograph showing follicles. B, High-power photomicrograph shows lymphoid follicle with boundary between germinal center and corona (arrowheads). Note the paler, relatively larger, immature lymphocytes in the germinal center, as compared to the darker, small, mature lymphocytes and plasma cells in the corona.

(Part A courtesy of Anthony J. Lubniewski, MD; part B courtesy of George J. Harocopos, MD.)

Granulomatous Conjunctivitis

Though less common than papillary or follicular conjunctivitis, granulomatous conjunctivitis does occur. Clinically, the nodular elevations observed in granulomatous conjunctivitis may be difficult to distinguish from follicles, but clinical history and other systemic symptoms may point to the diagnosis. Granulomatous conjunctivitis in association with preauricular lymphadenopathy is known as Parinaud oculoglandular syndrome. Bacteria such as Bartonella henselae (cat-scratch disease) and

Francisella tularensis (tularemia), mycobacteria (eg, tuberculosis), and treponemes (eg, syphilis) are possible causes. The diagnosis can be made by serology, culture, polymerase chain reaction (PCR), or a combination of these. If conjunctival biopsy is performed, the granulomas in infectious granulomatous conjunctivitis will typically demonstrate central necrosis (caseation). The bacteria may be demonstrated with Gram, acid-fast, or Warthin-Starry stains, depending on the organism.

There are also noninfectious causes of granulomatous conjunctivitis. Sarcoidosis may involve all ocular tissues, including the conjunctiva. It manifests as small, tan nodules, primarily within the forniceal conjunctiva (Fig 5-6). The nodules are often present even in the absence of an obvious conjunctivitis, that is, in noninjected, asymptomatic eyes. Conjunctival biopsy can be a simple, expedient way of providing diagnostic confirmation of this systemic disease. Histologically, noncaseating granulomatous “tubercles” (round to oval aggregates of epithelioid histiocytes) are present within the conjunctival stroma with a variable, but usually minimal, cuff of lymphocytes and plasma cells. Multinucleated giant cells may or may not be present within the granulomas. Central necrosis is not characteristic and, if present, should suggest infectious causes of granulomatous inflammation. The diagnosis of sarcoidosis is tenable only when supported by clinical findings and after other causes of granulomatous inflammation have been excluded by histochemical stains and/or by culture. See also Chapter 12 in this volume and BCSC Section 9, Intraocular Inflammation and Uveitis.

Figure 5-6 Sarcoidosis. A, Clinical appearance of sarcoid granulomas of the conjunctiva. B, Histology shows noncaseating granulomatous tubercle, with pale-staining histioctyes, including a multinucleated giant cell (arrowhead). Note the minimal surrounding cuff of lymphocytes and plasma cells. (Courtesy of George J. Harocopos, MD.)

As an exposed surface, the conjunctiva is vulnerable to contact with foreign bodies. Some may be transient and/or inert, whereas others may become embedded and incite a foreign-body reaction, identifiable histologically as a granuloma surrounding the foreign object. Multinucleated giant cells are common. Viewing the tissue section under polarized light may be helpful in identifying the offending foreign material (Fig 5-7).

Infectious Conjunctivitis

A wide variety of pathogens may infect the conjunctiva, including viruses, bacteria, atypical bacteria (eg, chlamydiae), fungi, and parasites. The most common offending agents in children are bacterial

(Haemophilus influenzae, Streptococcus pneumoniae) and, in adults, viral; the usual culprits are adenovirus and the herpesviruses (simplex and zoster). Viral infections, in addition to inciting a follicular conjunctivitis, often affect the cornea, resulting in ulcers in herpetic disease (see Chapter 6) and subepithelial infiltrates in adenoviral disease. Specific diagnosis of infectious conjunctivitis may be made based on clinical history and examination (typically sufficient for viral disease), or it may require Gram stain/culture, PCR, or serology, depending on the organism. In cases of diagnostic uncertainty or cases unresponsive to initial treatment, exfoliative (ie, impression) cytology of ocular surface epithelium or tissue biopsy may be helpful in establishing a definitive diagnosis.