Ординатура / Офтальмология / Английские материалы / Ocular Pathology_6th edition_Yanoff, Sassani_2009

or curlicued conjunctival capillary segments, mostly near

the limbus, often seemingly isolated from the vascular network (Paton’s sign).

Similar conjunctival capillary abnormalities may occasionally be seen in the nasal and temporal conjunctiva in patients without sickle-cell disease. Abnormalities in the inferior conjunctiva, however, are found almost exclusively in patients with sickle-cell disease. The vascular abnormalities seem positively related to the presence of sickled erythrocytes and may be useful in gauging the severity of the systemic disease. The comma-shaped capillaries are most easily seen after local application of phenylephrine.

III.Histologically, the capillary lumen is irregular and filled with sickled erythrocytes.

Conjunctival Hemorrhage

(Subconjunctival Hemorrhage)

I.Intraconjunctival hemorrhage (see Fig. 5.30) into the substantia propria, or hemorrhage between conjunctiva and

episclera, most often occurs as an isolated finding without any obvious cause.

II.The condition may occasionally result from trauma; severe conjunctival infection (e.g., leptospirosis and typhus); local vascular anomalies; sudden increase in venous pressure

(e.g., after a paroxysm of coughing or sneezing); local manifestation of such systemic diseases as arteriolosclerosis, nephritis, diabetes mellitus, and chronic hepatic disease; blood dyscrasias, especially when anemia and thrombocytopenia coexist; acute febrile systemic infection (e.g., subacute bacterial endocarditis); spontaneously during menstruation; and trichinosis.

III.Histologically, blood is seen in the substantia propria of the conjunctiva.

Lymphangiectasia

I.Abnormal di use enlargement of lymphatics appears clinically as chemosis. Localized, dilated lymphatics appear

clinically as a cyst or a series of cysts, the latter commonly in the area of the interpalpebral fissure.

II.When involvement is di use, the cause is not usually known.

An old scar, a pinguecula, or some other conjunctival lesion usually obstructs localized, dilated lymphatics secondarily.

III.Histologically, the lymphatic vessels are abnormally dilated.

Lymphangiectasia Hemorrhagica

Conjunctivae

I.The condition is characterized by a connection between a blood vessel and a lymphatic so that the latter is permanently or intermittently filled with blood.

II. The cause is not known.

Ataxia–Telangiectasia

See p. 36 in Chapter 2.

Diabetes Mellitus

See section Conjunctiva and Cornea in Chapter 15.

Hemangioma and Lymphangioma

See pp. 544 and 545 in Chapter 14.

INFLAMMATION

Basic Histologic Changes

I.Acute conjunctivitis (Fig. 7.2)

A.Edema (chemosis), hyperemia, and cellular exudates are characteristic of acute conjunctivitis.

B.Inflammatory membranes (Fig. 7.3)

1.A true membrane consists of an exudate of fibrin– cellular debris firmly attached to the underlying epithelium by fibrin.

a.Characteristically, when the true membrane is removed, the epithelium is also stripped o , leaving a raw, bleeding surface.

b.The condition may be seen in epidemic kerato-

conjunctivitis, Stevens–Johnson syndrome, and infections caused by Pneumococcus, Staphylococcus aureus, and Corynebacterium diphtheriae.

2.A pseudomembrane consists of a loose fibrin– cellular debris exudate not adherent to the underlying epithelium, from which it is easily stripped.

a.This finding can be associated with epidemic keratoconjunctivitis, Stevens–Johnson syndrome, pharyngoconjunctival fever, vernal con-

junctivitis, ligneous conjunctivitis, chemical burns (especially alkali), and infections caused by

C. diphtheriae and Streptococcus pyogenes.

3.Ligneous conjunctivitis (Fig. 7.4) is an unusual type of bilateral, chronic, recurrent, membranous or pseudomembranous conjunctivitis of childhood, most commonly in girls, of unknown cause.

a.The condition persists for months to years and may become massive.

b.The conjunctivitis is characterized by wood-like induration of the palpebral conjunctiva, chronicity, and rapid recurrence after medical or surgical treatment.

c.Severe corneal complications may occur.

d.Similar lesions may also occur in the larynx, vocal cords, trachea, nose, vagina, cervix, and gingiva.

e.Rarely, the middle ear may exhibit a similar histopathologic process.

f.Histologically, the conjunctival epithelium is thickened and may be dyskeratotic.

The subepithelial tissue consists of an enormously thick membrane composed primarily of fibrin, albumin, immunoglobulin G (IgG), and an amorphous eosinophilic material containing a sprinkling of T and B lymphocytes and plasma cells.

C.Ulceration, or loss of epithelium with or without loss of subepithelial tissue associated with an inflammatory cellular infiltrate, may occur with acute conjunctivitis.

D.A phlyctenule usually starts as a localized, acute inflammatory reaction, followed by central necrosis and infiltration by lymphocytes and plasma cells.

II.Chronic conjunctivitis (Fig. 7.5)

A.The epithelium and its goblet cells increase in number (i.e., become hyperplastic).

Infoldings of the proliferated epithelium and goblet cells may resemble glandular structures in tissue section and are called pseudoglands (Henle). Commonly, the surface openings of the pseudoglands, especially in the inferior palpebral conjunctiva, may become clogged by debris. They form clear or yellow cysts called pseudoretention cysts, containing mucinous secretions admixed with degenerative products of the epithelial cells.

B.The conjunctiva may undergo papillary hypertrophy (Fig.

7.6), which is caused by the conjunctiva being thrown into folds.

1.The folds or projections are covered by hyperplastic epithelium and contain a core of vessels surrounded

by edematous subepithelial tissue infiltrated with chronic inflammatory cells (lymphocytes and plasma cells predominate).

2.Papillary hypertrophy is primarily a vascular response.

3.The lymphocyte (even lymphoid follicles) and plasma cell infiltrations are secondary.

Clinically, the small (0.1 to 0.2 mm), hyperemic projections are fairly regular, are most marked in the upper palpebral conjunctiva, and contain a central tuft of vessels. The valleys between the projections are pale and relatively vessel-free. Papillae characterize the subacute stage of many inflammations (e.g., vernal catarrh and the floppyeyelid syndrome; decreased tarsal elastin may contribute to the laxity of the tarsus in the floppy-eyelid syndrome).

C.The conjunctiva may undergo follicle formation. Follicular hypertrophy (Fig. 7.7) consists of lymphoid hyperplasia and secondary visualization.

Lymphoid tissue is not present in the conjunctiva at birth but normally develops within the first few months. In inclusion blennorrhea of the newborn, therefore, a papillary reaction develops, whereas the same infection in adults may cause a follicular reaction. Lymphoid hyperplasia develops in such diverse conditions as drug toxicities (e.g., atropine, pilocarpine, eserine), allergic conditions, and infections (e.g., trachoma). It has been reported, presumably, as secondary to extremely thin sclera in high myopia. Clinically, lymphoid follicles are smaller and paler than papillae and lack the central vascular tuft.

D.Vitamin A deficiency or drying of the conjunctiva (e.g., chronic exposure with lid ectropion) may cause keratinization.

E.Chronic inflammation during healing may cause an overexuberant amount of granulation tissue to be formed (i.e., granuloma pyogenicum; see Fig. 6.11).

F.The conjunctiva may be the site of granulomatous inflammation (e.g., sarcoid; see p. 93 in Chapter 4).

G.Conjunctival epithelium of patients on chronic topical medical treatment, such as individuals with glaucoma, demonstrates increased expression of immunoinflammatory markers such as HLA-DR, and interleukins

IL-6, IL-8, and IL-10 in impression cytology specimens.

H.Clinical and/or histopathologic demonstration of tarsal conjunctival disease may be evidenced by: (1) conjunctival hyperemia and granuloma formation, areas of necrosis, or active fibrovascular changes in the tarsus or conjunctiva; or (2) an inactive fibrovascular scar associated with subglottic stenosis and nasolacrimal duct obstruction in patients with Wegener’s granulomatosis

(WG).

III.Ligneous conjunctivitis (see earlier, this chapter).

IV. Scarring of conjunctiva

A.Ocular cicatricial pemphigoid (benign mucous membrane pemphigoid, pemphigus conjunctivae, chronic cicatrizing conjunctivitis, essential shrinkage of conjunctiva)

1.Ocular cicatricial pemphigoid is a rare, T-cell immune-mediated, bilateral (one eye may be involved first), blistering, chronic conjunctival disease. It may involve the conjunctiva alone or, more commonly, other mucous membranes and skin in elderly people.

The conjunctiva is the only site of involvement in most cases. Drugs such as echothiophate iodide, pilocarpine, idoxuridine, and epinephrine may induce a pseudopemphigoid conjunctival reaction.

2.The disease results in shrinkage of the conjunctiva

(secondary to scarring),trichiasis,xerosis, and finally reduced vision from secondary corneal scarring.

At the onset of the condition, an acute or subacute papillary conjunctivitis and diffuse hyperemia are common. One or two small conjunctival ulcers covered by a gray membrane are often noted. Keratinization of the caruncu-

lar region (i.e., medial canthal keratinization) is a reliable early sign of ocular cicatricial pemphigoid, especially if entities such as Stevens–Johnson are excluded. The ulcers heal by cicatrization, as new ulcers form. The condition occurs more frequently in women.

3.About 22% of patients who have systemic, nonocular, mucous membrane pemphigoid develop ocular disease.

4.Histology

a.Subepithelial conjunctival bullae rupture and are replaced by fibrovascular tissue containing lymphocytes (especially T cells), dendritic (Langerhans’) cells, and plasma cells.

1). The epithelium has an immunoreactive deposition (immunoglobulin or complement) along its basement membrane zone. The presence of circulating antibodies to the epithelial basement membrane zone can also be helpful in making the diagnosis. Such immunohistochemical confirmation is important because the clinical characteristics of ocular mucous membrane pemphigoid and pseudopemphigoid are similar, which may lead to a clinical misdiagnosis.

a). Increased conjunctival expression of

IL-4 may play an important role in the regulation of local accumulation of macrophages by inducing macrophage colony-stimulating factor, and of matrix accumulation by inducing heat shock protein-47 during conjunctival scarring in patients with ocular cicatricial pemphigoid, thereby contributing to conjunctival inflammatory and subsequent

fibrotic responses associated with the disorder. Moreover, increased expression of collagen-binding heat shock protein-47 and transforming growth factor beta1 by conjunctival fibroblasts in ocular cicatricial pemphigoid may regulate increased synthesis, assembly, and production of collagens, thereby further contributing to conjunctival scaring in pemphigoid.

b). Increased expression of connective tissue growth factor has been demonstrated in the conjunctiva of patients with ocular cicatricial pemphigoid, and it is probably one of the factors involved in the pathogenesis of the typical conjunctival fibrosis in the disorder.

c). Macrophage colony-stimulating factor has increased expression in conjunctiva in ocular cicatricial pemphigoid, and there is a positive correlation between its expression and the accumulation of macrophages in conjunctival biopsies in patients with pemphigoid.

2). The use of the immunoperoxidase technique in biopsy material may increase the diagnostic yield in clinically suspected cases.

Ocular cicatricial pemphigoid, bullous pemphigoid, and benign mucous membrane pemphigoid, all immune-mediated blistering diseases, resemble each other clinically, histopathologically, and immunologically. Ocular cicatricial pemphigoid, however, appears to be a unique entity separated from the others by antigenic specificity of autoantibodies. Another systemic blistering condition, epidermolysis bullosa acquisita, can cause symblepharon and small, subepithelial corneal vesicles.

a). The vascular and inflammatory components lessen with chronicity, resulting in contracture of the fibrous tissue with subsequent shrinkage, scarring, symblepharon, ankyloblepharon, and so forth.

3). Expression of macrophage migration inhibitory factor is increased in cicatricial pemphigoid and may help regulate the inflammatory events in this disorder.

4). Elevated numbers of conjunctival mast cells are not only associated with atopic keratoconjunctivitis, but are also present in ocular cicatricial pemphigoid and Stevens–Johnson syndrome.

Pemphigus, a group of diseases that have circulating antibodies against intercellular substances or keratinocyte surface antigens, unlike pemphigoid, is characterized histologically by acantholysis, resulting in intraepidermal vesicles and bullae rather than subepithelial vesicles and bullae. The bullae of pemphigus, unlike those of pemphigoid, tend to heal without scarring. In pemphigus, the conjunctiva is rarely involved, and even then scarring is not a prominent feature. Unilateral refractory (erosive) conjunctivitis may be an unusual manifestation of pemphigus vulgaris.

B.Secondary scarring occurs in many conditions. Some examples are chemical burns, erythema multiforme

(Stevens–Johnson syndrome), old membranous conjunctivitis (diphtheria, β-hemolytic Streptococcus, adenovirus, primary herpes simplex), trachoma, trauma (surgical or nonsurgical), paraneoplastic pemphigus, and pemphigus vulgaris. Deliberate chronic use of high-dose topical hydrogen peroxide has resulted in severe corneal and conjunctival changes that can mimic ocular cicatricial pemphigoid. Cicatricial conjunctivitis may be a manifestation of porphyria cutanea tarda.

C.Conjunctival involvement in toxic epidermal necrolysis has been reported in association with autoimmune polyglandular syndrome type I, which is defined as the presence of two of the following diseases: Addison’s

disease, hypoparathyroidism, and chronic mucocutaneous candidiasis.

Specific Inflammations

Infectious

I.Virus—see subsection Chronic Nongranulomatous Inflammation in Chapter 1.

II.Bacteria—see sections Phases of Inflammation in Chapter

1 and Suppurative Endophthalmitis and Panophthalmitis in

Chapter 3.

III.Chlamydiae cause trachoma, lymphogranuloma venereum, and ornithosis (psittacosis).

A.Previously classified as “large” viruses, they have been

shown to be Gram-negative, basophilic, coccoid or spheroid bacteria. Because of certain similarities to rickettsiae, they may be classified in that group.

B.The chlamydiae are identified taxonomically into order

Chlamydiales, family Chlamydiaceae, genus Chlamydia, and species trachomatis and psittaci.

The agents that cause trachoma and inclusion conjunctivitis, both classified as Chlamydia trachomatis, are almost indistinguishable from each other, and the term TRIC agent encompasses both. Reproduction of chlamydiae starts with the

attachment and penetration of the elementary body, an infectious small particle 200 to 350 nm in diameter with an electrondense nucleoid, into the host cell cytoplasm. The phagocytosed agent surrounded by the invaginated host cell membrane forms a cytoplasmic inclusion body. The elementary body then enlarges to approximately 700 to 1000 nm in diameter to form a nonmotile obligate intracellular (cytoplasmic) parasite (called an energy parasite because of its dependence on the host cell for energy) known as an initial body that does not contain electron-dense material. Initial bodies then divide by binary fission into numerous, small, highly infectious elementary bodies. The host cell ruptures, the elementary bodies are released, and a new infectious cycle begins.

C.Trachoma (Fig. 7.8)

1.Trachoma, caused by the bacterial agent C. trachomatis and one of the world’s leading causes of blindness, primarily a ects the conjunctival and corneal epithelium.

2.Healing is marked by scarring or cicatrization.

3.Histology of MacCallan’s four stages:

a.Stage I: early formation of conjunctival follicles, subepithelial conjunctival infiltrates, di use punctate keratitis, and early pannus

1). The conjunctival epithelium undergoes a marked hyperplasia, and its cytoplasm contains clearly defined, glycogen-containing

e

i

intracellular microcolonies of minute elementary bodies and large basophilic initial bodies.

2). The bodies form the conjunctival and corneal epithelial cytoplasmic inclusion bodies of

Halberstaedter and Prowazek.

3). The subepithelial tissue is edematous and infiltrated by round inflammatory cells.

4). Fibrovascular tissue from the substantia propria proliferates and starts to grow into the cornea under the epithelium, destroying

Bowman’s membrane; the tissue is then called an inflammatory pannus.

b.Stage II: florid inflammation, mainly of the upper tarsal conjunctiva with the early formation of follicles appearing like sago grains, and then like papillae

1). The corneal pannus increases and large macrophages with phagocytosed debris (Leber cells) appear in the conjunctival substantia propria.

2). The follicles cannot be di erentiated histologically from lymphoid follicles secondary to other causes (e.g., allergic).

c.Stage III: scarring (cicatrization)

In the peripheral cornea, follicles disappear

and the area is filled with thickened, transparent epithelium (Herbert’s pits); as the palpebral conjunctiva heals, a white linear horizontal line

or scar forms near the upper border of the tarsus (von Arlt’s line). Cicatricial entropion and trichiasis may result.

1). Ocular rosacea can produce chronic cicatrizing conjunctivitis of the upper eyelids, which was previously thought to be unique to trachoma. Conjunctival impression cytology in ocular rosacea demonstrates significant ocular surface epithelial degeneration involving both the upper bulbar and inferonasal interpalpebral bulbar epithelium compared to normal individuals.

The inflammatory infiltrate of the tarsoconjunctiva is predominantly composed of T cells (CD4+ and CD8+), and suggests that T cells may be involved in the genesis of both tarsal thickening and conjunctival scarring in the late stages of trachoma.

d. Stage IV: arrest of the disease

D.Inclusion conjunctivitis (inclusion blennorrhea)

1.Inclusion conjunctivitis is caused by the bacterial agent C. trachomatis (oculogenitale).

2.It is an acute contagious disease of newborns quite similar clinically and histologically to trachoma, except the latter has a predilection for the upper rather than the lower palpebral conjunctiva and fornix.

Inclusion conjunctivitis can also occur in adults, commonly showing corneal involvement (mainly superficial epithelial keratitis, but also subepithelial nummular keratitis, marginal keratitis, and superior limbal swelling and pannus formation).

3.Histologically, a follicular reaction is present with epithelial cytoplasmic inclusion bodies indistinguishable from those of trachoma.

E.Lymphogranuloma venereum (inguinale)

1. Lymphogranuloma venereum, also caused by the bacterial agent C. trachomatis, is characterized

by a follicular conjunctivitis or a nonulcerating conjunctival granuloma, usually near the limbus and associated with a nonsuppurative regional

lymphadenopathy.

The clinical picture is that of Parinaud’s oculoglandular syndrome (see later).

Keratitis may occur, usually with infiltrates in the upper corneal periphery, associated with stromal vascularization and thickened corneal nerves. An associated anterior uveitis may also occur.

2.Histologically, a granulomatous conjunctivitis and lymphadenitis occur, the latter containing stellate abscesses.

Elementary bodies and inclusion bodies cannot be

identified in histologic sections.

IV. Fungal—see the subsection Fungal, section Nontraumatic

Infections in Chapter 4.

V.Parasitic—see the subsection Parasitic, section Nontraumatic Infections in Chapter 4 and pp. 88, and 273 in Chapter

8.

VI. Rickettsial—because of certain similarities to rickettsias,

chlamydiae may be classified in this group.

VII. Parinaud’s oculoglandular syndrome (granulomatous conjunctivitis and ipsilateral enlargement of the preauricular lymph nodes) consists of a granulomatous inflammation and may be caused most commonly by cat-scratch disease, but also by Epstein–Barr virus infection, tuberculosis, sar-

coidosis, syphilis, tularemia, Leptothrix infection, soft chancre (chancroid—Haemophilus ducreyi), glanders, lym-

phogranuloma venereum, Crohn’s disease, and fungi.

Noninfectious

I.Physical—see subsections Burns and Radiation Injuries

(Electromagnetic) in Chapter 5.

II.Chemical—see subsection Chemical Injuries in Chapter 5. III. Allergic

A.Allergic conjunctivitis is usually associated with a type

1 hypersensitivity reaction. It can be further subdivided into acute disorders (seasonal allergic conjunctivitis and perennial allergic conjunctivitis), and chronic diseases (vernal conjunctivitis, atopic keratoconjunctivitis, giant papillary conjunctivitis). Mast cells play a central role in the pathogenesis of ocular allergy. Their numbers are

increased in all forms of allergic conjunctivitis, and may participate in the process through their activation, resulting in the release of preformed and newly formed mediators. Chronic conjunctivitis may be accompanied by remodeling of the ocular surface tissues.

B.Vernal keratoconjunctivitis (vernal catarrh, spring catarrh; Fig. 7.9)

1.Vernal keratoconjunctivitis tends to be a bilateral, recurrent, self-limited conjunctival disease occurring mainly in warm weather and a ecting young people (mainly boys).

a.It is of unknown cause, but is presumed to be an immediate hypersensitivity reaction to exogenous antigens.

b.The disease is associated with increased serum levels of total IgE, eosinophil-derived products, and nerve growth factor.

Nerve growth factor may play a role in vernal keratoconjunctivitis by modulating conjunctival mast cell proliferation, differentiation, and activation. Also, the enzymatic degradation of histamine in both tears and plasma appears to be significantly decreased in patients who have vernal keratoconjunctivitis.

c.It has been postulated that vernal conjunctivitis is a Th2 lymphocyte-mediated disease in which

mast cells, eosinophils, and their mediators play major roles in the clinical manifestations. This process, therefore, involves the Th2-derived cytokines, IL-4, IL-5, and IL-13, as well as other chemokines, growth factors, and enzymes, which are overexpressed in the disorder. Eventually, structural cells, such as epithelial cells and fibroblasts, are involved both in the inflammatory process and in tissue remodeling, eventuating in the characteristic giant papillae.

d.Chronic conjunctival inflammation in vernal keratoconjunctivitis is associated with staining of alpha3, and alpha6 integrin subunits, epidermal growth factor (EGF) receptor, vascular endothelial growth factor, transforming growth factor-beta, basic fibroblast growth factor, and platelet-derived growth factor that might mediate conjunctival remodeling.

e.The CXC chemokine Mig is selectively and highly expressed in vernal keratoconjunctivitis, and it has been suggested that this finding indicates a pathogenic role for the chemokine receptor CXCR3 and the ligand Mig in the recruitment of activated T lymphocytes.

f.Unique intercellular communication between corneal epithelium and conjunctival cellular elements through the tear film, and mediated

by proinflammatory and T-helper 2 cytokines, chemokines such as eotaxin and thymus and activation-regulated chemokine (TARC), and adhesion molecules such as intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), may contribute to the pathogenesis of vernal keratoconjunctivitis.

g.Cultured fibroblasts and conjunctival papillae from patients with vernal keratoconjunctivitis demonstrate that trypase increases conjunctival fibroblast proliferation,and this response appears to be mediated by protease-activated receptor

(PAR)-2. Mast cells have been postulated to be the most likely source for the trypase.

A condition called giant papillary conjunctivitis resembles vernal conjunctivitis. It occurs in contact lens wearers as a syndrome consisting of excess mucus and itching, diminished or destroyed contact lens tolerance, and giant papillae in the upper tarsal conjunctiva.

2.Vernal conjunctivitis may be associated with, or accompanied by, keratoconus (or, more rarely, pellucid marginal corneal degeneration, keratoglobus, or superior corneal thinning).

3.Involvement may be limited to the tarsal conjunctiva (palpebral form), the bulbar conjunctiva (limbal form), or the cornea (vernal superficial punctate keratitis form), or combinations of all three. It is mediated, at least in part, by IgE antibodies produced in the conjunctiva.

4.Histology

a.The tarsal conjunctiva may undergo hyperplasia of its epithelium and proliferation of fibrovascular connective tissue along with an infiltration of round inflammatory cells, especially eosinophils and basophils.

Papillae that form as a result can become quite large, clinically resembling cobblestones.

b.The epithelium and subepithelial fibrovascular connective tissue of the limbal conjunctival region may undergo hyperplasia and round-cell inflammatory infiltration, with production of limbal nodules.

c.In the larger yellow or gray vascularized nodules,

concretions, containing eosinophils, appear clinically as white spots (Horner–Trantas spots).

d.Degeneration and death of corneal epithelium result in punctate epithelial erosions that are especially prone to occur in the upper part of the cornea.

Eosinophilic granule major basic protein (the core of the eosinophilic granule) may play a role in the devel-

opment of corneal ulcers associated with vernal keratoconjunctivitis.

C. Inflammatory cells (eosinophils and neutrophils) in

brush cytology specimens from the tarsus correlate with corneal damage in atopic keratoconjunctivitis.

In atopic blepharoconjunctivitis, the tear content of group IIA phospholipase A2 is decreased without any dependence on the quantity of di erent conjunctival cells.

Mast cell densities are increased in the bulbar and tarsal substantia propria in seasonal atopic keratoconjunctivitis and atopic blepharoconjunctivitis, but only in the bulbar substantia propria in atopic conjunctivitis. Ocular surface inflammation, tear film instability, and decreased conjunctival MUC5AC mRNA expression are thought to be important in the pathogenesis of noninfectious corneal shield ulcers in atopic ocular disease. Reactive oxygen species generated by NAD(P)H oxidases in pollen grains may intensify immediate allergic reactions and recruitment of inflammatory cells in the conjunctiva.

D.Hayfever conjunctivitis

E.Contact blepharoconjunctivitis

F.Phlyctenular keratoconjunctivitis IV. Immunologic

A.Graft-versus-host disease (GvHD) conjunctivitis

1.A significant percentage (perhaps 10%) of patients who have had an allogeneic (an HLA-identical donor, e.g., a sibling) bone marrow transplantation develop a distinct type of conjunctivitis, representing GvHD of the conjunctiva.

2.It presents with pseudomembrane formation secondary to loss of the conjunctival epithelium.

3.In approximately 20% of these cases, the corneal epithelium also sloughs.

4.Conjunctival ICAM-1 expression is increased in

GvHD patients, and the severity of the disease is associated with abnormal tear parameters, goblet cell decrease, and inflammatory markers such as

ICAM-1.

5.After autologous bone marrow transplant there appears to be a subclinical cell-mediated immune reaction; moreover, T cells and macrophages are major contributors to the conjunctivitis of chronic

GvHD.

Another ocular manifestation mediated by GvHD is keratoconjunctivitis sicca.

B.Wegerer’s granulomatosis (WG) should be considered when conjunctival inflammation is recurrent and not typical of other conjunctival inflammatory conditions. Based on assessment of the presence of major basic protein and eosinophil cationic protein, it has been suggested that activated eosinophils in the sclera or conjunctiva of patients with ocular limited WG may predict the progression to complete WG.

C.Isolated congenital histiocytosis has involved the palpebral conjunctival in a newborn infant. Histopathologic examination revealed a cellular infiltrate composed of eosinophils and histiocytes without skin or systemic involvement. Immunohistochemistry was positive for S-100 and CD1 antigenic determinant.

D.Inflammatory pseudotumor, characterized by the presence of aggregates of chronic inflammatory cells (lymphocytes, plasma cells, neutrophils, and fibroblasts) without noncaseating epithelioid granuloma formation, has been reported to occur simultaneously in the conjunctiva and lung.

E.Rarely, conjunctival ulceration may be a manifestation of Behçet’s disease, and is characterized on histopathologic examination by disrupted epithelium, infiltration by both acute and chronic inflammatory cells, and high endothelial venules. Immunohistologic studies of the inflammatory infiltrate reveal primarily T-cell populations admixed with several B cells and CD68-positive histiocytes.

V.Neoplastic processes (e.g., sebaceous gland carcinoma) can cause a chronic nongranulomatous blepharoconjunctivitis with cancerous invasion of the epithelium and subepithelial tissues.

A.Sebaceous carcinoma may involve the conjunctival epithelium in 47% of cases, of which the superior tarsal and forniceal conjunctiva are involved in 100%; inferior tarsal conjunctiva, 68%; inferior forniceal conjunctiva,

64%; superior bulbar conjunctiva, 68%; and inferior bulbar conjunctiva, 57%. The caruncle is involved in

54% and the cornea in 39%. Metastasis occur in

11%.

B.Impression cytology may be useful in the detection of conjunctival intraepithelial invasion by sebaceous gland carcinoma; however, full-thickness biopsies are necessary to confirm the diagnosis.

INJURIES

See Chapter 5.

CONJUNCTIVAL MANIFESTATIONS OF SYSTEMIC DISEASE

Deposition of Metabolic Products

I. Cystinosis (Lignac’s disease)—see Fig. 8.41. II. Ochronosis—see p. 314 in Chapter 8.

III. Hypercalcemia—see p. 279 in Chapter 8.

IV. Addison’s disease: melanin is deposited in the basal layer of the epithelium.

V. Mucopolysaccharidoses—see p. 298 in Chapter 8. VI. Lipidosis—see pp. 450–453 in Chapter 11.

VII. Dysproteinemias

VIII. Porphyria

IX. Jaundice

A.Bilirubin salts are deposited di usely in the conjunctiva and episclera, but not usually in the sclera unless the

jaundice is chronic and excessive; even in the latter case, the bulk of the bilirubin is in the conjunctiva (scleral icterus, therefore, is a misnomer).

B.Rarely, the icterus can extend into the cornea.

X. Malignant atrophic papulosis (Degos’ syndrome)—see

p. 186 in Chapter 6.

XI. The characteristic anterior-segment finding in Fabry disease is corneal verticillata, which is secondary to glycosphingolipid deposition in the cornea. In vivo confocal microscopy of the conjunctiva demonstrates abnormalities throughout the ocular surface, including bright roundish intracellular inclusions, which are more pronounced in tarsal than in bulbar conjunctiva.

XII. Consistent, qualitative abnormalities in conjunctival fibril- lin-1 staining pattern can be seen in the conjunctiva of patients with Marfan syndrome with ectopia lentis.

XIII. Squamous metaplasia of the conjunctival epithelium and corneoconjunctival calcification frequently accompany chronic renal failure requiring hemodialysis. Abnormal tear function is associated with squamous metaplasia, but not with corneoconjunctival calcification. Similarly, although impression cytology demonstrates more frequent and extensive deposits of calcium deposits in the conjunctiva of chronic failure patients on regular hemodialysis compared to control patients, the severity of conjunctival squamous metaplasia associated with chronic renal failure appears not to be related to calcium deposition, but rather, to acute conjunctival inflammation.

Deposition of Drug Derivatives

I.Argyrosis (Fig. 7.10)

A.Long-term use of silver-containing medications may result in a slate-gray discoloration of the mucous membranes, including the conjunctiva, and of the skin, including the lids. The discoloration may also involve the nasolacrimal apparatus.

B.Histologically, silver is deposited in reticulin (i.e., loose collagenous) fibrils of subepithelial tissue and in basement membranes of epithelium, endothelium (e.g., Descemet’s membrane), and blood vessels.

II. Chlorpromazine—see p. 313 in Chapter 8.

III. Atabrine

IV. Epinephrine

A.Conjunctival or corneal deposition can follow longterm use of epinephrine.

B.Epinephrine may deposit under an epithelial bleb, where it becomes oxidized to a compound similar to melanin.

1.Occasionally, the black corneal deposit (black cornea) has been mistaken for malignant melanoma of the cornea.

C.Histologically, an amorphous pink material that bleaches and reduces silver salts is found between