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

3.The condition is usually sporadic (frequency approximately 1 :3000 births), not inherited, and on occasion may be related to first-trimester maternal intake of a teratogenic agent.

4.Histologically, the epibulbar dermoids appear the same as those found elsewhere.

Encephalocraniocutaneous lipomatosis (congenital neurocutaneous syndrome including epibulbar choristomas and connective tissue nevi of the eyelids) should be considered, along with the sebaceous nevus and the Golden- har–Gorlin syndromes, in the differential diagnosis of epibulbar choristomas.

XI. Dentatorubropallidoluysian atrophy

A.This neurodegenerative disorder is characterized by choreoathetoid movements, myoclonic seizures, cerebellar ataxia, and dementia.

B.Decreased corneal endothelial density may be the only ocular finding.

C.The definitive diagnosis may be made on DNA

analysis. XII. Miscellaneous

Endothelial abnormalities have been reported in an

African American family having a syndrome also characterized by abnormal craniofacial features, and absence of the roof of the sella turcica. Other findings include abnormalities in the maintenance of retinal bipolar cells and of bipolar cells of the auditory system.

One variation and one mutation of the homeobox transcription factor gene, VSX1 (RINX), characterize this family.

INFLAMMATIONS—NONULCERATIVE

Epithelial Erosions and Keratitis

I.Epithelial erosion may be secondary to traumatic, toxic, radiation-induced (e.g., ultraviolet), or inflammatory (e.g., rubeola) keratitis, or to inherited corneal dystrophies such as lattice and Reis–Bücklers.

A.The condition is characterized by damage to the corneal epithelial cells, best seen after fluorescein staining of the cornea.

II.Epithelial keratitis may be caused by the same entities that cause epithelial erosions.

A.It is characterized by large areas of epithelial damage that can be seen grossly without the aid of fluorescein.

B.Thygeson’s superficial punctate keratitis is a recurrent corneal disease of unknown cause, characterized by focal epithelial lesions.

1.The condition is usually bilateral, corneal sensation remains intact, and no accompanying conjunctivitis occurs.

2.Patients have symptoms of tearing, irritation, and photophobia.

3. The disorder is chronic and may last for 11 years.

C.(See Chapters 3 and 4.)

Microsporidial keratitis is usually a disorder of immunocompromised individuals; however, it has been reported to involve apparently immunocompetent patients.

III.Histologically, epithelial erosion and keratitis show prominent basal cell edema of the epithelium, absent hemidesmosomes, and separation of the cells from their basement membrane.

Subepithelial Keratitis

I.Epidemic keratoconjunctivitis (EKC) is a combined epithelial and subepithelial punctate keratitis mainly caused by adenovirus type 8.

The subepithelial opacities, unlike the fine or medium-sized ones with adenoviruses types 3, 4, and 7, tend to be like a cluster of coarse, tiny bread crumbs. The epithelial component is evanescent. Similar findings may be seen with adenovirus type 19. Adenovirus type 8 is the most common cause of EKC. Adenoviruses 3 and 7 are the most common causes of sporadic EKC. Other types (e.g., 1, 2, 4 to 6, 9 to 11, 13 to 15, and 29) may also cause moderate to severe EKC. Among the many other causes of subepithelial keratitis are rosacea, pharyngoconjunctival fever, onchocerciasis, and Crohn’s disease. The causes of nummular keratitis must also be considered [e.g., Dimmer’s (and related processes of Westhoff and of Langraulet) nummular keratitis and the similar interstitial keratitis of Epstein–Barr virus infection, inclusion conjunctivitis (Chlamydia), herpes simplex and herpes zoster infection, and brucellosis].

II. Trachoma (see p. 231 in Chapter 7)

III. Leprosy (see p. 81 in Chapter 4)

Superior Limbic Keratoconjunctivitis

I.Superior limbic keratoconjunctivitis (SLK) is characterized by marked inflammation of the tarsal conjunctiva of the upper lid, inflammation of the upper bulbar conjunctiva, fine punctate fluorescein or rose Bengal staining of the cornea at the upper limbus and adjacent conjunctiva above the limbus, and superior limbic proliferation.

II.In approximately one-third of all attacks, filaments occur at the superior limbus or upper cornea.

III.SLK may be associated with thyroid dysfunction and appears to be a prognostic marker for severe Graves’ ophthalmopathy.

IV. The cause is unknown.

V.Histology

A.The conjunctiva shows prominent keratinization of the epithelium with dyskeratosis, acanthosis, cellular infiltration (neutrophils, lymphocytes, and plasma cells), and balloon degeneration of some nuclei.

B.Electron microscopy shows abnormal distribution and aggregation of nuclear chromatin, filaments in nuclei, dense accumulations of cytoplasmic filaments that surround nuclei and “strangulate” them, and formation of

multilobed nuclei or multinucleated inflammatory cells.

Stromal (Interstitial) Keratitis

I.Viral causes

A.Herpes simplex virus (HSV; see p. 270 in this chapter)

It is believed that CD4+ T cells orchestrate the immunologic and inflammatory processes involved in herpes stromal keratitis; however, other variables such as virus replication, cytokine and chemokine production, neovascularization, and contribu-

tions from other inflammatory cell types probably set the stage for CD4+ T-cell activities. Conversely, CD8+ T cells reactive to HSV are capable of clearing the virus. Interleukin-17 may play an important role in the induction and/or perpetuation of the immunopathologic processes in human HSV keratitis by modulating the secretion of proinflammatory and neutrophil chemotactic factors by resident corneal fibroblasts. It also probably plays an important role in angiogenesis and tumor growth.

B.Herpes zoster virus (see p. 78 in Chapter 4)

C.Epstein–Barr virus (see p. 63 in Chapter 3)

A

e

s

b

d

C

II.Bacterial causes

A. Syphilis (Fig. 8.10; see also Fig. 8.3B)

1.Widespread inflammatory infiltrate of the corneal stroma, especially of the deeper layers, is characteristic of luetic keratitis.

2.An associated anterior uveitis is present in the early stages.

3.The congenital form

a.Usually it is bilateral and develops in the second half of the first decade or in the second decade of life.

It is rare for it to occur before 5 years of age, but the keratitis may be present at birth.

b.Initially, the cloudy cornea is a result of inflammatory cell infiltration associated with an anterior uveitis that is followed by ingrowth of blood vessels just anterior to Descemet’s membrane.

Sarcoidosis, tuberculosis, leprosy, syphilis, and Cogan’s syndrome can all produce a deep interstitial keratitis with deep stromal blood vessels.

B

D

c.The acute inflammation may last 2 to 3 months, followed by a regression over many months.

d.The corneal changes are frequently associated with Hutchinson’s teeth and deafness (i.e.,

Hutchinson’s triad).

4.The acquired form

a.It is a late manifestation with an average time of appearance of 10 years after the primary luetic infection.

b.It is usually unilateral and often limited to a sector-shaped corneal area.

5.Histology

a.The cornea is edematous and infiltrated by lymphocytes and plasma cells.

1). Blood vessels are present just anterior to Descemet’s membrane.

2). With healing, the edema and inflammatory cells disappear, the stroma becomes scarred, and the deep stromal blood vessels persist.

b.In congenital chronic interstitial keratitis, the regenerating corneal endothelium produces excess basement membrane (Descemet’s) in a variety of forms.

This produces thickenings of Descemet’s membrane, linear cornea guttata, ridges or networks of transparent material (glasleisten), and even

networks and strands that project into the anterior chamber.

B.Lyme disease (see p. 83 in Chapter 4)

C.Tuberculosis (see p. 79 in Chapter 4)

III. Parasitic causes

A.Protozoal—leishmaniasis and trypanosomiasis can cause a chronic interstitial keratitis.

B.Nematodal—onchocerciasis (Fig. 8.11)

1.Onchocerciasis is one of the leading causes of blindness in the world, a ecting 18 million children and young adults in endemic areas in Africa, and Central and South America.

Uveitis and peripheral anterior and posterior synechiae commonly cause a secondary angle-closure glaucoma. Chorioretinitis secondary to posterior involvement also occurs. The glaucoma and chorioretinitis, along with the keratitis, are common causes of the blindness. The ubiquitous bacteria, Wolbachia, colonizes the major pathogenic filarial nematode parasites of humans, including Onchocerca volvulus, and may contribute significantly to the inflammatory reaction within the eye.

2.Onchocerciasis manifests itself as a severe disease of the skin and eyes (river blindness).

3.In the acute phase of the infestation, nummular or snowflake corneal opacities form a superficial punctate keratitis.

4.A stromal punctate interstitial keratitis may also occur.

With careful slit-lamp examination, the microfilariae can sometimes be seen in the aqueous fluid in the anterior chamber.

5.Healing induces scar tissue to form in the corneal stroma along with a corneal pannus; the cornea can become completely opaque.

6.Optic neuritis and chorioretinitis may also occur and lead to blindness, especially in heavily infested young people.

7.The adult nematode worms, Onchocerca volvulus, produce microfilariae that migrate through skin and subcutaneous tissue (not blood) to reach ocular tissue.

The small black fly, Simulium species, ingests the microfilariae from an infected person and transmits them to the next human it bites.

Other filarial nematodes that may involve ocular structures include Loa loa and organisms that cause filariasis (e.g.,

Wuchereria bancrofti and Brugia malayi).

8.Histologically, the tiny worm is found along with an infiltrate of lymphocytes and plasma cells.

a.Immunologic cross-reactivity of a recombinant antigen of O. volvulus to a host ocular component of 44 000 M(r) antigen suggests that intraocular presentation of the cross-reactive parasite

antigen by microfilariae is essential for development of the ocular disease.

IV. Other causes

A.Cogan’s syndrome

1.Cogan’s syndrome consists of nonsyphilitic interstitial keratitis and vestibuloauditory involvement.

2.Patients and their parents have serologies negative for syphilis.

3.In approximately 70% of cases, an underlying systemic process, often a vasculitis (e.g., periarteritis), occurs.

4.Atypical presentation of hearing loss may precede corneal symptoms, and result in stromal neovascularization and lipid deposition.

B.Sarcoidosis (see p. 93 in Chapter 4)

C.Many other entities, such as atopic keratoconjunctivitis, Hodgkin’s disease, lymphogranuloma venereum, hypoparathyroidism, and mycosis fungoides, may cause a secondary stromal keratitis.

D.Deep stromal keratitis with endothelial involvement and the deposition of polyrefringent crystals may be seen in association with systemic lupus erythematosus.

Bilateral corneal immune ring (Wessely ring) can occur in Behçet’s disease.

Endothelial

Viral

Endotheliitis may follow mumps parotitis without evidence of epithelial involvement or iridocyclitis.

INFLAMMATIONS—ULCERATIVE*

Peripheral

I.Marginal (catarrhal) ulcer (keratitis; Fig. 8.12)

A.Marginal ulcer is usually superficial, single, and localized at the limbus or just within the clear cornea.

B.It may become circumferential to form a superficial marginal keratitis or even a ring ulcer.

*An ulcer is characterized by inflammation, necrosis, loss of tissue, progression, and chronicity.

The lesion appears as a gray, crescentic ulcer. It does not spread centrally, but may recur.

C.It is an allergic reaction to toxins or allergens of bacterial conjunctival infections, especially staphylococcal (i.e., an endogenous sensitization to bacterial protein).

D.It may also occur secondary to such systemic diseases as atopy, rheumatoid arthritis, Wegener’s granulomatosis, periarteritis nodosa, systemic lupus erythematosus, scleroderma, bacillary dysentery, or Crohn’s disease.

E.Histologically, lymphocytes and plasma cells predominate.

II. Phlyctenular ulcer

A.A phlyctenular ulcer appears early as a small, pinkishwhite elevation in a hyperemic limbus; the elevation then develops a central gray crater.

The lesion may remain stationary and evolve through necrosis, shelling out, and healing, or it may travel toward the center of the cornea as a narrow, gray, necrotic, superficial ulcer surrounded by a white infiltrate, having a narrow vascularized scar to mark its path.

B.It occurs mainly in children, in the first and second decades of life.

C.It is an allergic reaction to toxins or allergens of conjunctival infections, especially tuberculosis and staphylococcal (i.e., an endogenous sensitization to bacterial protein).

D.Histologically, lymphocytes and plasma cells

predominate.

III.Scleritis-associated peripheral keratopathy

A.This finding is associated with increased likelihood of necrotizing scleritis, decreased vision, anterior uveitis, impending corneal perforation, and potentially lethal

specific-disease association.

IV. Ring ulcer

A.A ring ulcer (i.e., a superficial ulcer involving the corneal limbus) most often develops in the evolution of super-

ficial marginal keratitis. It may also result from coalescence of several marginal ulcers.

B.A ring ulcer may be seen with acute systemic diseases such as influenza, bacillary dysentery, ulcerative colitis, acute leukemia, scleroderma, systemic lupus erythematosus, periarteritis nodosa, rheumatoid arthritis, Sjögren’s syndrome, Wegener’s granulomatosis, midline lethal granuloma syndrome (polymorphic reticulosis), porphyria, brucellosis, gonococcal arthritis, dengue fever, tuberculosis, hookworm infestation, and gold poisoning.

C.Ischemia, secondary to occlusion of anterior ciliary arteries, may play a major role in its development.

D.Histologically, the corneal area of involvement is infiltrated with neutrophils, lymphocytes, and plasma cells. Occlusive vasculitis of arteries may be found.

V.Ring abscess (see Fig. 5.23)

A.Usually, a ring abscess follows trauma to the eye (accidental or surgical).

1.The cornea may not be the initial site of ocular injury.

B.It starts with a 1- to 2-mm, purulent corneal infiltrate in a girdle approximately 1 mm within clear cornea.

1.A peripheral zone of clear cornea always remains.

2.The central cornea rapidly becomes necrotic and may slough; a panophthalmitis ensues.

3.The eye is usually lost.

C.An infectious cause,bacterial or fungal,is most common, but it may also occur with collagen disease.

D.Histologically, the cornea is infiltrated with neutrophils and contains necrotic debris.

Central

I.Viral

A.HSV (Figs 8.13 and 8.14; see also Fig. 3.6), along with the varicella-zoster viruses, is a member of the subfamily alpha herpesviruses.

The HSV is modest in size, containing only 84 genes (compared with its large relative, the cytomegalovirus, which contains more than 200 genes). HSV consists of a nucleocapsid surrounded by the tegument, a protein compartment, and the envelope. The tegument and the envelope are essential for infectivity.

1.HSV (see p. 62 in Chapter 3) is the most common cause of central corneal ulcer.

2.Clinically, it presents as an epithelial infection with a dendritic pattern.

3.People who have atopic dermatitis are particularly susceptible to HSV infection and may even develop dissemination (eczema herpeticum).

Dendritic keratitis may occur rarely with herpes zoster. Also, tyrosinemia type II, an autosomal-recessive disease, is characterized by dendriform keratitis, hyperkeratotic lesions of the palms and soles, and mental retardation (Richner–Hanhart syndrome). The corneal pseudodendrites may mimic closely those seen in herpetic keratitis. Dendritic keratitis can also occur with contact lens wear.

4.A blepharoconjunctivitis associated with HSV may occur in the Wiskott–Aldrich syndrome (see p. 176 in Chapter 6).

5.HSV that is harbored in neurons in sensory ganglia (mainly trigeminal but possibly also the superior cervical, ciliary, and sphenopalatine) seems to be the main source of recurrent infection at peripheral sites.

a.A limited transcription of genes is expressed during the latent period.

b.The virus appears to be transported along the axons.

6.Complications—spread to stroma, especially with recurrence

a.Disciform keratitis is a chronic, localized, discoid opacity.

G.Haemophilus aphrophilus and Streptococcus viridans, relatively nonvirulent bacteria, may cause a crystalline keratopathy (see subsection Crystals, later).

III.Mycotic (Fig. 8.16)

A.Mycotic keratitis is characterized by a “dry” main lesion that may be accompanied by satellite lesions.

1. Hypopyon is common.

B.Fungus is found most readily in scrapings from viable tissue at the margin and depths of the ulcer rather than in the necrotic central debris.

C.The keratitis may be caused by molds (e.g., Aspergillus) or yeasts (e.g., Candida).

D.Fungal keratitis is usually a complication of trauma resulting from contamination by plant or animal

C

matter (e.g., as seen in farmers or contact lens wearers).

E.Histologically, the inflammatory infiltrate may be granulomatous, chronic nongranulomatous, or, rarely, purulent.

F.Fungal toxins may be important in the pathophysiology of these infections.

IV. Parasitic

A.Acanthamoeba (Fig. 8.17)

1.Acanthamoebic organisms are ubiquitous, freeliving, usually nonparasitic protozoa found in soil, fresh water (e.g., tap water, hot tubs, and swimming pools), and the human oral cavity.

Water storage tanks promote colonization of free-living Acanthamoeba and increase the risk of keratitis caused by Acanthamoeba in contact lens wearers who use tap water in contact lens care routines.

2.Most cases of acanthamoebic keratitis occur in contact lens wearers.

3.Typically, acanthamoebic keratitis presents with pain, central or paracentral disc-shaped corneal ulcerations, and anterior or mid stromal total or partial ring infiltration.

Rarely, Acanthamoeba can cause a chorioretinitis after the keratitis or with prolonged keratitis.

a.The keratitis has a waxing and waning course, with periods of improvement over days and weeks, but is generally progressive over months, often leading to corneal opacification, ulceration, and even perforation.

b.Scleral infection may also occur (sclerokeratitis) and may be responsible for much of the pain.

c.Corneal sensation is often decreased and may lead to the erroneous diagnosis of herpes simplex keratitis.

4.Histologically, numerous acanthamoebic cysts are seen in the corneal stroma by light microscopy and motile trophozoites by culture.

a.Neutrophils are the most common inflammatory cell.

1). Confocal microscopy (CFM) can be helpful in the diagnosis. Rarely, a florid granulomatous necrotizing reaction can involve both stroma and anterior chamber.

2). Impression cytology can also aid in the early diagnosis of the disorder.

b.Macrophages appear to play an important role in fighting the infestation by acting as a first line

of defense in eliminating significant numbers of

Acanthamoeba trophozoites.

INFLAMMATIONS—CORNEAL SEQUELAE

I. Descemetocele

II.Ectasia (i.e., thinned, protruding area)

III.Staphyloma (i.e., ectasia lined by uveal tissue)

IV. Cicatrization (i.e., scarring)

V. Vascularization (Fig. 8.18)

VI. Adherent leukoma (i.e., corneal perforating scar with iris adherent to posterior corneal surface; see Fig. 8.4)

VII. Exposure keratitis (xerosis) (see Fig. 7.11)

INJURIES

See Chapter 5.

DEGENERATIONS

Degenerations (Table 8.1) may be unilateral or bilateral and are secondary phenomena after previous disease (i.e., ocular “fingerprints” of prior disease).

Epithelial

I.Keratitis sicca

A.Because the watery part of the tear secretion is lacking, corneal epithelial punctate erosions develop in exposed areas.

An abnormal Schirmer’s test result is a universal finding. In addition, approximately 85% of patients show excess ocular tear film mucus, thinned tear film, and decreased marginal tear strip; 80% have corneal and conjunctival staining when tested with rose Bengal (see section Normal Anatomy, earlier); and 75% demonstrate an associated conjunctival staphylococcal infection or blepharitis. Corneal mucous plaques of various thicknesses, sizes, and shapes, firmly attached to the corneal epithelium, are also frequently found.

B.Epithelial filaments (filamentary keratitis; Fig. 8.19) may develop.

Filamentary keratitis occurs in approximately 55% of patients. It may also be found in conditions such as Sjögren’s syndrome, SLK, viral infections, and after cataract extraction. It is a particu-

TABLE 8.1 Degenerations

EPITHELIAL

I.Keratitis sicca

II.Recurrent erosion

III. Keratomalacia

IV. Neuroparalytic keratopathy

V.Exposure keratopathy

STROMAL

I.Arcus senilis

II.Pterygium

III. Terrien’s ulcer

IV. Calcific band keratopathy

V.Climatic droplet keratopathy

VI. Salzmann’s nodular degeneration

VII. Lipid keratopathy

VIII. Amyloidosis

IX. Limbus girdle of Vogt

X. Mooren’s ulcer

XI. Delle

XII. Anterior crocodile shagreen of Vogt

lar problem for patients in a chronic vegetative state. A common finding in individuals who develop filamentary keratitis is epithelial edema.

C.Keratitis sicca may be related to Sjögren’s syndrome (see Fig. 14.8), which consists of keratoconjunctivitis sicca, xerostomia, and rheumatoid arthritis or other connective tissue disease.

D.Corneal melting in Sjögren’s syndrome is rare; however, it has occurred as the initial presentation of the disorder.

Epstein–Barr virus may be a risk factor in the pathogenesis of Sjögren’s syndrome. Likewise, Sjögren’s syndrome (and other chronic autoimmune diseases) constitutes a risk factor for the development of non-Hodgkin’s lymphomas.

E.Histologically, filaments are composed of degenerated epithelial cells and mucus.

1.In Sjögren’s syndrome, aside from a mononuclear inflammation, squamous metaplasia of the conjunctival epithelium, extensive goblet cell loss, and mucus aggregates are seen.

2.Immunocytochemical studies of lacrimal gland biopsies from patients who have Sjögren’s syndrome

show that the major component of the mononuclear infiltrate consists of B cells and Leu-3+ T- helper cells.

II.Recurrent erosion

A.The epithelium forms small blebs and then desquamates in recurring cycles.

Frequently, the blebs rupture when the eyelids are opened in the morning. This leads to the complaint of sharp, severe pain on awakening with the pain subsiding as the day progresses.

B.The condition usually follows incomplete healing of a traumatic corneal abrasion, most commonly a fingernail, paper, or plant injury.