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

C.It may be inherited as an autosomal-dominant trait, but most are not inherited.

Probably at least 50% of recurrent erosions are associated with dot, fingerprint, and geographic patterns (see p. 286 in this chapter).

D.The cause is uncertain but seems to be a defect in the epithelium that produces an abnormal basement membrane.

III. Keratomalacia

A.Keratomalacia, caused by a deficiency of vitamin A, is characterized by di use, excessive keratinization of all mucous membrane epithelia, including the cornea and conjunctiva (xerophthalmia).

B.The condition occurs most often in children, who characteristically complain of night blindness.

Keratomalacia is caused by vitamin A deficiency itself or in association with kwashiorkor, protein deficiency, cystic fibrosis, or multiple vitamin deficiency, as seen in underdeveloped countries, in people on fad diets, or in the cachectic hospitalized patient. Keratomalacia leading to descemetocele formation may occur in cystic fibrosis. Vitamin A deficiency is a public health problem of great magnitude in underdeveloped countries; it is estimated that xerophthalmia develops in over 5 million children annually, of whom 250 000 or more become blind. It is thought to be the leading cause of blindness in children in many underdeveloped countries.

C.It may proceed to hypopyon ulcer, corneal necrosis, panophthalmitis, and even corneal perforation.

Secondary infection by bacteria probably plays a major role in causing the corneal ulceration that may ultimately lead to corneal perforation.

D.Bitot’s spot

1.Bitot’s spot is a localized form of keratomalacia, usually involving the limbus, and shows a thickened, bubbly appearance to the involved area.

2.It is usually associated with, or is a sequela of, vitamin A deficiency.

3.Young boys are a ected most commonly.

4.Corynebacterium xerosis bacteria are found in great numbers on the lesion.

E.Histologically, xerophthalmia shows a thickened and

keratinized corneal and conjunctival epithelium associated with loss of conjunctival goblet cells. Extreme cases appear as skin epithelium with rete ridges.

IV. Neuroparalytic keratopathy

A.Early neuroparalytic keratopathy, which may resemble recurrent erosion, often progresses to almost total corneal epithelial desquamation.

B.Frequently, it is complicated by secondary infection that leads to perforation.

C.The condition is caused by a lesion anywhere along the course of the ophthalmic division of the fifth cranial

nerve and results in partial or complete loss of corneal sensitivity. It usually runs a chronic, slow course.

Significant neurotrophic corneal disease can occur in diabetic patients. Decreased corneal sensitivity in many patients who have diabetes mellitus is believed to be part of a generalized polyneuropathy.

V.Exposure keratopathy—exposure of the cornea from any cause can lead to epidermidalization (xerosis; see Fig. 7.11) and scarring.

Stromal

I.Arcus senilis (gerontoxon; Fig. 8.20)

A.Lipid deposit is limited to the peripheral cornea and central sclera.

1.It starts earliest at the inferior pole of the cornea, then involves the superior, becoming annular in the late stage.

2.The lipid first concentrates in the area of Descemet’s membrane, then in the area of Bowman’s membrane, forming two apex-to-apex triangles (both clinically and histologically).

3.Clinically, the extreme anterior peripheral cornea appears free of lipid.

Rarely, lipid accumulates in such large quantities that it may extend into the visual axis (primary lipidic degeneration of the cornea). Also rarely, unilateral arcus senilis can occur, usually after blunt trauma or associated with unilateral carotid artery disease.

B.Arcus senilis may have a recessive inheritance pattern.

1.People younger than 50 years of age who have arcus senilis have a significantly higher incidence of coronary heart disease.

2.People older than 50 years of age who have arcus senilis have an increased chance of having hypercholesterolemia and hypertriglyceridemia.

3.Arcus senilis in some patients seems to have an association with alcoholism.

C.Histologically, a narrow peripheral ring of lipid deposit is characteristic.

1.An anterior stromal triangular lipid deposit is present with its base within Bowman’s membrane, near its termination.

2.A similar stromal triangular lipid deposit is present with its base along and within the periphery of Descemet’s membrane.

3.The peripheral margin of the arcus is sharply defined, whereas the central margin is less discrete.

4.Histologically (and clinically), it appears identical to an arcus juvenilis.

Histologically, a similar concentration of lipid is demonstrable in the superficial and deep layers of the anterior

A

C

sclera posterior to the vascular limbal region, which is free of lipid. Clinically, the lipid is not visible in the opaque, white sclera.

II.Pterygium (Fig. 8.21)

A.The cause is unknown.

p53 mutations within limbal epithelial cells, probably caused by ultraviolet irradiation, may be an early event in the development of pingueculae, pterygia, and some limbal tumors.

B.The conjunctival component is identical histologically to pinguecula (see p. 237 in Chapter 7).

C.Usually it develops nasally, rarely temporally, and is most often bilateral.

D.Histologically, both pterygia and pingueculae show basophilic degeneration (actinic or senile elastosis) of the subepithelial substantia propria (see Fig. 7.12).

B

Fig. 8.20 Arcus senilis. A, A white ring is in the peripheral cornea of each eye. The ring is separated from the limbus by a narrow clear zone. B, Histologic section shows that the lipid is concentrated in the anterior and posterior stroma as two red triangles, apex to apex, with the bases being Bowman’s and Descemet’s membranes, both of which are heavily infiltrated by fat (red staining), as is the sclera. C, Arrows indicate sites of lipidic deposits in two planes of Descemet’s membrane, as seen by transmission electron microscopy. (B, oil red-O stain; C, modified from Fine BS et al.: Am J Ophthalmol 78:12. Copyright Elsevier 1974.)

The epithelium overlying a pterygium and a pinguecula may show a variety of secondary changes such as orthokeratosis, acanthosis, and dyskeratosis.

1.The characteristic that distinguishes a pterygium from a pinguecula is the invasion of superficial cornea preceded by dissolution of Bowman’s membrane in pterygia.

2.Mast cells occur in increased numbers in pterygia.

3.Deep corneal changes at the level of endothelium and Descemet’s membrane may be seen in association with long-standing nasal pterygia in elderly individuals. Endothelial cell density may be reduced in these individuals.

4.Pterygium cells, which are altered limbal basal epithelial cells, stain positively for multiple types of matrix metalloproteinases, unlike normal conjunctival, limbal, and corneal cells. These cells may con-

tribute to the dissolution of Bowman’s membrane, a characteristic of pterygium. These cells may activate fibroblasts at the head of the pterygium, and may play an important role in the formation and migration of the pterygium.

III.Terrien’s ulcer (chronic peripheral furrow keratitis; symmetric marginal dystrophy; gutter degeneration; Fig. 8.22)

A.The lesion, a limbal depression or gutter, starts as fine, yellow-white, punctate opacities supranasally, usually bilaterally, and spreads circumferentially, rarely reaching inferiorly. It develops slowly, often taking 10 to 20 years.

B.The peripheral involvement is located similarly to an arcus senilis, so that a clear corneal ring is present between the peripheral margin and the limbus.

C.The central wall is very steep, and the peripheral wall slopes gradually. The sharp, steep central edge is demarcated by a white-gray line.

D.The epithelium remains intact, but the underlying stroma thins, and the gutter widens.

1.The base of the gutter later characteristically becomes vascularized with superficial radial blood vessels that extend across the groove to its anterior extent.

2.The base also shows scarring and lipid infiltration at the leading edge.

E.The floor may become so thin that normal intraocular pressure produces an ectasia. Rarely, the lesion may perforate.

F.The cause is unknown, but degeneration and hypersensitivity have been proposed.

Similar lesions may be seen in rheumatoid arthritis and Sjögren’s syndrome, but differ from marginal degeneration in that they are usually located inferiorly, are not vascularized, and rarely encircle the cornea.

G.Histologically, the main feature is a peripheral corneal stromal thinning.

1.Fewer than 25% of the resident cells express major histocompatibility complex class II antigens, the

ratio of CD4 cells (T-helper/inducer) to CD8 cells

(T-suppressor/cytotoxic) approaches 1 :1, and fewer than 5% of the infiltrating cells stain positively for

CD22 (B cells)—compare with Mooren’s ulcer on p. 284 of this chapter.

IV. Calcific band keratopathy (Figs 8.23 through 8.25)

A.Calcific band keratopathy starts in the nasal and temporal periphery with a translucent area at the level of Bowman’s membrane; the semiopaque area contains characteristic circular clear areas.

B.The extreme peripheral cornea remains clear, but the central cornea may ultimately become involved.

C.A deposition of calcium salts in and around Bowman’s membrane is apparently related to abnormal epithelial activity.

D.Calcific band keratopathy may be secondary to primary hyperparathyroidism; increased vitamin D absorption; chronic renal failure; ocular disease, especially uveitis, and particularly when associated with Still’s disease; long-standing glaucoma; local pilocarpine therapy (when pilocarpine contains phenylmercuric nitrate as a preservative); and some forms of nonspecific superficial injury (e.g., from experimental laser).

1.Calcific band keratopathy may develop rapidly in corneas treated with steroid–phosphate drops.

2.Calcific band keratopathy may coexist with climatic droplet keratopathy (CDK; see Fig. 8.25).

3.The degeneration can recur even bilaterally following corneal transplantation.

Superficial reticular degeneration of Kolby is an atypical form of band keratopathy.

E.Histologically, a blue granular material (calcium salts) is seen in and around Bowman’s membrane.

V.Climatic droplet keratopathy (CDK Labrador keratopathy; elastotic degeneration; spheroidal degeneration; noncalcific band keratopathy; Bietti’s nodular hyaline band-shaped keratopathy; chronic actinic keratopathy; oil droplet degeneration; Nama keratopathy; proteinaceous corneal degeneration; and other designations; see Fig. 8.25)

A.“Oil droplet” or hyaline-like deposits may occur in the superficial corneal stroma, usually bilaterally, in a variety of chronic ocular and corneal disorders having in common a relationship to climate (i.e., outdoor exposure).

The droplets usually appear as small, golden-yellow spherules in the subepithelial cornea and conjunctiva. In geographic areas where the eyes are exposed to climatic extremes and to the effects of wind-blown sand or ice, the deposits often occur in a band-shaped pattern across the central cornea. In areas with considerable sunlight but without the traumatic effects of wind-blown sand or ice, pingueculae may also be seen. CDK may occur along with calcific band keratopathy (see earlier discussion).

B.The condition may result from the cumulative e ect of chronic actinic irradiation, presumably ultraviolet irra-

diation. Ultraviolet exposure from welding may also contribute to this disorder.

C.Band-shaped, spheroidal keratopathy has been reported in a Chinese family.

Occasionally patients who have corneal elastotic degeneration also show lattice lines in all layers of corneal stroma. Histologically, the lines are positive for amyloid.

D.CDK may be divided into a primary type (degenerative, related to aging; or dystrophic in young people) and a

secondary type (secondary to other ocular disease, e.g., herpetic keratitis and lattice dystrophy, or secondary to the environment, e.g., climatic extremes, wind-blown sand).

1.CDK is an important cause of blindness in rural populations of the developing world.

E.Histologically, granules and concretions of variable size and shape are located in the superficial stroma and in and around Bowman’s membrane.

1.When extremely small and localized to Bowman’s membrane, the granules and concretions are di - cult to distinguish from calcium unless special stains are used.

2.The deposits resemble most the degenerated connective tissue of pingueculae and are considered a form of elastotic degeneration of collagen.

VI. Climatic proteoglycan stromal keratopathy (CPSK)

A.The condition appears mainly in the seventh decade, predominantly in men, and is usually bilateral, although sometimes asymmetric.

B.CPSK occurs in people exposed to the sunny, dry, dusty environment of the Middle East and is thought to be caused by climatic factors.

C.Clinically, CPSK shows a central, horizontally oval corneal stromal haze (ground-glass appearance), of a uniform or lamellar pattern, and occupying 50% to

100% stromal thickness but greatest density in anterior stroma.

D.Histologically, excessive focal intracellular and extracellular proteoglycan deposits are seen.

VII. Salzmann’s nodular degeneration (Fig. 8.26)

A.The condition, an elevated white or yellow corneal area, is usually unilateral (but may be bilateral), occurs mainly in women, and is often superimposed on an area of old corneal injury, especially along the edge of an old pannus.

In general, a characteristic history of keratitis is obtained. The keratitis may be phlyctenular, vernal, or secondary to systemic childhood infections such as scarlet fever or measles, or it may be from trachoma. In many cases, however, no previous history of eye disease is obtained.

B.The condition may recur after lamellar excision.

C.Histologically, the epithelium shows areas of both hypertrophy and atrophy, with a marked increase of

subepithelial basement membrane material and scar tissue. CFM reveals irregularly shaped basal epithelium with foci of prominent nuclei, and disrupted anterior stromal architecture having an increased reflectivity of the anterior stromal matrix within the nodules.

D.A degeneration characterized by subepithelial fibrosis atypical for Salzmann degeneration is termed “peripheral hypertrophic corneal degeneration.”

VIII. Lipid keratopathy (secondary lipidic degeneration; Fig. 8.27)

A.Lipid keratopathy may be unilateral or bilateral and follows old injury, especially surgical.

B.Clinically, it appears as a nodular, yellow, often elevated corneal infiltrate.

C.Histologically, the lipid deposition is mainly located in a thick pannus between Bowman’s membrane and epithelium.

Lipid keratopathy and primary lipidic degeneration are related.

Primary lipidic degeneration seems to be an exaggeration of an arcus senilis, whereas secondary lipidic degeneration follows corneal vascularization.

IX. Amyloidosis (see p. 238 in Chapter 7)

A.Secondary amyloidosis is rarely found as an isolated corneal degeneration.

1.For example, it has been reported in advanced congenital glaucoma.

B.It has been described as secondary to di erent ocular diseases (e.g., trachoma, interstitial keratitis, retinopathy of prematurity, trichiasis, and penetrating injury).

C.Primary amyloidosis of the cornea may be seen in three forms.

1.Lattice dystrophy (see p. 294 in this chapter)

2.Primary gelatinous droplike dystrophy (see p. 296 in this chapter)

3.Polymorphic amyloid degeneration (polymorphic stromal dystrophy) is characterized by deep, punctate, and filamentous stromal lesions, which resemble crystalline opacities in early lattice corneal dystrophy (LCD).

D.Histology (see Figs 7.13 and 7.14)

X.Limbus girdle of Vogt

A.The limbus girdle of Vogt appears as a symmetric, yel- lowish-white corneal opacity forming a half-moon-like

arc running concentrically within the limbus superficially in the interpalpebral fissure zone, most commonly nasally.

B.Histologically, Bowman’s membrane and superficial stroma are largely replaced by basophilic granular deposits.

XI. Mooren’s ulcer (chronic serpiginous ulcer; Fig. 8.28)

A.Mooren’s ulcer is a chronic, painful ulceration of the cornea. There appear to be two di erent types.

1.A comparatively benign type, which is usually unilateral, occurs in older people and clears with relatively conservative surgery.

2.A relentlessly progressive type, which is also usually bilateral (approximately 25% of all cases of Mooren’s ulcer are bilateral), occurs in younger people and does not clear with any therapy.

B.The ulcer starts in the peripheral cornea and spreads in three directions:

1.Initially, circumferentially

2.Then rapidly, centrally, with the leading edge deepithelialized, undermined, and often infiltrated with plasma cells and lymphocytes

3.Slowest movement is toward sclera

C.The ulcer may be relentlessly progressive or selflimited.

That inappropriate immunologic responses may be the cause of Mooren’s ulcer, or play an important role in the cause, is suggested by: the occasional association of Mooren’s-like ulcer with autoimmune disease; the finding of subepithelial tissue from Mooren’s ulcer packed with plasma cells and lymphocytes; the demonstration of immunoglobulins and complement bound to conjunctival epithelium and circulating antibodies to conjunctival and corneal epithelium; and, finally, the finding of cellular immunity in the form of positive macrophagic migration inhibition in response to corneal antigen. Bone marrow-derived cells have been noted in Mooren’s ulcer as evidenced by immunoreactivity for CD34 (a marker for hematopoietic progenitor cells and endothelium), c-kit (a marker for hematopoietic and stromal progenitor cells), and STRO-1 (a differentiation antigen present on bone marrow fibroblast cells and on nonhematopoietic progenitor cells) cells, particularly in the superficial stroma.

D.Histologically, the cornea is infiltrated by lymphocytes and plasma cells.

1.An ulcer undermines the central edge of the stroma and shows a blunt edge peripherally.

2.The inflammation is present primarily at the peripheral edge of the ulcer but is absent centrally. The latter findings are characteristic of a rodent ulcer and can be useful in making the diagnosis. The

peripheral portion of the ulcer is characterized by necrobiotic changes and hemorrhage, and absence of overlying epithelium and Bowman’s membrane.

3.Approximately 75% to 100% of the resident cells express major histocompatibility complex class II antigens, the ratio of CD4 cells (T-helper/inducer) to CD8 cells (T-suppressor/cytotoxic) approaches

2.4 :1, and approximately 25% to 50% of the infiltrating cells stain positively for CD22 (B cells)— compare with Terrien’s ulcer on p.278 of this chapter.

4.On histologic examination, the adjacent conjunctiva has an edematous stroma that is infiltrated primarily by plasma cells and lymphocytes without

evidence of vasculitis. XII. Delle (singular form of dellen)

A.A delle is a reversible, localized area of corneal stromal dehydration and corneal thinning owing to a break in the continuity of the tear film layer secondary to elevation of surrounding structures (e.g., with pterygium,

filtering bleb, or suture granuloma).

Dellen, also known as Fuchs’ dimples, may start as early as a few hours after the occurrence of a limbal elevation, but they seldom last longer than 2 days.

B.The histologic picture consists of a partial or full-

thickness epithelial defect with the underlying stromal tissues shrinking or even collapsing from dehydration.

XIII. Anterior crocodile shagreen of Vogt (mosaic degeneration of the cornea)

A.The condition consists of a central corneal opacification at the level of Bowman’s membrane that presents as a mosaic of polygonal gray opacities separated by clear areas.

1.The condition may occur as a dystrophy with bilaterality and a dominant inheritance pattern.

2.It may also occur as a degeneration after trauma or associated with such conditions as megalocornea, iris malformations, and band keratopathy.

3.A peripheral variety may be seen as an aging change.

B.Histologically, Bowman’s membrane is calcified and

found in ridges with flattening of the overlying epithelium.

T ehcorneal stroma underlying the ridges is thinned and scarred.

XIV. Microdot stromal degeneration

A.Stromal microdot deposits present in long-term contact lens wearers.

1.It may represent lipofuscin-like material within the stroma secondary to chronic oxygen deprivation and chronic microtrauma.

2.Soft contact lens wear time has the greatest statistical relationship to microdot density and size.

XV. Corneal fibrosis syndrome

A.An unusual, bilateral, superficial, corneal fibrosis has been described in a young woman with homocystinuria.

B.Clinical findings: whitish, elevated, irregular masses accompanied by superficial vascularization were noted in the peripheral cornea of both eyes.

C.Histopathology: variable epithelial thickness is accompanied by melanin pigmentation of the basal epithelium.Fibrovascular pannus with disruption of Bowman’s membrane and fibrosis of the anterior stroma is seen. Electron microscopy reveals empty intracytoplasmic vacuoles in the corneal epithelial cells, and intracytoplasmic inclusions incorporating fibrillogranular material in the corneal epithelium and keratocytes.

DYSTROPHIES

These are primary, usually inherited, bilateral disorders with fairly equal involvement of the corneas (Table 8.2). Because of their

TABLE 8.2 Dystrophies

EPITHELIAL

I. Heredofamilial—Primary in Cornea

A.Meesmann’s (Stocker–Holt)

B.Dot, fingerprint, and geographic map patterns (microcystic dystrophy; epithelial basement membrane dystrophy)

II. Heredofamilial—Secondary to Systemic Disease: Fabry’s Disease

SUBEPITHELIAL AND BOWMAN’S MEMBRANE

Subepithelial mucinous corneal dystrophy

Reis–Bücklers dystrophy

STROMAL

I. Heredofamilial—Primary in Cornea

A.Granular

B.Macular

C.Lattice

D.Avellino corneal dystrophy

E.Congenital hereditary stromal dystrophy

F.Hereditary fleck dystrophy

G.Central stromal crystalline corneal dystrophy (Schnyder)

H.Posterior crocodile shagreen

I.Posterior amorphous corneal dystrophy

II. Heredofamilial—Secondary to Systemic Disease

A.Mucopolysaccharidoses

B.Mucolipidoses

C.Sphingolipidoses

D.Ochronosis

E.Cystinosis

F.Hypergammaglobulinemia

G.Lecithin cholesterol acyltransferase deficiency

III. Nonheredofamilial

A.Keratoconus

B.Keratoglobus

C.Pellucid marginal degeneration

ENDOTHELIAL

I.Corneal guttata (Fuchs)

II. Posterior polymorphous dystrophy

III. Congenital hereditary endothelial dystrophy

IV. Nonguttate corneal endothelial degeneration