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

1.Most cases probably have a dominant inheritance pattern.

2.The association of cornea guttata and anterior polar cataract, dominantly inherited in people of Scandinavian origin, has also been reported.

B.Four stages are seen clinically and histologically.

1.Asymptomatic stage: excrescences resembling Hassall–Henle warts are present centrally.

a.Electron microscopic studies of cornea guttata demonstrate foci of hyperproduction of Descemet’s membrane in an abnormal format.

2.Stage of painless decrease in vision and symptoms of glare: early changes occur as a mild stromal and intraepithelial edema (mainly the basal layer— corneal bedewing) followed by a subepithelial ingrowth of a layer of cells from the superficial stroma through Bowman’s membrane, leading to production of a subepithelial fibrous membrane of varying thickness (degenerative pannus).

3.Stage of periodic episodes of pain: a later change is moderate to marked stromal edema and interepithelial edema leading to epithelial bullae (bullous keratopathy) that periodically rupture, causing pain.

The corneal epithelium shows areas of atrophy, hypertrophy, and increased basement membrane formation.

4.Stage of severely decreased vision but no pain: the degenerative pannus thickens so that the resultant scarring decreases vision. The advanced pannus tends to lessen bullae formation greatly.

Other late complications include glaucoma and ruptured bullae that may lead to corneal infection, ulceration, and even perforation.

5.Oxytalan (oxytalan, elaunin, and elastic fibers are all part of the normal elastic system of fibers), not normally present in the cornea, is found in cornea guttata in the corneal subepithelial tissues and most abundantly deep to the endothelium and surrounding, but not in, the guttate bodies.

6.Secondary lipid keratopathy is a frequent later finding.

a.Reticulin fibers are prominent in both the guttate bodies and posterior Descemet’s membrane.

A

C

b.Disturbance in the regulation of endothelial apoptosis may contribute to the guttata process.

c.Missense mutations in COL8A2, the gene that codes for the alpha-2 chain of type VIII collagen, have been detected in familial and sporadic cases of Fuchs’ corneal dystrophy, and in a family with posterior polymorphous corneal dystrophy.

II.Posterior polymorphous dystrophy (PPMD; hereditary deep dystrophy of Schlichting; Fig. 8.48; see Table 16.1)

A.Irregular, polymorphous opacities and vesicles with central pigmentation and surrounding opacification are seen in the central cornea at the level of endothelium and Descemet’s membrane.

1.CFM has demonstrated craters, streaks, and cracks over the corneal endothelial surface accompanied by endothelial pleomorphism and polymegathism. Wide variation in endothelial cell counts and other abnormalities of Descemet’s membrane have also been noted.

The corneal abnormalities may vary greatly, even within the same family. Some individuals show only a few isolated vesicles; others manifest severe secondary stromal and epithelial edema; still others show any stage in

B

Fig. 8.48 Posterior polymorphous dystrophy. A and B, Clinical appearance of cornea. C, Scanning electron micrograph of posterior surface of cornea shows epithelial-like appearance of endothelium, caused by numerous surface microvilli. (A and B, Courtesy of Dr. JH

Krachmer; C, courtesy of Dr. RC Eagle, Jr.)

between. Posterior corneal vesicles may also occur as an isolated finding unrelated to PPMD.

B.Ruptures in Descemet’s membrane and glaucoma

(either open-angle or associated with iridocorneal adhesions) may be associated.

The differential diagnosis between the bandlike structures in PPMD and Haab’s striae (see Fig. 16.6) depends on the clinical appearance. The edges of Haab’s striae are thickened and curled and contain a secondary hyperproduction of Descemet’s membrane; the area between the edges is thin and smooth. PPMD bands are just the opposite.

C.The condition is inherited as an autosomal-dominant or recessive trait.

PPMD should not be confused with the rare, autosomal-domi- nant disorder, posterior amorphous corneal dysgenesis (dystrophy), which is characterized by gray, sheetlike opacities in the posterior stroma. An association of Alport’s syndrome and PPMD has been seen in people of Thai origin. The association suggests a common defect in basement membrane formation in the two entities. A mutation in COL8A2 may cause PPMD in some families.

D.Histologically, the most posterior layers of stroma demonstrate fracturing, the endothelial cells are attenuated,

and Descemet’s membrane may be focally or di usely thickened, or occasionally thinned.

1.Electron microscopically, the posterior stromal lamellae are disorganized and Descemet’s membrane is interrupted by bands of collagen resembling stroma.

a.The posterior surface of the cornea is covered in a geographic pattern by endothelialand epithe- lial-like cells with numerous desmosomes, apical villi, and prominent bundles of intracytoplasmic filaments, sometimes creating vesicles and sometimes creating partially detached sheets of cells.

b.The microvilli-covered cells are present at the onset of the process, and are not a secondary change of long-standing disease.

c. The total number of endothelial cells is decreased.

2.A layer of cells may be present beneath the corneal epithelium, but epithelial edema is not common.

Although some of the changes may superficially resemble those seen in the iridocorneal endothelial syndrome (see Table 16.1) and in cornea guttata, they are usually easily distinguishable because they result from interstitial keratitis and keratoconus.

III.Congenital hereditary endothelial dystrophy (CHED; Fig. 8.49; see also Table 8.4)

A.Clinically, a di use blue-white opacity (ground-glass appearance) involves the cornea.

A

B

C D

Fig. 8.49 Congenital hereditary endothelial dystrophy (CHED), A, Clinical appearance right eye (left) and left eye (right) of a patient with CHED, previously reported as Hurler’s disease (patient #5 in Scheie HG et al.: Am J Ophthalmol 53:753, 1962). B, Left side shows banded (arrow) Descemet’s membrane near stroma and thickened posterior layer interspersed with fibrous basement membrane and patches of banded-type basement membrane. Right side shows high magnification of multilaminar patches (*) of homogeneous basement membrane interspersed with multilaminar sheets of fibrous basement membrane. C, Collagen fibrils in normal corneal stroma measure approximately 24 nm in diameter. D, Stromal collagen fibrils in CHED often measure approximately 48 nm, with some reaching diameters of up to 72 nm. (B–D, From Kenyon KR, Maumenee AE: Invest Ophthalmol 7:475. Copyright Elsevier 1968.)

B.CHED tends to be bilateral and progressive, and may be associated with nystagmus and glaucoma, or with agenesis of the corpus callosum.

C.The di erential diagnosis of CHED includes congenital hereditary stromal dystrophy, congenital glaucoma, cornea guttata, congenital leukoma, hereditary corneal edema, mucopolysaccharidoses, Peters’ anomaly, sclerocornea, and stromal dystrophies (e.g., macular corneal dystrophy).

Some cases previously classified as hereditary corneal edema are identical to CHED, whereas others are the same as congenital hereditary stromal dystrophy (see p. 297 in this chapter) and mucopolysaccharidoses.

D.Two modes of inheritance have been reported: an auto- somal-recessive and a rarer autosomal-dominant type.

1.In the autosomal-recessive type, corneal clouding is present at birth or within the neonatal period.

2.In the autosomal-dominant type (20q12–q13.1), the cornea is usually clear early in life. Corneal opacification develops slowly and is progressive.

E.Histologically, increased diameter of the stromal collagen fibrils may produce a thick cornea. Spheroidal degeneration may also be present. Descemet’s membrane shows fibrous thickening (similar, if not identical to, cornea guttata), implying an endothelial abnormality. Secondary corneal amyloidosis may occur, particularly in association with a subepithelial fibrous pannus.

F.Immunohistochemical staining of corneal endothelium in PPMD and CHED are similar relative to cytokeratins expressed, including CK 7, which is not present in

normal endothelium or surface epithelium. IV. Nonguttate corneal endothelial degeneration

A.The condition is characterized by spontaneous unilateral corneal edema in an otherwise normal eye.

B.Specular microscopy of the nonedematous contralateral cornea reveals endothelial pleomorphism and a cell count reduced to approximately half of normal for the age.

C.Histologically, the edematous cornea shows a Descemet’s membrane of variable thickness and composition.

1.Guttata are absent.

2.The endothelium is extremely attenuated or discontinuous.

The remainder of the corneal layers appear normal. Keratocytic invasion of the subepithelial plane has not been observed histologically.

PIGMENTATIONS

Melanin

I.Pigmentation of the basal layer of epithelium, especially in the peripheral cornea, is normally found in dark races (Fig.

8.50A).

II.A posterior corneal membrane may be caused by a proliferation of uveal melanocytes or pigment epithelial cells on to the posterior cornea after an injury.

Lipofuscin pigments, sometimes confused with melanin, may rarely become deposited in the cornea, a condition called corneal lipofuscinosis.

III.Krukenberg’s spindle (see Fig. 16.21)

When a Krukenberg’s spindle is present unilaterally, ocular trauma is the usual cause.

Fig. 8.50 A, Melanin pigment may extend into epithelium of cornea, as depicted in diagram.

B, Fleischer ring of keratoconus drawn as it would appear in left eye (i.e., slightly nasal and inferior to center of cornea). (A, From Gass JDM: Arch Ophthalmol 71:348, 1964, with permission. © American Medical Association. All rights reserved.)

Blood

I.Blood staining of the cornea occurs in the presence of a hyphema when intraocular pressure has been increased for at least 48 hours (see Fig. 5.31).

Staining may occur earlier or even without glaucoma if the endothelium is diseased.

II.Staining of the cornea is due to hemoglobin and other breakdown products of erythrocytes.

T e smallh amount of hemosiderin present is usually contained within keratocytes.

III.The cornea clears first peripherally, and may take several years to clear completely.

IV. Histologically, amorphous extracellular hemoglobin globules, and tiny round spheres and rods (all orange in hematoxylin and eosin-stained sections) are mainly seen between corneal lamellae, but also in keratocytes and in Bowman’s membrane.

T e extracellularh hemoglobin does not stain positive for iron, as does the intracellular oxidized hemoglobin (i.e., hemosiderin) in keratocytes.

keratoplasty, and in association with overnight orthokeratology.

Kayser–Fleischer Ring

I.The Kayser–Fleischer ring (Fig. 8.53) is associated with hepatolenticular degeneration (Wilson’s disease):

A.Increased absorption of copper from gut

B.Decrease in serum ceruloplasmin

C.Usually, an autosomal-recessive inheritance pattern

(defect on chromosome 12q14–21), but may have a

dominant type

II.The Kayser–Fleischer ring (i.e., copper in Descemet’s membrane) is usually apparent by late childhood or early adolescence and may be accompanied by a “sunflower” cataract.

Iron Lines

I. Fleischer ring (see Fig. 8.50B; see also Fig. 8.44; see section

Dystrophies, subsection Stromal, earlier)

II. Hudson–Stähli line (Figs 8.51 and 8.52)—deposition of iron in the corneal epithelium in a horizontal line just inferior to the center of the interpalpebral fissure

III.Stocker line (see Fig. 8.51)—deposition of iron in the epithelium at the advancing edge of a pterygium

IV. Ferry line (see Fig. 8.51)—deposition of iron in the corneal epithelium at the corneal margin of a filtering bleb

V.Iron lines may occur in many conditions, such as the annular lines in the donor epithelium of corneal grafts, around old corneal scars, centrally after refractive

Fig. 8.51 Iron lines. Ferry line depicted at top in front of (i.e., below) filtering bleb; Stocker line depicted on left in front of (to right) of advancing edge of pterygium; Hudson–Stähli line (see also Fig. 8.52) across (horizontal) cornea just below center. All three lines caused by iron in epithelial cells. (Modified with permission from Gass JDM: Arch Ophthalmol 71:348, 1964. © American Medical Association. All rights reserved.)

A.The ring is found in about 63% of children with Wilson’s disease, and in all patients with neurologic manifestations of the disease, but in only 58% of patients with only hepatic presentation.

III.Histologically, the foreign material is seen in the corneal stroma.

The Kayser–Fleischer ring can be simulated exactly as a result of a retained intraocular copper foreign body. In this event, however, the ring is only present in the eye containing the foreign body. Rarely, a Kayser–Fleischer ring may be the presenting sign of Wilson’s disease. Conversely, it may be present in other forms of liver diseases, such as alcoholic liver disease. Ocular deposition of copper involving central Descemet’s membrane, iris surface, and lens capsule of both eyes has been reported as the presenting sign of multiple myeloma.

III.Histologically, the copper, bound to sulfur, is deposited in the posterior half of the peripheral portion of Descemet’s membrane and in the deeper layers of the central anterior and posterior lens capsule.

Tattoo

I.Corneal tattooing (Fig. 8.54) is usually done to disguise unsightly leukomas.

II.It is performed by chemical reduction of metallic salts (e.g., gold chloride or platinum black).

Drug-Induced

I. Oxidized epinephrine

II.Chloroquine (see Fig. 11.32)

A.Long-term chloroquine used systemically causes a decreased corneal sensitivity.

B.The corneal epithelial deposits vary from di use, fine, punctate opacities to focal aggregations arranged in radial, whorling lines that diverge from just below the center of the cornea.

Similar corneal appearances are seen in Fabry’s disease, and in amiodarone (Fig. 8.55), suramin, clofazimine and indomethacin keratopathies. These are drug-induced lipidoses.

T eh deposits may disappear after stoppage of chloroquine.

C.Confocal microscopy (CFM) demonstrates that the impact of amiodarone on the cornea may extend deeper than the epithelium as, in eyes with advanced keratopathy, microdots can be seen in the anterior and posterior

stroma, and on the endothelial cell layer. Moreover, keratocyte density is decreased.

III.Chlorpromazine

A.The pigmentation (melanin-like) is present immediately under the anterior capsule of the lens in the central (axial) area and in the conjunctival substantia propria in the interpalpebral fissure area.

B.In the area of the interpalpebral fissure, the corneal pigmentation appears as epithelial curvilinear and linear opacifications.

1.In the corneal stroma, it appears as di use, granular yellow pigmentations.

2.In the corneal endothelium, it appears as fine

deposits. IV. Other drugs

Other drugs, such as indomethacin, suramin, amiodarone

(see Fig.8.55),and Argyrol (argyrosis; see p.235 in Chapter

7), can cause a corneal keratopathy. Antimetabolites, such as cytarabine, can result in degeneration of basal cells and secondary epithelial microcyst formation.

INFECTIONS

Keratitis secondary to dematiaceous fungal infection may result in the formation of a pigmented corneal plaque. The fungi are

A

septate and contain brown to black pigment in the cell walls in most cases.

Crystals

I.Infectious crystalline keratopathy (ICK; Fig. 8.56)

A.ICK is a distinctive microbial corneal infection, characterized by fernlike intrastromal opacities without significant inflammation, and most often occurring in donor grafts after penetrating keratoplasty.

B.The most common cause is Streptococcus species, but other Gram-positive and Gram-negative bacteria and fungi can cause ICK, such as Peptostreptococcus; Haemophilus aphrophilus; Staphylococcus epidermidis; Alternaria; Pseudomonas aeruginosa; and Candida albicans, C. guilliermondi, and C. tropicalis.

C.Histopathologically, the crystalline opacities consist of colonies of microbes insinuated between corneal stromal lamellae.

II.Noninfectious crystalline keratopathy

A.Many causes of noninfectious crystalline keratopathy exist, including Schnyder’s corneal dystrophy; lipid keratopathy; Bietti’s crystalline retinal and corneal dystrophy; infantile, adolescent, and adult forms of cystinosis; gout; chronic renal failure; hypercalcemia; some familial lipoprotein disorders; dysproteinemias

B

Fig. 8.56 Infectious crystalline keratopathy. A, Patient had “relaxing incisions” to correct postpenetrating keratoplasty astigmatism. Rounded crystallinelike infiltrates developed on both sides of one of the two incisions. B, Histologic section shows the posterior aspect of the healing cornea incision. C, Brown–Brenn stain shows multiple Gram-positive cocci in the region of the incision. (Case presented by Dr. MC Kincaid at the Eastern Ophthalmic Pathology Society, 1990, and reported by Kincaid MC et al.: Am J Ophthalmol 111:374. Copyright Elsevier 1991.)

associated with multiple myeloma, malignant lymphoma, and other lymphoproliferative disorders (gammopathies); Die enbachia keratitis; and longterm drug therapy with colloidal gold (chrysiasis), chlorpromazine, chloroquine, 5-fluorouracil subconjunctival injection, clofazimine, and immunoglobulin therapy for pyoderma gangrenosum. Gatifloxacin, a fourth-generation fluoroquinolone, may deposit as crystals in the stroma as a result of compromised corneal epithelium. A similar process has been described for ciprofloxacin.

B.Increasing longevity of patients with nephropathic cystinosis has led to varied anterior-segment manifestations in more mature patients. In addition to classic crystalline deposits, these findings include superficial punctate keratopathy, filamentary keratopathy, severe peripheral corneal neovascularization, band keratopathy, and posterior synechiae with iris thickening and transillumination.

C.The histologic appearance depends on the cause.

NEOPLASM

I.The cornea is rarely the primary site for neoplasms, but it is frequently involved secondarily in conjunctival tumors such as squamous cell carcinoma and malignant melanoma.

A.Corneal involvement may occur in 38% of 287 cases of conjunctival squamous cell carcinoma.

B.Occasionally conjunctival melanoma may present as a corneal mass. Such lesions have been termed “corneally displaced malignant conjunctival melanoma.”

II.Myxoma

A. Myxoma is rarely reported as a corneal tumor in an individual lacking a history of prior corneal disease.

B.The tumor is composed of spindle-shaped cells in a myxomatous ground substance.

1.Ultrastructurally, the cellular elements have features characteristic of keratocytes with no basement membrane, much rough endoplasmic reticulum, and vacuoles containing mucoid-like material.

2.Immunohistopathologic characteristics of the tumor cells are positivity for vimentin, musclespecific actin, and smooth-muscle antigen.

III.Nevi are rarely diagnosed as primary on the cornea. They were found in 2 eyes of 410 patients having ocular surface nevi in one study.

IV. Juvenile xanthogranuloma has been reported to involve the corneoscleral limbus in a child, and an adult.

V.Primary di use neurofibroma may involve the cornea in von Recklinghausen disease.

SCLERA

CONGENITAL ANOMALIES

Blue Sclera

I.Blue sclera may occur alone or with brittle bones and deafness.

A syndrome of red hair, blue sclera, and brittle cornea with recurrent spontaneous perforation, called Stein’s syndrome (brittle cornea syndrome), has been reported in Tunisian Jewish families. Blue sclera has also been reported in association with Alport’s syndrome.

II. There are three types of brittle bones.

A.Osteogenesis imperfecta—usually apparent at birth and consisting of four types:

1.Type I is dominantly inherited and is characterized by skeletal osteopenia, fractures, dentinogenesis imperfecta (in some patients), and blue sclera throughout life.

2.Type II usually results in death in the perinatal period.

3.Type III is a rare autosomal-recessive disorder in which severe, progressive skeletal deformities occur.

The sclera may be blue at birth but becomes normal by adolescence or adulthood.

4.Type IV is dominantly inherited and is characterized by skeletal osteopenia and blue sclera at birth, which become normal by adulthood.

B.Osteopsathyrosis—a variant of brittle bones without blue sclera

C.Osteogenesis imperfecta tarda—delayed onset with levis and gravis forms

III.The sclera retains its normal fetal translucency so that the

deep-brown uvea shows through as blue.

IV. In most cases, the disease is inherited as an autosomaldominant trait, but autosomal-recessive inheritance may occur.

V.Central corneal thickness is reduced in osteogenesis imperfecta, and negatively correlates with the blueness of the sclera in this disorder.

VI. Histologically, the sclera is usually thinner than normal but may be thicker and more cellular than normal. Its collagen fibers are abnormal, being reduced in thickness by approximately 25% in the cornea and more than 50% in the sclera.

Ochronosis (Alkaptonuria)

I.Because the enzyme homogentisic acid oxidase (homogentisate 1,2-dioxygenase) is lacking, homogentisic acid deposits in tissues (especially cartilage, elastic, and colla-

gen, e.g., sclera) and forms a melanin-like substance.

II.The condition is inherited as an autosomal-recessive trait and is caused by mutations in the homogentisate

1,2-dioxygenase gene located to a 16-cM region of the 3q2 chromosome.

III.Histologically, amorphous strands and curlicues are seen in the sclera and overlying substantia propria of the conjunctiva.

INFLAMMATIONS

Episcleritis

I.Episcleritis (Fig. 8.57) involves one eye two-thirds of the time, and is characterized by redness of the eye and discomfort, rarely described as pain.

A.Hyperemia, edema, and infiltration are entirely within the episcleral tissue; the sclera is spared.

B.The episcleral vascular network is congested maximally, with some congestion of the conjunctival vessels and minimal congestion of the scleral vessels.

C.Episcleritis is a benign recurring condition.

Episcleritis usually resolves without treatment in 2 to 21 days. Episcleritis does not progress to scleritis except in herpes zoster, which sometimes starts as an episcleritis and shows the vesicular stage of the eruption. It reappears approximately 3 months later as a scleritis in the same site.

D.No clear conclusions can be drawn as to the cause of episcleritis.

Although usually idiopathic, approximately one-third of the cases of episcleritis may be associated with systemic entities such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, relapsing polychondritis, and systemic vasculitic diseases (e.g., Wegener’s granulomatosis and Cogan’s syndrome); or with local eye diseases such as ocular rosacea, keratoconjunctivitis sicca, and atopic keratoconjunctivitis.

II.Classification

A.Simple episcleritis

1.Redness caused by engorged episcleral vessels that retain their normal radial position and architecture

In episcleritis, after local instillation of 2.5% phenylephrine, the redness usually mostly disappears, whereas in scleritis, the redness persists.

2.Di use edema

3.Sometimes small gray deposits

B.Nodular episcleritis

1.Localized redness and edema

2.An intraepiscleral nodule that is mobile on the underlying sclera

III.Histologically, chronic nongranulomatous inflammation of lymphocytes, plasma cells, and edema is found in the episcleral tissue. Rarely, a chronic granulomatous inflammatory infiltrate may be seen.

Scleritis (Fig. 8.58)

I.Anterior scleritis

A. Di use (most benign form)

1.Di use anterior scleritis in women is most common in the fourth to seventh decades, with no predilection for any of those decades, whereas in men it is most prevalent in the third to sixth decades and peaks during the fourth.

Rarely, mucosal-associated lymphoid tissue (MALT) lymphoma can present as a scleritis.

2.Approximately half of the patients have bilateral involvement.

3.Up to 42% of patients who have scleritis have an associated uveitis.