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

which produces aggregates of cytoid bodies (i.e., swollen axons of ganglion cells caused by interruption of axonal flow).

Cotton-wool spots may be seen in many conditions, such as collagen diseases, CRVO, blood dyscrasias, AIDS, and multiple myeloma.

4.Hard (waxy) exudates may be seen; these are lipophilic exudates located in the outer plexiform layer (see Figs 11.14, 15.13, and 15.14).

When the exudates are numerous in the macula and lie in the obliquely oriented and radially arranged fiber layer of Henle, they appear as a macular star.

D.Grade IV: all the changes of grade III plus optic disc edema

Necrosis, thinning, clumping, and proliferation of the RPE may occur as a result of obliterative changes in the choriocapil-

laris in malignant hypertension. Four types of fundus lesions associated with choroidal vascular changes have been recognized clinically: (1) pale yellow or red patches bordered to a varying extent by pigment deposits; (2) black, isolated spots of pigment with a surrounding yellow or red halo caused by complete obstruction of terminal choroidal arterioles and choriocapillaris by fibrin thrombi (Elschnig’s spots; see Fig. 11.14D); (3) linear chains of pigment flecks along the course of a yellow-white sclerosed choroidal vessel (Siegrist’s spots); and (4) yellow or red patches of chorioretinal atrophy.

II.Arteriolosclerotic retinopathy (Fig. 11.15)

A.Grade I: an increase in the arteriolar light reflex

Subintimal hyalin deposition and a thickened media and adventitia cause the normally transparent arteriolar wall to become semiopaque, producing an increased light reflex.

B.Grade II: grade I changes plus arteriolovenular crossing defects

The semiopaque wall of the arteriolosclerotic arteriole, which shares a common adventitia with the venule where they cross, obscures the view of the underlying venule. This results in the clinically seen arteriolovenular crossing defects, or “nicking.”

C.Grade III: grade II changes plus “copper-wire” arterioles

The arteriolar wall becomes sufficiently opaque so that the blood column can only be seen by looking perpendicularly through the surface of the wall (i.e., looking through the thinnest area). The arteriole has a burnished or copper appearance owing to reflection of light from the thickened and partially opacified wall.

D.Grade IV: grade II changes plus “silver-wire” arterioles

The wall becomes totally opaque so that the blood column in the lumen cannot be seen. The light is then reflected completely from the surface of the thickened vessel, giving a white or silver appearance. The lumen of the arteriole may or may not be patent. Patency can best be determined by fluorescein angiography.

Hemorrhagic Retinopathy

I.Neural retinal hemorrhages (see Figs 11.12 and 15.15) may be caused by many diseases, such as diabetes mellitus (see

Chapter 15), sickle-cell disease, retinal venous diseases, hypertension, blood dyscrasias, leukemias, polycythemia vera, subacute bacterial endocarditis, cytomegalovirus retinitis, acute retinal necrosis (ARN), lymphomas, idiopathic thrombocytopenia, trauma, multiple myeloma, pernicious

anemia, collagen diseases, carcinomatosis, anemia, and many others.

Anemia or thrombocytopenia alone rarely causes neural retinal hemorrhages. Anemia and thrombocytopenia combined, however, not infrequently result in neural retinal hemorrhages; when the two are severe (hemoglobin <8 g/100 ml and platelets <100 000/ mm), neural retinal hemorrhages may occur in 70% of patients.

II.Histologically, the size and anatomic location of the hemorrhage determine its clinical appearance (see Fig. 15.15).

III.Roth’s spots

A.Roth’s spots are a special type of neural retinal hemorrhage characterized by a white center and associated with bacterial endocarditis.

It was Litten who described the association (Litten’s sign) and referred to it as Roth’s spots.

B.Although the white spots are usually thought to represent septic microabscesses caused by septic microemboli, they probably represent capillary rupture, extravasation, and formation of a central fibrin–platelet plug.

Exudative Retinopathy

I.Retinal exudates (see Figs 11.14, 15.13, and 15.14)

A.Neural retinal exudates may be caused by the same conditions that cause hemorrhagic retinopathy (see earlier); waxy exudates may occur simultaneously with the hemorrhages, alone, or after the hemorrhage resorbs.

B.Cotton-wool spots (cytoid bodies), which are not exudates, are usually found in ischemic neural retinal conditions and represent microinfarction of the innermost

neural retinal layers, associated with interruption of axoplasmic flow.

II.Circinate retinopathy consists of a circular deposit of masses of hard, waxy exudates around a clear area, often within the anatomic macula.

A.It is degeneration secondary to ischemic vascular disease

(e.g., diabetes mellitus).

B.Histologically, the exudates are identical to isolated,

small, hard, waxy exudates.

III.Histology

A.Hard, waxy exudates (see p. 606 in Chapter 15)

B.Cotton-wool spots (cytoid bodies; see p. 404 in this chapter and p. 610 in Chapter 15)

Diabetes Mellitus

See Chapter 15.

Coats’ Disease, Leber’s Miliary Aneurysms, and

Retinal Telangiectasia

See p. 751 in Chapter 18.

Idiopathic Macular Telangiectasia (Idiopathic

Juxtafoveolar Retinal Telangiectasis)

See p. 753 in Chapter 18.

Retinal Arterial and Arteriolar Macroaneurysms

I.Macroaneurysms of the retinal arteries and arterioles (Fig.

11.16) may be congenital or acquired.

A.Congenital entities include angiomatosis retinae and the diseases of Eales, Leber, and Coats.

B.Acquired macroaneurysms occur in people (most often women) who have hypertension or arteriosclerosis, or both, and less often have diabetic retinopathy, retinal vein occlusion, retinal arteritis, cytomegalovirus retinitis, radiation and sickle-cell retinopathies, hyperviscosity entities, Takayasu’s disease, and aortic arch

syndromes.

II.Most macroaneurysms involute spontaneously without sequelae.

III.The macroaneurysms may be associated with circinate retinopathy, intraneural retinal hemorrhage, subneural retinal hemorrhage, or even intravitreal hemorrhage.

Hemorrhage in the neural retina along with a subneural retinal hemorrhage (“dumbbell shape”) should alert the clinician to the possibility of macroaneurysm.

IV. Histologically, spherical or fusiform aneurysms arise from arterial or arteriolar walls.

Sickle-Cell Disease

I.Sickle-cell disease (Figs 11.17 and 11.18) is caused by a point mutation in the hemoglobin gene.

A. Polymerization of the abnormal hemoglobin subunits

in an anoxic or acidic environment results in the typical sickle configuration of the erythrocytes.

B. The sickled erythrocytes are much more rigid than normal ones and cause occlusions of small vessels.

II.The retinopathy is most severe with sickle-cell hemoglobin C disease (SC disease) but may also occur in other sickle hemoglobinopathies, including sickle thalassemia, sicklecell disease, and even in occasional cases of sickle-cell trait.

III.Classification of retinopathy

A.Stage I: peripheral arteriolar occlusion (between the equator and the ora serrata)

1.The primary site of occlusion appears to be at the precapillary arteriole level.

2.The most likely cause of the occlusion is obstruction of the small precapillary arterioles by sickled erythrocytes.

B.Stage II: peripheral arteriolovenular anastomoses (most commonly in the temporal quadrant)

1.Arteriolovenular anastomoses appear to be the initial vascular remodeling at the junction of the

perfused central and nonperfused peripheral neural retina in the region of the equator.

2.The development of arteriolovenular anastomoses most likely is not a neovascular process but rather represents the formation of preferential vascular channels from pre-existing vessels.

C.Stage III: neovascular and fibrous proliferations

1.New vessels arise from pre-existing arteriolovenular anastomoses, on the venular side.

2.When a neovascular patch remains relatively iso-

lated from neighboring patches and coalescence does not occur, the characteristic sea-fan anomaly may be observed, most commonly in SC disease.

The characteristic fibrovascular extraretinal formation is called a sea fan because of its resemblance to the marine invertebrate sea fan, Geogonia flabellum.

3.Areas of retinal pigment epithelial hypertrophy, hyperplasia, and migration (black sunbursts), which

develop after intraneural and subneural retinal hemorrhage, may occur in all stages, occur posterior to the equator, and may be seen most commonly in sickle-cell disease but also in SC disease.

4.Salmon-patch hemorrhage may occur in sickle-cell disease and SC disease.

a.The salmon-patch hemorrhage, which may be single or multiple, may be seen in all stages of the retinopathy.

b.It is usually found in the mid-periphery adjacent to a retinal arteriole.

c.Initially, the hemorrhages are bright red (but not quite the same red as hemorrhages in a nonsickler), but within a few days become salmon

(orange-red)-colored.

d.Within weeks, the lesions evolve into yellow or yellow-white nodules or plaques.

Further resolution results in intraneural retinal retinoschisis, a focal patch of thinned neural retina, or a pigmented scar.

The pigmented scar is called a black sunburst (see earlier) and results from the resolution of a salmon patch.

D.Stage IV: vitreous hemorrhage (usually arising from a neovascular patch)

E.Stage V: neural retinal detachment. The detachment of the neural retina may be nonrhegmatogenous (traction) or rhegmatogenous (caused by a neural retinal tear).

IV. The pathogenesis of sickle-cell retinopathy is unknown, but is probably related to local hypoxia (secondary to sickled erythrocytes occluding preretinal arterioles), similar

to what occurs in diabetes mellitus, retinopathy of prematurity, carotid occlusive disease, and Takayasu’s disease.

Eales’ Disease (Primary Perivasculitis of

the Retina)

I.Eales’ disease occurs typically in young men, usually in their third decade.

It occurs most commonly in the Indian subcontinent.

II. Over 90% of the cases are bilateral.

III.The disease progresses slowly; rapid progression, however, is common as a late event.

A.Initially, a slight, localized edema of the peripheral neural retina involves only the small venous branches.

Exudates around the involved vessels or sheathing of the vessels can be seen.

B.Next, the larger venules become involved. Neovascularization develops from venules in the neural retina and the new vessels enter the subvitreal space, where they are vulnerable to hemorrhage.

C.A fibrous membranous component develops (i.e., retinitis proliferans). Shrinkage and traction by the fibrovascular membranes may cause a secondary neural retinal detachment.

The total progression is similar to that in diabetic retinopathy. Rarely, a central form occurs and affects the large central venules. Fluorescein shows obliteration of the venules, producing large areas of capillary nonperfusion toward the neural retinal periphery.

IV. The cause of the disease is unknown.

Retinopathy of Prematurity

See pp. 748–751 in Chapter 18.

Hemangioma of the Retina

I.Hemangioma of the neural retina, a hamartomatous lesion, may be associated with similar cavernous hemangiomas of brain and with angiomatous hamartomas of skin, or it may

occur alone.

II.Cavernous hemangioma of the neural retina as an isolated

finding is rare.

A.The hemangioma is congenital, benign, stationary, unilateral, most frequent in women, composed of clusters of dark red saccular aneurysms containing venous blood, and rarely the source of intraocular hemorrhage.

B.They are not usually discovered before adulthood, when they may be discovered as an incidental finding or may become symptomatic secondary to an overlying serous neural retina detachment.

Rarely, they may be associated with retinal neovascularization.

III.Histologically, a cavernous type of hemangioma of the neural retina is seen.

Hereditary Hemorrhagic Telangiectasia (Rendu–

Osler–Weber Disease)

See p. 225 in Chapter 7.

Disseminated Intravascular Coagulation

I.Disseminated intravascular coagulation (DIC; Fig. 11.19) is a syndrome in which a physiologic imbalance occurs between clotting and lysis of clot.

A.Inappropriate triggers to coagulation result in endothelial injury stimulating the intrinsic cascade, or tissue factor stimulating the extrinsic cascade.

DIC can develop secondary to septicemia in patients who have AIDS.

B. Characteristically, disseminated microthrombi form in small vessels, especially in the kidneys, heart, and brain.

C.Coincident with microthrombi formation, a gradual depletion of coagulation factors, platelets, and fibrin ensues, resulting in a change from a hypercoagulable to a hypocoagulable state.

1.Clinically, gross hemorrhage, thrombosis, or both, or only disordered coagulation parameters, may be found.

2.Detection of the cross-linked fibrin degradation fragment, D-dimer, in patients at risk for DIC is strong evidence for the diagnosis.

a.D-dimer confirms that both thrombin and plasmin generation have occurred.

b.Laboratory D-dimer measurements are less sensitive but highly specific, whereas the fibrinogen degradation product (FDP) test is more sensitive but less specific; performing the two tests in tandem (screening with FDP and confirming with D-dimer) maximizes sensitivity and specificity.

II.Histologically, fibrin thrombi are noted most frequently in the choriocapillaris, often in the macular region with secondary neural retinal detachment. Fibrin may be found in capillaries in the retina, iris, ciliary body, and optic nerve.

INFLAMMATIONS

Nonspecific Retinal Inflammations

Secondary retinitis is usually caused by a vasculitis.

A.It may be secondary to keratitis, iridocyclitis, choroiditis, or scleritis.

B.Perivasculitis occurs around venules with the perivascular infiltrate composed of lymphocytes and plasma cells.

Specific Retinal Inflammations

(See Chapters 2, 3, and 4)

I.A toxic, exudative retinopathy may occur with carbon monoxide intoxication.

II.Septic retinitis of Roth (Roth’s spots) occurs with a bacteremia, especially with subacute bacterial endocarditis (see p. 412 in this chapter).

III.Endogenous mycotic retinitis (e.g., candidiasis) results from fungus infection.

IV. Viral retinitis

A.Herpes simplex retinitis (see p. 270 in Chapter 8)

1.Type 1 herpes simplex virus produces lesions in nongenital sites, including the mouth, cornea (see Fig. 8.13), skin above the waist, and in the central nervous system.

a.Type 1 virus is a rare cause of retinitis in children and adults.

b.The virus may cause encephalitis.

2.Type 2 herpes simplex virus (see Fig. 3.6) is transmitted as a venereal infection, usually producing lesions below the waist, except in newborns, in whom it may infect any organ. Approximately 20% of neonates infected with type 2 virus have ocular manifestations, including retinitis.

B.Cytomegalic inclusion disease (see p. 77 in Chapter 4)

V.Acute posterior multifocal placoid pigment epitheliopathy

(APMPPE), also called acute multifocal ischemic choroidopathy, tends to occur in young women and shows multifocal, gray-white placoid lesions at the level of the RPE and involving predominantly the posterior pole, but occurring anywhere in the fundus.

Fluorescein angiography during the acute phase of the disease process shows early blockage of background fluorescence, followed by later staining of the lesions, similar to the findings in Dalen–Fuchs nodules. Cerebral vasculitis may accompany APMPPE. Indocyanine green videoangiopathy suggests choroidal hypoperfusion as the underlying cause.

A.The lesions resolve rapidly, but may leave permanent retinal pigment epithelial alterations.

B.The acute process may result from a primary retinal pigment epithelial inflammation, an acute multifocal choroiditis (choriocapillaris), or random occlusions of the precapillary arterioles feeding the lobules of the choriocapillaris.

C.The histology is unknown.

VI. Acute retinal pigment epitheliitis is characterized by an acute onset, mainly in the posterior pole, that resolves fairly rapidly, usually in 6 to 12 weeks.

A.The acute lesion is a deep, fine, dark gray, sometimes black spot, often surrounded by a halo and that may disappear with healing.

In the choroidal phase, fluorescein angiography shows a window defect of the depigmented halo that surrounds the lesion. The defect does not change in size or shape, nor leak dye, during the later phases of the angiogram.

B.The cause and histology are unknown.

VII. Acute macular neuroretinopathy

A.Acute macular neuroretinopathy, a rare condition, tends to occur bilaterally in young women and shows subtle, reddish-brown, wedgeor tear-shaped (pointing to the fovea) lesions in the fovea.

1.The symptoms are scotomata and minimal depression of visual acuity, which may be transient or permanent. An associated recent systemic immunologic disturbance is common and suggests an immune-based cause.

2.Fluorescein angiography is negative or shows mild dilatation and faint hypofluorescence of the lesion.

Rarely, acute macular neuroretinopathy and multiple evanescent white-dot syndrome (MEWDS; see later) occur in the same patient. Because of overlap and transitional

cases, the idiopathic entities acute macular neuroretinopathy, MEWDS, acute idiopathic blind-spot enlargement syndrome, multifocal choroiditis, or pseudopresumed ocular histoplasmosis syndrome (POHS) may be classified together under the term acute zonal occult outer retinopathy (AZOOR).

B. The cause and histology are unknown.

VIII. Birdshot retinopathy (vitiliginous retinochoroidopathy; di use inflammatory salmon-patch choroidopathy)

A.The condition is characterized by:

1.A quiet eye (rarely red or injected, but not painful), usually in children or young adults

2.Minimal, if any, anterior-segment inflammation but chronic inflammation in the vitreous

3.Usually bilateral, and fairly symmetric, retinal vascular leakage (retinal vasculitis), especially in the macula, so that cystoid macular edema and optic disc edema may result

4.Distinctive, multiple, cream-colored or depigmented spots, usually discrete, and mostly around the optic disc, radiating out toward the equator

5.Development of disc pallor, di use RPE changes, macular edema, and narrowed retinal arterioles over a period of 6 to 24 months (ERG abnormalities may be found)

Fig. 11.20 Acute retinal necrosis. A, Fundus view is cloudy because of vitreous reaction. B, Neural retina shows sharp demarcation from necrotic retina on right and viable retina on left. Intranuclear inclusion bodies found in necrotic retina. C, Electron micrograph shows herpeslike virus capsids in nucleus. (Presented by Dr. JDM Gass at the meeting of the Eastern Ophthimic Pathology Society, 1981.)

A strong association exists with the human leukocyte antigen (HLA)-A29 (especially HLA-A29.2 subtype) in vitro (approximately 80% to 90% of patients who have birdshot retinopathy are HLA-A29-positive) and with cell-mediated responses to S-antigen. Also, elevated EA rosettes and C4 complement level may be seen.

6. The ultimate visual prognosis is poor.

B.This uncommon uveitic syndrome is of presumed autoimmune cause; the histology is unknown.

Patients who have Lyme disease (see p. 83 in Chapter 4) may also carry the HLA-A29 antigen; conversely, patients who have birdshot retinopathy and carry the HLA-A29 antigen may also have antibodies against Borrelia burgdorferi. It is still unclear, however, whether this is a cause-and-effect relationship.

IX. Acute retinal nerosis (ARN) (Fig. 11.20)

A.The condition, which may a ect both healthy and immunocompromised people, consists of acute peripheral necrotizing retinitis, retinal arteritis, and vitreitis.

Atypical, severe toxoplasmic retinochoroiditis in the elderly can mimic ARN.

B.After 1 to 3 months,neural retinal detachments develop, followed by proliferative vitreoretinopathy.

C.Approximately 50% of cases are bilateral.

D.The condition is caused most commonly by the vari- cella-zoster virus (46%) and also by herpes simplex virus types 1 (25%) and 2 (21%).

1.ARN may result from activation of latent, previously acquired infection, usually herpes zoster dermatitis (shingles).

2.Rarely, ARN may develop during the course of primary varicella-zoster (chickenpox) infection.

3.Viral antibodies have been found in intrathecally produced cerebrospinal fluid from patients who have ARN, suggesting central nervous system involvement.

E.Histologically, by light microscopy, Cowdry type A intranuclear inclusions, and by electron microscopy, intranuclear aggregates of viral particles can be seen in the areas of disorganized, necrotic retina.

X. Multiple evaescent white dot syndrome (MEWS)

A.This transient choriorioretinopathy a ects young adults, mainly women, is unilateral, and has an acute onset of decreased visual acuity and paracentral scotomas.

B.Multiple, small, white or gray-white dots occur at the level of the superficial choroids–RPE posteriorly to mid peripherally.

C.Vitreal cells, reduced visual acuity, and abnormalities in

the ERG and early receptor potential may be found.

1. Fluorescein leakage occurs from optic nerve head capillaries along with late staining of the

RPE.

2.Late indocyanine green angiography shows duallayered highly specific, small, hypofluorescent lesions overlying larger hypofluorescent lesions.

3.Rarely, choroidal neovascularization (CNV) may occur. Also rarely, MEWDS and acute macular neuroretinopathy occur in the same patient.

Acute idiopathic blind-spot enlargement without optic disc edema may be a subset of MEWDS. Because of overlap and transitional cases, the idiopathic entities acute macular neuroretinopathy, MEWDS, acute idiopathic blind-spot enlargement syndrome, multifocal choroiditis, or POHS may be classified together under the term acute zonal occult outer retinopathy (AZOOR).

D.The cause and histology are unknown.

XI. Unilateral acute idiopathic maculopathy (UAIM)

A.UAIM occurs in young adults who experience sudden, severe visual loss (to 20/200 or worse), often after a

flulike illness, caused by an exudative maculopathy.

1.Initially, an irregular neural retinal detachment overlying a smaller, grayish thickening at the RPE level is noted.

2.Fluorescein angiography shows early irregular hyperfluorescence and hypofluorescence at the RPE level, followed in the late phase by complete staining of the overlying neural retina detachment (similar to the late staining of an RPE detachment).

3.A rapid and complete resolution usually takes place (vision 20/25 or better).

4.Some cases show eccentric macular lesions, subneural retinal exudation, papillitis, and bilaterality;

association with pregnancy and human immunodeficiency virus may also occur.

XII. Di use unilateral subacute neuroretinitis (see p. 91 in

Chapter 4)

XIII. Retinal pigment epitheliopathy associated with the amyotrophic lateral sclerosis/parkinsonism–dementia complex (ALS/PDC) of Guam

A.An extremely high rate of ALS/PDC exists among the native Chamorro population of Guam.

B.Approximately 10% of the Chamorro population have a pigment epitheliopathy that resembles ophthalmomyiasis; the rate is approximately 50% among those who have ALS/PDC.

C.Histologically, focal areas of attenuation of the RPE and a reduced amount of intracellular pigment correlate with the fundus lesions.

1.No larvae are found.

2.The pathogenesis is unknown.

XIV. Acute multifocal retinitis

A.Acute multifocal retinitis usually occurs in otherwise healthy, young to middle-aged adults who experience acute loss of vision, often preceded by a flulike prodrome.

B.The areas of retinitis tend to be posterior and localized to the inner retina, varying in size from 100 to 500 μm in diameter.

The retinal lesions are often multiple and bilateral.

a.Vision usually returns to normal without treatment in 1 to 4 weeks.

b.Optic disc edema may occur.

c.Fluorescein angiography shows early hypofluorescence and late staining of retinal lesions.

d.Occasional patients have a history of a cat scratch and test positively for Bartonella henselae antibodies (most patients test negatively).

INJURIES

See Chapter 5.

DEGENERATIONS

Definitions

Degenerations are a result of previous disease (i.e., ocular “fingerprints” left by prior disease).

Microcystoid Degeneration

I.Typical peripheral microcystoid degeneration (Blessig–

Iwano cysts; Figs 11.21 and 11.22)