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

Ocular findings include stromal keratitis, episcleritis, orbital myositis, and cortical blindness.

D.The pathologic mechanisms include direct invasion of tissues by the spirochete, vasculitis and small-vessel obliteration, perivascular plasma cell infiltration, and immunologic reactions.

V.Streptothrix (Actinomyces; Fig. 4.12)

A.The organism responsible for streptothrix infection of the lacrimal sac (see p. 210 in Chapter 6) and for a chronic form of conjunctivitis belongs to the class Schizomycetes, which contains the genera Actinomyces and Nocardia. The organism superficially resembles a fungus, but it is a bacterium.

The organism is best classified as an anaerobic and facultative capnophilic bacterium of the genus Actinomyces. The bacteria can be found in the normal microflora of the mouth of humans and animals.

B.Histologically, the organisms are seen in colonies as delicate, branching, intertwined filaments surrounded

by necrotic tissue with little or no inflammatory component (e.g., the lacrimal cast from the nasolacrimal system). The organisms are weakly Gram-positive and acid-fast.

The colonies can be seen macroscopically as gray or yellow “sulfur” granules. Inflammatory giant cells are seen on occasion.

VI. Cat-scratch disease [CSD: Bartonella (previously called Rochalimaea) henselae cat-scratch bacillus]

A.CSD is a subacute regional lymphadenitis following a scratch by a kitten or cat (or perhaps a bite from the cat flea, Ctenocephalides felis), caused by the cat-scratch bacillus, B. henselae, a slow-growing, fastidious, Gram-

negative, pleomorphic bacillus, which is a member of the α2 subgroup of the class Probacteria, order Rickettsiales, family Rickettsiaceae.

Another possible cause is Afipia felis, a polymorphous bacillus that is a fastidious and facultative intercellular bacterium.

1.Systemic manifestations in severe cases include splenohepatomegaly, splenic abscesses, mediastinal masses, encephalopathy, and osteolytic lesions.

2.Ocular findings include Parinaud’s oculoglandular fever (see p. 232 in Chapter 7), neuroretinitis, branch retinal artery or vein occlusion, multifocal retinitis (retinal white-dot syndrome), focal choroiditis, optic disc edema associated with peripapillary serous retinal detachment, optic nerve head inflammation, and orbital infiltrates.

3.CSD antigen skin test is positive in infected patients.

CSD may occur in immunologically deficient patients (e.g., AIDS; see p. 21 in Chapter 1). Infection with Bartonella may also cause bacillary angiomatosis in immunologically deficient patients.

B.The contemporary infections caused by the Bartonella species include CSD, bacillary angiomatosis, relapsing bacteremia, endocarditis, and hepatic and splenic peliosis. CSD is the most common, a ecting an estimated

22000 people annually in the United States.

C.The domestic cat and its fleas are the major reservoir for B. henselae.

D.Histopathologically, the characteristics are discrete granulomas (which in time become suppurative) and follicular hyperplasia with general preservation of the lymph node architecture.

1.Warthin–Starry silver stain demonstrates the catscratch bacillus in tissue sections.

2.Electron microscopy shows extracellular rod-shaped bacteria.

VII. Tularemia (Francisella tularensis, also called Pasteurella tularensis; Fig. 4.13)

A.The common ocular manifestation of tularemia is Parinaud’s oculoglandular syndrome [i.e., conjunctivitis and regional (preauricular) lymphadenopathy, which may progress to suppuration].

B.Histologically, a granulomatous inflammation is found in the involved tissue. Organisms are extremely di cult

to demonstrate histologically in the granulomatous tissue.

VIII. Other bacterial diseases

A.Crohn’s disease (see p. 67 in Chapter 3)

B.Rhinoscleroma is a chronic, destructive granulomatous disease caused by Klebsiella rhinoscleromatis, a Gramnegative, encapsulated rod. The infection can spread from the nose, pharynx, and larynx to involve the nasolacrimal duct, lacrimal sac, and other orbital structures.

Fungal

I.Blastomycosis (Blastomyces dermatitidis, thermally dimorphic fungus)

A.North American blastomycosis may involve the eyes in the form of an endophthalmitis as part of a secondary generalized blastomycosis that follows primary pulmonary blastomycosis, or it may involve the skin about the eyes in the form of single or multiple elevated red ulcers.

1.Cutaneous blastomycosis does not usually become generalized.

2.Involvement of the cornea, sclera, eyelid, and orbit, as well as choroiditis, endophthalmitis, and panophthalmitis, can occur.

B.Histologically, the use of special stains demonstrates single budding cells in a granulomatous reaction.

II.Cryptococcosis (Cryptococcus neoformans)

A.Cryptococcosis has also been called torulosis; another name for the causative agent is Torula histolytica. Cryptococcosis has increased in frequency because the causative agent is an opportunistic fungus that infects immunocompromised patients, especially those who are HIV-positive.

B.The fungus tends to spread from its primary pulmonary involvement to central nervous system tissue, including the optic nerve and retina.

C.Histologically, special stains demonstrate the budding organism surrounded by a thick, gelatinous capsule, often in inflammatory giant cells in a granulomatous reaction.

III.Coccidioidomycosis (Coccidioides immitis)

A.Coccidioidomycosis, endemic to the arid soils of the southern, central, southwestern, and western United States and Mexico, usually starts as a primary pulmonary infection that may spread to the eyes and cause an endophthalmitis.

Rarely, it may present as an anterior-segment ocular coccidioidomycosis without any clinical evidence of systemic involvement.

B.Histologically, spherules containing multiple spores

(endospores) are noted in a granulomatous inflamma-

tory reaction.

IV. Aspergillosis (Aspergillus fumigatus; Fig. 4.14B and C)

A.Aspergillosis can cause a painful fungal keratitis, a very indolent chronic inflammation of the orbit, or an endophthalmitis; the latter condition is usually found in patients on immunosuppressive therapy.

B.Histologically, septate, branching hyphae are frequently found in giant cells in a granulomatous reaction.

V. Rhinosporidiosis (Rhinosporidium seeberi)

A.Rhinosporidiosis is caused by a fungus of uncertain classification.

B.The main ocular manifestation of rhinosporidiosis is lid or conjunctival infection.

C.Histologically, relatively large sacs or spherules (200

to 300 μm in diameter) filled with spores are seen. The organisms may be surrounded by a granulomatous reaction but are more likely to be surrounded by a nongranulomatous reaction of plasma cells and lymphocytes.

VI. Phycomycosis (mucormycosis, zygomycosis; see Fig. 14.7)

A.The family Mucoraceae of the order Mucorales, in the class of fungi Phycomycetes, contains the genera Mucor and Rhizopus, which can cause human infections called

phycomycoses, usually in patients who have severe acidosis [e.g., diabetes, burns, diarrhea, and immunosuppression (see p. 532 in Chapter 14)] or iron overload (e.g., in primary hemochromatosis).

The term mucormycosis should only refer to those infections caused by agents in the genus Mucor. Because the hyphae of species in the two genera, Mucor and Rhizopus, look identical histologically, and because Mucor may be difficult to culture, the term phycomycosis (or zygomycosis) is preferred to mucormycosis.

B.The fungi can infect the orbit or eyeball, usually in patients with acidosis from any cause, but most commonly from diabetes mellitus.

C.Histologically, the hyphae of Mucor and Rhizopus are nonseptate, very broad (3 to 12 μm in diameter), and branch freely.

1.Unlike most other fungi, the Mucoraceae readily take the hematoxylin stain and are easily identified in routine hematoxylin and eosin-stained sections.

2.Typically, the hyphae infiltrate and cause thrombosis of blood vessels, leading to infarction.

3.Inflammatory reactions vary from acute suppurative to chronic nongranulomatous to granulomatous.

VII. Candidiasis (Candida albicans; see Fig. 4.13A)

A.C. albicans may cause a keratitis or an endophthalmitis.

B.The endophthalmitis is most likely to occur in patients who have an underlying disease that has rendered them immunologically deficient.

The increased incidence of disseminated candidiasis correlates with the use of modern chemotherapy and the increase in immunologically deficient patients (e.g., those with AIDS).

A B

C

C.Histologically, budding yeasts and pseudohyphal forms are seen surrounded by a chronic nongranulomatous inflammatory reaction, but sometimes by a granuloma-

tous one.

VIII. Histoplasmosis (Histoplasma capsulatum)

Disseminated histoplasmosis with ocular involvement can be seen in immunologically deficient patients (e.g., in HIV-positive persons; see p. 433 in Chapter 11).

IX. Sporotrichosis (Sporotrichum schenkii)

A.Ocular involvement in sporotrichosis is usually the result of direct extension from primary cutaneous lesions of the lids and conjunctiva eroding into the eye and orbit.

1.Lesions in adjacent bony structures may encroach on ophthalmic tissues.

2.Less frequently, ocular and adnexal lesions may result from hematogenous dissemination of the fungus.

B.Histologically, the fungi are seen as round to cigarshaped organisms, 3 to 6 μm in length, often surrounded by granulomatous inflammation.

X.Pneumocystis carinii (PC; Fig. 4.15)

A.PC pneumonia is the most common opportunistic infection in patients who have AIDS, occurring in more than 80% of such patients. The causative

m

Fig. 4.14 Fungal endophthalmitis. A, Immunosuppressed patient developed endophthalmitis. Note “snowball” opacities in the vitreous

(near the optic nerve head, just to right of opacities). Candida albicans was cultured from the blood. B and C, Another patient experienced decreased vision in his right eye, followed by renal failure 2 months after a kidney transplantation. He died 1 month later. The histologic section shows microabscesses (m) in the vitreous body characteristic of fungal infection (bacterial infection causes a diffuse vitreous abscess).

C, Scanning electron microscopy demonstrates septate branching Aspergillus hyphae. (C, Courtesy of Dr. RC Eagle, Jr.)

organism, PC, exists exclusively in the extracellular space.

Previously classified as a protozoan, molecular genetic evidence has shown that PC has more morphologic similarities to a fungus than to a protozoan. PC is now classified as a fungus.

B.Clinically, choroidal lesions are yellow to pale yellow, usually seen in the posterior pole.

1.An association exists between PC and CMV in immunologically deficient patients so that PC choroiditis and CMV retinitis can exist concurrently in the same person.

2.In addition, PC and Mycobacterium avium-intracel- lulare, two opportunistic organisms, have been reported in the same choroid at the same time in a patient with AIDS.

C.Histologically, choroidal lesions show “cysts,” few or no inflammatory cells, and characteristic abundant, eosinophilic, frothy material, probably composed of dead and degenerating microorganisms.

Parasitic

I.Protozoa

A. Toxoplasmosis (Toxoplasma gondii; Figs 4.16 and 4.17)

1.The definitive host of the intracellular protozoan T. gondii is the cat, but many intermediate hosts (e.g., humans, rodents, fowl) are known.

2.The parasite primarily invades retinal cells directly.

3.Clinically, the infestation starts as a focal area of retinitis, with an overlying vitritis.

Atypical, severe toxoplasmic retinochoroiditis in the elderly can mimic acute retinal necrosis.

4.The lesions slowly clear centrally, destroying most of the retina and choroid, and become pigmented peripherally, so that “healed” lesions appear as atrophic white scars surrounded by a broad ring of pigment.

Immunoglobulin G (IgG) is the major class involved in the humoral immune response to T. gondii, followed by IgA.

5.Years later, reactivation can occur in the areas of the scars, or sometimes in new areas.

Even after the fifth decade, ocular toxoplasmosis remains an important cause of posterior uveitis. A subgroup of Fuchs’ heterochromic iridocyclitis has an association, which may be causal, with toxoplasmic retinochoroiditis.

6.Both congenital and acquired forms are recognized.

a.The congenital form is associated with encephalomyelitis, visceral infestation (hepatosplenomegaly), and retinochoroiditis.

If a woman has dye-test antibodies when pregnancy is established, she will not transmit the disease to her fetus. If she is dye-negative at the onset of pregnancy, there is some risk of her transmitting toxoplasmosis to her infant if she acquires the disease during pregnancy. There is a 14% chance of the child showing severe manifestations of the disease. If the woman acquires toxoplasmosis during the first trimester, pregnancy may cause activation of ocular disease in the mother.

b.The acquired form usually presents as a posterior uveitis and sometimes as an optic neuritis.

A

C

The acquired form, usually a retinitis, rarely a scleritis, may occur in persons who have immunologic abnormalities of many types, especially in AIDS.

7.Histologically, the protozoa are found in three forms: free, in pseudocysts, or in true cysts.

a.Rarely, the protozoa may be found in a free form in the neural retina.

1). The free parasite, called a trophozoite, resides in an intracellular vacuole that is completely unable to fuse with other endocytic or biosynthetic vacuoles.

2). The protozoa are seen in an area of coagulative necrosis of the neural retina, sharply demarcated from the contiguous normalappearing neural retina.

3). They may also be seen in the optic nerve.

b.Commonly, a protozoan enters a retinal cell

(neural retina or retinal pigment epithelium) and multiplies in the confines of the cell membrane. All that is seen histologically, therefore, is a group of protozoa surrounded by the retinal cell membrane; the whole assemblage is called a pseudocyst.

B

Fig. 4.16 Toxoplasmosis. A, Acute attack in right eye in 12-year-old girl (white spots on blood vessels represent granulomatous cellular reaction on surface of retina). B, Early pigmentation present 7 years later.

C, Twelve years later, lesion looks like “typical” toxoplasmosis.

c.If the environment becomes inhospitable, an intracellular protozoan (trophozoite) may transform itself into a bradyzoite, surround itself with a self-made membrane, multiply, and then form a true cyst that extrudes from the cell and lies free in the tissue.

1). It is found in the late stage of the disease, at the time of remission.

2). The true cyst is resistant to the host’s defenses and can remain in this latent form indefinitely.

d.The underlying choroid, and sometimes sclera, contains a secondary di use granulomatous inflammation.

B.Pneumocystis carinii (see earlier, under Fungal)

C.Malaria (Plasmodium)

1.Ocular complications occur in approximately 10% to 20% of malarial patients, and include conjunctival pigmentation; conjunctival, epibulbar, and retinal hemorrhages; keratitis; optic neuritis; peripapillary edema; and temporary loss of vision.

2.Histologically, in a case of Plasmodium falciparum malaria, cytoadherence and rosetting of parasitized erythrocytes partially occluded small retinal and

uveal blood vessels; malarial pigment (hemozoin) can be demonstrated by polarized light.

D.Microsporidiosis (Encephalitozoon, Enterocytozoon,

Nosema, and Pleistophora)

1.Diseases caused by microsporidia, which are obligate intracellular parasitic protozoa, have increased in prevalence because of the increase in the prevalence of AIDS.

2.Clinically, ocular findings include punctate epithelial keratopathy, keratitis, and keratoconjunctivitis.

3.Histologically, extracellular and intracellular spores are found in and around degenerating keratocytes.

Electron microscopy shows encapsulated oval structures, approximately 3.5 to 4 μm in length and 1.5 μm in width.

E.Acanthamoeba species (A. casttellani, A. polyphaga, A. culbertsoni; see p. 273 in Chapter 8)

II. Nematodes

A.Toxocariasis (Toxocara canis; see Fig. 18.19)

1.Ocular toxocariasis is a manifestation of visceral larva migrans (i.e., larvae of the nematode T. canis).

Toxocara cati may also cause toxocariasis. Nematodiasis is not a correct term for the condition because nematodes other than Toxocara can also infest the eye (e.g., Onchocercus; see Fig. 8.11).

a.One eye tends to be involved, usually in children

6 to 11 years of age.

b.Rarely, bilateral ocular toxocariasis can be demonstrated by aqueous humor ELISA.

c.Often the child’s history shows that the family possesses a puppy rather than an adult dog.

2.The condition may take at least three ocular forms:

a.Leukokoria with multiple retinal folds radiating out toward the peripheral retina, where the necrotic worm is present

b.A discrete lesion, usually in the posterior pole and seen through clear media

c.A painless endophthalmitis

3.In all three forms, the eye is not inflamed externally; the only complaint is loss of vision; and only one eye is involved.

Although the condition presumably follows widespread migration of larvae, only one eye is involved and only one worm can be found. No inflammatory reaction occurs until the worm dies. The eosinophil appears to be the major killer cell of Toxocara. Toxocaral fluorescent antibody tests may be helpful in making the diagnosis of toxocariasis.

4.Histologically, a granulomatous inflammatory infiltrate, usually with many eosinophils, surrounds the necrotic worm. The infiltrate is zonal, with the necrotic worm surrounded by an abscess containing eosinophils, neutrophils, and necrotic debris; granulomatous inflammation surrounds the abscess.

Splendore–Hoeppli phenomenon is a local eosinophilic, amorphous precipitate consisting of debris (mainly from eosinophils) and granular material (probably an antigen– antibody complex). It is presumed to be caused by a parasite, perhaps a nematode, but the exact cause is unclear.

B.Di use unilateral subacute neuroretinitis (DUSN; unilateral wipe-out syndrome)

1.DUSN, which typically a ects young, healthy people, is probably caused by more than one type of motile, subneural retinal, nematode roundworm.

Clinically, if the worm can be identified, it can be destroyed by focal photocoagulation.

2.The early stage of the disease is characterized by unilateral vision loss, vitritis, mild optic disc edema, and successive crops of multiple, evanescent, graywhite, deep retinal lesions.

3.Over a period of many months, widespread, di use, focal depigmentation of the retinal pigment epithelium develops, accompanied by retinal arterial narrowing, optic atrophy, severe vision loss, and electroretinographic abnormalities.

4.Worms seen in the fundi of patients from the southern United States seem to be approximately one-half the size of those seen in patients from the northern and western United States, and the exact type of the small variant roundworm is not known. The large nematode variant is probably not caused by Toxocara but by the raccoon roundworm larva,

Baylisascaris procyonis.

DUSN has been reported in Europe, probably caused by T. canis, but with banding distinct from the usual human toxocariasis.

C.Trichinosis (Trichinella spiralis; Fig. 4.18)

1.The nematode T. spiralis is obtained by eating undercooked meat, classically pork that contains the trichina cysts.

A

B

C

Fig. 4.18 Trichinosis. A, Acute trichinosis with orbital involvement. Note swelling of lids. B, Top two cysts are empty; bottom cyst shows larva of Trichinella spiralis (pork nematode); seen with increased magnification in C. (A, Courtesy of Dr. ME Smith.)

2.Clinically, the lids and extraocular muscles may be involved as the larvae migrate systemically.

3.Histologically, the larvae encapsulate or encyst in striated muscle and cause little or no inflammatory reaction. If the larvae die before they encapsulate, however, a zonal granulomatous inflammatory reaction around the necrotic worm results.

D.Loa loa (Fig. 4.19)

1.The adult L. loa filarial worm wanders in the subcutaneous tissues. It may wander into the periorbital tissues and eyelids and often into the subconjunctival tissues, where its length makes it easily visible.

2.Histologically, little inflammatory reaction occurs while the worm is alive.

E.Dracunculiasis (Dracunculus medinensis; guinea worm; serpent worm)

1.Dracunculiasis, caused by the obligate, nematode parasite, D. medinensis, a ects the skin, subcutaneous tissues, and orbit.

2.Histologically, the worm, when dead, is surrounded by an abscess.

III.Cestoidea (tapeworms)

A.Cysticercosis (Cysticercus cellulosae; Fig. 4.20)

1.C. cellulosae is the larval stage of the pork tapeworm Taenia solium. The larvae, or bladderworms, hatch in the intestine, and the resultant systemic infestation is called cysticercosis.

Cysticercosis is the most common ocular tapeworm infestation and the most common parasitic infection of the central nervous system. The prognosis in untreated cases is uniformly poor. The best chance for cure is early surgical removal, although destruction of the parasite in situ by diathermy, light coagulation, or cryoapplication may prove successful.

2.The bladderworm has a predilection for the central nervous system and eyes. It induces no inflammatory response when alive.

3.Histologically, the necrotic bladderworm is surrounded by a zonal granulomatous inflammatory reaction that usually contains many eosinophils.

B.Hydatid cyst (Echinococcus granulosus)

1.The onchospheres of the dog tapeworm E. granulosus may enter humans and form a cyst called a

hydatid cyst that contains the larval form of the tapeworm.

a.In this form, the tapeworms appear as multiple scolices provided with hooklets.

b.Each scolex is the future head of an adult tapeworm.

2.In humans, the tapeworm has a predilection for the orbit.

3.Histologically, multiple scolices are seen adjacent to a thick, acellular, amorphous membrane that represents the wall of the cyst.

C.Coenurus (Multiceps multiceps)

1.Coenurus is a large, single bladderworm (larval cystic stage of M. multiceps), 5 cm or more in diameter. It contains several hundred scolices.

2.The bladderworm may involve the subconjunctival or orbital regions, or occur in the eye.

3.The adult tapeworm mainly has the domestic dog as its definitive host, but may also be found in other animals. The larval stage is usually found in sheep, but primates can be involved as incidental intermediate hosts.

4.Histologically, multiple inverted scolices line up against an outer cuticular wall.

IV. Trematodes (flukes): Schistosomiasis (Schistosoma haematobium, S. mansoni, and S. japonicum)

A.Trematodes of the genus Schistosoma can cause a chronic conjunctivitis or blepharitis in areas of the world where they are endemic.

B.The eggs of schistosomes hatch in water into miracidia, which penetrate snails, undergo metamorphosis, and

form cercariae. The cercariae emerge from the snail and enter the skin of humans as metacercariae or adolescariae.

C.Histologically, the eggs and necrotic adult worms incite a marked zonal granulomatous inflammatory response.

Other trematodes that may infest the eye include Paragonimus and Alaria species.

V. Ophthalmomyiasis (fly larva)

A.Myiasis is a rare condition in which fly larvae (maggots) invade and feed on dead tissue. Numerous di erent causative agents may be found, e.g., Cochliomyia macellaria, Oestrus ovis, Gasterophilus species, Hypoderma bovis, and Cuterebera species.

B.Usually the larvae can be seen macroscopically, but

exact identification relies on microscopic features.

VI. Retinal pigment epitheliopathy associated with the amyotrophic lateral sclerosis/parkinsonism–dementia complex of Guam—see p. 418 in Chapter 11.

VII. Many other parasites, including Leishmania (leishmaniasis), Trypanosoma (trypanosomiasis), Ascaris lumbricoides

(ascariasis), and Dirofilaria (dirofilariasis), can cause ocular infestations.

NONTRAUMATIC NONINFECTIOUS

Sarcoidosis (Figs 4.21 to 4.26)

I.Sarcoidosis is a systemic disease, a ecting black people predominantly, and having an equal sex incidence.

II.Systemic findings include hypercalcemia, bilateral hilar adenopathy and lung parenchymal changes, peripheral lymphadenopathy, skin lesions varying from extensive erythematous infiltrates to nondescript plaques and papules, hepatosplenomegaly, occasional enlargement of lacrimal and salivary glands, and osteolytic lesions of distal phalanges. Central nervous system findings are seen in 5% of sarcoid patients, usually the result of basilar meningitis with infiltration or compression of adjacent structures.

The Kveim test appears to be based on an immunologic reaction associated with persistent lymphadenopathy of diverse causes and