Ординатура / Офтальмология / Английские материалы / Clinical Pathways in Glaucoma_Zimmerman, Kooner_2001
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protozoan found in most parts of the world. The cat or its close feline relatives appear to be the definite hosts. The oocysts, which are excreted in cat feces, are highly resistant and may remain infective for more than 1 year. Usually only young cats are infective for a short period of time. The infected cat is not the primary source of infection for humans, but it is a very important cause of contamination of the environment.196 Ocular toxoplasmosis is usually considered a recurrence of a congenital infection, but can also be acquired postnatally.197,198 In the eye, the retinal tissue and adjacent choroid are the site of infection. The typical ocular lesion is a localized necrotizing retinitis or satellite lesion of an existing scar. Cells are present in the overlying vitreous causing the characteristic appearance of a “headlight in the fog.”
What Is Acanthamoebiasis and How Does It Affect the Eye?
Acanthamoeba species are an important cause of microbial keratitis that may cause severe ocular inflammation and visual loss. Like other protozoa, Acanthamoeba are unicellular and can exist in two forms: active trophozoite and dormant cyst. The trophozoite is motile, proliferates, and feeds on bacteria, fungi, and other unicellular organisms and cells, like corneal epithelium.199
What Is Leishmaniasis and How Does It Affect the Eye?
Leishmania protozoa are obligate intracellular parasites and are transmitted by bites of infected sand flies. Leishmaniasis presents as either cutaneous or visceral (kala-azar or dumdum fever) leishmaniasis depending on the Leishmania species and immune status of the patient. In ocular disease, the adnexae are most commonly involved,200 but anterior uveitis with elevated IOP and glaucoma have been reported.201–204
What Is Malaria and How Does It Affect the Eye?
Malaria is caused by infection with the protozoans Plasmodium falciparum, vivax, malariae, and ovale. It is transmitted through a bite by the female mosquito of the genus Anopheles. Malaria is characterized by fever with sweats, myalgia, headaches, malaise, and sometimes rigors.
Ocular complications occur especially with cerebral malaria. They include retinal hemorrhages, disc swelling, and retinal edema.205
What Is Trypanosomiasis and How Does It Affect the Eye?
African trypanosomiasis (African sleeping sickness) is caused by Trypanosoma brucei and transmitted by bites of the tsetse fly. American trypanosomiasis (Chagas’ disease) is caused by Trypanosoma cruzi or wrangle. Chagas’ disease has multiple modes of transmission: vector-borne (reduviid bugs) by contamination of the bite wound with vector feces, congenital, and transfusional.206 Intraocular involvement is rare and may consist of retinal pigment epithelial changes.207
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Epidemiology and Importance
How Common Is Toxoplasmosis?
Toxoplasmosis is the most common cause of posterior uveitis. In the U.S. approximately 3,000 infants are infected annually.208 In an adult population the annual incidence for ocular involvement is approximately 0.3 per 100,000 population,209 and 3% of patients with acquired toxoplasmosis have ocular disease.210
How Common Is Glaucoma in Toxoplasmosis?
Transient open-angle glaucoma occurs in about 13% of patients.211
How Common Is Acanthamoeba Keratitis?
Acanthamoeba is a ubiquitous, free-living protozoan that is found in all types of liquid media, including tap water, swimming pools, hot tubs, and contaminated contact lens solution. The organism’s prevalence seems to peak during warmer weather. The first cases of Acanthamoeba keratitis were recognized in 1975, but the disease remained very rare until the 1980s, when an increase in incidence mainly associated with contact lens wear was reported.199
How Common Is Glaucoma in Acanthamoeba Keratitis?
Secondary uveitic glaucoma has been reported but is rarely a problem.212,213
How Common Is Leishmaniasis?
Leishmaniasis is a worldwide disease. Kala-azar (visceral leishmaniasis) has reemerged from near eradication. The annual estimate incidence and prevalence of kala-azar cases worldwide is 0.5 million and 2.5 million, respectively. Of these, 90% of the confirmed cases occur in India, Nepal, Bangladesh, and Sudan.214
How Common Is Glaucoma in Leishmaniasis?
Intraocular involvement in leishmaniasis is rare, but probably underdiagnosed.
How Common Is Malaria?
Malaria is the most important infectious disease in the world with 300–500 million cases and approximately 2 million deaths per year.215
How Common Is Glaucoma in Malaria?
Glaucoma is a rare complication of malaria. There are only two reports in the literature about glaucoma secondary to malaria.216,217
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How Common Is Trypanosomiasis?
In Africa 60 million people are at risk of infection with human African trypanosomiasis or sleeping sickness, with about 300,000 new cases each year. However, only 10% of cases are probably diagnosed and treated.218 In Central and South America, Chagas’ disease is of great epidemiologic importance; 100 million persons are at risk of infection, approximately 18 million are infected, and 50,000 deaths annually can be attributed to the disease.219 The reservoir for the protozoa T. cruzi involves over 175 species.206
How Common Is Glaucoma in Trypanosomiasis?
Glaucoma has not been reported, but a marked postural drop of the IOP has been noted, possibly secondary to changes in the autonomic innervation secondary to the parasitic infection.220
Diagnosis and Differential Diagnosis
How Is Toxoplasmosis Diagnosed?
Classic ocular toxoplasmosis is diagnosed clinically. The typical ocular lesion is a localized necrotizing retinitis or satellite lesion of an existing chorioretinal scar. Cells are present in the overlying vitreous causing the characteristic appearance of a “headlight in the fog.” The anterior segment of the eye may also be involved in the inflammatory process. An anterior uveitis, which can be either granulomatous or nongranulomatous in character, can be seen only in an eye with an active toxoplasmosis lesion of the retina. Therefore, all patients presenting with an anterior uveitis should have a dilated examination of the retina to rule out an underlying disorder of the posterior segment.221
Laboratory tests can be used to help confirm the clinical diagnosis. More and more, polymerase chain reaction techniques are replacing the Sabin-Feldman test, which uses live Toxoplasma organisms, complement fixation, and enzymelinked immunosorbent assays.222
What Are the Ocular Complications of Toxoplasmosis?
Complications of ocular toxoplasmosis occur in approximately one-third of patients and include chronic iridocyclitis, cataracts, band keratopathy, cystoid macular edema, retinal detachment, and optic atrophy. Transient open-angle glaucoma occurs in about 13% of patients.211 An interesting association with Fuchs’ heterochromic iridocyclitis has been reported; however, its causal relationship is unproven and controversial.223–225
How Does Acanthamoeba Keratitis Present
and How Is It Diagnosed?
The clinical picture is often characterized by severe pain with an early superficial keratitis that is often treated as herpes simplex infection. Subsequently,
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a characteristic radial perineural infiltration may be seen, and ring infiltration is common. Limbitis and scleritis are frequent.226 Laboratory diagnosis is primarily by culture of epithelial samples inoculated onto agar plates spread with bacteria. Recently, Hartmannella has also been shown to cause amebic keratitis.227
How Is Leishmaniasis Diagnosed?
In endemic areas the diagnosis is made on clinical grounds. A definite diagnosis of leishmaniasis is made by documenting the parasite in smears of bone marrow, splenic aspirates, or in biopsies from cutaneous lesions.228 Ocular leishmaniasis is diagnosed by the temporal relationship to the systemic manifestation. However, the parasite has also been isolated from the anterior chamber.203,204
What Are the Ocular Complications of Leishmaniasis?
Most commonly the ocular adnexae are involved,200 but anterior uveitis with elevated IOP and glaucoma have been reported.201–204
How Is Malaria Diagnosed?
The diagnosis is made by demonstrating plasmodia in thick blood smears of suspected individuals.229
What Are the Ocular Complications of Malaria?
The Plasmodium causes hemolysis with anemia, which can lead to blotchy retinal hemorrhages,216 disc swelling, and vitreous hemorrhage.205 Bilateral iridocyclitis with elevated IOP217 and bilateral panuveitis with uveitic glaucoma216 have been reported.
How Is Trypanosomiasis Diagnosed?
Patients with African trypanosomiasis present with irregular fevers, enlarged lymph nodes, delayed sensation to pain, and skin rash. Definitive diagnosis depends on the demonstration of the parasite in blood, lymph node aspirates, bone marrow, and cerebrospinal fluid.
Acute Chagas’ disease should be suspected in any individual from endemic areas with acute febrile illness with lymphadenopathy and myocarditis. Definitive diagnosis is made through documentation of the parasite in the blood.
What Are the Ocular Complications of Trypanosomiasis?
If in Chagas’ disease the route of inoculation is through the conjunctiva, Romaña’s sign (periorbital edema, conjunctivitis, and dacryocystitis) may be present.230 A marked postural drop of the IOP has been noted, possibly secondary to changes in the autonomic innervation secondary to the parasitic infection.220
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Treatment and Management
The treatment of ocular complications of protozoan diseases has to be directed against the underlying parasitic infection. Topical symptomatic therapy (i.e., corticosteroids, cycloplegics, and aqueous suppressants) can be initiated as indicated.
How Is Glaucoma Associated with Toxoplasmosis Treated?
The treatment of ocular toxoplasmosis remains controversial, in particular due to side effects. Some lesions, if far enough in the ocular periphery of an immunocompetent host, can simply be followed up. The most commonly used treatment regimens consist of pyrimethamine, sulfadiazine, and corticosteroids, or pyrimethamine, clindamycin, and corticosteroids. Treatment usually lasts for 3 to 4 weeks, with careful attention to platelet counts if pyrimethamine is used, even though folinic acid is always added to the treatment regimen. Treatment of patients with AIDS cannot be stopped. More recently, atovaquone has been introduced as a therapeutic alternative.231
How Is Acanthamoeba Keratitis Treated?
A variety of topically applied therapeutic agents are thought to be effective, including propamidine isethionate, clotrimazole, polyhexamethylen biguanide, and chlorhexidine. Penetrating keratoplasty is preferably avoided in inflamed eyes, but may be necessary in severe cases to preserve the globe or, when the infection has resolved, to restore corneal clarity for optical reasons.226
How Is Glaucoma Associated with Leishmaniasis Treated?
The standard therapy for the underlying systemic infection consists of pentavalent antimonials (e.g., sodium stibogluconate or meglumine antimoniate).232 In addition, liposomal amphotericin B has recently been approved by the United States Food and Drug Administration for treatment as well.233 The associated uveitic glaucoma can be treated with topical corticosteroids, cycloplegics, and aqueous suppressants as indicated.201,202
How Is Glaucoma Associated with Malaria Treated?
Concomitant to systemic antimalarial therapy,215,229 topical corticosteroids, cycloplegics, and aqueous suppressants can be given as indicated.216,217
How Is Trypanosomiasis Treated?
All drugs currently used to treat African trypanosomiasis are very toxic and require prolonged administration. They include eflornithine, suramin, pentamidine isethionate, melarsoprol, and nifurtimox. Two percent of patients treated for central nervous system (CNS) disease experience relapse.
Although numerous drugs have been tried, including those used to treat African trypanosomiasis and leishmaniasis, few have proven to be effective for therapy of Chagas’ disease. Nifurtimox and benznidazole have both been tried in conjunction with allopurinol.234
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Future Considerations
Treatment of uveitic glaucoma secondary to infectious diseases ultimately has to be directed against treatment and prevention of the underlying infection. Vector control,159 prevention of infection,215 development of vaccines,214,235 and development of new chemotherapeutic agents236,237 are all important in achieving this goal.
GLAUCOMA CAUSED BY HELMINTHIC DISEASES
Definition
What Is Onchocerciasis (River Blindness)?
Onchocerciasis is caused by the parasite Onchocerca volvulus. The parasite is spread through bites of the black fly genus Simulium. After infection with the larva into connective tissue, it matures to filiform adults and may remain in tissues for years. Clinical manifestations vary according to the parasitic load, previous immunity, and duration of infection. A distressing, pruriginous dermatitis and subcutaneous nodules, which are produced by the inflammatory reaction to dying parasites, are very typical. Female adults produce large amounts of microfilaria that migrate through skin and connective tissue. Once an infected host is bitten, the infectious larvae develop again in the female Simulium black fly and the life cycle is completed.238
How Does Onchocerciasis Affect the Eye?
Infection with this tissue nematode may cause keratitis with corneal scarring chorioretinitis, optic neuritis, and uveitis with and without glaucoma.
What Is Toxocariasis?
Toxocara canis and cati are common intestinal parasites of dogs and cats with humans as natural hosts. Toddlers are usually affected by contact with puppies or eating dirt soiled by infected animals. In infected humans, the larvae spread hematologically and are found in multiple organs. The larvae migrate throughout the body for months or years before they complete their full life cycle, therefore the name visceral larva migrans for the disorder.
How Does Toxocariasis Affect the Eye?
Granuloma formation in the posterior segment and diffuse endophthalmitis represent the ocular manifestations. Rare larval migration within the anterior segment can lead to granulomatous uveitis and glaucoma.239–244
What Is Cysticercosis and How Does It Affect the Eye?
Cysticercosis results from infection with ingested eggs of the tapeworm Taenia solium. Oncospheres are released from the hatching eggs and migrate into the intestinal wall and disseminate via blood and lymph vessels and form
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fluid-filled bladder worms (cysticerci) throughout the body.245,246 Intraocular involvement can cause uveitis and secondary IOP elevation.
Epidemiology and Importance
How Common Is Onchocerciasis?
The habitat of the Simulium black fly is around rivers and streams in western and central Africa, central and northern South America, and the Arabian Peninsula. Onchocerciasis is the fourth leading cause of worldwide blindness and is responsible in endemic areas for blindness in millions.247 Infection in travelers is rare but is being recorded on a regular basis.238
How Often Is Onchocerciasis Associated with an Increased IOP and/or Glaucoma?
In Sierra Leone, uveitic glaucoma was reported in 11 of 1,625 individuals with onchocerciasis.248 In an endemic area for onchocerciasis in Nigeria, optic nerve disease was found in 9% of the population. In 50% of these cases onchocerciasis was thought to be the etiology either through direct involvement of the optic nerve or less likely secondary to uveitic glaucoma.
How Common Is Toxocariasis?
In puppies 2 to 6 months of age, the prevalence of T. canis is reported to be 80%. In the U.S. the disease is more prevalent in the south central and southeastern regions. From 10 to 30% of soil samples from public playgrounds and parks are contaminated with T. canis eggs.241
How Common Is Cysticercosis?
Infection most commonly occurs in areas where pigs and people are in close contact, hygienic standards are low, and undercooked pork is eaten. In some rural areas of Central America, the prevalence of Taeniasis is up to 9.8% of the total population, and autopsy data suggest that up to 3.6% of the population of Mexico have neurocysticercosis.245,246 Two to seven percent of individuals with cysticercosis have ocular involvement.249
Diagnosis and Differential Diagnosis
How Is Onchocerciasis Diagnosed?
Onchocerciasis has traditionally been diagnosed by skin snipping and parasitologic examination; however, screening for palpable skin nodules has been found to be a reliable method to identify communities at serious risk for the disease.250
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How Is Toxocariasis Diagnosed?
Diagnosis is made clinically with the help of enzyme-linked immunosorbent assays and cytologic diagnosis of intraocular aspirates.241–243
How Is Cysticercosis Diagnosed?
Cysticercosis can be diagnosed by documenting parasites in biopsy specimen or fine needle aspirates of palpable subcutaneous nodules. Stool examinations positive for adult T. solium constitute supporting evidence. In addition, the diffuse “millet seed” appearance of soft tissue calcifications are also pathognomonic for cysticercosis.245,246,251
Treatment and Management
How Is Onchocerciasis Treated?
Until 1987, suramin and diethylcarbamazine were the only drugs available for the treatment of onchocerciasis, and they could not be used for community therapy because of their toxicity and the dosage schedules required. The introduction of annual oral treatment with ivermectin and the donation of this drug by Merck & Co. provided a new opportunity for the safe treatment and control of the disease. Data indicate a significant reduction of microfilarial loads and regression of early lesions of the anterior segment, including iridocyclitis and sclerosing keratitis. Ivermectin was also found to have a beneficial effect on optic-nerve disease and visual field loss.252
Concurrent uveitis and elevated IOP is treated with topical antiinflammatory agents and aqueous suppressants as indicated.
How Is Ocular Toxocariasis Treated?
Treatment of ocular toxocariasis can be very difficult. Eradication of the parasite without damage to the ocular tissue due to the dying parasite is the goal. This can be achieved by combining medical therapy (i.e., oral thiabendazole or albendazole) with surgical removal of the parasite. Topical corticosteroids, cycloplegics, and aqueous suppressants are given as indicated to control inflammation and IOP.241–243
How Is Cysticercosis Treated?
Treatment consists of medical therapy with praziquantel or albendazole. However, in cases of neurocysticercosis and intraocular involvement, surgical removal of the parasite should be attempted before initiating medical therapy because a severe inflammatory reaction can occur due to the dying parasite. Resulting uveitic glaucoma can be treated with topical steroids, cycloplegics, and aqueous suppressants as indicated.245,246,253–255
ADDITIONAL HELMINTHIC INFECTIONS
Many other parasites can infest ocular and intraocular tissues and thus can cause inflammation and secondary IOP elevation with glaucoma. The following parasites have been isolated from intraocular tissues: Echinococcus multiloc-
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ularis,256–258 Loa loa,259,260 Schistosoma,261 Gnathostoma,262,263 Dracunculus,264
Wucheria,265,266 and Paragonimus.267,268 Several nematodes, including Baylisascaris and Toxocara, have been found as a causative agent in diffuse unilateral subacute neuroretinitis.269–272
Future Considerations
Screening of communities at risk for parasitic disease, vector and parasite control,159,244 and education,273 along with development and supply of new medications to endemic regions worldwide, will be needed to significantly decrease these diseases’ incidence and morbidity.274–279
GLAUCOMA ASSOCIATED WITH DERMATOLOGIC DISORDERS
Definition
How Can Dermatologic Disorders Cause Glaucoma?
Several dermatologic conditions also affect the ocular structures involved in aqueous outflow, which can cause elevation of the IOP and thus glaucoma if optic neuropathy occurs. Some conditions can cause uveitis and associated elevated IOP with possible resulting uveitic glaucoma. For management, see Figure 16–11.
Which Dermatologic Disorders Can Cause Glaucoma?
ROSACEA
Rosacea is a dermatologic condition that frequently affects the eyes. It is characterized by meibomian gland dysfunction and recalcitrant chronic blepharitis. Rosacea can cause keratitis, episcleritis, and iridocyclitis, which in return can cause secondary obstruction of the outflow pathways with resulting elevated IOP.280
VOGT-KOYANAGI-HARADA SYNDROME
Vogt-Koyanagi-Harada (VKH) syndrome is associated with bilateral panuveitis and neurologic and dermatologic manifestations. Uveitic glaucoma occurs in every third patient with VKH syndrome281 (see Chapter 8).
BEHÇET’S DISEASE
Behçet’s disease, which presents with acute hypopyon, iritis, aphthous and genital ulcers, and erythema nodosum in young adults, can also cause uveitic glaucoma in a significant number of adults.
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IOP, intraocular pressure
Figure 16-11. Management of a patient with glaucoma and dermatologic disorder.
OCULAR CICATRICIAL PEMPHIGOID
Ocular cicatricial pemphigoid has also been associated with glaucoma282; however, in many cases the disease is probably secondary to the topical antiglau-