Ординатура / Офтальмология / Английские материалы / Ocular Disease Mechanisms and Management_Levin, Albert_2010

sion of the iris vasculature leads to atrophic sectoral patches in approximately 20% of cases and can produce hypopigmentation or, infrequently, hyperpigmentation, and iris sphincter damage.18,19

Pathophysiology

matory cells consisting of plasma cells and lymphocytes. Occlusive vasculitis plays an important role in sectoral iris atrophy.1

Epidemiology

Ninety percent of the population demonstrates serologic evidence of exposure to VZV by age 60, but only 20% will have experienced an episode of viral reactivation.18,19

Diagnostic workup

The diagnosis is based on a typical clinical picture of unilateral involvement, corneal hypoesthesia, and pattern of keratic precipitates, mild flare and cells in the anterior chamber with foci of iris stromal sectorial atrophy. Aqueous humor aspirates can be analyzed for antibodies directed against VZV by enzyme-linked immunosorbent assay (ELISA). Viral DNA within the aqueous can be detected by PCR technology.18,20

Differential diagnosis

Other viruses of the herpes family, like CMV, EBV, and HSV, can mimic iridocyclitis caused by VZV. Syphilis, tuberculosis, leprosy, lymphogranuloma venereum, and chronic myelomonocytic leukemia can also be considered.1,18,19,21

Treatment

Systemic antivirals are the mainstay management of VZV uveitis – usually oral aciclovir but also famciclovir and valaciclovir (a prodrug of aciclovir). Topical corticosteroids are used to control iridocyclitis and the inflammatory manifestations of corneal disease, including disciform keratitis, endotheliitis, and keratouveitis. In the acute stages, cycloplegic agents are used to relieve the discomfort of photophobia and prevent the formation of synechiae.18,19,22

Prognosis and complications

The most frequent ocular complication is secondary glaucoma. Posterior pole complications can develop and these include cystoid macular edema, epiretinal membrane, papillitis, retinal fibrosis, and detachment. VZV uveitis typically runs a chronic course and visual prognosis is dependent on the severity of complications and its treatment.19,22

Pathology

Histologic reports on VZV uveitis have revealed perineuritis and perivasculitis with infiltration by chronic inflam-

Pathophysiology

VZV establishes its latent phase in the satellite cells of sensory ganglia; the thoracic and lumbar dermatomes are most frequently involved clinically. The trigeminal ganglion is often also infected. In the pathogenesis of persistent or recrudescent viral ocular disease, immune reactions against viral antigens and against tissue autoantigens produced from viral damage play a major role.18

HSV-1, HSV-2, VZV, and HHV-8 belong to the subfamily of alpha herpesviruses. The clinical picture of various forms of intraocular inflammation caused by alpha herpesviruses is similar and therefore it may be difficult to distinguish VZV from HSV. Nevertheless, HSV as a cause of iridocyclitis and trabeculitis is often overlooked. Corneal lesions (Figure 83.3) or a history of herpetic keratitis in an eye with iritis must be considered herpetic in origin unless proven otherwise. A high degree of suspicion for HSV anterior uveitis must be maintained in unilateral involvement diminished corneal sensation and typical iris stromal atrophy. This condition responds promptly to aciclovir therapy, which may be required chronically. Diagnosis of HSV can be confirmed by PCR testing of the aqueous humor for herpetic DNA (Box 83.1).

Other viruses causing uveitis are summarized in Table 83.1.

Figure 83.3  Dendrites with anterior stromal haze in herpes simplex virus-associated keratouveitis.

Bartonella

Clinical background

Key symptoms and signs

Systemic manifestations include myalgia, malaise, fatigue, low-grade fever, and lymphadenopathy. Ocular manifestations are typically unilateral and can present in both

Box 83.1  Ocular manifestations of herpesviruses

•Cytomegalovirus retinitis: slowly expanding white infiltrate in the peripheral retina

Granular, white, multifocal satellite lesions of patchy retinitis with limited or no retinal hemorrhages

Arc-shaped solitary expanding patch of retinitis with multiple retinal hemorrhages

Extensive perivasculitis with “frosted-branch angiitis” appearance

•Epstein–Barr virus: follicular conjunctivitis is the most frequent ocular feature

Anterior and posterior uveitis may occur

•Varicella-zoster virus: anterior/posterior-segment findings

Keratitis

Iritis/iridocyclitis

Trabeculitis

Acute retinal necrosis

•Herpes simplex virus: spectrum of ocular signs similar to varicella-zoster virus; high degree of suspicion if:

Corneal hypoesthesia

Iris stromal atrophy and transillumination defects

immunocompetent and immunocompromised patients. Neuroretinitis appears to be most common and is usually unilateral, with optic disc edema (Figure 83.4) and a macular star.23,24 A multifocal retinitis and/or choroiditis can also develop, as can chorioretinitis, serous macular detachments, intraretinal hemorrhages, cottonwool spots, Parinaud’s oculoglandular syndrome, conjunctivitis, anterior and posterior uveitis, and vascular lesions of the optic nerve.

Historical development

Barton described the first human Bartonella infection in 1909.25 Foshay created the term “cat-scratch fever” in 1932.26

Figure 83.4  Fluorescein angiogram in Bartonella-associated panuveitis with papilledema and cystoid macular edema.

Sweeny and Drance made the correlation between intraocular inflammation and cat-scratch disease (CSD) in 1970.27

Epidemiology

CSD has been shown to be a worldwide zoonotic infection with the reservoir for Bartonella henselae in domestic cats.23 CSD is the leading cause of regional lymphadenopathy in children and young adults worldwide. Prevalence of neuroretinitis in the context of CSD is approximately 1–2%.28,29 The infection is not known to be transmitted from human to human. The prevalence of CSD in the USA is approximately 22 000 cases per year.30

Diagnostic workup

The diagnosis of CSD is primarily based on clinical features supported by laboratory testing with detection of DNA of B. henselae by PCR technology using a very small sample of serum or other body fluids. Other tests include enzyme immunoassay (EIA) and Western blot test.24,25

Differential diagnosis

Other causes of regional lymphadenopathy and conjunctivitis include tularemia, sporotrichosis, tuberculosis, syphilis, lymphogranuloma venereum, leprosy, and Yersinia. Neuroretinitis may be seen in syphilis, tuberculosis, toxoplasmosis, varicella, herpes simplex, toxocariasis, leptospirosis, and infectious mononucleosis. A macular star with vitritis can be seen in toxoplasmosis and vascular disorders such as anterior ischemic optic neuropathy, acute systemic hypertension, and increased intracranial pressures.1,24,25

Treatment

There are no formalized guidelines which one can follow to treat the ocular complications associated with B. henselae. Despite this, several groups have used oral ciprofloxacin, prednisone, and doxycycline, with favorable responses.31,32 Elevated immunoglobulin (Ig) M or IgG titers for B. henselae can be suggestive of current or past infection.

Prognosis and complications

CSD typically runs a self-limiting course in immunocompetent hosts. Antimicrobial therapy in immunocompromised hosts results in a dramatic response and hence these have been recommended for severe ocular or systemic complications of CSD. Visual prognosis of most patients with CSDassociated neuroretinitis is therefore excellent.23

Etiology

B. henselae, one of the four human species of Bartonella, has been implicated as the cause of CSD. This species predominantly causes neuroretinitis, while the three others cause endocarditis (B. elizabethae), Carrion’s disease (B. bacilliformis), and trench fever (B. quintana).25 Regnery et al33 showed that 86% of patients with CSD had B. henselae antibodies as compared to 6% of those who were healthy

Clinical background

Box 83.2  Bartonella

•Zoonosis

•Reservoir of B. henselae in cats

•Affects children and young adults

•Presents with oculoglandular syndrome

•Neuroretinitis may be the foremost ocular manifestation

•Oral antibiotics (tetracyclines) and oral corticosteroids may be used for treatment

patients. PCR assays have shown that infected cats harbor fleas infected by B. henselae. Transmission from cat to cat occurs via the cat flea Ctenocephalides felis. It is thought to be central to the pathogenesis of CSD in human beings, perhaps by dropping contaminated feces on to the fur and dander of infested cats. The predominant mode of transmission of B. henselae is through a cat bite or scratch.1,23,24

Pathophysiology

The exact pathophysiology of CSD-associated neuroretinitis is not completely understood. Intraocular infection or direct involvement of the optic nerve by B. henselae has been implicated (Box 83.2). The ocular findings may also represent a parainfectious inflammatory response.1,23

Syphilis

Clinical background

Key symptoms and signs

Systemic manifestations

Primary syphilis is characterized by a chancre at the inoculation site that appears 2–6 weeks after infection and resolves about 4 weeks after its appearance. If untreated, the disease progresses to secondary syphilis, with generalized maculopapular rash and lymphadenopathy. The rash typically affects the palms and soles, and can be accompanied by fever, malaise, headache, nausea, hair loss, mouth ulcers, and joint pain. At this stage, the eyes are affected in 10% of cases.34 Then, during the latent stage, there are no evident systemic disease manifestations, and the infection is not contagious. This stage can last for the patient’s lifetime. Tertiary syphilis can affect any system, but mainly the cardiovascular (aortitis, aortic aneurysm, aortic valve insufficiency) and neurologic system (meningovascular syphilis, tabes dorsalis). The typical lesion in this stage is the gumma, which is a granuloma, and can be found anywhere in the body.

Ocular manifestations

Most patients with syphilitic uveitis develop it during the latent stage of the infection. Anterior uveitis may be unilateral or bilateral, granulomatous, or nongranulomatous. It can present with iris nodules or atrophy, anterior-chamber cells with or without anterior vitritis, dilated iris vessels, interstitial keratitis, and lens dislocation. Syphilis can affect

Figure 83.5  Syphilitic panuveitis with vitritis, vitreous hemorrhage, and papillitis.

the posterior segment (Figure 83.5), most commonly causing chorioretinitis. The fundus lesions are usually grayish yellow in color. Other manifestations include disc edema, arterial or venous vasculitis, vitritis, intermediate uveitis, serous RD, neuroretinitis, and necrotizing retinitis. Complications include glaucoma, cataracts, macular edema, and choroidal neovascular membranes.34–38

Historical development

Schaudin and Hoffman isolated the spirochete in 1905 from the skin lesions of infected patients.39

Epidemiology

Although it was the second leading cause of uveitis before the 1940s, currently it comprises about 1–2% of all uveitis cases.40

Diagnostic workup

Available nonspecific serological tests that quantify the amount of serum anticardiolipin antibody are the rapid plasma reagin (RPR) and the Venereal Disease Research Laboratory (VDRL). The results depend on the status of infection and treatment. Titers are usually high in active infection, but drop when the disease is not active (latent infection or after successful treatment). Specific tests measure the amount of serum antibody against treponemal antigens. The fluorescent treponemal antigen absorption test (FTA-ABS) is the one mostly used. This test becomes positive during the secondary stage of syphilis and remains positive for the patient’s lifetime. This test is more sensitive during the latent stage, which is when uveitis usually develops. With the microhemagglutination assay for T. pallidum (MHA-TP) test, treponemes can be visualized by incubating infected body fluid (from chancre or skin pustule) with fluorescent-tagged antibody and visualizing it under dark-field microscopy. The T. pallidum particle agglutination test (TP-PA) is used to confirm a positive FTAABS. Patients with uveitis who are diagnosed with syphilis must have examination of the cerebrospinal fluid.41–43

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Box 83.3  Syphilis

•Great masquerader

•Stages are primary, secondary, latent, and tertiary

No uveitis in primary stage

Uveitis may present in the remaining stages but most commonly in the latent stage

•Anterior uveitis, diffuse chorioretinitis, and necrotizing retinitis may be seen

•Diagnostic tests include:

Rapid plasma reagin (RPR)/Venereal Disease Research Laboratory (VDRL)

Fluorescent treponemal antibody absorption test (FTA-ABS)

Microhemagglutionation assay for Treponema pallidum (MHA-TP)

Treponema pallidum immobilization (TPI) test

Treponema pallidum particle agglutination (TP-PA)

Dark-field microscopy

Polymerase chain reaction (PCR)

•Treatment: benzathine penicillin or penicillin V

Differential diagnosis

Syphilitic uveitis must be differentiated from other causes of granulomatous uveitis like tuberculosis, leprosy, sarcoidosis, and herpes. It is also in the differential diagnosis of intermediate uveitis and therefore may be confused with Lyme disease or sarcoidosis.41

Treatment

Penicillin is the treatment of choice in syphilis, either intramuscular or intravenous. As syphilitic uveitis is considered a form of neurosyphilis, the intravenous regimen is favored. Alternative treatments for penicillin-allergic patients include doxycycline or tetracycline. Penicillin desensitization is another option for these patients.44

Prognosis and complications

Complications from syphilitic uveitis include cataracts, glaucoma, macular edema, epiretinal membranes, RD, chorioretinitis, and neovascular memebranes. Complications secondary to treatment include Jarisch–Herxheimer reaction manifesting as fever, myalgia, malaise, and headache.

Syphilis, if recognized early and treated appropriately, can result in a cure. If untreated, prolonged syphilitic disease can permanently damage the eye and can result in significant morbidity and mortality due to cardiovascular complications.42

Etiology

Syphilis is an infection caused by the spirochete Treponema pallidum. It can mimic many different diseases throughout its course, for which is has been called the “great imitator” (Box 83.3). It can persist in the affected person for a lifetime,

and if left untreated can progress through four stages. It is a sexually transmitted disease, which enters the body through the genitals, mouth, or skin breaks.

Pathophysiology

The inflammatory response against the spirochete causes the damage and destruction of ocular tissue. The host immune response role in syphilitic infection is being investigated. The difficulty in culturing T. pallidum in vivo has been an impediment in the study and of its pathogenic mechanisms. Long-term immunity against syphilis is not conferred after initial infection and reinfection can occur in previously treated individuals. A switch from Th1mediated process (during the first infection) to a Th2mediated process with subsequent infections has been implicated.1,43

Other bacteria causing uveitis are summarized in Table 83.2.

Clinical background

Figure 83.6  Congenital toxoplasmosis scar with temporal excavation and atrophy of the optic nerve with juxtapapillary scar along the inferior arcade.

Toxoplasmosis

Clinical background

Key symptoms and signs

Congenital toxoplasmosis involves the central nervous system and it may present several months or even years after infection, with several features characteristic of the disease, such as paralysis, encephalomyelitis, seizures, hydrocephalus, microcephaly, and intracranial calcifications. In the acquired form of the infection, lymphadenopathy is the most common finding. However, the disease is typically self-limiting in the immunocompetent patient.

Ocular manifestations vary. In the congenital form, the most common finding is retinochoroiditis, occurring in 70– 90% of the cases. Associated ocular sequelae include cataracts, nystagmus, optic atrophy, and strabismus. In the posterior segment, T. gondii has a strong predilection for invading the macula and optic nerve, with a tendency to recur. A yellow, elevated, fluffy lesion is seen in the hallmark “headlight in the fog” appearance of the active Toxoplasma lesion. In the active form of the disease, vitritis is almost always present in all cases. Vasculitis, choroiditis, neuroretinitis, papillitis, and necrotizing retinitis may present as well.45,46 Retinochoroidal scars (Figure 83.6) are typically found in both the acquired and congenital forms and can be solitary or multiple.

In the anterior segment, mutton-fat keratic precipitates, anterior-chamber reaction, and posterior synechiae may be present in the active part of the disease.

Historical development

In 1940, Pinkerton and Weinman described the first case of acquired toxoplasmosis with ocular manifestations.47 However, the initial case of congenital toxoplasmosis was reported by Janku in 1923.48

Epidemiology

Toxoplasmosis is the leading cause of posterior uveitis in the world in otherwise healthy individuals. Toxoplasmosis is a very widely distributed zoonosis. Seropositive individuals typically live in countries with tropical climates. In certain countries like France, by the fourth decade of life, 90% of the French population is seropositive for toxoplasmosis. In the USA, 70% of the population over 50 shows seropositivity. The incidence of congenital toxoplasmosis in the USA is approximately 0.2–1%.49–51

Diagnostic workup

The Sabin and Feldman dye, hemagglutination, ELISA, complement fixation, and immunofluorescence antibody tests may be used to detect for presence of toxoplasmosis.52,53 PCR of samples of the aqueous or vitreous humor can confirm the presence of T. gondii with high specificity and selectivity.

Fluorescein angiogram (FA) and indocyanine green angiography (ICGA)

During the early phase of an FA study, there is hypofluorescence of the lesion which then leaks dye in late phase. In ICGA, active retinochoroiditis may reveal areas of hypofluorescence or hyperfluorescence in the early phases and, in the later phase, hyperfluorescence predominates.

Differential diagnosis

Congenital toxoplasmosis must be differentiated from other infectious diseases of the TORCH group (rubella, CMV, and herpes) as well as tuberculosis, syphilis, and AIDS. Recurrent toxoplasma lesions adjacent to the older ones may resemble serpiginous choroiditis. Necrotizing retinitis caused by other agents must be considered, such as herpes viridae, fungal retinitis, septic retinitis, and toxocariasis. Atypical forms of toxoplasmosis may resemble white-dot syndromes.52–54

Treatment

Medical treatment of toxoplasmosis employs corticosteroids and various antimicrobial agents. The use of pyrimethamine, sulfadiazine, and corticosteroids is the gold standard since Eyles and Coleman advocated this triad of treatment in 1953.55 Folinic acid is used as adjuvant therapy to pyrimethamine, which has antifolate properties. Other agents used include clindamycin, spiramycin, atovaquone, tetracycline, minocycline, clarithromycin, azithromycin, trimethoprim, sulfamethoxazole, and trovafloxacin. Laser photocoagulation and pars plana vitrectomy have had limited success.

Prognosis and complications

Complications like granulomatous iritis, secondary glaucoma, retinal vasculitis, vascular occlusions, rhegmatogenous and serous RD, and secondary pigmentary retinopathies might disguise the original toxoplasmic lesion and make the correct diagnosis difficult. Prognosis of this disease depends on the presence of macular involvement as the active disease is typically self-limiting. Factors responsible for a poor visual prognosis include proximity to the fovea, large lesions, and duration of the disease. Early diagnosis and appropriate

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treatment are essential to minimize complications and loss of vision.53,56

Pathology

T. gondii is found in the host’s saliva, urine, semen, and peritoneal fluid. The organism presents in three forms: tachy­zoite, bradyzoite, and sporozoite. Tachyzoites are responsible for the acute form of the disease. Tachyzoites stain with Giemsa and have a bluish cytoplasm and a reddish ovoid nucleus. Cysts have eosinophilic walls with the bradyzoites inside and are periodic acid–Schiff-positive.53

Etiology

Toxoplasma gondii is an intracellular obligate protozoan, which causes ocular toxoplasmosis by the release of actively proliferating tachyzoites. It is transmitted to humans via ingestion of tissue cysts in raw or undercooked meat or through contact with the fecal matter of cats, which contains T. gondii oocysts. The disease may be congenital, acquired, and ocular (Box 83.4).53,54

Box 83.4  Toxoplasmosis

•Leading cause of posterior uveitis

•Congenital form presents with retinochoroiditis, cataracts, nystagmus, strabismus with or without systemic central nervous signs and symptoms

•Acquired form may present with focal retinitis, retinochoroiditis, and scarring

•Predilection for the macula and optic nerve with tendency to recur

•Gold standard for therapy is pyrimethamine, sulfadiazine, and corticosteroids

Key references

Pathophysiology

Cell-mediated immunity is the major mechanism involved in resolution of active disease. It is characterized by activation of macrophages, natural killer cells, and release of cytokines. The local ocular responses tend to be suppressed to limit tissue damage as the eye is an immune-privileged tissue. Another strategy developed by the organism to evade host defense mechanism is encystment. Tissue cysts become invisible to the immune system, thereby allowing the cysts to remain dormant for extended periods of time.56

Other parasites and fungi causing uveitis are summarized in Tables 83.3 and 83.4.

1.Heilingenhaus A, Helbig H, Fiedler M. Herpesviruses. In: Foster CS, Vitale AT (eds) Diagnosis and Treatment of Uveitis. Philadelphia: Saunders, 2002:315–332.

6.Jabs DA, Van Natta ML, Thorne JE, et al. Studies of Ocular Complications of AIDS Research Group. Course of cytomegalovirus retinitis in the era of highly active antiretroviral therapy: 1. Retinitis progression. Ophthalmology 2004;111:2224–2231.

11.Raymond LA, Wilson CA, Linnemann CC. Punctate outer retinitis in acute EBV infection. Am J Ophthalmol 1987;104:424–426.

20.Chan CC, Shen D, Tuo J. Polymerase chain reaction in the diagnosis of uveitis.

Int Ophthalmol Clin 2005;45:41– 55.

21.Baltatzis S, Romero-Rangel T, Foster CS. Sectorial keratitis and uveitis: differential diagnosis. Graefes Arch Clin Exp Ophthalmol 2003;241:2–7.

22.Miserocchi E, Waheed NK, Dios E, et al. Visual outcome in herpes simplex virus and varicella zoster virus uveitis: a clinical evaluation and comparison. Ophthalmology 2002;109:1532–

1537.

23.Cunningham ET, Koehler JE. Ocular bartonellosis. Am J Ophthalmol 2000;130:340–349.

34.Crouch ER, Goldberg MF. Retinal periarteritis secondar to syphilis. Arch Ophthalmol 1975;93:384–387.

35.Tamesis R, Foster CS. Ocular syphilis. Ophthalmology 1990;97:1281–1287.

45.Park SS, To KW, Friedman AH, et al. Infectious causes of posterior uveitis. In: Albert DM, Jakobiec FA (eds) Principles and Practice of Ophthalmology. Philadelphia: WB Saunders, 1994:460– 461.

52.Holland GN. Ocular toxoplasmosis: a global reassessment. Part II: disease manifestations and management. Am J Ophthalmol 2004;137:1–17.

56.Holland GN. Reconsidering the pathogenesis of ocular toxoplasmosis. Am J Ophthalmol 1999;128:502–505.

Overview

Sarcoidosis (from the Greek, meaning “tumor-like”) is a systemic inflammatory condition that may affect many organs. Its hallmark is the noncaseating granuloma, a nonspecific but highly suggestive pathologic finding. Although sarcoidosis most commonly affects the lungs and lymph nodes, the eyes are frequently affected. Because the ocular manifestations of sarcoidosis may be protean, this condition is considered in the differential diagnosis in nearly every case of ocular inflammatory disease. Significant progress has been made in the past several years in understanding the pathogenesis of sarcoidosis.

Clinical background

Historical development

Sarcoidosis was first recognized by the London physician, Dr. Jonathan Hutchinson, who in 1877 described a series of patients with purple skin plaques on the hands and feet. Twelve years later, Dr. Cesar Boeck gave the name “sarcoid” to a disease process featuring multiple benign skin lesions. The first description of sarcoidosis affecting the eye was in 1909 with the description of Heerfordt syndrome, featuring parotid inflammation, uveitis, facial nerve palsy, and fever.

Key symptoms and signs

Sarcoidosis most often presents in the eye as uveitis. Uveitis is a general term referring to inflammation of the iris (iritis), vitreous body (intermediate uveitis), or retina and choroid (retinitis and choroiditis; retinal vasculitis may also accompany these findings). Typical symptoms of anterior uveitis are redness, pain, and aversion to bright lights (photophobia). Intermediate uveitis typically presents as new “floaters” in the patient’s vision. Posterior uveitis may present with loss of central visual acuity, new visual field defects, or generalized blurring of the vision (often macular edema).

Ocular sarcoidosis can present with many different signs (Box 84.1). The conjunctiva may contain macroscopic granulomas that can be observed at the slit lamp. The lacrimal glands may be enlarged from granulomas, which may con-

Ocular sarcoidosis

Russell N Van Gelder and Suzanne M Dintzis

tribute to dry eye. The classic intraocular presentation of sarcoidosis is of an anterior or panuveitis, featuring large clumps of white blood cells adherent to the corneal endothelium, known as “mutton fat keratic precipitates” (Figure 84.1). The anterior chamber frequently contains free-floating leukocytes. These are quantified on a standardized scale by the clinician, with 1+ cells corresponding to 6–15 visible cells in a 1 × 1 mm slit beam, to 4+ cells which are too numerous to count. The clinician may also observe flare in the anterior chamber as visible diffusion of the slit-lamp beam. This phenomenon arises from increased protein concentration in the aqueous humor due to compromise of the blood–aqueous barrier. The iris can develop adhesions to the lens, called posterior synechiae. Intraocular pressure may be elevated from trabecular meshwork inflammation or anterior synechiae from the iris to the peripheral cornea, blocking the trabecular meshwork. The pressure may also be reduced from ciliary body inflammation. The vitreous cavity often features white blood cell infiltration, which can be diffuse in the liquid anterior vitreous, or more clumped in the formed vitreous. The clumped cells are sometimes referred to as “snowballs.” Posteriorly, the most common manifestation of sarcoidosis is the choroidal granuloma (Figure 84.2). These may be solitary or numerous, and may range from whitish in color to yellow. The vasculitis associated with sarcoidosis is most often seen on the veins. An unusual form of periphlebitis, called “tache de bougie” (candle wax drippings) occurs in patients with sarcoidosis. In a small proportion of cases sarcoid optic nerve head granulomas may be observed. Because of its protean ocular manifestations, sarcoidosis is often considered one of the “great masquerade” conditions, along with syphilis and tuberculosis.

Outside the eye, sarcoidosis typically presents in the lungs, where it may present as chronic cough or shortness of breath; approximately one-third of cases are found as an incidental finding on chest X-ray. Pulmonary sarcoidosis is staged based on the radiographic findings. The first stage is visible hilar adenopathy. In the second stage, pulmonary infiltrate is seen along with the hilar lymphadenopathy. In the third stage, the adenopathy is resolved but the infiltrates remain. Stage 4 sarcoidosis features pulmonary fibrosis; the prognosis for this stage of sarcoidosis is poor. Sarcoidosis may present in almost any other organ system. It is associated with liver granulomas, diffuse lymphadenopathy, deep