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Ocular tuberculosis masquerading as ocular tumors
SURVEY OF OPHTHALMOLOGY
VOLUME 49 • NUMBER 1 • JANUARY–FEBRUARY 2004
CLINICAL PATHOLOGIC REVIEW MILTON BONIUK AND STEFAN SEREGARD, EDITORS
Ocular Tuberculosis Masquerading As Ocular Tumors Hakan Demirci, MD,1 Carol L. Shields, MD,1 Jerry A. Shields, MD,1 and Ralph C. Eagle, Jr, MD2 1
Oncology Service, Wills Eye Hospital, Thomas Jefferson University, and 2Pathology Department, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
Abstract. Tuberculosis has re-emerged as a serious public health problem in recent years. The ocular manifestations of tuberculosis are uncommon and diverse. Occasionally, patients initially present with ocular symptoms that simulate intraocular malignancy or other inflammatory conditions. We present five patients with ocular tuberculosis who were referred with the suspicion of ocular malignancy. Four of the five patients had recently emigrated to the United States. The presenting features of these patients were panophthalmitis (one patient), endophthalmitis leading to scleral perforation (one patient), active choroidal granuloma associated with uveitis (two patients), and amelanotic choroidal lesion without inflammatory signs (one patient). Of these five cases, two had a known history of systemic tuberculosis, while the ocular findings in the other three cases were the presenting manifestation of systemic tuberculosis. Multi-drug antituberculous regimen were employed in all cases for a mean of 9 months (median 6 months, range 6–12 months). Three patients responded well to therapy with salvage of the globe and the two remaining patients underwent primary enucleation for blind painful eye or perforated eye. In conclusion, ocular tuberculosis can have variable clinical manifestations and occasionally appears as an intraocular or epibulbar tumor. A high degree of clinical suspicion is important, especially in immigrants from developing countries. (Surv Ophthalmol 49:78–89, 2004. 쑖 2004 Elsevier Inc. All rights reserved.) Key words. choroid • eye • granuloma culosis • tumor • uvea • uveitis
•
inflammation
Tuberculosis is a serious infectious disease that ranks as an important cause of death worldwide, accounting for nearly 2 million fatalities per year.1 The number of reported cases in the U.S. had been decreasing steadily until the mid 1980s. In recent years, however, tuberculosis has re-emerged as a serious health problem with an increase from 22,201 reported cases of tuberculosis in 1985 to 26,283 reported cases in 1991.41 Immigration from other countries, social problems such as homelessness and drug abuse, and the acquired immunodeficiency syndrome (AIDS) epidemic have been implicated in the increasing incidence of tuberculosis.41
•
melanoma
•
retina
•
tuber-
Tuberculosis generally affects the lungs, although other organs are involved in up to 20% of cases.41 The incidence of ophthalmic manifestations in patients known to have systemic tuberculosis is only 1–2%.16 Ocular and periocular involvement is most likely to occur as part of a postprimary infection because of direct hematogenous spread or, less commonly, a secondary hypersensitivity phenomenon alone. Although all parts of the eye can be involved, the most common presentations are chronic anterior uveitis, choroiditis, and sclerokeratitis.28 Occasionally, patients initially may present with ocular symptoms that simulate intraocular malignancy or other inflammatory 78
쑖 2004 by Elsevier Inc. All rights reserved.
0039-6257/04/$–see front matter doi:10.1016/j.survophthal.2003.10.009
OCULAR TUBERCULOSIS MASQUERADING AS OCULAR TUMORS
conditions.49,50 Failure to recognize the ophthalmic manifestations of tuberculosis and diagnose the underlying systemic disease may lead to the loss of an eye and even loss of life. We report five patients with ocular tuberculosis who were referred to us with the suspicion of ocular malignancy.
Patients and methods We reviewed the computerized files of the Ocular Oncology Service at Wills Eye Hospital between January 1974 and July 2000. We identified and reviewed five patients with the diagnosis of ocular tuberculosis (Table 1). We compared our findings with those reported in the literature.
Results PATIENT 1
A 37-year-old man from India presented with a 2month history of decreased vision and floaters in his right eye. Nine months earlier, while in India, he developed a fever of unknown origin, but systemic evaluation for infectious and inflammatory etiologies was reported to be negative. He was treated with oral corticosteroids for idiopathic unilateral choroiditis. Progressive deterioration of visual acuity raised concern about eye cancer and the patient was referred to the oncology service. The visual acuity was 20/30 in each eye. The left eye was normal, as was the anterior segment examination of the right eye. Fundus examination of the right eye showed an amelanotic choroidal lesion measuring 8.0 × 7.5 × 5.0 mm with surrounding retinal exudation and secondary retinal detachment (Fig. 1A). Intense vitreous inflammation and mild vitreous hemorrhage were present. Choroiditis was diagnosed and tuberculosis was suspected. Subsequent systemic evaluation showed a positive skin tuberculin test reaction (PPD), hilar adenopathy, multinodular apical infiltrates in the lung, multiple infiltrates in the liver and spleen and an erosive paravertebral mass. Computed tomograph (CT)guided aspiration biopsy of the paravertebral mass showed culture-positive granulomatous inflammation. A diagnosis of miliary tuberculosis was made and four-drug antituberculosis therapy (isoniazid and rifampin for 12 months, and ethambutol hydrochloride and pyrazinamide for the first 2 months) was started. Three weeks of systemic corticosteroid therapy was given after the first month of treatment. At 1-year follow-up, the choroidal lesion completely regressed but overlying traction retinal detachment and retinal folds were present (Fig. 1B).
79
PATIENT 2
A 23-year-old male student from India presented with a 1-month history of blurred vision in his right eye. A choroidal tumor was discovered, prompting a referral to the oncology service. One month previously, he developed pain and swelling at the left large toe, which was diagnosed as osteomyelitis. Aspiration biopsy revealed culture-positive granulomatous inflammation. A diagnosis of tuberculous osteomyelitis was made and 2 weeks prior to our evaluation, two-drug antituberculosis therapy (isoniazid and rifampin) and systemic antibiotic therapy (ciproflaxicin) were instituted. The visual acuity was 20/40 in the right eye and 20/20 in the left eye. Fundus examination of the affected right eye showed an amelanotic choroidal lesion measuring 3.0 × 3.0 × 1.0 mm with surrounding retinal detachment in the macula (Fig. 2). Based on the known history of systemic tuberculosis, the patient was treated with two-drug antituberculosis therapy (isoniazid and rifampin). At 6-month follow-up, his vision had improved to 20/20 and the lesion largely regressed to a small choroidal scar and subretinal fluid resolved. PATIENT 3
A 28-year-old man from Zaire presented with a 3month history of decreased vision and a 2-week history of severe pain in his left eye. Two months previously he had been treated elsewhere for unilateral idiopathic choroiditis with systemic corticosteroids. Progressive deterioration of visual acuity lead to suspicion of choroidal tumor and the patient underwent vitreous biopsy, which was unrevealing. The patient was referred to the oncology service to rule out a choroidal tumor. The visual acuity was 20/25 in the right eye and no light perception in the left eye. The affected left eye showed swollen eyelids, hyperemic and chemotic conjunctiva, corneal edema, aqueous inflammation, and iris neovascularization. There was no view of the fundus due to intense vitreous inflammation. Because the blind, painful left eye had signs of panophthalmitis, it was enucleated. Histopathologic examination showed granulomatous inflammation with areas of caseation, Langhan’s giant cells, and acid-fast bacilli (Fig. 3). Systemic evaluation for tuberculosis was negative, so there was no systemic therapy. Six months later, the patient developed tuberculous peritonitis and was treated with 4-drug antituberculosis regimen elsewhere. PATIENT 4
A 29-year-old African-American woman presented with a 2-week history of decreased vision in her right
80
Overview of 5 Patients with Intraocular Tuberculosis Age/Sex/Area Case of Origin
Initial Systemic Diagnosis Problem Elsewhere Eye Symptoms
1
37/M/Indian
No
2
23/M/Indian
No
3
28/M/Zairan
4
29/F/AfricanAmerican
537
29/F/Ecuadorian
Idiopathic OD Decreased unilateral vision, choroiditis floaters
Choroidal OD Blurred tumor vision No Idiopathic OS Decreased unilateral vision, choroiditis pain HIV⫹ Retinal OS Decreased tumor vision No
Sarcoidosis
Clinical Features
CXR
Involved Organs
PPD
Systemic Therapy
Ocular Outcome
Sytemic Outcome
Tuberculoma, Active Reac RD, Vit. Hem. disease and Inf.
Tuberculoma, NA RD Panophthalmitis Normal
Liver, spine, I, R for Regressed Good response paravertebral 12 mo lesion mass E, P for 2 mo CS for 1 mo NA Left large toe I, R for Regressed Good response 4 mo lesion Non-react Peritonium NA Enucleation Tb peritonitis in 6 mo
AC rxn, Active Reac Tuberculoma, disease RD OS Pain, redness Endopthalmitis Hilar LAP Reac
Follow-up (mo) 12
Surv Ophthalmol 49 (1) January–February 2004
Table 1
6 6
No
I, R, P for Regressed 3 mo lesion
Good response
10
No
I for 7 mo Enucleation Good response
7
M ⫽ Male; F ⫽ Female; OD ⫽ Right eye; OS ⫽ Left eye; Tuberculoma ⫽ Choroidal tuberculoma; RD ⫽ Retinal detachment; Vit. Hem ⫽ Vitreous hemorrhage; Vit. Inf. ⫽ Vitreous inflammation; AC rxn ⫽ Anterior chamber reaction; NA ⫽ Non-available; Reac ⫽ Reactive; Non-react ⫽ Non-reactive; LAP ⫽ Lymphadenopathy; I ⫽ Isoniazid; R ⫽ Rifampin; E ⫽ Ethambutol; P ⫽ Pyrazinamide; CS ⫽ Corticosteroid; mo ⫽ Months; Tb ⫽ Tuberculosis.
DEMIRCI ET AL
81
OCULAR TUBERCULOSIS MASQUERADING AS OCULAR TUMORS
enopathy, a positive PPD test reaction and apical pulmonary cavitation, and culture-negative granulomatous inflammation on hilar lymph node biopsy. Sarcoid uveitis was diagnosed, and oral corticosteroids and prophylactic isoniazid therapy were instituted. Deterioration of her ocular condition with the development of a pigmented lesion at the inferior limbus raised the suspicion of conjunctival melanoma and led to referral to the oncology service (Fig. 4). The visual acuity was 20/25 in the right eye and light perception in the left eye. In the affected left eye, a pigmented mass with a central, necrotic perforation was noted at the inferior limbus. The cornea was hazy and the anterior chamber was filled with inflammatory material. There was no view of fundus. Because the left eye was blind, perforated, and appearing infective, it was enucleated. Histopathologic examination showed a chronic, granulomatous inflammation without caseation obliterating the anterior segment of the eye with extraocular extension around the perforation site. The diagnosis of tuberculosis was established by the demonstration of multiple acid-fast bacilli. The patient received 7 months of isoniazid therapy. At 41-month follow-up, she was healthy. Fig. 1. A: Fundus photograph showing yellow, domeshaped choroidal lesion, extending superonasally from optic disk and associated with vitreous hemorrhage and inflammation. B: One year later, the lesion regressed with overlying vitreous traction and retinal folds.
eye. She was human immunodeficiency virus (HIV)positive and had been receiving three-drug antituberculosis therapy (isonazid, rifampin, and pyrazinamide) for pulmonary tuberculosis for 2 months. The visual acuity was hand motions in the right eye and 20/20 in the left eye. The affected right eye showed multiple fine keratic precipitates and aqueous inflammation. Fundus examination showed an amelanotic chorioretinal lesion measuring 10.0 mm × 7.5 mm × 3.5 mm with secondary retinal detachment in the juxtapapillary area. Our diagnosis was inflammatory chorioretinal tuberculoma, confirmed by fine-needle aspiration biopsy (FNAB). After 10 months of three-drug antituberculosis therapy, the lesion regressed and a macular chorioretinal scar developed. PATIENT 5
A 29-year-old woman from Ecuador presented with 5-month history of pain and redness in her left eye. Five months previously she developed anterior uveitis, and systemic evaluation revealed left hilar ad-
Discussion Tuberculosis is an acute or chronic infectious disease caused by acid-fast bacteria belonging to Mycobacterium tuberculosis complex.41 The most frequently encountered human agent is Mycobacterium tuberculosis. Closely related organisms that can infect humans include Mycobacterium bovis and Mycobacterium africany.41 The number of tuberculosis cases, which had been falling steadily, began to rise in many industrialized countries after the mid 1980s (Fig. 5).3 For example, there had been an annual decrease of tuberculosis of about 5–7% between 1950 and 1984, but the number of cases increased by 18% overall between 1985 and 1991.3 Using the trend for 1981 to 1984 to estimate the expected number of cases for 1985 to 1991, it was calculated that more than 39,000 excess cases of tuberculosis occurred between 1985 and 1991.3 The HIV epidemic is believed to be largely responsible for the increasing incidence of tuberculosis.4 Studies of patients at tuberculosis clinics in metropolitan areas have shown the prevalence of HIV seropositivity to be as high as 46%.4 Tuberculosis is still one of the most important causes for morbidity and mortality in developing countries such as India. The incidence of tuberculosis in India in 1998 was reported to be 115 cases per 100,000 population, as compared to 7 cases per 100,000 in the United States.1 One of our cases was HIV-positive and some
82
Surv Ophthalmol 49 (1) January–February 2004
DEMIRCI ET AL
Fig. 2. A: Fundus photography showing yellow, dome shaped choroidal lesion with subretinal fluid around it. B: Intravenous fluorescein angiography displaying mottled hyperfluoresence in the laminar venous phase. C: Intense staining in the late phase. D: Indocyanine green angiography showing hypofluoresence in the early phase. E: Hyperfluoresence in the late phase.
were evaluated for HIV, but no signs and symptoms were present in these cases. Tuberculosis is usually classified as pulmonary or extrapulmonary. Before the era of HIV infection, 83% of all cases of tuberculosis were limited to the lungs and 17% were in extrapulmonary locations.44 Today, extrapulmonary tuberculosis is more common. Extrapulmonary tuberculosis can involve lymph nodes (30%), pleura (23%), gastrointestinal tract (12%), bone and joints (10%), meninges (5%), and peritoneum (3%). The cases of miliary tuberculosis with widespread involvement comprise 7% of cases.44 The diagnosis is usually first entertained when
the chest radiograph of a patient being evaluated for respiratory symptoms is abnormal. Although the classic picture is that of upper lobe disease with infiltrates and cavities, various radiographic patterns may be seen.41 Skin testing with PPD is another widely used test for screening. However, it is of limited value in diagnosis because false-negative reactions are found in immunosuppressed patients and false-positive reactions are found in persons who have been sensitized by bacille Calmette-Gue´rin (BCG) vaccination.41 Definitive diagnosis depends on the isolation and identification of Mycobacterium tuberculosis from a specimen.41 The specimen is classically inoculated
OCULAR TUBERCULOSIS MASQUERADING AS OCULAR TUMORS
83
Fig. 5. Observed case rate per 100,000 (continuous line with dots) and expected case rate (dashed line) in the United States from 1979 through 1999. (Based on data from the American Thoracic Society.3)
Fig. 3. A: On histopathologic examination, granulomatous inflammation with areas of caseation, Langhan’s giant cells (Hematoxylin-eosin, ×25) (A) and acid-fast bacilli (×250) (B) were observed.
onto egg-based or agar-based media. In many laboratories, molecular diagnostic tests can augment the classic culture techniques. The most recent American Thoracic Society and Centers for Disease Control (CDC) guidelines for
Fig. 4. Anterior segment photograph showing pigmented lesion at the inferior limbus, which led to suspicion of conjunctival melanoma but later found to be scleral necrosis from intraocular tuberculosis.
treatment of active ocular tuberculosis is shown in Table 2.2,41 Despite sporadic claims of dramatic improvement of ocular tuberculosis treated with isoniazid alone, multi-drug antituberculous regimen has been accepted as standard therapy (Table 2). There exist some contrary reports about the efficacy of systemic antituberculous therapy for intraocular tuberculosis. Of 92 cases reported in the literature, multi-drug therapy was successful in 55 (60%) patients and unsuccessful in 30 cases (33%) who eventually underwent enucleation or evisceration. In 17 (18%) cases the diagnosis was established after enucleation and in 7 (8%) no information on result of therapy was provided (Table 3).5–15,17–27,29–40,42,43,45–48, 51–58,60 In our series, two patients (cases 1 and 2) responded to multi-drug therapy. One patient, who was HIV⫹ (case 4), developed a choroidal tuberculoma while on multidrug therapy and showed a satisfactory response. Deterioration of the ocular condition using isoniazid alone was found in one patient (case 5) and tuberculous peritonitis following no medical therapy in one patient (case 3) was found. Drug-resistant organisms, particularly in HIV patients, and delayed diagnosis can play a role in the variety of responses. Concomitant corticosteroid use in treating ocular tuberculosis is another controversial issue. Woods and associates have shown that the use of systemic corticosteroids in combination with antituberculosis therapy is associated with a prolonged course of tuberculosis and high incidence of recurrence.59 On the other hand, topical steroid in conjunction with cycloplegia can be helpful for anterior chamber reaction and prevention of synechia. In two cases (cases 3 and 5), delayed diagnosis and corticosteroid usage without antituberculosis medication led to panophthalmitis and scleral perforation.
84
Surv Ophthalmol 49 (1) January–February 2004
DEMIRCI ET AL Table 2
Advised Systemic Evaluation and Therapy of Ocular Tuberculosis Systemic Evaluation of Ocular Tuberculosis Chest X-ray PPD skin testing Computed tomography of brain, chest, abdomen AFB microscopy of specimen Mycobacterial culture of specimen Isoniazid diagnostic testing Therapy of Ocular Tuberculosis Months 1 2 3 4 5 6
Isoniazid
Rifampin
Pyrazinamide hydrochloride
Ethambutola
Streptomycina
X X X X X X
X X X X X X
X X
X X
X X
Dosage Daily Isoniazid Rifampin Pyrazinamide hydrochloride Ethambutol Streptomycin
5 mg/kg, max. 300 mg po or IM QD 10 mg/kg, max. 600 mg po QD 15–30 mg/kg, max. 2 g po QD 15–25 mg/kg, po QD 15 mg/kg, max. 1g IM QD
3 times per weekb 15 mg/kg, max. 900 mg 10 mg/kg, max. 600 mg 50–70 mg/kg, max. 3 g 25–30 mg/kg 25–30 mg/kg, max. 1,5 g
AFB ⫽ Acid fast bacilli. a Used in cases who had risk of drug resistance. b Dosage for twice-weekly administration are the same except for pyrazinamide (max. 4g/daily) and ethambutol (50 mg/kg).
Ocular and periocular tuberculosis occurs as a consequence of active infection from hematogenous or contiguous spread of viable bacilli or as a local manifestation of a hypersensitivity reaction to circulating tuberculoproteins. In a review of 10,524 tuberculosis cases seen between 1940 and 1966, Donahue reported that 154 cases (2%) manifested ocular involvement.16 The most common findings were choroiditis in 46 cases (0.44%), iritis in 28 (0.27%), sclerokeratitis in 23 (0.22%), interstitial keratitis in 14 (0.13%), and scleritis in 14 cases (0.13%). The review of 92 well-documented single cases of intraocular tuberculosis reported in the literature showed that the most common presenting manifestations included choroidal mass in 31 cases (34%) with or without obvious inflammatory signs, choroiditis/ choroiretinitis in 25 (27%), vitritis in 22 (24%), iridocylitis/anterior chamber reaction in 12 (13%), and panophthalmitis in 10 (11%) (Table 3).5–15,17–27,29–40, 42,43,45–48,51–58,60 Of five cases in this report, two patients had active choroidal granuloma associated with uveitis, one had choroidal granuloma without inflammatory signs, one had panophthalmitis, and one had endophthalmitis that led to scleral perforation. A number of granulomatous inflammatory diseases, including ocular tuberculosis, can simulate
ocular tumors.49,50 Four of our cases were referred to rule out choroidal melanoma, and one was suspected to have conjunctival melanoma. Ocular tuberculosis is more common in non-Caucasian immigrants from other countries or individuals with systemic immunodeficiency problems. It can be associated with signs of granulomatous inflammation in the anterior chamber and vitreous such as keratic precipitates, anterior chamber reaction, posterior synechia, nodules on iris, or vitreous cells. Choroid tuberculoma is an amelanotic lesion with indistinct margins, which is most commonly seen in the posterior pole. On intravenous fluorescein angiography, the lesion usually shows hypofluorescent in early phases and hyperfluorescent in the late phases. Ultrasonography displays a lesion with low internal reflectivity and high vascularity on A-scan, and with solid elevated mass with absence of scleral echo on B-scan. In conclusion, ocular tuberculosis can show a variety of different clinical presentations ranging from an amelanotic choroidal mass to panophthalmitis. It can simulate ocular neoplasms. A high degree of clinical suspicion is important in suspecting and managing this condition. Late diagnosis and delay in management can result in loss of the eye and can even be life-threatening in severe conditions.
Clinical Findings in 59 Well-Documented Cases with Intraocular Tuberculosisb First Author (Year)
Age/Sex/Race
Eye CXR
PPD
Involved Organs
Clinical Features
Therapy
Ocular Outcome
Systemic Outcome
Follow-up
Gadenigo (1869)24 O’Sullivan (1899)24
21 Ma 21 Fa 2 F AfricanAmerican 21 Fa 34 Fa 67 Fa 30 Fa
OU OD -
-
-
AC rxn, Choroiretinitis Choroidal mass, Papillitis
-
-
-
-
OS OS OS OD OD
N
-
Joint -
-
Enucleation Enucleation Enucleation
Joint tb later -
1 year -
Verhoeff (1940)56 Dvorak-Theobald (1958)17 Zimmerman (1958)60 Darrell (1967)15 Wassermann (1973)58 McMoli (1978)34
31 M Caucasian
OD N
-
LN
Optic nerve mass, RD Iridocyclitis Scleritis Sympathetic ophthalmia Choroiretinitis VH, Vasculitis, Glaucoma, CRVO
-
Enucleation
-
5 years
37 F Chinese 45 Ma 73 M Caucasian 63 M Caucasian 1 M African
OD OS OS OS
Tb Tb Tb
P (L) Kidney P P Miliary -
I I R, C AT
Enucleation Enucleation Regressed Enucleation
Good response 2 years 3 mo DO 6 mo Good response 4 weeks
Lana-Peixoto (1980)29
18 mo M Caucasian 22 M Caucasian 48 Fa 43 M AfricanAmerican 30 F Chinese
OS
Tb
-
Miliary
Endophthalmitis AC rxn Panophthalmitis Endophthalmitis Panophthalmitis, Choroidal mass, RD Optic nerve mass
-
-
DT
-
OD Tb OS OS Tb
P -
-
Choroidal mass, RD Endophthalmitis Choroidal mass
I, R, E AT I, E, P, R
Regressed Enucleation Regressed
-
3 mo
OS
Tb
-
Panophthalmitis
-
Enucleation
DT
6 mo
11 M Chinese 15 F Chinese 25 F Chinese
OS OS OS
Tb Tb N
R
Enucleation Enucleation Enucleation
-
-
30 F Chinese 58 M Chinese
OU N OS -
P -
Bone
-
Enucleation Enucleation
-
-
17 Fa 34 M AfricanAmerican 31 M Caucasian 3 M Indian
OS OS
N Tb
P -
-
Panophthalmitis Panophthalmitis CB mass, AC rxn, Episcleritis AC rxn Choroidal mass, Vitiritis Choroidal mass Choroidal mass
I, E I, R
Regressed Enucleation
Good response 1 year No response 3 mo
OD Tb OD Tb
P
Liver, LN -
Choroidal mass Choroidal mass
-
Not regressed DO Enucleation -
Knapp (1903)27 Ogilvy (1909)39 Verhoeff (1910)55 Verhoeff (1929)54 Finnoff (1931)18
Cangemi (1980)12 Smith (1980)52 Goldberg (1982)19 Ni (1982)38
Jabbour (1985)25 Lyon (1985)30 Croxatto (1986)14 Saini (1986)46
Periton joint, LN LN P (L) -
OCULAR TUBERCULOSIS MASQUERADING AS OCULAR TUMORS
Table 3
1 mo (Continued)
85
86
Table 3
Involved Organs
First Author (Year)
Age/Sex/Race
Eye CXR
PPD
Menezo (1987)35
20 F Caucasian
OD Tb
P (L) -
Gur (1987)23 Chung (1989)13 Blodi (1989)9
54 M Caucasian 54 F Chinese 34 M Hispanic
OD N OU Tb OU Tb
P P -
Shiono (1990)51
20 M Asian
OU Tb
-
(Joint H) Meninges Meninges, Bone Miliary
Mansour (1990)32 Rosen (1990)45
32 M Hispanic 37 F Ghanaian a Indian 35 M Indian
OD OU OD
N Tb Tb Tb (L)
P P P P
Miliary Brain, Liver
42 F Indian 21 Araba 56 M NA 29 W Ecuadoran 66 F AfricanAmerican
OD OD OD OS OU
N Tb N Tb Tb (L)
P Ne P P
-
31 28 35 19 40
OD OU OD OU OD
Tb
P
Miliary Miliary Miliary No Bone
Barondes (1991)5 Regillo (1991)43 Kim (1993)26 Blazquez (1994)8
Biswas (1995)7
Therapy
Ocular Outcome
Systemic Outcome
Choroidal mass Choroirenitis, AC rxn, Vitritis Multifocal choroiditis AC rxn, Vitritis, Choroidal mass Choroiditis, Choroidal hemorrhages Choroidal mass Choroidal mass Choroidal mass Vasculitis, Choroidal mass (L) AC rxn, Iris nodules Vasculitis Chorioretinitis Endophthalmitis Choroiretinitis, Uveitis
I, R, E
Enucleation
Good response -
I I, R, E, CS I, R, E
Regressed, NVD (L) Regressed -
7 mo Good response 3 years DO 2 mo
I, R, E
Regressed
Good response 4 mo
I, R R, E, P AT I, S, E
Regressed Regressed Regressed Regressed
Good response
AT I, R, E AT I I, R, P, E
Regressed Regressed Regressed Enucleation Regressed, VH, RD (L) Regressed Regressed Regressed Regressed Enucleation
Good response Good response 6 mo 4 years Good response 3 mo NA 3 mo Good response 10 mo -
I, R, P
Eviseration Regressed
DO
I, R, P
Eviseration
Good response -
I, R, E I, R, P, E R, P, CS
Regressed Enucleation Regressed
I, R, E I, E
Regressed Regressed
Good response Good response Pulmonary tb before Good response
42 F Indian 58 F Indian
OD N OD N
P P
Liver -
30 F Indian
OU Tb
P
-
35 F Caucasian 14 F Arab 29 F Caucasian
OD Tb OU Tb OS Tb
P -
Meninges LN -
Choroidal mass Choroidal mass Choroidal mass Choroidal mass AC rxn, Scleral rup., Uveal pr., Panophthalmitis Subretinal abscess, AC rxn. Choroidal mass, RD, Panophthalmitis, Subconj. mass Choroidal mass, vitritis AC rxn, Choroidal mass Chorioretinitis
36 M NA 29 M NA
OS OS
P P
-
Choroidal mass Optic disk granuloma
N Tb
I, I, I, I, I,
R, R, R, R, R,
P P P P P
Follow-up
1 mo 2 mo -
6 weeks
3 mo 6 mo 1 mo 16 weeks 2 years (Continued)
DEMIRCI ET AL
Muccioli (1996)37 Cameron (1996)11 Recillas-Gispert (1997)42 Berinstein (1997)6 Mansour (1998)31
M Caucasian M Caucasian F Caucasian M Caucasian M Indian
Clinical Features
Surv Ophthalmol 49 (1) January–February 2004
(Continued)
(Continued) First Author (Year)
Age/Sex/Race
Eye CXR
PPD
Involved Organs
Sarvananthan (1998)47
27 F Indian 53 M Indian
OS OS
Ne Ne
Spine, LN -
32 F Pakistanian OS N 31 T Mexican OU Tb 43 F Mexican OD Ne
Ne P P
Meninges -
59 Ma 8 F Caucasian 45 F AfricanAmerican 17 M Indian 20 M Indian
OD Tb OS Ne OS Tb
Ne P -
Miliary
OD Tb OD Ne
P Ne
-
27 32 18 25 22 30
OU OS OU OU OU OS
Tb Tb Ne Tb Tb Tb
P P P P P P
-
16 M Indian 18 M Indian
OU Tb OS Tb
P P
-
26 M Indian
OD Tb
P
-
20 M Indian 11 M Indian
OU Tb OU Tb
P P
-
75 F Chinese 68 F Chinese 47 M Chinese
OD Tb OS Tb OD Tb
-
Miliary Miliary
58 70 41 27 48 34
OD OS OD OS OD OU
Ne Ne Ne Ne
-
Grewal (1998)20 Stechschullte (1999)53 Bowyer (1999)10 Raina (2000)40 Mason (2000)33 Gupta (2001)22
Sheu (2001)48
Morimura (2002)36
F Indian F Indian M Indian F Indian M Indian F Indian
M Chinese M Chinese M Asian F Asian F Asian M Asian
N N
Ne Ne Ne Ne
Clinical Features
Therapy
Ocular Outcome
Systemic Outcome
Follow-up
Choroidal mass, Vitritis Choroidal mass, AC rxn, Vitritis Retinitis, Vitritis Multifocal choroiditis Choroiditis, Optic disk edema, Vitritis Choroidal mass, RD Endophthalmitis Choroidal mass
-
Enucleation Regressed
-
-
I, R, P, E I, R
Regressed Regressed Regressed
Good response 3 mo
CS I, R, E
Enucleation Enucleation Regressed
Good response 6 mo
Vitritis, Neuroretinitis Vitritis, Neuroretinitis, Choroiditis Vitritis, Choroiditis Vitritis, Choroiditis Vitritis, Neuroretinitis Vitritis, Choroiditis Vitritis, Neuroretinitis Vitritis, Neuroretinitis, Choroiditis Vitritis, Choroiditis Vitritis, Neuroretinitis, Choroiditis Vitritis, Neuroretinitis, Choroiditis Vitritis, Retinal hemorrhage Vitritis, Neuroretinitis, Choroiditis Panophthalmitis Panophthalmitis Posterior uveitis, Choroidal mass Corneal ulcer Lid mass Choroidal mass Choroidal mass Optic disk mass Retinal vasculitis
I, R, P, E, CS Regressed I, R, P, E, CS Regressed
-
1 yr 3 years
I, I, I, I, I, I,
Regressed Regressed Regressed Regressed Regressed Regressed
-
3 years 10 mo 2 years 1 year 6 mo 1 yr
I, R, P, E, CS Regressed I, R, P, E Regressed
-
1 yr 18 mo
I, R, P, E
Regressed
-
1 yr
I, R, P, E Regressed I, R, P, E, CS Regressed
-
1 yr 1 yr
I, R, P I, R, E I, RE
Enucleation Enucleation Regressed
Good response 1 yr Good response 5 yrs Good response 5 yrs
E, R, P, S I, R, E I, R I I I, R, E
Regressed Regressed Regressed Regressed Regressed Regressed
-
R, R, R, R, R, R,
P, P, P, P, P, P,
E E, E, E, E, E,
CS CS CS CS CS
OCULAR TUBERCULOSIS MASQUERADING AS OCULAR TUMORS
Table 3
3 yrs 3 yrs -
87
(Continued)
Wang (2002)57 Grosse (2002)21
CXR ⫽ Chest X-Ray; F ⫽ Female; M ⫽ Male; T ⫽ Transsexual; OS ⫽ Left eye; OD ⫽ Right eye; OU ⫽ Bilateral; Tb ⫽ Findings related with tuberculosis; N ⫽ Normal; P ⫽ Positive; Ne ⫽ negative; RD ⫽ Retinal detachment; tb ⫽ Tuberculosis; I ⫽ isoniazid; R ⫽ Rifampin; P ⫽ Pyrazinamide; E ⫽ Ethambutol hydrochloride; S ⫽ Streptomycine; AT ⫽ Antituberculosis therapy; CS ⫽ Corticosteroid; AC rxn. ⫽ Anterior chamber reaction; VH ⫽ Vitreous hemorrhage; CRVO ⫽ Central vein occlusion; subconj. ⫽ subconjunctival; rup. ⫽ rupture; pr. ⫽ proliferation; CB ⫽ Ciliary body; LN ⫽ Lymph node; L ⫽ later on follow-up; H ⫽ according to history; mo ⫽ months; NVD ⫽ Disk neovascularization; NA ⫽ Not applicable; yr ⫽ year; DO ⫽ Death due to other causes; DT ⫽ Death due to tuberculosis; C ⫽ Cycloserine. a No further information available. b Published in English literature and well-documented cases.
Good response Regressed Regressed Regressed Regressed Regressed Not regressed Regressed Enucleation 32 38 58 31 36 62 35 30
M Asian M Asian M Asian F Asian M Asian F Asian F Asian M African
OU OS OU OU OD OU OU OD
Tb Ne Ne Ne Ne Ne Tb Ne
P Ne P P P Ne P
Miliary Miliary
Retinal vasculatis Retinal vasculatis Choroiditis Choroiditis Choroiditis Choroiditis Choroidal mass Panophthalmitis
I, R I I I I I I, R, E I, R, P, E, S
Systemic Outcome Ocular Outcome Therapy Clinical Features Involved Organs PPD Eye CXR Age/Sex/Race First Author (Year)
(Continued)
Table 3
2 mos 18 mos
Surv Ophthalmol 49 (1) January–February 2004 Follow-up
88
DEMIRCI ET AL
Method of literature search Articles in all languages were searched with the combination of key words ocular tuberculosis and tuberculosis and eye between 1970 and 2002. Well-documented individual case reports and case series of ocular tuberculosis in English literature were reviewed. In addition, references cited in the articles obtained by Medline were sought for this review.
References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24.
:Estimates of future global tuberculosis morbidity and mortality. MMWR Morb Mortal Wkly Rep 42:961–5, 1993 American Thoracic Society: Control of tuberculosis in the United States. Am Rev Respir Dis 142:725–35, 1992 American Thoracic Society: Control of tuberculosis in the United States. Am Rev Respir Dis 146:1623–33, 1992 Barnes PF, Bloch AB, Davidson PT, et al: Tuberculosis in patients with human deficiency virus infection. N Engl J Med 324:1644–50, 1991 Barondes MJ, Sponsel WE, Stevens TS, Plotnik RD: Tuberculous choroiditis diagnosed by chorioretinal endobiopsy. Am J Ophthalmol 112:460–1, 1991 Berinstein DM, Gentile RC, McCormick SA, Walsh JB: Primary choroidal tuberculoma. Arch Ophthalmol 115:430–1, 1997 Biswas J, Madhavan HN, Gopal L, Badrinath SS: Intraocular tuberculosis. Clinicopathological study of five cases. Retina 15:461–8, 1995 Blazquez EP, Rodriguez MM, Ramos JM: Tuberculous choroiditis and acquired immunodeficiency syndrome. Ann Ophthalmol 26:50–4, 1994 Blodi BA, Johnson MW, McLeish WM, Gass JDM: Presumed choroidal tuberculosis in a human immunodeficiency virus infected host. Am J Ophthalmol 108:605–7, 1989 Bowyer JD, Gormley PD, Seth R, et al: Choroidal tuberculosis diagnosed by polymerase chain reaction. A clinicopathological case report. Ophthalmology 106:290–4, 1999 Cameron JA, Nasr AM, Chavis P: Epibulbar and ocular tuberculosis. Arch Ophthalmol 114:770–1, 1996 Cangemi FE, Friedman AH, Josephberg R: Tuberculoma of the choroid. Ophthalmology 87:252–8, 1980 Chung YM, Yeh T, Sheu S, Liu J: Macular subretinal neovascularization in choroidal tuberculosis. Ann Ophthalmol 21:225–9, 1989 Croxatto JO, Mestre C, Puente S, Gonzalez G: Nonreactive tuberculosis in a patient with acquired immune deficiency syndrome. Am J Ophthalmol 102:659–60, 1986 Darrell RW: Acute tuberculosis panophthalmitis. Arch Ophthalmol 78:51–4, 1967 Donahue HC: Ophthalmic experience in a tuberculosis senatorium. Am J Ophthalmol 64:742–8, 1967 Dvorak-Theobald G: Acute tuberculous endophthalmitis. Am J Ophthalmol 45:403–7, 1958 Finnoff WC: The relation of tuberculosis to chronic uveitis. Am J Ophthalmol 14:1208–27, 1931 Goldberg MF: Presumed tuberculous maculopathy. Retina 2:47–50, 1982 Grewal A, Kim RY, Cunningham ET: Miliary tuberculosis. Arch Ophthalmol 116:953–4, 1998 Grosse V, Bange FC, Tischendorf J, et al: A mass in the eye. Lancet 360:922, 2002 Gupta A, Gupta V, Arora S, et al: PCR-positive tubercular retinal vasculitis: clinical characteristics and management. Retina 21:435–44, 2001 Gur S, Silverstone BZ, Zylberman R, Berson D: Chorioretinitis and extrapulmonary tuberculosis. Ann Ophthalmol 19:112– 5, 1987 Helm CJ, Holland GN: Ocular tuberculosis. Surv Ophthalmol 38:229–56, 1993
OCULAR TUBERCULOSIS MASQUERADING AS OCULAR TUMORS 25. Jabbour NM, Faris B, Trempe CL: A case of pulmonary tuberculosis presenting with a choroidal tuberculoma. Ophthalmology 92:834–7, 1985 26. Kim JY, Carroll CP, Opremcak EM: Antibiotic-resistant tuberculous choroiditis. Am J Ophthalmol 115:259–61, 1993 27. Knapp A: A case of localized tuberculosis at the head of the optic nerve; microscopic examination. Arch Ophthalmol 32:22–6, 1903 28. Knox DL: Syphilis and tuberculosis, in Ryan SJ (ed): Retina. St Louis, CV Mosby Co, 1989, pp 647–54. 29. Lana-Peixoto MA, Bambirra EA, Pittella JE: Optic nerve tuberculoma. A case report. Arch Neurol 37:186–7, 1980 30. Lyon CE, Grimson BS, Peiffer RL, Merritt JC: Clinicopathological correlation of a solitary choroidal tuberculoma. Ophthalmology 92:845–50, 1985 31. Mansour AM: Optic disk tubercle. J Neuroophthalmol 18:201–3, 1998 32. Mansour AM, Haymond R: Choroidal tuberculomas without evidence of extraocular tuberculosis. Graefes Arch Clin Exp Ophthalmol 228:382–5, 1990 33. Mason JO: Treatment of large macular choroidal tubercle improves vision. Arch Ophthalmol 118:1136–7, 2000 34. McMoli TE, Mordi VPN, Grange A, Abiose A: Tuberculous panophthalmitis. J Pediatr Ophthalmol Strabismus 15:383– 5, 1978 35. Menezo JL, Martinez-Costa R, Marin F, et al: Tuberculous panophthalmitis associated with drug abuse. Int Ophthalmol 10:235–40, 1987 36. Morimura Y, Okada AA, Kawahara S, et al: Tuberculin skin testing in uveitis patients and treatment of presumed intraocular tuberculosis in Japan. Ophthalmology 109:851–7, 2002 37. Muccioli C, Belfort R Jr: Presumed ocular and central nervous system tuberculosis in a patient with the acquired immunodeficiency syndrome. Am J Ophthalmol 121:217–9, 1996 38. Ni C, Papale JJ, Robinson NL, Wu BF: Uveal tuberculosis. Int Ophthalmol Clin 22:103–24, 1982 39. Ogilvy A: Microscopic section from a case of tuberculous iridocyclitis in a man, aet. 75 years. Trans Ophthalmol Soc UK 29:8–9, 1909 40. Raina UK, Tuli D, Arora R, et al: Tubercular endophthalmitis simulating retinoblastoma. Am J Ophthalmol 130:843–5, 2000 41. Raviglione MC, O’Brien RJ: Tuberculosis. in Fauci AS, Braunwaid E, Isselbacher KJ, et al (eds): Harrison’s Principle of Internal Medicine. New York, McGraw-Hill, 1998, ed 14, pp 1004–14 42. Recillas-Gispert C, Ortega-Larrocea G, Arellanes-Garcia L, et al: Chorioretinitis secondary to mycobacterium tuberculosis in acquired immune deficiency syndrome. Retina 17:437– 9, 1997 43. Regillo R, Shields CL, Shields JA, Eagle RC Jr: Ocular tuberculosis. JAMA 266:1490, 1991 44. Rider HL, Snider DE, Cauthen GM: Extrapulmonary tuberculosis in the United States. Am Rev Respir Dis 141:347–51, 1990 45. Rosen PH, Spalton DJ, Graham EM: Intraocular tuberculosis. Eye 4:486–92, 1990
46. 47. 48. 49.
50.
51. 52. 53. 54. 55. 56. 57. 58. 59. 60.
89
Saini JS, Mukherjee AK, Nadkarni N: Primary tuberculosis of the retina. Br J Ophthalmol 70:533–5, 1986 Sarvananthan N, Wiselka M, Bibby K: Intraocular tuberculosis without detectable systemic infection. Arch Ophthalmol 116:1386–8, 1998 Sheu SJ, Shyu JS, Chen LM, et al: Ocular manifestations of tuberculosis. Ophthalmology 108:1580–5, 2001 Shields JA, Shields CL: Differential diagnosis of posterior uveal melanomas. in Shields JA, Shields CL (eds): Intraocular Tumors, A Text and Atlas. Philadelphia, PA, JB Lippincott, 1992, pp 137–51 Shields JA, Shields CL: Nonneoplastic conditions that stimulate posterior uveal melanoma,. in Shields JA, Shields CL (eds): Atlas of Intraocular Tumors. Lippincott: Philadelphia, PA, Williams and Wilkins, 1999, pp 141–50. Shiono T, Abe S, Horiuchi T: A case of miliary tuberculosis with disseminated choroidal haemorrhages. Br J Ophthalmol 74:317–9, 1990 Smith RE: Tuberculoma of the choroid. [discussion]. Ophthalmology 87:257–8, 1980 Stechschulte SU, Kim RY, Cunningham ET Jr: Tuberculous neuroretinitis. J Neuroophthalmol 19:201–4, 1999 Verhoeff FH: Histopathologic observations in a case of localized tuberculous chorioretinitis. Arch Ophthalmol 1:63– 70, 1929 Verhoeff FH: The histologic findings in a case of tuberculous cyclitis, and a theory as to the origin of tuberculous scleritis and keratitis. Trans Am Ophthalmol Soc 12:566–86, 1910 Verhoeff FH, Simpson GV: Tubercle within central retinal vein. Arch Ophthalmol 24:645–55, 1940 Wang JC, Chuah GC, Yap EY: Tuberculous choroidal granulomas in a patient with systemic lupus erythematosus. A case report. Int Ophthalmol 24:107–9, 2001 Wassermann HE: Avian tuberculosis endophthalmitis. Arch Ophthalmol 89:321–3, 1973 Woods AC, Wood R, Senterfit LB: Studies in expermental ocular tuberculosis. Arch Ophthalmol 59:559–78, 1958 Zimmerman L: Tuberculosis endophthalmitis. Arch Ophthalmol 59:559–78, 1958
Support provided by the Paul Kayser International Award of Merit in Retina Research, Houston, TX (J. Shields), Macula Foundation, New York, NY (C. Shields), the Noel T. and Sara L. Simmonds Endowment for Ophthalmic Pathology, Wills Eye Hospital (R. Eagle, Jr) and the Eye Tumor Research Foundation, Philadelphia, PA (C. Shields). The patients were referred to the authors by Brian C. Leonard, MD, John Lehr, MD, Richard Klein, MD, James Bastek, MD, Jay Biswas, MD. The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article. Reprint address: Carol L. Shields, MD, Oncology Service, Wills Eye Hospital, 900 Walnut St., Philadelphia, PA 19107, USA.
VOLUME 49 • NUMBER 1 • JANUARY–FEBRUARY 2004
CLINICAL PATHOLOGIC REVIEW MILTON BONIUK AND STEFAN SEREGARD, EDITORS
Ocular Tuberculosis Masquerading As Ocular Tumors Hakan Demirci, MD,1 Carol L. Shields, MD,1 Jerry A. Shields, MD,1 and Ralph C. Eagle, Jr, MD2 1
Oncology Service, Wills Eye Hospital, Thomas Jefferson University, and 2Pathology Department, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
Abstract. Tuberculosis has re-emerged as a serious public health problem in recent years. The ocular manifestations of tuberculosis are uncommon and diverse. Occasionally, patients initially present with ocular symptoms that simulate intraocular malignancy or other inflammatory conditions. We present five patients with ocular tuberculosis who were referred with the suspicion of ocular malignancy. Four of the five patients had recently emigrated to the United States. The presenting features of these patients were panophthalmitis (one patient), endophthalmitis leading to scleral perforation (one patient), active choroidal granuloma associated with uveitis (two patients), and amelanotic choroidal lesion without inflammatory signs (one patient). Of these five cases, two had a known history of systemic tuberculosis, while the ocular findings in the other three cases were the presenting manifestation of systemic tuberculosis. Multi-drug antituberculous regimen were employed in all cases for a mean of 9 months (median 6 months, range 6–12 months). Three patients responded well to therapy with salvage of the globe and the two remaining patients underwent primary enucleation for blind painful eye or perforated eye. In conclusion, ocular tuberculosis can have variable clinical manifestations and occasionally appears as an intraocular or epibulbar tumor. A high degree of clinical suspicion is important, especially in immigrants from developing countries. (Surv Ophthalmol 49:78–89, 2004. 쑖 2004 Elsevier Inc. All rights reserved.) Key words. choroid • eye • granuloma culosis • tumor • uvea • uveitis
•
inflammation
Tuberculosis is a serious infectious disease that ranks as an important cause of death worldwide, accounting for nearly 2 million fatalities per year.1 The number of reported cases in the U.S. had been decreasing steadily until the mid 1980s. In recent years, however, tuberculosis has re-emerged as a serious health problem with an increase from 22,201 reported cases of tuberculosis in 1985 to 26,283 reported cases in 1991.41 Immigration from other countries, social problems such as homelessness and drug abuse, and the acquired immunodeficiency syndrome (AIDS) epidemic have been implicated in the increasing incidence of tuberculosis.41
•
melanoma
•
retina
•
tuber-
Tuberculosis generally affects the lungs, although other organs are involved in up to 20% of cases.41 The incidence of ophthalmic manifestations in patients known to have systemic tuberculosis is only 1–2%.16 Ocular and periocular involvement is most likely to occur as part of a postprimary infection because of direct hematogenous spread or, less commonly, a secondary hypersensitivity phenomenon alone. Although all parts of the eye can be involved, the most common presentations are chronic anterior uveitis, choroiditis, and sclerokeratitis.28 Occasionally, patients initially may present with ocular symptoms that simulate intraocular malignancy or other inflammatory 78
쑖 2004 by Elsevier Inc. All rights reserved.
0039-6257/04/$–see front matter doi:10.1016/j.survophthal.2003.10.009
OCULAR TUBERCULOSIS MASQUERADING AS OCULAR TUMORS
conditions.49,50 Failure to recognize the ophthalmic manifestations of tuberculosis and diagnose the underlying systemic disease may lead to the loss of an eye and even loss of life. We report five patients with ocular tuberculosis who were referred to us with the suspicion of ocular malignancy.
Patients and methods We reviewed the computerized files of the Ocular Oncology Service at Wills Eye Hospital between January 1974 and July 2000. We identified and reviewed five patients with the diagnosis of ocular tuberculosis (Table 1). We compared our findings with those reported in the literature.
Results PATIENT 1
A 37-year-old man from India presented with a 2month history of decreased vision and floaters in his right eye. Nine months earlier, while in India, he developed a fever of unknown origin, but systemic evaluation for infectious and inflammatory etiologies was reported to be negative. He was treated with oral corticosteroids for idiopathic unilateral choroiditis. Progressive deterioration of visual acuity raised concern about eye cancer and the patient was referred to the oncology service. The visual acuity was 20/30 in each eye. The left eye was normal, as was the anterior segment examination of the right eye. Fundus examination of the right eye showed an amelanotic choroidal lesion measuring 8.0 × 7.5 × 5.0 mm with surrounding retinal exudation and secondary retinal detachment (Fig. 1A). Intense vitreous inflammation and mild vitreous hemorrhage were present. Choroiditis was diagnosed and tuberculosis was suspected. Subsequent systemic evaluation showed a positive skin tuberculin test reaction (PPD), hilar adenopathy, multinodular apical infiltrates in the lung, multiple infiltrates in the liver and spleen and an erosive paravertebral mass. Computed tomograph (CT)guided aspiration biopsy of the paravertebral mass showed culture-positive granulomatous inflammation. A diagnosis of miliary tuberculosis was made and four-drug antituberculosis therapy (isoniazid and rifampin for 12 months, and ethambutol hydrochloride and pyrazinamide for the first 2 months) was started. Three weeks of systemic corticosteroid therapy was given after the first month of treatment. At 1-year follow-up, the choroidal lesion completely regressed but overlying traction retinal detachment and retinal folds were present (Fig. 1B).
79
PATIENT 2
A 23-year-old male student from India presented with a 1-month history of blurred vision in his right eye. A choroidal tumor was discovered, prompting a referral to the oncology service. One month previously, he developed pain and swelling at the left large toe, which was diagnosed as osteomyelitis. Aspiration biopsy revealed culture-positive granulomatous inflammation. A diagnosis of tuberculous osteomyelitis was made and 2 weeks prior to our evaluation, two-drug antituberculosis therapy (isoniazid and rifampin) and systemic antibiotic therapy (ciproflaxicin) were instituted. The visual acuity was 20/40 in the right eye and 20/20 in the left eye. Fundus examination of the affected right eye showed an amelanotic choroidal lesion measuring 3.0 × 3.0 × 1.0 mm with surrounding retinal detachment in the macula (Fig. 2). Based on the known history of systemic tuberculosis, the patient was treated with two-drug antituberculosis therapy (isoniazid and rifampin). At 6-month follow-up, his vision had improved to 20/20 and the lesion largely regressed to a small choroidal scar and subretinal fluid resolved. PATIENT 3
A 28-year-old man from Zaire presented with a 3month history of decreased vision and a 2-week history of severe pain in his left eye. Two months previously he had been treated elsewhere for unilateral idiopathic choroiditis with systemic corticosteroids. Progressive deterioration of visual acuity lead to suspicion of choroidal tumor and the patient underwent vitreous biopsy, which was unrevealing. The patient was referred to the oncology service to rule out a choroidal tumor. The visual acuity was 20/25 in the right eye and no light perception in the left eye. The affected left eye showed swollen eyelids, hyperemic and chemotic conjunctiva, corneal edema, aqueous inflammation, and iris neovascularization. There was no view of the fundus due to intense vitreous inflammation. Because the blind, painful left eye had signs of panophthalmitis, it was enucleated. Histopathologic examination showed granulomatous inflammation with areas of caseation, Langhan’s giant cells, and acid-fast bacilli (Fig. 3). Systemic evaluation for tuberculosis was negative, so there was no systemic therapy. Six months later, the patient developed tuberculous peritonitis and was treated with 4-drug antituberculosis regimen elsewhere. PATIENT 4
A 29-year-old African-American woman presented with a 2-week history of decreased vision in her right
80
Overview of 5 Patients with Intraocular Tuberculosis Age/Sex/Area Case of Origin
Initial Systemic Diagnosis Problem Elsewhere Eye Symptoms
1
37/M/Indian
No
2
23/M/Indian
No
3
28/M/Zairan
4
29/F/AfricanAmerican
537
29/F/Ecuadorian
Idiopathic OD Decreased unilateral vision, choroiditis floaters
Choroidal OD Blurred tumor vision No Idiopathic OS Decreased unilateral vision, choroiditis pain HIV⫹ Retinal OS Decreased tumor vision No
Sarcoidosis
Clinical Features
CXR
Involved Organs
PPD
Systemic Therapy
Ocular Outcome
Sytemic Outcome
Tuberculoma, Active Reac RD, Vit. Hem. disease and Inf.
Tuberculoma, NA RD Panophthalmitis Normal
Liver, spine, I, R for Regressed Good response paravertebral 12 mo lesion mass E, P for 2 mo CS for 1 mo NA Left large toe I, R for Regressed Good response 4 mo lesion Non-react Peritonium NA Enucleation Tb peritonitis in 6 mo
AC rxn, Active Reac Tuberculoma, disease RD OS Pain, redness Endopthalmitis Hilar LAP Reac
Follow-up (mo) 12
Surv Ophthalmol 49 (1) January–February 2004
Table 1
6 6
No
I, R, P for Regressed 3 mo lesion
Good response
10
No
I for 7 mo Enucleation Good response
7
M ⫽ Male; F ⫽ Female; OD ⫽ Right eye; OS ⫽ Left eye; Tuberculoma ⫽ Choroidal tuberculoma; RD ⫽ Retinal detachment; Vit. Hem ⫽ Vitreous hemorrhage; Vit. Inf. ⫽ Vitreous inflammation; AC rxn ⫽ Anterior chamber reaction; NA ⫽ Non-available; Reac ⫽ Reactive; Non-react ⫽ Non-reactive; LAP ⫽ Lymphadenopathy; I ⫽ Isoniazid; R ⫽ Rifampin; E ⫽ Ethambutol; P ⫽ Pyrazinamide; CS ⫽ Corticosteroid; mo ⫽ Months; Tb ⫽ Tuberculosis.
DEMIRCI ET AL
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enopathy, a positive PPD test reaction and apical pulmonary cavitation, and culture-negative granulomatous inflammation on hilar lymph node biopsy. Sarcoid uveitis was diagnosed, and oral corticosteroids and prophylactic isoniazid therapy were instituted. Deterioration of her ocular condition with the development of a pigmented lesion at the inferior limbus raised the suspicion of conjunctival melanoma and led to referral to the oncology service (Fig. 4). The visual acuity was 20/25 in the right eye and light perception in the left eye. In the affected left eye, a pigmented mass with a central, necrotic perforation was noted at the inferior limbus. The cornea was hazy and the anterior chamber was filled with inflammatory material. There was no view of fundus. Because the left eye was blind, perforated, and appearing infective, it was enucleated. Histopathologic examination showed a chronic, granulomatous inflammation without caseation obliterating the anterior segment of the eye with extraocular extension around the perforation site. The diagnosis of tuberculosis was established by the demonstration of multiple acid-fast bacilli. The patient received 7 months of isoniazid therapy. At 41-month follow-up, she was healthy. Fig. 1. A: Fundus photograph showing yellow, domeshaped choroidal lesion, extending superonasally from optic disk and associated with vitreous hemorrhage and inflammation. B: One year later, the lesion regressed with overlying vitreous traction and retinal folds.
eye. She was human immunodeficiency virus (HIV)positive and had been receiving three-drug antituberculosis therapy (isonazid, rifampin, and pyrazinamide) for pulmonary tuberculosis for 2 months. The visual acuity was hand motions in the right eye and 20/20 in the left eye. The affected right eye showed multiple fine keratic precipitates and aqueous inflammation. Fundus examination showed an amelanotic chorioretinal lesion measuring 10.0 mm × 7.5 mm × 3.5 mm with secondary retinal detachment in the juxtapapillary area. Our diagnosis was inflammatory chorioretinal tuberculoma, confirmed by fine-needle aspiration biopsy (FNAB). After 10 months of three-drug antituberculosis therapy, the lesion regressed and a macular chorioretinal scar developed. PATIENT 5
A 29-year-old woman from Ecuador presented with 5-month history of pain and redness in her left eye. Five months previously she developed anterior uveitis, and systemic evaluation revealed left hilar ad-
Discussion Tuberculosis is an acute or chronic infectious disease caused by acid-fast bacteria belonging to Mycobacterium tuberculosis complex.41 The most frequently encountered human agent is Mycobacterium tuberculosis. Closely related organisms that can infect humans include Mycobacterium bovis and Mycobacterium africany.41 The number of tuberculosis cases, which had been falling steadily, began to rise in many industrialized countries after the mid 1980s (Fig. 5).3 For example, there had been an annual decrease of tuberculosis of about 5–7% between 1950 and 1984, but the number of cases increased by 18% overall between 1985 and 1991.3 Using the trend for 1981 to 1984 to estimate the expected number of cases for 1985 to 1991, it was calculated that more than 39,000 excess cases of tuberculosis occurred between 1985 and 1991.3 The HIV epidemic is believed to be largely responsible for the increasing incidence of tuberculosis.4 Studies of patients at tuberculosis clinics in metropolitan areas have shown the prevalence of HIV seropositivity to be as high as 46%.4 Tuberculosis is still one of the most important causes for morbidity and mortality in developing countries such as India. The incidence of tuberculosis in India in 1998 was reported to be 115 cases per 100,000 population, as compared to 7 cases per 100,000 in the United States.1 One of our cases was HIV-positive and some
82
Surv Ophthalmol 49 (1) January–February 2004
DEMIRCI ET AL
Fig. 2. A: Fundus photography showing yellow, dome shaped choroidal lesion with subretinal fluid around it. B: Intravenous fluorescein angiography displaying mottled hyperfluoresence in the laminar venous phase. C: Intense staining in the late phase. D: Indocyanine green angiography showing hypofluoresence in the early phase. E: Hyperfluoresence in the late phase.
were evaluated for HIV, but no signs and symptoms were present in these cases. Tuberculosis is usually classified as pulmonary or extrapulmonary. Before the era of HIV infection, 83% of all cases of tuberculosis were limited to the lungs and 17% were in extrapulmonary locations.44 Today, extrapulmonary tuberculosis is more common. Extrapulmonary tuberculosis can involve lymph nodes (30%), pleura (23%), gastrointestinal tract (12%), bone and joints (10%), meninges (5%), and peritoneum (3%). The cases of miliary tuberculosis with widespread involvement comprise 7% of cases.44 The diagnosis is usually first entertained when
the chest radiograph of a patient being evaluated for respiratory symptoms is abnormal. Although the classic picture is that of upper lobe disease with infiltrates and cavities, various radiographic patterns may be seen.41 Skin testing with PPD is another widely used test for screening. However, it is of limited value in diagnosis because false-negative reactions are found in immunosuppressed patients and false-positive reactions are found in persons who have been sensitized by bacille Calmette-Gue´rin (BCG) vaccination.41 Definitive diagnosis depends on the isolation and identification of Mycobacterium tuberculosis from a specimen.41 The specimen is classically inoculated
OCULAR TUBERCULOSIS MASQUERADING AS OCULAR TUMORS
83
Fig. 5. Observed case rate per 100,000 (continuous line with dots) and expected case rate (dashed line) in the United States from 1979 through 1999. (Based on data from the American Thoracic Society.3)
Fig. 3. A: On histopathologic examination, granulomatous inflammation with areas of caseation, Langhan’s giant cells (Hematoxylin-eosin, ×25) (A) and acid-fast bacilli (×250) (B) were observed.
onto egg-based or agar-based media. In many laboratories, molecular diagnostic tests can augment the classic culture techniques. The most recent American Thoracic Society and Centers for Disease Control (CDC) guidelines for
Fig. 4. Anterior segment photograph showing pigmented lesion at the inferior limbus, which led to suspicion of conjunctival melanoma but later found to be scleral necrosis from intraocular tuberculosis.
treatment of active ocular tuberculosis is shown in Table 2.2,41 Despite sporadic claims of dramatic improvement of ocular tuberculosis treated with isoniazid alone, multi-drug antituberculous regimen has been accepted as standard therapy (Table 2). There exist some contrary reports about the efficacy of systemic antituberculous therapy for intraocular tuberculosis. Of 92 cases reported in the literature, multi-drug therapy was successful in 55 (60%) patients and unsuccessful in 30 cases (33%) who eventually underwent enucleation or evisceration. In 17 (18%) cases the diagnosis was established after enucleation and in 7 (8%) no information on result of therapy was provided (Table 3).5–15,17–27,29–40,42,43,45–48, 51–58,60 In our series, two patients (cases 1 and 2) responded to multi-drug therapy. One patient, who was HIV⫹ (case 4), developed a choroidal tuberculoma while on multidrug therapy and showed a satisfactory response. Deterioration of the ocular condition using isoniazid alone was found in one patient (case 5) and tuberculous peritonitis following no medical therapy in one patient (case 3) was found. Drug-resistant organisms, particularly in HIV patients, and delayed diagnosis can play a role in the variety of responses. Concomitant corticosteroid use in treating ocular tuberculosis is another controversial issue. Woods and associates have shown that the use of systemic corticosteroids in combination with antituberculosis therapy is associated with a prolonged course of tuberculosis and high incidence of recurrence.59 On the other hand, topical steroid in conjunction with cycloplegia can be helpful for anterior chamber reaction and prevention of synechia. In two cases (cases 3 and 5), delayed diagnosis and corticosteroid usage without antituberculosis medication led to panophthalmitis and scleral perforation.
84
Surv Ophthalmol 49 (1) January–February 2004
DEMIRCI ET AL Table 2
Advised Systemic Evaluation and Therapy of Ocular Tuberculosis Systemic Evaluation of Ocular Tuberculosis Chest X-ray PPD skin testing Computed tomography of brain, chest, abdomen AFB microscopy of specimen Mycobacterial culture of specimen Isoniazid diagnostic testing Therapy of Ocular Tuberculosis Months 1 2 3 4 5 6
Isoniazid
Rifampin
Pyrazinamide hydrochloride
Ethambutola
Streptomycina
X X X X X X
X X X X X X
X X
X X
X X
Dosage Daily Isoniazid Rifampin Pyrazinamide hydrochloride Ethambutol Streptomycin
5 mg/kg, max. 300 mg po or IM QD 10 mg/kg, max. 600 mg po QD 15–30 mg/kg, max. 2 g po QD 15–25 mg/kg, po QD 15 mg/kg, max. 1g IM QD
3 times per weekb 15 mg/kg, max. 900 mg 10 mg/kg, max. 600 mg 50–70 mg/kg, max. 3 g 25–30 mg/kg 25–30 mg/kg, max. 1,5 g
AFB ⫽ Acid fast bacilli. a Used in cases who had risk of drug resistance. b Dosage for twice-weekly administration are the same except for pyrazinamide (max. 4g/daily) and ethambutol (50 mg/kg).
Ocular and periocular tuberculosis occurs as a consequence of active infection from hematogenous or contiguous spread of viable bacilli or as a local manifestation of a hypersensitivity reaction to circulating tuberculoproteins. In a review of 10,524 tuberculosis cases seen between 1940 and 1966, Donahue reported that 154 cases (2%) manifested ocular involvement.16 The most common findings were choroiditis in 46 cases (0.44%), iritis in 28 (0.27%), sclerokeratitis in 23 (0.22%), interstitial keratitis in 14 (0.13%), and scleritis in 14 cases (0.13%). The review of 92 well-documented single cases of intraocular tuberculosis reported in the literature showed that the most common presenting manifestations included choroidal mass in 31 cases (34%) with or without obvious inflammatory signs, choroiditis/ choroiretinitis in 25 (27%), vitritis in 22 (24%), iridocylitis/anterior chamber reaction in 12 (13%), and panophthalmitis in 10 (11%) (Table 3).5–15,17–27,29–40, 42,43,45–48,51–58,60 Of five cases in this report, two patients had active choroidal granuloma associated with uveitis, one had choroidal granuloma without inflammatory signs, one had panophthalmitis, and one had endophthalmitis that led to scleral perforation. A number of granulomatous inflammatory diseases, including ocular tuberculosis, can simulate
ocular tumors.49,50 Four of our cases were referred to rule out choroidal melanoma, and one was suspected to have conjunctival melanoma. Ocular tuberculosis is more common in non-Caucasian immigrants from other countries or individuals with systemic immunodeficiency problems. It can be associated with signs of granulomatous inflammation in the anterior chamber and vitreous such as keratic precipitates, anterior chamber reaction, posterior synechia, nodules on iris, or vitreous cells. Choroid tuberculoma is an amelanotic lesion with indistinct margins, which is most commonly seen in the posterior pole. On intravenous fluorescein angiography, the lesion usually shows hypofluorescent in early phases and hyperfluorescent in the late phases. Ultrasonography displays a lesion with low internal reflectivity and high vascularity on A-scan, and with solid elevated mass with absence of scleral echo on B-scan. In conclusion, ocular tuberculosis can show a variety of different clinical presentations ranging from an amelanotic choroidal mass to panophthalmitis. It can simulate ocular neoplasms. A high degree of clinical suspicion is important in suspecting and managing this condition. Late diagnosis and delay in management can result in loss of the eye and can even be life-threatening in severe conditions.
Clinical Findings in 59 Well-Documented Cases with Intraocular Tuberculosisb First Author (Year)
Age/Sex/Race
Eye CXR
PPD
Involved Organs
Clinical Features
Therapy
Ocular Outcome
Systemic Outcome
Follow-up
Gadenigo (1869)24 O’Sullivan (1899)24
21 Ma 21 Fa 2 F AfricanAmerican 21 Fa 34 Fa 67 Fa 30 Fa
OU OD -
-
-
AC rxn, Choroiretinitis Choroidal mass, Papillitis
-
-
-
-
OS OS OS OD OD
N
-
Joint -
-
Enucleation Enucleation Enucleation
Joint tb later -
1 year -
Verhoeff (1940)56 Dvorak-Theobald (1958)17 Zimmerman (1958)60 Darrell (1967)15 Wassermann (1973)58 McMoli (1978)34
31 M Caucasian
OD N
-
LN
Optic nerve mass, RD Iridocyclitis Scleritis Sympathetic ophthalmia Choroiretinitis VH, Vasculitis, Glaucoma, CRVO
-
Enucleation
-
5 years
37 F Chinese 45 Ma 73 M Caucasian 63 M Caucasian 1 M African
OD OS OS OS
Tb Tb Tb
P (L) Kidney P P Miliary -
I I R, C AT
Enucleation Enucleation Regressed Enucleation
Good response 2 years 3 mo DO 6 mo Good response 4 weeks
Lana-Peixoto (1980)29
18 mo M Caucasian 22 M Caucasian 48 Fa 43 M AfricanAmerican 30 F Chinese
OS
Tb
-
Miliary
Endophthalmitis AC rxn Panophthalmitis Endophthalmitis Panophthalmitis, Choroidal mass, RD Optic nerve mass
-
-
DT
-
OD Tb OS OS Tb
P -
-
Choroidal mass, RD Endophthalmitis Choroidal mass
I, R, E AT I, E, P, R
Regressed Enucleation Regressed
-
3 mo
OS
Tb
-
Panophthalmitis
-
Enucleation
DT
6 mo
11 M Chinese 15 F Chinese 25 F Chinese
OS OS OS
Tb Tb N
R
Enucleation Enucleation Enucleation
-
-
30 F Chinese 58 M Chinese
OU N OS -
P -
Bone
-
Enucleation Enucleation
-
-
17 Fa 34 M AfricanAmerican 31 M Caucasian 3 M Indian
OS OS
N Tb
P -
-
Panophthalmitis Panophthalmitis CB mass, AC rxn, Episcleritis AC rxn Choroidal mass, Vitiritis Choroidal mass Choroidal mass
I, E I, R
Regressed Enucleation
Good response 1 year No response 3 mo
OD Tb OD Tb
P
Liver, LN -
Choroidal mass Choroidal mass
-
Not regressed DO Enucleation -
Knapp (1903)27 Ogilvy (1909)39 Verhoeff (1910)55 Verhoeff (1929)54 Finnoff (1931)18
Cangemi (1980)12 Smith (1980)52 Goldberg (1982)19 Ni (1982)38
Jabbour (1985)25 Lyon (1985)30 Croxatto (1986)14 Saini (1986)46
Periton joint, LN LN P (L) -
OCULAR TUBERCULOSIS MASQUERADING AS OCULAR TUMORS
Table 3
1 mo (Continued)
85
86
Table 3
Involved Organs
First Author (Year)
Age/Sex/Race
Eye CXR
PPD
Menezo (1987)35
20 F Caucasian
OD Tb
P (L) -
Gur (1987)23 Chung (1989)13 Blodi (1989)9
54 M Caucasian 54 F Chinese 34 M Hispanic
OD N OU Tb OU Tb
P P -
Shiono (1990)51
20 M Asian
OU Tb
-
(Joint H) Meninges Meninges, Bone Miliary
Mansour (1990)32 Rosen (1990)45
32 M Hispanic 37 F Ghanaian a Indian 35 M Indian
OD OU OD
N Tb Tb Tb (L)
P P P P
Miliary Brain, Liver
42 F Indian 21 Araba 56 M NA 29 W Ecuadoran 66 F AfricanAmerican
OD OD OD OS OU
N Tb N Tb Tb (L)
P Ne P P
-
31 28 35 19 40
OD OU OD OU OD
Tb
P
Miliary Miliary Miliary No Bone
Barondes (1991)5 Regillo (1991)43 Kim (1993)26 Blazquez (1994)8
Biswas (1995)7
Therapy
Ocular Outcome
Systemic Outcome
Choroidal mass Choroirenitis, AC rxn, Vitritis Multifocal choroiditis AC rxn, Vitritis, Choroidal mass Choroiditis, Choroidal hemorrhages Choroidal mass Choroidal mass Choroidal mass Vasculitis, Choroidal mass (L) AC rxn, Iris nodules Vasculitis Chorioretinitis Endophthalmitis Choroiretinitis, Uveitis
I, R, E
Enucleation
Good response -
I I, R, E, CS I, R, E
Regressed, NVD (L) Regressed -
7 mo Good response 3 years DO 2 mo
I, R, E
Regressed
Good response 4 mo
I, R R, E, P AT I, S, E
Regressed Regressed Regressed Regressed
Good response
AT I, R, E AT I I, R, P, E
Regressed Regressed Regressed Enucleation Regressed, VH, RD (L) Regressed Regressed Regressed Regressed Enucleation
Good response Good response 6 mo 4 years Good response 3 mo NA 3 mo Good response 10 mo -
I, R, P
Eviseration Regressed
DO
I, R, P
Eviseration
Good response -
I, R, E I, R, P, E R, P, CS
Regressed Enucleation Regressed
I, R, E I, E
Regressed Regressed
Good response Good response Pulmonary tb before Good response
42 F Indian 58 F Indian
OD N OD N
P P
Liver -
30 F Indian
OU Tb
P
-
35 F Caucasian 14 F Arab 29 F Caucasian
OD Tb OU Tb OS Tb
P -
Meninges LN -
Choroidal mass Choroidal mass Choroidal mass Choroidal mass AC rxn, Scleral rup., Uveal pr., Panophthalmitis Subretinal abscess, AC rxn. Choroidal mass, RD, Panophthalmitis, Subconj. mass Choroidal mass, vitritis AC rxn, Choroidal mass Chorioretinitis
36 M NA 29 M NA
OS OS
P P
-
Choroidal mass Optic disk granuloma
N Tb
I, I, I, I, I,
R, R, R, R, R,
P P P P P
Follow-up
1 mo 2 mo -
6 weeks
3 mo 6 mo 1 mo 16 weeks 2 years (Continued)
DEMIRCI ET AL
Muccioli (1996)37 Cameron (1996)11 Recillas-Gispert (1997)42 Berinstein (1997)6 Mansour (1998)31
M Caucasian M Caucasian F Caucasian M Caucasian M Indian
Clinical Features
Surv Ophthalmol 49 (1) January–February 2004
(Continued)
(Continued) First Author (Year)
Age/Sex/Race
Eye CXR
PPD
Involved Organs
Sarvananthan (1998)47
27 F Indian 53 M Indian
OS OS
Ne Ne
Spine, LN -
32 F Pakistanian OS N 31 T Mexican OU Tb 43 F Mexican OD Ne
Ne P P
Meninges -
59 Ma 8 F Caucasian 45 F AfricanAmerican 17 M Indian 20 M Indian
OD Tb OS Ne OS Tb
Ne P -
Miliary
OD Tb OD Ne
P Ne
-
27 32 18 25 22 30
OU OS OU OU OU OS
Tb Tb Ne Tb Tb Tb
P P P P P P
-
16 M Indian 18 M Indian
OU Tb OS Tb
P P
-
26 M Indian
OD Tb
P
-
20 M Indian 11 M Indian
OU Tb OU Tb
P P
-
75 F Chinese 68 F Chinese 47 M Chinese
OD Tb OS Tb OD Tb
-
Miliary Miliary
58 70 41 27 48 34
OD OS OD OS OD OU
Ne Ne Ne Ne
-
Grewal (1998)20 Stechschullte (1999)53 Bowyer (1999)10 Raina (2000)40 Mason (2000)33 Gupta (2001)22
Sheu (2001)48
Morimura (2002)36
F Indian F Indian M Indian F Indian M Indian F Indian
M Chinese M Chinese M Asian F Asian F Asian M Asian
N N
Ne Ne Ne Ne
Clinical Features
Therapy
Ocular Outcome
Systemic Outcome
Follow-up
Choroidal mass, Vitritis Choroidal mass, AC rxn, Vitritis Retinitis, Vitritis Multifocal choroiditis Choroiditis, Optic disk edema, Vitritis Choroidal mass, RD Endophthalmitis Choroidal mass
-
Enucleation Regressed
-
-
I, R, P, E I, R
Regressed Regressed Regressed
Good response 3 mo
CS I, R, E
Enucleation Enucleation Regressed
Good response 6 mo
Vitritis, Neuroretinitis Vitritis, Neuroretinitis, Choroiditis Vitritis, Choroiditis Vitritis, Choroiditis Vitritis, Neuroretinitis Vitritis, Choroiditis Vitritis, Neuroretinitis Vitritis, Neuroretinitis, Choroiditis Vitritis, Choroiditis Vitritis, Neuroretinitis, Choroiditis Vitritis, Neuroretinitis, Choroiditis Vitritis, Retinal hemorrhage Vitritis, Neuroretinitis, Choroiditis Panophthalmitis Panophthalmitis Posterior uveitis, Choroidal mass Corneal ulcer Lid mass Choroidal mass Choroidal mass Optic disk mass Retinal vasculitis
I, R, P, E, CS Regressed I, R, P, E, CS Regressed
-
1 yr 3 years
I, I, I, I, I, I,
Regressed Regressed Regressed Regressed Regressed Regressed
-
3 years 10 mo 2 years 1 year 6 mo 1 yr
I, R, P, E, CS Regressed I, R, P, E Regressed
-
1 yr 18 mo
I, R, P, E
Regressed
-
1 yr
I, R, P, E Regressed I, R, P, E, CS Regressed
-
1 yr 1 yr
I, R, P I, R, E I, RE
Enucleation Enucleation Regressed
Good response 1 yr Good response 5 yrs Good response 5 yrs
E, R, P, S I, R, E I, R I I I, R, E
Regressed Regressed Regressed Regressed Regressed Regressed
-
R, R, R, R, R, R,
P, P, P, P, P, P,
E E, E, E, E, E,
CS CS CS CS CS
OCULAR TUBERCULOSIS MASQUERADING AS OCULAR TUMORS
Table 3
3 yrs 3 yrs -
87
(Continued)
Wang (2002)57 Grosse (2002)21
CXR ⫽ Chest X-Ray; F ⫽ Female; M ⫽ Male; T ⫽ Transsexual; OS ⫽ Left eye; OD ⫽ Right eye; OU ⫽ Bilateral; Tb ⫽ Findings related with tuberculosis; N ⫽ Normal; P ⫽ Positive; Ne ⫽ negative; RD ⫽ Retinal detachment; tb ⫽ Tuberculosis; I ⫽ isoniazid; R ⫽ Rifampin; P ⫽ Pyrazinamide; E ⫽ Ethambutol hydrochloride; S ⫽ Streptomycine; AT ⫽ Antituberculosis therapy; CS ⫽ Corticosteroid; AC rxn. ⫽ Anterior chamber reaction; VH ⫽ Vitreous hemorrhage; CRVO ⫽ Central vein occlusion; subconj. ⫽ subconjunctival; rup. ⫽ rupture; pr. ⫽ proliferation; CB ⫽ Ciliary body; LN ⫽ Lymph node; L ⫽ later on follow-up; H ⫽ according to history; mo ⫽ months; NVD ⫽ Disk neovascularization; NA ⫽ Not applicable; yr ⫽ year; DO ⫽ Death due to other causes; DT ⫽ Death due to tuberculosis; C ⫽ Cycloserine. a No further information available. b Published in English literature and well-documented cases.
Good response Regressed Regressed Regressed Regressed Regressed Not regressed Regressed Enucleation 32 38 58 31 36 62 35 30
M Asian M Asian M Asian F Asian M Asian F Asian F Asian M African
OU OS OU OU OD OU OU OD
Tb Ne Ne Ne Ne Ne Tb Ne
P Ne P P P Ne P
Miliary Miliary
Retinal vasculatis Retinal vasculatis Choroiditis Choroiditis Choroiditis Choroiditis Choroidal mass Panophthalmitis
I, R I I I I I I, R, E I, R, P, E, S
Systemic Outcome Ocular Outcome Therapy Clinical Features Involved Organs PPD Eye CXR Age/Sex/Race First Author (Year)
(Continued)
Table 3
2 mos 18 mos
Surv Ophthalmol 49 (1) January–February 2004 Follow-up
88
DEMIRCI ET AL
Method of literature search Articles in all languages were searched with the combination of key words ocular tuberculosis and tuberculosis and eye between 1970 and 2002. Well-documented individual case reports and case series of ocular tuberculosis in English literature were reviewed. In addition, references cited in the articles obtained by Medline were sought for this review.
References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24.
:Estimates of future global tuberculosis morbidity and mortality. MMWR Morb Mortal Wkly Rep 42:961–5, 1993 American Thoracic Society: Control of tuberculosis in the United States. Am Rev Respir Dis 142:725–35, 1992 American Thoracic Society: Control of tuberculosis in the United States. Am Rev Respir Dis 146:1623–33, 1992 Barnes PF, Bloch AB, Davidson PT, et al: Tuberculosis in patients with human deficiency virus infection. N Engl J Med 324:1644–50, 1991 Barondes MJ, Sponsel WE, Stevens TS, Plotnik RD: Tuberculous choroiditis diagnosed by chorioretinal endobiopsy. Am J Ophthalmol 112:460–1, 1991 Berinstein DM, Gentile RC, McCormick SA, Walsh JB: Primary choroidal tuberculoma. Arch Ophthalmol 115:430–1, 1997 Biswas J, Madhavan HN, Gopal L, Badrinath SS: Intraocular tuberculosis. Clinicopathological study of five cases. Retina 15:461–8, 1995 Blazquez EP, Rodriguez MM, Ramos JM: Tuberculous choroiditis and acquired immunodeficiency syndrome. Ann Ophthalmol 26:50–4, 1994 Blodi BA, Johnson MW, McLeish WM, Gass JDM: Presumed choroidal tuberculosis in a human immunodeficiency virus infected host. Am J Ophthalmol 108:605–7, 1989 Bowyer JD, Gormley PD, Seth R, et al: Choroidal tuberculosis diagnosed by polymerase chain reaction. A clinicopathological case report. Ophthalmology 106:290–4, 1999 Cameron JA, Nasr AM, Chavis P: Epibulbar and ocular tuberculosis. Arch Ophthalmol 114:770–1, 1996 Cangemi FE, Friedman AH, Josephberg R: Tuberculoma of the choroid. Ophthalmology 87:252–8, 1980 Chung YM, Yeh T, Sheu S, Liu J: Macular subretinal neovascularization in choroidal tuberculosis. Ann Ophthalmol 21:225–9, 1989 Croxatto JO, Mestre C, Puente S, Gonzalez G: Nonreactive tuberculosis in a patient with acquired immune deficiency syndrome. Am J Ophthalmol 102:659–60, 1986 Darrell RW: Acute tuberculosis panophthalmitis. Arch Ophthalmol 78:51–4, 1967 Donahue HC: Ophthalmic experience in a tuberculosis senatorium. Am J Ophthalmol 64:742–8, 1967 Dvorak-Theobald G: Acute tuberculous endophthalmitis. Am J Ophthalmol 45:403–7, 1958 Finnoff WC: The relation of tuberculosis to chronic uveitis. Am J Ophthalmol 14:1208–27, 1931 Goldberg MF: Presumed tuberculous maculopathy. Retina 2:47–50, 1982 Grewal A, Kim RY, Cunningham ET: Miliary tuberculosis. Arch Ophthalmol 116:953–4, 1998 Grosse V, Bange FC, Tischendorf J, et al: A mass in the eye. Lancet 360:922, 2002 Gupta A, Gupta V, Arora S, et al: PCR-positive tubercular retinal vasculitis: clinical characteristics and management. Retina 21:435–44, 2001 Gur S, Silverstone BZ, Zylberman R, Berson D: Chorioretinitis and extrapulmonary tuberculosis. Ann Ophthalmol 19:112– 5, 1987 Helm CJ, Holland GN: Ocular tuberculosis. Surv Ophthalmol 38:229–56, 1993
OCULAR TUBERCULOSIS MASQUERADING AS OCULAR TUMORS 25. Jabbour NM, Faris B, Trempe CL: A case of pulmonary tuberculosis presenting with a choroidal tuberculoma. Ophthalmology 92:834–7, 1985 26. Kim JY, Carroll CP, Opremcak EM: Antibiotic-resistant tuberculous choroiditis. Am J Ophthalmol 115:259–61, 1993 27. Knapp A: A case of localized tuberculosis at the head of the optic nerve; microscopic examination. Arch Ophthalmol 32:22–6, 1903 28. Knox DL: Syphilis and tuberculosis, in Ryan SJ (ed): Retina. St Louis, CV Mosby Co, 1989, pp 647–54. 29. Lana-Peixoto MA, Bambirra EA, Pittella JE: Optic nerve tuberculoma. A case report. Arch Neurol 37:186–7, 1980 30. Lyon CE, Grimson BS, Peiffer RL, Merritt JC: Clinicopathological correlation of a solitary choroidal tuberculoma. Ophthalmology 92:845–50, 1985 31. Mansour AM: Optic disk tubercle. J Neuroophthalmol 18:201–3, 1998 32. Mansour AM, Haymond R: Choroidal tuberculomas without evidence of extraocular tuberculosis. Graefes Arch Clin Exp Ophthalmol 228:382–5, 1990 33. Mason JO: Treatment of large macular choroidal tubercle improves vision. Arch Ophthalmol 118:1136–7, 2000 34. McMoli TE, Mordi VPN, Grange A, Abiose A: Tuberculous panophthalmitis. J Pediatr Ophthalmol Strabismus 15:383– 5, 1978 35. Menezo JL, Martinez-Costa R, Marin F, et al: Tuberculous panophthalmitis associated with drug abuse. Int Ophthalmol 10:235–40, 1987 36. Morimura Y, Okada AA, Kawahara S, et al: Tuberculin skin testing in uveitis patients and treatment of presumed intraocular tuberculosis in Japan. Ophthalmology 109:851–7, 2002 37. Muccioli C, Belfort R Jr: Presumed ocular and central nervous system tuberculosis in a patient with the acquired immunodeficiency syndrome. Am J Ophthalmol 121:217–9, 1996 38. Ni C, Papale JJ, Robinson NL, Wu BF: Uveal tuberculosis. Int Ophthalmol Clin 22:103–24, 1982 39. Ogilvy A: Microscopic section from a case of tuberculous iridocyclitis in a man, aet. 75 years. Trans Ophthalmol Soc UK 29:8–9, 1909 40. Raina UK, Tuli D, Arora R, et al: Tubercular endophthalmitis simulating retinoblastoma. Am J Ophthalmol 130:843–5, 2000 41. Raviglione MC, O’Brien RJ: Tuberculosis. in Fauci AS, Braunwaid E, Isselbacher KJ, et al (eds): Harrison’s Principle of Internal Medicine. New York, McGraw-Hill, 1998, ed 14, pp 1004–14 42. Recillas-Gispert C, Ortega-Larrocea G, Arellanes-Garcia L, et al: Chorioretinitis secondary to mycobacterium tuberculosis in acquired immune deficiency syndrome. Retina 17:437– 9, 1997 43. Regillo R, Shields CL, Shields JA, Eagle RC Jr: Ocular tuberculosis. JAMA 266:1490, 1991 44. Rider HL, Snider DE, Cauthen GM: Extrapulmonary tuberculosis in the United States. Am Rev Respir Dis 141:347–51, 1990 45. Rosen PH, Spalton DJ, Graham EM: Intraocular tuberculosis. Eye 4:486–92, 1990
46. 47. 48. 49.
50.
51. 52. 53. 54. 55. 56. 57. 58. 59. 60.
89
Saini JS, Mukherjee AK, Nadkarni N: Primary tuberculosis of the retina. Br J Ophthalmol 70:533–5, 1986 Sarvananthan N, Wiselka M, Bibby K: Intraocular tuberculosis without detectable systemic infection. Arch Ophthalmol 116:1386–8, 1998 Sheu SJ, Shyu JS, Chen LM, et al: Ocular manifestations of tuberculosis. Ophthalmology 108:1580–5, 2001 Shields JA, Shields CL: Differential diagnosis of posterior uveal melanomas. in Shields JA, Shields CL (eds): Intraocular Tumors, A Text and Atlas. Philadelphia, PA, JB Lippincott, 1992, pp 137–51 Shields JA, Shields CL: Nonneoplastic conditions that stimulate posterior uveal melanoma,. in Shields JA, Shields CL (eds): Atlas of Intraocular Tumors. Lippincott: Philadelphia, PA, Williams and Wilkins, 1999, pp 141–50. Shiono T, Abe S, Horiuchi T: A case of miliary tuberculosis with disseminated choroidal haemorrhages. Br J Ophthalmol 74:317–9, 1990 Smith RE: Tuberculoma of the choroid. [discussion]. Ophthalmology 87:257–8, 1980 Stechschulte SU, Kim RY, Cunningham ET Jr: Tuberculous neuroretinitis. J Neuroophthalmol 19:201–4, 1999 Verhoeff FH: Histopathologic observations in a case of localized tuberculous chorioretinitis. Arch Ophthalmol 1:63– 70, 1929 Verhoeff FH: The histologic findings in a case of tuberculous cyclitis, and a theory as to the origin of tuberculous scleritis and keratitis. Trans Am Ophthalmol Soc 12:566–86, 1910 Verhoeff FH, Simpson GV: Tubercle within central retinal vein. Arch Ophthalmol 24:645–55, 1940 Wang JC, Chuah GC, Yap EY: Tuberculous choroidal granulomas in a patient with systemic lupus erythematosus. A case report. Int Ophthalmol 24:107–9, 2001 Wassermann HE: Avian tuberculosis endophthalmitis. Arch Ophthalmol 89:321–3, 1973 Woods AC, Wood R, Senterfit LB: Studies in expermental ocular tuberculosis. Arch Ophthalmol 59:559–78, 1958 Zimmerman L: Tuberculosis endophthalmitis. Arch Ophthalmol 59:559–78, 1958
Support provided by the Paul Kayser International Award of Merit in Retina Research, Houston, TX (J. Shields), Macula Foundation, New York, NY (C. Shields), the Noel T. and Sara L. Simmonds Endowment for Ophthalmic Pathology, Wills Eye Hospital (R. Eagle, Jr) and the Eye Tumor Research Foundation, Philadelphia, PA (C. Shields). The patients were referred to the authors by Brian C. Leonard, MD, John Lehr, MD, Richard Klein, MD, James Bastek, MD, Jay Biswas, MD. The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article. Reprint address: Carol L. Shields, MD, Oncology Service, Wills Eye Hospital, 900 Walnut St., Philadelphia, PA 19107, USA.