Intraocular Tuberculosis Without Detectable Systemic Infection

Intraocular tuberculosis (TB) is rare; infection occurs via hematogenous spread, usually from the lung. Resurgence of tuberculosis in the developed world as a result of immigration, acquired immunodeficiency syndrome, and drug resistance has led to improved methods of diagnosis. Mycobacterium tuberculosis can be difficult to isolate in vitro. Amplification of DNA by polymerase chain reaction (PCR) has recently been used to identify M tuberculosis in ocular tissue samples of patients with systemic TB.¹ We describe 3 patients with ocular disease in whom routine investigations failed to identify systemic tuberculous infection. In 1 patient, initial misdiagnosis had serious consequences. The use of PCR on aqueous humor samples from 2 other patients confirmed the diagnosis and they received prompt treatment.

To our knowledge, this is the first report of patients without acquired immunodeficiency syndrome being diagnosed with ocular TB with no evidence of systemic disease, in whom PCR testing established the diagnosis.

A 27-year-old woman of Indian ethnic origin had a 2-week history of floaters and decreased vision. She had posterior vitritis and an elevated choroidal lesion, which increased in size over 3 weeks to a mass 6 disc diameters across, associated with proliferating disc new vessels (Figure 1). A chest x-ray film was normal and Mantoux testing (10 TU/0.1 mL) was negative. The serum angiotensin–converting enzyme level was elevated at 62 U/L and a gallium scan was positive (Figure 2). A transvitreal biopsy specimen demonstrated noncaseating granuloma (Figure 3). No acid-fast bacilli were seen. The presumptive diagnosis of sarcoidosis was made and oral steroid therapy was begun. Following initial ophthalmic improvement, she developed ocular, spinal, and axillary abscesses, from which M tuberculosis was eventually isolated. She subsequently underwent enucleation of the affected eye with microbiological confirmation of M tuberculosis.

A 53-year-old man of Indian ethnic origin was referred with a 6-day history of deteriorating vision in the left eye. There was no history of exposure to TB. Medical history was significant for ischemic heart disease. The visual acuity was hand movements OS and 20/30 OD. He had a left hypopyon, dense vitritis, and a choroidal lesion, 4 disc diameters across, superotemporal to the disc. Investigations revealed increased plasma viscosity (1.9 centipoise units), a negative autoantibody screen, and a normal serum angiotensin–converting enzyme level. A chest x-ray film showed pulmonary edema but no features of TB. No alcohol or acid-fast bacilli were isolated from early-morning urine samples, blood cultures, gastric secretions, or pleural fluid. Mantoux testing (1 and 10 TU/0.1 mL) was negative.

An aqueous tap was obtained and samples sent for culture and PCR testing for TB, toxoplasma, herpes simplex, and Toxocara species. Microscopy and cultures failed to isolate any organisis, but PCR testing identified M tuberculosis. Antituberculous therapy was begun with rapid resolution of the uveitis. The choroidal lesion involuted to a flat scar (Figure 4), with improvement in visual acuity to 20/40 OS.

A 32-year-old Pakistani woman was seen with a 5-day history of floaters in the left eye. Visual acuity at the initial visit was 20/30 OU. Anterior segment examination was unremarkable. She had vitritis in the left eye, overlying an area of retinitis superotemporal to the disc with associated retinal neovascularization (Figure 5). She was generally well and initial investigations revealed only a mildly raised plasma viscosity and normal chest x-ray films. There was no history of recent exposure to TB. Her most recent visit to Pakistan was 5 years previously.

Mantoux testing (1 and 10 TU/0.1 mL) failed to provoke a reaction. Two chest x-ray films, blood cultures, and early-morning urine samples were negative for TB. Toxoplasma, herpes simplex, cytomegalovirus, and Toxocara titers were unremarkable. An anterior chamber tap was performed and samples sent for culture (tuberculosis, bacteriology, viral, and fungal), along with PCR testing for TB. Cultures were negative but M tuberculosis was identified by PCR testing. The patient is responding well to triple antituberculous chemotherapy and the retinitis is resolving (Figure 6).

Ocular manifestations of systemic TB include granulomatous uveitis, retinal periphlebitis, and choroidal tubercles. The most common manifestation of intraocular TB is choroiditis; tuberculous infection of the retina is very rare and is thought to occur via retinal blood vessels.² In all cases described, ocular features were compatible with intraocular TB but conventional investigations for TB were unsupportive.

The diagnosis of ocular TB is based on a suggestive history and clinical signs in susceptible individuals. It may be supported by radiography, skin testing, early-morning urine samples, blood cultures, and direct biopsy. Transvitreal biopsy, however, is associated with significant hazards such as retinal detachment, vitreous hemorrhage, and endophthalmitis.

Microscopy of specimens can rapidly detect the presence of acid-fast bacilli but requires large quantities of sample material, which is difficult to obtain from ocular tissue. It is less sensitive than culture of specimens in specific media; however, culture requires skilled technicians, is costly, and may take 10 or more weeks to yield results.

In all our patients, sputum, urine, and blood cultures failed to isolate the causative organism. None of our patients had chest x-ray films suggestive of TB. It is possible they did not have pulmonary TB. Furthermore, a normal chest radiograph does not exclude endobronchial infection. Early-morning sputum specimens have a higher yield and lower contamination rate compared with random specimens, but the sensitivity remains quite low. Positive urinary cultures in nongenitourinary TB may be as low as 1.2% and so cannot be relied on.³

In all 3 patients Mantoux skin testing results were negative. False-negative results may have been due to incorrect administration or reading of the test (although these were carried out by experienced personnel in the infectious diseases unit), concurrent infections, or metabolic conditions such as renal failure, sarcoidosis, malnutrition, and immunosuppressive states. A negative Mantoux test cannot exclude TB.⁴

Recently evolved molecular biological techniques have provided rapid, sensitive, and specific methods of diagnosing M tuberculosis infection. Polymerase chain reaction has been used to detect the presence of mycobacterial tuberculous DNA from sputum samples, gastric aspirates, and tissue samples.⁵ Only 0.01 mL of sample is required and is easily accessed via aqueous aspiration in a minimally invasive procedure with fewer associated complications than transvitreal biopsy. A definitive diagnosis of intraocular TB is obtained.

Tuberculosis may manifest itself in the eye without obvious involvement of other commonly affected organs or evidence of a systemic illness. Our experience suggests that investigations conventionally used to detect TB are sometimes ineffective for diagnosing ocular infection. However, PCR testing on the aqueous humour samples made diagnosis of intraocular TB possible. We would advocate its early use in any instance where there is suspicion of ocular TB and conventional tests have been unhelpful. The consequences of a misdiagnosis or even a late diagnosis may be disastrous.

Corresponding author: Kim Bibby, FRCS, FRCOphth, Leicester Royal Infirmary, Infirmary Road, Leicester LE1 5WW, England.