AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Background

Tuberculosis (TB) is an infectious disease responsible for significant morbidity and mortality worldwide. The primary causative agent, Mycobacterium tuberculosis, is endemic in the world's population. Worldwide, TB is most common in Africa, the West Pacific, and Eastern Europe, but it may be encountered anywhere. As an AIDS-related opportunistic infection, TB is associated with HIV infections, with dual infections seen frequently. International public health efforts have put a huge curb on the rate of increase in TB in recent years; however, the regions named above are plagued with various combinations of limited resources, multidrug resistant TB, and HIV, and these regions account for continued increase in global TB incidence despite the significant reductions elsewhere.

As many as 2 billion humans are estimated to be infected with the tubercle bacillus. Infection with M tuberculosis is seen most commonly from infected aerosol exposure through the lung or mucous membranes. In immunocompetent individuals, this usually results in a latent/dormant infection. Alterations in the host immune system that can lead to decreased immune effectiveness can allow M tuberculosis organisms to reactivate, and tubercular disease results from a combination of both direct effects from the replicating infectious organism and from subsequent inappropriate host immune responses to tubercular antigens.

Over the last 50 years, anti-TB antibiotics have been developed, resulting in successful therapies for TB. Poor compliance with these therapies has promoted multiple drug resistant (MDR) strains of M tuberculosis, resulting in difficulties in controlling the disease, and threatened a global pandemic in the late 1980s and early 1990s. Reacting to these signals, the World Health Organization developed a plan to try to identity 70% of the world's cases of TB and to completely treat at least 85% of these cases by the year 2000. Out of these goals were born major TB surveillance programs and the concept of directly observed therapy requiring a third party to witness compliance with chemotherapy. With worldwide efforts, global detection of smear positive cases rose from 11% (1991) to 45% (2003), with 71-89% of those cases now being completely treated.

Pathophysiology

M tuberculosis primarily is spread as an airborne aerosol from infected to noninfected individuals. The organisms gain access to susceptible hosts through the lung. Initial TB infection usually results in a latent or dormant infection in hosts with normally functioning immune systems. M tuberculosis is a slow-growing obligate aerobe and a facultative intracellular parasite. Because of the unique ability to survive and proliferate within mononuclear phagocytes, M tuberculosis is able to invade local lymph nodes and spread to extrapulmonary sites, usually via hematogenous routes.

Infected end organs typically have high regional oxygen tension (apices of the lungs, kidneys, bones, meninges, eye, and choroid). The principal cause of tissue destruction from M tuberculosis infection is related to the organism's ability to incite intense host immune reactions to antigenic cell wall proteins. TB is a multisystemic disease with myriad presentations and manifestations. Mycobacteria are highly antigenic, and promote a vigorous, nonspecific immune response. Their antigenicity is due to multiple cell wall constituents, including glycoproteins, phospholipids, and wax D, which activate Langerhans cells, lymphocytes, and polymorphonuclear leukocytes.

Mycobacterium bovis is a key constituent of Freund's adjuvant, frequently used in basic immunology research to stimulate the response to injected antigens. TB is also one of the great imitators for its well-known ability to masquerade as other infectious and disease processes within the human body. The hallmark of extrapulmonary TB histopathology is the caseating granuloma consisting of giant cells with central caseating necrosis. Rarely, if ever, are any TB bacilli seen.

Frequency

United States

The United States has lower rates of TB infection than rates seen worldwide; these rates are comparable to other industrialized nations. An estimated 4-6% of the US population (10-15 million individuals) carries a latent TB infection, while 14,511 new cases of active TB were reported in 2004. A decrease in the number of cases has occurred in the new millennium compared to the dramatic increases of TB in the late 1980s and early 1990s, owing to substantial public health efforts for early detection and therapy compliance. While the initial flare in TB cases in the United States was associated with comorbid HIV, most US cases are now in non-US born individuals who are often immunocompetent.

International

Globally, latent TB infections are comparatively much more frequent and present in one third of the world's population with 20 million cases of active TB and 8-10 million new cases diagnosed each year. The World Health Organization estimated 9 million cases and 2 million deaths from TB for 2005. In Africa, TB incidence has tripled in association with high levels of HIV. Home to 13% of the world's population and 13 of the 15 countries with the highest TB incidence, Africa shoulders over 25% of the annual global TB burden in terms of both cases and deaths. Other areas plagued by high and/or increasing rates of TB include certain regions of Eastern Europe and Southeast Asia.

Mortality/Morbidity

TB is the principal infectious disease cause of morbidity and mortality in the world. TB is responsible for more deaths (2-3 million individuals annually) worldwide than all other infectious diseases combined. In the United States, 2800 TB deaths are reported annually. Immunocompromised patients are particularly vulnerable, with TB as the cause of death in 32% of AIDS patients and a contributor to death in the next 15%.

• In problem areas, multiple drug resistant tuberculosis (MDR-TB) is on the rise. Increasingly mutable strains are suspected. In Russia, 66% of cases of MDR-TB are associated with a specific strain known as the Beijing strain. These infections are much more difficult to treat because of resistance to standard therapy. In California, despite enormous effort to promote therapy compliance, MDR-TB prevalence persisted at 1-2% from 1999-2003.
• Extrapulmonary involvement occurs in one fifth of all TB cases, and 60% of patients with extrapulmonary manifestations of TB have no evidence of pulmonary infection on chest roentegram or sputum culture. Ocular TB can be especially difficult to identify for both its mimickry and its lack of accessible sampling; a high index of suspicion is required. In patients with confirmed active pulmonary or active nonocular extrapulmonary TB, ocular incidence ranges from 1.4-5.74%. In HIV patients, the incidence may be higher, reported from 2.8-11.4%.

Race

TB has no racial preferences for disease development. Within the United States, minorities account for approximately 70% of diagnosed TB cases. This skewed distribution is most likely due to socioeconomic factors. Elevated rates of TB infection are seen in individuals immigrating from Mexico, Philippines, Africa, Southeast Asia, the Caribbean, and Latin America.

Sex

TB has no sexual predilection for disease development.

Age

Higher rates of TB infection are seen in young nonwhite adults (peak incidence, 25-40 y) compared to white adults who manifest disease later (peak incidence, 70 y).

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

History

TB can affect any structure in the eye and typically presents as a granulomatous process. Keratitis, iridocyclitis, intermediate uveitis, retinitis, scleritis, and orbital abscess are within the spectrum of ocular disease. Choroidal tubercles and choroiditis are the most common ocular presentations of TB. Adnexal or orbital disease may be seen with preauricular lymphadenopathy. Because of the wide variability in the disease process, presenting complaints will vary.

• Most often, patients will complain of blurry vision that may or may not be associated with pain and red eye. In the rare case of orbital disease, proptosis, double vision, or extraocular muscle motility restriction may be the presenting complaint. Preseptal cellulitis in children with spontaneous draining fistula has also been recently reported. In cases of pulmonary and extrapulmonary TB, there may be ocular findings without ocular complaints.
• Careful history taking may reveal a history of HIV, recent immigration, homelessness, and/or known exposure to TB. Clinician suspicion for TB should increase in the presence of any of the above risk factors.
• Careful review of systems may, although rarely, reveal night sweats, fevers, weight loss, or productive cough.
• Mycobacterium avium-intracellulare complex (MAC) should be considered in AIDS patients, in addition to M tuberculosis.

Physical

Ocular TB usually is a granulomatous process but also may be nongranulomatous. The ocular inflammatory response may be unilateral or bilateral. Vision usually is decreased proportionately with increased duration and severity of the uveitis. The vision is ultimately limited by chronic cystoid macular edema (CME) or irreversible cystic macular edema.

• External ocular findings
• • Keratitis, phlyctenule, and conjunctival granulomas may be seen.
  • Scleritis can be diffuse, posterior, or nodular and associated with localized granuloma development.
• Anterior chamber findings
• • Iridocyclitis with cells in the anterior chamber are present. Iridocyclitis commonly leads to the development of mutton-fat keratic precipitates (KP) or large greasy appearing cellular deposits on the corneal endothelial surface. The classic inferior distribution of KP appears in the lower one third of the cornea, known as the Arlt triangle. KP on the endothelium may produce corneal edema, and KP in the angle may produce pressure elevations, particularly in individuals with preexisting peripheral anterior synechiae or poor outflow facility.
  • The iris may have posterior or anterior synechia development as well as iris granulomas. Granulomas may be seen at the angle of the iris base and over the trabecular meshwork. Long-standing inflammation can lead to cataract and secondary inflammatory glaucoma. Implanted intraocular lenses may adhere to persistent inflammatory cell precipitates.
• Vitreous findings
• • Anterior vitreous cell with the development of cellular aggregates known as "snowballs" in the anterior and inferior vitreous.
  • Pars plana "snowbank" development can be seen. TB is an important diagnosis in the differential of pars planitis syndrome, which is idiopathic and associated with multiple sclerosis.
• Posterior segment findings
• • Active and old multifocal choroidal and retinal scarring can be seen (multifocal choroiditis and panuveitis pattern).
  • Typically, choroidal granulomas develop singly or in a multifocal pattern and are a hallmark of ocular TB.
  • The retina overlying choroidal inflammation may exhibit secondary retinitis, localized retinal vasculitis, and serous retinal detachment.
  • CME frequently accompanies intraocular inflammation in ophthalmic TB. CME may be reversible if treated aggressively early in its course, but it may progress to permanent structural damage in the form of cystic macular edema with irreversible visual loss.
  • Optic nerve edema and inflammation may occur alone or in conjunction with other posterior segment inflammation. This papillitis is differentiated from anterior ischemic optic neuropathy by inflammation and concurrent vasculitis, and it is differentiated from papilledema by the absence of elevated intracranial pressure.

Causes

Uveitis caused by TB is the local inflammatory manifestation of a previously acquired primary systemic tubercular infection. The organism M tuberculosis is acquired through exposure to infected material usually an aerosol from the lungs of an infected individual. There is some debate regarding molecular mimicry as well as a nonspecific response to noninfectious tubercular antigens, which may produce active ocular inflammation in the absence of bacterial replication.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Other Problems to be Considered

Rheumatoid arthritis

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Lab Studies

• The primary screening and diagnostic test is the tuberculin skin testing with purified protein derivative (PPD) or intermediate strength purified protein derivative (IPPD). Control skin testing with another antigen, such as Candida, may be considered to validate the PPD or IPPD.
• • The tuberculin skin test is available in the following 3 strengths: 1 tuberculin unit (TU) (low strength for highly sensitive individuals), 5 TU (standard or intermediate strength), and 250 TU (for highly anergic individuals, not to be used for initial injection).
  • The PPD test is given in an intracutaneous injection, preferably with a 26-, 27-, or 30-gauge needle. Comparison can be made with simultaneous Candida or mumps control intracutaneous injections to rule out anergy. These dermal delayed-type hypersensitivity tests should be read within 48-72 hours after administration.
  • Qualified health care personnel can interpret the skin testing results. Any palpable induration measuring 10 mm or more is considered a positive reaction. A doubtful reaction measures 5-9 mm and might also be caused by previous bacille Calmette-Guérin (BCG) immunization in a person with normal immune responses. Exposure to atypical mycobacteria, especially in farm workers, also may produce a doubtful reaction. Five millimeters or more induration in a patient exposed to known active TB, particularly with a previously known negative response, should be considered positive. A negative response in immunologically intact individuals measures less than 5 mm. Repeat testing may cause a booster effect and false-positive results. Interpretation of equivocal testing and repeat administration with the same or higher concentrations of PPD can be left to pulmonary or infectious disease physician consultants.
• Culture for acid-fast bacilli (AFB) is the most specific and allows direct identification and susceptibility of the causative organism. Unfortunately, obtaining the test results is slow (3-8 wk), and they have a very low positivity in intraocular disease. AFB stain is quick but requires a very high organism load for positivity. This is more useful in patients with pulmonary disease.
• Refinement in molecular techniques has helped with the diagnosis of intraocular TB. Polymerase chain reaction (PCR) of subretinal fluid has been successful in identifying the presence of TB in cases where the culture result is negative. Nested-PCR further reduces the antigen density required to obtain a positive result but comes with an increased risk of false positivity.
• Enzyme-linked immunosorbent assay (ELISA) evaluates host immunoglobulin G (IgG) and immunoglobulin M (IgM) levels and can help identify recent infection but is not a particularly sensitive test.

Imaging Studies

• Obtain a chest x-ray to evaluate for possible associated pulmonary findings. A traditional lateral and PA view should be ordered in addition to the more sensitive apical lordotic view, which permits better visualization of the hyperoxygenated apices and increases the sensitivity of the chest x-ray for indolent or dormant disease. The chest film is also useful to screen for sarcoidosis, which closely imitates the clinical course of ocular TB. Radiologists look more decisively for signs of TB or sarcoid if the requesting physician simply asks to rule out sarcoid or TB.
• CT scan would be desirable to evaluate for a possible orbital mass from TB, but the results are nonspecific for the disease.

Other Tests

• More recently developed assays may be used to augment the PPD test. Interferon gamma titers correspond to the strength of PPD and appear to correlate more strongly to the risk of disease than PPD. While this test is nonspecific, it is not confounded by BCG exposure.

Histologic Findings

Biopsy of the eye or ocular tissue rarely is required. The specimen would be expected to demonstrate caseating granuloma. Organisms rarely are obtained from ocular samples.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Medical Care

As with most infectious uveitis, ocular TB requires specific antibiotic treatment. The chemotherapy necessary to eradicate M tuberculosis requires a bacteriocidal agent and a sterilizing agent, owing to the complex lifecycle of the tubercle bacilli, including a dormant, replicating, and intracellular phase. Isoniazid initially decreases bacterial load by bacteriocidal activity, while rifampin and pyrazinamide may be used for sterilization.

Anti-inflammatory medications (ie, topical steroids) to decrease the local inflammatory response and secondary scarring sequelae can and should be considered early for patients with response to antitubercular therapy.

• Patients with a suggestive pattern of ocular inflammation and who have a recent skin test conversion, positive sputum cultures, chest x-ray, or systemic findings consistent with TB clearly warrant treatment of pulmonary TB. Ocular inflammation improves with systemic treatment.
  • The American Thoracic Society recommends a 4-drug regimen for pulmonary TB. Isoniazid, rifampin, ethambutol, and pyrazinamide are taken for 2 months, at which point ethambutol and pyrazinamide are discontinued. Isoniazid and rifampin are continued for an additional 4-7 months for a total duration of therapy of 6-9 months depending on the response to therapy.
  • For ocular TB with other extrapulmonary involvement and without pulmonary involvement, the treatment is the same, except ethambutol may be left off and treatment is required for 9 months.
• Patients with uveitis who have a suggestive pattern of ocular inflammation for TB, a positive TB skin test with no systemic associations, and negative chest x-ray and laboratory findings for TB found on extensive testing are controversial in their management.
  • Who should receive anti-TB antibiotic therapy, how many antibiotics used and for how long, and the length of time required to see a response to treatment of tuberculous uveitis are all debatable points. While the American Thoracic Society has guidelines for the treatment of extrapulmonary TB, the basis for those guidelines does not reflect experience with the treatment of isolated ocular TB.
  • Patients with isolated ocular TB (as diagnosed by positive PPD and consistent ocular findings or by negative PPD with strongly suggestive ocular findings) require careful consideration and discussion of the risks of potential severe adverse effects of TB treatment versus the benefits of a therapeutic trial to establish whether TB is present or not. If the uveitis is severe, progressive, or difficult to manage with local and systemic immunosuppressive drugs or if the uveitis is sight threatening, then anti-TB therapy should be considered.
• Historically, the classic Schlaegel test, named after Indiana uveitis specialist Theodore Schlaegel, used a single drug, isoniazid (INH) (300 mg/d) as a therapeutic trial for 1 month. Because of concern for resistance with the improved understanding of the tubercle bacillis physiology, this method is no longer generally acceptable. With no other evidence of TB other than the ocular evidence with positive PPD, a 2-drug regimen of isoniazid (300 mg/d) and rifampin (600 mg/d) for 9-12 months is advocated. For iris nodules/ciliary body masses, the addition of pyrazinamide is often beneficial. Some clinicians may argue that all ocular TB should be treated under the same guidelines as all extrapulmonary TB, suggesting a 3-drug regimen, as described above.
• Begin and continue initial antibiotic therapy under the guidance of public health resources and with a primary care or infectious disease specialist trained and familiar with the use and significant toxicities associated with TB antibiotics. Directly observed therapy should be used whenever possible, as it increases compliance with chemotherapy regimens. For pediatric patients, parents should not be relied on for ensuring compliance of therapy.
• Isoniazid, pyrazinamide, and rifampin carry a risk of hepatotoxicity. Liver function should be monitored during therapy. Cessation of therapy typically resolves the toxicity.
• Combined drug formulations are available and promote compliance, thus discouraging the development of resistant strains. Although combined formulations are more expensive, an additional $60-120 per 2 months depending on a 2- or 3-drug regimen, medication administration is much easier.
• Renal function should be monitored for ethambutol administration, and, because of a risk of optic neuropathy, visual-evoked potentials or contrast sensitivity testing may be warranted for ethambutol therapy. In ethambutol toxicity, blue-yellow sensitivity changes (more than red-green) and may show up on a D-15 panel. Because the tests for ethambutol-related adverse effects are sophisticated, the use of ethambutol in children is generally avoided.

Surgical Care

Surgery is not required in treating ocular TB. When surgery is planned, it usually is directed to treating side effects of disease or treatment for the rehabilitation of vision. Occasionally, a surgical biopsy of conjunctiva, vitreous, choroid, or sclera may be required to help establish the diagnosis or to rule out other potential diagnostic etiologies.

• Cataract surgery should not be performed in a patient with tuberculous uveitis until all inflammation has been completely controlled, that is, cell free, for a period of at least 3 months. Younger patients, noncompliant patients, and patients with severe ocular damage should be cell free for 6 months prior to elective surgery.
• • Standard cataract procedures should be used to maximize outcome, using modern small incision, phaco techniques. Extracapsular surgery produces unwarranted excess inflammation due to the large incision size and requirement for sutures. Assiduous attention should be paid to the posterior capsule and in-the-bag placement of the intraocular lens (IOL), to avoid postoperative complications in these unforgiving eyes.
  • IOLs should be made of highly bio-inert materials. Those materials best suited to uveitic lens implantation include acrylic and hydrophilic materials. Traditional polymethyl methacrylate (PMMA) lenses have a higher posterior capsular opacification rate and may have higher bioadhesion to inflammatory cells and bacteria. Similarly, silicone is not generally considered to be the most appropriate material for uveitic implantation. Second-generation silicone polymers and hybrid collamer (silicone and collagen) materials may prove to be more biocompatible.
  • Concomitant pars plana vitrectomy for uveitic cataract implantation may provide patients with more complete visual rehabilitation, especially when floaters are a prominent complaint. This procedure can be performed immediately after lens implantation with an intact posterior capsule.
• Elective pars plana vitrectomy may provide patients who have TB uveitis with additional benefits. Despite a clear lens implant or noncataractous natural lens, and normal pupillary function, some patients with TB uveitis may complain bitterly of syneresis. In addition, the vitreous gel is believed to provide capacitance for inflammatory debris, cells, and mediators. Removal of the core vitreous, therefore, may benefit patients with uveitis by reducing the need for long-term inflammatory medications. Progressive vitreous opacification and organization in more severe cases also may predispose to cyclitic membrane formation and subsequent retinal detachment.

Consultations

• The public health sector should be notified and involved in cases of TB. Consultation with a primary care, pulmonology, internal medicine, or infectious disease specialist prior to initiating therapy is helpful, and it may be appropriate for this consultant to manage the antitubercular chemotherapy.
• Consultation with a uveitis or retinal specialist is helpful due to the complex management decisions encountered in patients with severe or chronic uveitis as frequently is seen in tuberculous uveitis.

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Effective management of ocular TB requires treatment of systemic infectious disease and local ocular inflammatory manifestations of the disease. The systemic infectious disease component is treated with specific antituberculous agents under the supervision of a primary care physician, internal medicine, or infectious disease specialist. In ocular TB, the eye is the primarily affected end organ; therefore, the ophthalmologist or uveitis specialist is principally responsible for managing the local ocular inflammatory manifestations. The secondary goal is to monitor the treatment of systemic antituberculous agents to minimize the potential sight-threatening complications that may arise from both treatment and the underlying disease process.

Drug Category: Antituberculous agents

Number of agents used depends on the estimated number of acid-fast bacilli in the body, likelihood of resistance, and desired duration of therapy.

Drug Name	Rifampin (Rifadin, Rimactane)
Description	Indicated for TB, meningococcal carriers, leprosy, meningitis atypical, and mycobacterial infections. Acts as a bactericidal agent that inhibits DNA-dependent RNA activity in bacterial cells. Well absorbed from GI tract, distributed in most body fluids, including CSF. Eliminated rapidly in the bile. Rifampin should always be used in conjunction with another anti-TB agent (usually INH) because of rapid emergence of resistance. Rifampin is available in combination with isoniazid (Rifamate, Hoechst Marion Roussel).
Adult Dose	600 mg PO/IV qd
Pediatric Dose	10-20 mg/kg PO/IV; not to exceed 600 mg
Contraindications	Documented hypersensitivity
Interactions	Induces liver enzymes and may reduce the activity of several drugs including oral contraceptives, digitalis glycosides, oral antidiabetics, anticoagulants, alcohol, antiepileptics, corticosteroids, and theophylline
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Can cause liver damage including death in susceptible individuals or in those with preexisting liver disease; patients should avoid concomitant usage of other drugs (acetaminophen, alcohol) that may damage the liver; perform regular laboratory measurement of hepatic function.

Drug Name	Ethambutol (Myambutol)
Description	Chemotherapeutic agent indicated in the treatment of TB. Should not be used as a sole therapy due to resistant organism development and should be used with another anti-TB agent. Mechanism of action is by inhibition of cell metabolism and resultant cell death. Adsorbed rapidly from the GI tract and well distributed in body tissues except CSF. Metabolized in the liver and excreted in both urine and feces.
Adult Dose	15 mg/kg PO in a single daily dose
Pediatric Dose	<13 years: Not recommended >13 years: Administer as in adults
Contraindications	Documented hypersensitivity; optic neuritis
Interactions	Aluminum salts may delay and reduce absorption (give several hours before or after ethambutol dose)
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Patients should have regular ophthalmic examinations to screen for optic neuritis; other adverse effects are gout or hyperuricemia, GI disturbances, headache, confusion, and disorientation, and peripheral neuritis; dosage may require adjustment in patients with reduced renal function

Drug Name	Pyrazinamide
Description	The pyrazine analog of nicotinamide, fully penetrates most body tissues. Actively hydrolyzed in the liver to active metabolite, pyrazinoic acid. Seventy percent excreted in urine. Should be given with other anti-TB drugs because of the rapid appearance of drug resistance. Pyrazinamide is available in a combination tablet with rifampin and isoniazid (Rifater, Hoechst Marion Russel).
Adult Dose	15-30 mg/kg PO qd
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; active gout; severe hepatic damage
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Use only in combination with other effective antituberculous agents; inhibits renal excretion of urates; may result in hyperuricemia (usually asymptomatic); perform baseline serum uric acid determinations; discontinue drug if signs of hyperuricemia with acute gouty arthritis; perform baseline LFTs (closely monitor in liver disease); discontinue pyrazinamide if signs of hepatocellular damage appear; caution in history of diabetes mellitus

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Further Inpatient Care

• Because of the prolonged course of anti-TB therapy, inpatient care is excessively costly and impractical. Local county health departments are expert and funded in the care of TB infection.

Further Outpatient Care

• Patients undergoing treatment for TB uveitis require close monitoring for both therapeutic response and drug toxicity by the treating ophthalmologist as well as a primary care or internal medicine specialist familiar with TB medications. The public health sector needs to be involved.
• After the TB uveitis has clearly responded to antibiotic therapy, topical or depot corticosteroids may be considered to decrease the local ocular inflammatory response and improve visual function. Oral corticosteroids are rarely required, and, in general, they should be avoided. Topical corticosteroids are essential to control cell, flare, synechiae formation, and CME.

Complications

• Complications of TB uveitis are those seen with chronic and severe ocular inflammation and may include the following:
• • Cataract
  • Glaucoma
  • Cystoid macular edema
  • Retinal and choroidal scarring
  • Corneal scarring
• Complications of antibiotic therapy in TB can be severe and include the following:
• Hepatitis
• Peripheral neuropathy
• Retrobulbar optic neuropathy

Prognosis

• When correctly identified and aggressively treated, TB uveitis can be managed successfully with elimination of inflammation and preservation of visual function. Early diagnosis prior to significant ocular involvement leads to better visual functional outcomes. Advanced, neglected, or particularly virulent presentations have a poorer outcome despite therapy.

Patient Education

• For excellent patient education resources, visit eMedicine's Bacterial and Viral Infections Center. Also, see eMedicine's patient education article Tuberculosis.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Medical/Legal Pitfalls

• Monitoring and screening evaluations for potential drug side effects should be carried out under the supervision of a physician familiar with the use of anti-TB agents.

ACKNOWLEDGMENTS

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, David Scales, MD, to the development and writing of this article.

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

• Aggarwal D, Suri A, Mahapatra AK. Orbital tuberculosis with abscess. J Neuroophthalmol. Sep 2002;22(3):208-10. [Medline].
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• Demirci H, Shields CL, Shields JA. Ocular tuberculosis masquerading as ocular tumors. Surv Ophthalmol. Jan-Feb 2004;49(1):78-89. [Medline].
• Dye C, Watt CJ, Bleed DM. Evolution of tuberculosis control and prospects for reducing tuberculosis incidence, prevalence, and deaths globally. JAMA. Jun 8 2005;293(22):2767-75. [Medline].
• Granich RM, Oh P, Lewis B. Multidrug resistance among persons with tuberculosis in California, 1994-2003. JAMA. Jun 8 2005;293(22):2732-9. [Medline].
• Gupta A, Gupta V. Tubercular posterior uveitis. Int Ophthalmol Clin. 2005;45(2):71-88. [Medline].
• Mistr S, Chavis PS. Treatment of neuro-ophthalmologic manifestations of tuberculosis. Curr Treat Options Neurol. Jan 2006;8(1):53-67. [Medline].
• Nussenblatt RB, Whitcup SM, Palestine AG. Uveitis: Fundamentals and Clinical Practice. 2nd ed. Mosby;1996:158.
• Opremcak EM. Uveitis: A Clinical Manual for Ocular Inflammation. Springer-Verlag;1994:139.
• Pai M, Gokhale K, Joshi R. Mycobacterium tuberculosis infection in health care workers in rural India: comparison of a whole-blood interferon gamma assay with tuberculin skin testing. JAMA. Jun 8 2005;293(22):2746-55. [Medline].
• Raina UK, Jain S, Monga S. Tubercular preseptal cellulitis in children: a presenting feature of underlying systemic tuberculosis. Ophthalmology. Feb 2004;111(2):291-6. [Medline].
• Salman A, Parmar P, Rajamohan M. Subretinal fluid analysis in the diagnosis of choroidal tuberculosis. Retina. Dec 2003;23(6):796-9. [Medline].
• Tabbara KF. Ocular tuberculosis: anterior segment. Int Ophthalmol Clin. 2005;45(2):57-69. [Medline].

Article Last Updated: Sep 26, 2006