eMedicine Specialties > Ophthalmology > Infectious Disease

Tuberculosis: Differential Diagnoses & Workup

Author: Pamela S Chavis, MD, Associate Professor, Department of Ophthalmology, Consulting Staff, Department of Neuro-Ophthalmology, Medical University of South Carolina
Coauthor(s): Susannah K Mistr, MD, Resident Physician, Department of Ophthalmology, University of Maryland Medical Center
Contributor Information and Disclosures

Updated: Nov 7, 2008

Differential Diagnoses

Cellulitis, Orbital
Ocular Manifestations of HIV
Cellulitis, Preseptal
Ocular Manifestations of Syphilis
Conjunctivitis, Bacterial
Onchocerciasis
Eales Disease
Papilledema
Endophthalmitis, Fungal
Retinal Detachment, Exudative
Glaucoma, Uveitic
Retinopathy, Birdshot
Hemorrhage, Vitreous
Sarcoidosis
Keratitis, Bacterial
Scleritis
Keratitis, Interstitial
Sjogren Syndrome
Keratoconjunctivitis, Epidemic
Synechia, Peripheral Anterior
Keratopathy, Band
Uveitis, Anterior, Granulomatous
Lyme Disease
Uveitis, Anterior, Nongranulomatous
Melanoma, Choroidal
Uveitis, Intermediate
Melanoma, Ciliary Body
White Dot Syndromes
Nasolacrimal Duct, Obstruction
Nonpseudophakic Cystoid Macular Edema
Ocular Hypotony

Other Problems to Be Considered

Rheumatoid arthritis

Workup

Laboratory 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; however, access to the organisms may require lymph node/sputum analysis, bronchoalveolar lavage, or aspirate of cavity fluid or bone marrow. 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, but a delay in diagnosis can increase mortality, as other diagnostic testing may need to be considered.
  • 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.
  • See related CME at Options for Screening and Treatment of Tuberculosis Reviewed.

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.
  • Optical coherence tomography (OCT) of choroidal lesions highlights an elevated choroid with localized contact of the choriocapillaris-retinal pigment epithelial complex with subretinal fluid.

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. This test is not confounded by BCG exposure since it relates to proteins found in M tuberculosis but not in BCG. However, immunosuppressed patients may yield inconclusive/negative results and positive tests can occur in latent TB.

Procedures

  • See Histologic Findings.

Histologic Findings

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

More on Tuberculosis

Overview: Tuberculosis
Differential Diagnoses & Workup: Tuberculosis
Treatment & Medication: Tuberculosis
Follow-up: Tuberculosis
References

References

  1. Aggarwal D, Suri A, Mahapatra AK. Orbital tuberculosis with abscess. J Neuroophthalmol. Sep 2002;22(3):208-10. [Medline].

  2. American Thoracic Society, CDC, Infectious Diseases Society of America. Treatment of tuberculosis. MMWR Recomm Rep. Jun 20 2003;52(RR-11):1-77. [Medline].

  3. Bramante CT, Talbot EA, Rathinam SR, et al. Diagnosis of ocular tuberculosis: a role for new testing modalities?. Int Ophthalmol Clin. Summer 2007;47(3):45-62. [Medline].

  4. Demirci H, Shields CL, Shields JA, et al. Ocular tuberculosis masquerading as ocular tumors. Surv Ophthalmol. Jan-Feb 2004;49(1):78-89. [Medline].

  5. Dye C, Watt CJ, Bleed DM, et al. Evolution of tuberculosis control and prospects for reducing tuberculosis incidence, prevalence, and deaths globally. JAMA. Jun 8 2005;293(22):2767-75. [Medline].

  6. Granich RM, Oh P, Lewis B, et al. Multidrug resistance among persons with tuberculosis in California, 1994-2003. JAMA. Jun 8 2005;293(22):2732-9. [Medline].

  7. Gupta A, Gupta V. Tubercular posterior uveitis. Int Ophthalmol Clin. 2005;45(2):71-88. [Medline].

  8. Gupta V, Gupta A, Rao NA. Intraocular tuberculosis--an update. Surv Ophthalmol. Nov-Dec 2007;52(6):561-87. [Medline].

  9. Mistr S, Chavis PS. Treatment of neuro-ophthalmologic manifestations of tuberculosis. Curr Treat Options Neurol. Jan 2006;8(1):53-67. [Medline].

  10. Nussenblatt RB, Whitcup SM, Palestine AG. Uveitis: Fundamentals and Clinical Practice. 2nd ed. Mosby; 1996:158.

  11. Opremcak EM. Uveitis: A Clinical Manual for Ocular Inflammation. Springer-Verlag; 1994:139.

  12. Pai M, Gokhale K, Joshi R, et al. 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].

  13. Raina UK, Jain S, Monga S, et al. Tubercular preseptal cellulitis in children: a presenting feature of underlying systemic tuberculosis. Ophthalmology. Feb 2004;111(2):291-6. [Medline].

  14. Salman A, Parmar P, Rajamohan M, et al. Optical coherence tomography in choroidal tuberculosis. Am J Ophthalmol. Jul 2006;142(1):170-2. [Medline].

  15. Salman A, Parmar P, Rajamohan M, et al. Subretinal fluid analysis in the diagnosis of choroidal tuberculosis. Retina. Dec 2003;23(6):796-9. [Medline].

  16. Tabbara KF. Ocular tuberculosis: anterior segment. Int Ophthalmol Clin. 2005;45(2):57-69. [Medline].

Further Reading

Keywords

tuberculosis, TB, TB uveitis, ocular tuberculosis, ocular TB, presumed ocular tuberculosis syndrome, Mycobacterium tuberculosis, M tuberculosis

Contributor Information and Disclosures

Author

Pamela S Chavis, MD, Associate Professor, Department of Ophthalmology, Consulting Staff, Department of Neuro-Ophthalmology, Medical University of South Carolina
Pamela S Chavis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Ophthalmology, and North American Neuro-Ophthalmology Society
Disclosure: Nothing to disclose.

Coauthor(s)

Susannah K Mistr, MD, Resident Physician, Department of Ophthalmology, University of Maryland Medical Center
Susannah K Mistr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, American Medical Association, American Medical Student Association/Foundation, American Society of Cataract and Refractive Surgery, and South Carolina Medical Association
Disclosure: Nothing to disclose.

Medical Editor

John D Sheppard Jr, MD, MMSc, Professor of Ophthalmology, Microbiology and Molecular Biology, Clinical Director, Thomas R Lee Center for Ocular Pharmacology, Program Director, Ophthalmology Residency Training, Eastern Virginia Medical School; President, Virginia Eye Consultants
John D Sheppard Jr, MD, MMSc is a member of the following medical societies: American Academy of Ophthalmology, American Society for Microbiology, American Society of Cataract and Refractive Surgery, American Uveitis Society, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.

Pharmacy Editor

Simon K Law, MD, PharmD, Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles
Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.

Managing Editor

J James Rowsey, MD, Former Director of Corneal Services, St Luke's Cataract and Laser Institute, Florida
J James Rowsey, MD is a member of the following medical societies: American Academy of Ophthalmology, American Association for the Advancement of Science, American Medical Association, Association for Research in Vision and Ophthalmology, Florida Medical Association, Pan-American Association of Ophthalmology, Sigma Xi, and Southern Medical Association
Disclosure: Nothing to disclose.

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

 
 
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