Interferon-gamma release assay and chest X-ray to classify intraocular tuberculosis among clinically undifferentiated uveitis

  • Mei Riasanti Master’s Programme in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • Ikhwanuliman Putera Department of Ophthalmology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Kirana Hospital, Jakarta, Indonesia; Department of Clinical Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands https://orcid.org/0000-0002-9350-5133
  • Priscilla Jessica Department of Ophthalmology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Kirana Hospital, Jakarta, Indonesia
  • Muhammad Zakiy Waliyuddin Department of Ophthalmology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Kirana Hospital, Jakarta, Indonesia https://orcid.org/0000-0001-9652-2695
  • Faiz Alwan Tagar Department of Ophthalmology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Kirana Hospital, Jakarta, Indonesia https://orcid.org/0000-0003-1894-5996
  • Andini Karlina CH Department of Ophthalmology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Kirana Hospital, Jakarta, Indonesia https://orcid.org/0000-0002-9967-3269
  • Yulia Aziza Department of Ophthalmology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Kirana Hospital, Jakarta, Indonesia https://orcid.org/0000-0002-8266-1974
  • Made Susiyanti Department of Ophthalmology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Kirana Hospital, Jakarta, Indonesia
  • Lukman Edwar Department of Ophthalmology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Kirana Hospital, Jakarta, Indonesia
  • Ratna Sitompul Department of Ophthalmology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Kirana Hospital, Jakarta, Indonesia
  • Rina La Distia Nora Department of Ophthalmology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Kirana Hospital, Jakarta, Indonesia; Department of Ophthalmology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Kirana Hospital, Jakarta, Indonesia; Universitas Indonesia Hospital, Depok, Indonesia https://orcid.org/0000-0002-7026-5341
Keywords: interferon-gamma release assay, tuberculosis, uveitis, X-ray
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Abstract

BACKGROUND Tuberculosis (TB) is a common cause of intraocular inflammation in Indonesia. As no accurate biomarker can confirm the diagnosis, ophthalmologists often rely on systemic findings, such as tuberculin skin test, interferon-gamma release assay (IGRA), and chest X-ray (CXR) for TB suspicion. This study aimed to evaluate IGRA and CXR in classifying intraocular TB among patients with a clinically undifferentiated cause of uveitis.

METHODS This cross-sectional study included 116 patients (a total of 163 affected eyes) with a clinically undifferentiated cause of uveitis. IGRA and CXR were performed as part of the workup. Data on visual acuity, anterior chamber inflammation grade, and anatomical classification of uveitis were recorded. As there were no confirmed ocular tuberculosis (OTB) in our cases, eyes were classified into probable OTB, possible OTB, and unclassified.

RESULTS Overall, 93 patients (80.2%) with a clinically undifferentiated cause of uveitis had positive IGRA, whereas 10 (8.6%) had CXR results suggestive of TB. More than one-third of the patients were blind (visual acuity <3/60), and panuveitis was the commonest anatomical classification. A trend was identified in patients with panuveitis, who often showed ≥2+ cell anterior chamber inflammation (p for trend = 0.023), according to OTB criteria (probable OTB = 3/4, 75.0%; possible OTB = 44/67, 65.7%; unclassified = 2/9, 22.2%). Furthermore, the clinically undifferentiated uveitis cases were eligible to be stratified into probable (8.6%) and possible (75.0%) OTB categories after IGRA and CXR examinations.

CONCLUSIONS The combination of IGRA and CXR is valuable for classifying and diagnosing TB-related uveitis. A multidisciplinary approach is essential when the cause of uveitis is unknown.

References

  1. Shakarchi FI. Ocular tuberculosis: current perspectives. Clin Ophthalmol. 2015;9:2223-7. https://doi.org/10.2147/OPTH.S65254

  2. La Distia Nora R, Sitompul R, Bakker M, Susiyanti M, Edwar L, Sjamsoe S, et al. Tuberculosis and other causes of uveitis in Indonesia. Eye (Lond). 2018;32(3):546-54. https://doi.org/10.1038/eye.2017.231

  3. Thompson MJ, Albert DM. Ocular tuberculosis. Arch Ophthalmol. 2005;123(6):844-9. https://doi.org/10.1001/archopht.123.6.844

  4. Gupta A, Sharma A, Bansal R, Sharma K. Classification of intraocular tuberculosis. Ocul Immunol Inflamm. 2015;23(1):7-13. https://doi.org/10.3109/09273948.2014.967358

  5. Testi I, Agrawal R, Mehta S, Basu S, Nguyen Q, Pavesio C, et al. Ocular tuberculosis: where are we today? Indian J Ophthalmol. 2020;68(9):1808-17. https://doi.org/10.4103/ijo.IJO_1451_20

  6. Jabs DA, Busingye J. Approach to the diagnosis of the uveitides. Am J Ophthalmol. 2013;156(2):228-36. https://doi.org/10.1016/j.ajo.2013.03.027

  7. Rahman S, Irfan M, Siddiqui MAR. Role of interferon gamma release assay in the diagnosis and management of Mycobacterium tuberculosis-associated uveitis: a review. BMJ Open Ophthalmol. 2021;6(1):e000663. https://doi.org/10.1136/bmjophth-2020-000663

  8. Agrawal R, Grant R, Gupta B, Gunasekeran DV, Gonzalez-Lopez JJ, Addison PKF, et al. What does IGRA testing add to the diagnosis of ocular tuberculosis? A Bayesian latent class analysis. BMC Ophthalmol. 2017;17(1):245. https://doi.org/10.1186/s12886-017-0597-x

  9. Agrawal R, Testi I, Bodaghi B, Barisani-Asenbauer T, McCluskey P, Agarwal A, et al. Collaborative ocular tuberculosis study consensus guidelines on the management of tubercular uveitis-report 2: guidelines for initiating antitubercular therapy in anterior uveitis, intermediate uveitis, panuveitis, and retinal vasculitis. Ophthalmology. 2021;128(2):277-87. https://doi.org/10.1016/j.ophtha.2020.06.052

  10. University of Oxford. Oxford centre for evidence-based medicine: levels of evidence (March 2009) [Internet]. University of Oxford; 2009 [cited 2022 Apr 11]. Available from: https://www.cebm.ox.ac.uk/resources/levels-of-evidence/oxford-centre-for-evidence-based-medicine-levels-of-evidence-march-2009.

  11. La Distia Nora R, Sitompul R, Bakker M, Versnel MA, Swagemakers SMA, van der Spek PJ, et al. Type 1 interferon-inducible gene expression in QuantiFERON Gold TB-positive uveitis: a tool to stratify a high versus low risk of active tuberculosis? PLoS One. 2018;13(10):e0206073. https://doi.org/10.1371/journal.pone.0206073

  12. Rathinam SR, Babu M. Algorithmic approach in the diagnosis of uveitis. Indian J Ophthalmol. 2013;61(6):255-62. https://doi.org/10.4103/0301-4738.114092

  13. Jabs DA, Nussenblatt RB, Rosenbaum JT; Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol. 2005;140(3):509-16. https://doi.org/10.1016/j.ajo.2005.03.057

  14. Vashist P, Senjam SS, Gupta V, Gupta N, Kumar A. Definition of blindness under National Programme for Control of Blindness: do we need to revise it? Indian J Ophthalmol. 2017;65(2):92-6. https://doi.org/10.4103/ijo.IJO_869_16

  15. Tugal-Tutkun I, Gupta V, Cunningham ET. Differential diagnosis of behçet uveitis. Ocul Immunol Inflamm. 2013;21(5):337-50. https://doi.org/10.3109/09273948.2013.795228

  16. Rao NA, Sukavatcharin S, Tsai JH. Vogt-Koyanagi-Harada disease diagnostic criteria. Int Ophthalmol. 2007;27(2-3):195-9. https://doi.org/10.1007/s10792-006-9021-x

  17. Park YH, Nam HW. Clinical features and treatment of ocular toxoplasmosis. Korean J Parasitol. 2013;51(4):393-9. https://doi.org/10.3347/kjp.2013.51.4.393

  18. Port AD, Orlin A, Kiss S, Patel S, D'Amico DJ, Gupta MP. Cytomegalovirus retinitis: a review. J Ocul Pharmacol Ther. 2017;33(4):224-34. https://doi.org/10.1089/jop.2016.0140

  19. Relvas LJ, Caspers L, Chee SP, Zierhut M, Willermain F. Differential diagnosis of viral-induced anterior uveitis. Ocul Immunol Inflamm. 2018;26(5):726-31. https://doi.org/10.1080/09273948.2018.1468470

  20. Hinthorn D, Bader MS. Tuberculin skin testing: indication, interpretation, and management. Adv Stud Med. 2004;4(10):534-42.

  21. Betzler BK, Gupta V, Agrawal R. Clinics of ocular tuberculosis: a review. Clin Exp Ophthalmol. 2021;49(2):146-60. https://doi.org/10.1111/ceo.13847

  22. Murphy CC, Hughes EH, Frost NA, Dick AD. Quality of life and visual function in patients with intermediate uveitis. Br J Ophthalmol. 2005;89(9):1161-5. https://doi.org/10.1136/bjo.2005.067421

  23. Diel R, Goletti D, Ferrara G, Bothamley G, Cirillo D, Kampmann B, et al. Interferon-γ release assays for the diagnosis of latent Mycobacterium tuberculosis infection: a systematic review and meta-analysis. Eur Respir J. 2011;37(1):88-99. https://doi.org/10.1183/09031936.00115110

  24. Barth RE, Mudrikova T, Hoepelman AI. Interferon-gamma release assays (IGRAs) in high-endemic settings: could they play a role in optimizing global TB diagnostics? Evaluating the possibilities of using IGRAs to diagnose active TB in a rural African setting. Int J Infect Dis. 2008;12(6):e1-6. https://doi.org/10.1016/j.ijid.2008.03.026

  25. Basu S, Elkington P, Rao NA. Pathogenesis of ocular tuberculosis: new observations and future directions. Tuberculosis (Edinb). 2020;124:101961. https://doi.org/10.1016/j.tube.2020.101961

  26. Faust L, Ruhwald M, Schumacher S, Pai M. How are high burden countries implementing policies and tools for latent tuberculosis infection? A survey of current practices and barriers. Health Sci Rep. 2020;3(2):e158. https://doi.org/10.1002/hsr2.158

  27. Al-Mezaine HS, Al-Muammar A, Kangave D, Abu El-Asrar AM. Clinical and optical coherence tomographic findings and outcome of treatment in patients with presumed tuberculous uveitis. Int Ophthalmol. 2008;28(6):413-23. https://doi.org/10.1007/s10792-007-9170-6

  28. Al-Shakarchi F. Mode of presentations and management of presumed tuberculous uveitis at a referral center. Iraqi Postgrad Med J. 2015;14(1):91-6.

  29. Standardization of Uveitis Nomenclature (SUN) Working Group. Classification criteria for tubercular uveitis. Am J Ophthalmol. 2021;228:142-51. https://doi.org/10.1016/j.ajo.2021.03.040

  30. Ang M, Chee SP. Controversies in ocular tuberculosis. Br J Ophthalmol. 2017;101(1):6-9. https://doi.org/10.1136/bjophthalmol-2016-309531

  31. Kee AR, Gonzalez-Lopez JJ, Al-Hity A, Gupta B, Lee CS, Gunasekeran DV, et al. Anti-tubercular therapy for intraocular tuberculosis: a systematic review and meta-analysis. Surv Ophthalmol. 2016;61(5):628-53. https://doi.org/10.1016/j.survophthal.2016.03.001

  32. Pandey TR, Sitaula RK, Shah DN, Pant RP. Pattern of presumed tuberculous uveitis in a tertiary eye care centre of Nepal. Cogent Med. 2018;5(1):1510302. https://doi.org/10.1080/2331205X.2018.1510302

  33. Uzorka JW, Wallinga J, Kroft LJM, Ottenhoff THM, Arend SM. Radiological signs of latent tuberculosis on chest radiography: a systematic review and meta-analysis. Open Forum Infect Dis. 2019;6(7):ofz313. https://doi.org/10.1093/ofid/ofz313

  34. Adams S, Ehrlich R, Baatjies R, Dendukuri N, Wang Z, Dheda K. Evaluating latent tuberculosis infection test performance using latent class analysis in a TB and HIV endemic setting. Int J Environ Res Public Health. 2019;16(16):2912. https://doi.org/10.3390/ijerph16162912

  35. American Academy of Ophthalmology. Ocular tuberculosis (TB) - Asia Pacific [Internet]. American Academy of Ophthalmology; 2014 [cited 2022 Apr 9]. Available from: https://www.aao.org/topicdetail/ocular-tuberculosis-tb-asia-pacific.

Published
2023-01-11
How to Cite
1.
Riasanti M, Putera I, Jessica P, Waliyuddin MZ, Tagar FA, Karlina CH A, Aziza Y, Susiyanti M, Edwar L, Sitompul R, La Distia Nora R. Interferon-gamma release assay and chest X-ray to classify intraocular tuberculosis among clinically undifferentiated uveitis. Med J Indones [Internet]. 2023Jan.11 [cited 2023Feb.4];1(1). Available from: https://mji.ui.ac.id/journal/index.php/mji/article/view/6324
Section
Clinical Research