Skip to main content

Advertisement

SpringerLink
Log in

Optical coherence tomography can measure axonal loss in patients with ethambutol-induced optic neuropathy

  • Clinical Investigation
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To map and identify the pattern, in vivo, of axonal degeneration in ethambutol-induced optic neuropathy using optical coherence tomography (OCT). Ethambutol is an antimycobacterial agent often used to treat tuberculosis. A serious complication of ethambutol is an optic neuropathy that impairs visual acuity, contrast sensitivity, and color vision. However, early on, when the toxic optic neuropathy is mild and partly reversible, the funduscopic findings are often subtle and easy to miss.

Methods

Three subjects with a history of ethambutol (EMB)-induced optic neuropathy of short-, intermediate-, and long-term visual deficits were administered a full neuro-ophthalmologic examination including visual acuity, color vision, contrast sensitivity, and fundus examination. In addition, OCT (OCT 3000, Humphrey-Zeiss, Dublin, CA) was performed on both eyes of each subject using the retinal nerve fiber layer (RNFL) analysis protocol. OCT interpolates data from 100 points around the optic nerve to effectively map out the RNFL.

Results

The results were compared to the calculated average RNFL of normal eyes accumulated from four prior studies using OCT, n=661. In all subjects with history of EMB-induced optic neuropathy, there was a mean loss of 72% nerve fiber layer thickness in the temporal quadrant (patient A, with eventual recovery of visual acuity and fields, 58% loss; patient B, with intermediate visual deficits, 68% loss; patient C, with chronic visual deficits, 90% loss), with an average mean optic nerve thickness of 26±16 μm. There was a combined mean loss of 46% of fibers from the superior, inferior, and nasal quadrants in the (six) eyes of all three subjects (mean average thickness of 55±29 μm). In both sets (four) of eyes of the subjects with persistent visual deficits (patients B and C), there was an average loss of 79% of nerve fiber thickness in the temporal quadrant.

Conclusions

The OCT results in these patients with EMB-induced optic neuropathy show considerable loss especially of the temporal fibers. This is consistent with prior histopathological studies that show predominant loss of parvo-cellular axons (or small-caliber axons) within the papillo-macular bundle in toxic or hereditary optic neuropathies. OCT can be a valuable tool in the quantitative analysis of optic neuropathies. Additionally, in terms of management of EMB-induced optic neuropathy, it is important to properly manage ethambutol dosing in patients with renal impairment and to achieve proper transition to a maintenance dose once an appropriate loading dose has been reached.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Reference

  1. Barron GJ, Tepper L, Iovine G (1974) Ocular toxicity from ethambutol. Am J Ophthalmol 77(2):256–260

    CAS  PubMed  Google Scholar 

  2. Buyske DA, Peets E, Sterling W (1966) Pharmacological and biochemical studies on ethambutol in laboratory animals. Ann NY Acad Sci 135(2):711–725

    CAS  PubMed  Google Scholar 

  3. Carelli V, Ross-Cisneros FN, Sadun AA (2002) Optic nerve degeneration and mitochondrial dysfunction: genetic and acquired optic neuropathies. Neurochem Int 40(6):573–584; Review

    Article  CAS  PubMed  Google Scholar 

  4. Carpineto P, Ciancaglini M, Zuppardi E, Falconio G, Doronzo E, Mastropasqua L (2003) Reliability of nerve fiber layer thickness measurements using optical coherence tomography in normal and glaucomatous eyes. Ophthalmology 110(1):190–195

    Article  PubMed  Google Scholar 

  5. Cole A, May PM, Williams DR (1983) Metal binding by pharmaceuticals. Part 3. Copper (II) and zinc (II) interactions with isoniazid. Agents Actions 1:91–97

    Google Scholar 

  6. DeVita EG, Miao M, Sadun AA (1987) Optic neuropathy in ethambutol-treated renal tuberculosis. J Clin Neuro-Ophthalmol 7(2):77–86

    CAS  Google Scholar 

  7. Gietzen DW, Leung PM, Rogers QR (1986) Norepinephrine and amino acids in prepyriform cortex of rats fed imbalanced amino acid diets. Physiol Behav 36(6):1071–1080

    Article  CAS  PubMed  Google Scholar 

  8. Hougaard JL, Kessel L, Sander B, Kyvik KO, Sorensen TI, Larsen M (2003) Evaluation of heredity as a determinant of retinal nerve fiber layer thickness as measured by optical coherence tomography. Invest Ophthalmol Vis Sci 44(7):3011–3016

    Article  Google Scholar 

  9. Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, Hee MR, Flotte T, Gregory K, Puliafito CA, et al (1991) Optical coherence tomography. Science 254(5035):1178–1181

    CAS  PubMed  Google Scholar 

  10. Hubert JP, Delumeau JC, Glowinski J, Premont J, Doble A (1994) Antagonism by riluzole of entry of calcium evoked by NMDA and veratridine in rat cultured granule cells: evidence for a dual mechanism of action. Br J Pharmacol 113(1):261–267

    CAS  PubMed  Google Scholar 

  11. Jones AL, Sheen NJ, North RV, Morgan JE (2001) The Humphrey optical coherence tomography scanner: quantitative analysis and reproducibility study of the normal human retinal nerve fibre layer. Br J Ophthalmol 85(6):673–677

    Article  CAS  PubMed  Google Scholar 

  12. Kozak SF, Inderlied CB, Hsu HY, Heller KB, Sadun AA (1998) The role of copper on ethambutol’s antimicrobial action and implications for ethambutol-induced optic neuropathy. Diagn Microbiol Infect Dis 30(2):83–87

    Article  CAS  PubMed  Google Scholar 

  13. Leibold JE (1966) The ocular toxicity of ethambutol and its relation to dose. Ann NY Acad Sci 135(2):904–909

    CAS  PubMed  Google Scholar 

  14. Liu X, Ling Y, Zhou W, Zheng X, Liang D (2000) Qualitative and quantitative measurement of retinal nerve fiber layer in primary open angle glaucoma by optical coherence tomography. Zhonghua YanKe ZaZhi 36(6):420–424, 428; Chinese

    CAS  Google Scholar 

  15. Manabe S, Kashii S, Honda Y, Yamamoto R, Katsuki H, Akaike A (2002) Quantification of axotomized ganglion cell death by explant culture of the rat retina. Neurosci Lett 334(1):33–36

    Article  CAS  PubMed  Google Scholar 

  16. Mok KH, Lee VW, So KF (2002) Retinal nerve fiber layer measurement of the Hong Kong Chinese population by optical coherence tomography. J Glaucoma 11(6):481–483

    Article  PubMed  Google Scholar 

  17. Monteiro ML, Medeiros FA, Ostroscki MR (2003) Quantitative analysis of axonal loss in band atrophy of the optic nerve using scanning laser polarimetry. Br J Ophthalmol 87(1):32–37

    Article  CAS  PubMed  Google Scholar 

  18. Puliafito CA, Hee MR, Lin CP, Reichel E, Schuman JS, Duker JS, Izatt JA, Swanson EA, Fujimoto JG (1995) Imaging of macular diseases with optical coherence tomography. Ophthalmology 102(2):217–229

    CAS  PubMed  Google Scholar 

  19. Saadati HG, Hsu HY, Heller KB, Sadun AA (1998) A histopathologic and morphometric differentiation of nerves in optic nerve hypoplasia and Leber hereditary optic neuropathy. Arch Ophthalmol 116:911–916

    CAS  PubMed  Google Scholar 

  20. Sadun A (1998) Acquired mitochondrial impairment as a cause of optic nerve disease. Trans Am Ophthalmol Soc 96:881–923

    CAS  PubMed  Google Scholar 

  21. Sadun AA (2002) Mitochondrial optic neuropathies. J Neurol Neurosurg Psychiatry 72(4):423–425

    CAS  PubMed  Google Scholar 

  22. Sadun AA, Carelli V, Salomao SR, Berezovsky A, Quiros PA, Sadun F, DeNegri AM, Andrade R, Moraes M, Passos A, Kjaer P, Pereira J, Valentino ML, Schein S, Belfort R (2003) Extensive investigation of a large Brazilian pedigree of 11778/haplogroup J Leber hereditary optic neuropathy. Am J Ophthalmol 136(2):231–238

    Article  PubMed  Google Scholar 

  23. Sadun AA, Win PH, Ross-Cisneros FN, Walker SO, Carelli V (2000) Leber’s hereditary optic neuropathy differentially affects smaller axons in the optic nerve. Trans Am Ophthalmol Soc 98:223–232; discussion 232–235

    CAS  PubMed  Google Scholar 

  24. Schuman JS, Hee MR, Puliafito CA, Wong C, Pedut-Kloizman T, Lin CP, Hertzmark E, Izatt JA, Swanson EA, Fujimoto JG (1995) Quantification of nerve fiber layer thickness in normal and glaucomatous eyes using optical coherence tomography. Arch Ophthalmol 113(5):586–596

    CAS  PubMed  Google Scholar 

  25. Sivakumaran P, Harrison AC, Marschner J, Martin P (1998) Ocular toxicity from ethambutol: a review of four cases and recommended precautions. NZ Med J 111:428–430; Review

    CAS  Google Scholar 

  26. Smith LJ (1987) Should ethambutol be barred? J Clin Neuro-Ophthalmol 7:84–86

    Google Scholar 

  27. Tweten S, Wall M, Schwartz BD (1990) A comparison of three clinical methods of spatial contrast sensitivity testing in normal subjects. Graefes Arch Clin Exp Ophthalmol 228:24–27

    CAS  Google Scholar 

  28. Varma R, Bazzaz S, Lai M (2003) Optical tomography-measured retinal nerve fiber layer thickness in normal Latinos. Invest Ophthalmol Vis Sci 44(8):3369–3373

    Article  Google Scholar 

  29. Weinreb RN, Shakiba S, Sample PA, Shahrokni S, van Horn S, Garden VS, Asawaphureekorn S, Zangwill L (1995) Association between quantitative nerve fiber layer measurement and visual field loss in glaucoma. Am J Ophthalmol 120(6):732–738

    CAS  PubMed  Google Scholar 

  30. Weinreb RN, Zangwill L, Berry CC, Bathija R, Sample PA (1998) Detection of glaucoma with scanning laser polarimetry. Arch Ophthalmol 116(12):1583–1589

    CAS  PubMed  Google Scholar 

  31. Zangwill LM, Bowd C, Berry CC, Williams J, Blumenthal EZ, Sanchez-Galeana CA, Vasile C, Weinreb RN (2001) Discriminating between normal and glaucomatous eyes using the Heidelberg retina tomograph, GDx nerve fiber analyzer, and optical coherence tomograph. Arch Ophthalmol 119(7):985–993

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We wish to thank Research to Prevent Blindness (RPB) Foundation for their constant support for DEI/USC studies.

Author information

Authors and Affiliations

  1. Doheny Eye Institute and the Department of Ophthalmology, Keck School of Medicine, University of Southern California, 1355 San Pablo St, DVRC 311, Los Angeles, CA, 90033, USA

    Christopher I. Zoumalan, Madhu Agarwal & Alfredo A. Sadun

Authors
  1. Christopher I. Zoumalan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Madhu Agarwal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alfredo A. Sadun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christopher I. Zoumalan.

Additional information

The authors have no relevant financial interest in this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zoumalan, C.I., Agarwal, M. & Sadun, A.A. Optical coherence tomography can measure axonal loss in patients with ethambutol-induced optic neuropathy. Graefe's Arch Clin Exp Ophthalmol 243, 410–416 (2005). https://doi.org/10.1007/s00417-004-1053-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-004-1053-1

Keywords

Search

Navigation