Home Print this page Email this page Users Online: 150
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
BRIEF COMMUNICATION
Year : 2017  |  Volume : 5  |  Issue : 1  |  Page : 40-42

Isolated reversible toxic optic neuropathy secondary to linezolid


Department of Ophthalmology, Rambam Health Care Campus, Haifa, Israel

Date of Submission14-Apr-2015
Date of Acceptance19-Jan-2016
Date of Web Publication6-Dec-2016

Correspondence Address:
Michael Mimouni
Department of Ophthalmology, Rambam Health Care Campus, Haifa
Israel
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2320-3897.195309

Rights and Permissions
  Abstract 

A 67-year-old male diagnosed with methicillin-resistant Staphylococcus aureus-induced osteomyelitis was started on second-line antibiotic therapy (linezolid). One year following initiation of treatment, he presented to the emergency room with bilateral painless acute deterioration in vision. Visual field testing suggested bilateral optic neuropathy. Following cessation of linezolid visual acuity and visual fields reverted to normal. A handful of case reports has described reversible optic neuropathy occurring shortly after initialization of linezolid treatment. This is, to the best of our knowledge, the first report of isolated delayed onset reversible optic neuropathy with concomitant use of linezolid unaccompanied by any other systemic toxic manifestations. Reversible optic neuropathy may occur in patients receiving long-term linezolid treatment. Ophthalmic follow-up including visual field testing in patients receiving long-term linezolid treatment may assist in early recognition.

Keywords: Linezolid, methicillin-resistant Staphylococcus aureus, optic neuropathy, osteomyelitis


How to cite this article:
Berkovitz L, Krasnitz I, Beiran I, Blumenthal EZ, Mimouni M. Isolated reversible toxic optic neuropathy secondary to linezolid. J Clin Ophthalmol Res 2017;5:40-2

How to cite this URL:
Berkovitz L, Krasnitz I, Beiran I, Blumenthal EZ, Mimouni M. Isolated reversible toxic optic neuropathy secondary to linezolid. J Clin Ophthalmol Res [serial online] 2017 [cited 2022 Jun 27];5:40-2. Available from: https://www.jcor.in/text.asp?2017/5/1/40/195309

In recent years, linezolid, a synthetic broad-spectrum oxazolidinone, gained popularity and is now considered an alternative to vancomycin for treating skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA). [1] S. aureus remains the predominant pathogen isolated in all forms and stages of osteomyelitis and strains are increasingly methicillin resistant. Linezolid is active against nearly all MRSA strains and is used to treat MRSA-induced osteomyelitis. [2] Despite its less than optimal safety profile, it has been successfully used as a long-term treatment for chronic S. aureus osteomyelitis. One study reported a cure rate of 80% with one-third of the patients demonstrating treatment-limiting toxicities. [3]

Acute optic neuropathy, in some cases reversible, has been previously described in patients treated with linezolid. [3],[4],[5] In one case, the reported neuropathy led to blindness. [5] We report a case of reversible optic neuropathy occurring after long-term use in a patient with osteomyelitis. The reversibility of the optic nerve involvement is well-demonstrated in the visual fields tests performed both before and after cessation of treatment.


  Case Report Top


A 67-year-old man was diagnosed with chronic osteomyelitis following fractures of thoracic vertebrae. He was initially treated with intravenous vancomycin until developing renal failure. Bacterial cultures from biopsies collected during surgical debridement were positive for MRSA. Systemic linezolid (600 mg twice daily) was initiated along with vitamin supplements.

One year after initiation of therapy, the patient presented to the emergency room with acute onset of painless bilateral deterioration of vision, right > left, starting 3 days before his admission. His best corrected visual acuity was 6/30 in the right eye and 6/8.5 in the left eye and denied complaints of dyschromatopsia in both eyes. He did not have any systemic symptoms suggestive of peripheral neuropathy.

On clinical examination, no pathological findings were noted, other than a small peripapillary dot hemorrhage, in an otherwise normal looking optic disc in the right eye. Pupils were round, central, equal in size and equally reactive to light. No relative afferent papillary defect was detected, and color vision was preserved in both eyes (tested via Ishihara plates) although the patient did mention that the colors seemed "faded." The brightness perception of the right eye was reduced compared with the left eye. Visual field testing performed on Humphrey automated field analyzer using full threshold 24-2 SITA-standard algorithm demonstrated - Right eye: A central scotoma 10° in the nasal, temporal, and upper aspect and 5° in the lower aspect of fixation in addition to a peripheral upper scotoma. Left eye: Loss of the upper half of visual field including the upper half of fixation [Figure 1].
Figure 1: Humphrey automated field analyzer using full threshold 24-2 SITA-standard algorithm. (a) Right eye: A central scotoma 10° in the nasal, temporal, and upper aspect and 5° in the lower aspect of fixation in addition to a peripheral upper scotoma. Left eye: loss of the upper half of visual field including the upper half of fixation. (b) Repeat visual field testing 2 months postdiscontinuation was within normal limits in both eyes showing full resolution of the previously documented visual field defects

Click here to view


Other possible causes of toxic optic neuropathy such as chronic or acute alcohol intoxication, history of tobacco, chloroquine, amiodarone, isoniazid, or methotrexate were ruled out, and the patient maintained a healthy diet. In view of previously reported cases of possible linezolid-related optic neuropathy, [3],[4],[5] in line with the 1 year treatment, linezolid was discontinued, and no substitute antibiotic was deemed necessary upon consulting and reassessing with an infectious disease specialist. One month following linezolid discontinuation, the patient's visual acuity improved to 6/8.5 and 6/6 in his right and left eyes, respectively, the peripapillary dot hemorrhage resolved and the fundus examination remained within normal limits. On follow-up examination, 2 months after drug discontinuation, the patient demonstrated 6/6 visual acuity in both eyes. Repeat visual field testing 2 months postdiscontinuation was within normal limits in both eyes showing full resolution of the previously documented visual field defects.


  Discussion Top


In the presented case, the patient developed isolated reversible toxic optic neuropathy secondary to linezolid. He did not demonstrate any other signs or symptoms associated with linezolid toxicity such as peripheral neuropathy, gastrointestinal complaints, anemia, or thrombocytopenia. [5]

Due to a paucity of effective antibiotics to treat multidrug-resistant strains of S. aureus, linezolid is being used as an alternative to vancomycin. In the presented case, the patient was switched to linezolid following vancomycin related renal failure. There are no randomized controlled clinical trials on the use of this drug for this indication nor are there are any large retrospective studies with regards to its safety and tolerability. [2] Sotgiu et al. reported a 13% rate of optic neuropathy in patients treated with linezolid. [5] They reported that the toxic effects were dose dependent and were observed more frequently with daily doses of more than 600 mg. [5]

In the presented case, the patient had been on linezolid for 1 year with a daily dose of 1200 mg before developing symptoms. This is consistent with a recent case series by Narita et al. in which the interval between initiation of linezolid therapy and onset of symptoms related to optic neuropathy ranged between 1 and 48 months with a median onset of 10 months. [6] Although the exact mechanism of its toxicity is uncertain, it has been postulated that it involves linezolid-induced mitochondrial damage. The optic nerve is highly dependent on mitochondrial function, which is compromised after cumulative amounts of linezolid have been reached. [3],[6] Although the patient presented with normal appearing optic discs, his visual acuity was severely affected, and visual field testing demonstrated defects typical of optic neuropathy. The only abnormal finding in his examination at presentation was a peripapillary dot hemorrhage that may have been a remnant of resolved optic disc edema. Upon cessation of linezolid both the decrease in visual acuity as well as the visual field defects resolved entirely. As this was the only identifiable factor modified in this patient's treatment, we believe that the complete resolution of his symptoms and findings are attributed to the cessation of linezolid.

A limitation of the presented case is that a more objective diagnostic examination in the form of a visual evoked potential test was not performed in this patient. In addition, it is hard to determine what the natural history of this patient would have been and whether or not additional factors may have been the cause of the resolution of his symptoms and signs.

In summary, the present case may suggest a need for baseline ophthalmic evaluation including visual field testing in patients commencing linezolid therapy. Patients receiving long-term linezolid therapy with higher doses maybe considered for periodic follow-up ophthalmic evaluations. Both physicians and patients should be aware of the possible symptoms and signs of linezolid-induced optic neuropathy as it may be reversible even after long periods of treatment as demonstrated in this case.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Fraimow HS. Systemic antimicrobial therapy in osteomyelitis. Semin Plast Surg 2009;23:90-9.  Back to cited text no. 1
    
2.
Senneville E, Legout L, Valette M, Yazdanpanah Y, Beltrand E, Caillaux M, et al. Effectiveness and tolerability of prolonged linezolid treatment for chronic osteomyelitis: A retrospective study. Clin Ther 2006;28:1155-63.  Back to cited text no. 2
    
3.
Agrawal R, Addison P, Saihan Z, Pefkianaki M, Pavesio C. Optic neuropathy secondary to linezolid for multidrug-resistant mycobacterial spinal tuberculosis. Ocul Immunol Inflamm 2015;23:90-2.  Back to cited text no. 3
    
4.
Azamfirei L, Copotoiu SM, Branzaniuc K, Szederjesi J, Copotoiu R, Berteanu C. Complete blindness after optic neuropathy induced by short-term linezolid treatment in a patient suffering from muscle dystrophy. Pharmacoepidemiol Drug Saf 2007;16:402-4.  Back to cited text no. 4
    
5.
Sotgiu G, Centis R, D'Ambrosio L, Alffenaar JW, Anger HA, Caminero JA, et al. Efficacy, safety and tolerability of linezolid containing regimens in treating MDR-TB and XDR-TB: Systematic review and meta-analysis. Eur Respir J 2012;40:1430-42.  Back to cited text no. 5
    
6.
Narita M, Tsuji BT, Yu VL. Linezolid-associated peripheral and optic neuropathy, lactic acidosis, and serotonin syndrome. Pharmacotherapy 2007;27:1189-97.  Back to cited text no. 6
    


    Figures

  [Figure 1]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Case Report
Discussion
References
Article Figures

 Article Access Statistics
    Viewed1752    
    Printed30    
    Emailed0    
    PDF Downloaded175    
    Comments [Add]    

Recommend this journal