1- The color vision testing was modified to include D15 Hue Test de-saturated as a primary test and the 28 Hue Test as a secondary test to increase the sensitivity of the testing in order to detect the more subtle changes in color vision that may be characteristic of linezolid-related optic neuropathy. 2- The Humphrey Visual Fields Test was added as a primary eye test to include the test of fovea sensitivity to better detect early signs of optic neuropathy. 3- The neurological examination requirements were updated to enable confirmation of peripheral neuropathy to be assessed by either a neurologist’s examination or a laboratory study (such as a nerve conduction study). 4- Additional instruction was included on how to follow-up on significant abnormalities (optic or peripheral neuropathy) noted during the study that had not resolved or stabilized either by the End of Study (EOS) visit and/or after 6 months of follow-up testing.

1- Plasma lactate was included as a required laboratory test for all study visits rather than designated as a secondary test to be run only if the bicarbonate was determined to be less than the lower limit of normal. This was done to ensure that laboratory findings suggestive of lactic acidosis were detected as soon as possible. 2- Vitamin B6 testing was added for all study visits in the treated and control groups as an indicator for potential underlying causes of neuropathy. 3- Glycosylated hemoglobin (HbA1c) testing was added at Baseline in the treated and control groups as an indicator for the risk of progression of diabetic complications, including diabetic neuropathy. 4- Hepatitis C serology was added at Baseline in the treated and control groups as an indicator for potential underlying causes of neuropathy. 5- The primary ophthalmologic examination for the treated and control groups at all visits was modified to include Intraocular pressure (IOP) and test for relative afferent pupillary defect. 6- The stereo optic nerve head photograph was added as a primary ophthalmologic test at Baseline to increase the likelihood of prospectively identifying optic nerve toxicity.

1- Optical Coherence Tomography -3 (OCT-3) test moved from ‘Secondary Ophthalmologic Testing’ to ‘Ophthalmologic Examination’. 2- ‘To evaluate newer research ophthalmologic testing in the assessment of optic neuropathy’ deleted from Study objectives. 3- Adverse events reporting, including suspected serious unexpected adverse reactions, were carried out in accordance with applicable local regulations. 4- Added Phosphorylated neurofilament, heavy subunit (PNF-H) to be collected if subject’s primary ophthalmologic testing was consistent with optic neuropathy.

1-The addition of pregnancy tests for safety and for enhanced monitoring of women of child bearing potential. 2- Birth control and pregnancy information were added in lifestyle guidelines for the safety of subjects. 3- Inclusion criteria changed to allow subjects receiving linezolid 600 mg BID for a minimum of 6 weeks. Previously, inclusion criteria allowed subjects who had received a minimum of 60 days of linezolid 600 mg BID to be eligible.