Antibiotics with Ocular Toxicity

The recent discussion whether fluoroquinolones (FQ) cause retinal detachment was short-lived and soon put to rest.   The issue was raised by 2 observational studies but no signal was seen in a larger and better designed  Danish study.  So it seems the association is probably spurious [i].smiley-150838_640

At first blush such an association is quite possible and imaginable:  First, there is the well-known ocular toxicity of chloroquine which has structural similarities to the quinolone nucleus.  Likewise, the fact that FQs have a high affinity to pigmented tissues in the retina and elsewhere makes this a reasonable connection and possible concern.

But as so often is the case, not all theoretical concerns are real; we now have some 30 years of experience with quinolones and if an adverse event has escaped us in all these years, it is likely to be a very rare bird.

Nonetheless, this serves as a reminder to review the list of antibiotics with known toxic effects on the eye.

DrugOcular SymptomsIndicationMoAComments
EthambutolOptic neuritis, visual field defects, color vision changesM. tuberculosisaffinity to pigmented epithelia; chelation of copper?Irreversible; dose-dependent; color vision changes after 2-8 mo of Rx; risk = dose-related
LinezolidOptic neuritisGram-positive antibacterialdisruption of mitochondrial function?After prolonged administration only; partially reversible
INH / isoniazidOptic neuritisM. tuberculosisvitamin B6 deficiency?Reversible; pyridoxine (vitamin B6)may be beneficial
ChloroquineRetinal toxicity; corneal depositsmalaria, rheumatoid arthritisbinding to melanin in pigmented retinal cellsMore problematic with long-term use like for RA; chloroquine has higher risk than hydroxychloroquine; usually irreversible;
VoriconazoleAbnormal vision, chromatopsia, photophobia, visual hallucinations, optic neuritis , papilledemaantifungalunknownAbnormal vision very common (19%), reversible after drug discontinuation
MinocyclinePapilledemaacneincreased intracranial pressure‘pseudotumor cerebri’ usually reversible
Rifampin / RifampicinYellow discoloration of tears, anterior uveitisM. tuberculosisdrug has intensely red colorMore a nuisance than a toxicity
CidofovirUveitis, hypotonyCMVunknownIritis can be treated with steroids + cycloplegic medx
SulfonamidesMyopic shiftbroad-spectrum antibacterial
AmantadineCorneal edemainfluenza A / Parkinson’sunknown; lower endothelial cell density?Reversible after discontinuation
TetracyclinesOptic neuropathybroad-spectrum antibacterialincreased intracranial pressure‘Pseudotumor cerebri’ usually reversible
InterferonsDecrease or loss of vision, retinopathy including macular edema, retinal artery or vein thrombosis, retinal hemorrhages and cotton wool spots, optic neuritis, papilledema and serous retinal detachmentHCVunknown / ischemiaInterferon associated Retinopathy in 19% to 69% of adults; in most cases reversible
ClofazamineBull’s eye maculopathyleprosy

NOTES:

  • Voriconazole is a drug very often associated with visual complaints.  It is prudent to inform patients about this before the 1st dose.
  • Linezolid (LZD) is often prescribed for > 14 days, e.g. in cases of vertebral osteomyelitis when surgery and other antibiotics are not an option.  The long-term safety of LZD is less well known but bone marrow toxicity, neuropathy and optic neuritis should be monitored.  Therapeutic Drug Monitoring (TDM) may be useful to reduce the risk of adverse events.
  • With ethambutol administration, ophthalmologic exams at baseline and during Rx are mandatory

General References:

Wren. Journal of Behavioral Optometry  Volume 11/2000/Number 6/Page 149
Zegans  Clinical Ocular Toxicology: Drugs, Chemicals, and Herbs


Reference:

[i] Uptodate.  http://www.uptodate.com/contents/fluoroquinolones?source=see_link&anchor=H142842158#H142842158

Print Friendly, PDF & Email

One Reply to “Antibiotics with Ocular Toxicity”

  1. Good summary and overview – thanks! I totally agree with your assessment of voriconazole: ocular side effects are to be reckoned with.
    Keep up the good work!

Leave a Reply

Your email address will not be published. Required fields are marked *