Eye, tuberculosis and antituberculosis drugs
Tuberculosis is a bacterial infection caused by Mycobacterium tuberculosis (Koch's bacillus) that attacks the lungs and sometimes the nervous system and eyes. In case of infection, a strong and prolonged course of antibiotics is necessary. Unfortunately, the drugs used can be toxic to the retina and optic nerve. Therefore, every patient with tuberculosis undergoes dual monitoring: screening for eye involvement and monitoring of treatment toxicity.
Tuberculosis and its treatment
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Tuberculosis is a contagious disease that mainly affects the lungs, but also the lymph nodes, bones, kidneys, adrenal glands, or heart.
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It is estimated that 2 billion people worldwide are infected, with a high prevalence in Africa and Asia.
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Known since at least antiquity, this disease has always been one of the leading causes of death worldwide. It was only at the end of the 19th century that it was formally identified, with the discovery of the bacterium responsible: Mycobacterium Tuberculosis.
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In the absence of treatment until the 1940s, infected patients were isolated in sanatoriums to rest and "calm the disease".
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The main antibiotics effective against tuberculosis (antituberculosis drugs) still used today were discovered between the 1940s and 1980s.
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Of the twenty or so known antituberculosis drugs, two have potentially toxic side effects on the optic nerve: Ethambutol and Isoniazid.
Ocular manifestations of tuberculosis
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In cases of prolonged tuberculosis infection, the disease can attack the central nervous system and the eyes. This results in inflammatory eye conditions known as uveitis .
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Uveitis can present either abruptly with the characteristic triad of redness, pain, and decreased vision; this is known as anterior uveitis. More insidiously, the retina can become inflamed, resulting in a simple decrease in vision without pain; this is known as posterior uveitis or retinitis.
Vaccine and ocular tuberculosis
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The tuberculosis vaccine (BCG) is a live attenuated vaccine. This means that an extremely weakened form of the bacteria is inoculated in order to train the immune system to resist attack by the form present in the environment.
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The vaccine does not prevent infection but significantly reduces its virulence, as do vaccines against COVID-19. BCG has demonstrated its effectiveness in reducing severe tuberculosis, particularly eye infections.
The main anti-tuberculosis drugs
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The first-line anti-tuberculosis antibiotics used are: Isoniazid (INH), Rifampicin (RMP), Pyrazinamide (PZA) and Ethambutol (EMB).
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The usual treatment consists of triple therapy (INH + RMP + PZA) or quadruple therapy (INH + RMP + PZA + EMB), depending on the bacteria's ability to resist antibiotics.
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The recommended dose for Isoniazid is 5 mg/kg/day and for Ethambutol is 15 mg/kg/day. The duration of treatment varies between 6 and 18 months depending on the organs affected.
Side effects on the optic nerve
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These conditions consist of acute bilateral optic neuropathy (optic neuritis), characterized by impaired color vision and a more or less pronounced decrease in visual acuity. The optic nerve is most often affected in its portion located at the back of the eye, hence the term retrobulbar optic neuritis (RON).
Ethambutol and eye
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Ethambutol is more specifically toxic to the optic nerve: it mainly causes retrobulbar optic neuropathy (NORB), but has also been implicated in cases of retinopathy.
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Its toxicity is also dose dependent, since the risk of NORB is very low below 15 mg/kg/day, while it is estimated at 3% for 25 mg/kg/day, and 10% for 45 mg/kg/day.
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Other factors that increase this risk are: association with isoniazid, zinc deficiency, chronic alcoholism, renal insufficiency and a treatment duration of more than 2 months.
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Visual disturbances can occur at any time, generally after the first month of treatment and up to 30 days after its completion. Ethambutol-induced optic neuritis is reversible within 3 to 12 months if diagnosed and treated early.
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Otherwise, optic nerve atrophy occurs, which manifests as a permanent decrease in visual acuity.
Isoniazid and the eye
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The neurological toxicity of isoniazid affects both the peripheral nerves and the optic nerve, which are often affected at the same time, resulting in a picture of polyneuropathy.
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These side effects affect approximately 2% of treated patients. They are dose-dependent, as this risk increases above 10 mg/kg/day.
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Other factors that increase this risk include malnutrition, concomitant use of ethambutol, and zinc deficiency. Visual impairment generally occurs after 2 to 6 weeks of treatment and may be reversible if diagnosed and treated early.
Ophthalmic monitoring and screening for complications
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Rigorous ophthalmological monitoring is required in case of treatment with Isoniazid and/or Ethambutol.
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A pre-treatment assessment must be performed before starting treatment to check for any pre-existing optic neuropathy that could contraindicate treatment: visual acuity, fundus examination, color vision, and visual field testing. This assessment should be repeated at 1 month and then at 2 months of treatment.
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From the third month onwards, follow-up appointments remain monthly while the patient is taking ethambutol. If isoniazid is continued without ethambutol, the schedule changes to every two months.
What to do in case of toxic optic neuropathy?
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The symptoms of optic neuropathy are usually perceived by the patient. Otherwise, the condition is detected during an ophthalmological examination by: a decrease in visual acuity, an abnormality of the optic nerve in the fundus of the eye, an abnormality in the color vision test, or a bilateral central or cecocentral scotoma in the visual field.
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If one or more of these symptoms occur, ethambutol must be stopped immediately. Regarding isoniazid, a discussion should take place among specialists to determine the best strategy: reducing the dose and/or introducing another antibiotic. In all cases, vitamin B6 supplementation should be prescribed for the patient.
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It is also advisable to eliminate all substances with potential toxicity to the optic nerve (tobacco, alcohol, other neurotoxic drugs).
Frequently Asked Questions
How often should one consult an ophthalmologist in the case of antituberculosis treatment?
Monitoring of anti-tuberculosis treatments requires a consultation BEFORE starting treatment, then monthly until Ethambutol is stopped. Once stopped, follow-up appointments are every 2 months.
What tests are performed for monitoring during antituberculosis treatment?
Follow-up examinations include visual acuity, color vision, visual field, and OCT.