Abstract
Tuberculosis
(TB) remains a major public health concern in India, and ethambutol is a key
component of first-line anti-tubercular therapy. Although generally well
tolerated, ethambutol can cause rare but serious adverse effects such as optic
neuritis, which may result in reversible or irreversible vision loss. We report
a case of a 54-year-old female with presumed tubercular meningitis who
developed optic neuritis after two months of ethambutol therapy. This case is
collected from medicine department Christian Medical College Ludhiana under
pharmacovigilance elective under the pharmacology department. The Naranjo
Adverse Drug Reaction Probability Scale yielded a score of 5, indicating a
probable link between ethambutol and the adverse event. Early recognition and
prompt withdrawal of the offending drug are crucial to prevent long-term visual
impairment. This case highlights the importance of regular ocular monitoring
during ethambutol therapy and the need for heightened awareness among
clinicians regarding its potential ocular toxicity, even when used within
therapeutic doses.
Keywords: Optic neuritis, Ethambutol, Tuberculosis, Adverse drug reaction
1. Introduction
India
being a developing nation, has a high rate of tuberculosis (TB). It is a
serious worldwide health concern and a contagious disease. The causative agent
for TB is mycobacterium tuberculosis1.
A severe kind of extrapulmonary tubercular infection of the meninges is called
tubercular meningitis (TBM). Usually,
the illness manifests as subacute fever, headache, vomiting, altered mental
status, and meningeal irritation symptoms. Non-specific symptoms and the low
sensitivity of traditional diagnostic methods make early diagnosis difficult.
The standard treatment for TB is an ATT (anti-tuberculosis treatment) regimen,
which uses first-line Anti-TB medications such as Isoniazid, Ethambutol,
Pyrazinamide, Rifampicin and Streptomycin2.
Ethambutol
is a first-line chemotherapeutic agent used along with isoniazid, rifampicin,
and pyrazinamide, for pulmonary TB3. It is part of combined therapy to prevent
development of drug resistance and improve treatment outcomes by supplementing
the bactericidal actions of the other drugs4.
Ethambutol
is a bacteriostatic drug that inhibits the arabinogalactan biosynthesis. It
attaches to protein EMBB to impede arabinose molecules polymerization into
arabinogalactan, making the cell wall weaker so Mycobacterium tuberculosis
could be vulnerable to damage and replication inhibition. It inhibits the
growth of the bacteria rather than killing them directly, allowing the immune
system to play its role in clearing the infection and also when it is used with
other anti-TB drugs4. As
Ethambutol can easily penetrate the CSF (Cerebro Spinal Fluid) there is
enhanced efficacy of ethambutol in TBM to treat meningeal TB5. The common Adverse Drug
Reactions (ADRS) associated with ethambutol are rash, pruritis, joint pain,
optic neuritis, gastrointestinal (GI) upset, malaise, headache, dizziness,
mental confusion, disorientation vision loss, and visual field defect6. A serious and uncommon
adverse effect of ethambutol is optic neuritis, which is either dose or
duration related and results in cecocentral scotomas in the visual field as
well as gradual painless vision loss. Ethambutol-induced optic
neuritis can result in loss of red-green colour discrimination, decreased
visual acuity, and visual field defects7. According to the Vigi Access database, only
749 cases of optic neuritis have been reported out of a total of 47,000
documented adverse drug reactions with Ethambutol8. Since optic neuritis is a
preventable ADR, increasing awareness is essential for early detection and
effective management. Therefore, this case merits reporting.
2. Case Report
A 54-year-old
female, known case of Diabetes Mellitus, presented to the emergency department
with a history of low-grade fever for two months, along with generalized
weakness, reduced appetite, and significant weight loss over the preceding 15-20
days. She also reported experiencing dizziness for two days prior to admission.
Given the constitutional symptoms, an HRCT (High Resolution Computed
Topography) chest was performed, which revealed multiple small pulmonary
nodules. Based on clinical suspicion and radiological findings suggestive of a
tubercular aetiology, she was empirically started on ATT on 1st
November 2024, including tablet Levofloxacin, tablet Ethambutol, and injectable
Streptomycin, considering a presumptive diagnosis of Tubercular Meningitis.
After approximately two months of treatment, she began experiencing visual
disturbances in the form of blurring of vision and pain around the eyes.
Concerned about these symptoms, an ophthalmological evaluation was conducted.
Detailed examination revealed findings consistent with optic nerve involvement.
By 6th March 2025, a diagnosis of ethambutol-induced optic neuritis was
confirmed. Ethambutol was subsequently discontinued, and appropriate management
for optic neuritis was initiated. On withdrawal of the suspect product, the
optic neuritis was recovering. Rest of the drugs were continued as per
schedule.
The Naranjo
Adverse Drug Reaction Probability Scale yielded a score of 5, suggesting a
probable link between ethambutol and the observed adverse event. This scale is
a validated, structured tool used to assess the likelihood that a specific drug
caused an adverse reaction. It consists of 10 questions, each assigned a score
of -1, 0, +1, or +2 based on the answers: “Yes,” “No,” or “Do not know.” The
total score helps categorize the causality as: definite (≥9), probable (5-8), possible (1-4), or doubtful (≤0). Overall scores can range from -4 to +13,
reflecting the strength of the evidence supporting drug-related causation9.
3. Discussion
World Health Organization
(WHO) defines adverse ADR as “a response to a medication that is noxious and
unintended and occurs at doses normally used in man10.” ADRs put a lot
of stress on healthcare systems since they lead to more hospital stays, longer
hospital stays, and higher treatment expenses. They also put a load on
healthcare resources by requiring more tests, monitoring, and treatments to
deal with drug-related harm that could have been avoided11. Optic neuritis
is defined as an inflammation of the optic nerve12. The probability of ethambutol
induced optic neuritis is higher with greater doses and longer use of
ethambutol. The occurrence is less than 1% of patients receiving a daily dose
of 15 mg/kg, 15% of patients taking 50 mg/kg daily and 5% of patients receiving
25 mg/kg daily7.
Though suggestions have been
proposed, the exact mechanism by which ethambutol induces optic neuritis is
unknown. Ethambutol and its metabolites have the ability to chelate zinc, which
disrupts retinal homeostasis, according to one such notion. Optic neuritis
caused by ethambutol is reversible after discontinuation of medication, however
recovery is time-consuming7. Even after discontinuing ethambutol, some
patients' colour vision does not improve. Although there is currently little
evidence, corticosteroids such as oral prednisone, zinc, and vitamin B
complexes are occasionally used as part of management. Early detection during
treatment requires careful ocular surveillance. In some circumstances,
desensitisation procedures including a gradual reintroduction of ethambutol
have been investigated in an effort to minimise ocular damage while maintaining
anti-tubercular efficacy13.
Considering how common
ethambutol is used to treat TB worldwide, documenting occurrences of optic
neuritis will help to strike a balance between minimising vision-threatening
side effects and providing effective TB treatment, thereby preserving patient quality
of life5. ADRs are known
to not only add to the overall disease burden but also significantly impair a
patient’s quality of life. Therefore, this case warrants documentation and
reporting14.
4. Conclusion
Ethambutol-induced optic neuritis,
though uncommon, is a serious and potentially reversible adverse drug reaction
that requires early recognition and intervention. Regular ophthalmic monitoring
during ethambutol therapy is essential, especially in high-risk patients.
Timely discontinuation of the drug can prevent permanent visual impairment.
This case underscores the need for vigilance among healthcare providers to
ensure patient safety while maintaining the efficacy of anti-tubercular
treatment.
5. References
8.
VigiAccess. World
Health Organisation; 2015.
12.
Kraker
JA, Chen JJ. An update on optic neuritis. J Neurol, 2023;270: 5113-5126.
13.
Dahiya M, Rathi M, Dua M, et al. Ethambutol-induced optic
neuropathy: a remerging ocular emergency needing strict vigilance and
screening. Indian J Clin Exp Ophthalmol, 2025;11: 545-548.
14.
Kaur J, Joseph G, Kaur P, et al. Ichthammol-induced
maculopapular rash and itching in a paediatric patient. NJPT, 2024;2: 162-164.