A 32-year-old woman from rural Maharashtra presents with a 3-month history of productive cough, fever, and weight loss. Chest X-ray shows bilateral upper lobe infiltrates with cavitation. Sputum smear microscopy is positive for acid-fast bacilli. She is started on standard first-line antitubercular therapy (RIPE: rifampicin, isoniazid, pyrazinamide, ethambutol) for 2 months. At the end of the intensive phase, she complains of sudden onset painless loss of vision in the left eye with colour vision defect (red-green). Visual acuity is 6/36 in the left eye. Fundoscopy shows optic disc hyperaemia and retinal oedema. What is the most likely causative drug and what is the recommended action?

Explanation

## Ethambutol-Induced Optic Neuritis **Key Point:** Ethambutol is the most common cause of optic neuritis among first-line antitubercular drugs, presenting with painless loss of vision, colour blindness (red-green), and optic disc changes. ### Clinical Features of Ethambutol Toxicity | Feature | Details | |---------|----------| | **Onset** | Usually after 2–6 months of therapy | | **Vision loss** | Painless, progressive, often unilateral initially | | **Colour vision** | Red-green colour blindness (pathognomonic) | | **Fundoscopy** | Optic disc hyperaemia, retinal oedema, temporal pallor | | **Reversibility** | Partially reversible if caught early; permanent if delayed | ### Mechanism Ethambutol inhibits arabinosyl transferase, disrupting mycobacterial cell wall synthesis. It accumulates in the optic nerve, causing demyelination and axonal degeneration, particularly affecting the papillomacular bundle. ### Risk Factors for Ethambutol Toxicity - High dose (>25 mg/kg/day) - Renal impairment (reduced clearance) - Prolonged duration of therapy - Pre-existing optic nerve disease - Diabetes mellitus ### Management of Ethambutol Optic Neuritis **High-Yield:** Ethambutol MUST be discontinued immediately upon suspicion of optic neuritis. Delay in cessation leads to irreversible blindness. 1. **Immediate action:** Stop ethambutol 2. **Alternative regimen:** Continue rifampicin, isoniazid, and pyrazinamide for the intensive phase 3. **Ophthalmology review:** Urgent assessment to confirm diagnosis and rule out other causes 4. **Monitoring:** Serial visual acuity and colour vision testing 5. **Continuation phase:** Proceed with rifampicin and isoniazid (± fluoroquinolone if needed) ### Prevention **Clinical Pearl:** Baseline colour vision testing (Ishihara chart) and visual acuity assessment should be performed before starting ethambutol. Monthly monitoring is recommended, especially in high-risk patients. **Mnemonic for first-line antitubercular drug toxicities — RIPE Toxins:** - **R** (Rifampicin): Hepatotoxicity, drug interactions, orange discolouration - **I** (Isoniazid): Peripheral neuropathy, hepatotoxicity, lupus-like syndrome - **P** (Pyrazinamide): Hyperuricaemia, hepatotoxicity, arthralgias - **E** (Ethambutol): **Optic neuritis** (red-green colour blindness) [cite:KD Tripathi 8e Ch 47] ## Why the Correct Answer is Correct The clinical presentation of painless vision loss with red-green colour blindness and optic disc changes in a patient on ethambutol is pathognomonic for ethambutol-induced optic neuritis. Immediate discontinuation is the standard of care to prevent irreversible blindness.