After discontinuing Ethambutol and following patients for an average of 11 months, the overall mean visual acuity improved from severe impairment to moderate impairment.
Published Aug 04, 2025 | 7:00 AM ⚊ Updated Aug 04, 2025 | 7:00 AM
The research covered 107 patients who had developed Ethambutol-induced Toxic Optic Neuropathy, a condition in which the optic nerve is damaged. (Representational Image/Creative Commons)
Synopsis: India’s TB burden is the highest in the world, accounting for 26 percent of cases worldwide. To improve adherence, the country’s National TB Elimination Programme moved to fixed-dose combinations in 2017, modifying the Ethambutol regimen by extending its use from two to six months and increasing frequency from three times per week to daily. And it is now a matter of concern.
A study has revealed that a widely used tuberculosis (TB) drug, Ethambutol, can cause significant—sometimes permanent—vision loss in patients, especially those who are older or on higher doses.
The research highlighted a growing public health concern as India battles the world’s highest TB burden while inadvertently creating new medical complications through well-intentioned policy changes.
The study, published in the Indian Journal of Ophthalmology, was conducted by Drs. Jenil Sheth, Virender Sachdeva, and colleagues at the Hyderabad-based LV Prasad Eye Institute (LVPEI) between 2019 and 2021.
This comprehensive research covered 107 patients (214 eyes) who had developed Ethambutol-induced Toxic Optic Neuropathy (ETON), a condition in which the optic nerve—essentially the body’s cable transmitting visual signals from the eye to the brain—is damaged.
Ethambutol interferes with the mitochondrial function of retinal ganglion cells and optic nerve axons by binding to essential copper and zinc ions, causing cellular disruption that damages the optic nerve and leads to progressive vision loss.
It is like pouring a corrosive chemical over a data cable. The message may still go through at first, but over time, the signal weakens—and eventually, it may stop altogether.
The study’s demographics revealed that most patients (69 percent) were men, and 58 percent were middle-aged (36-55 years). On average, patients took ethambutol for seven months at a dose of 1,042 mg/day.
All patients suffered profound vision loss in both eyes, with most having been taking the drug for more than six months. Over 80 percent had profound vision loss when they first came in, meaning they could barely see large letters on an eye chart. The mean visual acuity at presentation was severe (1.2 LogMAR), indicating substantial visual impairment across the patient population.
The research revealed alarming patterns in how Ethambutol affects different patient populations.
“Ethambutol dosage and duration were identified as significant risk factors for both the occurrence and severity of visual loss,” the researchers said. This finding underscored the critical relationship between drug exposure and visual damage, with prolonged use creating cumulative harm to the optic nerve.
Older patients faced the most severe consequences. Those above 60 not only presented with the poorest vision (1.3 LogMAR visual acuity) but also showed the least improvement over time.
This age-related vulnerability suggested that elderly patients’ optic nerves may be less resilient to ethambutol’s toxic effects or have reduced capacity for recovery.
The study also demonstrated a clear dose-response relationship. The best corrected visual acuity at presentation was significantly worse in patients taking higher doses of ethambutol—16 mg/kg or more—compared to those taking lower doses. This finding provided crucial evidence for dose-dependent toxicity that could inform future prescribing guidelines.
Physical examination findings were equally concerning. Temporal or diffuse optic disc pallor, a clear indication of optic nerve damage, was observed in 78 percent of patients.
Over half (58 percent) of the patients had some form of peripheral vision loss, including advanced field loss or temporal field defects, while the remaining 42 percent suffered from reduced central vision with central scotomas. These diverse manifestations highlighted how Ethambutol can affect different parts of the visual system.
While the damage caused by Ethambutol can be devastating, the study offered some hope, but only under specific circumstances. Stopping Ethambutol in time can help vision bounce back, as the researchers noted: “ETON may be partially reversible, especially with early drug discontinuation.”
After discontinuing Ethambutol and following patients for an average of 11 months, the overall mean visual acuity improved from severe impairment (1.2 LogMAR) to moderate impairment (0.8 LogMAR). Importantly, 56 percent of patients improved by at least two lines on the vision chart, representing clinically meaningful visual recovery.
However, recovery patterns revealed stark disparities across age groups. The study found that patients over 60 years showed no improvement and continued to have severe vision impairment with a final median visual acuity of 1.2 LogMAR. In contrast, those aged 40-60 years and patients under 40 years showed significant improvement, suggesting that younger patients retained greater capacity for optic nerve recovery.
Perhaps most surprisingly, neither the dose nor the patient’s age was the primary determinant of recovery success. Instead, the researchers discovered that “the only significant predictor was the mean VA at presentation, which showed a strong correlation with the final visual outcome.”
In simple terms: if you start worse, you’re more likely to end up worse. This finding emphasised the critical importance of early recognition and intervention before severe damage occurs.
India’s TB burden is the highest in the world, accounting for 26 percent of cases worldwide. To improve adherence, the country’s National TB Elimination Programme (NTEP) moved to fixed-dose combinations in 2017, modifying the Ethambutol regimen by extending its use from two to six months and increasing frequency from three times per week to daily.
However, the study warned that “the shift toward fixed-dose combination therapy has unintentionally increased both the prevalence and severity of ethambutol-induced optic neuropathy.” A recent study from LVPEI showed that NTEP’s revised Ethambutol regimen resulted in a sixfold increase in the number of ETON cases in just three years.
The team used advanced imaging—like OCT scans—to look at nerve layers in the retina, finding that the macular ganglion cell layer (mGCL) was notably thinner in patients affected by ETON. This thinning could serve as an early red flag, even before major symptoms appear.
The study strongly recommended that doctors monitor visual health early and often in TB patients on Ethambutol.
“Ethambutol-induced optic neuropathy has become more common and can lead to severe vision loss, especially in the elderly, those with a thin build, and those with renal dysfunction. Careful monitoring and early discontinuation of the drug are essential to prevent vision loss,” Dr Virender Sachdeva, the corresponding author, stated.
Warning signs
If symptoms like blurry vision, colour blindness, or dark spots emerge, the drug should be stopped immediately. “Early screening and prompt drug discontinuation remain essential for preventing severe vision loss,” the researchers emphasised.
(Edited by Majnu Babu).
