Histological Grading of Ethambutol Induced Optic Toxicity in Rabbits

BACKGROUND: Ethambutol is one of the first line anti tuberculous drug. Its toxicity is low with no evidence of teratogenecity. Optic toxicity is one of its major side effects which is dose and duration dependant. Etambutol causes both bulbar and retrobulbar neuritis, latter being more common ,which manifests as painless, subacute, symmetrical, progressive visual loss, reduced visual acuity, scotomas and dyschromatopsia. OBJECTIVES: To study and grade the dose and time related ethambutol induced toxic histological changes in optic nerves of rabbits. MATERIAL & METHODS: This experimental study was conducted on 24 rabbits of either sex weighing 1.5- 2.5 kg. Rabbits were randomly divided in to four groups comprising six animals in each group. Group A served as control (no drug given),while Group B,C and D were given ethambutol in doses of 35, 50 and 100 mg/kg/day. Three animals from each group were sacrificed at 6 and 12 weeks and their both optic nerves were taken out and subjected to histopathological examination. The histological changes were recorded and graded according to rating scale and analysed with SPSS version 17 to see the dose and time related ethambutol induced optic neuritis. Statistical analysis was done using SPSS version 17. Paired “t” test was applied to compute the differences in histological changes between various groups. The differences were statistically significant (P <0.05). RESULTS: The histological findings showed that optic nerves of group A were quite normal. At 6 weeks the histological changes at Ethambutol doses of 35, 50,100mg/kg/day were 3.17± 753, 4.00±.894 and 5.33±.816 respectively. At twelve weeks the histological changes at Ethambutol doses of 35, 50,100 mg/kg/day were 4.00±.894, 5.00±.00 and 7.00±00 respectively. Ethambutol toxicity did not increase significantly at 6 weeks versus 12 weeks with 35mg/kg/day (P value 0.185). Ethambutol toxicity increased with 50mg/kg/day at 6 weeks versus 12 weeks (P value 0.041). While Ethambutol toxicity also significantly increased with 100mg/kg/day at 6 weeks versus 12 weeks (P value 0.004). CONCLUSION: Our study confirmed that ethambutol induced optic toxicity is both dose and duration dependent in rabbits, which were graded on the basis of histological changes.