Mutation characteristics of ethambutol resistance gene of Mycobacterium tuberculosis in Guangxi / 实用医学杂志

Objective To investigate the mutation characteristics and influencing factors of ethambutol(EMB)resistance gene of Mycobacterium tuberculosis in Guangxi Zhuang Autonomous region,and to provide evidence for molecular diagnosis and clinical treatment of tuberculosis.Methods A total of 655 strains of Myco-bacterium tuberculosis(52 ethambutol resistant strains and 603 ethambutol sensitive strains)were collected continuously from 30 TB drug resistance monitoring sites in Guangxi in 2018-2019,and the mutation characteristics and influencing factors of ethambutol resistant genes were analyzed by whole genome sequencing.Results Among 655 strains of Mycobacterium tuberculosis,54 strains had ethambutol drug resistance gene mutation,the mutation rate was 8.24%(54/655).Among 52 EMB-resistant strains detected by proportional method,21 had gene mutation,the mutation rate was 40.38%(21/52),and 33 of 603 EMB-sensitive strains had gene mutation,the mutation rate was 5.47%(33/603).The gene mutation rate in drug-resistant strains was higher than that in sensitive strains(χ2 = 77.133,P = 0.000).The coincidence rate of EMB drug resistance phenotype and gene mutation was 40.38%(21/52),and the results of the two tests were not highly consistent(Kappa = 0.343,P<0.001).The mutant genes of 54 strains were embA,embB and embC,and there were 20 mutant forms,among which 29 were mutated at unit point,accounting for 53.70%(29/54),and 25 were mutated at joint site,accounting for 46.30%(25/54).Among the unit point mutations,embB306(35.19%)had the highest mutation proportion,followed by embB497(5.56%)and embB406(3.70%).Among the joint site mutations,embC270+embB378 had the highest mutation proportion(22.22%),The second was embB306+embA-12(3.70%).Gender,anti-tuberculosis treatment history,genotype and MDR might be related to EMB gene mutation(χ2 = 9.388,P = 0.004;χ2 = 27.084,P = 0.000;χ2 = 6.671,P = 0.010;χ2 = 68.826,P = 0.000).Multivariate logistic regression analysis showed that male(OR = 6.150),retreatment(OR = 2.636)and multidrug resistance(OR = 7.333)may be risk factors for EMB resistance gene mutation,and Beijing genotype may be a protective factor for EMB resistance gene mutation(OR = 0.511).Conclusion EMB resistance of Mycobacterium tuberculosis is related to embA,embB and embC gene mutations,and the incidence of EMB resistance phenotype is not high.For male,retreatable,MDR-resistant,and non-Beijing genotype TB patients,attention should be paid to the mutation of the EMB resistance gene.

Visual outcomes of toxic optic neuropathy secondary to Ethambutol: A retrospective observational study from India, an endemic country

Purpose: Ethambutol (EMB) is one of the first?line drugs used for treating tuberculosis. Vision loss due to optic nerve toxicity is a well?known potential side effect of the drug. Our aim was to evaluate the clinical features and visual outcomes of patients with EMB optic neuropathy (EON). Methods: A retrospective, observational, single?center study of all patients who were diagnosed to have EON during January 2017–December 2019 was done. All these patients were screened in the Department of Neuro?ophthalmology at a referral tertiary eye care institution in India. Clinical features, visual outcomes, and neuroimaging findings of these patients were analyzed. Results: Two hundred and fifty?six eyes of 128 patients were included. Of these, 73 were male and 55 were female. Mean age was 50.55 ± 15 years. Mean visual acuity at presentation was 1.12 ± 0.45 logarithm of the minimum angle of resolution (logMAR). One hundred and forty three eyes had normal optic disk on presentation, 111 had disk pallor, and two eyes had disk edema. The most common field defect was central/paracentral scotoma (26.2%) followed by temporal defects (24.6%). Magnetic resonance imaging (MRI) brain and orbit showed optic nerve signals in 19.6% and chiasmal signals in 5.2%. At the final follow?up, a ?2?line vision improvement was noted in 161 eyes (62.9%), which was statistically significant. Conclusion: Multiple prognostic factors were analyzed to predict the visual recovery of EON. We observed that patients presenting with visual acuity worse than 6/60 had poor visual outcome and long duration of follow?up showed better visual recovery, proving the possibility of a gradual recovery pattern of EON. Interestingly, we found in our study that the chances of favorable visual outcome were directly proportionate to early diagnosis and cessation of EMB.

From Scylla to Charybdis: Fixed drug combinations for tuberculosis and increased ethambutol-induced optic neuropathy in India

Purpose: To describe the increase in prevalence of ethambutol-induced optic neuropathy (EON) in patients presenting to a single tertiary referral eye care center in India after introduction of weight-based fixed dose combinations and an increase in duration of ethambutol use from 2016 in the Revised National Tuberculosis Control Program. Methods: This was a retrospective, observational, referral hospital-based study of 156 patients with a diagnosis of EON presenting to a single tertiary referral eye care center between January 2016 and December 2019. The main outcome measure was to assess the increase in prevalence of EON cases presenting to our tertiary care institute. Results: During the 4-year study period, 156 new patients were diagnosed with EON. A total of 101 patients (64.7%) were males and 55 (35.3%) were females. The most common age group affected was 41–60 years. The significant complaint at presentation was decreased vision in all the patients. A rising trend in the number of patients diagnosed as EON was seen, with the prevalence increasing from 16 cases in 2016, 13 cases in 2017, and 31 cases in 2018 to 96 cases in 2019. Conclusion: The results of this study indicated an alarming increase in the trend of EON cases presenting to our tertiary care institute.

Ethambutol Effect on Retinal and Optic Nerve Structural Changes in Toxic Optic Neuropathy Case: A Literature Review

Introduction: Ethambutol (EMB) is one of the first-line antituberculosis drugs that reported to cause toxic effects on the eye structure. This study aims to elucidate the histological mechanism of retinal and optic nerve damage in toxic optic neuropathy cases.Reference Sources: The literature search was conducted in the PUBMED and MEDLINE databases using the latest publication of the 2012-2022 series.Studies Selection: The observational and randomized controlled trial studies analyzing the effect of ethambutol on retinal nerve fiber layer, retinal ganglion layer, inner cell plexiform layer thickness, optic nerve tissue, best-corrected visual acuity (BCVA), color perception, visual evoked response, and patients' visual field were included.Data Extraction Method: Articles that met the inclusion criteria underwent a specific evaluation, whereby the main focus was the ethambutol on retinal and optic nerve tissue.Results: The results showed that ethambutol affects the thinning of the Retinal Nerve Fiber Layer (RNFL), decreasing the amount of Ganglion Cells and changing the optic nerve's histological function by damaging the mitochondria and axonal fiber.Conclusion: It was concluded that ethambutol has adverse effects on retinal and optic nerve tissue due to several mechanisms and significantly affects the patient's visual outcome.

Ocular side effects in tuberculosis patients receiving direct observed therapy containing ethambutol

Background: India is among the largest countries to implement the revised national tuberculosis (TB) control program (RNTCP). Ocular toxicity of ethambutol has been known since 1962. It can be halted with early detection and cessation of the contributing drug. Aims and Objectives: This study aims to detect early ocular toxicity of ethambutol in TB patients under directly observed treatment strategy (DOTS). Materials and Methods: This was a prospective cross-sectional study of 30 patients getting AKT including ethambutol along with isoniazid, rifampicin, and pyrazinamide under RNTCP?DOTS center at a tertiary care hospital. The detailed history, best-corrected visual acuity (BCVA), color vision, fundus examination, visual field, retinal nerve fiber layer (RNFL) thickness, and central subfield macular thickness were carried out in all patients pretreatment and then at the 2nd month of treatment. Results: The mean age of patient was 44.87 years. Reduced visual acuity from the baseline was noted at the second in 23.33% of the right eyes (P = 0.01) and 30% of the left eyes (P < 0.01). Mean temporal RNFL thickness was significantly reduced from baseline after 2 months of treatment (P = 0.046). No significant difference was observed with color vision and visual fields pre- and post-treatment. Conclusion: The assessment of BCVA, color vision, visual field, RNFL, and macular thickness is essential at baseline and thereafter at frequent intervals to detect early ethambutol toxicity and probable reversible visual loss.

Quality analysis of some drugs against tuberculosis an in vitro study / Монголын эм зүй, эм судлал

Introduction@#According to the statistical data of 2019, 10 million people in 202 countries have been registered as tuberculosis cases, 1.6 million people has died around the world. In 2019, 4,089 new tuberculosis cases were determined, of which 265 died in Mongolia.@*Purpose@#The purpose of this study is analyze quality of some drugs used in the treatment of certain groups of tuberculosis in accordance with international standards.@*Materials and methods@#Isoniazid 300 mg, Rifampicin 150 mg, Pyrazinamide 400 mg and Ethambutol 400 mg, which are commonly used in Mongolia, were analyzed according to the pharmacopoeia methods of United States, Chinese and British.@*Results@#Appearance - Complies with the requirements of the certificate for sensory examination. Identification - It was determined by an infrared spectrophotometry. Average weight - Isoniazid 547.5 mg, Rifampicin 277.6 mg, Pyrazinamide 640.8 mg, Etambutol 399.6 mg. DisintegrationIsoniazid decomposes in 2.5 minutes, Pyrazinamide decomposes in 4.6 minutes, Etambutol decomposes in 8.5 minutes. Friability – Isoniazid - 0.4%, Pyrazinamide 10.4%, Hardness – Isoniazid 0.4%, Pyrazinamide is - 49.7 N, Dissolution – Isoniazid not less than - 95.7%, Rifampicin - 78.7%, Pyrazinamide - 95.7%, Assay - Etambutol is - 399.6 mg, Rifampicin is 139.94 mg, Isoniazid is - 293.6 mg Pyrazinamide - 492.5 mg complied with the standard requirements. @*Conclusion@#Analysis of tuberculosis drugs quality by pharmacopoeia methods including its appearance, identification, average weight, friability, hardness, disintegration, dissolution and assay, the isoniazid 300 mg tablets are complied with the United States pharmacopoeia, Rifampicin 150 mg tablets met British pharmacopoeia, and Ethambutol 400 mg tablets are complied with Chinese pharmacopoeia. Pyrazinamide 400 mg tablets did not complies the friability requirements of the United States Pharmacopoeia and also satisfied with the other requirements.

Ethambutol induced optic neuritis: a case series

Ethambutol is one of the first line chemotherapeutic agents used in the treatment of tuberculosis used both in the intensive and continuation phase according to the new Revised National Tuberculosis Control Program guidelines. Patient acceptability is rather good with this drug as it produces comparatively lesser adverse effects. The most important and serious side effect reported is optic neuritis, resulting in loss of visual acuity, color vision and field defects. The incidence of optic neuritis is generally directly proportional to the dose and duration of ethambutol therapy. Here we report four cases of ethambutol induced optic neuritis in patients on fixed dose combinations (FDC) of ethambutol, isoniazid, pyrazinamide and rifampicin who presented in Ophthalmology OPD in a span of 2 months, between June and July 2019. Contradictory to the rare occurrence of ethambutol induced optic neuritis this comparatively higher incidence of optic neuritis is alarming. We observed that the presentation of ethambutol induced optic neuritis can vary and dose of ethambutol along with other factors can also contribute to it. So proper pre-treatment evaluation, dosage adjustment, periodic monitoring and early detection have a significant role in prevention and treatment of ethambutol induced optic neuritis.

Effectiveness of Intravenous Isoniazid and Ethambutol Administration in Patients with Tuberculosis Meningoencephalitis and HIV Infection / 결핵

Treatment Outcomes after Discontinuation of Ethambutol due to Adverse Events in Mycobacterium avium Complex Lung Disease

BACKGROUND: Long-term administration of ethambutol (EMB) for Mycobacterium avium complex lung disease (MAC-LD) sometimes leads to permanent discontinuation of EMB due to various adverse events. This study aimed to investigate treatment outcomes after discontinuation of EMB.METHODS: Among patients diagnosed with MAC-LD between January 2001 and December 2014, 508 patients whose treatment was initiated with standard regimen until May 2018 were enrolled at a tertiary referral center in Korea. Of these 508 patients, 60 (11.8%) discontinued EMB due to various adverse effects. Among these 60 patients, treatment outcomes were analyzed for 44 patients by comparing their outcomes with those of matched subjects who received the standard treatment regimen without EMB discontinuation.RESULTS: The mean age of the 60 patients who discontinued EMB was 64.4 years. Ocular toxicity was the most common cause of discontinuation of EMB (75.0%, 45/60). The mean duration of EMB administration before its discontinuation was 7.0 ± 4.6 months. The treatment failure rate of the 44 patients with EMB discontinuation analyzed for treatment outcome was 29.6%, which was higher than that of the matched patients who received the standard regimen (18.3%), although the difference was not significant (P = 0.095). Of these 44 patients, EMB was substituted with later-generation fluoroquinolone in 23 patients, and the treatment failure rate of these 23 patients was significantly higher than that of the matched patients who received the standard regimen (39.1% vs. 19.3%, P = 0.045).CONCLUSION: These findings suggest that treatment outcomes are unsatisfactory in patients with MAC-LD who discontinue EMB owing to adverse events. Notably, there was a statistically significant high failure rate in patients who were prescribed fluoroquinolone to replace EMB.

Cryo-EM snapshots of mycobacterial arabinosyltransferase complex EmbB-AcpM

Inhibition of Mycobacterium tuberculosis (Mtb) cell wall assembly is an established strategy for anti-TB chemotherapy. Arabinosyltransferase EmbB, which catalyzes the transfer of arabinose from the donor decaprenyl-phosphate-arabinose (DPA) to its arabinosyl acceptor is an essential enzyme for Mtb cell wall synthesis. Analysis of drug resistance mutations suggests that EmbB is the main target of the front-line anti-TB drug, ethambutol. Herein, we report the cryo-EM structures of Mycobacterium smegmatis EmbB in its "resting state" and DPA-bound "active state". EmbB is a fifteen-transmembrane-spanning protein, assembled as a dimer. Each protomer has an associated acyl-carrier-protein (AcpM) on their cytoplasmic surface. Conformational changes upon DPA binding indicate an asymmetric movement within the EmbB dimer during catalysis. Functional studies have identified critical residues in substrate recognition and catalysis, and demonstrated that ethambutol inhibits transferase activity of EmbB by competing with DPA. The structures represent the first step directed towards a rational approach for anti-TB drug discovery.

Cryo-EM snapshots of mycobacterial arabinosyltransferase complex EmbB-AcpM

Inhibition of Mycobacterium tuberculosis (Mtb) cell wall assembly is an established strategy for anti-TB chemotherapy. Arabinosyltransferase EmbB, which catalyzes the transfer of arabinose from the donor decaprenyl-phosphate-arabinose (DPA) to its arabinosyl acceptor is an essential enzyme for Mtb cell wall synthesis. Analysis of drug resistance mutations suggests that EmbB is the main target of the front-line anti-TB drug, ethambutol. Herein, we report the cryo-EM structures of Mycobacterium smegmatis EmbB in its "resting state" and DPA-bound "active state". EmbB is a fifteen-transmembrane-spanning protein, assembled as a dimer. Each protomer has an associated acyl-carrier-protein (AcpM) on their cytoplasmic surface. Conformational changes upon DPA binding indicate an asymmetric movement within the EmbB dimer during catalysis. Functional studies have identified critical residues in substrate recognition and catalysis, and demonstrated that ethambutol inhibits transferase activity of EmbB by competing with DPA. The structures represent the first step directed towards a rational approach for anti-TB drug discovery.

Clinical efficacy analysis of Qing Mang Yi Hao in the treatment of toxic optic atrophy / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To evaluate effects of Qing Mang Yi Hao in the treatment of toxic optic atrophy.<p>METHODS: A retrospective analysis of 7 patients(13 eyes)suffered from toxic optic atrophy in Department of Ophthalmology, Dongfang Hospital Beijing University of Chinese Medicine, who were diagnosed as liver stagnation and blood deficiency and treated with Qing Mang Yi Hao formula. The formula treatments patients received were varying from 1 to 12 courses, and the clinical follow-up unequally lasted from 6-24mo. Then the formula clinical efficacy was comprehensively evaluated by comparing their visual acuity, visual field, visual evoked potential(VEP)and retinal nerve fiber layer(RNFL)thickness before and after treatment.<p>RESULTS: Seven cases(13 eyes)consisted of 5 ethambutol-induced optic neuropathy cases(10 eyes), 1 alcohol toxic neuropathy case(1 eye)and 1 rabies vaccine toxic neuropathy case(2 eyes). OCT showed the RNFL thicknesses on nasal and temporal quadrants were significantly thin at their first visits and the tendency of decreasing was noticed on each quadrant of RNFL thickness at the last follow-up. However, the visual acuity of 7 cases(13 eyes)had varying improvements: ≥0.1 4 eyes(31%), 0.06-<0.1 2 eyes(15%), 0.04-<0.06 1 eyes(8%), 0.01-<0.04 4 eyes(31%), no improvements 2 eyes(15%). The total efficacy rate of Qing Mang Yi Hao formula was 64%(27% significant).<p>CONCLUSION: Qing Mang Yi Hao could improve visual function, delay the progressive optic atrophy of TON, thus plays a significant role in optic neuroprotection.

Simultaneous Quantification of Ethambutol and Amikacin in Human Sputum by HPLC-MS/MS / 中国药学杂志

OBJECTIVE: To develop an LC-MS method for simultaneously quantifying two anti-tuberculosis drugs (ethambuto land amikacin) in human sputum thus to help guide clinical medication. METHODS: The drugs in sputum were extracted by acetonitrile precipitation, and separated on ACQUITY UPLC HSS T3 column(2.1 mm×100 mm, 1.8μm) with mobile phase consisting of 0.1% formic acid aqueous solution and acetonitrile (containing 0.1% formic acid) (80∶20) at a flow rate of 0.35 mL•min-1. Multiple reaction monitoring (MRM) was performed in positive ionization mode with electrospray ionization source. RESULTS: The liner calibration curves of ethambutol and amikacin were obtained in the concentration ranges of 48-12 000(r=0.997 8) and 320-80 000(r=0.999 5)ng•mL-1, respectively. The intra- and inter-day precision RSD was less than 9.2% and the absolute recovery was between 96.65% and 106.35%. This method was successfully applied to analyze the drugs in sputum from five clinical samples, the concentration of ethambutol was 148.5 to 919 ng•mL-1, and no amikacin was detected. CONCLUSION: The method is rapid, simple, sensitive and accurate, and can be applied to the therapeutic drug monitoring of ethambutol and amikacin.

Ethambutol optic neuropathy / 国际眼科杂志(Guoji Yanke Zazhi)

@#Ethambutol(EMB)has been used as first-line antibiotics to treat tuberculosis. Side effects of ethambutol have been well documented since its original use, with the most serious one being optic neuropathy. EMB-induced optic neuropathy(EON)may be reversible in the early stages, but delayed diagnosis has been shown to result in permanent visual loss. Thus the reversibility of EON is dependent on early detection. In this review, we discuss risk factors, detection methods, treatment and prevention of EON.

Rapid detection of ethambutol-resistant Mycobacterium tuberculosis in clinical specimens by real-time polymerase chain reaction hybridisation probe method

Background: Early diagnosis of drug resistance (DR) to ethambutol (EMB) in tuberculosis (TB) remains a challenge. Simple and reliable method (s) are needed for rapid detection of DR Mycobacterium tuberculosis (MTB) in clinical specimens. Objectives: The aim of this study was to design fluorescence resonance energy transfer hybridisation probe-based real-time polymerase chain reaction (PCR) method for the early detection of EMB-resistant MTB direct from clinical sputa. Materials and Methods: Primers and probes were designed against 306 codon of embB gene which is commonly associated with EMB resistance. A comparative study was done between Lowenstein–Jenson (L–J) proportion and hybridisation probe-based real-time PCR method for susceptibility testing. DNA sequencing was used in nine representative isolates to validate the efficiency of real-time PCR method to detect emb306 mutation of MTB. Results: A total of 52 clinical sputum samples and corresponding culture isolates (from category II pulmonary TB cases) were included in this study. Out of 52 MTB isolates, 32 and 20 were resistant and susceptible to EMB, respectively, as determined by L–J proportion method. Real-time PCR showed 95% specificity, 75% sensitivity and 82.69% accuracy when compared with L–J proportion method. A 100% of concordance was observed by validating the real-time PCR results with DNA sequencing. Conclusions: Our real-time PCR hybridisation probe method promises for rapid detection of EMB-resistant MTB directly from clinical specimens. However, future studies and modifications of method by incorporating other potential loci along with targeted mutation (emb306) are still required to increase the sensitivity of method.

Therapeutic implications of nano-encapsulated rifabutin, azithromycin & ethambutol against experimental Mycobacterium avium infection in mice

Background & objectives: Mycobacterium avium causes atypical infection in both immunocompetent and immunocompromised individuals. Conventional chemotherapy for M. avium infection is not efficient due to lengthy course of treatment and drug-associated toxic side effects. The present study was aimed at reducing dosing frequency of antimicrobial regimen consisting of azithromycin (AZM), rifabutin (RBT) and ethambutol (EMB) by encapsulation of drugs in nanoparticles (NPs) in experimental M. avium infection in mice. Methods: Poly (DL-lactide-co-glycolide) NPs containing anti-M. avium drugs were prepared, characterized and studied for their pharmacokinetics and pharmacodynamics parameters. Drug-loaded NPs were further analyzed for their therapeutic efficacy against experimental M. avium infection in mice. Results: Drug-loaded NPs were of size 227.3�.4 for RBT, 334.35�.7 for AZM and 509.85�.5 for EMB with smooth surface morphology and negative zeta potential. AZM, EMB and RBT from NPs were detectable for 6, 4 and 5 days, respectively, in the mice plasma, whereas free drugs were cleared from mice circulation within 24 h. Chemotherapeutic effects of weekly administered drug-loaded NPs were equivalent to daily administered free drugs. Interpretation & conclusions: Our findings showed that NPs gave sustained release of drugs inside plasma and organs, thus decreasing dosage frequency, and their weekly dosage had therapeutic efficacy equivalent to daily dosage of free drugs.

Analysis of the Use of Medical Institutions and Prescription Drugs for Pulmonary Tuberculosis in Geriatric Patients

BACKGROUND: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that can affect many organs of the body but usually affects the lungs. The prevalence of TB in Korea is considerably higher than that in other countries with similar economic levels, and is much higher in elderly people. Pharmacotherapy is important in the treatment of TB and requires relatively high compliance for a prolonged duration. METHODS: We analyzed sample data of elderly patients obtained from the Health Insurance Review and Assessment Service. We used logistic regression analysis and frequency analysis to identify factors that could affect prevalence of TB in elderly patients, compliance with prescribed medication regimes in these patients, and use of medical institutions. Korean Standard Classification of Diseases, version 7 (KCD-7) was used to diagnose pulmonary TB, and medications were analyzed using Korean standardized drug classification codes. RESULTS: 1,276,331 patients were analyzed in the sample of the elderly population, and 16,658 TB patients were included in the study. The mean age of the TB patients was 76.19 years (SD 6.899). A total of 699 patients were prescribed isoniazid, rifampicin, ethambutol, or pyrazinamide at least once. Of these, 352 (50.4%) were prescribed all four medications and 101 (14.4%) were prescribed only isoniazid, rifampicin, and ethambutol. The mean duration of prescription was 28.75 days (SD 36.13). CONCLUSION: In the elderly population, old age and poor socioeconomic conditions correlated with TB prevalence. Most patients did not meet the criteria for effective pharmacotherapy of TB.

Establishment of a rat model of hyperuricemia associated with uric acid excretion disorder / 中国比较医学杂志

Objective To explore a reliable method to establish a rat model of hyperuricemia associated with abnormal uric acid excretion, and to lay the foundation for the study of pathogenesis of uric acid excretion disorder and the optimization of the treatment plan.Methods The models were established respectively by potasium oxonate(300 mg/kg) with pyrazinamide (300 mg/kg) or ethambutol(250 mg/kg).Continuous dosing for 1, 3 and 5 weeks, to determine the content of uric acid in rat blood, urine, and stool, the function of liver and kidney was detected and pathological examination was performed.Results The blood uric acid in the potasium oxonate and ethambutol group was increased first and then decreased, while in the potasium oxonate and pyrazinamide group were increased steadily and the excretion of uric acid in urine was stable during the continuous administration.The two methods showed no harmful effect on the liver and kidney function.Conclusions A stable rat model of hyperuricemia associated with uric acid excretion disorder can be effectively established by potassium oxonate and pyrazinamide, exhibiting similar manifestations of clinical hyperuricemia and uric acid excretion disorder.

Baseline retinal nerve fiber layer thickness and visual outcomes of eyes with ethambutol toxic optic neuropathy

Objectives@#To determine the retinal nerve fiber layer thickness (RNFL) in eyes with ethambutol-induced toxic optic neuropathy (ETON) at the time of diagnosis and to describe the visual outcomes at 1, 3, and 6 months after discontinuation of ethambutol@*Methods@#This was a retrospective chart review of 8 patients (15 eyes) diagnosed with ETON that had RNFL thickness measurements using Cirrus® spectral-domain optical coherence tomography (OCT) at the time of diagnosis. Visual function was measured on initial visit and at 1, 3, and 6-month follow-up. Snellen visual acuity was converted to logMAR. Color vision was measured using Ishihara 14-plate test chart. @*Results@#The mean duration from commencement of ethambutol intake to onset of visual symptoms was 16 weeks (range: 8-24). While, the mean duration from onset of visual symptoms to discontinuation of ethambutol was 4 weeks (range: 2-14). The mean global RNFL thickness at time of diagnosis was 101.2 ± 17.0 microns. Mean RNFL in the temporal, superior, nasal, and inferior sectors were as follows: 79.2 ± 15.4, 119.7 ± 27.9, 71.7 ± 9.2, and 136.7 ± 25.8 microns. Global and sectoral RNFL thicknesses were either normal or thick when compared to age-matched normal database. No eye displayed global or sectoral RNFL thinning. Mean baseline visual acuity and color vision were logMAR 1.2 and 5 plates, respectively. At 1, 3, and 6 months after discontinuation of ethambutol, mean visual acuity and color vision were 0.96 and 6, 0.63 and 11, and 0.44 and 13, respectively.@*Conclusion@#Patients with early ETON have normal or thick RNFL at time of diagnosis. They display good visual recovery 6 months following discontinuation of ethambutol.