Ethambutol-induced Optic Neuropathy Research Articles

Visual evoked potential as an early assessment tool in ethambutol-induced toxic optic neuropathy during treatment of tuberculosis

Visual evoked potential as an early assessment tool in ethambutol-induced toxic optic neuropathy during treatment of tuberculosis

OPA1 Mutation Presenting as Ethambutol-Induced Optic Neuropathy.

OPA1 Mutation Presenting as Ethambutol-Induced Optic Neuropathy.

Unmasking NMOSD: A Case of Misdiagnosed Ethambutol-Induced Optic Neuropathy (P9-14.014)

Unmasking NMOSD: A Case of Misdiagnosed Ethambutol-Induced Optic Neuropathy (P9-14.014)

Optical Coherence Tomography Parameters and Optimal Cut-off Values for Predicting Visual Prognosis in Ethambutol-Induced Optic Neuropathy.

The objective of this study was to evaluate the prognostic value of optical coherence tomography (OCT) parameters in patients with ethambutol-induced optic neuropathy (EON) and establish their optimal cut-off values for predicting visual acuity outcomes. A retrospective cross-sectional study was conducted on 64 eyes of 32 patients with EON who underwent OCT. Peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) thickness were measured using Cirrus high-definition OCT (HD-OCT) within 3 months after EON diagnosis. Visual acuity of patients was recorded and analyzed at the first visit, the 1-year visit, and the latest visit. Prognostic capacities of OCT parameters for visual prognosis were evaluated and their optimal cut-off values for predicting final visual acuity were established. Increased pRNFL thickness was significantly associated with better visual acuity at 1 year postdiagnosis and the latest visit. A significant association was established between increased pRNFL thickness and a higher rate of recovery to visual acuity >20/25 at 1 year postdiagnosis. Receiver-operating characteristic curves identified ideal cut-off values for OCT parameters as follows: pRNFL thickness of 83 μm (sensitivity 100%, specificity 48.3%) and mGCIPL thickness of 74 μm (sensitivity 100%, specificity 83.3%) for visual acuity >20/25 at 1 year, mGCIPL thickness of 61 μm (sensitivity 85.7%, specificity 71.4%) for visual acuity >20/40 at 1 year, with corresponding AUCs exceeding 0.7. Both pRNFL and mGCIPL thickness possess potential values for predicting visual outcomes in patients with EON. Future research should continue to explore the utility of OCT parameters in EON prognosis.

Ethambutol-induced optic neuropathy: should we mandate ophthalmic examination in TB treatment?

Ethambutol-induced optic neuropathy: should we mandate ophthalmic examination in TB treatment?

Association of mitochondrial mutations in patients with ethambutol-induced optic neuropathy

Association of mitochondrial mutations in patients with ethambutol-induced optic neuropathy

Effect of Steroid Pulse Therapy on Ethambutol-induced Optic Neuropathy

Purpose: This study investigated the effects of high-dose steroid injections for ethambutol-induced optic neuropathy.Methods: A retrospective study examined 13 patients diagnosed with ethambutol-induced optic neuropathy at Wonju Severance Christian Hospital from December 2016 to November 2020. Methylprednisolone was injected at 1,000 mg/day for 3 days. The patients were evaluated before treatment; immediately after it; and at 1, 6, and 12 months. Visual acuity and visual fields were tested (Humphrey Field Analyzer, Carl Zeiss Meditec, Dublin, CA, USA) and the visual field index (VFI) and mean deviation (MD) were recorded.Results: We analyzed 26 eyes of 13 patients (6 males, 7 females; average age 68.7 years). Immediately after treatment, there was no significant improvement in visual acuity, but the VFI improved by 10% or more in 11 eyes and MD improved by 2 dB or more in 16 eyes. After the end of treatment, 13 of 26 eyes showed improved visual acuity of two lines or more in the Snellen table; VFI improved by more than 10% in 16 eyes and MD b y 2 dB or more in 20 eyes. The average differences in the final VFI and MD were 25.96 (standard deviation [SD] = 29.33) and 7.29 (SD = 7.09), respectively.Conclusions: When patients with ethambutol-induced optic neuropathy were treated with high-dose steroid injections, 60% (16/26) showed visual field improvement immediately after treatment and 77% (20/26) ultimately showed improvement. This suggests that steroids have a therapeutic effect in patients with optic neuropathy caused by ethambutol. Further studies are needed.

Incidence, risk factors and ophthalmic clinical characteristic of ethambutol-induced optic neuropathy: 7-year experience.

The purpose of this research was to investigate the characteristics, clinical manifestations, incidence, and risk factors in ethambutol-induced optic neuropathy (EON) in the Thai population. Patients treated with ethambutol for tuberculosis (TB) were retrospectively identified in the medical record of a tertiary hospital in Thailand from January 2012 to August 2019. Development of EON was determined through review of ophthalmology records. Comparison was made between patients with EON and those without EON to identify possible risk factors. Ophthalmic outcomes were characterized. Among 4,141 patients who received ethambutol for TB treatment, 1,062 had an ophthalmology encounter, and 20 (0.5% overall, 1.88% with ophthalmology encounters) developed EON. In unadjusted analysis, compared to patients without EON, those with EON had a similar daily dose, but longer duration of ethambutol treatment (P=0.02). They were older (mean 43.74 vs. 58.60 years, P=0.001), more likely to have hypertension (P=0.02) and smoke (p=0.01). There were no differences in gender, body mass index, diabetes, dyslipidemia, HIV infection or glomerular filtration rate. The peripapillary retinal nerve fiber layer, ganglion cell analysis, and vascular density as measured using retinal optical coherence tomography were impacted by EON. In adjusted logistic regression analysis, age greater than 60 (OR = 8.71, p = 0.01) and smoking (OR = 7.06, p = 0.01) were independent risk factors for EON. In patients treated with ethambutol, the incidence proportion of EON was 0.5% among those with ethambutol administered and 1.88% among those with ethambutol and an eye visit. Potential EON risk factors were age, hypertension, smoking, and duration of ethambutol medication. Smoking has not been associated with EON in prior studies.

Factors Affecting Visual Recovery in Patients with Ethambutol-Induced Optic Neuropathy.

To study visual recovery and identify the factors that may affect it in patients with ethambutol-induced optic neuropathy (EON). Medical charts of patients who developed optic neuropathy after ethambutol (EMB) treatment for tuberculosis infection were retrospectively reviewed. Demographic details and clinical data were examined to assess visual recovery after discontinuation of ethambutol treatment. The univariate and multivariate relationships between various factors and visual recovery were evaluated using regression analysis. Of 5394 patients diagnosed with tuberculosis infection and treated with EMB, 23 patients (0.43%) were diagnosed with EON. Logistic regression analysis found that female sex was the categorical factor significantly associated with good visual recovery with an odds ratio of 12.0 (95% confidence interval 1.56, 92.29; p = 0.02), while linear regression analysis identified good initial visual acuity as the numerical factor significantly related with it (p < 0.001). After adjustment with multivariate analysis, initial visual acuity was found to be the only significant factor associated with visual recovery. All patients with initial visual acuity of better than 20/200 at first visit achieved good visual recovery. The incidence of EON in patients treated with EMB was 0.43% in this hospital-based study. Good visual recovery was noted in 39.13% of these patients, and initial visual acuity was the factor that affected visual recovery. It is recommended that patients on EMB have regular screening by an ophthalmologist for early detection of the disease, and if it is discovered, that the use of the drug be immediately discontinued in order to prevent potentially devastating visual loss.

Optic Chiasmal Enhancement Revealed by Magnetic Resonance Imaging in a Patient with Ethambutol-induced Toxic Optic Neuropathy

Purpose: We report a bitemporal visual field defect accompanied by optic chiasmal enhancement in a patient with ethambutol (EMB)-induced toxic optic neuropathy.Case summary: A 53-year-old woman presented with bilateral visual disturbance that had gradually worsened over the prior 2 months. She had been prescribed 800 mg EMB daily to treat pulmonary tuberculosis for the past 10 months but had stopped EMB 1 month prior because of visual disturbance. She had been prescribed 600 mg rifampicin and 1,000 mg clarithromycin daily for 11 months. Her visual acuity was 0.2 in the right eye and 0.1 in the left. Color vision was reduced. Automated perimetry demonstrated a bitemporal visual field defect, which was more severe in the left eye. Magnetic resonance imaging (MRI) of the optic chiasm revealed contrast enhancement in the body of the chiasm. The optic nerve of the left eye evidenced a higher signal intensity than did that of the right, consistent with the visual field test results. One month after her initial visit, the visual symptoms deteriorated further. We delivered high-dose, intravenous steroid pulse therapy (methylprednisolone 1,000 mg daily for 3 days). At the 1-year follow-up, the visual acuity was 0.4 in the right eye and 0.1 in the left.Conclusions: Bitemporal hemianopia may develop in patients with EMB-induced toxic optic neuropathy. Enhancement of the optic chiasm, consistent with the visual field defect, could be observed in MRI.

Reversible ethambutol-induced optic neuropathy: report of a rare case

BackgroundEthambutol (EMB) is one of the first-line anti-tuberculosis therapy. One of its precarious side effects is ethambutol-induced optic neuropathy (EON). The ocular manifestations of EON include painless loss of central vision and cecocentral scotomas in the visual field. Case DescriptionA 60-year old man presented with gradual and painless visual loss since 3 months prior to visit. The accompanying symptoms were frequent headache without double vision and photophobia. He had been diagnosed with pulmonary tuberculosis (TB) for 9 months and consumed EMB for 7 months before being advised to discontinue. There was neither history of systemic diseases nor family history of neuropathy. Examination showed reduced visual acuity with positive relative afferent pupillary defect (RAPD) on right eye. Humphrey test showed bilateral generalized visual loss. Ocular computed tomography (OCT) showed retinal nerve fiber layer (RNFL) thickness was within normal limit. Magnetic resonance Imaging (MRI) brain indicated unremarkable result for optic neuropathy. Based on the examinations listed above, this patient was diagnosed as EON and EMB was stopped immediately. Patient was given oral citicoline 1000mg and zinc supplementation for one month. After 1 st and 3 rd month follow up, patient’s visual function was gradually improved. The ophthalmic examinations indicated recovery of the visual function. ConclusionsThis case suggested that an early detection and intervention in patient with EON has promising result in visual outcome. EON is a reversible optic neuropathy if the ocular toxicity is monitored closely among the tuberculosis patients who are prescribed EMB regiment.

Ethambutol-induced optic neuropathy.

A case report of a 40-year-old patient with tuberculosis treated with ethambutol is described. Within six months of starting treatment, there was a painless sudden decline in visual function. Despite the known complications of ethambutol treatment, it was discontinued after another three months. In the case report, we highlight the damage to the dominantly peripheral visual pathways. Using electrophysiological examinations, we showed a significant alteration in the optic nerves. Optical Coherence Tomography (OCT) showed progressive loss of vessel density and nerve fibre layer of retinal ganglion cells. Perimetric examination showed both a central decrease in sensitivity and mainly scotomas in the temporal parts of the visual fields. Although there was improvement in visual fields over time, OCT findings indicated progression of ethambutol-induced optic neuropathy (EON). Magnetic Resonance Imaging confirmed the alteration in the peripheral part of the visual pathway (intraorbital, intracranial parts of optic nerves, chiasma, and optic tracts). Even though EON is not an unknown complication, new cases still occur and, unfortunately, with an irreversible course. Therefore, it is important to draw attention constantly to this complication and to consider it not only in ophthalmologists' surgeries.

Campimetry and visual changes after RHZE treatment for tuberculosis

BackgroundTuberculosis (TB) caused by Mycobacterium tuberculosis has a high prevalence in Brazil (Global tuberculosis report 2020. Geneva: World Health Organization; 2020). The ethambutol-induced optic neuropathy damage is partly reversible, making its early diagnosis essential to reduce permanent visual damage.PurposeTo observe alterations in the computerized campimetry, Ishihara test and visual acuity secondary to rifampicin, isoniazid, pyrimethamine, ethambutol (RHZE) treatment.MethodsPatients undergoing treatment with RHZE at the tuberculosis service of the Federal University of São Paulo were recruited from March 2019 to December 2020. The best-corrected visual acuity (VA) measurements, Ishihara test and visual fields were performed at baseline, monthly, until 2 weeks after treatment.ResultsTwenty-five patients were included. The VA decreased significantly (P = 0.0129) post-treatment compared to month 1. The mean deviation (MD) did not decrease significantly (P > 0.05); the pattern standard deviation (PSD) decreased post-treatment compared to month 1 (P = 0.0371). Changes in the Ishihara test increased significantly (P < 0.0001) in the second month.ConclusionThe VA and PSD decreased significantly after RHZE treatment. Changes in the Ishihara test were observed in the second month.Trial registration: The Research Ethics Committee of Federal University of São Paulo, Paulista School of Medicine approved the study in March 2019. CAAE 04297018.4.0000.5505.

Analysis of Peripapillary Vessel Density in Ethambutol-induced Optic Neuropathy Using Optical Coherence Tomography Angiography

Purpose: To investigate the changes in peripapillary and macular vessel density in ethambutol-induced optic neuropathy using optical coherence tomography angiography (OCTA).Methods: The medical records of patients diagnosed with ethambutol-induced optic neuropathy were analyzed retrospectively. Patient age, sex, daily dose (mg/day/kg), treatment duration, best-corrected visual acuity (logMAR), color vision (Ishihara color plate tests), and mean deviation of visual field test were evaluated in non-pathological individuals with age and sex controlled as the normal control group. Peripapillary retinal nerve fiber layer (RNFL) thickness, macular ganglion cell/inner plexiform layer (GC/IPL) thickness, radial peripapillary capillary (RPC) density, and macular superficial capillary plexus (SCP) density were also compared between the patient and control groups.Results: The study included 22 patient eyes and 31 control group eyes. Comparing the OCTA results between the groups, there were no significant differences in peripapillary RNFL thickness, but the temporal RPC density was significantly (p = 0.025) lower in the patient group (48.00 ± 8.23%) than in controls (52.39 ± 5.58%). For macular structures, the mean GC/IPL thickness and whole SCP density were lower in the patients (p = 0.001 and p = 0.008, respectively). In the patients, the changes in peripapillary RNFL thickness and RPC density were significantly positively correlated (r = 0.811, p &lt; 0.001), as were the mean macular GC/IPL thickness and whole SCP density (r = 0.445, p = 0.037).Conclusions: Patients with ethambutol-induced optic neuropathy had significantly lower temporal RPC and macular SCP densities. Ethambutol toxicity may affect not only axonal degeneration but also peripapillary and macular vascular function.

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

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. 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. 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. The results of this study indicated an alarming increase in the trend of EON cases presenting to our tertiary care institute.

Ethambutol-induced optic neuropathy: A case series

In this observational case series, we describe the clinical features and investigations of three patients with ethambutol-induced optic neuropathy (EION). All three patients had a significant visual loss within 3 months to 1 year of starting antitubercular treatment. Visual field examination revealed bitemporal hemianopia in one patient and central scotomas in another. Optical coherence tomography showed significant global thinning of the ganglion cell layer and thinning of the temporal quadrants of the retinal nerve fiber layer. Visual evoked potential revealed prolonged P1 or P2 latency and reduced amplitude in all three patients. Ethambutol was stopped in all three patients. The visual acuity continued to deteriorate even after stopping the drug but showed gradual improvement over a period of one and a half years. However, the visual recovery was not full in all three patients. Considering the severity and partially irreversible nature of the loss of vision caused by EION, it is imperative to detect it at an early and subclinical stage.

Optic Chiasm and Tract Involvement in Ethambutol-Induced Optic Neuropathy

Optic Chiasm and Tract Involvement in Ethambutol-Induced Optic Neuropathy

Mitochondrial Mutations in Ethambutol-Induced Optic Neuropathy.

Background: Ethambutol-induced optic neuropathy (EON) is a well-recognized ocular complication in patients who take ethambutol as a tuberculosis treatment. The aim of the current study was to investigate the presence of mitochondrial mutations, including OPA1 and Leber’s hereditary optic neuropathy (LHON)-mitochondrial DNA (mtDNA), in patients with EON and to determine their effect on clinical features of these patients.Methods: All 47 patients underwent clinical evaluations, including best-corrected visual acuity, fundus examination, and color fundus photography; 37 patients were then followed up over time. Molecular screening methods, including PCR-based sequencing of the OPA1 gene and LHON-mtDNA mutations, together with targeted exome sequencing, were used to detect mutations.Results: We detected 15 OPA1 mutations in 18 patients and two LHON-mtDNA mutations in four patients, for an overall mutation detection rate of 46.8%. The mean presentation age was significantly younger in the patients with the mitochondrial mutations (27.5 years) than in those without mutations (48 years). Fundus examination revealed a greater prevalence of optic disc hyperemia in the patients with mutations (70.5%) than without mutations (48%). Half of the patients with mutations and 91% of the patients without mutations had improved vision. After adjusting for confounders, the logistic regression revealed that the patients with optic disc pallor on the first visit (p = 0.004) or the patients with the mitochondrial mutations (p < 0.001) had a poorer vision prognosis.Conclusion: Our results indicated that carriers with OPA1 mutations might be more vulnerable for the toxicity of EMB to develop EON.

Incidence of mitochondrial mutations in cohort of patients with ethambutol-induced optic neuropathy

Background: Ethambutol-induced Optic Neuropathy (EtON) is a devastating complication of the Anti-tubercular therapy (ethambutol-based regime) which is a cornerstone for the treatment of Tuberculosis. Though the etiology of the disease is unknown yet it has been postulated to be mitochondrial associated for a long time. It is intriguing to understand the basis which will aid in recognizing the “at-risk” population. Aim and Objective: To assess the association of mitochondrial mutations in the cohort of patients with Ethambutol-induced Optic Neuropathy (EtON).

Diagnostic Value of Optical Coherence Tomography and Electroretinogram in Early Detection of Ethambutol-Induced Optic Neuropathy

&#x0D; &#x0D; &#x0D; Background: Ethambutol-induced optic neuropathy (EON) is one of the most compelling adverse effect of tuberculosis treatment. Recovery often occur several months after treatment discontinuation. Unfortunately, some studies noted that nearly half of patients still have permanent visual loss. Early detection before clinical symptoms appear is necessary to prevent this devastating adverse effect. Therefore, this review aims to evaluate the diagnostic value of retinal nerve fiber layer (RNFL) thickness and ganglion cell inner plexiform layer (GCIPL) thickness changes with OCT, pattern and multifocal electroretinogram (ERG) changes during ethambutol treatment as early detection of EON. &#x0D; Methods: A comprehensive search was conducted from electronic databases (PubMed, EBSCO, Google Scholar, and Springerlink) using relevant search terms. Articles from offline resources were also included. Included studies were selected based on predefined inclusion and exclusion criteria.&#x0D; Result: Three studies reported significant thinning of RNFL after ethambutol initiation. Increased RNFL thickness in patients with EON and subclinical EON found in 3 studies. Significant macular GCPIL thinning was noted in 1 study. One study reported shortening of P50 implicit time and reduced N95 wave amplitude in pattern ERG. &#x0D; Conclusion: Macular GCIPL thinning suggested to be the first pathological changes detected on patients with ethambutol treatment. It can be concomitant with thickening of peripapillary RNFL and followed by peripapillary RNFL thinning. Pattern ERG may reveal abnormality due to retinal ganglion cell (RGC) dysfunction before RGC loss. &#x0D; &#x0D; &#x0D;