Toxic optic neuropathy associated with lamotrigine and levetiracetam dual therapy.

We report the case of an early adolescent male on lamotrigine and levetiracetam therapy with a 1-month history of progressive, bilateral, painless visual loss which resolved on cessation of lamotrigine. To our knowledge, we present the first case of lamotrigine and levetiracetam dual therapy associated with toxic optic neuropathy, supported by electrophysiology and optical coherence tomography (OCT) changes. Electrophysiology findings were consistent with retinal ganglion cell dysfunction, with bilateral optic nerve involvement. Macula OCT showed mild retinal ganglion cell loss in all inner quadrants bilaterally. This case highlights the importance of asking patients with epilepsy treated with lamotrigine and levetiracetam about visual problems and considering early dose reduction or cessation of treatment.

Visual Recovery Time in Patients with Ethambutol-induced Toxic Optic Neuropathy.

PURPOSE: We aimed to investigate the visual recovery time in patients with ethambutol-induced toxic optic neuropathy (EON) and identify the factors associated with the visual recovery time. METHODS: In this retrospective cohort study, we reviewed the medical records of 35 eyes from 35 patients with EON. Visual recovery was defined as a gain of three or more lines from the nadir. RESULTS: Patients were observed following discontinuation of ethambutol (EMB), with the mean follow-up period of 21.0 ± 16.0 months. The visual acuity at nadir was logarithm of the minimum angle of resolution 1.4 ± 0.4, and the final visual acuity was logarithm of the minimum angle of resolution 0.6 ± 0.5. Twenty-seven eyes (77.1%) showed significant visual recovery. In Kaplan-Meier survival, the mean estimated time for visual recovery was 15.2 ± 3.0 months, and 50% of the patients experienced visual recovery at 8.3 ± 2.2 months following EMB discontinuation. Multivariate Cox regression analysis identified several significant risk factors for delayed visual recovery, including duration of EMB medication ≤6 months, period from symptom onset to EMB discontinuation >14 days, and baseline peripapillary retinal nerve fiber layer thickness >98 µm. CONCLUSIONS: Our study indicated a mean time of visual recovery of 15 months for EON cases. Therefore, patients diagnosed with EON should be followed up for more than 1 to 2 years to evaluate their visual recovery. Delayed EMB discontinuation, short duration of EMB use, and initial peripapillary retinal nerve fiber layer thickening were associated with delayed visual recovery. Therefore, patients taking EMB should be followed up regularly for early detection of EON and immediate discontinuation of EMB to prevent severe damage to the optic nerve.

Ethambutol and its ophthalmic effects; is screening and collaboration the new way forward?

AIM: To screen patients on ethambutol and evaluate its role on visual functions and toxic optic neuropathy. SETTING AND DESIGN: Retrospective, observational single tertiary centre cohort of 80 patients. METHODS AND MATERIAL: A total of 69 from the initial 80 patients with visual complaints were categorised into two groups A and B; ongoing anti-tubercular therapy with ethambutol and having stopped ethambutol for greater than six months respectively. All patients underwent vision (V) testing on ETDRS chart and anterior and posterior segment evaluation. Additionally, patients in group A recorded color vision (CV) on Ishihara chart and visual evoked potential (VEP). STATISTICAL ANALYSIS USED: P value was calculated using Chi square test (SPSS ver. 20). RESULTS: Out of 69 patients in our study, 58 (84.05%) patients recorded reduced visual acuity. The mean visual acuity was 0.58 logMAR units. 33 out of our 58 (57%) patients with reduced visual acuity showed normal optic discs while 25 out of 58 (43%) showed altered optic discs. In group B, 14 out of 32 patients with vision of less than 20/20 also had optic disc pallor (p = 0.02). 12 out of 15 patients in group A recorded an altered color vision and also had a vision of less than 20/20 (p = 0.023). 15 patients who recorded altered VEP also had vision of less than 20/20 (p = 0.037). CONCLUSION: Visual acuity, color vision and vep are sensitive and sustainable tools which can be implemented in regular screening. Ethambutol toxicity is a real problem and a collaborative approach is necessary to establish screening protocols and prevent ethambutol induced toxic optic neuropathy.

Potential underlying mechanisms of ethambutol induced optic neuropathy: Evidence from in vitro to clinical studies.

Ethambutol is an antibiotic widely used for treatment of Mycobacterium species. Although it is safe to use in patients, the ocular toxic impact, including optic neuropathy and retinopathy, can be observed in patients using ethambutol. After discontinuation of the drug, the ocular toxic effects can be reversible in some patients, but some are not. Ethambutol-induced optic neuropathy has been recognized for more than six decades and the prevalence of optic neuropathy from a standard dose of ethambutol has been reported as 0.7-1.29%. Several factors associated with ethambutol-induced optic neuropathy include dosage/duration of drug, the medical conditions of patients such as renal and hepatic dysfunction and preexisting mitochondrial mutations. Currently, there is no specific treatment and prevention of ethambutol-induced optic neuropathy. In addition, the potential underlying mechanisms of ethambutol-induced optic neuropathy is still unclear. Therefore, this review aimed to summarize and discuss evidence from clinical, in vitro, and in vivo studies in order to explore the potential pathophysiology of ethambutol-induced optic neuropathy. Any contradictory findings are also included and discussed. The insights gained from the review will facilitate the discovery of novel approaches for prevention and treatment of optic neuropathy-induced by ethambutol.

Linezolid optic neuropathy.

PURPOSE OF REVIEW: In this article, we reviewed 67 reported cases of linezolid optic neuropathy and describe the common characteristics and expectations for recovery with an emphasis on recent findings in the literature. RECENT FINDINGS: Linezolid classically causes a reversible, duration-dependent optic neuropathy. However, in our review, we found only 66.7% of patients recovered complete visual function. Vision loss most commonly affected visual acuity followed by visual field and color vision. We also found patients taking higher doses of linezolid experienced full recovery less often, suggesting a dose-dependent component of linezolid optic neuropathy. Linezolid use has increased in frequency and duration, especially in the treatment of drug-resistant tuberculosis, and data indicate that these patients experience lower rates of complete vision recovery compared with patients taking linezolid for other indications. SUMMARY: Linezolid is an effective medication for treating drug-resistant infections; however, it may result in optic neuropathy. It is reasonable for patients on linezolid to undergo screening examinations, especially those on higher doses or for prolonged duration of therapy.

Effect of adenosine triphosphate on amiodarone-induced optic neuropathy in rats: biochemical and histopathological evaluation.

OBJECTIVE: This study aims to investigate possible preventive effect of ATP on optic nerve damage caused by amiodarone in rats. MATERIAL AND METHOD: Thirty albino male Wistar rats weighing between 265 and 278 g were used in the study. Before the experiment, the rats were housed at 22 °C in a 12-h light/dark cycle under appropriate condition. The rats were equally divided into five groups of six animals each: healthy group, 50 mg/kg amiodarone (AMD-50), 100 mg/kg amiodarone (AMD-100), 25 mg/kg ATP + 50 mg/kg amiodarone (ATAD-50), and 25 mg/kg ATP + 100 mg/kg amiodarone (ATAD-100). At the end of 14th day, the animals were sacrificed using cardiac puncture under deep thiopental anaesthesia, and optic nerve tissues were harvested to measure superoxide dismutase (SOD), total glutathione (tGSH), malondialdehyde (MDA), and catalase (CAT) levels. RESULTS: The MDA levels were found to be significantly higher in the AMD-50 and AMD-100 groups compared to the healthy group (p ˂ 0.001). There was also a significant difference between the AMD-50 and ATAD-50 groups, and between the AMD-100 and ATAD-100 groups regarding MDA levels (p ˂ 0.001). tGSH, SOD, and CAT levels were significantly lower in the AMD-50 and AMD-100 groups compared to the healthy group (p ˂ 0.001). ATP was found to partially inhibit amiodarone-induced optic neuropathy. CONCLUSION: The biochemical and histopathological results of this study demonstrated that amiodarone at high doses caused more severe optic neuropathy inducing oxidative damage, but ATP could relatively antagonise these negative effects on the optic nerve. Therefore, we believe that ATP may be beneficial in preventing amiodarone-induced optic neuropathy.

[Ethambutol-induced toxic optic neuropathy during treatment of tuberculosis meningitis in a child]. / Neuropathie optique toxique à l'éthambutol au cours d'une méningite tuberculeuse chez un enfant.

INTRODUCTION: Toxic optic neuropathy is a severe optic nerve injury that can compromise the prognosis for vision, justifying early clinical and ancillary diagnosis. CASE DESCRIPTION: We report the case of an 11-year-old child being treated for tuberculous meningitis with a combination of ethambutol and three other anti-bacillary drugs, referred for a rapidly progressive bilateral decline in visual acuity. On ophthalmologic examination, the visual acuity was counting fingers within 1ft in both eyes, and bilateral optic disc pallor was noted, without other associated abnormalities. Neurological imaging was unremarkable, with red-green dyschromatopsia and a bilateral cecocentral scotoma. Faced with this clinical and paraclinical picture, we arrived at the diagnosis of ethambutol toxic optic neuropathy, with a multidisciplinary decision leading to a change in the antibacillary treatment protocol. No clinical improvement was noted after 3 months of follow-up. DISCUSSION: Optic nerve toxicity is rare in children and is classically described as dose- and time-dependent. CONCLUSION: Ethambutol ocular toxicity is extremely rare in children, and the required action when detected is to discontinue the drug. Reversibility is not always assured, which requires early detection of toxic optic neuropathy by close clinical and ancillary monitoring and, above all, sensitization of the treating physicians (pediatricians, pulmonologists and neurologists).

Pembrolizumab-induced optic neuropathy - a case report.

Background: Immune checkpoint inhibitor (ICI) treatment has become important for treating various cancer types, including Hodgkin's lymphoma. However, ICI can overstimulate the immune system, leading to a broad range of immunological side effects, known as immune-related adverse events (irAEs). Here, we report a case of optic neuropathy caused by pembrolizumab. Case presentation: A patient with Hodgkin's lymphoma received pembrolizumab every three weeks. Twelve days after the sixth cycle of pembrolizumab, the patient was admitted to the emergency department with blurred vision, visual field impairment and altered color perception affecting the right eye. The diagnosis of immune-related optic neuropathy was established. Pembrolizumab was stopped permanently and high-dose steroid treatment was immediately started. This emergency treatment led to a satisfactory binocular vision and an improvement of visual acuity testing results. After another 7 months, the left eye was affected with the same symptoms. At this time, only an extended immunosuppressive therapy consisting of high-dose steroid treatment, plasmapheresis, immunoglobulin treatment, retrobulbar injection of steroids and mycophenolate mofetil, successfully reduced the symptoms. Conclusions: This case highlights the need for prompt recognition and treatment of rare irAEs, such as optic neuropathy. Urgent treatment with initial high-dose steroid treatment is required to avoid persistent loss of visual acuity. Options for further treatment are mainly based on small case series and case reports. In our case, a retrobulbar injection of steroids in combination with mycophenolate mofetil showed significant success in treating steroid-refractory optic neuropathy.

Inhibition of p38 ameliorates axonal loss with modulation of autophagy in TNF-induced optic nerve damage.

PURPOSE: A relationship between p38 and autophagy remains debated. The aim of the current study is to investigate whether an inhibitor of p38 prevents axon loss induced by TNF and whether it affects autophagy. METHODS: Rats were given intravitreal injection of TNF, TNF plus SB203580, a p38 inhibitor, or SB203580 alone. Immunoblot analysis was performed to examine p62 expression which is a marker of autophagic flux and LC3-II expression which is an autophagy marker in optic nerves 1 week after intravitreal injection. Morphometric analysis of axons was performed to evaluate the effects of SB203580 against TNF-induced optic nerve damage 2 weeks after intravitreal injection. Immunohistochemical analysis was performed to evaluate the expressions of LC3, neurofilament, phosphorylated p38 and p62 in the optic nerve. RESULTS: Quantification of axon number showed that TNF-induced axon loss was significantly protected by SB203580. Immunoblot analysis showed that the increase of p62 induced by TNF was totally eliminated by SB203580, and the SB203580 alone injection decreased the expression of p62. The level of LC3-II was significantly upregulated in the TNF plus SB203580 group compared with the TNF alone group, and the SB203580 alone injection increased the expression of LC3-II. Immunohistochemical analysis showed that LC3 immunoreactivity was found in the neurofilament positive fibers and that these immunoreactivities were enhanced by SB203580. Some colocalizations of p-p38 and p62 were observed in the TNF-treated optic nerve. CONCLUSION: These results suggest that inhibition of p38 exerts axonal protection with upregulated autophagy in TNF-induced optic nerve damage.

Alemtuzumab-Induced Thyroid Eye Disease: A Comprehensive Case Series and Review of the Literature.

PURPOSE: To present 5 cases of alemtuzumab-induced thyroid eye disease (AI-TED) and review the literature to highlight the natural history, severity, and outcomes as compared with conventional thyroid eye disease (TED). METHODS: A multi-institutional retrospective case series of patients with AI-TED was compiled. Chart review evaluated for clinical characteristics, imaging findings, and treatment for AI-TED. Additionally, a comprehensive review of the literature identified all previously published cases of AI-TED. RESULTS: Five new patients with AI-TED were included in this series. The average clinical activity score on presentation was 2.8 (range 1-4) and reached an average peak of 5.0 during the active phase of the disease (4-7). Patients were treated medically with selenium (40%) or monoclonal antibodies including teprotumumab or tocilizumab (40%). Surgical treatment with orbital decompression for compressive optic neuropathy was performed on 2 (40%) patients. Combined with 11 previously reported cases, these 16 patients with AI-TED had an average clinical activity score on presentation of 3.3. The average length of the AI-TED phase was 14.0 months, and all patients were treated with medical and/or surgical interventions for their disease. CONCLUSIONS: Clinical and imaging findings in AI-TED mirror that of conventional TED, however, AI-TED may present with greater severity. AI-TED may develop many months after Graves' disease; therefore, providers should be aware of this association and monitor patients for the development of severe TED.

Immune Checkpoint Inhibitors and Optic Neuropathy: A Systematic Review.

INTRODUCTION: Immune checkpoint inhibitors are a class of monoclonal antibodies that are used as a mainstay of immunotherapy for multiple solid organ malignancies. With the recent increase in popularity of these agents, immune-related adverse events including optic neuropathy are becoming more frequently reported. This review aims to explore the association between immune checkpoint inhibitors and optic neuropathy through analysis of incidence, clinical features, investigations, treatment, and patient outcomes. METHOD: A systematic search of the databases PubMed/MEDLINE, Embase, and CENTRAL was performed from inception to September 2022. Data collection and risk of bias analysis was subsequently conducted in accordance with the PRISMA guidelines. RESULTS: Eleven articles fulfilled the inclusion criteria. The results showed an increased incidence of optic neuropathy among patients receiving immune checkpoint inhibitor therapy compared to the general population. Presentation with painless reduced visual acuity and optic disc swelling was most common. Investigation findings were poorly documented. The only two patients who achieved full resolution of symptoms were treated with oral prednisolone. CONCLUSION: There is a strong association between immune checkpoint inhibitor therapy and development of optic neuropathy. Although it remains uncommon, the incidence of optic neuropathy in this population exceeds that of the general population. Future research is needed to further characterise the risk profiles of patients who are most likely to develop ICI-associated optic neuropathy, and treatment pathways for these patients.

Ethambutol-induced optic neuropathy.

PURPOSE: 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. METHODS: 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). CONCLUSION: 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.

Optic neuropathy after COVID-19 vaccination: a report of two cases.

PURPOSE: We report two cases of optic nerve pathology after the administration of the Pfizer-BioNTech and AstraZeneca-Oxford COVID-19 vaccines, respectively, and describe the implications for management of post-vaccination central nervous system (CNS) inflammation. CASE REPORTS: A 69-year-old woman presented with bilateral optic nerve head oedema, 16 days after the second dose of the Pfizer-BioNTech vaccine. She was diagnosed with post-vaccination CNS inflammatory syndrome and was treated for five days with intravenous methylprednisolone at a dose of 1 gram per day. Her optic disc swelling improved, and her vision stabilised. A 32-year-old woman presented six days after her first dose of the AstraZeneca-Oxford vaccine with two days of sudden onset of progressive blurring of vision in her left eye. Posterior segment examination revealed left optic disc swelling, and an MRI of the brain, orbit, and cervical spine was significant for left optic nerve enhancement. The patient was diagnosed with a unilateral post-vaccination optic neuritis. She was treated with a three-day course of intravenous methylprednisolone followed by oral prednisone. Her optic disc swelling and visual field improved, and she recovered 6/6 vision. CONCLUSIONS: Clinicians and patients should be aware of the potential for post-vaccination CNS inflammatory syndromes associated with COVID-19 vaccine administration. Neuroimaging and cerebrospinal fluid analysis may aid in the diagnosis of the cause of vision loss. Further studies are needed to evaluate the spectrum and frequency of optic nerve involvement associated with COVID-19 vaccination.

Clinical and Mechanistic Review of Amiodarone-Associated Optic Neuropathy.

Amiodarone-associated optic neuropathy (AAON) is a complex clinical diagnosis, requiring distinction from non-arteritic ischemic optic neuropathy (NAION) due to a shared at-risk patient population. Diagnosis of AAON is complicated by a varied clinical presentation and incomplete pathophysiologic mechanisms. This article reviews pertinent literature for describing and clinically delineating AAON from NAION, as well as newly reported protective mechanisms of insulin-like growth factor 1 (IGF-1) and PI3K/Akt against amiodarone-induced oxidative and apoptotic injury in retinal ganglion and pigment epithelial cells. These studies offer a basis for exploring mechanisms of amiodarone toxicity in the optic nerve.