Amiodarone-Associated Optic Neuropathy: A Nationwide Study.

PURPOSE: To investigate whether amiodarone use is associated with an increased risk of optic neuropathy. DESIGN: Retrospective population-based cohort study. PARTICIPANTS: Patients newly treated with amiodarone between 2005 and 2009 were identified from the Taiwan National Health Insurance Research Database. For each case patient, the study also included 4 age- and gender-matched control subjects who did not receive amiodarone treatment. METHODS: Cox multivariate regression analysis was used to assess the association between amiodarone and the occurrence of optic neuropathy. MAIN OUTCOME MEASURES: Hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The analysis included 6175 amiodarone-treated patients and 24 700 controls. The mean age was 66.7 years and 55.3% of subjects were male. The mean follow-up was 688 days. During the observational period, optic neuropathy developed in 17 amiodarone-treated patients (0.3%) and 30 control patients (0.1%; P = 0.006). Multivariate Cox regression analysis showed that amiodarone-treated patients had a 2-fold increased risk of optic neuropathy (HR, 2.09; 95% CI, 1.13-3.85; P = 0.02). After stratification by gender, amiodarone use remained a significant factor for optic neuropathy development among male subjects (HR, 3.05; 95% CI, 1.42-6.55; P = 0.004), but not among female subjects (HR, 1.15; 95% CI, 0.38-3.47; P = 0.81). Among amiodarone-treated patients, male gender was associated with a nearly 3-fold increased risk of optic neuropathy development compared with female gender (HR, 2.91; 95% CI, 0.94-9.01; P = 0.06). We also detected a trend of increased cumulative incidence of optic neuropathy with longer treatment duration (>41 vs. ≤41 days; HR, 3.46; 95% CI, 0.99-12.07; P = 0.05). However, higher daily dose did not increase the risk of optic neuropathy (HR, 0.96; 95% CI, 0.91-1.00; P = 0.07). CONCLUSIONS: These results demonstrated a higher risk of optic neuropathy in patients treated with amiodarone, especially in males and possibly in patients with longer duration of treatment.

Desferrioxamine-related ocular toxicity: a case report.

A 29-year-old lady receiving repeated blood transfusions for ß thalassemia since childhood, presented with rapidly deteriorating symptoms of night blindness and peripheral visual field loss. She was recently commenced on high-dose intravenous desferrioxamine for reducing the systemic iron overload. Clinical and investigative findings were consistent with desferrioxamine-related pigmentary retinopathy and optic neuropathy. Recovery was partial following cessation of desferrioxamine. This report highlights the ocular side-effects of desferrioxamine mesylate and the need to be vigilant in patients on high doses of desferrioxamine.

Erythropoietin treatment for methanol optic neuropathy.

BACKGROUND: To present the effect of erythropoietin for the treatment of methanol optic neuropathy. METHODS: Two patients with methanol optic neuropathy were treated with 10,000 IU of intravenous erythropoietin twice a day for 3 days, 500 mg of methylprednisolone twice a day for 5 days (followed by 2 weeks of oral prednisolone [1 mg/kg per day]), and daily doses of vitamin B12, vitamin B6, and folic acid for 1 month. RESULTS: At presentation, the patients had no perception of light in both eyes, associated with mildly swollen optic discs. Both responded dramatically to the treatment regimen. In the first patient, visual acuity improved to 20/20 in both eyes within 3 days, whereas in the second patient, visual acuity returned to counting fingers at 6 feet, right eye, and 20/30, left eye, within 3 weeks. CONCLUSION: Intravenous erythropoietin may be an effective adjuvant when combined with current treatment for patients with methanol optic neuropathy.

Structural-functional dissociation in presumed ethambutol optic neuropathy.

A 55-year-old man with pulmonary Mycobacterium avium intracellulare infection developed decreased vision to 3/200 in the right eye, and 20/200 in the left eye, 11 months after starting ethambutol, rifampin, and isoniazid. A diagnosis of presumed ethambutol optic neuropathy was made, and the medications were discontinued. Visual acuity gradually improved to 20/30 and 20/70 over a period of 34 months. Despite improved central vision and visual field, the patient developed progressive bilateral optic disc cupping, disc pallor, and diffuse nerve fiber layer loss on optical coherence tomography. The observed optic nerve head structural changes in this patient did not correlate with the markedly improved visual function. Visual improvement may occur in ethambutol optic neuropathy despite progressive structural changes.

Visual field changes in methotrexate therapy. Case report and review of the literature.

PURPOSE: To present a unilateral central visual field defect in a patient with psoriatic arthritis treated with Methotrexate and folic acid supplement, probably induced by toxic posterior optic neuropathy. The scotoma incompletely resolved after cessation of Methotrexate (MTX) therapy. METHODS: Serial fundoscopic, perimetric and electrophysiological examination as well as comprehensive neurological investigation including lumbar puncture, carotid sonography, electroneurography, and MRI of the brain. RESULTS: A female patient with psoriatic arthritis on long-standing Methotrexate (MTX 15 mg IM/once a week) therapy suffered first from an acute attack of central visual field defect in her right eye and later on from two subsequent deteriorations of her scotoma within one year. A demyelinating retrobulbar optic neuritis was excluded through repeated comprehensive neurological investigations and unresponsiveness to systemic corticosteroid therapy. A MTX-induced posterior optic neuropathy was suspected and the patient experienced improvement of her visual field defects only six weeks after discontinuing MTX therapy. Further improvement was observed through follow-up perimetric examinations half a year after cessation. CONCLUSIONS: Central scotoma with unremarkable optic disc can occur after long-standing treatment with MTX and despite folic acid supplementary therapy. This is most probably due to posterior optic neuropathy. Early cessation of the drug or change to another antimetabolite therapy can stop the deterioration of the visual field changes and even improve them. The exact pathomechanism is still unclear and the involvement of only one eye requires more investigation. MTX-induced posterior optic neuropathy should be included in the differential diagnosis of toxic optic neuropathy. This is getting more frequent than before because of the nowadays standard use of MTX in treatment of many autoimmune collagen diseases.

Reversible optic neuropathy associated with low-dose methotrexate therapy.

A 66-year-old woman had progressive bilateral optic neuropathy with dense central scotomas and dyschromatopsia. She had been taking oral methotrexate 2.5 mg three times per week for rheumatoid arthritis for the previous 10 months (total intake 322.5 mg) without folic acid supplementation. She had never smoked or abused alcohol and her diet was healthy. Serum folate was reduced at 1.6 ng/mL (normal >4 ng/mL) and vitamin B12 levels were normal. After stopping methotrexate and after administration of oral folic acid, she experienced complete recovery of vision. Serum folate levels returned to normal during folic acid treatment but decreased to below normal once folic treatment was stopped. The persistently low folate level remains unexplained and may reflect a genetic defect in folate metabolism. Methotrexate can cause toxic side effects resulting from folate inhibition but has not been shown definitively to cause a reversible optic neuropathy associated with low serum folate.

Elevated intraocular pressure associated with steroid treatment for infantile spasms.

PURPOSE: To evaluate the ocular changes and medical and surgical therapy after high-dose systemic steroid treatment in babies with infantile spasm and hypsarrhythmia. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: In 5 of the 9 (55%) babies with infantile spasm exposed to systemic corticosteroid treatment, an increase in intraocular pressure (IOP) and optic disc cupping was observed. INTERVENTION: Ophthalmic examination under mild sedation was conducted 3 to 4 weeks after initiation of systemic therapy. Antiglaucoma treatment was given to the patients found to have high IOPs and cup-to-disc ratio changes. Routine follow-up was continued until systemic therapy was completed. MAIN OUTCOME MEASURES: Controlled IOP with a decrease in cupping damage after antiglaucoma therapy. RESULTS: Five patients required antiglaucoma treatment; one also underwent augmented trabeculectomy. Mean IOP decreased in this subgroup from 30.1 +/- 9.5 mmHg to 15.4 +/- 4.2 mmHg in the right eye (P = 0.043) and from 32.6 +/- 7.4 mmHg to 15.2 +/- 1.8 mmHg in the left eye (P = 0.043). Mean cup-to-disc ratio improved from 0.53 +/- 0.2 to 0.37 +/- 0.04 in the right eye (P = 0.06) and from 0.57 +/- 0.12 to 0.35 +/- 0.05 in the left eye (P = 0.042). CONCLUSIONS: The rapid onset of IOP and cup-to-disc ratio changes in patients with infantile spasm and hypsarrhythmia treated by high-dose corticosteroids necessitates early and intensive monitoring to prevent anatomic ocular damage and visual impairment in the future.

Metabolic optic neuropathies.

Metabolic optic neuropathies form a rubric of disease characterized by bilaterally symmetrical visual impairment with loss of central visual acuity, dyschromatopsia, centrocecal visual field defects, temporal optic disc atrophy, and specific loss of the nerve fiber layer in the papillomacular bundle. The three subcategories of metabolic optic neuropathies are heredodegenerative (such as Leber's hereditary optic neuropathy), nutritional deficiencies (such as vitamins B12 or folic acid), or toxicities (such as ethambutol or cyanide). It's interesting to note that the first of these three is a congenital cause of mitochondrial impairment, whereas the latter two are acquired injuries to mitochondria. Hence, most if not all causes of metabolic optic neuropathies are, in fact, related to mitochondrial impairment. At the present time there is no effective treatment for heredodegenerative optic neuropathy. Nutritional deficiency metabolic optic neuropathies are treated by giving supplements of the appropriate nutrient or vitamin, whereas toxic metabolic optic neuropathies are treated by removing or preventing exposure to the toxin in question.

Toxic optic neuropathy after concomitant use of melatonin, zoloft, and a high-protein diet.

Melatonin is a neuromodulating hormone found in the pineal gland and retina. It is involved in light-dark circadian rhythms and mediates retinal processes in a manner antagonistic to that of dopamine. Zoloft (sertraline) is an antidepressant drug that blocks the reuptake of serotonin at the neural synapse. Serotonin is the natural precursor of melatonin. A 42-year-old woman sought treatment for visual acuity loss, dyschromatopsia, and altered light adaptation. Neuro-ophthalmologic examination was otherwise normal except for evolving bilateral cecocentral scotomas. She had taken Zoloft for 4 years and began a high-protein diet with melatonin supplementation 2 weeks before onset of visual symptoms. Visual acuity and color vision improved within 2 months after melatonin and the high-protein diet were discontinued. Combined use of melatonin, Zoloft, and a high-protein diet may have resulted in melatonin/dopamine imbalance in the retina, manifesting as a toxic optic neuropathy. Physicians and patients should be alerted to this potential drug interaction.

Partly reversible visual failure with methanol toxicity.

Methanol is a highly toxic substance which is used as an industrial solvent and in automotive antifreeze. If accidentally ingested blindness or death may result. The case of a young woman who developed sudden onset of visual failure following ingestion of a methanol-fortified beverage is presented. Although she failed to seek immediate medical help visual function improved. Acute changes of bilateral optic disc hyperaemia and venous engorgement were present at initial examination. She subsequently developed optic disc atrophy together with glaucomatous-like cupping of the optic discs. The aetiology of visual failure in methanol poisoning is discussed, as are the current therapeutic guidelines in the management of acute cases.

Irreversible ocular toxicity from single "challenge" dose of deferoxamine.

Deferoxamine is a chelating agent used in the treatment of transfusional iron overload and more recently in the diagnosis and treatment of increased aluminum body stores in chronic renal failure patients. High dose chronic and short-term treatment has been associated with ocular toxicity. We present a case of irreversible visual loss that occurred with a single small "challenge" dose of deferoxamine.

Deferoxamine (Desferal)-induced ocular toxicity.

A 4-year-old girl with juvenile chronic myeloid leukemia relapsed after an allogeneic bone marrow transplantation (BMT) and became refractory to conventional chemotherapy. Treatment with two courses of high-dose deferoxamine, an iron chelator (130-180 mg/kg/day), along with low-dose ARA-c (5 mg/kg/day) caused a remarkable decrease of the WBC and fetal Hb. Three days following the last dose of deferoxamine, the patient experienced an acute visual loss, confirmed by electroretinogram (ERG) and visual evoked response (VER). Slight improvement occurred a few days later, but the patient developed severe pancytopenia and died of Klebsiella septic shock. The ocular manifestations were attributed to deferoxamine toxicity in light of the rapid onset after first exposure, the electrophysiological pattern of metabolic damage in the ERG and VER, and the long interval between the last chemotherapy and BMT. The pathogenesis of deferoxamine toxicity is discussed.

Ocular and auditory toxicity of long-term, high-dose subcutaneous deferoxamine therapy.

There have been few reported ocular side effects of parenterally administered deferoxamine when used for the treatment of transfusional iron overload or acute iron poisoning. No auditory side effects have previously been reported. We describe two siblings with beta-thalassemia major who, while receiving daily subcutaneous infusions of deferoxamine, experienced visual loss secondary to optic neuropathy and sensorineural hearing loss. After discontinuation of the drug one sibling showed almost complete reversal of the optic neuropathy, but the other had a permanent unilateral visual loss. Both had a permanent hearing loss but benefited from hearing aids. The mechanism of these complications is presently unknown. Patients receiving deferoxamine should be closely monitored for ocular and auditory side effects. When such effects are detected the drug should be discontinued and the patient observed for improvement. When improvement has stabilized, therapy should be restarted at a reduced dosage.

Deferoxamine (Desferal)-induced toxic retinal pigmentary degeneration and presumed optic neuropathy.

Eight patients (16 eyes) developed ocular toxicity while undergoing intravenous deferoxamine mesylate (Desferal) chelation therapy for transfusional hemosiderosis. Presenting symptoms included decreased visual acuity, color vision abnormalities, and night blindness. Six patients presented as presumed retrobulbar optic neuropathy demonstrating central scotomas and color vision abnormalities. The remaining two patients presented with pigmentary changes confined either to the macula or equator. Following cessation of therapy, vision improved in all but four eyes, which did not attain their pretreatment visual acuity. Optic neuropathy resolved in all cases. However, follow-up revealed development of retinal pigmentary degeneration in seven patients, involving the macula in six and the equatorial retina in one. Fluorescein angiography and electrophysiological tests suggested toxicity at the level of retinal pigment epithelium and photoreceptors.