Jacinthe Rouleau

A randomized placebo-controlled trial of idebenone in Leber’s hereditary optic neuropathy

Abstract Major advances in understanding the pathogenesis of inherited metabolic disease caused by mitochondrial DNA mutations have yet to translate into treatments of proven efficacy. Leber’s hereditary optic neuropathy is the most common mitochondrial DNA disorder causing irreversible blindness in young adult life. Anecdotal reports support the use of idebenone in Leber’s hereditary optic neuropathy, but this has not been evaluated in a randomized controlled trial. We conducted a 24-week multi-centre double-blind, randomized, placebo-controlled trial in 85 patients with Leber’s hereditary optic neuropathy due to m.3460G>A, m.11778G>A, and m.14484T>C or mitochondrial DNA mutations. The active drug was idebenone 900 mg/day. The primary end-point was the best recovery in visual acuity. The main secondary end-point was the change in best visual acuity. Other secondary end-points were changes in visual acuity of the best eye at baseline and changes in visual acuity for both eyes in each patient. Colour-contrast sensitivity and retinal nerve fibre layer thickness were measured in subgroups. Idebenone was safe and well tolerated. The primary end-point did not reach statistical significance in the intention to treat population. However, post hoc interaction analysis showed a different response to idebenone in patients with discordant visual acuities at baseline; in these patients, all secondary end-points were significantly different between the idebenone and placebo groups. This first randomized controlled trial in the mitochondrial disorder, Leber’s hereditary optic neuropathy, provides evidence that patients with discordant visual acuities are the most likely to benefit from idebenone treatment, which is safe and well tolerated.

Neuro-ophthalmic sarcoidosis: The University of Iowa experience

Purpose: To report a case series of neuro-ophthalmic sarcoidosis manifestations from a predominantly Caucasian Midwest population. Design: Retrospective non-comparative case series and literature review. Participants: Twenty patients with biopsy proven sarcoidosis cases and neuro-ophthalmic manifestations. Methods: We reviewed 67 consecutive charts with the clinical diagnosis of neurosarcoidosis at the University of Iowa Hospital and Clinics (UIHC) Department of Ophthalmology database in Iowa City, Iowa, seen from 1984 to 2006. Main Outcome Measures: Charts were reviewed for the following: 1) demographic information; 2) neuro-ophthalmic findings; 3) biopsy location and results; 4) pre-existing sarcoidosis; 5) neuroimaging studies (e.g., cranial magnetic resonance imaging and computed tomography scans); 6) cerebrospinal fluid results; 7) sarcoid related testing (serum angiotensin converting enzyme, chest radiograph, chest computed tomography scans, Gallium scan, bronchoalveolar lavage, pulmonary function testing); 8) treatment; and 9) course of disease. Results: Twenty of the 67 charts (30%) had biopsy proven sarcoidosis and neuro-ophthalmic manifestations. Of the 20 included cases, 4 (20%) were men and 16 (80%) were women. Six (30%) patients were African-American and 14 (70%) were Caucasian. The average age at diagnosis was 43.1 years with a standard deviation of 14.1 and a range of 22 to 80 years. Neuro-ophthalmic manifestations included optic neuropathy (14), cranial neuropathy (4), Horners Syndrome (1), tonic pupil (1), and optic tract involvement (1). Of the 14 patients presenting with optic neuropathy, 8 had optic disc edema, 5 had optic disc pallor and 1 had an optic disc granuloma. Contrast cranial magnetic resonance imaging (MRI) showed pathologic contrast enhancement (16 of 19 cases) involving optic nerve (9), optic chiasm (1), optic radiations (1), cavernous sinus (1), leptomeninges (3), and cerebral parenchyma (3). Chest imaging was abnormal in the course of disease for 12 of 18 and serum angiotensin-converting enzyme was only elevated in 5 of 15 patients tested. All 20 patients were treated with corticosteroids but five required additional immunosuppressive therapy to control disease activity. The neuro-ophthalmic course was relapsing and remitting in 8 cases, stable or resolved in 7, and chronic in 5 patients. After treatment of patients with optic neuropathy, visual acuity at last follow-up visit was improved in 5, worsened in 5, and stable (i.e., within one Snellen acuity line of baseline) in 4. Conclusion: In our Midwest retrospective case series of biopsy proven neuro-ophthalmic sarcoidosis, patients were predominately white females with a wide age range. Consideration for the diagnosis of neurosarcoidosis should therefore not be limited by age, gender, or race. Optic neuropathy was the most common manifestation, typically presenting with optic disc edema and severe visual loss. No light perception vision was relatively common and should be considered a “red flag” for the diagnosis. Contrast cranial MRI frequently shows pathologic enhancement of the visual pathway. Serum angiotensin converting enzyme and chest radiography had relatively poor sensitivity for detecting biopsy proven disease in our study and therefore additional testing for tissue diagnosis might still be necessary for extrapulmonary neuro-ophthalmic sarcoidosis. Corticosteroids are the mainstay of therapy but some patients may require additional immunosuppressive therapy.

What is the treatment for giant cell arteritis

Although giant cell arteritis (GCA) is a well-known vasculitis sensitive to corticosteroid-mediated immunosuppression, numerous issues of long-term therapeutic management remain unresolved. Because GCA encompasses a broad spectrum of clinical subtypes, ranging from devastating visual loss and neurological deficits to isolated systemic symptoms, the treatment of GCA must be adjusted to each case, and recommendations vary widely in the literature. This article systematically reviews the treatment options for patients with neuro-ophthalmic and neurological complications of GCA, as well as the evidence for possible adjuvant therapies for patients with GCA. Although there is no randomized controlled clinical trial specifically evaluating GCA patients with ocular and neurological complications, we recommend that GCA patients with acute visual loss or brain ischemia be admitted to the hospital for high-dose intravenous methyl-prednisolone, close monitoring, and prevention of steroid-induced complications. Aspirin may also be helpful in these cases. The evidence supporting the use of steroid-sparing immunomodulatory agents such as methotrexate for long-term management remains debated.