UNASSIGNED: Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder that typically presents with painless, central visual loss, hyperaemia of the optic nerve head, and peripapillary telangiectasias. Most LHON cases are due to one of three variants, but several less common variants also exist. We describe a clinical case of LHON associated with the variant m.3866T>C, which is possibly linked to LHON.
UNASSIGNED: A 59-year-old Caucasian woman experienced acute, bilateral, and painless visual loss. She reported cigarette smoking, and elevated phosphatidylethanol suggested harmful alcohol consumption. Her best-corrected visual acuity (BCVA) was 20/100 for the right eye and 20/50 for the left eye. She could only read the Ishihara demonstration plate, and threshold perimetry demonstrated reduced central sensitivity bilaterally. Her optic nerve heads were hyperaemic, with peripapillary telangiectasias. The visual symptoms and clinical findings suggested LHON. Magnetic resonance imaging demonstrated a tuberculum sella meningioma and two cerebral aneurysms, which we regarded as incidental findings. Genetic testing did not identify common LHON variants but a rare homoplasmic variant, m.3866T>C, which studies suggest might cause LHON or act in synergy with other variants to increase the disease penetrance. After initiating test-of-treatment with idebenone 900 mg per day, the patient\'s BCVA improved to 20/32 for both eyes and then stabilized.
UNASSIGNED: This case strengthens the evidence for m.3866T>C as a causative LHON variant. The case also raises the question as to whether this particular variant can respond favourably to treatment with idebenone.

UNASSIGNED: Leber Hereditary Optic Neuropathy (LHON) is the most common inherited mitochondrial disease characterized by bilateral, painless, subacute visual loss with a peak age of onset in the second to third decade. Historically, LHON was thought to be exclusively maternally inherited due to mutations in mitochondrial DNA (mtDNA); however, recent studies have identified an autosomal recessive form of LHON (arLHON) caused by point mutations in the nuclear gene, DNAJC30.
UNASSIGNED: In this study, we report the cases of three Eastern European individuals presenting with bilateral painless visual loss, one of whom was also exhibiting motor symptoms. After a several-year-long diagnostic journey, all three patients were found to carry the homozygous c.152A>G (p.Tyr51Cys) mutation in DNAJC30. This has been identified as the most common arLHON pathogenic variant and has been shown to exhibit a significant founder effect amongst Eastern European individuals.
UNASSIGNED: This finding adds to the growing cohort of patients with arLHON and demonstrates the importance of DNAJC30 screening in patients with molecularly undiagnosed LHON, particularly in Eastern European individuals. It is of heightened translational significance as patients diagnosed with arLHON exhibit a better prognosis and response to therapeutic treatment with the co-enzyme Q10 analog idebenone.

UNASSIGNED: We report the sperm characteristics of a male patient who developed, when he was 18 years old, a Leber hereditary optic neuropathy, a hereditary optic neuropathy due to mtDNA mutation as well as variants in the nuclear DNA. At the age of 30 years-old, he complained of infertility lasting for 2 years. Semen analyses showed low motility spermatozoa and a high percentage of morphological or ultrastructural abnormalities. Levels of epididymal markers were strongly atypical. Idebenone was prescribed as treatment of his Leber hereditary optic neuropathy in order to improve his visual acuity. After 5 months of this treatment, motility of spermatozoa increased, and their vitality improved. A natural conception occurred.
UNASSIGNED: This case is the first description of an anomaly of spermatozoas and of the epididymis epithelium in a patient with Leber hereditary optic neuropathy. It draws attention to sperm pathologies in patients with mitochondrial disorders. The role of the mtDNA mutations must be suspected since it plays an important role in the development and motility of spermatozoa. In addition, idebenone can by-pass the complex I and transfer electrons to complex III. It has been suspected to have a favorable effect on spermatogenesis.
UNASSIGNED: This case confirms the possibility of sperm dysfunction in Leber hereditary optic neuropathy and the interest of idebenone as a treatment for infertility due to mtDNA mutations in human.

UNASSIGNED: To report a rare case of reversible vision loss from tacrolimus-associated toxic optic neuropathy.
UNASSIGNED: A 30-year-old man with cystic fibrosis requiring bilateral lung transplantation developed painless, bilateral, gradual onset central vision loss with dyschromatopsia two years after starting tacrolimus. Visual fields revealed bilateral cecocentral scotomas. Fundoscopy demonstrated bilateral temporal pallor of the optic nerves. Testing for nutritional deficiencies was unremarkable. Tacrolimus was switched to cyclosporine and the patient was started on idebenone. Two months later, the patient demonstrated marked improvement in his visual acuity and dyschromatopsia.
UNASSIGNED: Neurotoxicity is a rare but major potential side effect of tacrolimus. Idebenone should be considered as a potential, low-risk supplement for transplant patients who are immunosuppressed in whom toxic optic neuropathy is a concern.

Objective: Stabilizers, especially carbohydrate polymers, have been shown to be necessary for the stabilization of drug nanocrystals. However, the impacts of select stabilizers on the in vitro and in vivo efficacy of therapeutics have rarely been reported. The aim of this study was to evaluate the importance of stabilizers in the formulation of drug nanocrystals.Research design and methods: Idebenone nanocrystals (IDBNC) stabilized by various stabilizers were formulated using a milling method. The in vitro dissolution profiles in water and in situ absoprtion were compared. Finally, an in vivo pharmacokinetic study was performed.Results: The IDBNC profiles were found to have acceptable sizes and similar morphology and crystallinity. The dissolution profiles of IDBNC stabilized by different stabilizers were notably different, indicating the critical influence of stabilizers on the release rate of IDB. The Soluplus-stabilized IDBNC (IDBNC400 nm/Soluplus) achieved better absorption than HPMC stabilized IDBNC (IDBNC400 nm/HPMC). The pharmacokinetic study demonstrated that Soluplus-stabilized IDBNC had preferable kinetics, with an AUC0-24h of IDBNC400 nm/Soluplus (3.08-fold relative to IDB suspension), compared to IDBNC400 nm/HPMC (1.88-fold).Conclusions: Choice of stabilizer plays an important role in the formulation of IDBNC. We anticipate that the role of stabilizers in the pharmacokinetic disposition of IDBNC has significant implications for a wide range of other drug crystal formulations.

Purpose. To report a case of a young patient with a clinical condition suggestive of Leber\'s hereditary optic neuropathy (LHON) confirmed by genetic testing. Material and methods. We present a case of a 21-year-old Caucasian male with bilateral visual loss. The patient complained of visual loss, initially in the right eye and two weeks thereafter in the left eye. Ophthalmological examination revealed visual acuity of 20/ 400 in both eyes, anterior segment of normal appearance, normal direct and consensual pupillary light reflexes, and absence of a relative afferent pupillary defect. Fundus examination demonstrated bilateral protruding, hyperemic, with blurred margins in the nasal quadrant papilla and reduced excavation, tortuous vessels, peripapillary telangiectasias. The optical coherence tomography (OCT) revealed bilateral increase of the retinal nerve fiber layer (RNFL) thickness and ganglion cell layer - inner plexiform layer complex (GCL-IPL complex) severely thinned. Results. The clinical suspicion of Leber\'s hereditary optic neuropathy was confirmed by the 3460 mutation, which was identified on blood mitochondrial analysis. Meantime, the visual acuity decreased to CF in both eyes. We initiated treatment with idebenone (300 mg T.I.D.). After three months of follow-up, visual acuity was CF in both eyes, bilateral pupillary light reflexes within normal limits and optic disc pallor was noticed in both eyes. Conclusion. No visual recovery was noticed after one year. We recommended that the idebenone treatment was continued and the patient was followed-up further.

Leber\'s hereditary optic neuropathy is the most common mitochondrial condition and is characterized by bilateral, painless, subacute visual loss that develops during young adult life. LHON is a rare condition and this lack of knowledge can make doctors suspect and treat for other causes of vision loss. Typically, a series of tests are performed to confirm LHON diagnosis or exclude any other conditions. We presented the case of two brothers, HB, of 40 years old and HF, of 38 years old, who presented with a decrease in visual acuity in both eyes. The patients had been diagnosed with optic atrophy of unknown cause a long time ago, but no further investigations were made. They were treated with corticosteroids, antioxidants and vasodilators, but with no significant benefit. A blood test of the mitochondrial DNA, a magnetic resonance imaging and an optic coherence tomography of the optic nerve and macula were part of the following assessment of our patients. The mitochondrial DNA analyses revealed the 3460 G>A mutation on the mtND1 gene in both patients. Based on the medical history, the fundus aspect, the optic coherence tomography and the paraclinical investigations of the diagnosis of Leber\'s hereditary optic neuropathy were established in both patients. We started the treatment with idebenone and we evaluated the patients after three months.
BACKGROUND: LHON = Leber\'s hereditary optic neuropathy, mtDNA = mitochondrial DNA, VA = visual acuity, CF = count fingers, OCT = optical coherence tomography, RNFL = retinal nerve fiber layer, GCL = ganglion cells layer, MS = multiple sclerosis, MRI = magnetic resonance imaging, MTI = magnetization transfer imaging, MTR = magnetization transfer ratio.