scholarly journals Prognostic factors for visual acuity in patients with Leber's hereditary optic neuropathy after rAAV2‐ND4 gene therapy

2019 ◽  
Vol 47 (6) ◽  
pp. 774-778 ◽  
Author(s):  
Yong Zhang ◽  
Xin Li ◽  
Jiajia Yuan ◽  
Zhen Tian ◽  
Hongli Liu ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Visual Acuity ◽  
Prognostic Factors ◽  
Optic Neuropathy ◽  
Leber’S Hereditary Optic Neuropathy ◽  
Leber's Hereditary Optic Neuropathy ◽  
Hereditary Optic Neuropathy

scholarly journals Three Cases of Leber’s Hereditary Optic Neuropathy with Rapid Increase in Visual Acuity After Gene Therapy

2019 ◽  
Vol 19 (2) ◽  
pp. 134-138 ◽  
Author(s):  
Yong Zhang ◽  
Jia-jia Yuan ◽  
Hong-li Liu ◽  
Zhen Tian ◽  
Si-wei Liu ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Visual Acuity ◽  
Optic Neuropathy ◽  
Ganglion Cells ◽  
Mitochondrial Gene ◽  
Genetic Diagnosis ◽  
Leber’S Hereditary Optic Neuropathy ◽  
Leber's Hereditary Optic Neuropathy ◽  
Spontaneous Improvement ◽  
Hereditary Optic Neuropathy

Background: During the first few trials of gene therapy for Leber’s hereditary optic neuropathy performed by our group, the visual acuity of the patients increased gradually over several months, or even years. However, in the current round of gene therapy for Leber’s hereditary optic neuropathy, we noted that the visual acuity of three patients increased rapidly, within a few days after treatment. Case presentation: Three patients who were diagnosed with mitochondrial gene 11778 mutation (associated with a G-to-A transition at Mt-11778 in the ND4 subunit gene of complex I of mitochondrial DNA that changes an arginine to histidine at amino acid 340) by genetic diagnosis were followed up three times before gene therapy, which lasted for 1 year, without spontaneous improvement of vision. Visual acuity in one or both eyes of each of the three patients increased rapidly after the initial gene therapy treatment. Conclusions: We suspect that in some patients with Leber’s hereditary optic neuropathy, a portion of the retinal ganglion cells might remain in a “dormant” state for a certain period of time; these may be activated, within an optimal timeframe, during gene therapy for Leber’s hereditary optic neuropathy.

scholarly journals Progress in Gene Therapy to Prevent Retinal Ganglion Cell Loss in Glaucoma and Leber’s Hereditary Optic Neuropathy

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Sara E. Ratican ◽  
Andrew Osborne ◽  
Keith R. Martin
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Optic Nerve ◽  
Genome Editing ◽  
Optic Neuropathy ◽  
Single Gene ◽  
Leber’S Hereditary Optic Neuropathy ◽  
Leber's Hereditary Optic Neuropathy ◽  
Potential Use ◽  
Hereditary Optic Neuropathy

The eye is at the forefront of the application of gene therapy techniques to medicine. In the United States, a gene therapy treatment for Leber’s congenital amaurosis, a rare inherited retinal disease, recently became the first gene therapy to be approved by the FDA for the treatment of disease caused by mutations in a specific gene. Phase III clinical trials of gene therapy for other single-gene defect diseases of the retina and optic nerve are also currently underway. However, for optic nerve diseases not caused by single-gene defects, gene therapy strategies are likely to focus on slowing or preventing neuronal death through the expression of neuroprotective agents. In addition to these strategies, there has also been recent interest in the potential use of precise genome editing techniques to treat ocular disease. This review focuses on recent developments in gene therapy techniques for the treatment of glaucoma and Leber’s hereditary optic neuropathy (LHON). We discuss recent successes in clinical trials for the treatment of LHON using gene supplementation therapy, promising neuroprotective strategies that have been employed in animal models of glaucoma and the potential use of genome editing techniques in treating optic nerve disease.

scholarly journals Leber’s hereditary optic neuropathy following unilateral painful optic neuritis: a case report

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Chaeyeon Lee ◽  
Kyung-Ah Park ◽  
Ga-In Lee ◽  
Sei Yeul Oh ◽  
Ju-Hong Min ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Optic Neuritis ◽  
Optic Neuropathy ◽  
Visual Loss ◽  
Early Stage ◽  
Leber’S Hereditary Optic Neuropathy ◽  
Leber's Hereditary Optic Neuropathy ◽  
Intravenous Methylprednisolone ◽  
The Right ◽  
Hereditary Optic Neuropathy

Abstract Background Leber’s hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disease, characterized by acute or subacute, painless, bilateral visual loss. LHON is often misdiagnosed as optic neuritis at an early stage because of the similarity of their clinical presentation. To date, there has been no reported case of actual optic neuritis and LHON in one patient. Case presentation A 40-year-old, healthy man was referred to our clinic with acute painful visual loss in the right eye for 2 weeks. In the right eye, visual acuity decreased to 20/40, and the Ishihara colour test score was 8/14 with a relative afferent pupillary defect. Optic disc swelling was found only in the right eye, and magnetic resonance imaging revealed enhancement of the the right optic nerve, consistent with optic neuritis. After receiving 1 g of intravenous methylprednisolone daily for three days, his ocular pain resolved, and visual acuity improved to 20/20 within 2 weeks. Seven months later, the patient developed acute painless visual loss in the right eye. Visual acuity decreased to 20/200 in the right eye. There was no response to the intravenous methylprednisolone therapy at that time. Eight months later, he developed subacute painless visual loss in the left eye. Genetic testing for LHON was performed and revealed the pathologic mtDNA 11778 point mutation. Conclusions We report a case with painful unilateral optic neuritis preceding the onset of LHON. Even if a typical optic neuritis patient has completely recovered from steroid treatment once in the past, it is advisable to keep in mind the possibility of LHON if acute or subacute loss of vision subsequently or simultaneously occurs in both eyes and does not respond to steroids.

scholarly journals Wolff-Parkinson-White syndrome and noncompaction in Leber’s hereditary optic neuropathy due to the variant m.3460G>A

2018 ◽  
Vol 46 (5) ◽  
pp. 2054-2060 ◽  
Author(s):  
Josef Finsterer ◽  
Claudia Stollberger ◽  
Edmund Gatterer
Keyword(s):  
Visual Acuity ◽  
Optic Neuropathy ◽  
Systolic Function ◽  
Cardiac Conduction ◽  
Leber’S Hereditary Optic Neuropathy ◽  
Leber's Hereditary Optic Neuropathy ◽  
Wpw Syndrome ◽  
Myocardial Thickening ◽  
Ventricular Tachycardias ◽  
Hereditary Optic Neuropathy

This report describes a 66-year-old Caucasian male who acutely developed severe, bilateral impairment of visual acuity at 24 years of age. Leber’s hereditary optic neuropathy (LHON) was suspected but the diagnosis was not genetically confirmed until the age of 49 years when the primary LHON mutation m.3460G>A was detected. Since onset, visual acuity had slightly improved. The family history was positive for LHON (brother, two sisters of mother, female cousin) and genetically confirmed in his brother and one aunt. Since the age of 65 years, he had experienced recurrent vertigo. His cardiological history was positive for arterial hypertension, noncompaction, myocardial thickening, intermittent right bundle-branch-block (RBBB) and Wolff-Parkinson-White (WPW) syndrome. In addition to LHON, he presented with polyneuropathy, hyperCKaemia, carotid artery occlusion, and a history of stroke. Cardiological investigations at 66 years of age revealed mildly reduced systolic function, enlarged atria, and nonsustained ventricular tachycardias. He underwent an electrophysiological investigation, but radiofrequency ablation was ruled out due to a ‘bizarre’ cardiac conduction system. Instead, an implantable cardioverter defibrillator was proposed but refused by the patient. Since the vertigo did not resolve it was attributed to polyneuropathy. This case demonstrates that LHON may be associated with noncompaction, myocardial thickening, reduced systolic function, enlarged atria, RBBB, WPW syndrome and nonsustained ventricular tachycardias. WPW syndrome in LHON may require invasive antiarrhythmic treatment.

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