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      What are the characteristics and progression of visual field defects in patients with Leber hereditary optic neuropathy: a prospective single-centre study in China

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          Abstract

          Objective

          To study the characteristics and progression of visual field defects in patients with Leber hereditary optic neuropathy.

          Design

          Prospective study.

          Setting

          3-A-class hospital in China; single-centre study.

          Participants

          From 100 patients diagnosed with Leber hereditary optic neuropathy, 80 (160 eyes; 68 men and 12 women; youngest patient, 6 years; oldest patient, 35 years) were recruited.

          Exposure

          All patients were followed up for at least 12 months. Each patient underwent at least three visual field examinations. Patient groups 1–6 were created according to the time of visual field data acquisition. Patient group 7 included patients with a different onset of disease between eyes. Group 8 was composed of patients with a course of disease of 12–24 months when one of the examinations performed. Patients who performed the third examination made up patient group 9.

          Primary outcome measures

          Prevalence of the different visual field defect types on the basis of severity in groups 1–6. Mean of the difference of visual function between eyes in group 7.

          Result

          In groups 1–6, the prevalences of defects classified using Visual Field Index values were significantly different between groups 1 and 3. In group 7, with the prolongation of the course of the disease, the mean of the difference of visual function between eyes decreased. There was no significant correlation between age and the severity of visual field defect. There was significant correlation between visual acuity and the severity of visual field defect.

          Conclusion

          Visual field defects in patients with Leber hereditary optic neuropathy (G11778A) may continuously progress within 6 months of disease development, and remain stable after 9 months. With the progression of the disease, the differences in visual function between eyes may decrease. The severity of visual field defect seems to be independent of age; however, could be related to visual acuity.

          Trial registration number

          NCT03428178, NCT01267422.

          Related collections

          Most cited references11

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          Inherited mitochondrial optic neuropathies

          Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA) are the two most common inherited optic neuropathies and they result in significant visual morbidity among young adults. Both disorders are the result of mitochondrial dysfunction: LHON from primary mitochondrial DNA (mtDNA) mutations affecting the respiratory chain complexes; and the majority of DOA families have mutations in the OPA1 gene, which codes for an inner mitochondrial membrane protein critical for mtDNA maintenance and oxidative phosphorylation. Additional genetic and environmental factors modulate the penetrance of LHON, and the same is likely to be the case for DOA which has a markedly variable clinical phenotype. The selective vulnerability of retinal ganglion cells (RGCs) is a key pathological feature and understanding the fundamental mechanisms that underlie RGC loss in these disorders is a prerequisite for the development of effective therapeutic strategies which are currently limited.
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            Gene Therapy for Leber Hereditary Optic Neuropathy

            To determine the effects of AAV2(Y444,500,730F)-P1ND4v2 in patients with Leber hereditary optic neuropathy (LHON).
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              A neurodegenerative perspective on mitochondrial optic neuropathies

              Mitochondrial optic neuropathies constitute an important cause of chronic visual morbidity and registrable blindness in both the paediatric and adult population. It is a genetically heterogeneous group of disorders caused by both mitochondrial DNA (mtDNA) mutations and a growing list of nuclear genetic defects that invariably affect a critical component of the mitochondrial machinery. The two classical paradigms are Leber hereditary optic neuropathy (LHON), which is a primary mtDNA disorder, and autosomal dominant optic atrophy (DOA) secondary to pathogenic mutations within the nuclear gene OPA1 that encodes for a mitochondrial inner membrane protein. The defining neuropathological feature is the preferential loss of retinal ganglion cells (RGCs) within the inner retina but, rather strikingly, the smaller calibre RGCs that constitute the papillomacular bundle are particularly vulnerable, whereas melanopsin-containing RGCs are relatively spared. Although the majority of patients with LHON and DOA will present with isolated optic nerve involvement, some individuals will also develop additional neurological complications pointing towards a greater vulnerability of the central nervous system (CNS) in susceptible mutation carriers. These so-called “plus” phenotypes are mechanistically important as they put the loss of RGCs within the broader perspective of neuronal loss and mitochondrial dysfunction, highlighting common pathways that could be modulated to halt progressive neurodegeneration in other related CNS disorders. The management of patients with mitochondrial optic neuropathies still remains largely supportive, but the development of effective disease-modifying treatments is now within tantalising reach helped by major advances in drug discovery and delivery, and targeted genetic manipulation. Electronic supplementary material The online version of this article (doi:10.1007/s00401-016-1625-2) contains supplementary material, which is available to authorized users.
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                Author and article information

                Journal
                BMJ Open
                BMJ Open
                bmjopen
                bmjopen
                BMJ Open
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2044-6055
                2019
                15 March 2019
                : 9
                : 3
                : e025307
                Affiliations
                [1 ] departmentDepartment of Ophthalmology , Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
                [2 ] departmentDepartment of Ophthalmology , Taihe Hospital, Hubei University of Medicine , Shiyan, China
                Author notes
                [Correspondence to ] Professor Bin Li; libin-12@ 123456163.com
                Article
                bmjopen-2018-025307
                10.1136/bmjopen-2018-025307
                6429856
                30878986
                bac4bbaf-0c9e-43c6-b079-2c9f31c9c972
                © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 14 July 2018
                : 09 February 2019
                : 12 February 2019
                Funding
                Funded by: the National Natural Science Foundation of the People’s Republic of China;
                Categories
                Ophthalmology
                Research
                1506
                1718
                Custom metadata
                unlocked

                Medicine
                leber hereditary optic neuropathy,visual fields,genetic therapy
                Medicine
                leber hereditary optic neuropathy, visual fields, genetic therapy

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