Tiffany Jean Hwang1, Rustum Karanjia2, Milton Nunes Moraes-Filho3, Jesse Gale4, Jeffrey Show Tran1, Edward R Chu1, Solange R Salomao5, Adriana Berezovsky5, Rubens Belfort6, Milton Nunes Moraes3, Federico Sadun7, Anna Maria DeNegri8, Chiara La Morgia9, Piero Barboni10, Carolina do V F Ramos11, Carlos Filipe Chicani1, Peter A Quiros12, Valerio Carelli9, Alfredo A Sadun13. 1. Doheny Eye Institute, University of California Los Angeles, Los Angeles, California. 2. Doheny Eye Institute, University of California Los Angeles, Los Angeles, California; Doheny Eye Center, Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, California; Ottawa Eye Institute, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Health Research Institute, Ottawa, Ontario, Canada. 3. Instituto de Olhos de Colatina, Colatina, Espírito Santo, Brazil. 4. Surgery and Anaesthesia, University of Otago, Wellington, New Zealand. 5. Departamento de Oftalmologia e Ciências Visuais, Escola Paulista de Medicina, Universidade Federal de São Paulo, Hospital São Paulo, São Paulo, Brasil. 6. Departamento de Oftalmologia e Ciências Visuais, Escola Paulista de Medicina, Universidade Federal de São Paulo, Hospital São Paulo, São Paulo, Brasil; Instituto Paulista da Visão, São Paulo, Brasil. 7. Department of Ophthalmology, Ospedale Parodi Delfino, Colleferro, Rome, Italy. 8. Azienda Ospedaliera San Camillo-Forlanini, Roma, Italy. 9. IRCCS Institute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, Italy; Neurology Unit, Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy. 10. Studio Oculistico d'Azeglio, Bologna, Italy. 11. Hospital Federal da Lagoa, Rio de Janeiro, Brazil. 12. Doheny Eye Institute, University of California Los Angeles, Los Angeles, California; Doheny Eye Center, Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, California. 13. Doheny Eye Institute, University of California Los Angeles, Los Angeles, California; Doheny Eye Center, Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, California. Electronic address: sadun@jsei.ucla.edu.
Abstract
PURPOSE: To illustrate the natural history of Leber's hereditary optic neuropathy (LHON). DESIGN: Prospective observational case series. PARTICIPANTS: The Soave-Brazil pedigree of m.11778G>A/ND4 mitochondrial DNA LHON mutation. METHODS: A prospectively acquired database of the Soave-Brazil pedigree was reviewed. Data from 285 individuals were included in the database over a 15-year period. The pedigree was reviewed for unaffected mutation carriers who converted to affected status, 6 patients with LHON were identified. The medical records were reviewed 1 year preconversion to 1 year postconversion for visual acuity (logarithm of the minimum angle of resolution [logMAR]), Humphrey Visual Field (HVF) mean deviation (MD), and retinal nerve fiber layer (RNFL) thickness, as measured by Cirrus (Carl Zeiss, Oberkochen, Germany) optic coherence tomography (OCT). The RNFL thickness values were normalized for age. Visual acuity, HVF, and processed RNFL data from each of the 12 eyes were then sorted into 2-month time periods relative to the date of conversion, within which they were averaged. MAIN OUTCOME MEASURES: The main outcome measures were visual acuity, HVF MD, and RNFL thickness. RESULTS: Decreased visual acuity preceded conversion by up to 2 months and then declined up to 8 months postconversion. Decrease in HVF MD occurred at least 4 months preceding conversion, after which values decreased until plateau at 6 to 8 months. Average RNFL thickness was above normal baseline thickness in all 4 quadrants as measured by OCT at the time of conversion. Increase in RNFL thickness preceded conversion as early as 4 to 6 months, peaked at conversion, and decreased until individual plateaus. The temporal quadrant was first to be involved, then the inferior and superior quadrants, and the nasal quadrant showed the latest and least changes. CONCLUSIONS: Subclinical changes preceded the date of conversion and may reflect the complicated nature of identifying the date of conversion in LHON. Early increases in RNFL preceding conversion suggest that structural changes precede clinically significant vision loss. Asynchronous quadrant involvement supports a previously published mathematical model. The natural history of LHON is not a subacute process, as previously believed, but progresses more slowly, taking up to 8 months to plateau.
PURPOSE: To illustrate the natural history of Leber's hereditary optic neuropathy (LHON). DESIGN: Prospective observational case series. PARTICIPANTS: The Soave-Brazil pedigree of m.11778G>A/ND4 mitochondrial DNA LHON mutation. METHODS: A prospectively acquired database of the Soave-Brazil pedigree was reviewed. Data from 285 individuals were included in the database over a 15-year period. The pedigree was reviewed for unaffected mutation carriers who converted to affected status, 6 patients with LHON were identified. The medical records were reviewed 1 year preconversion to 1 year postconversion for visual acuity (logarithm of the minimum angle of resolution [logMAR]), Humphrey Visual Field (HVF) mean deviation (MD), and retinal nerve fiber layer (RNFL) thickness, as measured by Cirrus (Carl Zeiss, Oberkochen, Germany) optic coherence tomography (OCT). The RNFL thickness values were normalized for age. Visual acuity, HVF, and processed RNFL data from each of the 12 eyes were then sorted into 2-month time periods relative to the date of conversion, within which they were averaged. MAIN OUTCOME MEASURES: The main outcome measures were visual acuity, HVF MD, and RNFL thickness. RESULTS: Decreased visual acuity preceded conversion by up to 2 months and then declined up to 8 months postconversion. Decrease in HVF MD occurred at least 4 months preceding conversion, after which values decreased until plateau at 6 to 8 months. Average RNFL thickness was above normal baseline thickness in all 4 quadrants as measured by OCT at the time of conversion. Increase in RNFL thickness preceded conversion as early as 4 to 6 months, peaked at conversion, and decreased until individual plateaus. The temporal quadrant was first to be involved, then the inferior and superior quadrants, and the nasal quadrant showed the latest and least changes. CONCLUSIONS: Subclinical changes preceded the date of conversion and may reflect the complicated nature of identifying the date of conversion in LHON. Early increases in RNFL preceding conversion suggest that structural changes precede clinically significant vision loss. Asynchronous quadrant involvement supports a previously published mathematical model. The natural history of LHON is not a subacute process, as previously believed, but progresses more slowly, taking up to 8 months to plateau.
Authors: Nancy J Newman; Patrick Yu-Wai-Man; Valerio Carelli; Valerie Biousse; Mark L Moster; Catherine Vignal-Clermont; Robert C Sergott; Thomas Klopstock; Alfredo A Sadun; Jean-François Girmens; Chiara La Morgia; Adam A DeBusk; Neringa Jurkute; Claudia Priglinger; Rustum Karanjia; Constant Josse; Julie Salzmann; François Montestruc; Michel Roux; Magali Taiel; José-Alain Sahel Journal: Front Neurol Date: 2021-05-24 Impact factor: 4.003
Authors: Pilar Rojas; Ana I Ramírez; Rosa de Hoz; Manuel Cadena; Antonio Ferreras; Blanca Monsalve; Elena Salobrar-García; José L Muñoz-Blanco; José L Urcelay-Segura; Juan J Salazar; José M Ramírez Journal: Diagnostics (Basel) Date: 2020-01-29
Authors: Gabriel Izan Santos Botelho; Solange Rios Salomão; Célia Harumi Tengan; Rustum Karanjia; Felipo Victor Moura; Daniel Martins Rocha; Paula Baptista Eliseo da Silva; Arthur Gustavo Fernandes; Sung Eun Song Watanabe; Paula Yuri Sacai; Rubens Belfort; Valerio Carelli; Alfredo Arrigo Sadun; Adriana Berezovsky Journal: Front Neurol Date: 2021-01-18 Impact factor: 4.003