Rustum Karanjia1,2,3,4, Adriana Berezovsky5, Paula Yuri Sacai5, Nivea Nunes Cavascan5, Henry Yuheng Liu3, Samir Nazarali3, Milton Nunes Moraes-Filho6, Kirsten Anderson1,2, Jeffrey Show Tran1, Sung EunSong Watanabe5, Milton Nunes Moraes6, Federico Sadun7, Anna Maria DeNegri8, Piero Barboni9, Carolina do Val Ferreira Ramos10, Chiara La Morgia11,12, Valerio Carelli11,12, Rubens Belfort5, Stuart Glenn Coupland3,4, Solange Rios Salomao5, Alfredo A Sadun1,2. 1. Doheny Eye Institute, Los Angeles, California, United States. 2. Doheny Eye Centers of UCLA, Department of Ophthalmology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, United States. 3. Ottawa Eye Institute, University of Ottawa, Ottawa, Ontario, Canada. 4. Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. 5. Departamento de Oftalmologia e Ciências Visuais, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil. 6. Instituto de Olhos de Colatina, Colatina, ES, Brazil. 7. Department of Ophthalmology, Ospedale Parodi Delfino, Colleferro, Rome. 8. Azienda Ospedaliera San Camillo-Forlanini, Roma, Italy. 9. Studio Oculistico d'Azeglio, Bologna, Italy. 10. Hospital Federal da Lagoa, Rio de Janeiro, Brazil. 11. Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Institute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, Italy. 12. Unit of Neurology, Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.
Abstract
Purpose: The photopic negative response (PhNR) is a slow negative component of a flash photopic full-field ERG that has been shown to be specific for retinal ganglion cell (RGC) activity. Direct evaluation of RGC function is desirable in patients with Leber's hereditary optic neuropathy (LHON) in which the loss of central acuity can make it difficult to monitor patients with standard metrics. The purpose of this study was to evaluate the use of PhNR as an objective noninvasive clinical metric in LHON. Methods: Full-field photopic ERG recordings were collected in subjects with the mt.11778G>A/ND4 LHON mutation using a red on blue stimulus. The PhNR was identified using a computer-based automated detection system, and data were manually examined to remove movement artifacts. Results: The PhNR amplitude was compared between controls (n = 13), carriers (n = 17), and affected (n = 6). Mean PhNR amplitude decreased significantly across groups (P < 0.0001). Post hoc Tukey's test revealed a significant decrease in PhNR amplitude between carriers and controls (P < 0.05) and between carriers and affected (P < 0.01). Conclusions: We are able to demonstrate that the PhNR amplitude is significantly decreased in patients affected by LHON compared to carriers in a well-described pedigree. Surprisingly, there was also a decrease in PhNR in carriers, suggesting potential subclinical RGC dysfunction in some carriers. This is important in patients affected with LHON who typically have a dense central scotoma. The PhNR may be a useful objective outcome measure for future clinical trials.
Purpose: The photopic negative response (PhNR) is a slow negative component of a flash photopic full-field ERG that has been shown to be specific for retinal ganglion cell (RGC) activity. Direct evaluation of RGC function is desirable in patients with Leber's hereditary optic neuropathy (LHON) in which the loss of central acuity can make it difficult to monitor patients with standard metrics. The purpose of this study was to evaluate the use of PhNR as an objective noninvasive clinical metric in LHON. Methods: Full-field photopic ERG recordings were collected in subjects with the mt.11778G>A/ND4 LHON mutation using a red on blue stimulus. The PhNR was identified using a computer-based automated detection system, and data were manually examined to remove movement artifacts. Results: The PhNR amplitude was compared between controls (n = 13), carriers (n = 17), and affected (n = 6). Mean PhNR amplitude decreased significantly across groups (P < 0.0001). Post hoc Tukey's test revealed a significant decrease in PhNR amplitude between carriers and controls (P < 0.05) and between carriers and affected (P < 0.01). Conclusions: We are able to demonstrate that the PhNR amplitude is significantly decreased in patients affected by LHON compared to carriers in a well-described pedigree. Surprisingly, there was also a decrease in PhNR in carriers, suggesting potential subclinical RGC dysfunction in some carriers. This is important in patients affected with LHON who typically have a dense central scotoma. The PhNR may be a useful objective outcome measure for future clinical trials.
Authors: Yolandi van der Merwe; Anne E Faust; Ecem T Sakalli; Caroline C Westrick; George Hussey; Kevin C Chan; Ian P Conner; Valeria L N Fu; Stephen F Badylak; Michael B Steketee Journal: Sci Rep Date: 2019-03-05 Impact factor: 4.379
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
Authors: Samuel Asanad; Christian M Felix; Michele Fantini; Michael G Harrington; Alfredo A Sadun; Rustum Karanjia Journal: Sci Rep Date: 2021-03-18 Impact factor: 4.379