TY - JOUR
T1 - A longitudinal study of Stargardt disease
T2 - Clinical and electrophysiologic assessment, progression, and genotype correlations
AU - Fujinami, Kaoru
AU - Lois, Noemi
AU - Davidson, Alice E.
AU - Mackay, Donna S.
AU - Hogg, Chris R.
AU - Stone, Edwin M.
AU - Tsunoda, Kazushige
AU - Tsubota, Kazuo
AU - Bunce, Catey
AU - Robson, Anthony G.
AU - Moore, Anthony T.
AU - Webster, Andrew R.
AU - Holder, Graham E.
AU - Michaelides, Michel
N1 - Funding Information:
All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. Publication of this article was supported by grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and University College London, Institute of Ophthalmology (UK), Fight For Sight (UK), Moorfields Eye Hospital Special Trustees (UK), Macular Disease Society (UK), the Foundation Fighting Blindness (USA), Suzuken Memorial Foundation (Japan), Mitsukoshi Health and Welfare Foundation (Japan), and Daiwa Anglo-Japanese Foundation (Japan). M.M. is supported by an FFB Career Development Award (USA). Contributions of authors: conception and design (K.F., N.L., A.D., A.W., G.H., M.M.); analysis and interpretation (K.F., N.L., A.D., D.M., C.H., E.S., K. Tsunoda., C.B., A.R., A.M., A.W., G.H., M.M.); writing the article (K.F., A.D., A.R., A.W., K. Tsubota., C.B., G.H., M.M.); critical revision of the article (K.F., N.L., A.D., E.S., K.Tsunoda, K.Tsubota, C.B., A.W., G.H., M.M.); final approval of the article (K.F., K. Tsunoda., C.B., A.T., A.W., G.H., M.M.); data collection (K.F., A.D., D.M., C.H., E.S., A.R., A.M., A.W., G.H., M.M.); provision of materials, patients, or resources (K.F., A.R., A.M., A.W., G.H., M.M.); statistical expertise (K.F., K. Tsubota., C.B., M.M.); obtaining funding (K.F., D.M., K. Tsunoda., A.M., A.W., M.M.); literature search (K.F., A.D., D.M., K. Tsunoda., A.R., M.M.); and administrative, technical, or logistic support (K.F., C.H., A.R., M.M.). The authors are grateful to those who contributed to the assembly of the ABCA4 panel, particularly Naushin Waseem, Bev Scott, Genevieve Wright, Sophie Devery, and Ravinder Chana (University College London, Institute of Ophthalmology, London, United Kingdom). The authors thank Professor Yozo Miyake (Aichi Medical University, Aichi, Japan), Panagiotis Sergouniotis, Rajarshi Mukhopadhyay, Arundhati Dev Borman, Eva Lenassi (University College London, Institute of Ophthalmology, London, United Kingdom), and Jean Andorf (University of Iowa Institute for Vision Research, Howard Hughes Medical Institute, Iowa City, Iowa, USA) for their insightful comments.
PY - 2013/6
Y1 - 2013/6
N2 - Purpose: To investigate the clinical and electrophysiologic natural history of Stargardt disease and correlate with the genotype. Design: Cohort study of 59 patients. Methods: Clinical history, examination, and electrophysiologic assessment were undertaken in a longitudinal survey. Patients were classified into 3 groups based on electrophysiologic findings, as previously published: Group 1 had dysfunction confined to the macula; Group 2 had macular and generalized cone system dysfunction; and Group 3 had macular and both generalized cone and rod system dysfunction. At baseline, there were 27 patients in Group 1, 17 in Group 2, and 15 in Group 3. Amplitude reduction of >50% in the relevant electroretinogram (ERG) component or a peak time shift of >3 ms for the 30 Hz flicker ERG or bright flash a-wave was considered clinically significant ERG deterioration. Molecular screening of ABCA4 was undertaken. Results: The mean age at baseline was 31.7 years, with the mean follow-up interval being 10.5 years. A total of 22% of patients from Group 1 showed ERG group transition during follow-up, with 11% progressing to Group 2 and 11% to Group 3. Forty-seven percent of patients in Group 2 progressed to Group 3. There was clinically significant ERG deterioration in 54% of all subjects: 22% of Group 1, 65% of Group 2, and 100% of Group 3. At least 1 disease-causing ABCA4 variant was identified in 47 patients. Conclusions: All patients with initial rod ERG involvement demonstrated clinically significant electrophysiologic deterioration; only 20% of patients with normal full-field ERGs at baseline showed clinically significant progression. Such data assist counseling by providing more accurate prognostic information and are also highly relevant in the design, patient selection, and monitoring of potential therapeutic interventions.
AB - Purpose: To investigate the clinical and electrophysiologic natural history of Stargardt disease and correlate with the genotype. Design: Cohort study of 59 patients. Methods: Clinical history, examination, and electrophysiologic assessment were undertaken in a longitudinal survey. Patients were classified into 3 groups based on electrophysiologic findings, as previously published: Group 1 had dysfunction confined to the macula; Group 2 had macular and generalized cone system dysfunction; and Group 3 had macular and both generalized cone and rod system dysfunction. At baseline, there were 27 patients in Group 1, 17 in Group 2, and 15 in Group 3. Amplitude reduction of >50% in the relevant electroretinogram (ERG) component or a peak time shift of >3 ms for the 30 Hz flicker ERG or bright flash a-wave was considered clinically significant ERG deterioration. Molecular screening of ABCA4 was undertaken. Results: The mean age at baseline was 31.7 years, with the mean follow-up interval being 10.5 years. A total of 22% of patients from Group 1 showed ERG group transition during follow-up, with 11% progressing to Group 2 and 11% to Group 3. Forty-seven percent of patients in Group 2 progressed to Group 3. There was clinically significant ERG deterioration in 54% of all subjects: 22% of Group 1, 65% of Group 2, and 100% of Group 3. At least 1 disease-causing ABCA4 variant was identified in 47 patients. Conclusions: All patients with initial rod ERG involvement demonstrated clinically significant electrophysiologic deterioration; only 20% of patients with normal full-field ERGs at baseline showed clinically significant progression. Such data assist counseling by providing more accurate prognostic information and are also highly relevant in the design, patient selection, and monitoring of potential therapeutic interventions.
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U2 - 10.1016/j.ajo.2013.01.018
DO - 10.1016/j.ajo.2013.01.018
M3 - Article
C2 - 23499370
AN - SCOPUS:84877745361
VL - 155
SP - 1075-1088.e13
JO - American Journal of Ophthalmology
JF - American Journal of Ophthalmology
SN - 0002-9394
IS - 6
ER -