A longitudinal study of Stargardt disease: Clinical and electrophysiologic assessment, progression, and genotype correlations

Kaoru Fujinami, Noemi Lois, Alice E. Davidson, Donna S. Mackay, Chris R. Hogg, Edwin M. Stone, Kazushige Tsunoda, Kazuo Tsubota, Catey Bunce, Anthony G. Robson, Anthony T. Moore, Andrew R. Webster, Graham E. Holder, Michel Michaelides

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Abstract

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.

Original languageEnglish
JournalAmerican Journal of Ophthalmology
Volume155
Issue number6
DOIs
Publication statusPublished - 2013 Jun

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Longitudinal Studies
Genotype
Vertebrate Photoreceptor Cells
Stargardt disease 1
Physiologic Monitoring
Natural History
Patient Selection
Counseling
Cohort Studies

ASJC Scopus subject areas

  • Ophthalmology

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A longitudinal study of Stargardt disease : Clinical and electrophysiologic assessment, progression, and genotype correlations. / Fujinami, Kaoru; Lois, Noemi; Davidson, Alice E.; Mackay, Donna S.; Hogg, Chris R.; Stone, Edwin M.; Tsunoda, Kazushige; Tsubota, Kazuo; Bunce, Catey; Robson, Anthony G.; Moore, Anthony T.; Webster, Andrew R.; Holder, Graham E.; Michaelides, Michel.

In: American Journal of Ophthalmology, Vol. 155, No. 6, 06.2013.

Research output: Contribution to journalArticle

Fujinami, K, Lois, N, Davidson, AE, Mackay, DS, Hogg, CR, Stone, EM, Tsunoda, K, Tsubota, K, Bunce, C, Robson, AG, Moore, AT, Webster, AR, Holder, GE & Michaelides, M 2013, 'A longitudinal study of Stargardt disease: Clinical and electrophysiologic assessment, progression, and genotype correlations', American Journal of Ophthalmology, vol. 155, no. 6. https://doi.org/10.1016/j.ajo.2013.01.018
Fujinami, Kaoru ; Lois, Noemi ; Davidson, Alice E. ; Mackay, Donna S. ; Hogg, Chris R. ; Stone, Edwin M. ; Tsunoda, Kazushige ; Tsubota, Kazuo ; Bunce, Catey ; Robson, Anthony G. ; Moore, Anthony T. ; Webster, Andrew R. ; Holder, Graham E. ; Michaelides, Michel. / A longitudinal study of Stargardt disease : Clinical and electrophysiologic assessment, progression, and genotype correlations. In: American Journal of Ophthalmology. 2013 ; Vol. 155, No. 6.
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abstract = "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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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

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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