Measurement and Reproducibility of Preserved Ellipsoid Zone Area and Preserved Retinal Pigment Epithelium Area in Eyes With Choroideremia

Amir H Hariri; Swetha B Velaga; Aniz Girach; Michael S Ip; Phuc V Le; Byron L Lam; M Dominik Fischer; Eeva-Marja Sankila; Mark E Pennesi; Frank G Holz; Robert E MacLaren; David G Birch; Carel B Hoyng; Ian M MacDonald; Graeme C Black; Stephen H Tsang; Neil M Bressler; Michael Larsen; Michael B Gorin; Andrew R Webster; SriniVas R Sadda; Natural History of the Progression of Choroideremia (NIGHT) Study Group

doi:10.1016/j.ajo.2017.05.002

Measurement and Reproducibility of Preserved Ellipsoid Zone Area and Preserved Retinal Pigment Epithelium Area in Eyes With Choroideremia

Am J Ophthalmol. 2017 Jul:179:110-117. doi: 10.1016/j.ajo.2017.05.002. Epub 2017 May 10.

Authors

Amir H Hariri¹, Swetha B Velaga², Aniz Girach³, Michael S Ip¹, Phuc V Le¹, Byron L Lam⁴, M Dominik Fischer⁵, Eeva-Marja Sankila⁶, Mark E Pennesi⁷, Frank G Holz⁸, Robert E MacLaren⁹, David G Birch¹⁰, Carel B Hoyng¹¹, Ian M MacDonald¹², Graeme C Black¹³, Stephen H Tsang¹⁴, Neil M Bressler¹⁵, Michael Larsen¹⁶, Michael B Gorin¹⁷, Andrew R Webster¹⁸, SriniVas R Sadda¹⁹; Natural History of the Progression of Choroideremia (NIGHT) Study Group

Affiliations

¹ Doheny Image Reading Center, Doheny Eye Institute, Los Angeles, California; Department of Ophthalmology, David Geffen School of Medicine of the University of California-Los Angeles, Los Angeles, California.
² Doheny Image Reading Center, Doheny Eye Institute, Los Angeles, California.
³ NightstaRx Ltd, London, United Kingdom.
⁴ Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida.
⁵ Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
⁶ Helsinki University Eye Hospital, Finland.
⁷ Casey Eye Institute, Oregon Health & Science University, Portland, Oregon.
⁸ Department of Ophthalmology, University of Bonn, Bonn, Germany.
⁹ Nuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford and Oxford University Eye Hospital, NHS Foundation Trust, NIHR Biomedical Research Centre, Oxford, United Kingdom; Moorfields Eye Hospital, NHS Foundation Trust, NIHR Biomedical Research Centre, London, United Kingdom.
¹⁰ Retina Foundation of the Southwest, Dallas, Texas.
¹¹ Department of Ophthalmology, Radboud University Medical Center, Nijmegen, Netherlands.
¹² Department of Ophthalmology and Visual Sciences, University of Alberta, Edmonton, Alberta, Canada.
¹³ Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, St Mary's Hospital, Manchester, United Kingdom.
¹⁴ Departments of Ophthalmology and of Pathology and Cell Biology, Columbia University, New York, New York.
¹⁵ Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
¹⁶ Department of Ophthalmology, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
¹⁷ Department of Ophthalmology, David Geffen School of Medicine of the University of California-Los Angeles, Los Angeles, California.
¹⁸ Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom; UCL Institute of Ophthalmology, London, United Kingdom.
¹⁹ Doheny Image Reading Center, Doheny Eye Institute, Los Angeles, California; Department of Ophthalmology, David Geffen School of Medicine of the University of California-Los Angeles, Los Angeles, California. Electronic address: ssadda@doheny.org.

PMID: 28499705
DOI: 10.1016/j.ajo.2017.05.002

Abstract

Purpose: To identify valid and reproducible methods for quantifying anatomic outcome measures for eyes with choroideremia (CHM) in clinical trials.

Design: Reliability analysis study.

Methods: In this multicenter study, patients with confirmed genetic diagnosis of CHM were enrolled. All cases underwent spectral-domain optical coherence tomography (SDOCT) and fundus autofluorescence (FAF) imaging. Two graders independently delineated boundaries of preserved autofluorescence (PAF) and preserved ellipsoid zone (EZ) on FAF and OCT images, respectively. The results of the 2 independent gradings of both FAF and OCT images were compared to assess the reproducibility of the grading methods.

Results: A total of 148 eyes from 75 cases were included. In 21% of eyes PAF and in 43% of eyes preserved EZ had extended beyond the image capture area. After exclusion of these eyes and low-quality images, 114 FAF and 77 OCT images were graded. The mean PAF areas from 2 independent gradings were 3.720 ± 3.340 mm² and 3.692 ± 3.253 mm², respectively. Intraclass correlation coefficient (ICC) for these gradings was 0.996. The mean preserved EZ areas from 2 independent gradings were 2.746 ± 2.319 mm² and 2.858 ± 2.446 mm², respectively. ICC for these gradings was 0.991.

Conclusions: Quantifying preserved retinal pigment epithelium and EZ areas on FAF and OCT images, respectively, in CHM patients is highly reproducible. These variables would be potential anatomic outcome measures for CHM clinical trials and could be studied and tracked longitudinally in choroideremia.

Publication types

Multicenter Study

MeSH terms

Aged
Choroideremia / diagnosis*
Choroideremia / physiopathology
Female
Fluorescein Angiography / methods*
Fundus Oculi
Humans
Male
Middle Aged
Ophthalmoscopy / methods*
Reproducibility of Results
Retinal Pigment Epithelium / pathology*
Tomography, Optical Coherence / methods*
Visual Acuity*

Grants and funding

EME/12/66/35/DH_/Department of Health/United Kingdom