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Predicting Progression of ABCA4-Associated Retinal Degenerations Based on Longitudinal Measurements of the Leading Disease Front
Journal article   Open access   Peer reviewed

Predicting Progression of ABCA4-Associated Retinal Degenerations Based on Longitudinal Measurements of the Leading Disease Front

Artur V Cideciyan, Malgorzata Swider, Sharon B Schwartz, Edwin M Stone and Samuel G Jacobson
Investigative ophthalmology & visual science, Vol.56(10), pp.5946-5955
09/2015
DOI: 10.1167/iovs.15-17698
PMCID: PMC4572941
PMID: 26377081
url
https://doi.org/10.1167/iovs.15-17698View
Published (Version of record) Open Access

Abstract

To evaluate the progression of the earliest stage of disease in ABCA4-associated retinal degenerations (RDs). Near-infrared excited reduced-illuminance autofluorescence imaging was acquired across the retina up to 80 degrees eccentricity in 44 patients with two ABCA4 alleles. The eccentricity of the leading disease front (LDF) corresponding to the earliest stage of disease was measured along the four meridians. A mathematical model describing the expansion of the LDF was developed based on 6 years of longitudinal follow-up. The extent of LDF along the superior, inferior, and temporal meridians showed a wide spectrum from 3.5 to 70 degrees. In patients with longitudinal data, the average centrifugal expansion rate was 2 degrees per year. The nasal extent of LDF between the fovea and ONH ranged from 4.3 to 16.5 degrees and expanded at 0.35 degrees per year. The extent of LDF beyond ONH ranged from 19 to 75 degrees and expanded on average at 2 degrees per year. A mathematical model fit well to the longitudinal data describing the expansion of the LDF. The eccentricity of the LDF in ABCA4-RD shows a continuum from parafovea to far periphery along all four meridians consistent with a wide spectrum of severity observed clinically. The model of progression may provide a quantitative prediction of the LDF expansion based on the age and eccentricity of the LDF at a baseline visit, and thus contribute significantly to the enrollment of candidates appropriate for clinical trials planning specific interventions, efficacy outcomes, and durations.
Predictive Value of Tests Retinal Degeneration - genetics Tomography, Optical Coherence Humans Middle Aged Male Visual Acuity Disease Progression Young Adult ATP-Binding Cassette Transporters - genetics Adolescent Alleles Adult Female Retinal Degeneration - pathology Child Longitudinal Studies Optical Imaging - methods

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