June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Phenotype and progression of retinal degeneration in patients nullizygous for ABCA4
Author Affiliations & Notes
  • Ana Fakin
    Institute of Ophthalmology, UCL, London, United Kingdom
    Moorfields Eye Hospital, London, United Kingdom
  • Anthony G Robson
    Institute of Ophthalmology, UCL, London, United Kingdom
    Moorfields Eye Hospital, London, United Kingdom
  • Graham E Holder
    Institute of Ophthalmology, UCL, London, United Kingdom
    Moorfields Eye Hospital, London, United Kingdom
  • Kaoru Fujinami
    Department of Ophthalmology, Keio University, School of Medicine, Tokyo, Japan
    National Institute of Sensory Organs, Tokyo Medical Center, Tokyo, Japan
  • Rando Allikmets
    Department of Ophthalmology, Columbia University, New York, NY
    Department of Pathology and Cell Biology, Columbia University, New York, NY
  • Jana Zernant
    Department of Ophthalmology, Columbia University, New York, NY
  • Anthony T Moore
    Institute of Ophthalmology, UCL, London, United Kingdom
    Moorfields Eye Hospital, London, United Kingdom
  • Michel Michaelides
    Institute of Ophthalmology, UCL, London, United Kingdom
    Moorfields Eye Hospital, London, United Kingdom
  • Andrew Webster
    Institute of Ophthalmology, UCL, London, United Kingdom
    Moorfields Eye Hospital, London, United Kingdom
  • Footnotes
    Commercial Relationships Ana Fakin, None; Anthony Robson, None; Graham Holder, None; Kaoru Fujinami, None; Rando Allikmets, None; Jana Zernant, None; Anthony Moore, None; Michel Michaelides, None; Andrew Webster, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 2897. doi:
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      Ana Fakin, Anthony G Robson, Graham E Holder, Kaoru Fujinami, Rando Allikmets, Jana Zernant, Anthony T Moore, Michel Michaelides, Andrew Webster; Phenotype and progression of retinal degeneration in patients nullizygous for ABCA4. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2897.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

To describe the phenotype and progression of patients with severe ABCA4 retinopathy.

 
Methods
 

A retrospective study was undertaken of 29 patients from 25 families harboring two likely-null ABCA4 mutations including stop mutations (25 alleles), frame-shifting indels (7 alleles) and splice-site mutations (18 alleles). Consecutive corrected visual acuity (VA) of the better eye, equal or above a threshold of 3/60 (1.3 LogMAR), were used for Kaplan-Meier survival analysis. Fundus autofluorescence imaging (FAF) was performed on the central 30 x 30 degrees (78 mm2) of the retina (Spectralis, Heidelberg, Germany). Regions of reduced fundus autofluorescence (FAF) were measured using RegionFinder tool included in the imaging software and plotted against age. Pattern and full-field electroretinography (PERG; ERG) were performed (N=19) and the results classified according to the published data1.

 
Results
 

There were 20 male and 9 female patients with median age at onset at 8 years (range 4 - 29). Median age at their last visit was 21 years (range 6 - 75); median VA of the better eye was 3/60 (range 6/36 - light perception). VA correlated significantly with age (Spearman’s correlation, r = 0.61, p < 0.001); survival analysis showed that VA ≥ 3/60 in the better eye was retained in 50 % of patients until the age of 38 years. Areas of reduced FAF were observed in 96 % (22/23) patients. The median total area of reduced FAF at the last imaging was 9 mm2 (range 0 - 72 mm2). There was a strong correlation between size of reduced FAF and age (Pearson’s correlation, r = 0.89, p < 0.001). In 8 patients with repeated imaging at median follow up of 5 years the median rate of enlargement was 1.2 mm2 per year. The PERG and ERG data showed evidence of macular dysfunction with generalized cone and rod system involvement (group 3) in all.

 
Conclusions
 

Nullizygosity for ABCA4 is associated with a relatively homogenous phenotype characterized by early onset of visual loss, rapid progression of central atrophy and concomitant peripheral retinal involvement. The description of progression rates in this disorder will inform the design and interpretation of novel treatment trials.<br /> <br /> Reference:<br /> 1. Lois N, et al. Phenotypic subtypes of Stargardt macular dystrophy-fundus flavimaculatus. Arch Ophthalmol. 2001.  

 
A. Visual acuity in correlation with age. B. Expansion of reduced FAF in 5 years in a patient homozygous for p.Y1027X mutation.
 
A. Visual acuity in correlation with age. B. Expansion of reduced FAF in 5 years in a patient homozygous for p.Y1027X mutation.

 
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