June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
A Retrospective Longitudinal Study of 458 Patients with Molecularly Confirmed ABCA4-Associated Retinal Disease
Author Affiliations & Notes
  • Beau Fenner
    Ophthalmology and Visual Sciences, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
    Singapore National Eye Center Vitreoretinal Division, Singapore, Singapore
  • Adam P DeLuca
    Institute for Vision Research, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
  • S Scott Whitmore
    Institute for Vision Research, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
  • Jeaneen L Andorf
    Institute for Vision Research, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
  • Heather T Daggett
    Institute for Vision Research, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
  • Meagan A Luse
    Institute for Vision Research, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
  • Todd E Scheetz
    Institute for Vision Research, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
  • Budd A. Tucker
    Institute for Vision Research, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
  • Ian Han
    Ophthalmology and Visual Sciences, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
    Institute for Vision Research, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
  • Edwin M Stone
    Ophthalmology and Visual Sciences, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
    Institute for Vision Research, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
  • Footnotes
    Commercial Relationships   Beau Fenner None; Adam DeLuca None; S Scott Whitmore None; Jeaneen Andorf None; Heather Daggett None; Meagan Luse None; Todd Scheetz None; Budd Tucker None; Ian Han None; Edwin Stone None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 1520. doi:
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    • Get Citation

      Beau Fenner, Adam P DeLuca, S Scott Whitmore, Jeaneen L Andorf, Heather T Daggett, Meagan A Luse, Todd E Scheetz, Budd A. Tucker, Ian Han, Edwin M Stone; A Retrospective Longitudinal Study of 458 Patients with Molecularly Confirmed ABCA4-Associated Retinal Disease. Invest. Ophthalmol. Vis. Sci. 2023;64(8):1520.

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

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Abstract

Purpose : To investigate the natural history of ABCA4-associated retinal disease with regard to genotype, age at first vision loss, fundus appearance, OCT measurements, LogMar visual acuity and Goldmann visual field volume.

Methods : Samples from patients seen by the retina service at the University of Iowa between 1959 and 2022 and who were eventually suspected to have disease caused by mutations in ABCA4 were subjected to a tiered testing strategy progressing from allele-specific screening to whole genome sequencing. Charts were reviewed to identify the age at which the patient first experienced uncorrectable vision loss and to record the best corrected visual acuities for each visit. The latter were converted to LogMar for analysis. Goldmann visual fields were traced using a custom iPad-based tool and the volumes of the hill of vision were calculated. OCTs were segmented computationally. The pathogenic severity of the more common alleles was estimated by studying groups of patients that shared one allele.

Results : A total of 458 patients from 390 families had convincing clinical features of ABCA4-associated retinal disease. Complete genotypes were identified in 400 patients and partial genotypes in 58. There were 1730 clinic visits among the members of this cohort (median 3, range 1-22 visits) with a median follow-up duration of 4 years (range 0-52 years). The median age of first vision loss was 16 years (range 4-77 years). The ten most common alleles in order of decreasing severity were: Ala1038Val/Leu541Pro, Pro1380Leu, Val256Val, IVS38-10, Arg1108Cys, IVS40+5, Gly1961Glu, Leu2027Phe, Gly863Ala, and Ala1038Val. Twenty genotypes, each composed of 2 of these 10 common alleles, were each present in 2 or more patients (65 patients total). Careful review of these patients with shared genotypes revealed evidence of modifying factors that in several cases resulted in a greater than 15 year difference in age of first vision loss.

Conclusions : ABCA4-associated retinal disease ranges from a very severe photoreceptor disease with an onset before age 5 years to a very late onset (>60 years) RPE-based condition resembling pattern dystrophy or geographic atrophy. Reliable and objective sorting of ABCA4 patients into severity classes will be essential for successful clinical trials of treatments for this disease.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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