Investigative Ophthalmology & Visual Science Cover Image for Volume 65, Issue 7
June 2024
Volume 65, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2024
Age-Related Changes in Macular Structure and Symptom Onset in ABCA4 Stargardt Disease (STGD1)
Author Affiliations & Notes
  • Hanna De Bruyn
    Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
  • Nadine AlMuasher
    Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
    Northeastern University College of Science, Boston, Massachusetts, United States
  • James D Akula
    Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
    Harvard Medical School, Boston, Massachusetts, United States
  • Russell L Woods
    Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
  • Anne B Fulton
    Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
    Harvard Medical School, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Hanna De Bruyn None; Nadine AlMuasher None; James Akula None; Russell Woods None; Anne Fulton None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2024, Vol.65, 6041. doi:
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    • Get Citation

      Hanna De Bruyn, Nadine AlMuasher, James D Akula, Russell L Woods, Anne B Fulton; Age-Related Changes in Macular Structure and Symptom Onset in ABCA4 Stargardt Disease (STGD1). Invest. Ophthalmol. Vis. Sci. 2024;65(7):6041.

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

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Abstract

Purpose : To estimate the age-at-appearance of conspicuous changes in infrared scanning light ophthalmograms (SLOs), and the ellipsoid zone (EZ) and external limiting membrane (ELM) in optical coherence tomograms (OCTs), and relate each to the patient’s reported age of Stargardt disease (STGD1) symptom onset.

Methods : From our patients with secure biallelic diagnosis of STGD1, we assessed SLO and OCT images obtained at ages 2.7-25 years using the Heidelberg Spectralis. We selected 104 images obtained at 53 visits from 21 patients with a plausible age of symptom onset (from 18 families), as evaluable for analysis. On the SLO, we traced the boundary of any conspicuous macular lesion and calculated the area (square degrees). Then, we identified the EZ and ELM in each corresponding OCT volume and calculated the area of missing EZ and ELM. Though there was occasional difficulty in identifying these layers (the ELM especially), careful effort was made to ensure the same layers were assessed in every eye by two independent graders (the average of both graders’ areas was used in the analyses).

To estimate the ages at which each imaging measure would first appear, we generated respective linear mixed-effects models (SLO, EZ, ELM) with fixed effect for area and random effects of patient within family. We then determined an estimate of the intercept for each patient (the intercept extrapolates the appearance of abnormality in the image feature). We compared the extrapolated age-at-appearance to the reported age of symptom onset.

Results : SLO (z=7.40, p<0.001), EZ (z=7.96, p<0.001), and ELM (z=6.04, p<0.001) were each related to age. The appearance of SLO changes was estimated to occur, on average, 4.3 years before patient-reported symptoms (t=14.6, p<0.001), while EZ loss was estimated to appear 3.0 years before symptom onset (t=3.38, p=0.003) and ELM loss at approximately the same age as the symptom onset (t=1.61, p=0.12).

Conclusions : By estimating the age-at-appearance of changes in the SLO, EZ, and ELM from their respective progression, we characterized early features of this common juvenile macular degeneration. Of these measures, the SLO may have the greatest early prognostic significance, while the ELM may most closely associate with the onset of symptoms. This is of potential clinical importance in the assessment of patients early in the course of STGD1 and may impact planning for early interventions.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

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