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. 2022 Jun;100(4):395-402.
doi: 10.1111/aos.14996. Epub 2021 Aug 25.

Stargardt disease: monitoring incidence and diagnostic trends in the Netherlands using a nationwide disease registry

Esmee H Runhart  1   2 , Patty Dhooge  1   2 , Magda Meester-Smoor  3 , Jeroen Pas  1 , Jan Willem R Pott  4 , Redmer van Leeuwen  5 , Hester Y Kroes  6 , Arthur A Bergen  7   8 , Yvonne de Jong-Hesse  9 , Alberta A Thiadens  3 , Mary J van Schooneveld  9   10 , Maria van Genderen  5   10 , Camiel Boon  9   11 , Caroline Klaver  1   3   12 , L Ingeborg van den Born  13   14 , Frans P M Cremers  2   15 , Carel B Hoyng  1   2
Affiliations

Stargardt disease: monitoring incidence and diagnostic trends in the Netherlands using a nationwide disease registry

Esmee H Runhart et al. Acta Ophthalmol. 2022 Jun.

Abstract

Purpose: To assess the incidence of Stargardt disease (STGD1) and to evaluate demographics of incident cases.

Methods: For this retrospective cohort study, demographic, clinical and genetic data of patients with a clinical diagnosis of STGD1 were registered between September 2010 and January 2020 in a nationwide disease registry. Annual incidence (2014-2018) and point prevalence (2018) were assessed on the basis of this registry.

Results: A total of 800 patients were registered, 56% were female and 83% were of European ancestry. The incidence was 1.67-1.95:1,000,000 per year and the point prevalence in 2018 was approximately 1:22,000-1:19,000 (with and without 10% of potentially unregistered cases). Age at onset was associated with sex (p = 0.027, Fisher's exact); 1.9x more women than men were observed (140 versus 74) amongst patients with an age at onset between 10 and 19 years, while the sex ratio in other age-at-onset categories approximated one. Late-onset STGD1 (≥45 years) constituted 33% of the diagnoses in 2014-2018 compared to 19% in 2004-2008. Diagnostic delay (≥2 years between the first documentation of macular abnormalities and diagnosis) was associated with older age of onset (p = 0.001, Mann-Whitney). Misdiagnosis for age-related macular degeneration (22%) and incidental STGD1 findings (14%) was common in patients with late-onset STGD1.

Conclusion: The observed prevalence of STGD1 in real-world data was lower than expected on the basis of population ABCA4 allele frequencies. Late-onset STGD1 was more frequently diagnosed in recent years, likely due to higher awareness of its phenotype. In this pretherapeutic era, mis- and underdiagnosis of especially late-onset STGD1 and the role of sex in STGD1 should receive special attention.

Keywords: ABCA4; STGD1; Stargardt Disease; incidence; prevalence.

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Figures

Figure 1
Figure 1
Distribution of the age at onset of Stargardt disease by sex. Age at onset was associated with sex (p = 0.027, Fisher’s exact). Women were overrepresented (1.9:1) amongst patients with an age at onset of 10‐19 years (n = 214)
Figure 2
Figure 2
Annual incidence of Stargardt disease based on the national registry. The number of registered STGD1 diagnoses increased over time, which was mostly attributed to an increase in the diagnosis and registration of late‐onset STGD1 (≥45 years). The incidence of early‐onset Stargardt disease (<11 years) remained fairly constant
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