Abstract
Purpose :
To assess the clinical, genetic and demographic characteristics of patients with “measurable” atrophic lesions in ABCA4 disease.
Methods :
The presence and measurability of atrophic lesions on 488-nm autofluorescence (AF) images acquired using the Spectralis HRA+OCT (Heidelberg Engineering), previously defined as definitely decreased autofluorescence (DDAF), was assessed in a genetically confirmed cross-sectional cohort of patients with ABCA4 disease (n=415). Lesion size was determined using the HEYEX software. Circularity index for lesion shape was defined as 4π*area/perimeter2. Mild allele genotypes were defined as those consisting of p.(Gly1961Glu) and/or hypomorphic variants: p.(Asn1868Ile), p.(Thr1526Met), p.(Pro1486Leu), p.(Ile1562Thr), p.(Ala1038Val) and c.[4253+43G>A].
Results :
Out of 415 patients, 216 (52%) presented with DDAF in at least one eye. Of these 216, a distinct form of heterogeneous DDAF (h-DDAF) characterized by multiple small coalescing lesions with indistinguishable borders was observed in 28 patients, including all individuals below age 20. After excluding h-DDAF cases, only 79 (out of 188) patients were identified to have measurable lesions on AF – i.e., have lesion with (1) well-defined borders and (2) a perimeter that is entirely visible within a 30° field. The age range of these patients was 24 to 80 years; however the majority of cases fell between 40-60 years (Q1 = 45, Q3 = 58). Mild ABCA4 allele genotypes consisting of p.(Gly1961Glu) and hypomorphic variants comprised 49 out of the 79 (62%) of patients with measurable lesions. Mild allele genotypes were collectively associated with well-defined lesions (P < 0.0001) and the shape of lesions in p.(Gly1961Glu) were the least irregular (circularity index ≈ 0.9) relative to all other ABCA4 genotypes.
Conclusions :
Measuring DDAF growth in ABCA4 disease is a suitable endpoint in only a small fraction of patients due to the prevalence of non-quantifiable lesions. Patient cohorts with measurable DDAF lesions will consist largely of middle-aged individuals with mild ABCA4 genotypes. Inclusion of younger patients (below age 20 years) and/or those with severe ABCA4 alleles will require alternative primary endpoints for reliable quantification.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.