Fig 1.
Visual acuity as a function of degrees of retinal eccentricity.
Fig 2.
Schematic and representative images of measurements in fundus autofluorescence imaging and spectral-domain optical coherence tomography.
Patient 9: area of questionably decreased autofluorescence (QDAF, blue), 1.37 mm2; area of definitely decreased autofluorescence (black), 0.33 mm2; transverse loss of external limiting membrane (ELM-loss, red), 1.75 mm, transverse loss of ellipsoid zone (EZ-loss, blue), 2.24 mm; best-corrected visual acuity, 20/100; ABCA4 variants, c.1622T>C;3113C>T:p.[Leu541Pro;Ala1038Val] and c.6316C>T:p.(Arg2106Cys).
Fig 3.
Highest potential mean-to-standard deviation ratio (MSDR) for each single outcome measure at different weightings with all possible weight combinations of the other metrics.
MSDRs for best-corrected visual acuity (grey) decrease at increasing weight. MSDRs for transition zones of questionably decreased autofluorescence (blue) increase until 25% weight, but gradually decrease at higher weights. MSDRs for transition zones of definitely decreased autofluorescence decrease at weights higher than 5%. MSDRs for loss of the ellipsoid zone (green) are constant, but decrease substantially at weights higher than approximately 70%. MSDRs for loss of the external limiting membrane (black) decrease at weights higher than approximately 80%.
Fig 4.
Weighted composite score and predicted outcome.
Matching colors represent the right and left eye of the same patient. (A) Results from six early-onset Stargardt patients. (B) The predicted outcome in the replication cohort showed comparable results.
Table 1.
Yearly progression rate of changes in retinal eccentricity (ε) by visual function, fundus autofluorescence and optical coherence tomography.
Table 2.
Characteristics of early-onset Stargardt cohorts from Radboud university medical center (Radboudumc) and Moorfields Eye Hospital (MEH).
Fig 5.
Power calculations of a simulated therapeutic trial based on fourteen early-onset Stargardt patients.
Dark blue line: a power of 80% is reached with a 25% overall treatment effect and a two-year follow-up period. Purple line: the power will drastically decrease when best-corrected visual acuity is included in the outcome measure. Turquoise line: worse eye treated. Green line: one-year follow-up. Ocher line: unweighted structural composite. Red line: non-paired trial design. Yellow line: best-corrected visual acuity as a single outcome measure.
Table 3.
ABCA4 variants in early-onset Stargardt patients from Radboud university medical center (Radboudumc) and Moorfields Eye Hospital (MEH).