Abnormal Visual Function Outside the Area of Atrophy Defined by Short-Wavelength Fundus Autofluorescence in Stargardt Disease

Abstract

To examine the extent of visual function abnormality outside the dark lesion on short-wavelength fundus autofluorescence (SW-AF), and its correlation with background SW-AF features and optical coherence tomography (OCT) in recessive Stargardt disease (STGD1) METHODS. Forty-nine eyes of 25 participants in the ProgStar (the Natural History of the Progression of Atrophy Secondary to Stargardt Disease) study at our center were included. Patients underwent microperimetry (both threshold and dense scotoma mapping), OCT, SW-AF, and visual acuity testing. The Fisher's exact test, the χ 2 test, and unpaired t-tests were used to analyze the data. RESULTS. Of 40 eyes without central fixation, 33 (82%) placed fixation remote (most ≥5°) from the dense scotoma edge, despite good intervening retinal sensitivity. OCT findings accounted for the remote fixation in 75%. Eighteen (37%) of all 49 eyes had dense scotoma extending past the dark lesion border. OCT was not adequate to define the edge of the scotoma. Of the 49 eyes, 28 (57%) had the mottled background pattern, 10 (20%) had the uniform pattern, and 11 (22%) had the other pattern, with >75% of eyes in each pattern having remote fixation. The dense scotoma exceeded the dark lesion primarily in the mottled pattern. The two eyes of each patient were concordant in all features. CONCLUSIONS. Functional abnormalities in STGD1 extend past the SW-AF dark lesion. The disruption of the ellipsoid zone shows that photoreceptor abnormality extends peripheral to the dark lesion, and it explains in part the remote fixation pattern and the dense scotoma exceeding the dark lesion. This has implications for clinical trials for STGD1.

Photoreceptor degeneration in ABCA4-associated retinopathy and its genetic correlates

“…2018-001496-20]) as outcome measures. While DDAF in STGD1 is well established in terms of reproducibility and progression rates ( 8 , 21 ), the boundaries of absolute scotomata may exceed the boundaries of DDAF in STGD1 (in contrast to age-related macular degeneration) ( 9 , 22 ). Thus, the application of DDAF as a surrogate of disease severity in STGD1 may represent the trailing edge of the disease.…”

“…Changes in hypoFAF area are currently being used as the primary outcome measure for a clinical trial involving Stargardt disease (i.e., ClinicalTrials.gov NCT03772665). Functionally, the boundary of deep scotomata often exceeds the margins of RPE atrophy in STGD1 (9). In early stages of disease, markers of disease progression have also been proposed, including the leading disease front as observed in the distribution of flecks (10), and lipofuscin accumulation measured by (quantitative) autofluorescence imaging (11)(12)(13).…”

Intraocular iron injection induces oxidative stress followed by elements of geographic atrophy and sympathetic ophthalmia

“…The near-infrared AF images displayed intense pan-retinal hyper-autofluorescent (yellow arrows) and hypo-autofluorescent spots (red arrows), corresponding to hyper-reflective subretinal foci (yellow arrows) and hyporeflective spots (red arrows), respectively, on optical coherence tomography scans (Figure 1g). Atrophic or amelanotic RPE cells have been reported to be hypo-autofluorescent in infrared AF imaging (Duncker et al, 2014;Sunness et al, 2020). RPE atrophy was present in optical coherence tomography scans in the superior retina after FAC injection (right side of scan, yellow box).…”

Comparisons Among Optical Coherence Tomography and Fundus Autofluorescence Modalities as Measurements of Atrophy in ABCA4-Associated Disease

“… 21 The latter study showed that photoreceptor dysfunction assessed by microperimetry extended peripheral to the dark lesions detected in SW-AF images. 21 The width of EZ loss in OCT scans has been compared to atrophy in NIR-AF and SW-AF findings in a study which measured abnormal reflectivity in en face slab images generated from B-scans acquired by wide-field swept-source OCT. 17 The area of the central hyperreflective zone attributable to RPE atrophy in the sub-RPE slab was in agreement with the hypoAF SW-AF area but both underestimated RPE atrophy based on the area of hypoAF in NIR-AF images. 17 The area of abnormal reflectivity attributable to EZ loss in the inner segment/outer segment (IS/OS) slab corresponded to the zone of combined hypoAF and hyperAF in SW-AF images.…”