Quantification of Peripapillary Sparing and Macular Involvement in Stargardt Disease (STGD1)

Mutations in the ABCA4 gene are the known cause of autosomal recessive Stargardt disease (STGD1).1 The ABCA4 protein is the transporter of vitamin A derivatives in the outer segment disc membranes of photoreceptors. In the absence of functional protein due to mutations in the gene, vitamin A aldehyde forms bis-retinoid adducts that are deposited in retinal pigment epithelial (RPE) cells during the process of disc shedding and phagocytosis. One of the features of ABCA4 disease is relative peripapillary sparing, characterized by the absence of flecks and RPE atrophy in the peripapillary region of the retina.2–5 The presence of either is termed peripapillary atrophy. Recent reports have shown that a small percentage of patients with STGD1 develop peripapillary atrophy.6,7 We have demonstrated peripapillary atrophy using fundus autofluorescence (FAF) in patients classified as ERG group II or III STGD1.8 The classification was based on full-field electroretinogram (ERG) results. Patients with a normal scotopic and photopic ERGs are classified as group I).9 Patients with ERG group II disease have decreased photopic ERGs, whereas patients with ERG group III disease have decreased scotopic and photopic ERGs.9 In our previous study, 1 of 15 patients in group I, all 7 patients in group II, and 9 of 10 patients in group III demonstrated peripapillary atrophy.8 Because of the relative sparing of the peripapillary area in ABCA4 disease, it has been suggested that this is a region of interest for monitoring the efficacy of treatment in this disease.2 Therefore detailed structural and functional characterization of this retinal region is of interest. Whereas previous methods of assessing the peripapillary retina have focused on its appearance using en face imaging,2–5,8 we used spectral-domain optical coherence tomography (SD-OCT) to evaluate the integrity of the outer retinal layers and RPE and microperimetry to assess visual function in this region and across the macula. Both modalities use retinal tracking features to compensate for eye movement during examination, a feature essential in assessing ABCA4 disease phenotypes with reduced visual acuity and unstable fixation.