The natural history of the progression of atrophy secondary to Stargardt disease type 4 (Progstar-4 Study): Baseline demographics and ocular characteristics of patients with PROM-1 related retinal dystrophy.

Abstract

Purpose : The longitudinal, multicenter ProgStar-4 study aims to characterize the natural history of Prominin-1 (PROM1) related retinal dystrophy (Stargardt disease type 4/STGD4; OMIM #603786). The baseline characteristics of patients enrolled in the ProgStar-4 Study are described.

Methods : Patients with disease-causing mutations in the PROM1 gene and associated retinal dystrophy were enrolled. At baseline, best corrected visual acuity (BCVA), fundus autofluorescence (AF, Heidelberg Engineering), optical coherence tomography (OCT, Heidelberg Engineering) and microperimetry (MP-1, Nidek Technologies) were obtained and analyzed by the Quantum Vision Reading Center (QVRC).

Results : Ten eyes from 5 patients with mean age of 38.2±7.6 years have been enrolled to date into the study. The mean age at onset of symptoms was 25.8±10.5 years with an average disease duration of 12.4±12.4 years. Mean BCVA at baseline was 60.8±19.2 letters (range: 38-91). All patients had areas of decreased AF with a mean area of 6.2±2.2 mm². Eight (80%) eyes had poorly demarcated questionably decreased AF (PD-QDAF) and 2 (20%) had definitely decreased AF (DDAF) with one multifocal subfoveal DDAF lesion. Eight out of 10 eyes had an increased edge AF and none had any flecks. Mean central subfield thickness was 181.7±42.0 µm, total macular volume was 6.8 ± 0.6 mm² and 6 eyes had loss of outer retinal architecture involving the fovea. Mean sensitivity (MS) as measured by MP-1 was 9.5±5.0 dB, with unstable fixation in 4 eyes (40%) and an average 1 standard deviation bi-contour ellipse area (BCEA) of 2.17±3.3 degrees². Fixation was eccentric in 5 eyes (50%) with an average PRL location of 3.9±3.5 degrees from the center of the anatomic fovea.

Conclusions : Progstar-4 is the first multicenter study to prospectively follow patients with STGD4 to characterize disease progression. Our baseline characteristics show that the main AF lesion type was PDQDAF. Four eyes from 2 patients showed preservation of the sub-foveal outer retina, but only one of them had both preservation on OCT and absence of AF lesions involving the fovea. Longitudinal data will provide valuable insights into the natural history of STGD4 and will inform clinical trial design for interventional studies that aim to slow down disease progression.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.