Researchers at the Institute of Molecular and Clinical Ophthalmology Basel, Switzerland (a consortium led by the ProgStar Study Group) have reported that autofluorescence imaging in Stargardt disease has been used as a monitoring tool over a 12-month period. Outcome measures for interventional clinical trials aimed to slow pathology and progression of the disease are related on initial lesion size. In a commentary article for the work, the research results indicated that “the US Food and Drug Administration has deemed progression of atrophy a suitable primary outcome measure for randomized clinical trials”.
The clinical research has aimed to assess the progression rate of atrophic lesions in the prospective natural history study over a 12-month period used a cohort study of tertiary referral centers from October 21, 2013 to February 15, 2017. The patients, recruited by several centers in the US, UK, and continental Europe, ranged from 6 years and older at baseline with disease-causing variants of the ABCA4 gene. The results of the study comprised a total of 259 study participants (488 eyes; 230 individuals, enrolled by mean [SD] age at first visit, 33.3 [15.1] years; 118 [54.4%] female). According to the researchers, gradable images were available for evaluation for 480 eyes at baseline and 454 eyes after 12 months. At baseline, definitely decreased autofluorescence was present in 306 eyes, and the mean (SD) lesion size was 3.93 (4.37) mm2. The mean total area of decreased autofluorescence at baseline was 4.07 (4.04) mm2. The estimated progression of definitely decreased autofluorescence was 0.76 (95% CI, 0.54-0.97) mm2 per year (P < .001), and the total area of both questionably and definitely decreased autofluorescence was 0.64 (95% CI, 0.50-0.78) mm2 per year (P < .001).
An analysis of the research outcomes indicated that using atrophy as an outcome for a randomized clinical trial was not straightforward for the study. The “careful, meticulous work” performed by the research team identified “lesion size and multifocality” for 2 key parameters that predict the progression of atrophy. In the discussion of the research work the investigators stated that the results were “the first international, multicentre study to evaluate the natural history of STGD1 prospectively and was designed as a hybrid study with a retrospective review of medical records and/or a prospective follow-up of patients.” The results indicated that autofluorescence “is a suitable tool to monitor disease progression in autosomal-recessive Stargardt macular dystrophy (STGD1), especially of definitely decreased autofluorescence lesions.” As a consequence, the researchers believe that AF may be used in interventional trials to slow down disease progression.