Abstract
Purpose :
Mutations in USH2A are a leading cause of Usher syndrome and a major contributor of non-syndromic Retinitis Pigmentosa (RP). The advent of small molecule systemic therapies opens new avenues of gene augmentation therapy, but also adds complexity in trial design and randomisation. One challenge is lack of understanding regarding how similar patterns of degeneration are between syndromic and non-syndromic RP patients and how this affects future trial design.
Methods :
Patients with molecularly confirmed biallelic USH2A variants, at least 3 visits with gradable OCT and AF data were selected from the Moorfields Eye Hospital genetic eye disease database. Previous work showed the hyper autofluorescence ring area (HyperAF), horizontal diameter and Ellipsoid width (EZ length) were most sensitive metrics to measure degeneration, while retinal thickness and acuity were poor indicators of progression. Images acquisition and analysis was done on the Heidelberg Spectralis and repeated by two trained graders to ensure repeatability. Due to the high degree of symmetry between eyes, the eye with the largest dimension at baseline was used for subsequent analysis.
Results :
Eighty patients (56 syndromic and 24 non-syndromic) met the inclusion criteria and were included in the analysis. The syndromic cohort was slightly younger (38.75 yrs [range 15-64 yrs] vs 45.21 yrs [range 23-68]), with similar distribution of ages. Average duration between visits was similar for both groups. EZ length was correlated with age for syndromic (p<0.0001) and non-syndromic (p=0.0019), the correlation was not different between the groups (p =0.28). HyperAF area was correlated for syndromic (p =0.0017) and non-syndromic (p=0.0083), this was not statistically different (p=0.53). There were no significant differences in rate of degeneration between cohorts (baseline – timepoint 1:EZ width, p=0.08; HyperAF, p=0.1; timepoint 1 - timepoint 2: EZ width, p=0.89; HyperAF, p=0.7).
Conclusions :
The slight age differences maybe selection bias or may represent a slight difference in age of onset between syndromic and non-syndromic RP associated with mutations in USH2A. However, the degeneration rates, when matched to baseline size are equivalent. Given the lack of difference in correlation coefficients the conditions can be considered equivalent for trial purposes and randomized accordingly for future trials.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.