Reliability of kinetic visual field testing in children with mutation-proven retinal dystrophies: Implications for therapeutic clinical trials

Purpose: Kinetic visual field testing is used to monitor disease course in retinal dystrophy clinical care and treatment response in treatment trials, which are increasingly recruiting children. This study investigates Goldmann visual field (GVF) changes in young children with mutation-proven retinal dystrophies as they age and with progression of the retinal degeneration. Methods: Retrospective review of children <= 17 years old with a mutation-proven retinal dystrophy. Objective clinical disease activity was assessed by a retinal degeneration specialist masked to GVF results. Digital quantification of GVF area was performed. Results: Twenty-nine children (58 eyes), ages 5-16, were identified. GVF area increased with age despite progression in 20 children and clinical stability in nine children. Mean +/- standard error increase in GVF area/year was 333 +/- 130 mm(2) (I4e, p = 0.012), 720 +/- 155 mm(2) (III4e, p < 0.001), and 759 +/- 167 mm(2) (IV4e, p < 0.001), with greater increases at earlier ages. Repeatability coefficients were 7381 mm(2) (I4e), 9379 mm(2) (III4e), and 10346 mm(2) (IV4e), indicating a large variability. At 2.5 years after the baseline GVF the area increased >= 20%, the criterion for positive treatment outcome defined in recent published therapeutic trials, in 38% (I4e), 34% (III4e), and 33% (IV4e) of eyes. Conclusion: In a substantial proportion of children with mutation-proven retinal dystrophies, there is a significant increase in GVF area with age, particularly those < 12 years, despite progression or stability of disease. These findings suggest that change in GVF area in children with retinal dystrophies can be an unreliable measure of response to treatment and on which to base appropriate counseling about visual impairment.