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

Abstract

Purpose : Kinetic visual field (VF) testing is used to monitor disease course and treatment response in retinal dystrophy treatment trials, which are increasingly recruiting children. We hypothesize that in children, despite stability or progression of the retinal degeneration, there is increase in Goldmann visual field (GVF) areas of different isopters as a child gets older and becomes a better test taker.

Methods : Retrospective review of 30 children (60 eyes) with mutation-proven retinal dystrophies (gene mutations in: ABCA4, RPGR, CNGB3, RP2, CHM, RPE65, USH2A, PDE6C, RHO, MYO7A, KCNV2 and NYX), and at least 2 GVFs, evaluated between 2005 and 2015. Objective clinical disease progression or stability was assessed by a retinal dystrophy specialist, masked to GVF results, by evaluation of fundus autofluorescence, the ellipsoid zone width on macular optical coherence tomography or Snellen visual acuity at initial and follow-up visits. Digital quantification of GVF areas was performed.

Results : GVF areas in children aged 6 to 16 years increased with age despite progression of retinal degeneration in 21 children and no clinical progression in 9 children. Mean (±SD) GVF area for each isopter was 6065±5264 mm² (I4e), 12009±5209 mm² (III4e) and 15016±5563 mm² (IV4e). The mean increase in GVF area per year, by linear mixed model analysis, was 107 mm² (p = 0.02), 746 mm² (p <0.001) and 814 mm² (p <0.001) for the I4e, III4e and IV4e targets, respectively, with greater increases at earlier ages. Repeatability coefficients were 7821 mm² (I4e), 10794 mm² (III4e) and 12051 mm² (IV4e), indicating that there is a large variability in GVF areas. In 46% (I4e), 45% (III4e) and 39% (IV4e) of patients in our study there was an increase in VF area of at least 20% from baseline, which is the threshold of success defined in published therapeutic trials.

Conclusions : There is a significant increase in GVF area with age in children, despite progression or stability of retinal degeneration. These findings suggest that kinetic VF testing in children with retinal dystrophies can be an unreliable measure of response to treatment or assessment of the natural history in a clinical trial setting, as well as in clinical practice when counseling patients and parents about the severity of visual impairment.

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

 

There is an increase in VF area despite progression or stability of retinal degeneration.