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

Abstract

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 mm² (I4e, p = 0.012), 720 ± 155 mm² (III4e, p < 0.001), and 759 ± 167 mm² (IV4e, p < 0.001), with greater increases at earlier ages. Repeatability coefficients were 7381 mm² (I4e), 9379 mm² (III4e), and 10346 mm² (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.

Keywords: Children; Goldmann visual field; kinetic visual field; retinal degeneration; retinal dystrophy; visual field testing.

Figure 1

Goldmann visual field (GVF) area. Boxplots display medians, interquartile ranges, and ranges of GVF area for each isopter (I4e, III4e and IV4e) among all children at baseline.

Figure 2

Goldmann visual field (GVF) area versus age. Change in GVF area for isopters (A) I4e, (B) III4e and (C) IV4e demonstrates an increase in area with age that is greater at younger ages for all isopters. Plot includes line traces for measurements of individual eyes and a lowess summary of the mean isopter area by age.

Figure 3

Goldmann visual field of the right eye of one patient at (A) presentation at 8 years of age, (B) 10 years of age and (C) 14 years of age. There is an increase in all 3 isopters over time (I4e—black line, III4e—green line and IV4e—red line) despite progression of disease.