Test-Retest, Within-Visit Variability of Goldmann Visual Fields in Retinitis Pigmentosa

Reliable outcome measures documenting visual function changes in mid- and far-peripheral areas are vital for clinical trials examining the safety and efficacy of treatments for retinal degenerative disease patients with peripheral visual field (VF) loss. Many treatments may preferentially affect VF area rather than, or in addition to, local VF sensitivity, and these changes may occur in peripheral locations not probed by most automated perimeters. Examples of such treatments already in early-phase clinical trials are transcorneal electrical stimulation for retinitis pigmentosa (RP),1 gene therapy for Leber's congenital amaurosis (LCA),2 and oral synthetic cis-retinoid therapy for some forms of LCA or RP (Koenekoop RK, et al. IOVS. 2011;52:ARVO E-Abstract 3323). Therefore, it is valuable to establish the typical short-term variability of VF measures obtained with an instrument likely to be used in such trials for its capacity to assess visual areas located beyond 60° eccentricity, such as the Goldmann VF (GVF). There are only a few previous publications of VF variability in RP. A search of PubMed and similar sources revealed only two publications specifically examining GVF variability3,4 and two other publications on the variability of Humphrey VF sensitivity measures in RP.5,6 Ross et al.3 found that the variability of GVF area between sessions determined by planimetry using the V4e or II4e target was 12% on average in normally sighted observers and up to 50% in a group of RP subjects with visual acuity (VA) of 20/100 or better. The authors did not comment on the magnitude of the variability of GVF area in relation to subjects' mean GVF extent. Examination of their published data indicates that as the GVF area decreased, some subjects' eyes demonstrated increased variability between sessions, whereas others maintained low variability. Berson et al.4 determined intervisit GVF variability within 2 months in RP subjects with VA of 20/200 or better and found that a 22% decrease or a 29% increase in GVF diameter with the V4e test target was significant at the P < 0.01 level. We are not aware of any other publications in more than 25 years that have attempted to confirm these reports of GVF repeatability in other populations with RP or involving other trained GVF operators. Intersession Humphrey 30–2 VF variability in RP has been reported to range up to approximately 5 to 10 dB for each test location with the size V and III targets,6 which would be equivalent to test-retest differences ranging up to 16% in patients with good mean sensitivity (∼32 dB) or up to 100% in patients with poor mean sensitivity (∼10 dB). Thus, the limitation of the Humphrey VF is that it also appears to demonstrate significant variability across RP subjects, with a potential for particularly high variability in areas in which sensitivity is reduced; moreover, unlike the GVF, it is unable to assess areas of peripheral vision. As one maps peripheral visual field locations, increasing planimetric distortion occurs relative to the retinal areas involved.7 This is due to two sources: the cartographic distortion between the chart and the perimeter bowl (i.e., from the flat paper to the hemispheric bowl of the GVF instrument) and the geometric optical projection of the perimeter bowl onto the retina (i.e., from the hemispheric bowl of the GVF instrument to the concave retinal surface). This has led to the recommendation to convert the GVF chart results to retinal rather than planimetric areas when monitoring changes in the peripheral VF in patients with retinal degeneration because natural progression and possible treatment effects are acting on the retina rather than the chart. Otherwise, the importance of changes occurring in peripheral VF areas will be overestimated relative to central areas. As part of an investigation of possible causes of vision fluctuations reported by RP patients, we conducted a study of the effects of laboratory-induced stress on vision using a highly standardized protocol, the Trier Social Stress Test,8 by obtaining GVF results in RP subjects before and after the stress-inducing procedure involving mental arithmetic and public speaking. However, we found no statistically significant relationships between GVF changes and the magnitude of either the physiological stress level measured or the anxiety level reported by the subjects. Because the effects of stress played no demonstrable role in GVF variability in this subject group, the GVF changes between test and retest can be used as an estimate of GVF variability in a representative population of RP patients. Therefore, our objectives in study were to explore the magnitude of within-visit GVF fluctuations measured by a single experienced operator in a group of RP patients with a relatively wide range of VA and VF loss and to determine whether GVF variability was correlated with subjects' age, sex, level of vision, or cystoid macular edema (CME) status.