In the present study we have shown that the typical variability of GVF results ranged up to ±20% for the test-retest differences across most RP patients tested with V4e and III4e targets. It is important to note that large amounts of test-retest variability >50% are possible but occurred in a only small sample (3 of 8 subjects with GVF diameter <14° with the V4e target). We excluded these outliers from our estimate of the typical GVF variability because clinical trials may use a screening process to identify and exclude a minority of potential participants exhibiting high test-retest variability. The present study demonstrated that increased RP severity (assessed by mean GVF, VA, CS, age, CME) did not tend to significantly predict increased GVF variability across subjects, although the greatest test-retest differences were present in some but not all the subjects with relatively poor CS or reduced mean GVF area/diameter. We used two different methods to calculate GVF within-session variability based on planimetric and retinal areas. Our findings suggest that retinal areas should be used for patients with central GVF diameters >60° because planimetric areas and the resultant variability are greater (and, in fact, distorted) for subjects with preserved far peripheral visual fields.
The primary difference between the present study and the previous study of GVF variability by Ross et al.3
was the longer test-retest follow-up time in that study (mean, 20 days) because it examined variability between sessions and between operators rather than within session for a single operator. Within-visit variability is more likely to reflect the inherent fluctuations from patient- and examiner-related factors, whereas between-visit variability may also include true vision fluctuations or changes in addition to the inherent variability we measured within a 1- to 2-hour period during a single visit. To explore this, a future study could compare within- and between-visit GVF variability within subjects in the placebo group tested with a single operator during an upcoming clinical trial. The previous study by Ross et al.3
documented that the planimetric area test-retest difference was approximately 12% on average between sessions and within operator for RP patients tested with the II4e target,3
which is the same as the within-session test-retest difference across all subjects tested with the III4e target in the present study. The Ross et al. study3
did not test a large proportion of patients with the V4e target (n
= 5); therefore, its ability to compare variability between test target sizes was limited. In addition, the participants in that study tended to have larger GVF diameters on average than our participants,3
and the study included only one participant with a GVF diameter <14°, limiting the ability to assess variability among persons with severely constricted GVFs.
The study by Berson et al.4
on intervisit GVF repeatability used 99% rather than 95% probability and found asymmetric and slightly larger (−21%, +29%) confidence limits for variability in GVF diameter compared with our symmetric (−19%, +19%) limits derived from log retinal areas. However, the Berson et al.4
use of diameter rather than area would, on average, be expected to yield a confidence interval half the size of ours, whereas (under assumption of a normal distribution) the 99% versus 95% confidence would increase the interval by a factor of 1.5; thus, the findings of the that study4
are, in fact, similar to ours. The asymmetry in their results matches the symmetry in ours if one bears in mind that the differences in our study, derived from log areas, are proportions, and that the proportion 100/79 is very similar to the proportion 129/100.
Several possibilities explain the high test-retest variability we encountered in a limited a number of subjects in whom the percentage change exceeded 45%. Our results indicate that this tends to occur in some patients with advanced RP with severely reduced GVF and CS or when far peripheral islands are included in the total area. The increased variability may be due in part to a limited number of diseased or sporadically located photoreceptors that are less able to consistently respond to the GVF test stimulus. However, patient-related factors, such as reduced attention during the test procedure because of sleepiness or distracting thoughts were not assessed during our study and therefore cannot be ruled out as another possible source of variability.
Although we did not find that laboratory-induced stress was related to GVF decrements across subjects, previous research in normally sighted subjects without RP suggested that real-life stressful situations produce greater perceptual peripheral VF constrictions than laboratory-induced stress procedures, possibly because of increased anxiety.10
In addition, normally sighted subjects with higher life event stress experienced much greater decrements in peripheral vision during a laboratory-induced stress condition (mean change, 14.3°) than those with lower life event stress scores (mean change, 2.2°).11
We administered the Life Experiences Survey to assess positive and negative major life changes within the past year (e.g., marriage, new job, death of a close friend/relative),12
and found that the three subjects with test-retest differences >50% for the V4e target had higher negative life event scores than the less variable subjects. However, we are limited in our ability to generate conclusions regarding this association because of the small proportion of subjects with high variability and high negative life event scores; therefore, we are recommending this as an area for future research in a larger sample.
The results of this study can be used to check for the proficiency of newly trained operators by comparing the variability of their results with those of our experienced operator. Caution must be used in generalizing our results to all GVF operators because the variability for untrained or newly trained operators is unknown and may be an appropriate topic to explore during future research. It is also preferable to have a single, well-trained, and experienced operator perform all GVF tests within a center, or at least within a clinical trial. At the very minimum, given that previous research has demonstrated that the within-session GVF test-retest difference is approximately 13.5% on average when comparing results between two operators, we recommend assigning a single well-trained operator to a particular subject for longitudinal monitoring. However, when this is not feasible or changes in staff are anticipated over long periods of time, a rigorous training program to certify operators in proper, consistent GVF technique is highly recommended. Most of our subjects had previous experience with the GVF, and we recommend a “practice ” GVF session to familiarize patients who are new to the GVF procedure.
Our findings may be used to guide the design and conduct of future clinical trials in which measurement of peripheral VF is required to study the natural progression of a retinal disease or the possible effect of treatment. There is a paucity of GVF instruments, and most are located in academic centers. This is unfortunate given the potential value and role of the GVF in future clinical trials for patients with retinal degeneration and should be an important consideration for manufacturers of perimetric equipment. This study highlights the need to screen potential clinical trial subjects for large within-session GVF variability, especially when enrolling those who are legally blind because of constricted visual fields. An important finding of this study is that longitudinal GVF changes >20% may be considered outside the range of typical variability and therefore indicative of significant change as long as researchers have taken proper precautions to reduce subject-based variability by excluding prospective subjects who show large within-session GVF changes from participation in clinical trials and to ensure operator-based variability by using a single well-trained, experienced operator for within-subject repeated testing.