Study design

This was a prospective, multiple crossover study with four different environments in a two by two design: real and virtual indoor environments, and real and virtual outdoor environments. Each participant (n = 19) experienced all four environments in a randomised order. Participants were aged between 18–35 years (mean age 24.7 SD 4.0 years, 10 females), and were either emmetropic (n = 9) or wore their habitual contact lenses (n = 10, mean refractive error −1.66 SD 2.20D) to eliminate spectacle lens prism and difficulties fitting glasses under the HMD.

Participants gave written informed consent, were free to withdraw at any stage without giving reason, and their data has been deidentified and presented as pooled distributions. Exclusion criteria included stereopsis worse than 200 minarc, treatment for the progression of myopia (e.g. atropine, orthokeratology, or myopia control contact lenses), corrected visual acuity poorer than 6/7.5 in either eye, or a history of motion-sickness.

All participants took a battery of tests immediately prior, then immediately after exposure to each environment. The tests were completed in the following order: fixation stability, binocular vision tests and then choroidal thickness measures. After 40 minutes inside each environment, the battery of tests was repeated in reverse order: choroidal thickness, binocular vision, and then fixation stability, so that choroidal thickness was measured immediately before and after the trial. All tests were completed within five minutes of completing each environment, with equipment located to minimise participant movement. The optics of the HMD had a fixed lens centre separation of 65 mm, and light emitted from the headset focussed at approximately 1-meter from the headset. Participants were instructed to align the HMD on their head so that the screen appeared clear. A default stereoscopic camera setup was used with an in-game height of 180 cm, and a lateral camera separation of 65 mm. The participants were instructed on the use of the gamepad to move and interact in the virtual world, and they could converse with the experimenters if required. To normalise the conditions before each trial, participants worked at a computer for at least 45 minutes prior to baseline measurements. Each participant began each trial on different days, but at a similar time of day, to minimise any diurnal effects. The study was approved by The University of Auckland Human Participants Ethics Committee (Ref: 015908), and adhered to the Tenets of the Declaration of Helsinki.

Environments

Each environment had a different combination of perceived viewing distance, accommodative demand, proximity cues for accommodation, convergence demand and luminance, to assist in determining which environmental parameters or combinations, might be important in any observed effects of HMD wear.

The virtual environments were created in the Unity game engine (Version 5, Unity Technologies, USA), compiled for the Oculus DK2 (SDK version 0.8.0) and executed on a virtual reality capable machine (Intel Xeon E5–1650, nVidia GTX970, 16 Gb RAM). Audio was 3-D positional, and delivered through over-the-ear headphones to maximise immersion. The VR outdoor (VRO) environment consisted of a 1 km2 island, with features designed to mimic the real-world environment (Fig. 1). The island was bounded by water (to expose a distant horizon) on one side, and by mountain ranges along the three other sides. The island was scattered with ruins, hills, trees, and other items which rewarded exploration, and there were several treasure chests around the island which the participants were encouraged to find. Maximum speed of movement was restricted to a fast walking pace (1.5 meters per second) to minimise nausea, and to mimic the instructions given for the real-world environments. The VR indoor (VRI) environment was a small (~9 m2) cabin with dim lighting, and a large virtual television on the wall. The television played a documentary on the future of virtual reality (https://goo.gl/aDSGNr), and there were many objects on shelves and a table inside the cabin which provided a range of vergence demands. The maximum viewing distance in this environment was 3.5 m, designed to match the indoor environment in the real world. Light levels, measured by placing a lux meter sensor (LT300, Extech, USA) inside the headset in a darkened room, was approximately 180 lux in VRO, and 130 lux in VRI.

Figure 1 Examples of the four environments and comparison of their features. The outdoor real (RWO) and virtual (VRO) environments were brighter and spacious, while the indoor real (RWI) and virtual (VRI) environments were dimmer and more contained. Both virtual environments had constant accommodative demands, while accommodative demands in the real world varied by fixation distance. All environments except RWO had proximal near cues – in the virtual reality environments proximal cues were also due to the perception of wearing a headset. Full size image

The real world outdoor (RWO) environment was the Auckland Domain, a large city park across the road from the University campus. Participants were instructed to walk around the park, avoiding near activities such as reading or using cell phones. Light level was measured during the middle of each RWO trial, and ranged from 150 to 90000 lux (median: 45000, interquartile range: 24500–81500 lux). The real world indoor (RWI) environment was a small office (approximately 9 m2), with no window. As was the case for the virtual indoor room, there was a range of items at various distances, and the maximum viewing distance was 3.5 m. Participants remained seated, and were encouraged to either work on or watch videos on an LCD computer monitor at approximately 1 m viewing distance. Overhead florescent tubes provided a 210-lux illumination in the vertical plane at eye height. Heart rate was measured with a wrist worn optical tracker (Charge HR, Fitbit, USA) throughout each trial, and served as a timer for the 40-minute trial duration.

Binocular Vision Tests

Fixation disparity and stability at 50 cm was assessed on a binocular infrared eyetracker (Eyelink 1000, SR Research, Canada), which was calibrated before every measurement. The eyetracker camera was set to ‘remote’ mode, which uses a calibrated sticker positioned on the forehead to allow more naturalistic free-space measures, rather than requiring a chin/headrest. Participants were instructed to look at a maximum contrast target consisting of a combined bullseye and crosshair, which has been shown to be the most stable fixation target23. The target subtended 0.85 degrees, and was in the centre of an LCD monitor (Asus VG278H, 1920 × 1080 resolution, 120 Hz refresh, 28 pixels per degree). After a one second stabilisation period, the eyetracker recorded binocular eye position at 500 Hz for 4 seconds. If monitoring of the pupil or corneal reflex was disturbed during this period (e.g. due to a blink), the data was discarded and the test restarted. The pixel co-ordinates of the gaze position of each eye were captured directly into Matlab (2016a, Mathworks, USA). Fixation disparities were calculated as right eye minus left eye, with the result that a positive horizontal value represented an uncrossed ocular misalignment, and a positive vertical value a right eye hypo- misalignment.

Fixation stability was computed as 95% confidence interval bivariate contour ellipse areas (BCEA, minarc2) of binocular eye movements within the four second measurement interval24,25, as:

$$95 \% BCEA=2.291\times \pi \times {\sigma }_{x}\times {\sigma }_{y}\times \sqrt{1-{p}^{2}}$$

where σ x = horizontal SD, σ y = vertical SD, 2.291 is the χ2 value corresponding to two standard deviations, and p is the Pearson product moment correlation coefficient between X and Y data.

Accommodation, phorias and stereopsis Tests of binocular vision status included amplitude of accommodation (mean of three binocular push-up RAF rule measures), dissociated phorias at both distance (6 m) and near (0.4 m) using modified Thorington26, and stereopsis (Wirt Stereo fly test, Stereo Optical Co Inc). Inter-pupillary distance at both distance and near (0.4 m) were measured (Digital pupillometer, Essilor, France), so the effect of HMD lens decentration could be computed and correlated with changes in binocular vision, fixation stability, and fixation disparity.

Choroidal thickness, used as a proxy for the risk of myopia progression22,27, was measured using swept-source optical coherence tomography (SS-OCT, Atlantis DRI, Topcon, Japan) in horizontal and vertical cross scan mode (6 mm length, 1024 intervals, 96 averaged samples per line). The SS-OCT uses 1050 nm light to better penetrate the choroid, and minimises visibility of the scan line, which reduces patient tracking. The scan takes less than two seconds, and captures 100,000 A-scans per second at a resolution of 20 μm across the surface, and 8μm in depth, and is interpolated to give 1024 measures across the full 6 mm length. As the environmental exposure was binocular, but the eyes are not independent, one eye was randomly determined by coin-toss per-participant at the first visit, and this eye was used for all subsequent visits (42% left eyes). Automatic segmentation of the choroidal-scleral interface was performed by the machine software (Topcon FastMap, Version 9, Topcon Medical Systems, USA), and the segmented data was exported into Matlab for analysis. In rare cases where any of the 96 scan lines were missed (e.g. due to blink), or if the software reported poor choroidal image quality (<30), or if the choroidal-scleral boundary was incorrectly identified by the automated software, the scan was immediately repeated. Mean choroidal thickness measures, centred on the middle of the scan, were calculated for across the subfoveal (central 1 mm), parafoveal (3 mm) and perifoveal regions (6 mm)28.

Statistical analysis

Baseline comparisons were normally distributed and compared with 1-way ANOVA with environment as the factor. Some of the changes (post-pre) in the measures of binocular vision, fixation stability, and choroidal thickness were not normally distributed, and were compared with non-parametric Kruskal Wallis tests, with post-hoc, paired-wise testing using Wilcoxon–Mann–Whitney using Šidák p-value correction for multiple comparisons, as required. As all 19 participants completed four environments, this gave 3 degrees of freedom between factors and 75 total degrees of freedom for all measures. Correlations were made with Pearson’s R. Heart rate was monitored throughout each trial, rather than pre and post, so the mean heart rate measure of the 40-minute period was compared between conditions. The datasets analysed during the current study are available from the corresponding author on reasonable request. Differences were treated as significant at p < 0.05.