Comparison of the TEMPO Binocular Perimeter and Humphrey Field Analyzer

This study compared between TEMPO, a new binocular perimeter, with the Humphrey Field Analyzer (HFA). Patients were tested with both TEMPO 24 − 2 AIZE-Rapid and HFA 24 − 2 SITA-Fast in a randomized sequence on the same day. Using a mixed-effects model, visual field (VF) parameters and reliability indices were compared. Retinal nerve fiber layer (RNFL) thickness was measured using Cirrus OCT, and coefficient of determinations for visual field and OCT parameters were calculated and compared using Akaike information criteria. 740 eyes (including 68 healthy, 262 glaucoma suspects, and 410 glaucoma) of 370 participants were evaluated. No significant differences were seen in mean deviation and visual field index between the two perimeters (P > 0.05). A stronger association between VF mean deviation and circumpapillary RNFL was found for TEMPO (adjusted R2 = 0.28; AIC = 5210.9) compared to HFA (adjusted R2 = 0.26; AIC = 5232.0). TEMPO had better reliability indices (fixation loss, false positive, and false negative) compared to HFA (all P < 0.05). Measurement time was faster for TEMPO compared to HFA (261sec vs. 429sec, P < 0.001). Further investigations are needed to assess the long-term monitoring potential of this binocular VF test.


Introduction
Glaucoma is an optic neuropathy characterized by the gradual loss of retinal ganglion cells and their axons, which can lead to vision loss. 1 Clinical detection and monitoring of glaucoma involves the assessment of functional vision loss using visual eld (VF) testing, and also measuring structural loss through optical coherence tomography (OCT). 2 VF testing demands active participation from patients and presents several challenges such as lengthy test durations and high variability due to its subjective nature. 35][6] Recent studies have suggested that binocular VF testing may effectively suppress eye movements and stabilize xation, thus potentially enhancing the reliability of test results. 7Moreover, this device also adjusts the stimulus presentation point by tracking eye movements. 6,8,9 hypothesized that this new technology could reduce testing duration and patient fatigue, minimize variability in test results, and improve the correlation between structural and functional data.The purpose of this study was to compare the TEMPO with the Humphrey visual eld analyzer (HFA), the most widely used automated perimeter.1.
Supplemental Figure 2 provides a summary of the usability ndings.73% of participants preferred TEMPO, while 17% preferred HFA.83% of participants reported no di culties with TEMPO.Furthermore, TEMPO received positive feedback in terms of screen readability, ease of concentration, and shorter test duration, as compared to HFA.

Discussion
In this study, we prospectively performed VF testing with both TEMPO AIZE-Rapid and HFA SITA-Fast in a randomized order and identi ed a stronger structure-function relationship and better reliability indices with TEMPO compared to HFA.TEMPO reduced measurement time by approximately 40% without compromising perimetric performance.Even though the participants were inexperienced with TEMPO prior to the study, it was strongly preferred by patients.
Effective glaucoma management necessitates functional and structural exams, and correlating these changes ensures reliable tracking of disease progression. 10,11Clinicians should optimize and balance considerations such as medical burden, patient preferences, and e cient detection of disease progression to prevent lifelong visual loss.3][14] The current cross-sectional study shows that TEMPO had a stronger structure-function relationship with Cirrus OCT compared to HFA, both globally and sectorally.Our ndings support the study by Bowd et al.,   investigating structure-function relationships using Stratus OCT.They found stronger associations (R 2 = 0.33-0.38) in the inferotemporal disc, followed by modest associations in the superotemporal disc area (R 2 = 0.19-0.25),and weak associations in the temporal disc area (R 2 = 0.02-0.03). 15The lower structure-function relationship in the temporal quadrants, compared to the superior/inferior quadrants, may be attributed to two factors: the higher variability caused by relatively fewer measurement points for visual eld and the position of the optic nerve head in relation to the fovea. 16Individual anatomical differences, such as variations in the shape, rotation, and tilt of the ONH, can affect the results of structure-function relationship. 10Both VF and OCT measurements are prone to inter-subject and testretest variability, which are major causes of discrepancy in structure-function relationship. 10,17We speculate that due to its reduced fatigue and higher reliability of TEMPO lead to reduced variability.However, both short-term and long-term reproducibility need to be con rmed in future studies.
HFA SITA-Fast and TEMPO AIZE-Rapid have several items in common regarding reliability indices, but there are some differences.First, false positives are calculated by both devices using reaction time.HFA SITA-Fast uses the percentage of stimuli responded to within a minimum reaction time with an adjustment for the average reaction time of the individual patient. 18In contrast, TEMPO AIZE-Rapid uses the percentage of those that have a reaction time of less than 0.3 seconds.Second, false negatives are calculated as percentage of not responding by presenting a 9 dB bright target to the determined threshold in HFA SITA-Fast, while TEMPO AIZE-Rapid uses percentage of not responding by presenting ≥ 2 dB bright target in the process of threshold determination for all stimuli.Third, xation loss is calculated as percentage in response to stimulus to blind spots, which is known as Heijl Krakau method, in HFA SITA-Fast.In contrast, TEMPO AIZE-Rapid uses the percentage of stimuli with Gaze tracking greater than 5 degrees.Although the Heijl-Krakau method was introduced in the 1970s and is considered the gold standard, 19 it has several disadvantages that include time-consuming catch trials, infrequent xation check, and inaccuracy of xation loss ratio when the blind spot location is dislocated.In principle, gaze tracking, which monitors the movement of the pupils, should be expected to measure xation monitoring more accurately, and also is used in HFA SITA-Faster. 20In the current study, TEMPO AIZE-Rapid demonstrated lower values than HFA SITA-Fast for all reliability indices.This may be related to the reduction of patient fatigue due to shorter examination time and the difference in approach of nonocclusion.The manufacturer-recommended limits agged 17.1% of HFA and 10.6% of TEMPO results as low reliability.Fixation losses were the main cause of low reliability for both perimeters (14.4% for HFA and 8.2% for TEMPO).Previous studies have also identi ed xation losses as the primary cause of unreliable VF classi cations. 21,22Comparing these numbers is challenging due to methodological differences, but incorporating more accurate and reliable techniques into future device, while maintaining e cacy, is crucial.
This study has several limitations.First, it was based on participants from a tertiary care academic practice, which could introduce certain biases in socio-economic status, demographics, and severity of disease, which could differ from those of patients treated in other settings.This could potentially restrict the generalizability of our ndings.Second, the current software is derived from a database that only consists of data from the Japanese population.Regardless of this limitation, HFA and TEMPO exhibited excellent agreement.Third, certain situations, such as conditions of binocular vision dysfunction like strabismus, anisometropia, nystagmus among others, can render binocular open-eye examinations unfeasible. 23These conditions were not evaluated in our study.Last, all participants were using TEMPO for the rst time, while they had previous experience with HFA.Although learning effects tend to increase the false positive rate for inexperienced examinees, 24 false positives were relatively low for TEMPO in our study.
In conclusion, TEMPO showed a stronger structure-function relationship with Cirrus OCT.It also showed better reliability compared to the HFA.Further studies are necessary to evaluate the potential of this binocular VF test for longitudinal monitoring.

Methods
Participants Participants were recruited from patients at the Shiley Eye Institute, University of California, San Diego.The research protocol followed the tenets of the Declaration of Helsinki and was approved by the University of California, San Diego Institutional Review Board.All study participants provided written informed consent.
The participants' eyes were divided into three diagnostic groups: healthy, glaucoma suspect, and glaucoma.Healthy eyes were characterized by IOP ≤ 21 mmHg, normal-appearing optic discs and neuroretinal rims, and normal VF test results de ned as pattern standard deviation (PSD) within the 95% CI and Glaucoma Hemi eld Test (GHT) results within normal limits using Swedish Interactive Threshold Algorithm (SITA) 24 − 2 FAST.Glaucoma suspects were de ned as eyes with IOP of ≥ 22mmHg or glaucomatous-appearing optic discs (glaucomatous optic neuropathy) without repeatable glaucomatous VF damage.Glaucomatous optic neuropathy was de ned as excavation, the presence of focal thinning, notching of the neuroretinal rim, or localized or diffuse atrophy of the RNFL by attending physicians based on ophthalmoscopic examination or fundus photographs.Glaucoma was de ned as eyes showing at least two reliable ( xation losses and false negatives ≤ 33% and ≤ 15% false positives) and repeatable abnormal (GHT outside normal limits or PSD outside 95% normal limits) VF results using the 24 − 2 SITA-FAST with similar glaucomatous defect patterns on consecutive testing as evaluated by study investigators.Glaucoma included all types, such as primary open-angle glaucoma, primary angle closure glaucoma, and secondary glaucoma.Eyes were excluded if they had any other ocular or systemic conditions, apart from glaucoma, that could affect VF test results, such as age-related macular degeneration.
Visual Field Testing TEMPO (CREWT Medical Systems, Tokyo, Japan) is the improved successor to the portable headmounted perimeter device known as imo. 8This device has two optical systems and pupil-monitoring systems for each eye, allowing independent target presentations and pupil monitoring. 8It enables separate testing of each eye and can randomly present test indicators to either eye, with both eyes open, without the examinee knowing which eye is being tested (binocular random single-eye test).AIZE employs Bayesian inference and maximum likelihood methods to determine the threshold, and reduces test time by around 70% compared to the 4 − 2 dB bracketing method. 8AIZE-Rapid maintains the AIZE test method but enhances the representation of interaction with adjacent measurement points. 4r the current study, all patients underwent HFA 24 − 2 SITA-Fast and TEMPO 24 − 2 Ambient Interactive Zippy Estimated by Sequential Testing (AIZE)-Rapid on the same day in a randomized order using Goldmann size III (0.431° visual angle) stimuli.Since the purpose of this study was to compare HFA and TEMPO, no exclusions were made at speci c cutoff values for reliability indices ( xation losses, false negatives and false positives) for both devices.The binocular random testing mode was selected for testing with TEMPO.In addition, to evaluate usability for patients, there was a questionnaire, as follows: 1) Which device do you prefer?, 2) Did you have any di culty with the simultaneous examination of both eyes using the novel device?, 3) Was the screen easy to see?, 4) Was it easy to concentrate?, 5) Was the test time short?.These questions were assessed using a 5-point Likert scale.

Structure-function relationship
Retinal nerve ber layer thickness (RNFL) was measured using Cirrus spectrum-domain OCT (Carl Zeiss Meditec, Inc, Dublin, CA) Optic Disc Cube 200×200 protocol scans.A 3.46 mm diameter circle was automatically placed around the optic disc, providing RNFL thickness globally and in superior, inferior, temporal, and nasal sectors.Coe cient of determination for VF and OCT parameters was calculated and compared using Akaike information criteria (AIC).Age adjusted R 2 values and AIC were used to compare the models for goodness of t.The higher R 2 and smaller AIC mean better t.To compare the strength of structure-function relationship between HFA and TEMPO, the absolute value of the residuals from each model were calculated and compared using mixed effects model. 15Structure-function relationships were investigated for global (VF mean deviation [MD] and circumpapillary RNFL) and sectoral parameters (VF mean sensitivity and quadrant RNFL) based on simpli ed map proposed by Garway-Heath et al. (Fig. 1). 26,27Mean sensitivity was calculated in dB by converting the threshold sensitivity of each test point to a linear scale and then averaging them to obtain the mean sensitivity values.

Statistical analysis
Patient and eye characteristics were reported as mean (95% CI) for continuous data and count (percentage) for categorical data.MD, pattern standard deviation (PSD), foveal threshold (FT), and visual eld index (VFI), and reliability indices ( xation loss, false positive, and false negative) were compared using mixed-effects model between the two perimeters.Reliability indices were illustrated in a kernel density estimate plot to compare the values from two perimeters.Kernel density estimate is a nonparametric way to estimate the probability density function of a random variable.In other words, it provides a smoothed version of a histogram, giving a continuous curve.The Bland-Altmann plot assessed the limits of agreement (LoA) between the two perimeters.Measurement time for performing VF for both eyes was recorded for each device.It only accounted for the actual examination time and excluded the setup time needed for testing the second eye with HFA.

Table 1 .
All statistical analyses were performed with Stata software (version 15; StataCorp, College Station, Texas).Statistical signi cance for tests was set at P ≤ 0.05.Demographic and Baseline Clinical Characteristics of the Participants

Table 2 .
Comparison between Humphrey Field Analyzer and IMOvifaValues are shown in mean (95% con dence interval), unless otherwise indicated.a Mixed-effects model

Table 3 .
Comparison of Topographic Structure-functional Relationship between Humphrey Field Analyzer and TEMPO AIC = Akaike information criteria; RNFL = retinal nerve ber layer; MS = mean sensitivity.Age was adjusted in all models.Figures Page 12/14