Agreement and Precision Study of the Nidek Mirante OCT Compared to the Optovue RTVue XR Avanti OCT and SLO Image Comparison of the Nidek Mirante and the OPTOS P200DTx
Phase: NA
Conditions: Glaucoma, Retinal Disease, Corneal Disease
Sponsor: Nidek Co. LTD.

 
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1. TITLE PAGE 
Protocol Title: 
Agreement and Precision Study of the Nidek Mirante OCT 
Compared to the Optovue RTVue XR Avanti OCT and SLO 
Image Comparison of the Nidek Mirante and the OPTOS 
P200DTx 
Protocol Number: 
Nidek Mirante-001 
Protocol Version: 
Amendment 2 December 23, 2020 
Name of Test Device/ 
Investigational Device: 
Scanning Laser Ophthalmoscope Mirante 
Proposed Indication for Use: 
The 
Nidek 
Mirante, 
including 
scanning 
laser 
ophthalmoscope function with Image Filing Software 
NAVIS-EX is a non-contact system for imaging the fundus 
and for axial cross sectional imaging of ocular structures.  
 
It is used for in vivo imaging and measurement of the retina, 
retinal nerve fiber layer, and optic disc as an aid in the 
diagnosis and management of the retinal disease.  
In addition, the anterior segment adapter (special lens unit) 
attached over the objective lens of the main body enables 
non-invasive and non-contact observation of the shape of the 
anterior segment of the eye such as the cornea or anterior 
chamber angle. 
Investigator: 
Anthony Joseph, MD 
Clinical site: 
Andover Eye Associates 
Name of Sponsor: 
Nidek Co., Ltd. 
Address of Sponsor: 
34-14 Maehama, Hiroishi-cho, Gamagori, Aichi 443-0038, 
JAPAN 
NCT Number 
NCT04318132 
Original Protocol: 
January 10, 2020 
Amendment 1: 
February 5, 2020 
Amendment 2: 
December 23, 2020 
 
 

 
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2. STUDY PROTOCOL 
This was a prospective comparative clinical study to be conducted at one clinical site located in the United 
States. Three Nidek Mirante devices, three Optovue RTVue XR Avanti devices and one OPTOS P200DTx 
will be used. For agreement and precision analysis of OCT scans and agreement analysis of image quality 
of OCT ACA scans, each Nidek Mirante device will be paired with one of the Optovue RTVue XR Avanti 
devices. One device operator will be assigned to each device pair to create three distinct operator/device 
configurations.  
For agreement analysis of SLO image quality, one OPTOS P200DTx will be included in one of three 
operator/device configurations.  
Both eyes of normal subjects must meet all inclusion and none of the exclusion criteria in order for the 
subject to be enrolled in the study. Eligible subjects will be randomized to testing sequence of devices, 
the starting device (Nidek Mirante, Optovue RTVue XR Avanti or OPTOS P200DTx) and for the normal 
subject population, the study eye. For subjects in the glaucoma, retinal disease or corneal groups, the 
investigator will select the study eye based on presence of qualifying pathology. The eye with the greater 
severity of disease will be selected as the study eye. If both eyes are of equal disease severity, the right 
eye will be selected as the study eye. Otherwise, the study eye will be the qualifying eye.  
The Nidek Mirante, Optovue RTVue XR Avanti, and OPTOS P200DTx will be used in accordance with 
this clinical protocol and each device’s User Manual. 
Normal, glaucoma, and retinal disease subjects as well as corneal disease subjects enrolled to obtain 
measurements to demonstrate both agreement and precision will be randomized to the device 
configuration order and to the starting device within each configuration. Separate randomization schedules 
will be created for each subject population group (normal, glaucoma, retinal disease and corneal disease).  
Corneal disease subjects enrolled to obtain only measurements to demonstrate qualitative agreement will 
be assessed at configuration 3 (C3) only and randomized using the next available corneal disease group 
randomization with C3 starting configuration to assign subject ID and starting device. 
The device order will be randomly assigned as one of 2 sequences of Device (D), with D1: Test: Nidek 
Mirante and D2: Control: Optovue RTVue XR Avanti (OCT) and OPTOS P200DTx (SLO). 
For the configurations with OPTOS P200DTx, the SLO scans for both devices will be taken after the 
OCT scans are completed for both devices. The SLO scans will be obtained in the same device order as 
for OCT. 
 

 
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3. STATISTICAL ANALYSIS PLAN 
Analysis of Agreement Endpoints 
Analysis of the agreement study endpoints will include measurements from Nidek Mirante and the 
predicate device. Descriptive statistics of each agreement study endpoint will be provided by subject 
population for each device. Additionally, the correlation between devices will be reported. Agreement 
will also be assessed for consistency across the measurement range and image quality measurements. 
Device comparison will be performed using the following methods by subject population for all 
configurations and for each configurations, with separate analyses stratified by variables (image quality) 
for which performance of the devices differs, assuming sufficient sample size:  
1. Descriptive statistics, including mean and standard deviation of the differences in units measured, 
mean difference as a percentage of the mean of the predicate results and the 95% LOA between 
the Nidek Mirante and the predicate device will be provided (Bland and Altman, 1986). 
Additionally, the 95% CIs of the upper and lower LOAs will be provided. 
2. The Bland-Altman plot for each study endpoint will be provided (Bland and Altman, 1986). This 
is a scatter plot in which the difference (Nidek Mirante results minus the predicate results) is on 
the y-axis and the average of the device results is on the x-axis. The mean difference and the LOA 
will also be indicated in the plot, as well as the 95% CIs of the upper and lower LOAs. Similar 
plots will be provided with the difference between devices as a percentage of the within eye mean 
on the y-axis. 
3. In order to estimate the potential systematic differences between the devices, the Deming 
Regression Method (also known as errors-in-variables model) accounting for measurement errors 
in both devices will be fitted for the Nidek Mirante and the predicate device results for each study 
endpoint, assuming that the ratio of variances is 1 (Carroll and Ruppert, 1996 and Linnet, 1990). 
The estimated intercept, slope, and their 95% CIs will be reported. Additionally, the ratio of the 
actual variances (calculated as the variance of Nidek Mirante / variance of predicate device) will 
be reported. To obtain the CIs for the intercept and slope, the jackknife method will be used to 
estimate the standard errors. For the jackknife procedure, one pair of data will be omitted at a time, 
and the Deming Regression estimates for the intercept and slope will be calculated for the 
remaining subsets of data. Then the standard errors of the estimates from these subset-based 
regression models will be calculated and used for the CIs of the overall model. The 95% CI for the 
intercept can be used to test the hypothesis that the intercept (denoted as A) = 0. This hypothesis 
is accepted if the CI for A contains the value 0. If the hypothesis is rejected, then it is concluded 
that A is significantly different from 0 and both devices differ at least by a constant amount. The 
95% CI for the slope can be used to test the hypothesis that the slope (denoted as B) = 1. This 
hypothesis is accepted if the CI for B contains the value 1. If the hypothesis is rejected, then it is 
concluded that B is significantly different from 1 and there is at least a proportional difference 
between the two devices. A scatter plot of the Nidek Mirante results (y-axis) versus the predicate 
device results (x-axis) will also be provided together with a 45° line and the best fitting regression 
line.  
 
Agreement Analysis of Scan Size and Tracing HD Functions 

 
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Analysis of the agreement study endpoints of the scan size and tracing HD functions will include 
measurements from one Nidek Mirante and be analyzed in the same fashion as detailed above.  
Analysis of Precision Endpoints 
Analysis of the precision study endpoints will include measurements from the Nidek Mirante and 
predicate device, summarizing the precision results in units measured and as a percentage of the mean 
across all eyes (% CV). Plots of the within-eye SD for each machine versus the within-eye mean will be 
provided with different symbols for the two different device types.   
A Crossed Analysis of Variance (ANOVA) model will be used to estimate the repeatability and 
reproducibility limits of each precision study endpoint by subject population. The METHOD = REML 
option will be employed in this crossed ANOVA. The crossed ANOVA model includes the following 
variance components: operator + device, subject, interaction of operator + device with subject, and 
residual within subject. Additionally, precision will be assessed for consistency across the measurement 
range and image quality. Analyses will also be presented stratifying by variables (ocular conditions and 
image quality) for which the performance of the devices differs, assuming sufficient sample size. 
The repeatability limit is calculated as 2.8 times the residual standard error (ISO 5725-6). The 
reproducibility limit is calculated as 2.8 times the reproducibility standard deviation, which is equal to the 
square root of (the sum of the variance components of operator + device, interaction of operator + device 
with subject and the residual within subject). 
The variance components, the repeatability limit and the reproducibility limit will be reported for each 
precision study endpoint by subject population in a side-by-side presentation by device. Repeatability and 
reproducibility will also be presented as a ratio of Nidek Mirante / predicate device. 
Analysis of the Image Quality Assessments 
The number of eyes with unacceptable and acceptable image quality will be summarized and compared 
by device, subject population and for all subjects.   
The first acceptable ACA images captured by the Mirante and Optovue RTVue XR Avanti will be 
compared to assess image quality. 
The first acceptable SLO image captured by the Mirante and P200DTx will be compared to assess image 
quality. 
Within each image type, device, and subject population (and for all subjects), inter-grader agreement 
among the 3 pairs of the three masked graders will be assessed using a linearly weighted Cohen’s kappa 
statistic to take into account the order of the ordinal quality scores.  
Paired comparisons of image quality between devices (Mirante vs Optovue RTVue XR Avanti and 
Mirante vs P200DTx) within an eye will be completed using a one-tailed (alpha = 0.05) Wilcoxon signed-
rank test. These comparisons will be made within each image type, scan type, subject population, and 
grader (and for all subjects and across all graders using the average grade across the three graders). 
Assuming a common standard deviation of 0.8 units, a correlation of 0.50 between image types within an 

 
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eye, a one-sided alpha = 0.05, the Wilcoxon signed-rank test will have 90% power to detect a difference 
of -0.5 (Mirante minus predicate) in the image quality with a sample size of 30. 
Analysis of Safety Endpoints 
Adverse events reported will be listed by subject.