Vision Science

Multivariate analysis of repeatability for the Near Eye Tool for Refractive Assessment (NETRA)

Abstract

Objective To investigate repeatability of refractive state using a smartphone-based assessment tool, the Near Eye Tool for Refractive Assessment (NETRA).

Methods and analysis This study included 279 participants, predominantly female (66.7%) of African descent (49.1%). The age range was 9–63 years with mean age (s) 22.6 (8.9) years. Two consecutive measurements per eye with the NETRA were measured for both eyes of all participants. However, analyses for the right eyes only are included here. Multivariate statistical analysis included stereo-pair comets and scatterplots with 95% surfaces of constant probability density. Correlation coefficients for repeated samples were determined. Repeatability and agreement for NETRA were assessed with Bland-Altman plots, coefficients of repeatability ( Inline Formula  ;  Inline Formula  is the SD of differences) and intraclass correlation coefficients (ICCs).

Results Bland-Altman plots, within-subject SD (sw), coefficients of repeatability and ICC indicated that repeated measurements were similar for many but not all eyes and there was good agreement (ICC=0.96) for the spherical coefficient (FI=M) but less so for antistigmatic coefficients (FJ=J0 and FK=J45) of power. Although mean differences for repeated samples were almost zero, 95% limits of agreement widths were larger for the stigmatic coefficients. Without cycloplegia, repeatability (2.77sw) was 1.63 D, 0.58 D and 0.56 D for the stigmatic and antistigmatic coefficients, respectively.

Conclusion NETRA is a potentially useful and inexpensive portable method in clinical and primary health settings, and especially in less-developed regions of the world. The subjective nature of the self-refraction task can be challenging for younger individuals, and cycloplegia is recommended for NETRA with such patients.

What is already known on this topic

  • Only very limited information is known about short-term agreement, variability and repeatability of measurements of refractive error from the Near Eye Tool for Refractive Assessment (NETRA).

What this study adds

  • This is the first study that provides detailed multivariate analysis for repeatability and agreement for the NETRA.

  • For the spherical coefficient of power and based on intraclass correlation coefficients (ICC), repeatability was good (ICC=0.96) even in the absence of cycloplegia.

  • However, 95% repeatability coefficients (=2.77  Inline Formula ) ranged from 0.5 D to 1.6 D and were better (smaller) for astigmatism rather than for the spherical coefficients of power.

How this study might affect research, practice or policy

  • The relatively inexpensive NETRA and similar mobile methods for ophthalmic refraction can be used in resource-limited environments to constructively address the global concerns of uncompensated refractive error and especially of rapidly increasing prevalence of myopia.

Introduction

Clinical refraction of the eye measures and compensates for refractive error by determining a combination of spherical and/or cylindrical lenses that establishes the optimal visual acuity for distant objects. Where necessary, a similar process is followed for objects at closer distances. Spectacles, contact lenses or refractive surgery demands precise measurement of ophthalmic refractive error and the underlying assumption of clinical refraction is that visual acuity is optimised when the retinal image is optically focused.1 2 Vision impairment (VI) due to uncompensated refractive error (URE) such as with myopia is a global health concern and inexpensive and portable technology to address the unmet needs of patients with mild to severe VI due to URE is important and the repeatability2 of an example of such technology2–9 is addressed here. The necessary analytical methods1–27 to effectively explore refractive error obtained via such technology are also demonstrated.

Scientists at the Massachusetts Institute of Technology and the company Eyenetra (https://eyenetra.com/) in the USA created a low-cost smartphone-based refractive tool, NETRA (Near Eye Tool for Refractive Assessment) that incorporates both objective and subjective techniques to allow for self-evaluation of refractive error.3–8 Essentially the instrument combines objective (based on wavefront aberrometry and Scheiner principles) and subjective (patient-dependent) methods to determine refractive state. The instrument uses a smartphone display within a plastic-moulded binocular fixation system with three external dials for centration, alignment of the Vernier lines (with targets consisting of simple curves and lines to resemble a pair of umbrellas with handles to act as Vernier lines) and then confirmation of alignment.3–8 NETRA has 6 D lenses to limit excess ocular accommodation and an inverse Shack-Hartmann technique and sensors to measure the wavefront aberration function of both eyes simultaneously, and Vernier alignment in different meridians is used rather than ocular blur to precisely estimate second-order ocular wavefront aberrations (mainly defocus and astigmatism) from which refractive state is determined.3 9 The patient looks binocularly into the handheld NETRA that houses the smartphone, and an adjustable dial is used to align the handles of two (red and green) umbrellas10–13 that appear sequentially in different meridians (8 or 34) over 360° to determine monocular refractive errors under binocular viewing conditions. Once the umbrellas are rotated, their handles are aligned for the specific meridians concerned. Besides clinical refractions, the device also provides a confidence message that objectively assesses the user’s compliance.5 6 (Recently8 in BMJ Open Ophthalmology, diagrams, and a more detailed description of NETRA by these authors were included and thus are not repeated here. Alternatively, the company website above can be used to find diagrams and further information about the device.)

The primary aim for this study was to investigate repeatability for NETRA through two samples obtained for the refractive states of 279 right eyes with NETRA.

Methods

Study design and population

The study used a prospective observational and quantitative design in a university setting. The study applied the tenets of the 2013 Declaration of Helsinki.28 The research sample consisted of 279 participants and selection of participants was by non-random convenience sampling. The participants were predominantly female (66.7%) of African descent (49.1%). The age range was from 9 years to 63 years with mean age and SD (s) 22.6 ±8.9 years. Exclusion criteria were the presence of any systemic or ocular disease including any conditions (keratoconus, tear deficiency, strabismus, nystagmus, etc) that might interfere with NETRA performance or where intellectual ability in children or adults was deemed possibly insufficient to adequately perform the method. Since the software application in the smartphone computes refractive errors from ‒12 D to 5.50 D for the spherical component, and 0 D to ‒7 D in 0.25 D increments for the cylindrical component,26 participants with refractive states outside the NETRA range were excluded from the study via measurements obtained using retinoscopy26 and subjective refractions,8 26 both with and without cycloplegia, and a comparison of these results including validity of NETRA was published by the authors,8 and also constitutes part of the first author’s doctoral thesis.26

Two consecutive measurements (repeatability) per eye were taken for all participants (n=279). Repeated measurements for the right eyes of the participants without cycloplegia are compared here as these measurements represent worst-case conditions where ocular accommodation and other issues affecting repeatability such as possible outliers and departure from sample normality remain relevant.

Statistical analysis

In the past, most studies involving refractive state treated refractive error components (sphere and cylinder powers and cylinder axes) as independent and univariate entities, whereas they should be evaluated with linear algebra and multivariate statistics.1 14–28 Therefore spheres, cylinders and their axes are first transformed from conventional or clinical terms to a vector representation (f or t)1 8 14–16 26 or to the dioptric power matrix, F.14–16 (Necessary equations are included below.) Thereafter quantities such as means and variances are properly determined.14–26 Research on repeatability using multivariate statistics and methods is thus applied here to NETRA data. (Validity of NETRA against ophthalmic subjective refractions, with and without cycloplegia, was addressed recently by the authors,8 26 and, as expected, validity improved with cycloplegia in younger participants.)

Analysis of refractive states in clinical notation (Fs Fc A) from NETRA is performed using symmetrical dioptric power matrices, F and vector f:8 14–27

Display Formula

Display Formula

Display Formula

where vector f is the same here as vector t. Although vector t and vector f are treated as being equivalent here, strictly, f, has another entry, FL, but for refractive states, FL= 0 D and the power matrices are symmetrical rather than asymmetrical.27 So, the approach here involves graphical representation and quantification that is based on the use of matrices, F, as well as vector f and we prefer this nomenclature. (Readers, if they prefer, can simply substitute M, J0 and J45, respectively, for all instances where FI, FJ and FK appear.)

Multivariate statistical analysis includes stereo-pair scatterplots with comets8 26 27 and 95% distribution ellipsoids,21 and hypothesis testing of variances and covariances.20 21 A comet is simply a line plotted between two points here to link repeated measurements for an eye. The closer to zero the length of a comet, the smaller is the difference between the two measures at the ends of the comet. If a comet length is exactly zero, the paired measures are exactly equal, and repeatability is perfect for that eye. Using a stereo-pair allows one to visualise the directions of the comets in three-dimensional space. (Comets can also be used to compare measurements over time, say, in two separate sessions as in reproducibility studies.) Correlations (Pearsons, r) between repeated samples were determined for the coefficients of power (FI=M, FJ = J0 and FK = J45) as well as for differences of repeated samples to investigate possible associations and repeatability. Agreement29 and repeatability30–32 for NETRA were assessed with Bland- Altman plots with 95% limits of agreement (LoA) with exact CIs,29 33 coefficients of repeatability (CR)29 31 and intraclass correlation coefficients (ICC). If CR=0 then repeated measurements for participants are exactly matching.29 31 If CR<0.4 the two samples have high repeatability while where CR is 0.4–0.7 there is moderate repeatability. For low repeatability CR>0.7. So, the larger the CR the less similar or repeatable are the two samples under comparison.29 31 Repeatability is the closeness of agreement between consecutive measurements (in a single session per participant) for the same method under the same or similar conditions of measurement for one or more participants.30 Thus, in this paper, repeatability is assessed using a range of methods, some that are well known such as Bland-Altman-plots for agreement, CR, ICCs and 95% repeatability limits, and some such as comets8 26 27 that may be less familiar to readers. Software14–27 for dioptric power analysis1 14–27 34 ,35 developed by Harris, Malan and Rubin based on Matlab was used to draw the stereo-pairs,14–27 surfaces of constant probability density (confidence ellipsoids for means18 21 and distribution ellipsoids34) and comets.8 26 27 Surfaces of constant probability density21 34 are three-dimensional equivalents of two-dimensional confidence ellipses for sample means and distributions of data. They inform us about the probable or estimated distributions (sample and population of the means and data) for the specific variable/s concerned. We infer results from the sample to the population and the accuracy of the inference is dependent on factors such as data normality and outliers.21 26 27

Results

Correlation coefficients for the repeated samples (test and retest) for the right eyes were r=0.92, p=0.00; r=0.72, p=0.00; and r=0.47, p=0.00 for the stigmatic components (FI=M) and antistigmatic components (FJ = J0 and FK = J45) of power, respectively. The reason/s for the weaker correlations for FJ and especially for FK are unknown but might relate to outliers or possibly sampling size and methodology. Normality tests20 21 26 27 applied to repeated samples for the right eyes indicated that the two samples departed from normal distributions with mainly leptokurtosis but minimal skewing (for conciseness, plots for these statistics are not included here but are available in reference 26).26

Stereo-pair comets for repeated NETRA samples

Stereo-pair scatterplots with comets (see figure 1) illustrate variation of refractive behaviour in three-dimensional symmetrical dioptric power space. Figure 1 has three axes; the stigmatic (FII, or MI if the reader prefers) axis which represents stigmatic (scalar or spherical) powers, the ortho-antistigmatic (FJJ or J0J) axis which is an axis of Jackson cross cylinders (JCC) with principal meridians, at 0° and 90°, and the oblique-antistigmatic (FKK or J45K) axis, which represents JCC with oblique principal meridians (45° and 135°). In figure 1, the measurement (first or test) from NETRA is joined with a straight line to the corresponding second (retest) measurement for the participant concerned, thereby allowing one to easily assess similarity for each participant, and we can also see how refractive state differed across participants (variation is mainly spherical or stigmatic).

Figure 1
Figure 1

(A) Stereo-pair scatterplots with comets joining paired or repeated Near Eye Tool for Refractive Assessment (NETRA) measurements of 279 right eyes. The origin is O D or emmetropia, and the axis length is 5I D or in clinical terms 5 D (with tick intervals of 1 D). Each comet represents a single eye and consists of a dot and a line segment with the dot representing the initial refractive error measurement and the end of the line representing the second or repeated measurement. A single dot or point indicates that first and second measurements were identical for the eye concerned, whereas the longer the length between the edges (of a comet) the greater the dissimilarity of the two measurements for the eye concerned. If repeatability were perfect for all eyes, only points would be seen on the plot. Readers should allow their eyes to diverge to an imaginary point behind the page when observing each of the stereo-pairs in the figure. This results in a third plot appearing in the middle between the two halves of each stereo-pair and this central plot will have a three-dimensional appearance. (B) Plot of comet lengths using the Euclidean distances from the head to tails of comets, and (C) The 95% confidence ellipsoid on mean difference (0.09 –0.06 × 107 in clinical terms). The origin is a zero difference or the null matrix, O D with axis length of 1 D. (Individual differences between the repeated samples are not shown as they would obscure the ellipsoid.)

About 50% of the NETRA comets for the right eyes (figure 1A) are short (< 0.5 D) or very short (< 0.25 D) suggesting similarity of paired measurements. However, some measurements are more dissimilar with longer comets (>1 D in length) and there are one or two extremely long comets, and such participants could be considered as potential outliers which could be attributed to factors such as large changes in ocular accommodation between their repeated measurements. (By changing the axis scaling, one can see individual comets more easily and the software allows one to view the plot as the comets are added, thus also making analysis of the respective comets easier.) The dioptric lengths of the comets (ie, differences of paired measurements per participant) can be represented graphically (figure 1B) and statistics such as mean and median comet lengths (or differences) and SDs can be used to better understand issues such as repeatability. For figure 1A,B, the mean comet length and SD are 0.61±0.70 D with a median comet length of 0.49 D. Comet lengths range from 0.02 D to 10.47 D.

Stereo-pair scatterplots with 95% distribution ellipsoids

Figure 2 includes stereo-pair scatterplots for the NETRA measurements for the right eyes of the 279 participants. The stereo-pair includes two 95% surfaces of constant probability density (sometimes called distribution ellipsoids).21 34 Surfaces of constant probability density are three-dimensional correlates of two-dimensional confidence ellipses. Since refractive state (and its behaviour or variation over time) involve trivariate quantities, three-dimensional distribution ellipsoids are applicable to understanding sample distributions and how they relate to population distributions. In figure 2 the 95% distribution ellipsoids overlap closely with very similar shapes, orientations and positions, confirming that the samples are not too different. Figure 2 can be used in conjunction with figure 1 and, for example, at the bottom of figure 2 two points (one red and one black) can be seen to be very close to one another and in figure 1A the corresponding comet (see lower text box and arrow) can be found for this right eye of the participant concerned. Descriptive statistics for these distribution ellipsoids can be found in table 1 and SII, SJJ and SKK represent the stigmatic and antistigmatic variances18 23 for FI, FJ and FK (or M, J0 and J45), respectively. Variances are always positive and the larger the variance the greater the variability of that coefficient of power in the sample concerned. The remaining entries in table 1 are the covariances SJI, SKI and SKJ that represent the linear relationships and covariation between variances for FI and FJ, FI and FK and FJ and FK, respectively.

Figure 2
Figure 2

Stereo-pair scatterplots and 95% distribution ellipsoids for the right eyes of 279 participants for repeated Near Eye Tool for Refractive Assessment (NETRA) measurements. The first and second measurements (refractive errors) per participant are indicated with black and red points, respectively. The axis lengths are 5I D, and tick intervals of 1I D, 1J D and 1K D and the origin is at O D (or emmetropia). For each sample, approximately 95% of measurements are within the ellipsoid concerned with 5% of measurements outside the ellipsoid.

Table 1
|
Descriptive statistics for 95% distribution ellipsoids (see figure 2) for repeated NETRA samples for 279 right eyes.

Covariances can be negative or positive and the further away from zero the greater the strength of the positive or negative linear relationship. If no linear relationships exist, then the covariances will all be zero (0 D2). The square roots of the variances are their corresponding SDs ( Inline Formula ). From this table, clinical means for the NETRA samples are very similar for the 279 right eyes (–-1.87 –-0.09 × 167 and -–1.90 –-0.13 × 178), suggesting, on average, that refractive errors did not differ much across the repeated samples. In addition, similar stigmatic variation is seen for paired measurements for the right eyes (test: SII=4.36 D2; retest: SII=4.27 D2). Antistigmatic variances were small (≤ 0.17 D2 or s=0.41 D) and relatively close to zero. Covariances are generally small and almost zero thereby suggesting little or no linear relationships between variances for the different coefficients of power (FI, FJ and FK) involved. The volumes for the NETRA 95% distribution ellipsoids for the right eyes are dissimilar (51.43 D3 and 63.26 D3) due to the presence of a possible outlier (see two adjacent points far below the ellipsoids in figure 2).

Hypothesis tests for refractive state18 21 27 34 at a 95% confidence level were applied to the repeated samples for the right eyes (see table 1) and sample variances and covariances were equal at a 95% confidence level ( Inline Formula , u=7.826, p<0.05). Given the equality of variances and covariances, sample means for these samples were also compared and found to be equal (Fα,3, 554 = 2.67, w=0.296, p<0.05). This supports figure 2 where closely overlapping ellipsoids and similarity of the centroids (means) for the ellipsoids were observed.

Bland-Altman plots

In figure 3, Bland-Altman plots8 26 27 29 for the NETRA samples for the right eyes only of the 279 participants illustrate agreement for repeated measurements.35 Descriptive results for the Bland-Altman plots are included in table 2. If agreement was exact or perfect,  Inline Formula  = 0 D, SD=0 D, SE=0 D, 95% LoA range (or width) = 0 D, CR=0, ICC=1 and all points would be located on the horizontal line with a y-coordinate of 0 D. This is clearly not the case for figure 2 and table 2 for the NETRA samples, although some values are close to zero, and generally this is truer for the antistigmatic coefficients (FJ and Fk) than for the scalar coefficients (FI). However, ICC suggested good (0.7< ICC < 0.9) to excellent (ICC ≥0.9) agreement for the repeated measurements for the stigmatic coefficients (FI) but less so for the ortho-antistigmatic coefficients (FJ) and particularly the oblique antistigmatic coefficients (FK) where ICC is 0.72 or 0.47. Outliers are important here (see figure 3A) and removal (figure 3D) of a single outlier markedly changes the plot and the two plots are shown here specifically to emphasise the importance of even a single outlier in this type of analysis. (Other factors such as data normality and sample size might also be relevant.)

Figure 3
Figure 3

Bland-Altman plots of means versus differences of repeated Near Eye Tool for Refractive Assessment (NETRA) measurements for right eyes of 279 participants, aged 9–63 years. Results for participants are indicated with black dots. Each plot has a title that refers to the coefficient concerned, that is, FI, FJ or FK. In each part, the solid black horizontal line indicates the estimated mean difference ( while the upper and lower 95% limits of agreement (LoA) are represented by the dashed black lines which each lie within their own 95% exact CIs33 as represented by the red shaded regions. Two black dotted lines represent Differences were calculated by subtracting the corresponding first from second NETRA measurements for the right eyes of each of the participants. Note the differences in scales in the different parts. For the stigmatic (FI) coefficients, an additional Bland-Altman plot (figure 3D) was included after the removal of an outlier to illustrate its effects. The Bland-Altman plots also include Pearson’s correlation coefficients (and corresponding p values) for the specific means and differences concerned. If the means and differences are not correlated, then r would be close to zero. If p<0.05 then the correlation is significant at a 95% level of confidence.

Table 2
|
Descriptive statistics for the Bland-Altman plots (see figure 3) for the right eyes of 278 participants (one outlier was removed). SDs (s) in dioptres (D) are provided for both the means as well as for the differences (of repeated measures per eye). The quantity  formula image  is the SD of the differences of repeated measures per eye.30 Coefficients of repeatability ( formula image , unit is D) are also given. Units are dioptres throughout except for the intraclass correlation coefficients (ICC) which are unitless

The means ( Inline Formula ) in table 2 are the global averages for the NETRA samples for the 278 right eyes after removal of the outlier concerned. Thus, the mean power and its SD (s) for the stigmatic coefficient (FI or M) are –1.94±2.04 D. For FJ (or J0), 0.05±0.37 D and for FK (or J45), -0.01±0.24 D. Thus, the stigmatic coefficients of power of the sample as compared with the ortho-antistigmatic or oblique-antistigmatic coefficients demonstrate greater variation as indicated by the much larger SD. Outliers and the absence of cycloplegia in the younger participants are important here.

The mean differences ( Inline Formula ) for all three coefficients of power in table 2 for the right eyes are approximately zero (-–0.02 D or 0.02 D) indicating, on average, good repeatability, and agreement across the two samples. The 95% LoA for the ortho-antistigmatic and oblique-antistigmatic coefficients for the right eyes as given in table 2 spans narrower intervals than that for the stigmatic (or spherical) powers which would also suggest that repeated antistigmatic coefficients are more similar and all SE associated with the  Inline Formula  and the LoAs are small (≤0.07 D). For the antistigmatic powers (ortho-antistigmatic and oblique-antistigmatic coefficients) in table 2, CR is 0.72 D or 0.47 D suggesting that the antistigmatic powers had moderate repeatability for the right eyes. Stigmatic powers suggest low repeatability for right eyes with larger CR of 1.63 D and 1.49 D, respectively. Absence of cycloplegia and outliers had important influences here.

Repeated measurements for the same eyes should not differ by more than 2.77σd2 ≈ 2.77  Inline Formula 2; 2.77 is  Inline Formula  ×1.96.31 32 These are the probable limits within which 95% of the differences between repeated measurements should fall. Thus, for the right eyes and the stigmatic coefficients,  Inline Formula  in table 2 is 0.83 D and 2.77  Inline Formula 2 = 2.77 (0.83 D) = 2.30 D. Such limits are smaller for the antistigmatic coefficients, and possible outliers and absence of cycloplegia are important. Removal of an outlier for the right eyes (n=278) resulted in:

  • Decreased 95% repeatability limits (eg, 2.3 D to 1.52 D for FI=M)

  • Decreased 95% LoA widths (3.29 D to 2.21 D for FI).

  • SD for the mean differences decreased (0.83 D to 0.55 D).

  • CR decreased (1.63 to 1.08 for FI)

  • ICC moved closer to unity (1).

Hence, removing the outlier strengthened repeatability (and agreement) between repeated stigmatic (FI) samples, and although the decrease in variation (s and SD) was minor, this and figure 3A,D nonetheless illustrate the importance of outliers during analysis of refractive data.

Discussion

Only right eyes were included in this study with NETRA36 to avoid any concerns about combining right and left eyes in single samples.37 Previous studies3–5 7–13 suggest that measurements with NETRA are valid6–10 13 26 27 and repeatable, even in the absence of cycloplegia8 26 27 but repeatability increases with cycloplegia.3 8 11 12 26 27 Direct comparisons of the results for repeatability from this paper to previous publications are difficult as other studies mainly analysed the validity of NETRA against subjective and/or objective refraction,3–7 9–13 including one paper by the authors here.8 However, with reference to McAlinden et al31 and Bland and Altman,38 95% within-subject SDs  Inline Formula  and repeatability values were calculated as well as SEs for quantities such as the mean differences of repeated samples as well as the LoA (table 2).8 26 27 31 The SEs are small (0.02 D to 0.03 D) for the mean differences and also for the LoA where SE is 0.03 D or 0.06 D. Thus, the mean differences and LoA for the repeated samples are precisely known. The mean differences are also small (table 2) even in the absence of cycloplegia; thus, for the participants their repeated measurements, on average, hardly differed but the differences themselves are more widely spread as seen in the Bland-Altman plots (figure 3). Repeatability,39 or measurement error (the estimated differences from the true and measured values),39 at a 95% level of confidence is:29–31 38 39 Repeatability  Inline Formula  (=2.77  Inline Formula ) and this provides the probable limits within which 95% of differences occur. So, for the right eyes (OD) and the stigmatic coefficients (FI=M) after removal of one outlier, the  Inline Formula  and the 95% repeatability is  Inline Formula  (Use of cycloplegia would likely reduce this value.) Thus, the differences of repeated measurements for participants is ≤1.6 D at a 95% level of confidence. So, even though the mean differences (see table 2) are very small, individual differences (see figure 3) with NETRA can be relatively large in the absence of cycloplegia and outliers can have marked effects. However, repeatability values are smaller (≈0.57 D) for the antistigmatic coefficients of power (FJ and FK or J0 and J45).

Previous studies3–10 13 40–44 including one8 by the authors addressed the issue of validity of NETRA in relation to methods such as subjective refraction,6 8–10 13 40–44 retinoscopy11 or objective refraction.12 43 In some studies,3 10–12 26 44 cycloplegia was included and, for example, Pamplona, found that with cycloplegia NETRA measured refractions within 0.5 D to that of subjective refractions and within 1 D to autorefraction.3 With cycloplegia, Pamplona3 found that absolute mean SE difference of NETRA and subjective refractions reduced from 1.35 D to 0. 4 D. (The authors here (NH and AR) also confirmed this where NETRA was compared with subjective refraction and absolute mean SE difference reduced from 1.17 D to 0.04 D,8 26 without and with cycloplegia.) Further studies by Pamplona et al4 5 found that, for example, NETRA and subjective refractions, even without cycloplegia, gave similar results on average (absolute mean differences for M, J0 and J45 −0.22, 0.07 and −0.01 D) but, as anticipated, there were individual eyes where the absolute differences were larger than these averages.

Bastawrous et al,9 in 34 eyes of adults (23–81 years, but mostly presbyopic) found mean SE difference of −0.32 D as against −0.31 D (Hasrod26) when comparing NETRA and subjective refractions, both without cycloplegia. Solaka et al10 similarly compared NETRA and subjective refraction without cycloplegia but analysed the clinical components of refractions separately10 without transformation to power vectors and the absolute mean differences for the spherical component ( Inline Formula ) was 0.48 D to 0.64 D depending on which version of NETRA was used whereas Hasrod,26 without cycloplegia, found this to be greater at 0.98 D. Sample sizes were 48 eyes and 279 for Solaka et al10 and Hasrod,26 respectively. Gaiser et al,13 also compared NETRA and subjective refraction without cycloplegia in 27 adult participants and found absolute mean SE difference to be 0.31 D as against 0.94 D (for 279 right eyes) and 0.71 D (279 left eyes) from Hasrod.26 Hasrod’s sample included younger participants and the differences here might relate to factors such as fatigue with younger participants, possible outliers, and difficulties that younger individuals might experience with understanding and using NETRA. Tousignant et al40 found the following when comparing NETRA and subjective refractions without cycloplegia: mean difference for FI (=M) of 0.53 D and the 95% LoA width of 2.80 D. Hasrod26 measured the mean difference for FI (=M) of 0.97 D and 95% LoA width of 3.29 D (right eyes). With removal of an outlier for the right eyes, the LoA range decreased to 2.21 D (see table 2), and this emphasises the importance of outliers and their effects in analyses of refractive state (see figure 3). (Although not included here, the LoA range was smaller for the 279 left eyes at 1.42 D,26 even without cycloplegia.) Jeganathan et al42 also found small but significant differences when comparing NETRA to subjective refractions.42 Their study involved refractive states measured with (75 eyes) and without cycloplegia (152 eyes) and analysis was based on spherical equivalent (SE=FI=M). Mean differences for SE for NETRA and subjective refraction ranged from 0.25 D to 0.67 D, depending on whether cycloplegia was used and whether absolute SE or SE were applied to the analysis.

When comparing NETRA to methods other than subjective refraction, generally similar conclusions are reached, namely that cycloplegia is necessary with younger participants but repeatability is generally adequate to good. For example, Jeganathan et al42 also compared NETRA and retinoscopy while Li et al43 compared non-cycloplegic NETRA to table-mounted autorefraction (Topcon KR-800S) in a sample of 100 participants (19–92 years with mean age 54.6 years) and found that the mean SE difference was 0.11 D with 95% LoA width of 2.18 D. (Mean SE difference in NETRA refraction and subjective refraction was slightly larger at 0.34 D but with smaller 95% LoA width of 1.87 D.) They point out that NETRA produces results that are slightly less negative in power than for autorefraction or subjective refraction. However, cylinders across methods were similar and they recommend checking the spherical component of power before prescribing spectacle or contact lens compensations should NETRA be used in that process.

Ee and Samsudin44 compared NETRA with automated refraction and subjective refraction. They had 204 participants with mean age 36.6 years (SD, 15.7 years) and they found that NETRA had wider 95% LoA than for automated refraction (3.63 D vs 3.06 D, respectively). NETRA gave similar refractive results as for automated refraction but sometimes overminused results in comparison with subjective refraction, and they mentioned that there were practical issues that complicated the use of NETRA. (Authors such as Rosenfield and Ciuffreda45 or Rao et al46 compared other types of handheld instruments such as the SVOne Handheld Autorefractor (also uses a smartphone like NETRA) or Instaref R20 (also uses wavefront aberrometry as for NETRA) to autorefraction and subjective refraction but studies involving NETRA to methods such as autorefraction or retinoscopy are limited in number.)

The stereo-pair comets8 26 27 47 (figure 1A) and comet lengths (figure 1B) showed that for many eyes, there was little difference between repeated measurements as indicated by the mostly short comets (median length ≤0.5 D). There are, however, exceptions and longer comets are seen in figure 1A and an outlier with a comet length of 10.47 D was noted (see figure 1B). This outlier was retained in the analysis specifically to demonstrate that ocular accommodation can have profound effects with measurements with NETRA in the absence of cycloplegia. However, figure 1B illustrates that except for two eyes, the comet lengths were mostly <1.5 D. Repeatability and the differences in repeated measures for the right eyes can also be evaluated using figure 1C where a 95% confidence ellipsoid21 is shown for the mean difference. The ellipsoid is small (volume: 0.004 D3) with its centroid (a mean difference in clinical terms of only 0.09 –0.06 × 107) just above the origin that represents the null matrix (O D) or a zero difference in repeated measures. The ellipsoid overlaps the origin, so, on average, NETRA produces a mean difference that is very close to zero and the instrument is repeatable even in the absence of cycloplegia. However, repeatability for individual eyes is not necessarily as good and the outlier (see figures 1A, B and 3A) is an example here.

Similarly, the scatterplots with 95% distribution ellipsoids (figure 2), overlap closely with similar centroids (means) as provided in table 1, suggesting that the repeated samples for these right eyes, and by inference, their populations did not differ much. If this was untrue, the two ellipsoids would be seen as separate. Hypothesis tests of 95% level of confidence also indicated equality of sample variances and covariances, and likewise for their means.

Bland-Altman plots (figure 3) with mean differences (all very close to 0 D, see table 2) and their SDs (0.29–0.31 D, table 2) suggested that, in general, the distributions for the differences between repeated measurements for the antistigmatic coefficients of power (FJ and FK; or J0 and J45 if one prefers) had similar variability and good agreement. LoA widths at a 95% confidence level (see table 2) are smaller (1.12 to 1.23 D) for FJ and FK than for FI. So, stigmatic coefficients (FI=M) were less similar with weaker agreement (although mean differences remained close to 0 D, and the SD for the differences was greater at 0.55 D), and 95% LoA widths were larger (>3 D); outliers and the absence of cycloplegia probably had important influences. Outliers within the samples (see figures 1–3) could be due to instrument myopia.47 As for autorefractors, when a near target is viewed within NETRA without the use of a cycloplegic, the proximity of the perceived target stimulates proximal accommodation which can lead to overaccommodation and more negative or myopic readings. Other factors include internal and external illumination levels, astigmatic aberrations, optical decentration, the contrast and type of targets and direction of focus and extraneous variables such as age and user experience and possibly fatigue that may also influence instrument myopia.40–48

Possible limitations here are that the sample (n=279 participants) was relatively small and selected via non-random convenience sampling and various ophthalmic procedures (to exclude eyes with ocular disease or refractive states that would be outside the measurement range of NETRA) rather than via a randomised selection and thus results are not necessarily representative of the cultural, age, ethnic and gender diversity present in the general population. However, given the primary aim of this study that concerns NETRA repeatability, this sampling method was not regarded as a serious limitation. Previous studies3–7 9–13 involving NETRA used much smaller sample sizes (≤36 participants), and right and left eyes were analysed together in their sample/s and no mention was made of issues such as reflection of cylinder axes for, say, all left eyes or the impact this might have regarding analysis and effects on independence of interocular data. Although only results for the right eyes are included here, the investigation involved both eyes of 279 participants but analysed right and left eyes separately.8 26 27 Additionally, results were assessed using mainly multivariate statistical methods for dioptric power and refractive behaviour and this is one of very few studies8 26 27 where such methods were applied to NETRA to assess repeatability.

Further studies comparing non-cycloplegic and cycloplegic results would be useful in understanding the nature and extent of ocular accommodation on NETRA validity and reliability, especially concerning the spherical (stigmatic) component (FI) of power, and future papers by the authors will address these issues. NETRA measurements and possible correlations to factors such as ethnicity, gender, age and pupil size would also be helpful. Age and NETRA in very large samples would be useful, with and without cycloplegia, and subjective refractions also would be helpful. The use of NETRA (or similar mobile devices) for the self-monitoring of refractive behaviour of specific individuals with diabetes, keratoconus, juvenile myopia or during pregnancy might be other areas for exploration. The relationship between NETRA and prescribed lenses is another interesting topic to determine the extent to which such compensating lenses could be directly prescribed using only NETRA, again with and without cycloplegia for younger individuals. Interoperative use of NETRA, for example, with refractive surgery might be another area for investigation.

Conclusions

Departure from normality and outliers have important influences on measurements and samples with NETRA, but, on average, and for many eyes the instrument provides similar measurements on repetition, even in the absence of cycloplegia. However, repeatability is less satisfactory without the use of cycloplegia and is less so for the stigmatic (FI=M) as against the antistigmatic coefficients (FJ = J0 and FK =J45) of power. The method (due to its portability, method of operation where self-refraction is used and repeatability in general) could be potentially helpful in resource-limited environments where other alternatives for ophthalmic refraction might not be readily available. It is not, however, a substitute for subjective refraction by skilled clinicians and cycloplegia is recommended where NETRA is used with younger patients. Spectacle prescriptions should not be provided directly from NETRA as there are limitations in repeatability, not so much on average, but for individual eyes in some instances.8 26 27 46 Nonetheless, NETRA could provide a starting point for subjective refraction and subsequent spectacle or contact lens prescriptions, should methods such as retinoscopy not be available.

As a research tool, NETRA is potentially useful and the analyses here suggest that NETRA can be used as a cost-effective, mobile and generally reliable self-refraction refractive error screening tool in rural or other communities, especially where eye care clinicians and/or other methods of ocular refraction might not be available. The use of cycloplegia with younger individuals will further enhance the uses and applications of the instrument, although young children may struggle with the subjective alignment method in NETRA, and other methods such as retinoscopy, mobile wavefront aberrometers or objective autorefractors, may be indicated.