Abstract
Purpose.:
The purpose of this study was to compare the accommodative performance of the amblyopic eye of children with unilateral amblyopia to that of their nonamblyopic eye, and also to that of children without amblyopia, during both monocular and binocular viewing.
Methods.:
Modified Nott retinoscopy was used to measure accommodative performance of 38 subjects with unilateral amblyopia and 25 subjects with typical vision from 3 to 13 years of age during monocular and binocular viewing at target distances of 50, 33, and 25 cm. The relationship between accommodative demand and interocular difference (IOD) in accommodative error was assessed in each group.
Results.:
The mean IOD in monocular accommodative error for amblyopic subjects across all three viewing distances was 0.49 diopters (D) (95% confidence interval [CI], ±1.12 D) in the 180° meridian and 0.54 D (95% CI, ±1.27 D) in the 90° meridian, with the amblyopic eye exhibiting greater accommodative errors on average. Interocular difference in monocular accommodative error increased significantly with increasing accommodative demand; 5%, 47%, and 58% of amblyopic subjects had monocular errors in the amblyopic eye that fell outside the upper 95% confidence limit for the better eye of control subjects at viewing distances of 50, 33, and 25 cm, respectively.
Conclusions.:
When viewing monocularly, children with unilateral amblyopia had greater mean accommodative errors in their amblyopic eyes than in their nonamblyopic eyes, and when compared with control subjects. This could lead to unintended retinal image defocus during patching therapy for amblyopia.
Measurements were performed by the same examiner at each clinical site (VM at IU and AMC at SCCO). The study was conducted at each site with a written protocol that was established before the study was initiated. Study procedures were performed with subjects wearing their habitual refractive correction in order to elicit habitual accommodative performance. Any residual uncorrected refractive error was adjusted for in the data analysis. Monocular distance visual acuity was measured by using the ATS-HOTV protocol
25 on an electronic visual acuity test system.
27 Stereoacuity was measured at 40 cm by using the Randot Preschool Stereoacuity Test (Stereo Optical, Inc., Chicago, IL, USA).
28
Accommodative responses were measured by using Nott dynamic retinoscopy,
29 which is a commonly used clinical method to evaluate accommodative performance. Studies have suggested that when used in similar viewing conditions, Nott retinoscopy and objective autorefraction measurements of accommodative response are comparable at a range of target distances.
30–32 Examiners used a retinoscope to determine the refractive state of the eye while the subject viewed an animated cartoon movie on a 15 cm × 8.5 cm LCD screen mounted on a motorized track. The subject's viewing distance was stabilized by using a forehead rest. The movie was used as the target to mimic naturalistic daily visual experience (approximately 1/f spatial amplitude spectra), and the subjects were simply instructed to watch the movie in an attempt to elicit their habitual viewing effort. The examiner adjusted her working distance from the subject to neutralize the retinoscopic reflex, and the resulting retinoscope-to-cornea dioptric distance was recorded as the subject's accommodative response. In this study, the Nott dynamic retinoscopy technique was modified with the use of a beam-splitter, allowing the examiner to perform retinoscopy to the side of the subject (
Fig. 1), while a linear potentiometer attached to the retinoscope allowed the distance between the examiner's retinoscope and the subjects' corneas to be recorded and stored automatically with the press of a trigger button. The range of measurable dioptric distances (corresponding to measurable accommodative responses) was between 0.68 D at the farthest measurable distance and 4.69 D at the closest measurable distance. The instruments used at the two sites were designed, manufactured, and calibrated at Indiana University School of Optometry.
Nott dynamic retinoscopy was performed for the 180° and 90° meridia of each eye, at target distances of 50 cm (2.00 D), 33 cm (3.00 D), and 25 cm (4.00 D), in both binocular and monocular viewing conditions (two meridia of two eyes at three distances generated 12 measurements for each viewing condition). The right eye and the 180° meridian of each eye were always tested first. The accommodative demand either increased (2.00 D, 3.00 D, 4.00 D) or decreased (4.00 D, 3.00 D, 2.00 D) for each subject, assigned in a random fashion by the investigator. The results were pooled across sequence of testing (increasing or decreasing target distance), as there have been no observed effects of the order of stimulus presentation on accommodative response.
14 The examiner monitored the stability of accommodation by noting fluctuations of the retinoscopic reflex and asked subjects questions about the movie to encourage interest and steady fixation when necessary. Measurements were only taken when the retinoscopic reflex appeared stable. For subjects who sustained attentive fixation after the primary study measurements were completed, measurements were repeated for one eye in either binocular or monocular viewing to assess the intra-examiner, intra-instrument, and intrasession repeatability of the Nott retinoscopy approach. Intra-examiner, interinstrument, and intersession repeatability data were collected from one pre-presbyopic adult, as were another set of interexaminer, intra-instrument, and intrasession data.
The subjects' clinical charts were reviewed after completing the study procedures to determine medical history, surgical history, habitual spectacle prescription, cycloplegic refraction, duration of spectacle wear, duration of patching treatment (if any), and eye alignment measurements with distance and near fixation.
Residual uncorrected refractive error was calculated as spectacle lens power subtracted from cycloplegic refraction. This was added to the accommodative demand (dioptric distance of the target) and measured accommodative response to derive the total accommodative demand and total accommodative response, respectively. Accommodative error was defined as the total accommodative response subtracted from the total accommodative demand. If the accommodative error was positive (i.e., underaccommodation), an accommodative lag was present; if the accommodative error was negative (i.e., overaccommodation), an accommodative lead was present. The IOD in accommodative error was calculated as better/nonamblyopic eye error subtracted from worse/amblyopic eye error, with positive values indicating a larger lag or smaller lead in the worse/amblyopic eye than in the better/nonamblyopic eye.
The IOD in accommodative error during binocular viewing was corrected by subtracting any residual uncorrected anisometropia, as illustrated in the following example: a cycloplegic refractive error of +1.00 D might be found in the nonamblyopic eye and +5.00 D in the amblyopic eye. On lensometry, the subject's habitual spectacle lenses might be +1.00 D in the nonamblyopic eye and +4.50 D in the amblyopic eye. The residual uncorrected anisometropia (amblyopic eye − nonamblyopic eye) would then be +0.50 D. The accommodative error during binocular viewing with the habitual spectacle correction might be +1.00 D in the nonamblyopic eye and +1.50 D in the amblyopic eye. The unadjusted IOD in accommodative error during binocular viewing (amblyopic eye − nonamblyopic eye) would then be +0.50 D. This IOD could, however, be attributed to residual uncorrected anisometropia. To control for this, the residual uncorrected anisometropia is subtracted from the IOD in accommodative error for binocular viewing, yielding an adjusted IOD for binocular viewing of zero in this example.
Error in variables (EIV) regression analysis (STATA [StataCorp LP, College Station, TX, USA] function designed to incorporate variability in the predictor variable) was used to describe total accommodative response as a function of total accommodative demand. Four regressions were performed for each eye in each group (amblyopic and control): binocular viewing/90° meridian, binocular viewing/180° meridian, monocular viewing/90° meridian, and monocular viewing/180° meridian. Error in variables regression analysis was also used to assess the relationship between the IOD in accommodative error and total accommodative demand, and to compare better eye accommodative responses between amblyopic and control subjects.
A stepwise multiple linear regression analysis was performed to evaluate whether amblyopic eye logMAR visual acuity, presence or absence of stereoacuity (with a criterion of 800 seconds of arc on the Randot Preschool Stereoacuity Test), or duration of patching treatment (in months), was associated with amblyopic eye accommodative error during monocular viewing at the highest accommodative demand of 4.00 D. A P value of 0.007 was used to determine significance for each factor (Bonferroni correction for multiple comparisons based on seven models).
To assess intra-examiner repeatability in amblyopic and control subjects as well as interinstrument and interexaminer repeatability of Nott retinoscopy, the mean difference between initial and repeated accommodative response measurements was derived with the associated 95% limits of agreement. A Bland-Altman plot, where the difference between initial and repeated measurements of accommodative response was plotted against the average of the two measurements,
33 was also generated to evaluate whether repeatability varied systematically with average accommodative response.
All calculations and statistical testing were performed with Microsoft Excel (Microsoft, Redmond, WA, USA) or STATA.
Thirty-eight subjects with unilateral amblyopia and 28 typically developing subjects were recruited. For children who were enrolled into the study, if it was determined during poststudy review of their clinical records that they had worn their refractive correction for less than 4 weeks at the time of data collection, they were excluded from the data analysis (three control subjects). This yielded a total of 38 amblyopic subjects (mean age = 6.89 years, SD = ±1.94 years; 11 IU, 27 SCCO) and 25 control subjects (mean age = 6.84, SD = ±2.83 years; 19 IU, 6 SCCO) who were included in the data analysis.
In the control group, median visual acuity in the worse eye was 0 logMAR (interquartile range [IQR]: −0.1 to 0 logMAR) and median stereoacuity was 40″ (IQR: 40″ to 60″). In the amblyopic group, visual acuity in the amblyopic eye ranged from 0.1 logMAR to 1.0 logMAR with a median of 0.3 logMAR (IQR: 0.2–0.4 logMAR). Of the 38 amblyopic subjects, 20 (52.6%) had no measurable stereopsis (i.e., worse than 800″). Twenty-two (57.9%) had anisometropic amblyopia, 7 (18.4%) had strabismic amblyopia, and 9 (23.7%) had combined-mechanism amblyopia (
Fig. 2). All amblyopic subjects and no control subjects wore optical correction. The median SE cycloplegic refractive error was +0.75 D (IQR: 0.38–1.00 D) in both the better and worse eyes of control subjects and +1.88 D (IQR: 0.97–3.94 D) in the nonamblyopic eye and +5.25 D (IQR: 3.75–6.25 D) in the amblyopic eye of amblyopic subjects (
Fig. 3). The median astigmatism was 0 D (IQR: 0–0.25 D) in both the better and worse eyes of control subjects and 0.50 D (IQR: 0–0.5 D) in the nonamblyopic eye and 0.75 D (IQR: 0.5–1.5 D) in the amblyopic eye of amblyopic subjects.
Interinstrument repeatability of Nott dynamic retinoscopy for one pre-presbyopic adult, assessed by both of the two study examiners on two different days (one instrument on one day and the other instrument on another day), revealed a mean signed difference of +0.03 D (95% Limits of Agreement [LOA]: ±0.76 D; Fig, 4) and a mean unsigned difference of 0.30 D. Interexaminer repeatability for one pre-presbyopic adult, performed on the same instrument within 1 hour, revealed a mean signed difference of +0.02 D (95% LOA: ±0.42 D) and a mean unsigned difference of 0.16 D. Intra-examiner, intra-instrument, and intrasession repeatability of Nott dynamic retinoscopy were assessed in a subset of subjects who sustained attentive fixation after the primary study measurements were completed. No significant differences were found between the characteristics of the subjects who participated in the repeatability analysis and those who did not. Neither age (amblyopes,
P = 0.34; controls,
P = 0.97) nor presence of strabismus (amblyopes,
P = 0.85) was predictive of the ability to participate in collection of repeatability data. There was a mean signed difference of −0.06 D (95% LOA: ±0.80 D) and a mean unsigned difference of 0.30 D for the 15 amblyopic subjects, and a mean signed difference of −0.08 D (95% LOA: ±0.48 D) and a mean unsigned difference of 0.19 D for the 16 control subjects (
Figs. 5A,
5B). Neither intra-examiner, nor interexaminer, nor interinstrument repeatability varied with average total accommodative response.
All of the subjects attended to the target well during the data collection. A total of 960 accommodative response measurements were collected from amblyopic subjects and 600 from control subjects. Thirty-nine data points from the amblyopic group and 32 data points from the control group could not be collected, primarily due to the limited range of the potentiometer (39/39 cases in amblyopes and 31/32 in controls). In one case, the trigger button was not pressed to record the measurement. In amblyopic subjects, most missing data were due to accommodative responses < 0.68 D, while in controls, missing data were typically due to responses > 4.69 D.
No subject had residual oblique astigmatism (axis > 15° from 90° or 180°) with his/her habitual correction and 25 (65.8%) amblyopic subjects and 18 (72%) controls had no residual regular astigmatism. Those with residual regular astigmatism were undercorrected by ≤1.00 D. The median residual uncorrected astigmatism in amblyopic subjects was 0 D (IQR: 0–0 D) in both amblyopic and nonamblyopic eyes. The median residual uncorrected astigmatism in control subjects was 0 D (IQR: 0–0.25 D) in both the worse and better eyes.
The median residual uncorrected SE refractive error in amblyopic subjects was +1.00 D (IQR: +0.25 to +1.50 D) in amblyopic eyes and +1.00 D (IQR: +0.25 to +1.50 D) in nonamblyopic eyes. The median residual uncorrected SE refractive error in control subjects was +0.75 D (IQR: +0.5 to +1.00 D) in the worse eyes and +0.75 D (IQR: +0.25 to +1.00 D) in the better eyes. There were no significant differences in residual uncorrected SE refractive error between the amblyopic and control subjects in any meridian of either eye, using the Wilcoxon signed-rank test (P > 0.24).
The median signed residual uncorrected SE anisometropia (defined as the nonamblyopic eye/better eye subtracted from the amblyopic eye/worse eye residual uncorrected SE refractive error) in amblyopic and control subjects was 0 D (IQR: 0–0 D). Twenty-five (65.8%) amblyopic and 15 (60%) control subjects had zero residual uncorrected anisometropia. There was no significant difference in residual uncorrected SE anisometropia between the groups, using a Wilcoxon signed-rank test (P > 0.84). The median uncorrected astigmatic anisometropia was 0 D (IQR: 0–0 D) in both amblyopic and control groups.
An EIV regression analysis was used to assess the accommodative stimulus-response relationship within each group. The residuals around the fitted function in all conditions did not differ significantly from a normal distribution and had no systematic trend in variance, indicating that the regression approach was appropriate. The coefficients (slopes), constants, and
R2 values for each of the four regression analyses performed for each eye (monocular and binocular viewing for each meridian) for amblyopic and control subjects are listed in
Table 1. Data from monocular and binocular viewing for the 90° meridian, including the out-of-range data points (accommodative responses > 4.69 D or < 0.68 D) and linear regression, for both amblyopic and control groups are shown in
Figure 6.
Table 1. Summary of EIV Regressions Performed on Total Accommodative Response as a Function of Total Accommodative Demand
Table 1. Summary of EIV Regressions Performed on Total Accommodative Response as a Function of Total Accommodative Demand
Viewing Condition | Group | Meridian | Eye Condition | EIV Regression Model |
Coefficient | Constant | R2 |
Binocular | Controls | 90° | Better eye | 0.91 | −0.44 | 0.93 |
Worse eye | 0.88 | −0.32 | 0.91 |
180° | Better eye | 0.89 | −0.46 | 0.93 |
Worse eye | 0.93 | −0.56 | 0.96 |
Amblyopes | 90° | Nonamblyopic eye | 0.85 | −0.35 | 0.77 |
Amblyopic eye | 0.78 | −0.10 | 0.65 |
180° | Nonamblyopic eye | 0.75 | −0.26 | 0.76 |
Amblyopic eye | 0.70 | −0.06 | 0.66 |
Monocular | Controls | 90° | Better eye | 0.79 | −0.27 | 0.83 |
Worse eye | 0.86 | −0.52 | 0.86 |
180° | Better eye | 0.80 | −0.36 | 0.84 |
Worse eye | 0.85 | −0.51 | 0.84 |
Amblyopes | 90° | Nonamblyopic eye | 0.74 | 0.12 | 0.80 |
Amblyopic eye | 0.50 | 0.49 | 0.41 |
180° | Nonamblyopic eye | 0.68 | 0.05 | 0.78 |
Amblyopic eye | 0.54 | 0.17 | 0.49 |
There was no apparent difference between the nonamblyopic/better eye and amblyopic/worse eye slopes or intercepts during binocular viewing in either subject group, or during monocular viewing in controls, for either meridian. However, during monocular viewing in amblyopic subjects, the slope for the amblyopic eye was shallower (90° meridian = 0.50, 180° meridian = 0.54) than that of the nonamblyopic eye (90° meridian = 0.74, 180° meridian = 0.68), with the amblyopic eye exhibiting poorer accommodative responses with increasing total accommodative demands. The greatest variance in accommodative responses other than that attributable to variation in accommodative demand was exhibited by the amblyopic eyes during monocular viewing conditions (average R2 value of 0.45 across the two meridia).
The limits of the current instrumentation prevented the measurement of accommodative responses of >4.69 D or <0.68 D, and approximately 5% of data points could not be obtained in this study. In control subjects, most (91%) of the missing points were due to accommodative responses of >4.69 D, especially when the stimulus was placed at an accommodative demand of 4.00 D. Subjects with normal vision and only spherical refractive error do not normally exhibit accommodative leads, especially to a 4.00-D stimulus. The leads we observed might have been secondary to the presence of astigmatism (≤1.00 D in all subjects) or subjects looking at their own reflections in the beam-splitter. Conversely, in amblyopic subjects, most (72%) of the missing data points were due to accommodative responses of <0.68 D, especially when the stimulus was placed at a target demand of 2.00 D, further reinforcing the conclusion that amblyopic subjects have reduced accommodative responses.
Off-axis observation can affect retinoscopy measurements. For a fixing eye, the maximum possible off-axis fixation while the subject was viewing the LCD screen was 16.7° horizontally and 9.6° vertically. Off-axis retinoscopy errors of 1.08 D and 0.35 D have been reported for 20° horizontal and vertical eccentricities,
69 while induced astigmatism at 20° eccentricity may be up to 1 D.
70,71 However, off-axis fixation of 20° was evident to the trained examiners, and subjects were prompted to refixate when this occurred. Therefore, errors from off-axis retinoscopy in fixing eyes are presumed to be less than these values and unlikely to have significantly impacted our results. In the case of strabismic subjects viewing binocularly, the nonfixing eye could have been up to 14.5° (≤25 PD) deviated from the path of the retinoscope beam when the subject was viewing the center of the screen with the fixing eye. However, the finding of minimal IOD in accommodative error between amblyopic and nonamblyopic eyes under binocular viewing conditions suggests a negligible effect of off-axis measurements even for strabismic subjects viewing binocularly.
Variability of accommodative responses was greater in amblyopic subjects than controls, as evidenced by repeatability testing. Assuming this is due to increased variability of accommodative performance itself, a corresponding short-term variability of accommodative responses would be expected in amblyopic eyes during the period of observation for any single measurement. If examiners were biased toward preferentially sampling the worst accommodative performance occurring during the period of observation, rather than the average performance during the period of observation, this might bias our findings toward larger differences between amblyopic and nonamblyopic eyes. In fact, however, examiners were cognizant that transiently larger lags of accommodation might be an artifact of a temporary lapse of attention on the part of the child, and consequently were biased, if at all, toward preferentially sampling the best accommodative performance in any period of observation. Therefore, we do not believe that the lower repeatability of amblyopic eye accommodative performance has biased our results toward finding larger differences between amblyopic and nonamblyopic eyes.
Finally, the amblyopic subjects represented a wide range of clinical states; some subjects had been treated, while others had not. The amount of monocular visual experience during therapy may impact accommodative performance, but we did not find duration of patching to be a significant predictor of monocular accommodative lag in the amblyopic eyes at a 4.00-D demand. In addition, some subjects were fully corrected optically while others were not. Adaptation to different levels of optical correction may also impact accommodative responses, but this was not tested in the data analysis owing to the small sample size.
Supported by National Eye Institute R01 EY014460 (TRC), K23 EY016699 (KTH), and P30 EY019008 (Indiana University).
Disclosure: V. Manh, None; A.M. Chen, None; K. Tarczy-Hornoch, None; S.A. Cotter, None; T.R. Candy, None