Binocular Benefits Of Optical Treatment In Anisometropic .

Journal of Vision (2018) 18(4):6, 1–10Wang et al.All participants received a complete initial ophthalmological examination, including cycloplegic refraction, best corrected visual acuity at distance (5 m) foreach eye, eye alignment by cover testing, slit-lampbiomicroscopy for anterior segment examination, anddilated fundus examination. Exclusion criteria includedhistory of prior treatment with spectacles, history ofocclusion or penalization therapy, presence of strabismus (including monofixation or any movements in thecover/uncover test), corneal opacity, cataract, glaucoma, ocular pathology, and previous eye surgery.Objective streak retinoscopy was done after instillation of cycloplegic eye drops (1% tropicamide, six dropsat 5-min intervals to relax ciliaris sufficiently, the lastdrop being provided at 30 min before the refractionmeasurement). Note that unlike previous studies thatused cyclopentolate for the refraction (Harvey et al.,2008), here tropicamide was used, as it is the preferredmedication when used in the dose application justdescribed. This dosage regimen stems from someprevious reports on the cycloplegic effects of tropicamide (Lin et al., 1998; Manny et al., 2001), in whichpeople used two drops of 1% tropicamide at 5-minintervals and showed that it is an effective cycloplegicagent. There are also studies using three drops of 1%tropicamide, given every 5 min (Lai, Hsu, Wang,Chang, & Wu, 2009). Here, six drops were given every 5min to provide adequate cycloplegia.All patients were prescribed spectacles by author LFbased on the cycloplegic refraction performed on theinitial visit. Optical treatment was conducted by usingthe following prescriptions: Myopic and astigmaticrefractive errors were fully corrected. Hyperopicrefractive errors were corrected within 1.00 D of the fullcorrection, while anisometropia was corrected to lessthan 1.00 D. All patients were asked to wear spectaclesall day long, and compliance was determined by self- orparent report. At the follow-up visit, patients and/ortheir parents were asked how long the spectacles wereworn on each day. Only patients with good reportedall-day compliance (i.e., all waking hours) wereincluded in the study.Baseline performance (include the best correctedvisual acuity at distance, sensory eye balance, andstereopsis) was measured after at least 6 hr of opticaltreatment (usually after 1 or 2 days of opticaltreatment). This enabled patients to adapt to the newspectacles—e.g., the minification caused by myopicshifts in refractive correction and magnification causedby hyperopic shifts (Applegate & Howland, 1993).The study protocol was approved by the institutionalreview boards of Anhui Medical University, McGillUniversity, and Wenzhou Medical University. Writteninformed consent was obtained from each participantor a parent or legal guardian (for participants youngerthan 18) after explanation of the nature and possibleDownloaded from jov.arvojournals.org on 10/04/20193consequences of the study. The methods and datacollection were carried out in accordance with approved guidelines.ApparatusParticipants’ best spectacle-corrected visual acuitywas measured monocularly using the full Tumbling EChart (Mou, 1966) at 5 m. Patients were asked to readthe optotypes one after another and were stopped whenthey could not respond within 10 s. The amblyopic eyewas always examined first during the experiment.Visual acuity was defined as the score associated with75% correct judgments. This was achieved by measuring participants’ percentage correct at different linesand using linear interpolation to calculate the scoreassociated with 75% correct judgments.Sensory eye balance was measured with custom-builtprograms using MATLAB (MathWorks, Natick, MA)and PsychToolBox 3.0.9 extensions (Brainard, 1997;Pelli, 1997). The stimuli were displayed on a gammacorrected LG D2342PY 3D LED screen (LG LifeScience, Seoul, South Korea) with a 1,920 3 1,080resolution and a 60-Hz refresh rate. Participants wereasked to wear their prescribed spectacles with thepolarized glasses to view the display dichoptically in adimly lit room at a viewing distance of 136 cm. Thebackground luminance was 46.2 cd/m2 on the screenand 18.8 cd/m2 through the polarized glasses. A chinand forehead rest was used to minimize head movements during the experiment.DesignParticipants’ monocular best corrected visual acuityand sensory eye balance were measured before andafter 2 months of optical treatment. All the visualacuity tests were conducted by the same nurse, who wasuninformed as to the purpose of this study, and all thesensory eye-dominance measures were conducted byauthor JW.The experimental design and procedure for measuring sensory eye balance were similar to what we used inour previous studies (Feng, Zhou, Chen, & Hess, 2015;Zhou, Huang, & Hess, 2013), in which we quantitatively assessed the sensory eye balance of individualswith anisometropic amblyopia using a binocular phasecombination paradigm. In this measure, two monocular horizontal sine-wave gratings of different contrastand with phase-shifts in opposite directions (upward ordownward 22.58 relative to the center of the screen,respectively) were dichoptically presented throughpolarized glasses. Binocularly, one stimulus is seen, andits perceived phase was measured for a 100% fixed

Journal of Vision (2018) 18(4):6, 1–10Wang et al.4Statistical methodsFigure 1. An illustration of the binocular phase-combinationparadigm. Two monocular horizontal sine-wave gratings withdifferent contrast and phase shifts in opposite directions weredichoptically presented to the two eyes; the two eyes werebalanced when the binocular perceived phase was 08. Theinterocular contrast ratio where the two eyes were balancedindicated the sensory eye balance and was termed the effectivecontrast ratio at balance point (or balance point for short).contrast in the amblyopic eye and a variable contrast(0, 10%, 20%, 40%, 80%, and 100%) for the grating seenby the fellow eye. These data defined the relationship ofphase versus interocular contrast ratio (Huang et al.,2011) and allowed the derivation of the specificinterocular contrast ratio at which the binocularperceived phase was 08—in other words, the point atwhich the two eyes contributed equally to the binocularphase combination. This specific interocular contrastratio, which we refer to as the effective contrast ratio atbalance point (or more simply the balance point), isaround 0.9 in adults with healthy vision (Ding &Sperling, 2006; Feng et al., 2015; Zhou et al., 2013).To cancel any potential positional bias (i.e., the biasin favor of one phase-shift direction), the perceivedphase at each interocular contrast ratio was measuredboth when the phase shift of the grating was 22.58 in theamblyopic eye and 22.58 in the fellow eye and viceversa. The binocularly perceived phase at that interocular contrast ratio was defined as half of thedifference between these two configurations. Eachcondition was measured eight times. The perceivedphase and its standard error were then calculated basedon the eight repetitions (Figure 1).The binocularly perceived phase was measured byusing an adjustment task, in which participants wereasked to move a reference line to indicate the center ofthe dark stripe of the binocularly perceived grating; thefinal position of this reference line indicated theperceived position of the dark stripe of the binocularperceived grating and thus was used to calculate thebinocularly perceived phase. Eye alignment was carriedout before the test, and the coordinates were used foradjusting the stimuli positions from the two eyes for thefollowing test to make sure the two eyes were well fusedduring the test.Before measurement began, proper demonstrationsof the task were provided through practice trials;during the test, a short break was given to participantswhenever they felt tired.Downloaded from jov.arvojournals.org on 10/04/2019For statistical analysis, participants who had nostereopsis (.3,000 arcsec) were assigned a stereoacuityof 3,000 arcsec. Visual acuity was defined as the scoreassociated with 75% correct judgments and convertedto logMAR. The normality of the data sets was testedusing a one-sample Kolmogorov–Smirnov test. Themeasures before and after optical treatment werecompared using paired-samples t tests. And thedifference between children ( 11 years) and adults( 17 years) was compared using independent-samples ttests. The relationship between age and the restorationof sensory eye balance (or visual acuity) was evaluatedusing Spearman’s correlation analysis; the relationshipbetween the magnitude of anisometropia and therestoration of sensory eye balance (or visual acuity) wasevaluated using Pearson’s correlation analysis. For allof these statistical analyses, SPSS 24.0 (IBM Corp.,Armonk, NY) was used.ResultsChange in sensory eye balanceAs plotted in Figure 2, the mean effective contrastratio at the balance point was 0.22 6 0.11 (M 6 SD)before optical treatment, and it significantly increasedto 0.31 6 0.09 after 2 months of spectacle wearing,t(13) ¼ 3.289, p ¼ 0.006 (Figure 2). The mean differenceof post- and pre- sensory eye balance was 0.08, and the95% confidence interval of the difference was [0.03,0.14].Change in visual acuityThe mean visual acuity (in logMAR) of theamblyopic eyes before optical treatment was 0.59 60.26, and it significantly improved to 0.44 6 0.25 after2 months of spectacle wearing, t(13) ¼ 5.940, p ,0.001 (Figure 3), indicating that the poor visual acuityof the amblyopic eye could also be improved by opticaltreatment alone, something that has been noted in anumber of clinical studies (Cotter et al., 2006; Stewartet al., 2004). The mean difference of post- and previsual acuity was 0.14, and the 95% confidenceinterval of the difference was [ 0.19, 0.09].Change in stereopsisThe mean stereopsis of the participants at baselinewas 1,670 6 1,399 arcsec before optical treatment, and

Journal of Vision (2018) 18(4):6, 1–10Wang et al.5Figure 2. The change of sensory eye balance after 2 months ofoptical treatment. Individuals’ average effective contrast ratio atbalance point after the 2 months of optical treatment is plottedas a function of performance before optical treatment.Fourteen patients participated in this study. Each dot representsresults of one participant; the square symbol represents theiraveraged results; the dotted line is the unity line, and dotsabove this line (in the gray area) indicate improved sensory eyebalance. Error bars represent standard errors across participants. **p , 0.01 (two-tailed paired-samples t test).Figure 3. The change of amblyopic eyes’ visual acuity (inlogMAR) after 2 months of optical treatment. Individuals’average visual acuity in the amblyopic eye after the 2 months ofoptical treatment is plotted as a function of performance beforeoptical treatment. Each dot represents results of one participant; the square symbol represents their averaged results; thedotted line is the unity line, and dots below this line (in the grayarea) indicate improvement in visual acuity. Error bars representstandard errors across participants. ***p , 0.001 (two-tailedpaired-samples t test).it significantly improved to 947 6 1,351 arcsec after 2months of spectacle wearing, t(13) ¼ 2.362, p ¼ 0.034.also compared the treatment outcomes for these twosubgroups. We found that there was no significantdifference between these two subgroups in improvement of visual acuity, t(4.728) ¼ 1.655, p ¼ 0.162, orimprovement of balance point, t(12) ¼ 1.165, p ¼ 0.266.In this case, the improvements of visual acuity as wellas binocular balance measures were not different forthese two groups. These results suggest that the visualimprovements from optical treatment are comparablein children and adults with amblyopia. Our sample sizeis small, and this conclusion needs to be confirmed witha larger sample of participants (Figure 4).The effect of age on visual outcomes fromoptical treatmentIn the current study, our participants had ages thatranged from 6 to 35 years, which was not normallydistributed (p ¼ 0.007, one-sample Kolmogorov–Smirnov test). All other parameters—improvement ofvisual acuity, improvement of balance point, magnitude of anisometropia—were normally distributed (p .0.05). One relevant question is whether the visualoutcomes from optical treatment that we observed hereare age dependent, as would be expected from clinicalexperience. First, we conducted a Spearman’s correlation analysis and found that the correlation betweenage and improvement of visual acuity was notsignificant (q ¼ 0.435, p ¼ 0.12). The relationshipbetween age and improvement of balance point wasalso not significant (q ¼ 0.06, p ¼ 0.84). Since nineparticipants were 11 years old and five were 17, weDownloaded from jov.arvojournals.org on 10/04/2019The effect of the magnitude of anisometropiaon visual outcomes from optical treatmentTo investigate the effect of the magnitude ofanisometropia on the visual benefits from the 2 monthsof optical treatment, we first conducted a Pearson’scorrelation analysis, and found that the relationshipbetween magnitude of anisometropia and visual-acuityimprovement was significant, r ¼ 0.732, p ¼ 0.003; the

Journal of Vision (2018) 18(4):6, 1–10Wang et al.6Figure 4. The relationship between age and improvement in visual acuity (or improvement in balance point) after 2 months of opticaltreatment. The age of the 14 patients is plotted as a function of (a) the change of the amblyopic eye’s visual acuity or (b) the changeof effective contrast ratio at balance point. Results of Spearman’s correlation analysis are provided in each panel.relationship between magnitude of anisometropia andimprovement of balance point was not significant, r ¼0.214, p ¼ 0.463 (Figure 5b). According to the Spearman’s correlation analysis, age significantly correlatedwith magnitude of anisometropia (q ¼ 0.662, p ¼ 0.010).Thus, to better understand whether these anisometropia-related improvements in visual acuity were due tothe magnitude of anisometropia per se or were drivenby the covariation between age and magnitude ofanisometropia, we undertook a partial correlationanalysis (with age as a partial factor). We found thatthe correlation between magnitude of anisometropiaand improvement of visual acuity was not significant, r¼ 0.462, p ¼ 0.112 (Figure 5a), once the correlationbetween age and anisometropia was factored out.Again, it should be noted that our sample size is small.DiscussionIn the present study, we quantitatively assessed thevisual acuity and sensory eye balance of 14 individualsnewly diagnosed with anisometropic amblyopia beforeand after 2 months of optical treatment. We show thattheir sensory eye balance could be significantlyimproved by optical treatment alone and that therestoration of a healthier sensory eye balance wasDownloaded from jov.arvojournals.org on 10/04/2019accompanied by an improvement of visual acuity in theamblyopic eye after 2 months of optical treatment(approximately 0.15 logMAR).To the best of our knowledge, no study hasquantitatively assessed the change of sensory eyebalance by optical treatment alone in anisometropicamblyopia. One technical concern is whether our mainobservation (i.e., the change of sensory eye balance)was simply due to repeated testing (i.e., participantswere more familiar with the procedures in the posttest).We do not believe this is the case, as our design inassessing sensory eye balance took into considerationthe influence of the potential positional bias by using atwo phase strategy across trials—the phase shift of thegrating was 22.58 in the amblyopic eye and 22.58 in thefellow eye in some trials and vice versa in other trials.Therefore, there is no way for participants to use thephase-shift direction as a cue to the task. Thus, theimprovement we report is unlikely to be due to bias andrepeated testing per se. This is confirmed by ourreanalysis of our original test data before the opticaltreatment, in which we divided the data from the eightrepetitions into two parts and calculated two balancepoints for each subject from the first four repetitions(test1) and the last four repetitions (test2). The balancepoints derived from these two tests were similar: 0.24 60.10 (test1) versus 0.22 6 0.13 (test2), t(13) ¼ 0.64, p ¼0.53 (two-tailed paired-samples t test).

Journal of Vision (2018) 18(4):6, 1–10Wang et al.7Figure 5. The relationship between magnitude of anisometropia and improvement in visual acuity (or improvement in balance point)after 2 months of optical treatment. The change of the amblyopic eye’s visual acuity (or the change of effective contrast ratio atbalance point) is plotted as a function of the magnitude of anisometropia. Results of Pearson’s (partial) correlation analysis areprovided in each panel.The restoration of better sensory eye balance fromoptical treatment is consistent with a recent study(Zhou et al., 2016) which showed in a cross-sectionalcohort study that the two eyes of individuals withuncorrected anisometropia (but without amblyopia)were more imbalanced compared to those of individuals with anisometropia who have worn their spectaclesfor 16 weeks or more. Both studies suggest that opticalcorrection plays an important role in rebalancing thecontribution from each eye to the binocular sum. Arelevant question is: To what extent are the changes insensory eye balance a consequence of the changes invisual acuity? Since individuals with nonamblyopicanisometropia exhibit comparable changes in sensoryeye balance after optical correction (Zhou et al., 2016),it would seem that these two benefits of opticaltreatment (sensory eye balance and visual acuity) areindependent. Comparing the two studies, the sensorybalance in individuals with anisometropia and amblyopia is worse than in those without amblyopia (0.22compared with 0.5), and the improvement obtained byoptical treatment is also smaller in the amblyopic group(0.1 compared with 0.2). This suggests that amblyopiaper se makes a contribution to eye imbalance that isdifferent from that of the anisometropia, and theinterocular imbalance is more severe and less responsive to optical treatment in anisometropic amblyopiaDownloaded from jov.arvojournals.org on 10/04/2019than it is in anisometropia without amblyopia. Thislesser responsiveness could also be dependent on theduration (i.e., 2 months) of optical treatment used inthis study. It will be interesting to see whether greaterbinocular benefits are achieved with longer-term opticaltreatment.After optical treatment, stereopsis also improved inparticipants with anisometropic amblyopia, consistentwith previous studies (Richardson, Wright, Hrisos,Buck, & Clarke, 2005; Stewart, Wallace, Stephens,Fielder, & Moseley, 2013). We did not analyze therelationship between improvement in sensory eyebalance and in stereopsis, as we believed that theclinical stereopsis measure we used is too coarse (Hesset al., 2016) and may not be precise enough in reflectingthe real improvement after optical treatment comparedwith the precise measure of sensory eye balance that wemade here. In fact, some participants did not havemeasurable stereovision with this clinical test beforeoptical treatment (i.e., those marked as .3,000 arcsec).In addition, the measurement of sensory eye balancewas conducted at a low spatial frequency (1 c/deg),while the stereopsis measurement using the clinicalbook was conducted with broadband stimuli. As bothstereopsis (Reynaud, Zhou, & Hess, 2013) and sensoryeye balance (Ding, Klein, & Levi, 2013; Kwon, Wiecek,Dakin, & Bex, 2015) are spatial-frequency dependent,

Journal of Vision (2018) 18(4):6, 1–10Wang et al.our current study cannot provide a precise relationshipbetween them.Optical treatment over a duration of 2 monthsimproves not only visual acuity in the amblyopic eyebut also sensory eye balance. Participants’ baselineperformance was measured after at least 6 hr of opticaltreatment, to lessen the discomfort from the differentspherical equivalents between the two eyes. We shouldnote that this could miss some effects, in which case theoptical treatment’s true effect could be slightly greaterthan we report here. It should be pointed out thattropicamide was used as the cycloplegic in our study,which may or may not be able to reveal the full amountof hyperopic refractive errors and thus could miss someeffects.Even though the correlation between visual outcomes from the 2 months of optical treatment and theage of the participants was not significant (within thelimits and small sample size tested here), the magnitudeof the correlation coefficients was relatively large (i.e., 0.06 for age and improvement in balance point, and 0.435 for age and improvement in visual acuity). Thisresult may suggest that optical treatment could be moreeffective for children than adults with anisometropicamblyopia. However, because it is not easy to findadults who have been newly diagnosed with amblyopiaand have never received any treatment, we had onlyfour adults with amblyopia in the current study. A clearanswer for the effect of optical treatment in adults withanisometropic amblyopia needs further study withlarger samples.It should be noted that we used the Tumbling EChart rather than the standard methods of measuringvisual acuity in individuals with amblyopia (e.g.,ETDRS or HOTV charts; Cotter et al., 2007; Stewart etal., 2004), and thus the acuity measurements may notbe as precise. This is because presently, the Tumbling EChart is a common and standard visual-testing chart inChina (Mou, 1966), where English is not the nativelanguage. To minimize the potential bias in the visualacuity measure, a nurse who was uninformed as to thepurpose of this study measured participants’ visualacuities at different visits. Furthermore, visual acuitywas calculated as the score associated with 75% correctjudgments. Even though visual acuity was not the mainfocus of this study, we confirm the conclusion reachedby previous studies in terms of the effect of opticaltreatment (i.e., refractive adaptation) in improving theamblyopic eye’s visual acuity in anisometropic amblyopia (Cotter et al., 2006; Stewart et al., 2004).On the other hand, the visual outcomes from the 2months of optical treatment were not significantlycorrelated with the magnitude of anisometropia oncewe controlled for the correlation between age andanisometropia. This is probably due to a limitation ofour sample, because all of our participants had aDownloaded from jov.arvojournals.org on 10/04/20198moderate magnitude of anis

Optometry and Vision Science, Wenzhou Medical University, Wenzhou, China Robert F. Hess McGill Vision Research, Department of Ophthalmology, McGill University, Montreal, Canada In this study, we investigated the effect of optical treatment on sensory eye balance in anisometropic amblyopia. Fourteen individuals (age: 13.7 6 8.4 years