A randomized study of network-based perception learning in the treatment of amblyopia children

INTRODUCTION

Amblyopia reduces the best-corrected visual acuity(BCVA) of one or both eyes without any organic cause.It is a common eye disease and the most common cause of vision loss among children and adults, with the pooled prevalence rate of amblyopia was about 1.44%

. Amblyopia affects vision and visual function, such as spatial resolution,contrast sensitivity, color vision, stereoscopic vision, which have different effects on all aspects of life

.

Participants that met the inclusion criteria were randomly assigned to either NBPL group (

=28) or control group (

=28) based on the random number table method.After being enrolled in the two groups, they were given corresponding treatment. All results were based on the comparison between NBPL and the control group. Because of the small sample size, we did not further stratify the analysis within the group.

For centuries the main approach to the treatment of amblyopia consisted of optical correction of any refractive error and occlusion or penalization of the “strong” eye, thus “forcing”the brain to use the input from the “weaker” amblyopic eye

.However, it does not help much in building binocular function.Furthermore, due to the lack of binocular vision, there is always a high recurrence rate, and some patients have residual amblyopia

. Research in recent years suggested that binocular cortical communication persists in subjects with amblyopia

.These findings prompted that activation of these persistent binocular neural circuits might be exploited to ‘a(chǎn)waken’an amblyopic eye. Therefore, binocular vision training is considered necessary to treat amblyopia, which is essential for establishing visual function

.

In the past, we used traditional visual training eyesight exercises to improve children’s stereoacuity, such as needle threading, wearing beads, and tracing. Nowadays, with the development of computer technology, many visual perception trainings have emerged

. Visual perceptual learning is the improvement in visual task performance with practice or training. It reflects learning and plasticity in the visual system and a network of other brain substrates of behavior

.Visual perceptual learning has been used to improve visual performance in different conditions, including amblyopia,presbyopia, low vision, cortical blindness, and rehabilitation after surgical interventions

.

The network-based perception learning (NBPL) system is a multimedia bio-stimulation perceptual learning software program. The program directly targets the binocular function using dichoptic presentation and presents 3D images using a complete split screen view. The program is based on visual biometric information stimulation and has various perceptual learning training games, making the training process attractive.It utilizes cloud medical technology; when the data center receives the patient’s visual function test results or medical record data uploaded by the client, the intelligent expert system in the cloud can instantly develop targeted, individualized visual training plans for amblyopia patients. With this program, all patients’ treatment information will be preserved,facilitating the doctor’s tracking and management of the patient’s treatment.

It is unclear whether visual perceptual training or traditional training is better in the treatment of amblyopia, especially in the improvement of visual acuity (VA) and stereopsis.Therefore, we evaluated the effectiveness of visual perceptual training in untreated amblyopic children between 4-12y using the NBPL system.

SUBJECTS AND METHODS

The study protocol was approved by the Ethics Committee of Tongji Hospital affiliated to Tongji University in Shanghai. Detailed signed informed consent was obtained from each subject and their guardians before the research. Trial registration: Chinese Clinical Trial Registry,ChiCTR. Trial ID: ChiCTR1800015444. Registered March 30,2018.

This study is a randomized controlled trial to assess the effectiveness of a network vision treatment for amblyopia.Between February 20, 2016, and May 20, 2018, a total of 56 amblyopic subjects (25 males, 31 females) with a mean age of 6.7y (range, 4-12y) were enrolled in this study.

Participants were recruited

ophthalmologists in Tongji Hospital affiliated to Tongji University, Shanghai. Eligible children 4 to 12 years old were diagnosed as having anisometropic and/or strabismic amblyopia. All patients underwent a baseline ophthalmological examination, including visual testing, manifest and cycloplegic refraction, cover test, Worth four dot test, anterior segment examination with the slit lamp, corneal topography, and funduscopy. The eligible children had amblyopic eye BCVA of 0.2 to 1.0 logMAR (20/32 to 20/200). Children who had prior treatment with either patching or atropine penalization were not eligible for recruitment providing.

正如習(xí)近平總書(shū)記所言，要回答“世界怎么了、我們?cè)趺崔k？”的問(wèn)題，首先要弄清楚“我們從哪里來(lái)、現(xiàn)在在哪里、將到哪里去？”這一最基本的問(wèn)題，首先需要把握人類的共同價(jià)值訴求。對(duì)此，習(xí)近平總書(shū)記認(rèn)為：“和平、發(fā)展、公平、正義、民主、自由，是全人類的共同價(jià)值，也是聯(lián)合國(guó)的崇高目標(biāo)?！保?］522而這些任務(wù)至今遠(yuǎn)遠(yuǎn)沒(méi)有完成。

None of the children had systemic disease, congenital infections, malformations, or coexisting ocular disease (previous ocular surgery, corneal irregularity,opacification of ocular media including cataracts, and active ocular disease).

我的婀娜美艷，讓身邊的樹(shù)都不敢直視。我的萬(wàn)般風(fēng)情，使我成了西莊山的圣樹(shù)，西莊坪人的驕傲?，F(xiàn)在坪里胡子花白的老人，都是我看著從穿開(kāi)襠褲長(zhǎng)大的。我見(jiàn)證了西莊坪兩百多年的歷史，從看見(jiàn)三五個(gè)人來(lái)到這片荒野，到陸續(xù)發(fā)展到三五十戶人家；從男人們蓄著辮子穿著長(zhǎng)衫，到剃成短發(fā)穿上中山裝；從農(nóng)業(yè)學(xué)大寨的熱鬧鼎沸，到聯(lián)產(chǎn)承包的自豪激情；一直到當(dāng)下人口外流，農(nóng)田拋荒后的退耕還林。

高職學(xué)生相對(duì)本科學(xué)生來(lái)說(shuō)，其學(xué)習(xí)力較低，對(duì)于學(xué)習(xí)沒(méi)有強(qiáng)大的欲望，比較重視自身的興趣發(fā)展，他們的群體意識(shí)較強(qiáng)，天生便擁有一種融入群體的渴望。高校社團(tuán)就是有興趣愛(ài)好一致的同學(xué)組成自發(fā)的組織，社團(tuán)活動(dòng)也是基于學(xué)生的共同目標(biāo)開(kāi)展的，如他們能在社團(tuán)學(xué)到許多課本上所沒(méi)有的知識(shí)，更早的積累社會(huì)實(shí)踐的寶貴經(jīng)驗(yàn)，不僅對(duì)自身實(shí)踐能力提升有好處，更堅(jiān)定了自身目標(biāo)和追求，擴(kuò)大自己的交際圈的同時(shí)，更是提高自己的人際交往能力，因此其自治性也比較凸顯。

NBPL group (

=28) and the control group (

=28) got patching and corresponding training (NBPL and traditional training)for 3mo. Follow-up was performed at 1, 2, and 3mo after treatment in both groups. BCVA and visual function tests were performed, including three-level visual function examination using synoptophore and a comprehensive refractometer.Unfortunately, the total number of samples is small, so it is not enough for further subgroup analysis.

浙江省境內(nèi)公家單位所藏東晉至宋初的敦煌寫(xiě)本201件，這批文獻(xiàn)包括浙江博物館藏176件、浙江圖書(shū)館藏20件、杭州市文物保護(hù)管理所藏4件和靈隱寺藏1件。這批敦煌寫(xiě)本內(nèi)容豐富，除佛教經(jīng)卷外，可以確定的還有道經(jīng)、經(jīng)濟(jì)文書(shū)、齋文、詩(shī)詞、小說(shuō)、書(shū)儀、畫(huà)像等。藏品大部分為漢文寫(xiě)本，也有6件藏文和少量回鶻文寫(xiě)本，另有零星裱裝及包裹寫(xiě)卷的唐代實(shí)物。后有學(xué)者增錄3件，包括浙江博物館藏仕女像壁畫(huà)殘塊和2件溫州博物館藏敦煌文獻(xiàn)，將浙藏敦煌文獻(xiàn)的數(shù)量擴(kuò)展至204件。

VA was measured with a standard logarithmic VA chart. The stereoacuity was automatically determined according to the stereoscopic test in the NBPL system. Patients in the NBPL group were instructed to do NBPL with red/green anaglyphic glasses and optical correction if applicable.

Vision Training

以SPSS19.0統(tǒng)計(jì)學(xué)軟件進(jìn)行數(shù)據(jù)的處理和分析,應(yīng)用(±s)和(%)進(jìn)行計(jì)量和計(jì)數(shù),由t值和χ2檢驗(yàn),P<0.05代表對(duì)比具有統(tǒng)計(jì)學(xué)意義。

Many researchers discovered that using multimedia games in amblyopia therapy could effectively improve VA, although the treatment time and specific methods of different experiments differ

. The binocularity-stimulating therapy is even beneficial in children with residual amblyopia

. There are also some different options regarding the therapy. Holmes

found there was no extra benefit to VA from 4 or 8wk of treatment with the dichoptic binocular Dig Rush iPad game in children aged 7 to 12y. From our study, after three months of training, we found that there was no significant difference in the improvement of BCVA comparing with traditional training.The result is consistent with Holmes

s’

.

where A is constant, h is Planck’s constant, and Eg is the band gap width. n is a parameter that depends on the nature of the transition. For direct permitted transitions n= 1/2,while for indirect allowed transitions n = 2, and for direct forbidden transitions n = 3/2.

The system recorded the patient’s training time and performance in each training module. Based on the patient’s compliance and accuracy rate, a training score from level 1 to level 5 was given and result was sent to the ophthalmologist. If there was a sudden change larger than 2 levels, the ophthalmologist had to contact the patient for follow up and decide if any adjustment needed to be made.

Stereoacuity was carried out by line-element stereograms in NBPL program and guided by the same doctor on the same computer. Each test was repeated 3 times to obtain stable results.

The control group was treated according to the traditional training method. A total of 28 children of developmental amblyopia underwent traditional exercise, such as needle threading, wearing beads, and tracing,

. The training duration and policy were the same as that of the NBPL group, except for the training method.

除了使用樟腦丸以外，還有哪些防蛀小妙招呢？如果家里有木工，在做完工后可以把杉木或樟木的刨花收集起來(lái)，放在塑料袋里扎緊。等到有需要時(shí)，找來(lái)舊襪子，把刨花裝在里面，扎成小球塞到衣柜里，防蛀效果也不錯(cuò)。此外，樟木條、綠茶、竹炭等都可以用來(lái)除味、防霉、防蟲(chóng)。（來(lái)源：科普中國(guó)）

通過(guò)鄉(xiāng)土體育資源在農(nóng)村學(xué)校陽(yáng)光體育活動(dòng)的廣泛應(yīng)用和實(shí)踐，我們也有了更多的思考：（1）鄉(xiāng)土體育資源的利用，完全可作為校本課程開(kāi)發(fā)利用，其意義在于更有效地達(dá)成體育課程教學(xué)目標(biāo)，立足于學(xué)生身心的全面發(fā)展，從而滿足中、小學(xué)生的多元文化的特殊需求。（2）西北農(nóng)村鄉(xiāng)土統(tǒng)體育項(xiàng)目復(fù)雜多樣，可將其歸納為投擲類、奔跑類、力量類、跳躍類、技巧類、舞蹈類及其他幾大類，以供在日常教學(xué)中選擇應(yīng)用。（3）鄉(xiāng)土傳統(tǒng)體育課程資源開(kāi)發(fā)與利用具有符合地域性特點(diǎn)，有著豐厚的群眾基礎(chǔ)等優(yōu)勢(shì)，可帶動(dòng)社區(qū)體育的蓬勃發(fā)展，造福于父老鄉(xiāng)親。

RESULTS

A total of 56 patients were enrolled in the study, with 28 randomized to the network-based perception treatment and 28 to traditional treatment. All 56 children completed the 3mo visit. There was no dropout during the trial.

Baseline characteristics are listed in Table 1. Seven children (12.5%) had strabismic amblyopia,45 (80.36%) had anisometropic amblyopia, and 4 children(7.14%) had combined-mechanism amblyopia. Their mean age was 6.71y (age range, 4-12y), and 25 (44.64%) patients were male. The mean (SD) amblyopic eye BCVA at enrollment was 0.42 logMAR [approximately 20/52; range, 0.2-1.0 logMAR(20/32 to 20/200)]. Mild amblyopia [0.1-0.2 logMAR (20/25 to 20/32)] was present in 12 children (21.43%), moderate amblyopia [range, 0.3-0.6 logMAR (20/40 to 20/80)] was present in 36 children (64.29%), and severe amblyopia[range, 0.7-1.0 logMAR (20/100 to 20/200)] was present in 8 cases (14.29%). None children had received prior amblyopia treatment.

(1)為保持開(kāi)挖后基巖的完整性和開(kāi)挖面的平整度，對(duì)巖質(zhì)基礎(chǔ)、邊坡、馬道的所有輪廓線上的垂直、斜坡面必須采用控制爆破。

There were no significant differences in age, gender ratio, and BCVA between the two groups, as shown in Table 1.

At 3mo,mean amblyopic-eye BCVA improved from baseline by 2.07 lines in the NBPL group and by 1.93 lines in the control group(Figure 2), respectively. There is no significant difference in the change of amblyopic eye BCVA between the two groups with

=0.481 (Figure 3).

At 3mo, amblyopic-eye BCVA improved by 2 lines or more from baseline for 21 (75%) and 20 (71.43%) participants in the NBPL group and the control group, respectively (

=0.725),and amblyopia resolved (BCVA of 20/25 or better and within 1 logMAR line of the fellow eye) for 13 (46.4%) participants in both groups. Most of the patients gained lines of BCVA improvement except for one 11-year-old girl with the lowest BCVA (0.9 logMAR) in the control group.

At 1, and 2mo, the mean change from baseline in the NBPL group was 0.75 and 1.36 lines; and in the control group was 0.43 and 1.21 lines, respectively.

2017年貴德縣農(nóng)業(yè)氣象條件不論從氣溫、降水，還是從日照時(shí)間上都和往年具有著一定的差異性，這樣影響了其當(dāng)?shù)剞r(nóng)作物的生長(zhǎng)和發(fā)育。通過(guò)對(duì)2017年貴德縣農(nóng)業(yè)氣象條件進(jìn)行分析，可以有效的掌握同時(shí)期氣象的變化趨勢(shì)，進(jìn)而對(duì)其農(nóng)作物的生長(zhǎng)發(fā)育進(jìn)行探討，來(lái)了解其對(duì)其農(nóng)作物生產(chǎn)的影響。

StataMP 13 (StataCorp LP, College Station,Texas, USA) was used for statistical analysis, and R 3.5.1(R Development Core Team, New Zealand) was used for graphical display. The stereoacuity was represented by themedian (25%, 75%). The primary outcome was a change in amblyopic eye BCVA and the distribution of stereoacuity. The change in amblyopic eye BCVA from baseline to 3mo postrandomization between the two groups was compared with independent-samples

-test. The distribution of stereoacuity at 3mo was compared with CMH Chi-square test.

The distribution of stereoacuity at baseline, 1,2, and 3mo post-randomization was shown in Figure 4 and Table 2.

In the NBPL group, a total of 16 patients (57.14%) had unmeasurable stereoacuity (≥800’’) before the treatment, while this only occurred in 3 patients (10.71%) after 3mo training.In the control group, 15 patients (53.6%) had unmeasurable stereoacuity before treatment, while this occurred in 10 patients (35.71%) after training. The number of patients with improvement of stereoacuity was 25 and 13 in the NBPL group and control group (

=0.041).

At 3mo, the median stereoacuity was 150” (60”, 400”)and 450” (120”, 800”) in the NBPL group and the control group, respectively. The median change in stereoacuity from baseline to 3mo was 650” in the NBPL group and 350” in the control group. The ratio of central fovea stereoacuity (≤60”)presented by bright orange bar seems better in the NBPL group(

=0.051) at the 3mo point.

The distribution of stereopsis at baseline and the end of treatment in the two groups is shown in Figure 5, and a significant difference exists at 3mo (

=0.015). Besides, considering that the degree of stereopsis of patients with stereoacuity ≥800”between the two groups might be different, and the two groups’basic stereoacuity might not be well compared, we screened out patients with stereoacuity ≥800’’. At the same time, patients with stereoacuity ≤60” had limited room for improvement, and we further screened them out. Then we compared the number of patients with stereoacuity improvement in the two groups.There were 11 people in each group who were within the measuring range and had room for improvement. An increase in stereoacuity by one level was considered an effective improvement in stereoacuity. The number of participants with improvement of stereoacuity in NBPL and control group was 10 and 4 respectively. The results showed that the NBPL group also achieved better stereoscopic improvement, with

＜0.05.

DISCUSSION

Amblyopia is a condition in which one eye is more dominant than the other. It is commonly treated by patching the dominant eye to encourage activity in the lazy eye. However,the traditional treatment is relatively monotonous, and children are not easy to cooperate with.

Perceptual learning is a process by which the ability of sensory systems is improved through experience. Visual perceptual learning, an essential branch of perception learning, has been used to treat visual impairment, and it has proven useful in different situations

. The training system we used in this study is a multimedia bio-stimulation perceptual learning software. With the software, all patients’ treatment information will be preserved, facilitating the doctor’s management of the patient’s treatment. The training system is based on visual biometric information stimulation and has various perceptual learning training games, making the training process attractive.It utilizes cloud medical technology; the data could be synchronized automatically by the training system and specific therapy plan will be generated for each patient by the built-in intelligent expert system. Ophthalmologists can also adjust the training parameters remotely. Overall, our research has found that it has certain advantages over traditional training methods,such as diversified training modes and shorter treatment time,which improve children’s treatment compliance.

Multimedia bio-stimulation perceptual learning visual training system (Guangzhou Vision Medical Software Co., Ltd., China) was used to train amblyopia in the NBPL group. After the patient’s name, age,treatment history, VA, BCVA, diopter, eye movement, eye position, simultaneous vision function, fusion function, and stereoscopic function were input into the treatment system,the system automatically generated a treatment plan, which contained stimulation training, fine training, simultaneous visual training, fusion training and stereoscopic training(Figure 1). The training time and training program differed depending on the BCVA of the amblyopia eye. Amblyopia eye with BCVA worse than 0.4 logMAR was trained separately,with 15min each time, twice a day, and 5min between two times. If the BCVA of amblyopia eye was better than 0.4 logMAR,and the BCVA difference between two eyes was less than 3 lines, both eyes were trained simultaneously, 15min each time,twice a day. When BCVA of amblyopia eye increased to 0.2 logMAR, and BCVA difference between eyes did not exceed 2 lines, simultaneous vision, fusion training, and stereo training were added. Exotropia patients did the convergence training when they had the fusion function, and esotropia patients did the separate training. All trainings were done

computer (recommended display setting: monitor screen size:19-inch or larger; refresh rate: 60 Hz; resolution 1920×1080;color depth: true color/24-bit). Patients could visit the hospital for training or use their computers to conduct online training at home. The ophthalmologist monitored the patient’s daily training through network back-end management software.

On the contrary, Manh

evaluated binocular iPad game therapy’s effectiveness on amblyopic teenagers aged 13 to 17y with amblyopia compared to part-time patching and found that the outcome could be worse with the binocular iPad game therapy. Manh

’s

result is different from other experiments. We believe that the major variation is patching.Patching has essential value in the early stage of the treatment,especially in severe amblyopia

. A single binocular game without the patching of the relative healthy eye may have a weaker effect on promoting the use of amblyopia eye.

In the study with 2 children age 9 to 12 years old, the amblyopia children had moderate improvement in the visual acuities after about 15h’ perceptual learning, and the improvement reached a plateau after about 50h’ training

.Similarly, our study found the NBPL group had a better result at the 1-mo point (0.75 lines in NBPL group

0.43 lines in control group), which confirmed that the perceptual learning could speed the recovery time. But we did not notice any obvious plateau period in our study as our total training time was around 50h.

Our study found that in patients with measurable stereopsis improvement degree, the NBPL group achieved better stereoscopic improvement. The difference in stereoacuity improvement between the two training methods could be due to the higher compliance, more personalized therapeutic plan for binocular function in the NBPL group. Besides,an essential characteristic of amblyopia is crowding,limiting object recognition in individuals with amblyopia

.Perceptual learning can reduce crowding in amblyopia and the normal periphery

, which may also contribute to the more remarkable improvement of stereoacuity in the NBPL group.Our result is in accordance with prior studies that dichoptic game played by amblyopic adults and children resulted in significant improvements in stereoacuity

. In the present study, 4 children’s stereoacuity did not improve significantly in those amblyopic children whose VA improved while taking binocular vision training. It may be related to their relatively older age (9 and 11y) and higher amblyopia severity. Although some studies have found that adult amblyopia patients are also malleable

, it may require longer perceptual training time.

Overall, this research has shown that the NBPL program has a significant vision and stereoacuity improvement, especially in stereoacuity. Besides, compared with traditional training,NBPL has certain advantages over traditional training methods,such as diversified training modes, which significantly improve children’s treatment compliance and makes the training process attractive. Recent years, the study of virtual reality has become more and more mature. We will combine virtual reality glasses with perception learning software later, and it is believed that the combination will have more significant effects on the treatment of amblyopia.

However, this study has some defects. Its sample size was small, and a larger sample size research needs to be further organized. Other visual functions, such as contrast sensitivity, were not observed in this study. For the children with insufficient vision or stereoacuity improvement in this study, whether the therapeutic efficacy could be further enhanced by extending training time, intensity, or increasing training frequency deserves further research. The two training treatments’ recurrence rates were not reported, and we will continue to follow up with these patients.

In conclusion, this study showed that the multimedia biostimulation perceptual learning visual training system was better than traditional training in the treatment of amblyopia,mainly in terms of the improvement of stereoacuity.Multimedia bio-stimulation perceptual learning visual training is practical for children of amblyopia, improving patient compliance, and reducing treatment time.

Design of the study (Xu W); Conduct of the study, data collection, analysis and interpretation (Zheng CY, Wu SQ, Han DX); Manuscript preparation and review

(Zheng CY, Xu W). All authors read and approved the final manuscript.

Supported by Shanghai Health Situation Project(No.201540252); Shanghai Tongji Hospital Clinical Research Incubation Project [No.ITJ(QN)1812]; Shanghai Science and Technology Committee (STCSM) Science and Technology Innovation Program (No.20S31906000).

為驗(yàn)證該算法的可行性，運(yùn)用軟件仿真。利用簡(jiǎn)單海洋環(huán)境地圖，視無(wú)人艇為一質(zhì)點(diǎn)，起始點(diǎn)坐標(biāo)為(0,0)，終點(diǎn)坐標(biāo)為(40,40)。

None;

None;

None;

None.

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