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高非球微透镜框架眼镜联合0.01%阿托品滴眼液的近视控制效果分析

赵雨暄, 杨必, 李晓莹, 马薇, 刘陇黔, 闫乃红

赵雨暄, 杨必, 李晓莹, 等. 高非球微透镜框架眼镜联合0.01%阿托品滴眼液的近视控制效果分析[J]. 四川大学学报(医学版), 2024, 55(5): 1280-1287. DOI: 10.12182/20240960109
引用本文: 赵雨暄, 杨必, 李晓莹, 等. 高非球微透镜框架眼镜联合0.01%阿托品滴眼液的近视控制效果分析[J]. 四川大学学报(医学版), 2024, 55(5): 1280-1287. DOI: 10.12182/20240960109
ZHAO Yuxuan, YANG Bi, LI Xiaoying, et al. Efficacy of Combining Highly Aspherical Lenslets Spectacles With 0.01% Atropine Eye Drops in Myopia Control[J]. Journal of Sichuan University (Medical Sciences), 2024, 55(5): 1280-1287. DOI: 10.12182/20240960109
Citation: ZHAO Yuxuan, YANG Bi, LI Xiaoying, et al. Efficacy of Combining Highly Aspherical Lenslets Spectacles With 0.01% Atropine Eye Drops in Myopia Control[J]. Journal of Sichuan University (Medical Sciences), 2024, 55(5): 1280-1287. DOI: 10.12182/20240960109

高非球微透镜框架眼镜联合0.01%阿托品滴眼液的近视控制效果分析

基金项目: 四川省科技计划项目(No. 2022YFS0368)和四川大学华西医院学科卓越发展1·3·5工程临床研究基金(No. 2024HXFH043)资助
详细信息
    通讯作者:

    杨必: E-mail: yangbi19830418@126.com

Efficacy of Combining Highly Aspherical Lenslets Spectacles With 0.01% Atropine Eye Drops in Myopia Control

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  • 摘要:
    目的 

    探究高非球微透镜(highly aspherical lenslets, HAL)框架眼镜联合0.01%阿托品 (atropine, AT)滴眼液与单独使用HAL框架眼镜或普通单焦(single vision lenses, SVL)框架眼镜在儿童青少年中的近视控制效果差异。

    方法 

    回顾性队列研究,共纳入105例6~15岁近视患儿,根据近视矫正和控制的方式分为HAL+0.01%阿托品组(HAL+AT)、HAL组和SVL组,每组各35人。收集患者基线和戴镜1年的睫状肌麻痹验光、眼轴长度(axial length, AL)等相关数据。采用单因素方差分析或秩和检验比较3组患者基线和戴镜1年后AL和等效球镜度(spherical equivalent refraction, SER)的变化量。

    结果 

    各组间基线资料和戴镜时长均无明显差异(P>0.05)。戴镜1年后,HAL+AT组、HAL组和SVL组SER变化量分别为-0.13(-0.25, 0.00) D、-0.25(-0.63, -0.25) D和-0.63(-1.00, -0.25) D;AL变化量分别为(0.09±0.11) mm、(0.19±0.16) mm和(0.34±0.16) mm,HAL+AT组SER变化量(PHAL+AT vs. HAL=0.001, PHAL+AT vs. SVL=0.002)和AL变化量(PHAL+AT vs. HAL=0.009, PHAL+AT vs. SVL=0.001)均低于HAL组和SVL组。相比于SVL组,HAL+AT组近视进展延缓率和眼轴增长延缓率分别是79.4%和73.5%,HAL组的近视进展延缓率和眼轴增长延缓率分别是60.3%和44.1%。根据年龄和近视进展速度进行分层分析,结果显示,无论是低龄(6~8岁)儿童还是大龄(9~15岁)儿童,相较于SVL组,HAL+AT组既降低了近视进展较快(AL>0.36 mm/year)的人群比例,又增加了近视进展较慢(AL≤0.18 mm/year)人群比例(P<0.017)。

    结论 

    联合使用HAL框架眼镜和0.01%阿托品滴眼液能有效控制儿童青少年近视进展,在各年龄段的近视患儿中使用联合手段均能取得较好的近视控制效果。

     

    Abstract:
    Objective 

    To explore the difference in myopia control efficacy between spectacle lenses with highly aspherical lenslets (HAL) combined with 0.01% atropine eye drops and spectacle lenses with HAL alone or single vision spectacle lenses (SVL) in children and adolescents.

    Methods 

    A retrospective cohort study was conducted with a total of 105 myopic children aged 6-15 years. According to the specific myopia correction and control methods of each subject, they were evenly divided into the HAL+0.01% atropine (HAL+AT) group, the HAL group, and the SVL group, with 35 subjects in each group. Relevant data, such as cycloplegic refraction and axial length (AL) at baseline and 12 months after wearing spectacles, were retrieved. One-way analysis of variance, or the Kruskal-Wallis test, was used to analyze the changes in AL and spherical equivalent refraction (SER) after wearing spectacles for 12 months in comparison to those at baseline in the three groups.

    Results 

    There was no statistically significant difference in the baseline parameters and duration of wearing spectacles among the three groups (P>0.05). After wearing spectacles for 12 months, the changes in SER were -0.13 (-0.25, 0.00) D, -0.25 (-0.63, -0.25) D, and -0.63 (-1.00, -0.25) D in the HAL+AT group, HAL group, and SVL group, respectively; AL elongation in the three groups was (0.09±0.11) mm, (0.19±0.16) mm, and (0.34±0.16) mm, respectively. The HAL+AT group exhibited slower SER changes (PHAL+AT vs. HAL=0.001, PHAL+AT vs. SVL=0.002) and AL elongation (PHAL+AT vs. HAL=0.009, PHAL+AT vs. SVL=0.001) than those of the HAL and the SVL groups. Compared with those of the SVL group, myopia progression was reduced by 79.4% and AL elongation was slowed down by 73.5% in the HAL+AT group, while in the HAL group, myopia progression and AL elongation were reduced by 60.3% and 44.1%, respectively. According to stratified analysis based on age and myopia progression rate, among younger children aged 6 to 8 years and older children aged 9 to 15 years, the HAL+AT group had a significantly lower proportion of subjects experiencing fast AL elongation (AL>0.36 mm/year) and a significantly higher proportion of subjects experiencing slow AL elongation (AL≤0.18 mm/year) compared to the SVL group (P<0.017).

    Conclusion 

    The combination intervention of spectacle lenses with HAL and 0.01% atropine eye drops is effective in controlling myopia progression in children and adolescents, with better myopia control effect achieved using this combination intervention in myopic children of all ages.

     

  • 近视是导致视觉损害最常见的原因之一,并已经成为一个全球性的公共卫生问题[1]。近年来近视的发病率不断升高,我国部分地区调查显示儿童青少年近视发病率达到30%~75%[23],并且这一数据可能会继续增加。据推测,截止2050年,我国近视患病率将超过80%[4]。高度近视可能导致严重的眼底并发症,如后巩膜葡萄肿、视网膜脱离、近视性黄斑病变、白内障、青光眼等[5]。因此,及早开展有效的近视防控尤为重要。

    已有研究证实多种干预手段能够有效延缓儿童青少年的近视进展,包括光学手段和药物手段[6]。光学手段包括角膜塑形镜(orthokeratology, OK)、特殊设计框架眼镜、多焦软镜等,其控制近视的效果能够达到30%~63%[7]。由于框架眼镜具有经济、方便、眼部感染风险低等优势,越来越多的患者选择配戴特殊设计的框架眼镜来控制近视进展。BAO等[8]提出一种高非球微透镜(highly aspherical lenslets technology, HAL)设计的框架眼镜,中央区9 mm用于矫正远视力,中周边部由连续的11个同心圆环非球面微透镜组成(直径为1.1 mm),最终能够在视网膜前1.2 mm形成深度为0.7 mm的近视性离焦区。经过为期3年的临床研究,结果显示HAL框架眼镜近视进展延缓率和眼轴增长延缓率分别是52%和50%,并且在3年内效果持续稳定[9]。药物手段主要有低浓度的阿托品(atropine, AT)滴眼液,其控制近视副作用小,安全性高,已经成为有效的近视控制手段之一[10]。然而目前关于阿托品控制近视的机制还有待明确,此外单独使用0.01%阿托品滴眼液控制近视效果仍存在一定争议。在ZADNIK等[11]为期3年的研究中,相比于安慰剂组,0.01%阿托品降低了近视进展和眼轴增量〔等效球镜度(spherical equivalent refraction, SER):0.24 D,眼轴长度(axial length, AL):-0.13 mm〕;而REPKA等[12]在两年的研究中,0.01%阿托品组与安慰剂组近视进展和眼轴增量差异并无统计学意义。近年来,许多研究证据表明0.01%阿托品作为一种辅助手段,联合光学方法能够提升控制近视的效果[1316]。部分研究显示,相比于单独使用0.01%阿托品滴眼液或OK镜,0.01%阿托品滴眼液联合OK镜具有更好的近视控制效果[14-15]。这提示阿托品作为辅助手段可能是一种更好的治疗方式。

    然而目前尚无研究证实HAL框架眼镜联合0.01%阿托品滴眼液对青少年近视患儿的近视控制效果。因此,该回顾性研究通过比较联合HAL框架眼镜和0.01%阿托品滴眼液、单独使用HAL框架眼镜、单独使用普通单焦(single vision lenses, SVL)框架眼镜1年后延缓近视进展的差异,并分析HAL框架眼镜联合0.01%阿托品滴眼液在不同年龄段儿童中的近视控制效果,从而为青少年近视防控提供更多的循证依据。

    本研究为回顾性队列研究,收集2021年6月–2023年12月于四川大学华西医院眼科青少年近视门诊就诊患者的病例信息,本研究已获得四川大学华西医院伦理委员会批准,批准号2024年审(649)号。研究纳入标准为:①年龄6~15岁;②睫状肌麻痹验光SER:-0.75~-5.00 D;③睫状肌麻痹验光散光度数<1.50 D;④双眼SER相差<1.50 D;⑤单眼和双眼最佳矫正视力≤0.0 LogMAR;⑥无眼部器质性病变;⑦无其他全身疾病。排除标准为:①斜视、弱视或其他双眼视异常者;②使用过角膜塑形镜或其他控制近视的手段;③检查记录不完整者。

    最终研究共纳入105人,按近视矫正和控制的方式将患者分为3个组,每组各35人,研究筛选流程图如图1所示。HAL联合0.01%阿托品组(HAL+AT组):每天配戴HAL框架眼镜,并在每晚睡前双眼各点1滴0.01%阿托品滴眼液(沈阳兴齐眼药股份有限公司,中国);HAL组:仅配戴HAL框架眼镜(依视路,法国);SVL组:仅配戴SVL框架眼镜(依视路,法国)。所有患者均遵循医嘱,除睡觉时间外都配戴眼镜,每天配戴时间至少10 h。

    图  1  研究筛选流程图
    Figure  1.  Flow diagram of the subject enrollment process
    SER: spherical equivalent refraction; BCVA: best corrected visual acuity; HAL+AT: highly aspherical lenslets combined with 0.01% atropine; HAL: highly aspherical lenslets; SVL: single vision lenses.

    所有患者均按照四川大学华西医院青少年近视门诊标准检查流程进行,所有检查均由专业的视光师完成。既往完成的检查内容包括:使用裂隙灯显微镜(Topcon SL7,拓普康有限公司,日本)检查患者双眼外眼及眼前节情况,直接检眼镜(YZ11D,苏州六六视觉科技股份有限公司)检查患者散瞳后双眼眼底。使用IOLMaster眼光学生物测量仪(IOL Master-700,卡尔蔡司有限公司,德国)测量AL,测量3次取平均值。所有患者均使用0.5%复方托吡卡胺滴眼液(卓比安,沈阳兴齐眼药股份有限公司,中国)进行散瞳,每隔5 min双眼各点1滴,共点3次,之后休息20 min,待瞳孔充分散大后进行验光。验光统一由1名经验丰富的视光师进行操作,通过客观和主觉验光,以最正之最佳视力(maximum plus to maximum visual acuity, MPMVA)原则获得患者的最佳矫正视力。验光结果以SER表示,SER为球镜度数+1/2柱镜度数。

    从电子病历系统中采集3组患者的资料,包括性别、年龄、基线和戴镜1年后AL和SER以及戴镜时长(即患者从开始使用该矫正方式至1年左右复查所经历的时间)。研究评估指标为戴镜1年后3组AL增量和SER变化量。分别计算HAL+AT组和HAL组近视进展延缓率和眼轴增长延缓率,计算方式为近视进展延缓率=〔 (SVL组SER变化量中位数-HAL+AT组或HAL组SER变化量中位数)/SVL组SER变化量中位数 〕,眼轴增长延缓率=〔(SVL组AL增量平均值-HAL+AT组或HAL组AL增量平均值)/SVL组AL增量平均值 〕。参考CHO等[17]的研究,将AL增长和SER变化量划分为快、中、慢3个类别。每年SER变化量不超过0.50 D或AL增量不超过0.18 mm为近视进展缓慢组,每年SER变化量超过1.00 D或AL增量大于0.36 mm为近视进展快速组,其余则为近视进展中等组(SER变化量0.51~1.00 D或AL增量0.19~0.36 mm)。

    使用SPSS26.0进行统计分析,仅对纳入研究对象的右眼数据进行分析。采用K-S检验分析数据分布的正态性,满足正态分布的计量资料用$ \bar {x}\pm s $表示,非正态分布的资料用中位数(P25,P75)表示,分类变量用频数表示。基于数据分布特征,采用单因素方差分析或秩和检验比较3组患者的基线和戴镜1年后AL增量和SER的变化量,若差异有统计学意义,进一步进行两两比较(P<0.017为差异有统计学意义,3组间两两比较共3次,Bonferroni法矫正:0.05/3=0.017)。分类变量采用卡方检验或Fisher精确概率检验。采用多元线性回归分析各组基线参数与AL增量、SER变化量的相关性。P<0.05为差异有统计学意义。

    3组基线资料如表1所示,HAL+AT组、HAL组和SVL组间年龄、性别、基线SER和AL以及戴镜时长之间差异均无统计学意义(P>0.05)。

    表  1  研究对象基线特征
    Table  1.  Baseline characteristics of the subjects
    Variable HAL+AT group (n=35) HAL group (n=35) SVL group (n=35) χ2/F P
    Age/yr., median (P25, P75) 10 (9, 11) 10 (9, 11) 10 (9, 11) 0.330 0.848
    (Male/female)/case 10/25 17/18 18/17 4.433 0.109
    SER/D, median (P25, P75) -2.63 (-3.75, -1.63) -2.25 (-3.50, -2.03) -2.50 (-3.25, -1.81) 0.116 0.944
    AL/mm, $ \bar {x} $±s 24.77±0.97 24.63±0.91 24.82±0.84 0.407 0.667
    Duration of wearing spectacles/month, $ \bar {x} $±s 11.65±0.98 11.77±0.70 12.01±0.36 2.227 0.113
     SER: spherical equivalent refraction; AL: axial length; HAL+AT: highly aspherical lenslets combined with 0.01% atropine; HAL: highly aspherical lenslets; SVL: single vision lenses.
    下载: 导出CSV 
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    AL和SER的具体变化量如表2所示。戴镜1年后,3组AL增量差异有统计学意义(P=0.001),进一步两两比较,HAL+AT组AL增量低于HAL组(P=0.001)和SVL组(P=0.010),且HAL组AL增量低于SVL组(P=0.001)。

    表  2  一年后各组眼轴和等效球镜度的变化
    Table  2.  Changes in AL and SER after 12 months in each treatment group
    Outcomes HAL+AT group (n=35) HAL group (n=35) SVL group (n=35) F/H P
    AL/mm, $ \bar {x} $±s 0.09±0.11 *, # 0.19±0.16 * 0.34±0.16 23.713 0.001
    SER/D, median (P25, P75) -0.13 (-0.25, 0.00)*, # -0.25 (-0.63, -0.25) -0.63 (-1.00, -0.25) 27.851 0.001
     SER: spherical equivalent refraction; AL: axial length; HAL+AT: highly aspherical lenslets combined with 0.01% atropine; HAL: highly aspherical lenslets; SVL: single vision lenses. * P<0.017, vs. SVL group; # P<0.017, vs. HAL group.
    下载: 导出CSV 
    | 显示表格

    戴镜1年后,3组SER变化量差异有统计学意义(P=0.001),进一步两两比较,HAL+AT组SER增量小于HAL组(P=0.002)和SVL组(P=0.001),HAL组和SVL组SER增量间差异无统计学意义(P>0.017)。相较于SVL组,HAL+AT组近视进展延缓率为79.4%,眼轴增长延缓率为73.5%;HAL组近视进展延缓率为60.3%,眼轴增长延缓率为44.1%。

    3组儿童戴镜1年后AL增长和SER变化快慢的分布如表3表4所示。在延缓眼轴增长方面,HAL+AT组1年AL增量较慢(AL≤0.18 mm)的比例分别高于HAL组和SVL组(P<0.017),而HAL组和SVL组间差异无统计学意义(P>0.017);AL增长较快(AL>0.36 mm)的比例HAL+AT组和HAL组均低于SVL组(P<0.017),HAL+AT组和HAL组间差异无统计学意义(P>0.017)。

    表  3  戴镜1年各组眼轴长度增长分布
    Table  3.  Distribution of axial elongation after 12 months in each treatment group
    AL/mm HAL+AT group/
    case (%), n=35
    HAL group/
    case (%), n=35
    SVL group/
    case (%), n=35
    χ2 P
    ≤0.18 27 (77.10)*, # 16 (45.70) 8 (22.80) 20.817 0.001
    0.19-0.36 8 (22.90) 15 (42.90) 10 (28.60) 3.447 0.215
    >0.36 0 (0.00)* 4 (11.40)* 17 (48.60) 28.214 0.001
     AL: axial length; HAL+AT: highly aspherical lenslets combined with 0.01% atropine; HAL: highly aspherical lenslets; SVL: single vision lenses. * P<0.017, vs. SVL group; # P<0.017, vs. HAL group.
    下载: 导出CSV 
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    表  4  戴镜1年各组近视进展的分布
    Table  4.  Distribution of Myopia progression after 12 months in each treatment group
    SER/D HAL+AT group/
    case (%), n=35
    HAL group/
    case (%), n=35
    SVL group/
    case (%), n=35
    χ2 P
    ≤0.50 32 (91.40)* 25 (71.40) 17 (48.60) 15.471 0.001
    0.51-1.00 3 (8.60)* 10 (28.60) 12 (34.30) 7.035 0.030
    >1.00 0 (0.00)* 0 (0.00)* 6 (17.10) 9.953 0.003
     SER: spherical equivalent refraction; HAL+AT: highly aspherical lenslets combined with 0.01% atropine; HAL: highly aspherical lenslets; SVL: single vision lenses. * P<0.017, vs. SVL group; Fisher's exact test.
    下载: 导出CSV 
    | 显示表格

    在延缓近视进展方面,HAL+AT组1年近视进展较慢(SER≤0.50 D)的比例高于SVL组(P<0.017);在近视进展一般儿童中(SER:0.51~1.00 D),HAL+AT组低于SVL组(P<0.017);近视进展1年增长超过1.00 D的比例HAL+AT组和HAL组均低于SVL组(P<0.017),其余各组间差异均无统计学意义(P>0.017)。

    以AL增量和SER变化量分别作为因变量,以基线各项资料作为自变量进行多元线性回归分析。由于基线AL与SER具有相关性(r=-0.408,P=0.001),因此仅将矫正和控制近视方式(HAL+AT=1,HAL=2,SVL=3)、基线年龄、性别(男=1,女=2)、基线SER、戴镜时长纳入回归模型进行分析。

    各项基线资料与戴镜1年后AL增量和SER变化量多元线性回归结果如表5所示,AL增量与近视矫正和控制方式、基线年龄具有相关性(P<0.05),但近视矫正和控制方式对AL增量的影响更大(标准化回归系数=0.573);而SER变化量与近视矫正和控制方式、性别有关(P<0.05),同样近视矫正和控制方式对SER变化量的影响更大(标准化回归系数=-0.540)。

    表  5  眼轴增量和等效球镜度变化量的相关因素
    Table  5.  Factors associated with changes in axial length and spherical equivalent refraction
    Variable ΔAL ΔSER
    Non-standardized β Standardized β P Non-standardized β Standardized β P
    Myopia correction and control method 0.124 0.573 0.001 -0.263 -0.540 0.001
    Age -0.022 -0.204 0.018 0.015 0.061 0.492
    Sex 0.054 0.152 0.069 -0.152 -0.190 0.031
    Baseline SER -0.001 -0.005 0.948 -0.013 -0.037 0.678
    Duration of wearing spectacles 0.012 0.049 0.561 -0.028 -0.051 0.564
     AL: axial length; SER: spherical equivalent refraction.
    下载: 导出CSV 
    | 显示表格

    根据年龄进行分层分析,以年龄分布的中位数9岁为界限,年龄小于9岁(6~8岁)为低龄(younger)组,年龄大于等于9岁(9~15岁)为大龄(older)组。在6~8岁儿童中,HAL+AT、HAL和SVL组中眼轴增量分别为(0.07±0.13) mm、(0.19±0.16) mm和(0.40±0.17) mm,其中HAL+AT组和HAL组AL增量分别低于SVL组(PHAL+AT vs. SVL=0.001, PHAL vs. SVL=0.001),HAL+AT组和HAL组间差异无统计学意义(P=0.084)。在9~15岁儿童中,HAL+AT、HAL和SVL组中眼轴增量分别为(0.12±0.10) mm、(0.19±0.17) mm和(0.29±0.15) mm,其中仅HAL+AT组AL增量低于SVL组(P=0.001),其余各组间差异均无统计学意义(PHAL+AT vs. HAL=0.398, PHAL vs. SVL=0.091)(图2)。

    图  2  两个年龄亚组中眼轴长度变化的比较
    Figure  2.  Comparison of axial length changes in two age subgroups
    HAL+AT: highly aspherical lenslets combined with 0.01% atropine; HAL: highly aspherical lenslets; SVL: single vision lenses.

    同时,在眼轴增长快、中、慢儿童中按儿童年龄进行划分,结果如表6所示。HAL+AT组在低龄儿童和大龄儿童中,AL增长较快比例均低于SVL组(P<0.017),而HAL组仅在AL增长较快的低龄儿童中与SVL组差异有统计学意义(P<0.017)。此外, HAL+AT组无论在低龄儿童还是年龄较大儿童中,AL增长较慢的比例均高于SVL组,差异有统计学意义(P<0.017),其余各组间差异无统计学意义(P>0.017)。

    表  6  按年龄分层,分析不同组别眼轴增长快、中、慢的比例
    Table  6.  Analysis of the composition ratio of the fast, medium, and slow eye axial length growth in different groups by age subgroups
    Group AL≤0.18 mm/case (%) AL 0.19-0.36 mm/case (%) AL>0.36 mm/case (%)
    Younger (n=24) Older (n=27) Younger (n=12) Older (n=21) Younger (n=12) Older (n=9)
    HAL+AT 13 (81.25)* 14 (73.70)* 3 (18.75) 5 (26.30) 0 (0.00)* 0 (0.00)*
    HAL 9 (52.90) 7 (38.90) 6 (35.30) 9 (50.00) 2 (11.80)* 2 (11.10)
    SVL 2 (13.30) 6 (30.00) 3 (20.00) 7 (35.00) 10 (66.70) 7 (35.00)
    χ2 14.375 8.217 1.420 2.273 19.324 8.835
    P 0.001 0.016 0.537 0.321 0.001 0.006
     HAL+AT: highly aspherical lenslets combined with 0.01% atropine; HAL: highly aspherical lenslets; SVL: single vision lenses; Younger: 6-8 years old; Older: 9-15 years old. * P<0.017, vs. SVL group; Fisher's exact test.
    下载: 导出CSV 
    | 显示表格

    近视在亚洲地区的早发性和高发性要求眼保健从业人员及早开展有效的近视防控。特殊设计的框架眼镜具有配戴方便、不良反应少、没有年龄限制等优势[18]。其中,周边微结构设计的框架眼镜主要包括多焦点正向光学离焦(defocus incorporated multiple segments, DIMS)框架眼镜和HAL框架眼镜,其在临床和真实世界的研究中均取得了良好的近视控制效果[19]。HAL框架眼镜基于多点近视离焦设计,镜片中央区有清晰的单焦光学矫正区,在镜片旁周边利用紧密排列的微透镜产生旁周边视网膜近视离焦,从而延缓近视进展[8]。阿托品是一种非选择性毒蕈碱受体拮抗剂,其控制近视的机制可能为阿托品作用于视网膜和巩膜M受体,阻止巩膜成纤维细胞转分化和眼轴增长,同时起到改善脉络膜血供和散大瞳孔增加进入视网膜光照的作用[20]。目前关于低浓度阿托品控制近视的效果还存在争议,但其作为一种辅助手段联合光学方式的治疗效果已得到证实[13-16]。根据2023 IMI近视管理白皮书调查显示,近视防控从业者一致认为联合治疗仍然是现阶段最有效的治疗方法[21]。HUANG等[22]和NUCCI等[23]分别比较了DIMS框架眼镜联合0.01%阿托品滴眼液在中国和欧洲地区近视控制的效果,其结果均表明联合使用效果优于单一使用。然而,目前还没有研究比较HAL框架眼镜联合0.01%阿托品滴眼液的近视控制效果,因此本研究通过一项回顾性的队列研究分析了HAL框架眼镜联合0.01%阿托品滴眼液在儿童青少年中的近视控制效果。

    本研究结果显示,HAL框架眼镜联合0.01%阿托品滴眼液相较于单独使用HAL框架眼镜和单独使用SVL框架眼镜能够显著降低近视进展和眼轴增长的速度。戴镜1年后,联合组儿童近视增速较慢(AL≤0.18 mm/year)的比例分别高于HAL组和SVL组。相比于SVL组,联合组近视进展延缓率和眼轴增长延缓率分别是79.4%和73.5%,单独使用HAL框架眼镜的近视进展延缓率和眼轴增长延缓率分别是60.3%和44.1%,通过联合使用0.01%阿托品的方式能够使近视进展延缓率提升19.1%,眼轴增长延缓率增强29.4%。然而,在本研究中,SVL组的近视增长速度相比BAO等[8]研究中的SVL组近视进展更慢,其原因可能是部分配戴SVL框架眼镜且近视增速较快的儿童已经转为使用其他控制近视的手段(OK镜、离焦软镜等),继续配戴SVL框架眼镜的儿童近视增速可能相对较慢。因此,本研究结果可能会一定程度低估HAL框架眼镜联合0.01%阿托品滴眼液以及单独使用HAL框架眼镜的真实效果。

    光学方法联合药物方法已被认为是近视防控中最有效的方式之一[21]。大量研究比较了联合使用OK镜和0.01%阿托品滴眼液控制近视的效果,其1年内平均眼轴增量为0.07~0.15 mm[24]。这与本研究结果相似,联合使用HAL框架眼镜和0.01%的阿托品滴眼液1年平均眼轴增量为(0.09±0.11) mm。HUANG等[22]的一项回顾性研究表明DIMS联合0.01%阿托品滴眼液1年内眼轴增量为0.28 mm;NUCCI等[23]的一项前瞻性非随机对照试验联合DIMS和0.01%阿托品滴眼液1年内眼轴增量为0.06 mm。但是,一项为期3年的非随机对照试验表明多焦点软镜(离焦量:+2.50 D)联合0.01%阿托品滴眼液相比于单独使用多焦点软镜并不能显著延缓近视的进展[25]。同样,另一项为期3年的回顾性研究表明使用Misight离焦软镜联合0.01%阿托品滴眼液相比于单一治疗并没有明显优势[26]。不同联合方式之间的效果存在差异的原因可能在于不同屈光度儿童视网膜周边远视性离焦不同,因此使用光学手段所产生的近视性离焦量也不同[27]。DONOVAN等[28]的一项Meta分析显示亚洲儿童的近视进展速度要快于欧洲儿童。因此,种族及视网膜屈光状态的不同可能是研究结果之间存在差异的原因。

    目前还没有明确证据表明特殊设计的框架眼镜和阿托品联合控制近视的具体机制,其可能的原因是低浓度阿托品能够起到散大瞳孔的作用,增加了进入视网膜的光线,从而加强了光学手段所产生的视网膜中周区近视性离焦。此外,低浓度阿托品可能通过视网膜和巩膜上某些靶点发挥药物作用,最终以光学离焦叠加药物作用,加强了近视控制的效果[16]

    多元线性回归分析结果表明戴镜1年后AL增量与近视矫正和控制方式、年龄有关,但SER变化量与近视矫正和控制方式、性别有关。这与GUO等[19]研究结果一致,即年龄仅与AL增量相关,而与SER变化量不具有显著相关性。这可能是由于在近视化的过程中,由于生理性眼轴增长[29],控制近视的不同方式对AL增量影响较大,而对SER变化影响较小。此外,由于本研究录入的SER数据是患者最终的主觉验光结果,考虑眼轴作为一种更客观的指标,且年龄不是SER变化量的显著影响因素,仅对AL进行了年龄分层分析。而性别仅与SER变化量相关,不与AL增量具有相关性的原因可能是由于本研究样本量相对较少。

    许多研究表明年龄较小的儿童近视进展速度快于年龄较大儿童[30]。这与本研究结果一致,配戴SVL框架眼镜的研究对象中,6~8岁儿童平均眼轴增量(0.40±0.17) mm,而9~15岁儿童平均眼轴增量(0.29±0.15) mm。本研究结果还显示,在SVL组中,低龄儿童近视进展较快者占比较高(66.70%),而在HAL组(11.80%)和HAL+AT组(0.00%)这一比例有所下降。这与CHO等[17]和LI等[31]的研究结果一致,即光学或药物干预能够通过降低年龄较小儿童快速近视进展人群比例,降低高度近视的发生风险。此外,本研究发现,在各年龄段儿童中,联合使用HAL框架眼镜和0.01%阿托品滴眼液相比于配戴SVL框架眼镜,不仅降低了近视进展较快比例,同时增加了近视进展较慢人群比例,提示在各年龄段的近视患儿中使用联合手段都能达到较好的控制效果。

    本研究尚有以下局限性:由于本研究是一项回顾性队列研究,没有患者其他基线资料的记录,如干预前的近视进展情况、用眼习惯、父母近视状态、依从性等,因此无法排除其对干预效果可能产生的影响。其次,本研究的随访时间仅1年,而CHIA等[32]的研究表明低浓度阿托品在第二年效果优于第一年。因此,联合HAL框架眼镜和0.01%的阿托品滴眼液长期效果还未知。此外,有研究者发现瞳孔大小在阿托品联合OK镜控制近视的效果中起到一定作用[14]。因此推断在HAL联合阿托品的研究中,瞳孔大小可能也对近视控制效果有一定影响,但本研究未测量患者的瞳孔直径。最后,本研究每组样本量较少,可能增加Ⅱ类错误的风险。因此,未来还应开展大样本量的前瞻性随机对照研究,进一步探索HAL框架眼镜联合0.01%阿托品滴眼液长期近视控制效果及其潜在作用机制,同时验证不同年龄段儿童使用联合手段效果差异。

    综上所述,本研究表明联合使用HAL框架眼镜和0.01%阿托品滴眼液能够有效控制儿童青少年近视进展和眼轴增长速度,在各年龄段的近视患儿中使用联合手段均能取得较好的近视控制效果。

    *    *    *

    作者贡献声明 赵雨暄负责数据审编、正式分析、研究方法、验证、可视化、初稿写作和审读与编辑写作,杨必负责论文构思、数据审编、正式分析、经费获取、调查研究、研究方法和研究项目管理,李晓莹和马薇负责数据审编和调查研究,刘陇黔负责经费获取、研究项目管理、提供资源和监督指导,闫乃红负责研究项目管理和监督指导。所有作者已经同意将文章提交给本刊,且对将要发表的版本进行最终定稿,并同意对工作的所有方面负责。

    Author Contribution  ZHAO Yuxuan is responsible for data curation, formal analysis, methodology, validation, visualization, writing--original draft, and writing--review and editing. YANG Bi is responsible for conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, and project administration. LI Xiaoying and MA Wei are responsible for data curation and investigation. LIU Longqian is responsible for funding acquisition, project administration, resources, and supervision. YAN Naihong is responsible for project administration and supervision. All authors consented to the submission of the article to the Journal. All authors approved the final version to be published and agreed to take responsibility for all aspects of the work.

    利益冲突 本文作者刘陇黔是本刊编委会编委。该文在编辑评审过程中所有流程严格按照期刊政策进行,且未经其本人经手处理。除此之外,所有作者声明不存在利益冲突。

    Declaration of Conflicting Interests LIU Longqian is a member of the Editorial Board of the journal. All processes involved in the editing and reviewing of this article were carried out in strict compliance with the journal's policies and there was no inappropriate personal involvement by the author. Other than this, all authors declare no competing interests.

  • 图  1   研究筛选流程图

    Figure  1.   Flow diagram of the subject enrollment process

    SER: spherical equivalent refraction; BCVA: best corrected visual acuity; HAL+AT: highly aspherical lenslets combined with 0.01% atropine; HAL: highly aspherical lenslets; SVL: single vision lenses.

    图  2   两个年龄亚组中眼轴长度变化的比较

    Figure  2.   Comparison of axial length changes in two age subgroups

    HAL+AT: highly aspherical lenslets combined with 0.01% atropine; HAL: highly aspherical lenslets; SVL: single vision lenses.

    表  1   研究对象基线特征

    Table  1   Baseline characteristics of the subjects

    Variable HAL+AT group (n=35) HAL group (n=35) SVL group (n=35) χ2/F P
    Age/yr., median (P25, P75) 10 (9, 11) 10 (9, 11) 10 (9, 11) 0.330 0.848
    (Male/female)/case 10/25 17/18 18/17 4.433 0.109
    SER/D, median (P25, P75) -2.63 (-3.75, -1.63) -2.25 (-3.50, -2.03) -2.50 (-3.25, -1.81) 0.116 0.944
    AL/mm, $ \bar {x} $±s 24.77±0.97 24.63±0.91 24.82±0.84 0.407 0.667
    Duration of wearing spectacles/month, $ \bar {x} $±s 11.65±0.98 11.77±0.70 12.01±0.36 2.227 0.113
     SER: spherical equivalent refraction; AL: axial length; HAL+AT: highly aspherical lenslets combined with 0.01% atropine; HAL: highly aspherical lenslets; SVL: single vision lenses.
    下载: 导出CSV

    表  2   一年后各组眼轴和等效球镜度的变化

    Table  2   Changes in AL and SER after 12 months in each treatment group

    Outcomes HAL+AT group (n=35) HAL group (n=35) SVL group (n=35) F/H P
    AL/mm, $ \bar {x} $±s 0.09±0.11 *, # 0.19±0.16 * 0.34±0.16 23.713 0.001
    SER/D, median (P25, P75) -0.13 (-0.25, 0.00)*, # -0.25 (-0.63, -0.25) -0.63 (-1.00, -0.25) 27.851 0.001
     SER: spherical equivalent refraction; AL: axial length; HAL+AT: highly aspherical lenslets combined with 0.01% atropine; HAL: highly aspherical lenslets; SVL: single vision lenses. * P<0.017, vs. SVL group; # P<0.017, vs. HAL group.
    下载: 导出CSV

    表  3   戴镜1年各组眼轴长度增长分布

    Table  3   Distribution of axial elongation after 12 months in each treatment group

    AL/mm HAL+AT group/
    case (%), n=35
    HAL group/
    case (%), n=35
    SVL group/
    case (%), n=35
    χ2 P
    ≤0.18 27 (77.10)*, # 16 (45.70) 8 (22.80) 20.817 0.001
    0.19-0.36 8 (22.90) 15 (42.90) 10 (28.60) 3.447 0.215
    >0.36 0 (0.00)* 4 (11.40)* 17 (48.60) 28.214 0.001
     AL: axial length; HAL+AT: highly aspherical lenslets combined with 0.01% atropine; HAL: highly aspherical lenslets; SVL: single vision lenses. * P<0.017, vs. SVL group; # P<0.017, vs. HAL group.
    下载: 导出CSV

    表  4   戴镜1年各组近视进展的分布

    Table  4   Distribution of Myopia progression after 12 months in each treatment group

    SER/D HAL+AT group/
    case (%), n=35
    HAL group/
    case (%), n=35
    SVL group/
    case (%), n=35
    χ2 P
    ≤0.50 32 (91.40)* 25 (71.40) 17 (48.60) 15.471 0.001
    0.51-1.00 3 (8.60)* 10 (28.60) 12 (34.30) 7.035 0.030
    >1.00 0 (0.00)* 0 (0.00)* 6 (17.10) 9.953 0.003
     SER: spherical equivalent refraction; HAL+AT: highly aspherical lenslets combined with 0.01% atropine; HAL: highly aspherical lenslets; SVL: single vision lenses. * P<0.017, vs. SVL group; Fisher's exact test.
    下载: 导出CSV

    表  5   眼轴增量和等效球镜度变化量的相关因素

    Table  5   Factors associated with changes in axial length and spherical equivalent refraction

    Variable ΔAL ΔSER
    Non-standardized β Standardized β P Non-standardized β Standardized β P
    Myopia correction and control method 0.124 0.573 0.001 -0.263 -0.540 0.001
    Age -0.022 -0.204 0.018 0.015 0.061 0.492
    Sex 0.054 0.152 0.069 -0.152 -0.190 0.031
    Baseline SER -0.001 -0.005 0.948 -0.013 -0.037 0.678
    Duration of wearing spectacles 0.012 0.049 0.561 -0.028 -0.051 0.564
     AL: axial length; SER: spherical equivalent refraction.
    下载: 导出CSV

    表  6   按年龄分层,分析不同组别眼轴增长快、中、慢的比例

    Table  6   Analysis of the composition ratio of the fast, medium, and slow eye axial length growth in different groups by age subgroups

    Group AL≤0.18 mm/case (%) AL 0.19-0.36 mm/case (%) AL>0.36 mm/case (%)
    Younger (n=24) Older (n=27) Younger (n=12) Older (n=21) Younger (n=12) Older (n=9)
    HAL+AT 13 (81.25)* 14 (73.70)* 3 (18.75) 5 (26.30) 0 (0.00)* 0 (0.00)*
    HAL 9 (52.90) 7 (38.90) 6 (35.30) 9 (50.00) 2 (11.80)* 2 (11.10)
    SVL 2 (13.30) 6 (30.00) 3 (20.00) 7 (35.00) 10 (66.70) 7 (35.00)
    χ2 14.375 8.217 1.420 2.273 19.324 8.835
    P 0.001 0.016 0.537 0.321 0.001 0.006
     HAL+AT: highly aspherical lenslets combined with 0.01% atropine; HAL: highly aspherical lenslets; SVL: single vision lenses; Younger: 6-8 years old; Older: 9-15 years old. * P<0.017, vs. SVL group; Fisher's exact test.
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