查桂平 汪卓瓊
[摘要] 目的 比較單獨使用阿托品與阿托品聯(lián)合中藥離子導入控制兒童中低度近視進展的療效。 方法 收集2017年4月~2018年6月在我院眼科就診的6~12歲中低度近視兒童115例,隨機分為3組,分別接受0.01%阿托品聯(lián)合中藥離子導入、0.05%阿托品、0.01%阿托品治療12個月。觀察治療后等效球鏡、眼軸、視力、瞳孔直徑、調(diào)節(jié)近點的變化。 結果 治療12個月后,0.01%阿托品聯(lián)合中藥離子導入組、0.05%阿托品組、單獨使用0.01%阿托品組等效球鏡分別為(-2.38±0.52)D、(-2.43±0.45)D、(-2.52±0.29)D,眼軸長度分別為(24.33±0.28)mm、(24.36±0.37)mm、(24.51±0.15)mm,三組等效球鏡度數(shù)與眼軸長度比較,差異均有統(tǒng)計學意義(F=4.969,P=0.011;F=3.315,P=0.039)。0.05%阿托品組明室瞳孔直徑(5.75±0.83)mm比0.01%阿托品聯(lián)合中藥離子導入組(5.20±0.61)mm、0.01%阿托品組(5.35±0.91)mm增加明顯(P<0.001)。調(diào)節(jié)近點0.05%阿托品組(10.11±0.42)cm比0.01%阿托品聯(lián)合中藥離子導入組(8.74±0.72)cm、0.01%阿托品組(8.55±0.83)cm增加明顯(P<0.001)。結論 中藥離子導入加強了0.01%阿托品控制近視進展作用,其作用效果相當于0.05%阿托品。同時,需要進一步觀察等效球鏡及眼軸的變化情況。
[關鍵詞] 0.01%阿托品;中藥離子導入;中低度近視;兒童
[中圖分類號] R778.11? ? ? ? ? [文獻標識碼] B? ? ? ? ? [文章編號] 1673-9701(2020)09-0097-04
[Abstract] Objective To compare the effect of atropine alone and atropine combined with traditional Chinese medicine iontophoresis on the development of middle and low myopia in children. Methods 115 middle and low myopia children aged 6 to 12 years treated in our hospital from April 2017 to June 2018 were selected. They were randomly divided into three groups. And the three groups were given 0.01% atropine combined with traditional Chinese medicine iontophoresis, 0.05% atropine and 0.01% atropine for 12 months respectively. After treatment, the changes of equivalent spherical lens, ocular axis, visual acuity, pupil diameter and accommodation of near point were observed. Results After 12 months of treatment, the spherical equivalent in 0.01% atropine combined with traditional Chinese medicine iontophoresis group, 0.05% atropine group and 0.01% atropine group were (-2.38±0.52) D, (-2.43±0.45) D, (-2.52±0.29) D respectively, and the length of the ocular axis was (24.33±0.28) mm, (24.36±0.37) mm, (24.51±0.15) mm respectively. The differences in the equivalent spherical lens and the length of the ocular axis between the three groups were statistically significant(F=4.969, P=0.011; F=3.315, P=0.039). The pupil diameter (5.75±0.83 mm) in the 0.05% atropine group was significantly higher than that in the 0.01% atropine combined with traditional Chinese medicine iontophoresis group(5.20±0.61 mm) and 0.01% atropine group (5.35±0.91 mm) (P<0.001). The accommodation of near point of 0.05% atropine group(10.11±0.42 cm) was significantly higher than that of 0.01% atropine combined with traditional Chinese medicine iontophoresis group (8.74±0.72 cm) and 0.01% atropine group (8.55±0.83 cm) (P<0.001). Conclusion Iontophoresis of traditional Chinese medicine strengthens the effect of 0.01% atropine on myopia progression, which is equivalent to 0.05% atropine. At the same time, it is necessary to further observe the changes of equivalent spherical lens and ocular axis.
表3? ?三組治療后瞳孔直徑及NPA比較(x±s)
3討論
阿托品眼液是非選擇性睫狀肌麻痹劑,高濃度阿托品作用于M1~M5受體,但低阿托品主要作用于M1受體和M4受體,從而保留了大部分針對控制近視進展的作用,對M3受體影響較小,故對瞳孔及調(diào)節(jié)影響較小。Lee JJ等[9]嘗試使用0.05%阿托品,研究發(fā)現(xiàn)0.05%阿托品每年近視進展(-0.28±0.26)D,而對照組進展(-0.75±0.35)D。Fang PC等[10]使用0.025%阿托品每年近視進展(-0.14±0.24)D,對照組(-0.58±0.34)D。同時,Moon JS等[11]發(fā)現(xiàn)0.01%阿托品治療1年后近視增加-0.84 D,0.025%阿托品增加-0.56 D,0.05%阿托品組增加-0.23 D。Chia A等[12]發(fā)現(xiàn)0.01%阿托品治療2年近視加深(-0.49±0.63)D,0.1%阿托品加深(-0.38±0.60)D,0.5%阿托品加深(-0.30±0.60)D,通過對比可以看出控制近視進展與阿托品濃度相關。低濃度阿托品眼液的療效及安全性一直是研究的熱點,學者們試圖找到能控制近視進展且副作用小的阿托品濃度。近年來很多研究使用0.01%阿托品,發(fā)現(xiàn)0.01%阿托品眼液既能控制近視進展,又能減少副作用[13-14],且停藥后近視屈光度反彈要比0.1%、0.5%阿托品小[15],且有研究認為亞洲人群使用阿托品其副作用不引起臨床癥狀的最高濃度為0.02%[16]。但從上述研究中發(fā)現(xiàn)阿托品控制近視進展的療效與其濃度相關,若既要降低阿托品濃度又要達到理想的治療效果就要考慮聯(lián)合治療。Liang CK等[7]發(fā)現(xiàn)0.25%阿托品聯(lián)合眼部針灸治療比單獨使用0.25%阿托品效果好。韓雯婷等[8]認為消旋山莨菪堿聯(lián)合阿托品滴眼液能有效控制青少年近視進展及眼軸增長。近年來學者們試圖通過聯(lián)合用藥來降低阿托品濃度,提升阿托品控制近視進展的作用。
本研究通過治療1年觀察發(fā)現(xiàn)0.01%阿托品聯(lián)合中藥離子導入近視加深-0.29 D,眼軸延長0.23 mm;0.05%阿托品組近視加深-0.26 D,眼軸延長0.20 mm;單獨使用0.01%阿托品組近視加深-0.61 D,眼軸延長0.36 mm,可見聯(lián)合治療比單獨使用0.01%濃度阿托品效果更好。再結合治療后瞳孔大小及調(diào)節(jié)近點的變化,單獨使用0.01%阿托品瞳孔直徑約增加0.6 mm,調(diào)節(jié)近點(NPA)約增加1.2 mm,0.01%阿托品聯(lián)合中藥離子導入瞳孔直徑約增加0.5 mm,調(diào)節(jié)近點約增加1.5 mm,0.05%阿托品瞳孔直徑約增加1.1 mm,調(diào)節(jié)近點約增加2.5 mm。單獨使用0.01%阿托品和0.01%阿托品聯(lián)合中藥離子導入均未出現(xiàn)明顯的近距離閱讀困難、畏光等癥狀,但0.05%阿托品有部分受試者畏光,近距離閱讀需要遠視鏡片協(xié)助,與Kaymak H等[17]報道0.01%阿托品的副作用基本一致。
綜上所述,阿托品眼液濃度增加,控制近視進展效果越好,但副作用增加,如瞳孔直徑增加、調(diào)節(jié)障礙,引起畏光、近距離閱讀困難。聯(lián)合治療既保證了治療效果又可以降低阿托品濃度,進一步減少副作用。但也有研究認為0.01%阿托品對中低度近視控制有效,對近視進展很快的部分人群可能效果一般[18]。有研究認為以往實驗觀察到低濃度阿托品的副作用小,但觀察時間不夠,需5~10年以上的觀察,其長期的副作用仍不明確[19],故臨床使用阿托品眼液控制近視進展尚未達成共識[20],需要長時間觀察療效及可能的副作用。本研究不足之處沒有對照組,且觀察時間較短,這些部分將在下一步研究計劃中進一步得到完善。
[參考文獻]
[1] Holden BA,Jong M,Davis S,et al. Nearly 1 billion myopes at risk of myopia-related sight-threatening conditions by 2050-time to act now[J].Clin Exp Optom,2015, 98(6):491-493.
[2] Flitcroft DI.The complex interactions of retinal,optical and environmental factors in myopia aetiology[J].Prog RetinEye Res,2012,31(6):622-660.
[3] Hayashi K,Ohno-Matsui K,Shimada N,et al.Long-term pattern of progression of myopic maculopathy:A natural history study[J].Ophthalmology,2010,117(8):1595-1611.
[4] Weiss RS,Park S. Recent updates on myopia control: preventing progression 1 diopter at a time[J]. Curr Opin Ophthalmol,2019,30(4):215-219.
[5] Kinoshita? N,Konno Y,Hamada N,et al. Additive effects of orthokeratology and atropine 0.01% ophthalmic solution in slowing axial elongation in children with myopia:first year results[J]. Jpn J Ophthalmol,2018,62(5):544-553.
[6] Zhao Y,F(xiàn)eng K,Liu RB,et al.Atropine 0.01% eye drops slow myopia progression:A systematic review and Meta-analysis[J]. Int J Ophthalmol,2019,12(8):1337-1343.
[7] Liang CK,Ho TY,Li TC,et al.A combined therapy using stimulating auricular acupoints enhances lower-level atropine eyedrops when used for myopia control in school-aged children evaluated by a pilot randomized control led clinical trail[J].Complement Ther Med,2008,16:305-310.
[8] 韓雯婷,榮翱,徐蔚.消旋山莨菪堿聯(lián)合阿托品滴眼液預防青少年近視療效分析[J].中華醫(yī)學雜志,2019,99(24):1859-1863.
[9] Lee JJ,F(xiàn)ang PC,Yang IH,et al.Prevention of myopia progression with 0.05% atropine solution[J].J O Cul Pharmacol Ther,2006,22(1):41-46.
[10] Fang PC,Chung MY,Yu? HJ,et al.Prevention of myopia onset with 0.025% atropine in premyopic children[J]. J Ocul Pharmacol Ther,2010,26(4):341-345.
[11] Moon JS,Shin SY.The diluted atropine for inhibition of myopia progression[J]. Int J Ophthalmol,2018,11(10):1657-1662.
[12] Chia A,Chua WH,Cheung YB,et al.Atropine for the treatment of childhood myopia:Satety and efficacy of 0.5%,0.1%,and 0.01% doses(Atropine for the Treatment of Myopia2)[J].Ophthalmology,2012,119(2):347-354.
[13] Joachimsen? L,B?觟hringer D,Gross NJ,et al. A pilot study on the efficacy and safety of 0.01% atropine in German[J].Schoolchildren with Progressive Myopia[J]. Ophthalmol Ther,2019,8(3):427-433.
[14] Kesarwani SS. Mumbai group of paediatric ophthalmologists and strabismologists.consensus statement and guidelines for use of dilute atropine sulphate in myopia control[J].Indian J Ophthalmol,2019,67(4):461-463.
[15] Chia A,Chua WH,Wen L,et al.Atropine for the treatment of childhood myopia:Changesafter stopping atropine 0.01%,0.1% and 0.5%[J].Am J Ophthalmol,2014, 157(2):451-457.
[16] Cooper J,Eisenberg N,Schulman E,et al.Maximum atropine dose without clinical signs or symptoms[J]. Optom Vis Sci,2013,90(12):1467-1472.
[17] Kaymak? H,F(xiàn)ricke? A,Mauritz Y,et al. Short-term effects of low-concentration atropine eye drops on pupil size and accommodation in young adult subjects[J]. Graefes Arch Clin Exp Ophthalmol,2018,256(11):2211-2217.
[18] Clark TY,Clark RA. Atropine 0.01%eyedrops significantly reduce the progression of childhood myopia[J]. J Ocul Pharmacol Ther,2015,31(9):541-545.
[19] Prousali E,Haidich AB,F(xiàn)ontalis A,et al.Efficacy and safety of interventions to control myopia progression in children:An overview of systematic reviews and meta-analyses[J]. BMC Ophthalmol,2019,19(1):106.
[20] Zloto O,Wygnanski-Jaffe T,F(xiàn)arzavandi? SK,et al. Current trends among pediatric ophthalmologists to decrease myopia progression-an international perspective[J]. Graefes Arch Clin Exp Ophthalmol,2018,256(12):2457-2466.
(收稿日期:2019-10-30)