대한안과학회지 2017 년제 58 권제 1 호 J Korean Ophthalmol Soc 2017;58(1):13-20 ISSN 0378-6471 (Print) ISSN 2092-9374 (Online) https://doi.org/10.3341/jkos.2017.58.1.13 Original Article 라식혹은라섹후근시퇴행시안압하강제와 0.1% 플루오로메토론의병합치료효과 The Effect of Anti-glaucoma Eyedrops and 0.1% Fluorometholone on Myopic Regression after LASIK or LASEK 류익희 김희선 이희경 김정섭 김진국 김욱겸 Ik Hee Ryu, MD, Hee Sun Kim, MD, Hee Kyung Lee, MD, Jung Sub Kim, MD, Jin Kuk Kim, MD, Wook Kyum Kim, MD 비앤빛강남밝은세상안과의원 B&VIIt Eye Center, Seoul, Korea Purpose: To evaluate the effect of combined medical treatment with anti-glaucoma eyedrops and 0.1% fluorometholone on visual acuity and refractive errors in patients complaining of blurred vision due to myopic regression after laser-assisted in-situ keratomileusis (LASIK) or laser-assisted sub-epithelial keratectomy (LASEK). Methods: This study comprised 155 patients (155 eyes) who were diagnosed with myopic regression after LASIK or LASEK and received medical treatment from January 2015 to January 2016. The visual acuity and refractive errors were compared before and after medical treatment and evaluated to determine whether the results differ between LASIK and LASEK. Results: The mean time of medical treatment was 64.1 ± 36.8 months after surgery. The responder group whose vision was improved and whose myopic error was decreased after medical treatment was comprised of 63 patients (41%). Their visual acuity in this group improved -0.21 ± 0.11 logmar, and the amount of myopic error decreased 0.56 ± 0.32 diopters. The full responder group was 24 patients (15%), and the partial responder group was 39 patients (26%). The frequency of response to medical treatment was higher after LASIK than after LASEK, but the difference was not statistically significant. Conclusions: The combined medical treatment with anti-glaucoma eyedrops and 0.1% fluorometholone was effective in 41% of patients with regard to visual acuity improvement when used for post-lasik or post-lasek myopic regression. The medical treatment was effective after both LASIK and LASEK. J Korean Ophthalmol Soc 2017;58(1):13-20 Keywords: Anti-glaucoma eyedrops, Fluorometholone, Laser-assisted in-situ keratomileusis (LASIK), Laser-assisted sub-epithelial keratectomy (LASEK), Myopic regression 라식라섹의안정성및유효성은이미여러연구 1,2 를통 Received: 2016. 8. 11. Revised: 2016. 10. 25. Accepted: 2016. 12. 21. Address reprint requests to Wook Kyum Kim, MD B&VIIt Eye Center, #411 Seocho-daero, Seocho-gu, Seoul 06615, Korea Tel: 82-2-501-6800, Fax: 82-2-590-2048 E-mail: kiki0306@hanmail.net 하여입증되었다. 레이저장비의발전과노모그램의정확도향상에도불구하고라식후근시퇴행을보이는경우가 5% 에서 28% 까지보고되고있으며 3-8 수술후 6개월경에가장빈도가높고, 1-2년후에도발생하는것으로보고되었다. 대부분의연구 4,9-11 에서는시기와상관없이술후 -0.25디옵터이상의근시변화를근시퇴행으로정의하였다. 각막굴절수술후발생하는근시퇴행의원인은각막의전방이동, 각막실질두께의증가, 각막상피의변화등으로 c2017 The Korean Ophthalmological Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 13
- 대한안과학회지 2017 년제 58 권제 1 호 - 생각되고있다. 4,12-15 라식후근시퇴행의원인중가장널리받아들여지고있는설명은수술중각막절편의제작과각막절삭으로인한각막의생역학적변화로눈뒤쪽에서앞쪽으로작용하는안압에대하여저항하는힘이약화되어각막의전방이동으로발생된다는것이다. 각막의전방이동을유발하는안압을낮추어주는안압하강제가근시퇴행예방및치료에효과가있다는보고는이를뒷받침해주는근거로볼수있다. 16-18 근시퇴행환자에서티몰롤안연고 (timolol ointment) 를 6개월간사용하였을때인공눈물을사용한대조군에비하여근시가유의하게줄어들었다는보고가있다. 17 라섹후근시퇴행은창상치유과정에서발생하는각막혼탁이나각막상피두께의변화와관련되는것으로알려져있다. 19 라섹후발생한각막혼탁과근시퇴행에는스테로이드점안액이효과가있음이알려져있다. 19,20-24 라식후근시퇴행의치료로써안압하강제를사용하여효과가있었음을보고한연구가있었고, 라섹후근시퇴행에는스테로이드점안액사용이효과적이라는보고가있었다. 그러나라섹후근시퇴행의치료로안압하강제를사용한결과는보고된적이없었다. 라섹후에도각막의생역학적변화가발생하므로안압하강제가효과가있을수있으며, 라식후에도각막상피두께의변화가발생하며각막상피의증가는근시퇴행과관련이있다는연구들이있고, 25-29 라식후건조증이나각막신경감소로인한각막상피증의발생등으로 30-32 스테로이드점안액에효과가있을수있을것이다. 안압하강제와 0.1% 플루오로메토론을함께사용하는병합약물치료가라식라섹후근시퇴행환자에서약물치료에반응하는빈도를높일수있을것으로생각되나아직까지이러한연구는없었다. 본연구는라식라섹후근시퇴행과시력저하를보이는환자를대상으로안압하강제와 0.1% 플루오로메토론의병합치료결과에대한보고이며, 라식을받았던환자와라섹을받았던환자에서그효과가차이가있는지비교하였다. 대상과방법 본원에서라식혹은라섹수술을받은환자중 2015년 1 월부터 2016년 1월까지근시변화를동반한시력저하로내원하여약물치료를받은환자 155명 (155안) 의의무기록을후향적으로분석하였다. 인증된연구윤리심의위원회 (institutional review board, IRB) 의심의를거쳐연구계획을승인 ( 승인번호 P01-201609-21-007) 받았다. 수술후안정된시력을보이다가시력저하를호소하여내원한환자중굴절검사에서근시가이전에비하여증가되어있고시력저하를호소하는환자를대상으로약물치료를시행하였다. 수 술후 1.0 시력을회복한후 1-2년마다의시력검사에서시력변화가없었던환자를대상으로하였으며, 교정시력이 1.0이며, 기타안과적질환이없는경우를약물치료의대상으로하였다. 수술직후부터 -0.50디옵터이상의근시를보여저교정이의심되는환자, 굴절수술이외의안과수술을받은병력이있는환자, 약물치료를받은경력이있는환자, 재수술을받은적이있는환자, 원추각막이나각막확장증이의심되는환자, 각막혼탁, 각막이상증, 익상편이있는환자, 망막질환, 백내장, 시신경질환, 약시가있는환자, 임신중이거나수유중인환자는제외하였다. 근시퇴행으로양안에약물치료를시행한경우는단안 ( 우안 ) 만분석대상에포함시켰다. 근시퇴행이전에시행한수술방법라식은 ifs 펨토초레이저 (ifs TM Femtosecond Laser, AMO, Santa Ana, CA, USA) 를사용하여두께 100 µm, 크기 8.7 mm, 경첩의위치는상측으로하여각막절편을만들었으며, 각막절제는알레그레토레이저 (Allegretto Wave Eye-Q Laser; WaveLight, Alcon, Fort Worth, TX, USA) 를사용하였다. 술후 0.5% 목시플록사신 (Vigamox, Alcon, Fort Worth, TX, USA) 과 0.1% 플루오로메토론을첫 1주간하루 4회사용하고, 다음 1주간하루 2회사용하였다. 라섹은 Amoil 브러쉬 (Amoils epithelial scrubber, Innovative eximer solution, Inc., Ontario, Canada) 를이용하여각막상피를제거한후알레그레토레이저를이용하여각막절제술을시행하였다. 그리고 0.02% mitomycin C (MMC) 를면봉에묻혀절제부위에 10-20초간접촉시킨뒤차가운평형염류용액으로 20초간각막표면과결막낭을충분히세척하였다. 그후치료용콘택트렌즈를착용하고항생제안약을점안하였다. 수술당일부터 0.5% 레보플록사신 (Cravit, Santen pharmaceutical Co., Osaka, Japan) 을 3시간마다사용하였으며, 술후 3-5일째치료용콘텍트렌즈를제거한후, 하루 4 회 1주간더사용하였다. 0.1% 플루오로메토론은치료용콘텍트렌즈를제거한후사용하였으며 1주간은 3시간마다사용하고, 그후 1달간하루 4번씩사용하였으며점차사용빈도를줄여술후 4-5개월간사용하였다. 약물치료방법약물치료는 dorzolamide/timolol 복합제제인코솝점안액 (Cosopt, MSD, Whitehouse Station, NJ, USA) 을하루에두번, 0.1% 플루오로메토론점안액 (Ocumetholone, Samil, Seoul, Korea) 을하루에 4-6회사용하였다. 외래진료는약물치료중 2-4주간격으로내원하여굴절검사, 시력및안압검사를시행하였다. 약물치료기간은시력호전여부와 14
- 류익희외 : 라식혹은라섹후근시퇴행시약물치료 - 정도에따라서 3개월까지시행하였다. 약물치료에대한호전여부는환자의주관적증상과시력호전여부, 근시감소로판단할수있다. 약물치료에효과가있다는판단은약물치료후 2주혹은 4주마다시행한검사결과에서시력호전과근시감소가모두동반되는경우로정의하였으며, 치료효과가약 3개월간계속유지되는경우에약물치료에반응이있다고최종판단하였다. 약물치료중에도호전이없는경우최소 2개월까지는호전이될수있다고설명하여치료를지속하려고하였다. 2달후에도효과가없는경우에는약물치료에반응이없는것으로판단하여치료를중단하였다. 안압은비접촉안압계 (NT-510; NIDEK, Aichi, Japan) 로측정하였으며시력에관한분석은측정시력을 logmar 시력으로환산하여계산하였고, 중심각막두께는초음파각막두께검사계 (SP-3000; Tomey, Aichi, Japan) 로측정하였다. 통계적검정은 SPSS 18.0 프로그램 (SPSS Inc., Chicago, IL, USA) 을이용하였으며 Paired-samples t-test, independent t-test, Chi-square test를이용하였고, p값이 0.05 미만을통계학적으로유의하다고정의하였다. 결과 약물치료를받은 155명의평균나이는 31.3 ± 5.9세였고, 시기는수술후평균 64.2 ± 36.8개월이지난후였다. 라식을받은환자는 103명 (66%), 라섹을받은환자는 52명 (34%) 이었으며약물치료기간은 11.1 ± 8.5주였다. 약물치료시작시시력은 0.21 ± 0.14 logmar였으며굴절이상은근시 -1.11 ± 0.45디옵터, 난시 -0.41 ± 0.29디옵터였다 (Table 1). 약물치료에의해시력이호전된환자는 78명 (50%) 이었으며, 이중근시량도감소한경우는 63명 (41%) 이었다. 약물치료에대한반응에따라서대상을치료반응군, 치료무반응군으로나누었다. 약물치료로시력이호전되고 Table 1. The general characteristics of 155 patients who were treated with 0.1% fluorometholone and anti-glaucoma eyedrop Characteristics Data Number of patients 155 Age (years) 31.3 ± 5.9 Gender (male, %) 39 (25) Primary operation method (LASIK:LASEK) (%) 103:52 (66:34) Preoperative myopia (diopters) -4.72 ± 1.75 Preoperative astigmatism (diopters) -0.86 ± 0.81 Preoperative BCVA (logmar) -0.04 ± 0.05 Preoperative IOP (mmhg) 14.9 ± 2.6 Preoperative CCT (μm) 534.4 ± 30.9 Time interval from operation to treatment (months) 64.2 ± 36.8 Periods of medical treatment (weeks) 11.1 ± 8.5 Transient visual acuity improvement (n, %) 105 (68) Persistent visual acuity improvement (n, %) 78 (50) Persistent vision improvement and myopia decrease (n, %) 63 (41) Full recovery of vision and myopia (n, %) 24 (15) LASIK= laser assisted in situ keratomileusis; LASEK = laser assisted sub epithelial keratectomy; BCVA = best corrected visual acuity; IOP = intraocular pressure; CCT = central corneal thickness. A B Figure 1. The effect of combined medical treatment with anti-glaucoma eyedrops and 0.1% fluorometholone on myopic regression patients after laser-assisted in-situ keratomileusis (LASIK) or laser-assisted sub-epithelial keratectomy (LASEK). Visual acuity improvement (A) and spherical equivalent decrease (B) of 63 patients in responder group. 15
- 대한안과학회지 2017 년제 58 권제 1 호 - 근시량이줄어든환자를치료반응군으로정의하였고그렇지않은환자를치료무반응군으로정의하였다. 치료반응군중에서약물치료후시력이 1.0 이상이고구면대응치가 -0.75디옵터이내인경우를완전반응군, 나머지를불완전반응군으로정의하였다. 전체환자중치료반응군은 63명, 치료무반응군은 92명이었다. 치료반응군 63명의치료전시력은 0.24 ± 0.13 logmar였으며치료후시력은 0.04 ± 0.13 logmar 였다 (p<0.01). 반응군 63명의시력호전정도는평균 -0.21 ± 0.11 logmar, 근시량의감소는평균 0.56 ± 0.32디옵터였다 (Fig. 1). 치료반응군의치료전안압은 10.5 ± 1.7 mmhg 였고, 치료후안압은 9.7 ± 1.7 mmhg 로감소하였다 (p<0.01) (Table 2). 반응군과무반응군을비교하여보면, 반응군이무반응군에비하여수술전근시가더심하였다. 약물치료전에는반응군이시력이더나쁘고근시가더많았으나약물치료후에는무반응군에비하여시력이더좋고근시는더적어진것으로나타났다. 각막곡률과안압은약물치료전에는두군에서차이가없었으나약물치료후에는반응군의안압이더낮았고, 반응군의각막곡률이더편평하였다 (Table 3). 63명의반응군을완전반응군과불완전반응군으로나누 어보면, 완전반응군은 24명 (38%), 불완전반응군은 39명 (62%) 이었다. 완전반응군은불완전반응군에비하여약물치료전에시력이더좋았고근시량이더적은것으로나타났다 (Table 4). 라식을받은환자 ( 라식군 ) 와라섹을받은환자 ( 라섹군 ) 를비교하여보면, 수술후근시퇴행으로약물치료를시작한시기는라식군이조금더길었으나통계적으로유의하지않았다. 라식군과라섹군에서약물치료전과후의시력, 근시량, 안압, 각막곡률은차이가없었으며, 반응군의비율과완전반응군의비율도라식군에서높았으나통계적으로유의한차이는없었다 (Table 5). 고찰 현재까지각막굴절수술후근시퇴행에대한연구로서, 라식후에는안압하강제를사용한치료들의효과를보고한연구들 16-18 이많으며, 라섹후에는스테로이드점안액의효과를보고한연구들이있다. 19,20-24 본연구는각막굴절수술후근시퇴행의원인과기전이다양하고복합적으로작용할것으로생각하여 4,12-15,25-36 안압하강제와스테로이드점안액 Table 2. The comparison between before and after medical treatment in 63 patients who showed response to medical treatment Characteristics Before treatment After treatment p-value Uncorrected visual acuity (logmar) 0.24 ± 0.13 0.04 ± 0.13 <0.01 Spherical equivalent (diopters) -1.42 ± 0.39-0.86 ± 0.41 <0.01 Intraocular pressure (mmhg) 10.5 ± 1.7 9.7 ± 1.7 <0.01 Average corneal keratometry 39.42 ± 1.69 39.07 ± 1.76 <0.01 Table 3. The comparison between the responders and non responders to medical treatment Characteristics Responders Non responders p-value Number of patients (n, %) 63 (41) 92 (59) Age (years) 31.2 ± 5.5 31.4 ± 6.1 0.80 UCVA before treatment (logmar) 0.24 ± 0.13 0.19 ± 0.14 0.03 UCVA after treatment (logmar) 0.04 ± 0.13 0.25 ± 0.17 <0.01 SE before treatment (diopters) -1.42 ± 0.39-1.24 ± 0.46 0.01 SE after treatment (diopters) -0.86 ± 0.41-1.08 ± 0.47 <0.01 IOP before treatment (mmhg) 10.5 ± 1.7 11.0 ± 1.9 0.13 IOP after treatment (mmhg) 9.7 ± 1.7 10.3 ± 1.6 0.03 Average corneal keratometry before treatment 39.42 ± 1.69 39.76 ± 1.88 0.25 Average corneal keratometry after treatment 39.07 ± 1.76 39.72 ± 1.92 0.03 Time interval from operation to treatment (months) 63.4 ± 39.5 64.7 ± 35.1 0.83 Periods of medical treatment (weeks) 11.8 ± 8.1 10.6 ± 8.7 0.39 Preoperative myopia (diopters) -5.08 ± 1.75-4.47 ± 1.71 0.03 Preoperative astigmatism (diopters) -0.77 ± 0.71-0.92 ± 0.86 0.25 Preoperative corneal thickness (μm) 530.9 ± 28.3 536.7 ± 32.5 0.25 Cornea ablation depth (μm) 85.36 ± 27.2 81.07 ± 24.4 0.31 Preoperative intraocular pressure 14.6 ± 2.5 15.1 ± 2.7 0.32 UCVA = uncorrected visual acuity; SE = spherical equivalent; IOP = intraocular pressure. 16
- 류익희외 : 라식혹은라섹후근시퇴행시약물치료 - Table 4. The comparison between full responders and half responders to medical treatment Characteristics Full responders Half responders p-value Number of patients (n, %) 24 (38) 39 (62) Age (years) 31.8 ± 5.0 30.8 ± 5.7 0.46 UCVA before treatment (logmar) 0.19 ± 0.10 0.27 ± 0.14 0.02 UCVA after treatment (logmar) -0.05 ± 0.05 0.09 ± 0.13 <0.01 SE before treatment (diopters) -1.19 ± 0.29-1.56 ± 0.39 <0.01 SE after treatment (diopters) -0.48 ± 0.19-1.09 ± 0.33 <0.01 IOP before treatment (mmhg) 10.5 ± 1.9 10.5 ± 1.6 0.90 IOP after treatment (mmhg) 9.8 ± 1.8 9.6 ± 1.6 0.71 Average corneal keratometry before treatment 39.11 ± 1.9 39.60 ± 1.54 0.27 Average corneal keratometry after treatment 38.68 ± 1.98 39.31 ± 1.58 0.17 Time interval from operation to treatment (months) 63.0 ± 44.4 63.7 ± 36.8 0.95 Periods of medical treatment (weeks) 12.0 ± 9.1 11.6 ± 7.5 0.83 Preoperative myopia (diopters) -5.48 ± 1.74-4.83 ± 1.74 0.16 Preoperative astigmatism (diopters) -0.67 ± 0.72-0.83 ± 0.70 0.38 Preoperative corneal thickness 535.5 ± 20.2 528.1 ± 32.3 0.32 Preoperative intraocular pressure 14.5 ± 2.8 14.7 ± 2.3 0.66 UCVA = uncorrected visual acuity; SE = spherical equivalent; IOP = intraocular pressure. Table 5. The comparisons between LASIK group and LASEK group Characteristics LASIK group LASEK group p-value Number of patients 103 52 Time from operation to treatment (months) 67.7 ± 37.0 57.3 ± 35.9 0.10 UCVA before treatment (logmar) 0.22 ± 0.14 0.20 ± 0.12 0.48 SE before treatment (diopters) -1.31 ± 0.41-1.32 ± 0.50 0.84 IOP before treatment (mmhg) 10.9 ± 1.8 10.5 ± 2.0 0.25 UCVA after treatment (logmar) 0.16 ± 0.18 0.18 ± 0.20 0.42 SE after treatment (diopters) -0.98 ± 0.46-1.02 ± 0.45 0.62 IOP after treatment (mmhg) 10.1 ± 1.7 9.8 ± 1.6 0.39 Response numbers to medical treatment (n, %) 45 (44) 18 (35) 0.28 * Full response number to medical treatment (n, %) 20 (19) 4 (8) 0.06 * LASIK = laser assisted in situ keratomileusis; LASEK = laser assisted sub epithelial keratectomy; UCVA = uncorrected visual acuity; SE = spherical equivalent; IOP = intraocular pressure. * Chi-square test was done. 을병합하여치료한결과이며치료환자중 41% 에서근시감소와시력호전의효과를보였다. 라식후근시퇴행환자에서안압하강제를단독으로사용한기존연구 17 에서는근시가치료전 -1.48 ± 0.99디옵터에서치료후 -0.88 ± 0.91디옵터로호전되었다고보고한것이있다. 본연구에서치료반응군 63명에서근시호전은치료전 -1.42 ± 0.39디옵터에서치료후 -0.86 ± 0.41디옵터로기존연구와비슷한결과이다. 안압하강제를단독으로치료한기존연구에비하여스테로이드점안액을추가하여치료한본연구의결과가근시를감소시키는정도에서는차이를보이지않았으나부가적인효과가있는지에대해서는추가적인연구가필요할것으로생각된다. 본연구는근시퇴행의다양한원인을고려한것으로서, 근시퇴행의원인을여러가지로생각해볼수있다. 수술 로인한각막의생역학적변화로발생하는각막의전방이동, 16-18 각막실질및각막상피두께의변화등이주된원인으로알려져있다. 12-15 이것외에도근시퇴행의원인으로꼭생각해야하는원인중하나는자연적인근시진행이다. 15세이상에서는대부분굴절값이안정되지만일부에서근시량이늘어나는근시진행이발생한다는연구들이있었다. 33-35 또한퇴행이없는수술방법으로알려진안내렌즈삽입술후에도안축장의길이가증가한다는보고 36 는각막굴절수술후에도근시진행이시력저하의원인이될수있음을의미한다. 최근에는스마트폰과컴퓨터의사용시간의증가로인하여성인에서도근시진행이발생하는빈도가늘어남에따라서술후전체적인근시퇴행빈도의증가로이어질수있을것이다. 37-39 근시퇴행의원인중근거리작업에의한근시진행의원인이차지하는비율이많아질 17
- 대한안과학회지 2017 년제 58 권제 1 호 - 수록기존의약물치료에반응하지않고, 수술적치료를필요로하는비율이높아질것으로생각된다. 그러므로근시진행을예방하기위한교육의중요성과필요성이높아질것으로생각된다. 약물치료에대한반응이환자에따라서차이가많으며, 수술적치료가필요한경우도있다는것은근시퇴행의기전이다양하다는것에대한근거가될수있을것이다. 라식후근시퇴행을재교정수술로좋은결과를보였다는보고들도있다. 3,4 이는술후근시퇴행이모두약물치료에반응하지는않는것을의미하는것으로, 본연구에서도 59% 의환자들은약물치료에전혀반응을보이지않았다. 치료무반응군에속한환자는약물치료에반응한환자들과는다른기전들에의하여근시퇴행이이루어졌다고유추해볼수있다. 치료반응군중에는약물치료에반응은하였지만완전회복되지는않은불완전반응군도있었는데이러한환자들은약물치료에반응하는기전과그렇지않은기전이함께작용하여근시퇴행이발생했다고볼수있을것이다. 근시퇴행의약물치료에대한기존의연구들은시력과근시의호전정도에대해서만보고하였으나, 16-18 본연구에서는약물치료에대한효과에따라반응군과무반응군으로나누어시력호전과근시량의감소를분석하였다. 두군에서수술전인자와약물치료시작전인자들을비교함으로써약물치료에대한반응여부에영향을주는인자가있는지알아보고자하였다. 약물치료시작시의시력이반응군에서무반응군보다더욱낮았다. 이는약물치료전시력이약물치료반응여부를예측할수있는요소가될수없음을시사한다. 약물치료전시력저하가많지않더라도약물치료에반드시반응할것이라고예측할수없으며, 시력저하가심하더라도약물치료에반응할수있으므로약물치료를시도하는것이필요함을의미한다. 약물치료시작시의시력이완전반응군에서불완전반응군보다좋았다. 이는약물치료전시력이좋았던환자가약물치료후시력이완전히회복될가능성이높다는것을의미한다. 그러므로, 약물치료에반응하여시력이호전되는정도는완전반응군과불완전반응군에서비슷하다고볼수있으며, 만약어떤환자가약물치료에반응을한다면최종시력이완전히회복될지불완전하게회복될지여부를약물치료전시력으로예측해볼수있을것이다. 근시퇴행의시기는술후 1주부터발생하여 6개월에최대에이르고술후 1, 2년후까지지속되는것으로보고되었으나, 17 본연구에서는술후시력저하를보이는시기가술후 5-6년후인것으로나타났다. Shojaei et al 17 은티몰롤을사용한근시퇴행약물치료의효과가수술과약물치료사이의시간이짧을수록근시퇴행치료및예방에효과가 크며, 술후초기에치료하는것이더욱효과적이라고보고하였다. 이는술후시간이많이경과한후발생한근시퇴행일수록약물치료에반응하지않는기전에의한요소가증가하는것때문으로생각해볼수있다. 그러나본연구에서는수술과약물치료사이의시간은반응군과무반응군두군에서차이가없는것으로나타났다. 이러한결과는술후시간이오래경과한환자에서도약물치료가효과가있을수도있음을의미한다. 약물치료에반응하였던 41% 의환자들이있다는사실은수술적치료전에약물치료를시행해보는것으로불필요한수술을줄일수있을것이라생각되며, 약물치료에반응하는기전에의한근시퇴행인지다른기전에의한것인지를구분하는데도약물치료는유용한방법이될것이다. 따라서술후근시변화가발생한환자에서재교정수술전에반드시약물치료에의한시력호전을확인하는과정이필요할것으로생각된다. 본연구는근시퇴행환자에서수술적치료전에약물치료를해볼수있는좋은근거가되는연구로서궁극적으로굴절수술의만족도를높이는데기여할것으로생각된다. 라식과라섹은수술방법에차이가있으므로근시퇴행의기전도차이가나며, 그로인해약물치료에대한반응도다르게나타날것으로생각되어왔으나, 4,12-15 본연구에서는라식라섹후약물치료에대한반응은유의한차이가없었다. 라식군에서약물치료에반응을보인반응군의비율과완전반응군의비율이라섹군에비하여각각높게나타났으나통계적으로유의하지는않았다. 약물치료기간에대해서는 6개월정도까지치료한연구들도있었으나, 본연구에서는시력호전이대부분약물치료시작후 2주에서 1개월이내에나타났으며, 스테로이드점안액및안압하강제의장기점안으로인한부작용의가능성등을고려하여평균 2개월에서 3개월정도유지하다가중단하였다. 3개월이라는기간은안전하게약물치료에대한반응여부를판단할수있는충분한기간으로생각된다. 약물치료에효과를보이지않는환자에게장기간약물치료를권하는것은현실적으로어려운점이있으며, 이는조기에수술적치료나안경착용을원하는경우가많아서약물치료에순응도가낮기때문이다. 약물치료에대한반응을미리예측하는방법을발견한다면더욱선택적으로환자들에게약물치료를시행해볼수있을것이다. 최근각막상피의두께를측정할수있는장비가소개되어서각막상피의두께가두꺼운경우에약물치료에반응할가능성이높으므로이러한경우만을선택적으로약물치료의대상으로하는것이바람직하다는의견이있으나이에대해서는추가적인연구가뒷받침되어야할것으 18
- 류익희외 : 라식혹은라섹후근시퇴행시약물치료 - 로생각된다. 결론적으로, 라식라섹후근시퇴행을보이는환자에서안압하강제와 0.1% 플루오로메토론을병합하여약물치료를시행한결과 41% 의환자에서시력호전을보였으며, 라식, 라섹두수술모두에서효과가있었다. 그러므로수술후근시퇴행시약물치료는수술적치료전에반드시시행해보아야할치료방법이라고생각된다. REFERENCES 1) O Brart DP, Shalchi Z, McDonald RJ, et al. Twenty-year follow-up of a randomized prospective clinical trial of excimer laser photorefractive keratectomy. Am J Ophthalmol 2014;158:651-63. e1. 2) Yuksel N, Bilgihan K, Hondur AM, et al. Long term results of Epi-LASIK and LASEK for myopia. Cont Lens Anterior Eye 2014;37:132-5. 3) Lyle WA, Jin GJ. Retreatment after initial laser in situ keratomileusis. J Cataract Refract Surg 2000;26:650-9. 4) Chayet AS, Assil KK, Montes M, et al. Regression and its mechanisms after laser in situ keratomileusis in moderate and high myopia. Ophthalmology 1998;105:1194-9. 5) Hu DJ, Feder RS, Basti S, et al. Predictive formula for calculating the probability of LASIK enhancement. J Cataract Refract Surg 2004;30:363-8. 6) Albietz JM, Lenton LM, McLennan SG. Chronic dry eye and regression after laser in situ keratomileusis for myopia. J Cataract Refract Surg 2004;30:675-84. 7) Lian J, Zhang Q, Ye W, et al. An analysis of regression after laser in situ keratomileusis for treatment of myopia. Zhonghua Yan Ke Za Zhi 2002;38:363-6. 8) Condon PI, Mulhern M, Fulcher T, et al. Laser intrastromal keratomileusis for high myopia and myopic astigmatism. Br J Ophthalmol 1997;81:199-206. 9) Chen YI, Chien KL, Wang IJ, et al. An interval-censored model for predicting myopic regression after laser in situ keratomileusis. Invest Ophthalmol Vis Sci 2007;48:3516-23. 10) Melki SA, Azar DT. LASIK complications: etiology, management, and prevention. Surv Ophthalmol 2001;46:95-116. 11) Sridhar MS, Rao SK, Vajpayee RB, et al. Complications of laser-in-situ-keratomileusis. Indian J Ophthalmol 2002;50:265-82. 12) Kamiya K, Miyata K, Tokunaga T, et al. Structural analysis of the cornea using scanning-slit corneal topography in eyes undergoing excimer laser refractive surgery. Cornea 2004;23(8 Suppl):S59-64. 13) Qi H, Hao Y, Xia Y, Chen Y. Regression-related factors before and after laser in situ keratomileusis. Ophthalmologica 2006;220: 272-6. 14) Baek T, Lee K, Kagaya F, et al. Factors affecting the forward shift of posterior corneal surface after laser in situ keratomileusis. Ophthalmology 2001;108:317-20. 15) Pan Q, Gu YS, Wang J, et al. Differences between regressive eyes and non-regressive eyes after LASIK for myopia in the time course of corneal changes assessed with the Orbscan. Ophthalmologica 2004;218:96-101. 16) El-Awady HE, Ghanem AA, Gad MA. Evaluation of the role of timolol 0.1% gel in myopic regression after laser in situ keratomileusis. Saudi J Ophthalmol 2010;24:81-6. 17) Shojaei A, Eslani M, Vali Y, et al. Effect of timolol on refractive outcomes in eyes with myopic regression after laser in situ keratomileusis: a prospective randomized clinical trial. Am J Ophthalmol 2012;154:790-8.e1. 18) Wang X, Zhao G, Lin J, et al. Efficacy and safety of topical timolol eye drops in the treatment of myopic regression after laser in situ keratomileusis: a systematic review and meta-analysis. J Ophthalmol 2015;2015:985071. 19) Tuft SJ, Gartry DS, Rawe IM, Meek KM. Photorefractive keratectomy: implications of corneal wound healing. Br J Ophthalmol 1993;77:243-7. 20) Tengroth B, Fagerholm P, Söderberg P, et al. Effect of corticosteroids in postoperative care following photorefractive keratectomies. Refract Corneal Surg 1993;9(2 Suppl):S61-4. 21) Brancato R, Carones F, Venturi E, Bertuzzi A. Corticosteroids vs diclofenac in the treatment of delayed regressionafter myopic photorefractive keratectomy. Refract Corneal Surg 1993;9:376-8. 22) Carones F, Brancato R, Venturi E, et al. Efficacy of corticosteroids in reversing regression after myopic photorefractive keratectomy. Refract Corneal Surg 1993;9(2 Suppl):S52-6. 23) O Brart DP, Lohmann CP, Klonos G, et al. The effects of topical corticosteroids and plasmin inhibitors on refractive outcome, haze, and visual performance after photorefractive keratectomy. A prospective, randomized, observer-masked study. Ophthalmology 1994;101:1565-74. 24) Gartry DS, Muir MG, Lohmann CP, Marshall J. The effect of topical corticosteroids on refractive outcome and corneal haze after photorefractive keratectomy. A prospective, randomized, double-blind trial. Arch Ophthalmol 1992;110:944-52. 25) Kanellopoulos AJ, Asimellis G. Epithelial remodeling after femtosecond laser-assisted high myopic LASIK: comparison of stand-alone with LASIK combined with prophylactic high-fluence cross-linking. Cornea 2014;33:463-9. 26) Spadea L, Fasciani R, Necozione S, Balestrazzi E. Role of the corneal epithelium in refractive changes following laser in situ keratomileusis for high myopia. J Refract Surg 2000;16:133-9. 27) Reinstein DZ, Silverman RH, Raevsky T, et al. Arc-scanning very high-frequency digital ultrasound for 3D pachymetric mapping of the corneal epithelium and stroma in laser in situ keratomileusis. J Refract Surg 2000;16:414-30. 28) Reinstein DZ, Archer TJ, Gobbe M. Change in epithelial thickness profile 24 hours and longitudinally for 1 year after myopic LASIK: three-dimensional display with Artemis very high-frequency digital ultrasound. J Refract Surg 2012;28:195-201. 29) Reinstein DZ, Srivannaboon S, Gobbe M, et al. Epithelial thickness profile changes induced by myopic LASIK as measured by Artemis very high-frequency digital ultrasound. J Refract Surg 2009;25:444-50. 30) Ambrósio R Jr, Tervo T, Wilson SE. LASIK-associated dry eye and neurotrophic epitheliopathy: pathophysiology and strategies for prevention and treatment. J Refract Surg 2008;24:396-407. 31) Toda I. LASIK and the ocular surface. Cornea 2008;27 Suppl 1:S70-6. 32) Toda I. LASIK and dry eye. Compr Ophthalmol Update 2007;8: 79-85; discussion 87-9. 33) Kinge B, Midelfart A, Jacobsen G, Rystad J. The influence of near-work on development of myopia among university students. 19
- 대한안과학회지 2017 년제 58 권제 1 호 - A three-year longitudinal study among engineering students in Norway. Acta Ophthalmol Scand 2000;78:26-9. 34) Bullimore MA, Gilmartin B, Royston JM. Steady-state accommodation and ocular biometry in late-onset myopia. Doc Ophthalmol 1992;80:143-55. 35) Bullimore MA, Reuter KS, Jones LA, et al. The Study of Progression of Adult Nearsightedness (SPAN): design and baseline characteristics. Optom Vis Sci 2006;83:594-604. 36) Apel W, Apel A, Stephensen D, Versace P. Axial myopic progression following phakic intraocular lens implantation. J Cataract Refract Surg 2013;39:1435-8. 37) Flitcroft DI. A model of the contribution of oculomotor and optical factors to emmetropization and myopia. Vision Res 1998;38: 2869-79. 38) Abbott ML, Schimid KL, Strang NC. Differences in the accommodation stimulus response curves of adult myopes and emmetropes. Ophthalmic Physiol Opt 1998;18:13-20. 39) McBrien NA, Adams DW. A Longitudinal investigation of adult-onset and adult-progression of myopia in an occupational group. Refractive and biometric findings. Invest Ophthalmol Vis Sci 1997;38:321-33. = 국문초록 = 라식혹은라섹후근시퇴행시안압하강제와 0.1% 플루오로메토론의병합치료효과 목적 : 라식라섹후근시퇴행으로인해시력저하를호소하는환자에서안압하강제와 0.1% 플루오로메토론을함께사용하여약물치료를시행하였을때시력과굴절값에미치는효과를알아보고자하였다. 대상과방법 : 본원에서라식혹은라섹수술을받은환자중 2015 년 1 월부터 2016 년 1 월까지시력저하로내원하여근시퇴행으로진단받고약물치료를받은환자 155 명 (155 안 ) 을대상으로약물치료전후의시력및굴절이상을비교하고, 라식라섹에서그결과가차이있는지알아보았다. 결과 : 약물치료시작시기는수술후평균 64.1 ± 36.8 개월후였다. 약물치료후시력이호전되고근시량이감소한약물치료반응군은 63 명 (41%) 이었으며, 이들에서시력호전은 -0.21 ± 0.11 logmar, 근시량의감소는 0.56 ± 0.32 디옵터였다. 약물치료반응군중완전히회복되는경우는 24 명 (15%), 부분적으로회복된경우는 39 명 (26%) 이었다. 약물치료에시력이호전되는빈도는라섹후보다라식후에더높았으나통계적으로유의하지는않았다. 결론 : 라식라섹후근시퇴행으로인한시력저하시안압하강제와 0.1% 플루오로메토론을함께사용한약물치료는약 41% 환자에서시력을호전시킬수있는방법이며, 라식, 라섹후모두에서효과적인방법이다. < 대한안과학회지 2017;58(1):13-20> 20