대한안과학회지 2019 년제 60 권제 1 호 J Korean Ophthalmol Soc 2019;60(1):32-39 ISSN 0378-6471 (Print) ISSN 2092-9374 (Online) https://doi.org/10.3341/jkos.2019.60.1.32 Original Article 알파차단제를복용하는환자의백내장수술시홍채이완증후군에대한호마트로핀점안제의효과 The Effect of Preoperative Homatropine for Intraoperative Floppy Iris Syndrome in Patients Taken Alpha Blockers 문현식 1 최정한 1 고병이 2 윤경철 1 Hyun Sik Moon, MD 1, Jung Han Choi, MD 1, Byung Yi Ko, MD, PhD 2, Kyung-Chul Yoon, MD, PhD 1 전남대학교의과대학안과학교실 1, 건양대학교의과대학안과학교실 2 Department of Ophthalmology, Chonnam National University Medical School 1, Gwangju, Korea Department of Ophthalmology, Konyang University College of Medicine 2, Daejeon, Korea Purpose: To investigate the effects of homatropine eye drops before cataract surgery to prevent intraoperative floppy iris syndrome (IFIS) in patients treated with alpha blockers. Methods: The medical records of 98 eyes from 68 patients taking alpha blockers who underwent cataract surgery were retrospectively reviewed and divided into three groups: patients with preoperative instillation of homatropine (group 1), patients with preoperative instillation of atropine (group 2), and patients without preoperative eye drops (group 3) for three days. Age, sex, underlying disease, type of alpha blocker, preoperative and postoperative pupil size, parameters of phacoemulsification, surgical complication, and the degree of IFIS of patients were measured to compare among the three groups. Results: No significant differences were found in age and underlying diseases. Significant differences were found in the preoperative and postoperative pupil size, cumulative dissipated energy, and the incidence rate of iris prolapse through the incision sites among the three groups, but no significant difference was detected in other findings, or with regard to intraoperative or postoperative complications. In addition, the preoperative pupil size and preoperative instillation of 1% atropine were significant factors for decreasing the degree of IFIS. Conclusions: Preoperative instillation of homatropine as well as atropine before cataract surgery minimized the degree of IFIS in patients taking alpha blockers. In addition, the pupil size recovered more rapidly after surgery in the homatropine group than in the atropine group. J Korean Ophthalmol Soc 2019;60(1):32-39 Keywords: Alpha blocker, Cataract, Homatropine, Intraoperative floppy iris syndrome Received: 2018. 6. 28. Revised: 2018. 8. 29. Accepted: 2018. 12. 28. Address reprint requests to Kyung-Chul Yoon, MD, PhD Department of Ophthalmology, Chonnam National University Hospital, #42 Jebong-ro, Dong-gu, Gwangju 61469, Korea Tel: 82-62-220-6753, Fax: 82-62-227-1642 E-mail: kcyoon@jnu.ac.kr * Conflicts of Interest: The authors have no conflicts to disclose. 백내장수술시발생할수있는홍채이완증후군 (intraoperative floppy iris syndrome, IFIS) 은수술중홍채의펄럭임, 진행성동공축소, 각막절개창으로의홍채탈출소견을대표적인특징으로하는질환으로 2005년 Chang and Campbell 1 에의해처음소개되었는데, 이는수술시야를좁히고안정적인동공확대의유지를어렵게하여결국수정체낭원형절개의실패, 후낭파열, 섬모체소대해리, 홍채출혈, 그리 c2019 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. 32
- 문현식외 : 홍채이완증후군에대한호마트로핀의효과 - 고각막절개창벌어짐등의수술합병증을발생시키고성공적인백내장수술을방해하는요인이된다. 홍채이완증후군의발생과연관성이높은것으로알려져있는알파차단제는전립선비대증, 고혈압등의질환에치료제로사용되고있으며대표적으로 tamsulosin, naftopidil, alfuzosin, silodosin, doxazosin 등이있으며, 그중 tamsulosin 이홍채이완증후군발생및그정도와가장관련이높은것으로보고되어왔다. 1-12 이러한홍채이완증후군에대비하기위해다양한연구가있었으며수술도중에페닐에프린이나리도카인을주입하는방법, 낮은관류속도를유지하거나동공확대기, 홍채당김기구등의여러수술적도구를사용하는방법, 그리고여러수술기법등이시도되어왔다. 13-17 또한수술전에미리홍채이완증후군을예방하는법에대해서도역시여러연구가이루어졌는데알파차단제의중단은거의효과가없었으며, 아트로핀점안액의경우수술전 10일간하루 2회점안을한경우나수술전 2일간하루 3회아트로핀점안과더불어수술중에전방내로에피네프린을주입한경우등에서홍채이완증후군발생이나정도를경감시킬수있었다는보고가있었다. 18,19 그러나아트로핀과유사하게작용하지만그작용지속시간이짧은것으로알려진호마트로핀과홍채이완증후군의관련성에대한보고는현재까지없었다. 이에본연구는알파차단제를복용하는환자에서백내장수술전호마트로핀점안이홍채이완증후군의발생과정도에미치는영향을조사하고, 이를기존에알려진백내장수술전아트로핀점안의효과와비교하여홍채이완증후군을예방하고합병증의최소화함으로써백내장수술의안정성확보에효과가있는지알아보고자하였다. 대상과방법 2014년 1월부터 2017년 7월까지본원에서수정체초음파유화술및인공수정체후방삽입술을시행받은환자중수술전알파차단제를복용한기왕력이있고백내장수술전기간에따라 3일동안하루 2회호마트로핀 2% 점안액 (Homapine oph. solution, Hanlim Pharm, Seoul, Korea) 을점안한 20명 28안 (1군) 과아트로핀 1% 점안액 (ISOPTO- ATROPINE oph. solution, Alcon Laboratories, Fort Worth, TX, USA) 을점안한 26명 32안 (2군), 수술전정해진용법대로산동제 ( 미드린- 피점안액, Phenylephrine hydro-chloride 5mg/mL and tropicamide 5 mg/ml, Santen, Osaka, Japan) 의점안외엔수술전 3일동안여타산동제를점안하지않았던 22명 38안을대조군으로선정하여총 68명 98안의의무기록을후향적으로분석하였다. 대상자중안축장길이가 22.0 cm 미만이거나 26.0 cm 초과인경우와외상백내장을비롯한합병백내장으로수술받은경우나, 홍채섬모체염, 홍채혈관신생, 폐쇄각녹내장을동반하거나홍채관련수술력이있는경우를제외하였고, 수술중에발생한후낭파열, 섬모체소대해리, 홍채손상의정도가심하여추가로수술적처치가필요했던경우등도대상에서제외되었다. 모든환자에서자세한문진과함께고혈압, 당뇨등의전신질환, 전립선비대증의동반유무에대하여조사하였다. 안과적수술전검사로나안시력, 최대교정시력, 세극등현미경검사, 안압검사, 안저검사등의일반적인안과검사와안구생체계측치의측정및동공크기측정등을시행하였다. 세극등현미경검사를이용하여백내장의핵경화도를확인하였고 LOCS Ⅲ 분류에따라분류하였다. 나안시력및최대교정시력은 logarithm of the minimal angle of resolution (logmar) 을이용하여나타냈다. 안축장및전방깊이등의안구생체계측치의측정은안구생체계측계 (Lenstar, Haag Streit AG, Koeniz, Switzerland) 를이용하여시행되었다. 동공크기의측정은 Ko et al 20 의보고를참고하여동공크기측정기 (Colvard pupillometer, Oasis Medical Inc., Glendora, CA, USA) 를이용하여 4 cd/m 2 의어두운장소에서반대편눈은먼곳의한지점을주시하도록한상태에서, 검사자가기계를앞뒤로움직여서초점을맞추고측정하였다. 모든수술은한사람의술자 (YKC) 에의해시행되었다. 모든환자에서수술 4시간전과 30분전미드린-피를점안하여동공을충분히확장시킨다음, 0.5% proparacaine hydrochloride (Alcaine oph. solution, Alcon-Couvreur nv, Puurs, Belgium) 으로점안마취하에진행되었다. 2.20 mm 넓이의이측투명각막절개를시행한후점탄물질 (Hyaluronic Acid, LG Life Sciences, Seoul, Korea) 을전방내로주입하여, 전방을유지한상태에서직경 5.5 mm 정도의수정체낭원형절개를시행하였다. 관류액을사용하여수력분리술과수력분층술을시행한뒤초음파유화기 (Infiniti Vision System, Alcon Laboratories) 를사용하여수정체조각내기로수정체초음파유화술및관류흡입을시행하고, 인공수정체주입기를이용하여소수성재질의일체형비구면인공수정체 (AcrySof IQ SN60WF, Alcon Laboratories) 를낭내에삽입하였다. 수술중시행된수정체초음파유화술의초음파시간, 누적소비에너지 (cumulative dissipated energy) 및평형염액 (BSS Plus, Alcon Laboratories) 사용량을기록하였다. 수력분리술후와수정체초음파유화술후의동공크기의측정은수술현미경에부착된카메라로촬영된수술동영상에서캡처하여얻은정면주시사진을기반으로수술전검사에서얻은각막수평너비를기준으로측정하여구하였다 (Fig. 1). 술중동공크기에영향을줄수있는평형염액높이 33
- 대한안과학회지 2019 년제 60 권제 1 호 - 는각각초음파유화술중수정체조각내기단계에서 55 cm, 수정체조각제거단계에서 85 cm, 관류흡입단계에서 85 cm, 후낭연마단계 85 cm, 그리고점탄물질제거단계에서 70 cm 와같이설정하였다. 수술당일, 수술후 1일그리고수술후 1주일째수술전과동일한장비에의해나안시력, 최대교정시력, 세극등현미경검사, 안압측정, 동공크기측정등을시행하였다. 수술후임상결과는수술전과후의최대교정시력, 동공크기, 홍채이완증후군의발생및정도를분류하고세군간에비교분석하였다. 홍채이완증후군의정도분류는 1등급이특징적인홍채펄럭임과진행성동공축소가나타나는경우, 2등급은진행성동공축소와홍채펄럭임이심하여각막절개창으로홍채가탈출하는경향이약하게나타나는경우, 3등급은매우심한진행성동공축소와함께홍채펄럭임이매우심하여각막절개창으로홍채가탈출하는경향이강하게나타나는경우로하였다. 홍채이완증후군의발생과환자들이복용한알파차단제, 연령, 성별, 고혈압, 당뇨병, 이상지질혈증및전립선비대증과의상관관계를분석하였고, 홍채이완증후군의정도를 0과 1등급, 2와 3등급두군으로나누어수술 3일전부터사용한산동제의종류, 수술전동공크기, 백내장의핵경화도, 수술중시행된초음파수정체유화술의초음파시간및누적소비에너지등과의상관관계를분석하였다. 본연구는후향적인의무기록분석으로전남대학교병원 IRB에승인을받았다 (CNUH-2018-157). 통계학적인분석은 IBM SPSS ver. 22.0 (IBM Corp., Armonk, NY, USA) 을이용하였다. 세군간의비교를위해범주형태에따라 One-way analysis of variance (ANOVA) test, Pearson Chi-Square test를시행하였고, One-way ANOVA test를이용한연속형범주에서각군별차이가있을경우, 사후검정을위해 Tukey 방법을사용하였다. 백내장수술중및후발생한홍채이완증후군과다른합병증의발생률비교에는 Pearson Chi-Square test를시행하였다. 홍채이완증후군의정도를두군으로나누어단변량로지스틱회귀분석에서 p값이 0.05 미만인변수를이용하여다변량로지스틱회귀분석을실시하였고 p값이 0.05 미만인경우를의의있다고하였다. 결과 총 68명 98안중남자가 94안 (94.3%), 여자가 4안 (5.7%) 이었으며, 평균연령은 76.08 ± 5.95세였다. 수술전최대교정시력의평균값은 0.54 ± 0.40 logmar, 핵경화도는평균 3.67 ± 0.60, 고혈압과당뇨, 이상지질혈증그리고전립선비대증이있는경우는각각 60건 (61.2%), 34건 (34.7%), 16건 (16.3%), 그리고 94건 (95.9%) 이었다. 수술전최대동공크기평균은 6.57 ± 0.87 mm, 평균안축장길이는 23.43 ± 0.83 mm이었으며, 전방깊이의평균은 3.15 ± 0.40 mm이었다. 98안중에서홍채이완증후군이발생한경우는 34건 (34.7%) 이었다. 환자들이복용했던알파차단제는 tamsulosin (Harnal-D 0.2 mg, Astellas Pharma Inc., Tokyo, Japan), naftopidil (Flivas 25 mg Dong-A ST, Seoul, Korea), alfuzosin (Xatral XL 10 mg, Sanofi Synthelabo Pharma Inc., Tokyo, Japan), silodosin (Thrupas 4 mg, JW Pharmaceutical., Seoul, Korea), 그리고 doxazosin (Cardura XL 4 mg, Pfizer Ltd., Seoul, Korea) 로다섯가지종류이며그빈도에따라 tamsulosin 50건 (51.0%), naftopidil 18건 (18.4%), alfuzosin 8건 (8.2%), silodosin 16건 (16.3%) 그리고 doxazosin 6건 (6.1%) 순이었고, 각군별로가장많이사용한알파차단제 Figure 1. Calculation of the intraoperative pupil size. The pupil size was calculated with the ratio of the horizontal length of the pupil (*) and the length between the limbus of cornea ( ) compared with the preoperative horizontal diameter of the cornea. Intraoperative pupil size = ( *, mm)/(, mm) preoperative corneal diameter. Figure 2. Distribution of the use of α-blockers among three group. Tamsulosin made up the largest number of α-blockers in all the groups. 34
- 문현식외 : 홍채이완증후군에대한호마트로핀의효과 - Table 1. Comparison of characteristics among three groups taking α-blockers before cataract surgery Variable Group 1 Group 2 Group 3 p-value * 1 vs. 2 1 vs. 3 2 vs. 3 All Number of patients 20 26 22 Number of eyes 28 32 38 Age (years) 76.21 ± 7.11 76.94 ± 6.57 76.26 ± 4.30 0.89 0.80 0.48 0.50 Gender (male/female) 28/0 (100/0) 28/4 (87.5/12.5) 38/0 (100/0) 0.04 1.00 0.02 0.01 Nuclear density of cataract 3.25 ± 0.52 3.47 ± 0.67 3.37 ± 0.59 0.34 0.71 0.77 0.37 Systemic condition Hypertension (present) 12 (42.9) 22 (68.8) 26 (68.4) 0.10 0.09 1.00 0.06 Diabetes mellitus (present) 10 (35.7) 10 (31.3) 14 (36.8) 0.93 0.99 0.88 0.88 Dyslipidemia (present) 8 (28.6) 4 (12.5) 4 (10.5) 0.07 0.07 0.07 0.17 Benign prostate hyperplasia (present) 28 (100) 28 (87.5) 38 (100) 0.04 1.00 0.02 0.01 Preoperative BCVA (logmar) 0.44 ± 0.17 0.59 ± 0.50 0.59 ± 0.44 0.35 0.32 0.99 0.28 Preoperative maximum pupil diameter (mm) 6.78 ± 0.36 6.89 ± 0.92 6.14 ± 0.93 0.86 <0.01 <0.01 <0.01 Axial length (mm) 23.26 ± 0.22 23.30 ± 1.02 23.69 ± 0.89 0.98 0.09 0.12 0.06 Anterior chamber depth (mm) 3.18 ± 0.22 3.25 ± 0.46 3.04 ± 0.43 0.77 0.35 0.08 0.09 Values are presented as mean ± standard deviation or number (%) unless otherwise indicated. Group 1 means preoperative instillation of Homatropin 2%, Group 2 means preoperative instillation of Isopto atropine 1%, Group 3 means no preoperative instillation. BCVA = best corrected visual acuity; logmar = logarithm of the minimum angle of resolution. * One-way analysis of variance (ANOVA) test with Tukey s post-hoc test; Chi-square test. Table 2. Comparison of characteristics among three groups taking α-blockers before cataract surgery (continued from Table 1) Variable Group 1 Group 2 Group 3 p-value * 1 vs. 2 1 vs. 3 2 vs. 3 All Intraoperative floppy iris syndrome (present/absent) 8/20 (28.6/71.4) 10/22 (31.3/68.7) 12/26 (31.6/68.4) 0.62 0.62 1.00 0.57 Grade of IFIS None (grade 0) 20 (71.4) 22 (68.7) 26 (68.4) 0.99 0.02 0.01 <0.01 Mild (grade 1) 8 (28.6) 9 (28.1) 0 (0) Moderate (grade 2) 0 (0) 1 (3.1) 6 (15.8) Severe (grade 3) 0 (0) 0 (0) 6 (15.8) Intraoperative phacodynamics Ultrasonic time (seconds) 43.38 ± 11.12 44.77 ± 20.38 61.12 ± 48.62 0.74 0.21 0.60 0.23 CDE (mj) 4.11 ± 0.97 4.14 ± 0.82 7.24 ± 6.28 0.99 0.02 0.01 <0.01 BSS (used, ml) 65.89 ± 19.91 66.67 ± 21.46 77.53 ± 32.63 0.99 0.20 0.28 0.17 Aspiration time (seconds) 202.57 ± 83.33 209.67 ± 56.75 236.60 ± 89.84 0.94 0.24 0.43 0.23 Intraoperative pupil diameter (mm) After hydrodissection 5.97 ± 0.46 6.00 ± 0.56 5.82 ± 0.95 0.98 0.67 0.52 0.51 After phacoemulsification 6.20 ± 0.43 6.12 ± 0.78 5.65 ± 0.90 0.91 0.01 0.03 <0.01 At conclusion of surgery 6.63 ± 0.51 6.63 ± 0.83 5.55 ± 0.95 1.00 <0.01 0.00 <0.01 Postoperative BCVA (logmar) 0.01 ± 0.02 0.01 ± 0.04 0.01 ± 0.02 0.99 0.67 0.58 0.55 Postoperative maximum pupil diameter (1 day, mm) 5.01 ± 0.19 5.53 ± 0.76 4.46 ± 0.46 <0.01 <0.01 0.00 <0.01 Postoperative maximum pupil diameter (7 days, mm) 3.42 ± 0.34 3.44 ± 0.34 3.39 ± 0.38 0.99 0.94 0.90 0.90 Values are presented as mean ± standard deviation or number (%) unless otherwise indicated. Group 1 means preoperative instillation of Homatropin 2%, Group 2 means preoperative instillation of Isopto atropine 1%, Group 3 means no preoperative instillation. CDE = cumulative dissipated energy; BSS = balanced salt solution; BCVA = best corrected visual acuity; logmar = logarithm of the minimum angle of resolution. * One-way analysis of variance (ANOVA) test with Tukey s post-hoc test; Chi-square test. 는세군모두 tamsulosin이가장많았으며, 각군간에약물사용양상에는유의한차이가없었다 (p=0.20) (Fig. 2). 1, 2군및대조군, 3개의군으로나누어비교하였을때, 성별 (p=0.01), 전립선비대증의기왕력 (p=0.01) 과최대동공 크기 (p<0.01) 등에서유의한차이가있었다. 모두남자로 구성된 1 군및대조군과는달리 2 군에서고혈압에대해서 35
- 대한안과학회지 2019 년제 60 권제 1 호 - Table 3. Intraoperative and postoperative complications among three groups taking α-blockers before cataract surgery Complications Group 1 Group 2 Group 3 Patients 20 26 22 Eyes 28 32 38 Zonular dialysis 2 (2.6) 2 (6.3) 3 (7.9) Posterior capsule rupture 0 (0) 1 (3.1) 2 (5.3) Iris bleeding 1 (3.6) 2 (6.3) 2 (5.3) Wound dehiscence 0 (0) 1 (3.1) 1 (2.6) Values are presented as number (%) unless otherwise indicated. Group 1 means preoperative instillation of Homatropin 2%, Group 2 means preoperative instillation of Isopto atropine 1%, Group 3 means no preoperative instillation. Table 4. Comparison of intraoperative floppy iris syndrome manifestations among 3 group Complications Group 1 Group 2 Group 3 Patients 20 26 22 Eyes 28 32 38 Progressive miosis 4 (14.3) 5 (15.6) 8 (21.1) Iris billowing 6 (21.4) 10 (31.3) 12 (31.6) Iris prolapse 2 (7.1) 1 (3.1) 10 (26.3) Values are presented as number (%) unless otherwise indicated. Group 1 means preoperative instillation of Homatropin 2%, Group 2 means preoperative instillation of Isopto atropine 1%, Group 3 means no preoperative instillation. Table 5. Factors affecting the grade of intraoperative floppy iris syndrome in patients taking α-blocker before cataract surgery Grade 2 vs. Grade 1 Univariate analysis Multivariate analysis Risk ratio 95% CI p-value Risk ratio 95% CI p-value Preoperative use of mydriatics Homatropine 2% 0.17 0.03-0.82 0.03 1.18 0.15-9.55 0.09 Isopto atropine 1% 0.14 0.03-0.71 0.02 0.25 0.04-1.63 0.02 Preoperative maximum pupil diameter (mm) 0.18 0.08-0.39 <0.01 0.20 0.07-0.54 <0.01 Nuclear density of cataract 2.22 0.95-5.20 0.07 2.21 0.93-5.30 0.07 Cumulative dissipated energy 1.12 1.00-1.25 0.05 1.05 0.71-1.15 0.90 Variables with p > 0.20 in the univariate model were not shown in this table. Variables with p < 0.20 in the univariate model were entered in a multivariate model. CI = confidence interval. 알파차단제를복용하는여자 4명이포함되었고, 전립선비대증의기왕력도고혈압에대해서알파차단제를복용하는환자를제외하고모두양성이었고수술전최대동공크기는 1군 (6.78 ± 0.36 mm) 과 2군 (6.89 ± 0.92 mm) 에서대조군 (6.14 ± 0.93 mm) 에비해서유의하게컸다 (p<0.01, p<0.01) (Table 1). 또한수술중홍채이완증후군의발생은세군간에차이는없었지만 (28.6%, 31.3%, 31.6%, p=0.57) 그정도를등급 0, 1과 2, 3 두군으로나누어비교하였을때 1군과 2군에서대조군에비해서등급이유의하게낮았다 (p=0.02, p=0.01). 수정체초음파유화술중누적소비에너지는 1군 (4.11 ± 0.97 mj) 과 2군 (4.14 ± 0.82 mj) 이대조군 (7.24 ± 6.28 mj) 에비해낮았으며 (p=0.02, p=0.01), 수력분리술이후와수정체초음파유화술시행후그리고수술종료후측정한최대동공크기는 1군 (5.97 ± 0.46, 6.20 ± 0.43, 6.63 ± 0.51 mm), 2군 (6.00 ± 0.56, 6.12 ± 0.78, 6.63 ± 0.83 mm) 이대조군 (5.82 ± 0.95, 5.65 ± 0.90, 5.55 ± 0.95 mm) 에비해컸고수력분리술이후의최대동공크기를제외하고통계적유의성을보였다 (p=0.51, p<0.01, p<0.01). 수술 1일후측정한최대동공크기는 1군 (5.01 ± 0.19 mm), 2군 (5.53 ± 0.76 mm) 그리고대조군 (4.46 ± 0.46 mm) 각각서로간의유의한차이를보였고 (p<0.01, p<0.01, p<0.01), 7일후최대동공크기는세군간의유의한차이는없었다 (p=0.90) (Table 2). 홍채이완증후군을제외한수술관련합병증의발생은세군간에유의한차이를보이지않았고 (Table 3), 홍채이완증후군이발생한경우동공축소와홍채펄럭임의발생은세군간의유의한차이가없었으나, 각막절개창으로의홍채탈출의발생은 1군 (2건, 7.14%), 2군 (1건, 3.13%) 에서대조군 (10건, 26.32%) 에비해적었으며세군간발생에유의한차이가있었다 (p<0.01) (Table 4). 알파차단제를복용하는환자에서백내장수술중발생한홍채이완증후군의정도를두군 (0, 1과 2, 3) 으로나누어이 36
- 문현식외 : 홍채이완증후군에대한호마트로핀의효과 - 에영향을주는인자에대해서단변량분석을시행하였을때, 수술 3일전부터호마트로핀 2% 점안액을같은용법으로사용한환자일수록 (p=0.03), 아트로핀 1% 점안액을하루 2회사용한환자일수록 (p=0.02), 수술전최대동공크기가클수록 (p<0.01), 백내장의핵경화도가작을수록 (p=0.02), 수술중수정체초음파유화술의누적소비에너지가작을수록 (p=0.02) 홍채이완증후군의정도를낮추는데기여하는인자임을알수있었다. 다변량분석을시행하였을때홍채이완증후군의정도를낮추는인자는수술전아트로핀 1% 점안액의사용 (p=0.02) 및수술전동공크기의확장 (p<0.01) 임을알수있었다 (Table 5). 고찰 홍채이완증후군은수술전알파차단제를복용한환자에서호발하는것으로알려져있는데, 알파차단제는전립선비대증및고혈압약제로주로사용되고, 안과적영역에서는홍채이완근의기능을억제하는것으로알려져있다. 그중에서도선택적알파 1A 차단제인 tamsulosin은홍채이완증후군발생및그강도와가장연관이높은약제로알려져있는데, 3-5 백내장수술을받은전체환자의 2-3% 에서홍채이완증후군이보고되었으며, 백내장수술을받는환자의약 1-3% 는전립선비대증의치료를위해 tamsulosin을복용하고있었고, 이중 57-100% 가홍채이완증후군의세소견중적어도하나이상의소견을보였었다. 11 Tamsulosin 이외에다른알파차단제인 terazosin, doxazosin, alfuzosin 등은알파 1B 수용체와관련해서작용하는것으로알려져있는데, 이들을복용한환자에서홍채이완증후군의발생과유의한관련을보고한여러보고가있었지만그유병률과정도는 tamsulosin보다상대적으로낮게보고되고있다. 8-10,12 최근알파차단제와홍채이완증후군의연관성에대한연구외에도고혈압, benzodiazepine, 5-α-reductase inhibitor, labetalol 등이 IFIS 발생에관여한다는보고가있다. 21-23 홍채이완증후군과관련된알파차단제에대한여러연구에서수술전약제의중단은유의한홍채이완증후군예방효과는없었다. 1,4-9 Lorente et al 14 에의한연구에서수술중에전방내페닐에프린을주입한군이대조군에비해홍채이완증후군의발생이유의하게감소하였다고보고하였고, Klysik and Korzycka 15 의보고에서는테논낭하리도카인주입을시행한군이전방내로리도카인을주입한군에비해서홍채이완증후군의발생이감소하였다. Armarnik et al 16 에의한연구에서수정된각막절개를이용하여단순하고효과적으로홍채이완증후군을예방할수있다고보고한바있고, 낮은초음파유화기관류속도의사용, 동공확대기, 홍 채당김기구등의동공확대를위한기구의사용과다른성질의두가지점탄물질을이용한소프트셀기법등이홍채이완증후군과관련되어보고되어왔다. 13-17 여러연구에서홍채이완증후군의예방을위한수술전아트로핀점안액사용에대해서보고가되어왔다. 아트로핀은동공조임근의무스카린성콜린성수용체를다른산동제, 조절마비제에비해더효과적으로차단함으로써홍채이완근의작용을강화, 유지시킴으로써알파차단제에의해홍채이완근이약화시키는것을중화시키는기전으로홍채이완증후군의발생혹은발생시그정도를최소화할수있었다. 이점을이용하여수술전홍채이완증후군을예방하기위한여러연구중아트로핀을수술전 10일간하루 2회점안을하여최대동공크기가수술중더크게유지시키고수술시간을절반으로줄일수있었다는 Bendel and Phillips 18 의보고나수술전 2일간아트로핀사용과함께수술중전방내에피네프린주입을시행하여홍채이완증후군발생을줄일수있다는 Masket and Belani 19 에의한보고등이있었다. 이러한연구결과들에더불어같은기전으로작용하여점안후 45분이지난시점부터아트로핀과유사한산동효과를나타내지만, 동공확대유지시간및정상동공크기로회복되는시간이각각 24시간, 48시간이상인아트로핀에비해 12시간, 24시간정도로 2배더짧다고알려진호마트로핀의효과 24,25 를알아보고자본연구에서는홍채이완증후군의예방에대한호마트로핀의효과를확인하고아트로핀과그효과를비교하며통계적유의성을확보하고자하였다. 본연구에서얻은수술전최대동공크기가홍채이완증후군과유의한상관관계를갖는것은그동안의 Neff et al 21, Chatziralli et al 22 의여러보고와일관된결과를보인것이다. 누적소비에너지가 1군및 2군에서대조군에비해서유의하게적은것으로나타났는데, 이는수술전아트로핀과호마트로핀점안에의해최대동공크기의유지가가능하여얻어진결과로볼수있겠다. 이와관련해서각막절개창으로의홍채탈출발생률이 3군간에유의한차이가있었던점도, 그로인해홍채이완증후군의정도를낮추는것과유의한상관관계가있음을설명할수있다. 홍채이완증후군의정도를낮추기위한인자에대한단변량분석을시행하였을때, 수술전아트로핀점안뿐만아니라호마트로핀점안도유의하게인자로작용함을확인할수있었다. 그러나다변량분석에서아트로핀점안만홍채이완증후군의정도를낮추는인자로나타나고, 호마트로핀의경우엔유의한인자로관찰되지않았고추후추가적인연구및더많은환자를대상으로한연구가필요한것으로보인다. 37
- 대한안과학회지 2019 년제 60 권제 1 호 - 본연구는기존의아트로핀을이용한홍채이완증후군의 정도를감소시켰던연구보고들에더나아가유사한약제인호마트로핀의사용또한같은수준의수술전동공확대및수술중동공유지효과, 그리고상대적으로수술후동공크기의빠른회복을유도할수있는것을통계적으로도출해낸첫연구라는것에그의의가있다고할수있겠다. 본연구의한계점으로는대상환자수가상대적으로적어세군간의비교분석에한계가있었던점, 환자의양안간의비교에대한연구가부족했던점, 후향적인의무기록분석특성상검사수치및각막소견, 장기적합병증에대해정확한자료획득에한계가있는점, 그리고호마트로핀점안의효과중수술후동공크기가비교적빠른회복을보이는것이환자에게주는영향에대한조사나수술후합병증과의상관성조사가미흡한점이있었다. 또한일반적으로동공의크기가커질수록전방깊이등의안구생체계측치의변화가발생할수있고, 이는다시수술중동공유지와연관될수있으나본연구의대상자들의결과분석에서그러한경향만보일뿐통계적으로유의한차이는보이지않았다는점도제한점의한부분으로볼수있다. 향후이러한부분을고려하여추가적인연구를시행할때보완이필요할것이라생각된다. 결론적으로알파차단제를복용하는환자의백내장수술에서홍채이완증후군의발생은예상가능한상황이므로수술전최대동공크기의확보등충분한대비가필요하며, 이를위해수술전호마트로핀 2% 점안액의사용은아트로핀 1% 점안액의사용의경우와같이수술전동공을효과적으로확대시키고수술중동공크기를최대한유지시켜홍채이완증후군발생시그정도를줄이는데유의한효과가있는것으로관찰되었다. 또한호마트로핀 2% 점안액의사용이아트로핀 1% 점안액사용시보다수술후동공의회복이더빠를것으로예측되며수술후동공확대에따른불편감을호소할환자들을위한하나의선택사항으로고려할수있을것이다. REFERENCES 1) Chang DF, Campbell JR. Intraoperative floppy iris syndrome associated with tamsulosin. J Cataract Refract Surg 2005;31:664-73. 2) Chang DF, Braga-Mele R, Mamalis N, et al. ASCRS White Paper: clinical review of intraoperative floppy-iris syndrome. J Cataract Refract Surg 2008;34:2153-62. 3) Blouin MC, Blouin J, Perreaulti S, et al. Intraoperative floppy-iris syndrome associated with alpha1-adrenoreceptors: comparison of tamsulosin and alfuzosin. J Cataract Refract Surg 2007;33:1227-34. 4) Cheung CM, Awan MA, Sandramouli S. Prevalence and clinical findings of tamsulosin-associated intraoperative floppy-iris syndrome. J Cataract Refract Surg 2006;32:1336-9. 5) Nguyen DQ, Sebastian RT, Kyle G. Surgeon's experiences of the intraoperative floppy iris syndrchome in the United Kingdom. Eye (Lond) 2007;21:443-4. 6) Goseki T, Ishikawa H, Ogasawara S, et al. Effects of tamsulosin and silodosin on isolated albino and pigmented rabbit iris dilators: possible mechanism of intraoperative floppy-iris syndrome. J Cataract Refract Surg 2012;38:1643-9. 7) Friedman AH. Alpha1-adrenergic blockers and intraoperative floppy-iris syndrome. Arch Ophthalmol 2009;127:1538-9. 8) Schwinn DA, Afshari NA. Alpha(1)-adrenergic receptor antagonists and the iris: new mechanistic insights into floppy iris syndrome. Surv Ophthalmol 2006;51:501-12. 9) Oshika T, Ohashi Y, Inamura M, et al. Incidence of intraoperative floppy iris syndrome in patients on either systemic or topical alpha(1)-adrenoceptor antagonist. Am J Ophthalmol 2007;143:150-1. 10) Herd MK. Intraoperative floppy-iris syndrome with doxazosin. J Cataract Refract Surg 2007;33:562. 11) Leibovici D, Bar-Kana Y, Zadok D, Lindner A. Association between tamsulosin and intraoperative floppy-iris syndrome. Isr Med Assoc J 2009;11:45-9. 12) Chadha V, Borooah S, Tey A, et al. Floppy iris behaviour during cataract surgery: associations and variations. Br J Ophthalmol 2007; 91:40-2. 13) Manvikar S, Allen D. Cataract surgery management in patients taking tamsulosin staged approach. J Cataract Refract Surg 2006; 32:1611-4. 14) Lorente R, de Rojas V, Vázquez de Parga P, et al. Intracameral phenylephrine 1.5% for prophylaxis against intraoperative floppy iris syndrome: prospective, randomized fellow eye study. Ophthalmology 2012;119:2053-8. 15) Klysik A, Korzycka D. Sub-tenon injection of 2% lidocaine prevents intra-operative floppy iris syndrome (IFIS) in male patients taking oral α-adrenergic antagonists. Acta Ophthalmol 2014;92: 535-40. 16) Armarnik S, Mimouni M, Rosen E, et al. Modified corneal incisions in intraoperative floppy iris syndrome (IFIS)-prone patients. Graefes Arch Clin Exp Ophthalmol 2016;254:123-7. 17) Goldman JM, Karp CL. Adjunct devices for managing challenging cases in cataract surgery: capsular staining and ophthalmic viscosurgical devices. Curr Opin Ophthalmol 2007;18:52-7. 18) Bendel RE, Phillips MB. Preoperative use of atropine to prevent intraoperative floppy-iris syndrome in patients taking tamsulosin. J Cataract Refract Surg 2006;32:1603-5. 19) Masket S, Belani S. Combined preoperative topical atropine sulfate 1% and intracameral nonpreserved epinephrine hydrochloride 1:4000 [corrected] for management of intraoperative floppy-iris syndrome. J Cataract Refract Surg 2007;33:580-2. 20) Ko BU, Ryu WY, Park WC. Pupil size in the normal Korean population according to age and illuminance. J Korean Ophthalmol Soc 2011;52:401-6. 21) Neff KD, Sandoval HP, Fernández de Castro LE, et al. Factors associated with intraoperative floppy iris syndrome. Ophthalmology 2009;116:658-63. 22) Chatziralli IP, Sergentanis TN, Papazisis L, Moschos MM. Risk factors for intraoperative floppy iris syndrome: a retrospective study. Acta Ophthalmol 2012;9:e152-3. 23) Calotti F, Steen D. Labetalol causing intraoperative floppy-iris syndrome. J Cataract Refract Surg 2007;33:170-1. 38
- 문현식외 : 홍채이완증후군에대한호마트로핀의효과 - 24) Whelan NC, Castillo-Alcala F, Lizarraga I. Efficacy of tropicamide, homatropine, cyclopentolate, atropine and hyoscine as mydriatics in Angora goats. N Z Vet J 2011;59:328-31. 25) Stadtbäumer K, Frommlet F, Nell B. Effects of mydriatics on intraocular pressure and pupil size in the normal feline eye. Vet Ophthalmol 2006;9:233-7. = 국문초록 = 알파차단제를복용하는환자의백내장수술시홍채이완증후군에대한호마트로핀점안제의효과 목적 : 알파차단제를복용하는환자에서백내장수술시발생할수있는홍채이완증후군을예방하기위해수술전에사용하는호마트로핀점안제의효과에대해분석하였다. 대상과방법 : 알파차단제를복용하고백내장수술을받은 68 명 98 안을대상으로, 수술전호마트로핀을점안한 1 군, 아트로핀을점안한 2 군과대조군 (3 군 ) 으로나누어연령, 성별, 기저질환, 알파차단제의종류, 수술전, 중및후동공크기, 수정체유화술의역동학변수및수술합병증을비교하였으며, 또한수술중홍채이완증후군의발생및정도와관련된위험인자를분석하였다. 결과 : 세군간연령, 기저질환의유무에유의한차이는없었다. 세군모두 tamsulosin 이알파차단제종류중가장많았다. 수술전후동공크기와수정체유화술의소비에너지는 1 군과 2 군이대조군에비해서유의한차이를보였다. 수술 1 일째엔 1 군과 2 군사이에도유의한차이는보였다. 세군간각막절개로의홍채탈출소견의발생엔유의한차이를보였으나, 그외소견이나합병증발생엔유의한차이는없었다. 홍채이완증후군의정도또한 1 군과 2 군이대조군보다낮았는데, 수술전동공크기와아트로핀점안이그정도를낮추는인자였다. 결론 : 홍채이완증후군정도를낮추기위해예방적으로시행한호마트로핀점안법은기존에알려진아트로핀점안법과비슷하게그정도를경감시켰고, 수술후동공크기의회복은더빨랐다. 수술전호마트로핀점안이알파차단제를복용하는환자의홍채이완증후군정도를낮출수있는선택사항이될수있을것으로사료된다. < 대한안과학회지 2019;60(1):32-39> 문현식 / Hyun Sik Moon 전남대학교의과대학안과학교실 Department of Ophthalmology, Chonnam National University Medical School 39