대한안과학회지 2016 년제 57 권제 5 호 J Korean Ophthalmol Soc 2016;57(5):724-733 ISSN 0378-6471 (Print) ISSN 2092-9374 (Online) http://dx.doi.org/10.3341/jkos.2016.57.5.724 Original Article 마이봄샘기능이상환자에서자동온열압박치료기기의임상적효과및예후분석 Effects and Prognostic Factors of Automated Thermodynamic System Treatment for Meibomian Gland Dysfunction 남승완 임동희 현주 정태영 Seung Wan Nam, MD, Dong Hui Lim, MD, Joo Hyun, MD, Tae-Young Chung, MD, PhD 성균관대학교의과대학삼성서울병원안과학교실 Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Purpose: To evaluate the effect and prognostic factors of automated thermodynamic treatment (thermal compression therapy device [KCL 1100 ]) for Meibomian gland dysfunction (MGD). Methods: Patients (48 eyes of 24 subjects) with MGD were recruited for a prospective clinical trial. Patients received 15-minute treatments twice a day using the KCL 1100. Severity of dry eye symptoms were evaluated using the Standard Patient Evaluation for Eye Dryness (SPEED) and Ocular Surface Disease Index (OSDI), and severity of Meibomian gland function was evaluated using the Meibomian gland expressibility (MGE), Meibomian gland secretion (MGS) score and lipid layer thickness measured by LipiView. To evaluate ocular surface, we measured tear break-up time (BUT) and fluorescein corneal staining score (Oxford scale). Data were presented for baseline and at 2 weeks and 1 month post-treatment. Results: Dry eye symptom (SPEED, OSDI), Meibomian gland function (MGE, MGS), and ocular surface index (BUT, Oxford scale) of patients were significantly improved from baseline to 2 weeks (p < 0.05) and 1 month post-treatment (p < 0.05). In addition, patients with more severe dry eye symptom and Meibomian gland index at baseline examination achieved improvement in mild to moderate MGD (p < 0.05). Improvement of Meibomian gland function (MGE) was associated with improvement of ocular surface index (BUT, Oxford scale) (p < 0.05), but not with improvement of dry eye symptom (SPEED, OSDI) (p > 0.05). There were no significant adverse events during the treatment. Conclusions: KCL 1100 automated thermodynamic treatment is an effective and safe treatment for MGD. Additionally, KCL 1100 is more effective in patients with moderate dry eye symptom and MGD. J Korean Ophthalmol Soc 2016;57(5):724-733 Keywords: Dry eye, KCL 1100, Meibomian gland dysfunction, Thermodynamic treatment 마이봄샘기능이상은만성적으로마이봄샘에서분비되 Received: 2016. 2. 25. Revised: 2016. 3. 18. Accepted: 2016. 4. 19. Address reprint requests to Tae-Young Chung, MD, PhD Department of Ophthalmology, Samsung Medical Center, #81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea Tel: 82-2-3410-3548, Fax: 82-2-3410-0074 E-mail: Wanmin2000@gmail.com 는지질의양과성분이변하고일부는마이봄샘폐쇄또는위축이동반되는질환이다. 1-8 이는눈물층의변화를일으키게되므로안구건조증의주요한원인중하나로알려져있다. 3,8 그러므로건성안환자에서마이봄샘기능이상의평가는중요하며, 마이봄샘을표적으로한치료법들이현재다양하게개발되고있다. 현재사용되고있는마이봄샘기능이상의치료법으로는안검위생관리, 온열압박치료, 안약및전신항생제치료 c2016 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. 724
- 남승완외 : 자동온열압박치료기기의효과및예후 - A B Figure 1. Photographs of the thermal compression therapy device (KCL 1100, Korea KCL, Bucheon, Korea). (A) The KCL 1100 is an automated thermodynamic treatment device system that generates heat and vibration, and massages the eyelid to treat Meibomian gland dysfunction (MGD). (B) Before the therapy, patients wore a moisturized cotton eye patch and then the device was used. 가있다. 9-12 마이봄샘기능이상환자에서는마이봄샘분비물의지질구성변화가분비물의녹는점및점도를증가시켜마이봄샘폐쇄및분비장애를만들게되는데온열압박치료시행시안검에열을가해주어마이봄샘내에침착된마이봄샘분비물들을녹여압출이쉽게만들어주게된다. 13,14 온열압박치료의장점은많은연구에서밝혀져있지만, 현재표준치료기준이마련되지않았고, 적정온열치료온도유지및자가및타가안검압박이번거로워환자순응도가낮은단점이있다. 15,16 하지만자동온열압박치료기기는 (KCL 1100, Korea KCL, Bucheon, Korea) (Fig. 1) 기존온열압박치료의단점을개선한자동온열압박치료기기이다. 자동온열압박치료기기 (KCL 1100 ) 사용전면섬유안대에물을적셔서착용한뒤기기를사용하며공기를이용하여패드를수축, 이완시키면서안검을마사지하며 42 kpa의압력을가할수있다. 또한전력에의해패드가최고 55 까지가열되어온열효과를얻을수있게된다. 기존국내논문에서는자동온열압박치료후안구건조증의호전에대한보고는있었으나 17 초기요인에따른치료효과의차이, 치료시각지표변화의상관성에대한보고는없었다. 상기논문에서는전향적으로, 자동온열압박치료후마이봄샘기능이상과안구건조증의치료효과와안전성, 초기요인에따른치료효과, 치료시각지표의상관성을확인하여그예후를분석해보고자하였다. 대상과방법 본연구는전향적연구로서 2015년 3월부터 2015년 5월까지본원에서마이봄샘기능이상환자 25명을대상으로연구를진행하였다. 18세이상의마이봄샘기능이상으로양안의 불편감이있는환자를대상으로양안모두의 SPEED 점수가 8점이상이며하안검에서측정한 Meibomian gland expressibility (MGE) 가총 15점중 4점이하또는 LipiView Ocular Surface Inferometer (TearScience, Morrisville, NC, USA) 를이용해측정한 lipid layer thickness (LLT) 가 61 nm 이하인환자를본연구에포함하였다. 18 LLT는마이봄샘에서분비되어안구표면을덮고있는지질층의두께에따라반사되는빛에따라간섭무늬의색깔이변화되는원리를이용해안구표면의지질층두께를측정하는것으로 LipiView 로측정가능한 LLT의최대값은 100 nm였다. 19 LLT 측정은오차를최소화하기위해내원시마다가장먼저시행하였으며내원직전에는안약점안및안구접촉을하지않도록교육하였다. 전신약제복용자 (tetracycline derivatives, antihistamine, isotretinoin), 안구건조증을유발할수있는전신질환자, 급성안구감염및염증, 콘택트렌즈착용력, 알레르기결막염, 3달이내안과수술력및외상력, 1달이내점안스테로이드및점안눈물분비촉진제사용자, 녹내장병력, 안검질환또는구조이상, 망막박리위험이있는고도근시, 망막열공, 망막격자변성이있는경우는환자군에서제외하였다. 상기요인들은온열압박치료시치료관련위해가가해질수있거나, 치료효과를감소시킬수있으며, 결과해석에간섭할수있으므로제외하였다. 대상환자들은연구에포함된이후연구에대한충분한설명을들은후삼성서울병원기관윤리심의위원회 (Samsung Medical Center Institutional Review Board [SMC IRB], 승인번호 : 2015-02-038) 에서허가된동의서에서명하였고자동온열압박치료기기사용법에대해자세한설명을들은이후자동온열압박치료기기를무상으로제공받고자택에서매일하루 2회, 15분씩사용하도록하였다. 순응도를 725
- 대한안과학회지 2016 년제 57 권제 5 호 - 확인하기위해매일일지를작성하였으며, 이는매내원시및종료후연구자가확인하였다. 연구중에는무방부제인공눈물인 Refresh Plus (carboxymethyl cellulose, Allergan, Parsippany, NJ, USA) 이외모든안약사용은금지되었으며, 내원 4시간전부터는인공눈물사용도금지하여지질층에대한측정오차를최소로하였다. 또한첫내원시에는상기검사이외에도자동굴절검사, 무산동안저사진, 전안부사진을시행하여제외기준이포함되는지확인하였다. 모든검사치는양안각각에대해측정하였다. 환자들은치료전, 치료 2주후, 치료 1달후내원시양안각각에대해나안시력, 안압, Standard Patient Evaluation for Eye Dryness (SPEED), Ocular Surface Disease Index (OSDI), LLT, Meibomian gland expressibility (MGE), Meibomian gland secretion score (MGS), 눈물막파괴시간 (tear break up time, BUT), 플루오레신각막염색점수 (Oxford scale 20,21 ) 를측정하였다. MGE 측정시하안검의내측, 중앙, 가측부위를숙련된각막전문의가 Meibomian gland evaluator (TearScience, Morrisville, NC, USA) 를이용하여일정한힘으로누르며총 15개의마이봄샘중분비가있는마이봄샘의개수를세극등현미경으로확인하여 0-15점범위로측정하였다. Meibomian gland evaluator는하안검에서만측정이가능하도록제작되었다. MGS 측정시에는 Meibomian gland evaluator로눌렀을때마이봄샘각각에서나오는분비물유무와성질에따라분비되지않는경우는 0점, 치약같은분비물이나오는경우 1점, 탁한분비물이나오면 2점, 깨끗한분비물이나오는경우는 3점으로분류하여 15개의마이봄샘에서의점수를합산하여 0-45점범위로환산하였다. 22 자동온열압박치료의효과및안전성분석시치료전후마이봄샘기능이상및안구건조와관련된지표 ( 나안시력, 안압, SPEED, OSDI, LLT, MGE, MGS, BUT, Oxford scale) 들을대상으로짝지은 t 검정을시행하였으며, 자동온열압박치료효과에영향을주는예후인자들을확인하기위해치료전건조증증상 (SPEED, OSDI), 마이봄샘지표 (MGE, LLT) 각각의치료전과치료 1달간의변화량에대해단일회귀분석을시행하였다. 자동온열압박치료에따른마이봄샘기능변화와증상호전, 및안구표면의변화의관계를확인하기위해마이봄샘지표 (MGE) 의치료 1 달간변화량과다른지표 (SPEED, OSDI, BUT, Oxford scale) 의치료 1달간변화량을단일회귀분석시행하였다. 또한증상호전에미치는인자를확인하기위해안구건조증상의치료 1달간변화량 (SPEED, OSDI) 을다른지표들의치료 1달간변화량 (MGE, MGS, BUT, Oxford scale) 과 단일회귀분석시행하였다. p값의유의수준은 0.05 미만으로하였고, 통계분석은 IBM SPSS version 22.0 (SPSS Inc., Chicago, IL, USA) 을사용하였다. 결 과 마이봄샘기능이상환자로진단받아본연구에참여하게된 25명중자의로스테로이드안약을점안한 1명을제외한 24명, 48안에대하여분석을시행하였다. 분석에포함된 24명의평균연령은 61.92세였고, 남자가 7명 (14안), 여자는 17명 (34안) 이었다 (Table 1). 이들중치료 2주째내원하지않은 2명은자동온열압박기기의효과및안전성분석에서는제외하였다. 자동온열압박기기의치료효과자동온열압박기기 (KCL1100 ) 치료전, 치료 2주후, 1달후의측정치를비교해보면안구건조증상의정도를나타내는 SPEED 점수는치료전 13.21 ± 6.08에서치료 2 주후 6.07 ± 5.04로통계적으로유의한호전을보였고 (p<0.001), 치료 1달뒤에는 5.87 ± 4.78로치료 2주째와비교해도유의한호전이있었다 (p=0.040). OSDI 점수는치료전, 치료 2주후각각 35.41 ± 25.43, 16.52 ± 20.92로유의한호전이있었고 (p<0.001), 치료 1달후도 8.82 ± 9.87로치료 2주후에비해서도통계적으로유의한호전을보여주었다 (p=0.001) (Fig. 2A). 눈물층의안정성을나타내는지표인 BUT는치료전 2.63 ± 1.30초에서치료 2주후 3.66 ± 1.75초로유의하게호전되었지만 (p=0.002), 치료 1달후는 3.67 ± 1.98초로치료 2주후와통계적으로유의한차이는없었다 (p=0.822). 또한안구표면상태를나타내는 Oxford Table 1. Pretreatment demographics of patients who underwent automated thermodynamic therapy (48 eyes of 24 subjects) Characteristics Value (range * ) Age 61.9 ± 12.3 (22-79) Sex (male:female) 7:17 SPEED 13.2 ± 6.08 (0-24) OSDI 35.4 ± 25.4 (0.00-77.7) MGE 3.08 ± 1.77 (0-10) MGS 4.11 ± 3.05 (0-17) LLT (nm) 73.0 ± 23.9 (29.00-100.00) BUT (sec) 2.63 ± 1.30 (1.0-6.0) Corneal staining score (Oxford scale) 0.75 ± 0.91 (0-3) Values are presented as mean ± SD unless otherwise indicated. SPEED = standard patient evaluation for eye dryness; OSDI = ocular surface disease index; MGE = meibomian gland expressibility; MGS = meibomian gland secretion score; LLT = lipid layer thickness; BUT = tear breakup time. * Range: minimum value-maximum value. 726
- 남승완외 : 자동온열압박치료기기의효과및예후 - A B C Figure 2. Improvement of dry eye symptom, ocular surface and Meibomian gland index. (A) The mean Standard Patient Evaluation of Eye Dryness (SPEED) and Ocular Surface Disease Index (OSDI) at baseline, 2 weeks, and 1 month. (B) The mean tear break-up time (BUT) and fluorescein corneal stain score (Oxford scale) measured at baseline, 2 weeks and 1 month. (C) The mean Meibomian gland expressibility (MGE) and Meibomian gland secretion (MGS) score for the 15 Meibomian test glands of the lower eyelid and lipid layer thickness (LLT) using LipiView (TearScience, Morrisville, NC, USA) measured at baseline, 2 weeks and 1 month. Dry eye symptom (SPEED, OSDI), ocular surface index (BUT, Oxford scale), and Meibomian gland index (MGE, MGS) were significantly improved after 1 month of treatment with KCL 1100 (Korea KCL, Bucheon, Korea). * Significant (p < 0.05). scale은치료전 0.75 ± 0.91에서치료 2주후 0.30 ± 0.63으로사용전에비해유의한호전이있었으나 (p<0.001), 치료 1달후는 0.20 ± 0.50으로사용 2주후에비해통계적으로유의한호전은없었다 (p=0.400) (Fig. 2B). 또한마이봄샘의기능을나타내는 MGE는치료전 3.08 ± 1.77, 치료 2주후 6.06 ± 1.64로치료전에비해유의한호전이있었고 (p<0.001), 치료 1달후에도 8.63 ± 2.10으로사용 2주후에비해서도유의한호전이있었으며 (p<0.001), MGS도치료전 4.11 ± 3.05, 치료 2주후 9.14 ± 3.06으로치료전에비 해유의한호전이있었고 (p<0.001), 치료 1달후 15.37 ± 6.43으로치료 2주후에비해통계적으로유의하게호전되었다 (p<0.001). 하지만 LLT는치료전 73.04 ± 23.89에서치료 1달후 76.86 ± 22.80으로치료 1달간유의한차이는없었다 (p=0.227) (Fig. 2C). 자동온열압박기기의치료예후인자분석자동온열압박치료효과에영향을주는초기요인을확인하기위해치료 1달간각지표의변화량과치료전각지 727
- 대한안과학회지 2016 년제 57 권제 5 호 - A B C D Figure 3. Relationship between pre-treatment index and improvement during 1 month of thermodynamic treatment. (A, B) Scatter plots showed a negative correlation between initial value and change in dry eye symptom (Standard Patient Evaluation of Eye Dryness [SPEED], Ocular Surface Disease Index [OSDI]) and (C, D) Meibomian gland index (lipid layer thickness [LLT], Meibomian gland expressibility [MGE]). The patients with more severe dry eye symptom (SPEED, OSDI) and Meibomian gland index (LLT, MGE) at baseline examination achieved improvement with thermal compression therapy in mild to moderate Meibomian gland dysfunction (MGD). 표들에대해단일회귀분석을시행하였다. 분석결과, 치료전안구건조증상 (SPEED, OSDI) 이심할수록치료 1달간안구건조증상호전정도도컸다 (SPEED: b= 0.634, p<0.0001; OSDI: b= 0.845, p<0.0001). 또한치료전마이봄샘기능 (LLT, MGE) 이상이심할수록치료 1달간마이봄샘기능호전정도도컸다 (LLT: b= 0.489, p=0.0003; MGE: b= 0.708, p=0.0001) (Fig. 3). 자동온열압박치료에따른마이봄샘기능변화와안구건조증상변화, 그리고안구표면의변화간의상관관계 를확인하기위해 1달간 MGE 변화량과다른지표 (SPEED, OSDI, BUT, Oxford scale) 들의 1달간변화량에대해단일회귀분석을시행하였다. 치료 1달간마이봄샘기능호전정도 (MGE 변화량 ) 는안구건조증상의호전정도와는유의한상관관계를보이진않았으나 (SPEED: b=0.127, p=0.401; OSDI: b= 0.176, p=0.242), 안구표면상태의호전정도와유의한상관관계가있음을확인할수있었다 (BUT: b=0.327, p=0.027; Oxford scale: b= 0.446, p=0.002) (Fig. 4). 또한증상호전에영향을미치는인자를확인하기 728
- 남승완외 : 자동온열압박치료기기의효과및예후 - A B C D Figure 4. Relationship between change of Meibomian gland opening and ocular surface index, and change in Meibomian gland opening and dry eye symptom. (A, B) Scatter plots showed a correlation between change in Meibomian gland opening (Meibomian gland expressibility [MGE]) and change in ocular surface index (tear breakup time (BUT), Oxford scale). (C, D) However, dry eye symptom (Standard Patient Evaluation of Eye Dryness [SPEED], Ocular Surface Disease Index [OSDI]) was not correlated with Meibomian gland opening (MGE). Meibomian gland opening (MGE) was associated with ocular surface index (BUT, Oxford scale), but not with dry eye symptom (SPEED, OSDI). 위해안구건조증상의 1달간변화량 (SPEED, OSDI) 을다른지표 (MGE, MGS, BUT, Oxford scale) 들의 1달간변화량과회귀분석을시행한결과유의한관계가없었다 (p>0.05). 자동온열압박기기의안전성평가안전성평가를위해안압측정및나안시력측정, 증상확인, 세극등검사, 안저검사를시행하였으며안압측정치는기기사용전 14.95 ± 2.90 mmhg에서사용 2주후 14.39 ± 2.74 mmhg, 사용 1달후 14.54 ± 2.41 mmhg로사용전에비해사용이후에도통계적으로유의한차이는없었으며, logmar 시력으로측정한나안시력도사용전 0.19 ± 0.25, 사용 2주후 0.19 ± 0.25, 사용 1달후 0.18 ± 0.26으로통계적으로유의한차이는없었다. 이외외래추적기간동안온열압박치료기기로인한안검부종, 결막충혈, 각막변형, 망막박리등의중대한합병증은나타나지않았다. 729
- 대한안과학회지 2016 년제 57 권제 5 호 - 고찰 마이봄샘기능이상은안구건조증을유발하는주요한원인중하나이다. 1-8 마이봄샘기능이상의기전으로온도가비교적낮은마이봄샘개구부에서마이봄샘에서분비되는지질의응고가일어나게되고, 이로인해마이봄샘의폐쇄, 위축이발생하여, 지질의분비가줄어든다고알려져있다. 15,23 마이봄샘에서지질분비가감소하게되면이는눈물의안정성을감소시켜, 증발성안구건조증의원인이될수있다. 24,25 현재까지알려진마이봄샘기능이상의치료로는안검위생관리, 온열치료, 압박치료, 국소및전신항생제치료, 국소스테로이드치료등이있다. 12,26 이중온열및압박치료는효과가빠르다는장점이있지만이전에는수동으로이루어져번거로워순응도가낮다는단점이있었다. 하지만최근자동화치료기기들이개발되어연구가이루어지고있는데, 대표적인것들이 KCL1100 (Korea KCL), Nurieye-5800 (Seodong Medical, Busan, Korea), Lipiflow (TearScience Inc., Morrisville, NC, USA), Blephasteam (Spectrum Thea Pharmaceuticals LTD, Macclesfield, UK) 이다. 하지만 Lipiflow 의경우기계 (Activator) 를안검내외로밀착하여야하며, 고가의부피가큰장비이므로개인적인사용이어렵고, Blephasteam 의경우, 온열치료만가능하고, 압박효과는없다는단점이있다. 그에비해 KCL1100 및 Nurieye-5800 은부피가작고, 온열및압박치료기능이함께있어개인적인마이봄샘기능이상치료가가능하다. 본연구에서는자동온열압박치료기기 KCL1100 을자택에서매일하루 2회, 15분씩사용한지 2주째부터안구건조증상 (SPEED, OSDI) 및마이봄샘지표 (MGE, MGS), 안구표면지표 (BUT), 각막염색 (Oxford scale) 이통계적으로유의하게호전되는것을확인할수있었다. 이는기존의연구결과들에부합되는결과로마이봄샘지표인 MGE, MGS가호전되는것은막혔던마이봄샘이자동온열압박치료기기사용이후지질의액화를촉진하여마이봄샘의분비가촉진된것을의미하며, 27 BUT, Oxford scale이호전된것은눈물층의안정성이증가되어안구표면지표가호전된것으로생각된다. 또한 SPEED, OSDI가호전된것은실제온열압박치료가안구건조증상호전에도효과가있다는것을의미한다. 그러나 LLT의경우는본연구에서치료 1달간유의한변화를보이지않았다. 이에대한가설로첫째, 본연구의대상자들에폐쇄성마이봄샘기능이상이외과분비성마이봄샘기능이상 28 환자들이포함되었을수있고이환자들에선마이봄샘의개방이이루어져도안구표면의지질의 양이증가하지않을수있다. 둘째, LLT 측정에사용한 LipiView 기계의재현성의문제가있을수있으며, 셋째, LipiView 기계의측정값상한선이 100 nm로마이봄샘에서분비된지질의양이증가하더라도 100 nm 이상이될경우정확히측정되지않아증가량이저평가되기때문인것으로생각된다. 따라서추후과분비성마이봄샘기능이상군에대한추가연구가필요할것으로생각된다. Nelson et al 29 은과분비성마이봄샘기능이상이지루성피부염, 아토피성피부염등과연관되어이차성으로발병하는경우도있지만, 특별한원인없이일차성으로발생할수도있다고언급하고있으며본연구의대상군도상기와같은환자들이포함되었을것으로생각된다. 마이봄샘지표 (MGE, MGS) 및안구건조증상 (SPEED, OSDI) 은자동온열압박기기사용 2주이후에도호전이되었지만, 반면에안구표면지표 (BUT, Oxford scale) 들은자동온열압박기기사용 2주이후에는별다른호전이없었다. Arita et al 30 은마이봄샘이상환자에서온열치료를건식과습식으로나누어시행하였는데습식온열치료보다는건식온열치료시안구건조증상, 안구표면지표, 마이봄샘기능지표가효과적으로호전되었으며이는건식온열치료가더효과적으로열전달이되기때문인것으로설명하였다. 본연구에서사용한 KCL1100 은습식온열치료기기로치료 2주이후안구표면지표가호전되지않은것은습식치료기기의효과의한계로보인다. 향후건식과습식온열치료의효과를비교하는추가연구가필요할것으로보인다. 자동온열압박치료효과에영향을주는초기요인분석에서마이봄샘지표 (MGE, LLT) 및안구건조증상 (SPEED, OSDI) 이초기에심했던환자들이온열압박치료에더효과가있음이본연구에서확인되었다. 하지만이는마이봄샘기능이상의정도가심한군에서는마이봄샘위축으로인해자동온열압박치료기기의효과가감소된다는기존의연구들 31,32 과는다른결과이다. Finis et al 32 에의하면진행된마이봄샘기능이상의경우, 마이봄샘의위축으로온열압박치료시에도마이봄샘의기능을되돌릴수없고, 이로인해온열압박치료의효과가떨어진다고주장하였다. 하지만 Finis의연구 32 는대상환자군의치료전평균 OSDI 42 ± 19, MGE 2.9 ± 1.6, LLT 44.0 ± 15.6으로본연구에서치료전평균 OSDI 35.41 ± 25.43, MGE 3.08 ± 1.77, LLT 73.04 ± 23.89인것에비해안구건조증상이심한폐쇄성마이봄샘기능이상환자가본연구보다많이포함되었고, 반면에본연구에서는마이봄샘이완전히막혀마이봄샘의위축이올정도로기능이상이극도로심한환자가거의포함되지않았기때문으로생각된다 (MGE 1 730
- 남승완외 : 자동온열압박치료기기의효과및예후 - 이하 : 2안 ). 따라서향후 meibography 등을이용해마이봄샘의위축이온심한마이봄샘기능이상환자들을선별하여경도및중등도의마이봄샘폐쇄, 과분비성마이봄샘이상환자들과비교하는연구가필요할것으로생각된다. 자동온열압박치료효과에영향을주는인자들을분석하기위해마이봄샘지표 (MGE) 의변화량과안구건조증상 (SPEED, OSDI) 및안구표면지표 (BUT, Oxford scale) 의변화량에대해상관분석시, 치료에따른안구표면상태의개선은마이봄샘이열린것과유의한상관관계가있었으나, 치료에따른증상의호전은마이봄샘이열린것과유의한상관관계가없었다. 이는마이봄샘개방이안구표면상태의호전에영향이있지만, 실제환자들이느끼는안구건조증증상의호전은마이봄샘의개방뿐만아니라, 이외여러요인들의영향이있었을것이라생각되며, 그중가능한원인으로각막상태호전및온도변화로인한각막신경예민도감소 33-38 와온열치료자체로인한마이봄샘에서분비되는지질의양적, 질적인변화도있었을것이라생각된다. Belmonte 39 는굴절수술이후각막신경세포막의이온채널의발현이변화가있어신경전달에문제가생길수있다는것을처음제안하였고, 이후상기제안은건조증에서통증을느끼는기전을설명하는토대가되었다. 이후 De Paiva and Pflugfelder 40, Tuisku et al 41 은안구건조증환자에서각막이더민감해질수있음을주장하였고, Hirata and Rosenblatt 37 에의하면각막온도변화로인해각막신경예민도가변화할수있고, 안구건조증이심할때각막신경이더예민해진다고주장하였다. 본연구에서도각막예민도감소가온열효과로인한각막온도증가및각막상태호전으로인해발생하였고건조증상을완화시키는데유의한영향을주었을것이라생각된다. 또한 KCL 1100 과치료방식이유사한 Nurieye-5800 을이용한 Lee et al 42 의연구에의하면안구건조증환자들을 Nurieye-5800 을사용한군과인공눈물사용군으로나누어 1달동안치료하였으며 Nurieye-5800 치료전과후에안구건조증상 (OSDI) 및안구표면지표 (BUT, fluorescein staining of the cornea) 가유의하게호전되었으며, 인공눈물사용군보다 Nurieye-5800 사용군에서안구건조증상 (OSDI) 과안구표면지표 (BUT, fluorescein staining of the cornea) 의호전정도가크긴했지만이중안구건조증상 (OSDI) 만유의하게두군간호전정도의차이가있었다고보고하였다. 이에대한설명으로온열치료기기가마이봄샘의지질분비를증가시켜눈물의빠른증발을억제하는것이외에도, 온열치료로인한미주신경자극으로염증물질이감소되어만성염증억제효과및신경말단자극으로인한통증완화도역할이있을것으로생각된다고하였다. 이외안전성지표인안압, 나안시력수치는본연구기간중유의한변화가없었으며, 온열압박치료시가능한안검부종, 결막충혈, 각막변형, 망막박리등의안과적합병증을겪은환자는없었다. 이는상기자동온열압박치료기기의안전성을입증할수있는결과로생각된다. 이전에도자동온열압박치료기기에대한많은연구가있었지만, 본연구는 KCL 1100 을이용하여마이봄샘지표 LLT, MGE, MGS와안구표면지표 BUT, Oxford scale 및안구건조증상 SPEED, OSDI의변화를같이확인했다는점에서그의의가있다. 하지만상기연구의제한점으로대상환자에서양안을각각분석에사용하여독립성이충분히보장되지않았으며, 대조군이설정되지않아, 위약효과에대한배제가완벽히이루어지지않았고, 장기적인경과관찰이이루어져있지않아효과가지속되는지, 장기부작용이있는지확인이불가하였다. 이는추후에더연구가필요할것으로생각된다. 또한이후연구에서는적외선마이봄샘촬영기 (meibography) 로측정하여마이봄샘위축이심한군에서상기지표의호전여부를확인하는것도마이봄샘기능이상에서자동온열압박치료기기의적응증및역할을확인하는데에필요할것으로생각된다. 결론적으로마이봄샘기능이상으로인한안구건조증환자에서 KCL 1100 을이용한자동온열압박치료는중등도이하의마이봄샘기능이상환자를안전하게치료할수있는치료법으로사용될수있으며, 중등도이하의마이봄샘기능이상환자에서는안구건조증상과마이봄샘기능이상정도가심한경우에서더욱효과적이었다. 하지만장기적인추적관찰이필요하며, 대조군을이용한대규모연구및중증도의마이봄샘기능이상환자에대한추가연구가더필요할것으로생각된다. REFERENCES 1) Auw-Haedrich C, Reinhard T. Chronic blepharitis. Pathogenesis, clinical features, and therapy. Ophthalmologe 2007;104:817-26; quiz 827-8. 2) Finis D, Schrader S, Geerling G. Meibomian gland dysfunction. Klin Monbl Augenheilkd 2012;229:506-13. 3) Geerling G, Tauber J, Baudouin C, et al. The international workshop on meibomian gland dysfunction: report of the subcommittee on management and treatment of meibomian gland dysfunction. Invest Ophthalmol Vis Sci 2011;52:2050-64. 4) Green-Church KB, Butovich I, Willcox M, et al. The international workshop on meibomian gland dysfunction: report of the subcommittee on tear film lipids and lipid-protein interactions in health and disease. Invest Ophthalmol Vis Sci 2011;52:1979-93. 5) Knop E, Knop N. Meibomian glands: part IV. Functional interactions in the pathogenesis of meibomian gland dysfunction (MGD). Ophthalmologe 2009;106:980-7. 731
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- 남승완외 : 자동온열압박치료기기의효과및예후 - = 국문초록 = 마이봄샘기능이상환자에서자동온열압박치료기기의임상적효과및예후분석 목적 : 마이봄샘기능이상환자에서자동온열압박치료기기 (KCL 1100, Korea KCL, Bucheon, Korea) 의효과및안전성평가를시행하고, 자동온열압박치료효과에영향을주는요인을알아보고자하였다. 대상과방법 : 마이봄샘기능이상으로진단된환자 24 명 48 안을대상으로 1 달간전향적연구를시행하였다. 대상환자는매일하루 2 회, 15 분씩자동온열압박치료기기 (KCL 1100 ) 를사용하였고, 치료전, 치료 2 주후및 1 달후내원하여나안시력, 안압, Standard Patient Evaluation for Eye Dryness (SPEED), Ocular Surface Disease Index (OSDI), Lipid Layer Thickness (LLT), Meibomian Gland Secretion score (MGS), Meibomian Gland Expressibility (MGE), 눈물막파괴시간 (tear break-up time, BUT), 플루오레신각막염색점수 (Oxford scale) 를측정하였다. 자동온열압박치료의효과및안전성분석시내원시마다측정한각각의지표를짝지은 t 검정을시행하였다. 자동온열압박치료효과에영향을주는초기요인을확인하기위해이지표들의치료전과치료 1 달간변화량에대해단일회귀분석을시행하였다. 자동온열압박치료에따른마이봄샘기능변화와증상호전및안구표면변화의관계를확인하기위해치료 1 달간마이봄샘기능의변화량과치료 1 달간건조증증상및안구표면지표들의변화량에대해단일회귀분석을시행하였다. 결과 : 대상환자들은중등도이하의마이봄샘기능이상환자로치료전 MGE 의평균은 3.08 ± 1.77, MGS 의평균은 4.11 ± 3.05 였다. 자동온열압박치료이후안구건조증상 (SPEED, OSDI) 과안구표면지표 (BUT, Oxford scale), 마이봄샘기능지표 (MGE, MGS) 는치료 2 주후와 1 달후에치료전에비해모두유의한호전이있었다 (p<0.05). 또한치료전증상이심했던군과치료전마이봄샘기능이상정도가심했던군에서치료후개선정도가컸다 (p<0.05). 치료후마이봄샘의기능개선정도 (MGE 변화량 ) 는안구표면상태의호전 (BUT, Oxford scale 변화량 ) 과유의한관계를보였지만, 건조증상의개선 (SPEED, OSDI 변화량 ) 과는유의한관계가없었다. 치료기간동안임상적으로유의한부작용은관찰되지않았다. 결론 : 마이봄샘기능이상환자에서자동온열압박치료기기는안전성있게마이봄샘기능이상및안구건조증을호전시켰으며, 특히중등도이하의마이봄샘기능이상에서는안구건조증상과마이봄샘기능이상정도가심한경우에서더욱효과적이었다. < 대한안과학회지 2016;57(5):724-733> 733