대한안과학회지 2015 년제 56 권제 4 호 J Korean Ophthalmol Soc 2015;56(4):499-508 ISSN 0378-6471 (Print) ISSN 2092-9374 (Online) http://dx.doi.org/10.3341/jkos.2015.56.4.499 Original Article 원추각막및각막확장증에서각막링삽입술의임상성적비교분석 Clinical Results of Intacs Ring Implantation in Keratoconus or Keratectasia 김지아 1,2 김동현 1,2 위원량 1,2 김미금 1,2 Ji Ah Kim, MD 1,2, Dong Hyun Kim, MD 1,2, Won Ryang Wee, MD, PhD 1,2, Mee Kum Kim, MD, PhD 1,2 서울대학교의과대학안과학교실 1, 서울대학교병원의생명연구원인공안구센터안면역각막재생연구실 2 Department of Ophthalmology, Seoul National University College of Medicine 1, Seoul, Korea Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Clinical Research Institute 2, Seoul, Korea Purpose: To report the clinical results after the implantation of intrastromal corneal ring segments (Intacs ) for the correction of keratoconus or keratectasia. Methods: This retrospective study was comprised of 16 eyes treated by insertion of intrastromal corneal ring and 30 eyes treated by penetrating keratoplasty (PKP) who were diagnosed with keratoconus or keratectasia. Visual acuity, refractive outcome, keratometric values were evaluated before and at 3 months, 6 months, and 12 months postoperatively. In addition, the implanted ring segment depth was measured by anterior segment optical coherence tomography and the results were compared based on the depth of the ring. Results: Twelve months after treatment, best corrected visual acuity (BCVA) was log MAR 0.32 at the ring group and log MAR 0.20 at the PKP group. BCVA change was larger at the PKP group than the ring group. Postoperative keratometric value was smaller at the ring group than at the PKP group. 3 mm irregular astigmatism was larger at the ring group than at the PKP group. The shallowly implanted ring group had a larger effect than the deeply implanted ring group. Conclusions: Intrastromal corneal ring segment implantation appears to be effective in improving the visual acuity and refractive outcome, although it cannot substitute for PKP. J Korean Ophthalmol Soc 2015;56(4):499-508 Key Words: Intacs ring, Keratectasia, Keratoconus, Penetrating keratoplasty 원추각막또는굴절수술후발생한각막확장증은각막기질이얇아지고앞으로밀려각막돌출을보이는비염증성각막확장질환이다. 1 질환초기에는안경이나경성콘택트렌 Received: 2014. 8. 23. Revised: 2014. 9. 22. Accepted: 2015. 3. 23. Address reprint requests to Mee Kum Kim, MD, PhD Department of Ophthalmology, Seoul National University Hospital, #101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea Tel: 82-2-2072-2665, Fax: 82-2-741-3187 E-mail: Kmk9@snu.ac.kr * This study was presented as a narration at the 111th Annual Meeting of the Korean Ophthalmological Society 2014. 즈착용으로교정이가능하지만진행되어교정이되지않거나경성콘택트렌즈착용이어려워지게되는경우수술적치료를고려하는것이일반적이다. 2 각막이식술이표준치료이나국내기증각막공급이수요에훨씬미치지못하는점, 거부반응이올수있다는점, 장기관찰시내피세포의수가많이줄어든다는점, 고도난시가여전히발생한다는점등이단점이다. 3 이에본인의각막을유지하면서교정시력을유지해보려는노력이이루어지고있다. 한예로리보플라빈과자외선을이용하여각막확장증의진행을억제하려는시도가있어좋은결과가보고되고있으나한편으로주변각막윤부세포, 실질세포, 내피세포등을손상시킬수있다는우려도 c2015 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. 499
- 대한안과학회지 2015 년제 56 권제 4 호 - 있어아직안정성측면에서논란이있다. 4 각막링삽입술은각막실질에수기또는펨토초레이저를이용하여만들어진터널로삽입되어기질층을벌려서각막중심부가편평해지게되는원리를이용한다. 5 초기에근시의치료를목적으로만들어졌으나현재는원추각막의치료에효과가있음이발견된이후최근그사용이증가되고있고, 국내에서도초기임상성적에대한보고가있다. 6,7 그러나, 아직도그효과의유효성에는논란이있는상태이다. 8,9 면역억제제및수술기법의발달로전층각막이식술의성공률및시력호전정도가양호하며, 특히수술후발생하는고도난시도난시교정인공수정체의삽입으로많이개선되고있다는점을고려할때, 비보험으로고비용인각막링삽입술이환자에게먼저권유할만한수술인지에대해저자들은확신이서지않았다. 즉, 저자들은중등도이상의각막확장증환자에서전층각막이식술을시행하는것이환자의시력교정, 난시교정, 술후합병증면에있어나은선택일지, 중간단계로라도각막링삽입술을시행하는것이시력이나난시교정면에서나은선택일지그실질적인임상적용가능성에대하여의문을가지게되었다. 이에본연구에서는인택스링을사용한각막링삽입술의단기임상경과를제시하는동시에그결과를전층각막이식술의결과와함께비교하여봄으로써, 고비용의각막링삽입술이각막이식술의임시대치로서의임상효과를보일수있는지를확인하고자하였다. 대상과방법 2012 년 1 월부터 2013 년 1 월사이에본원에서수기인택 스각막링삽입술을받은후 3개월이상경과한원추각막또는각막확장증환자 16명, 16안을대상으로의무기록후향분석을시행하였다. 대조군으로 2004년 1월부터 2013년 1월사이에본원에서원추각막또는각막확장증으로진단받고전층각막이식술을받고나서수술후봉합사제거를받은지적어도 1년이상경과한환자중연령- 매칭을하여 30안을선정하여의무기록후향분석을시행하였다. 수기인택스각막링삽입술및전층각막이식술시행당시다른수술이추가되거나수술중합병증이있었던경우는제외되었다. 모든각막링삽입술과전층각막이식술은한명의술자 (M.K.K.) 에의해이루어졌다. 분석대상에는원추각막과시력교정술후발생한각막확장증모두를포함하였으며원추각막은세극등검사상특징적인소견을보이면서각막지형도검사 (Orbscan II, Bausch and Lomb Inc., Rochester, NY, USA) 에서원추형돌출이발견되며경과관찰시진행소견이관찰되는경우로진단하였다. 인택스각막링삽입술은평균각막곡률이 60D 미만인경도의원추각막환자중콘택트렌즈를이용한시력교정이불량한경우이거나통증, 불편감, 눈물등으로지속적인콘택트렌즈착용이힘든환자를대상으로하였다. 중심각막의혼탁이있거나각막링삽입부위의각막두께가 450 μm 이하로얇은경우, 이전에각막의수술적치료, 자가면역질환, 외상력이있는안구는대상에서제외하였다. 인택스링삽입의방향과깊이는술전환자의 Orbscan II (Bausch and Lomb Inc., Rochester, NY, USA) 로측정한각막지형도를분석하여방향을정하고, anterior segment optical coherence tomography (Visante, Carl Zeiss Meditec, Dublin, CA, USA) 로측정한각막두께지도를참조해가장얇은각막두께의 80% A B Figure 1. Corneal topography (A) and pachymetric map of anterior segment OCT (B) were used to design axis and stromal depth of the ring location. OCT = optical coherence tomography; S = superior; I = inferior; T = temporal; N = nasal. 500
- 김지아외 : 각막링삽입술의임상성적비교분석 - 이내면서절개축부위의약 75% 인값을취해결정하였다 (Fig. 1). 모든환자에서 6 mm 지름의각막링이사용되었고, 링의두께는제조사에서제시한노모그램을참고하여결정되었다. 링의두께는 450 mm 3안, 500 mm 2안으로삽입한평균사용한링두께는 419.4 ± 73.07 μm이었다. 본연구의환자군에서는평균총절개축각막두께의 78.3 ± 3.09% (484.9 ± 29.44 μm) 깊이를타겟으로각막링을삽입하도록산출되었다. 인택스 (Intacs, Addition Technology Inc., Sunnyvale, California, USA) 를이용한수기각막링삽입술은전신마취하에시행되었다. 11 mm zone marker와 sinskey hook을이용하여중심표시를하였으며 incision and placement marker (IPM) 에잉크를묻혀표시해둔중심과맞추어절개축을표시한후 diamond knife로미리술전에결정한절개깊이로고정하여절개하였다. Pocketing hook을이용하여절개부위의바닥까지누른상태를유지하면서절개부위바깥쪽으로포켓을만들고 symmetric glide를이용하여포켓을넓혔다. Vacuum centering guide (VCG) 를삽입하고 450 mmbar의낮은압력으로눈을고정한후시계방향 dissector 를포켓에삽입하고 630 mmbar의높은압력으로변환한후시계방향으로천천히 dissector를돌려내측반경 6.0 mm, 외측반경 7.5 mm의 180도터널을만들었다. 반시계방향으로 dissector를삽입해동일한방법으로 180도터널을만들었다. 진공을풀고 VCG를제거한후양쪽터널로인택스링을삽입하고각막절개부위를 10-0 나일론으로한바늘봉합한후봉합사는각막실질내로묻었다. 대조군인전층각막이식술에서총 30안중 21안에서공여각막-수여부위크기차이는 0.25 mm였고, 평균차이는 0.24 ± 0.15 mm이었다. 각막링을삽입한환자군은술후 1개월동안 0.5% moxifloxacin (Vigamox, Alcon Laboratories, Fort Worth, Texas, USA) 점안액을하루 4회점안하였고술후 2주동안 1% prednisolone acetate (Pred Forte ; Allergan, Inc., Irvine, CA) 점안액을하루 4회점안한후 0.1% Fluorometholone (Ocumetholone, Samil, Korea) 을 1개월동안점안하였다. 봉합사는술후 1개월후제거하였다. 전층각막이식술을시행한대조군역시술후 2개월동안 0.5% moxifloxacin 점안액을하루 4회점안하였고술후 1% prednisolone acetate 점안액은환자의경과에따라점안기간및횟수를조정하여점안하였다. 검사항목은나안시력, 최대교정시력, 구면렌즈대응치, 각막지형도 (Orbscan II, Bausch and Lomb Inc., Rochester, NY, USA) 를이용한최대각막곡률값, 최소각막곡률값, 평균각막곡률값, 각막난시, K 3 mm IR, K 5 mm IR 등을측 정하여결과를비교하였다. Gold Standard Grading Scheme 10 에따라원추각막의진행정도를분류하였다. 수술전에비하여평균각막곡률값이 3D 이상증가한경우진행소견으로판정하였으며수술중혹은수술후합병증의유무를함께조사하였다. 술후전안부빛간섭단층촬영기 (Visante, Carl Zeiss Meditec, Dublin, CA, USA) 를이용하여각막링의각막실질내실제삽입깊이를 180도축으로잘라 3회측정하여평균값을구하였고, 링앞 (A) 과뒤 (B) 의잔여각막두께를측정하여 A 두께가 B 두께의 2배이상이되는경우를깊게삽입된군, A 두께가 B 두께의 2배미만이되는경우를얕게삽입된군으로나누어삽입두께에따른임상효과의변화를비교분석하였다 (Fig. 2). 난시벡터분석을시행하여각막링삽입전후난시변화를비교하였다. 11 M은 spherical equivalent, B는굴절오차에대한벡터크기이다. J 0 및 J 45 는각기준각도에서의 Jackson crossed cylinder of power이며각값에대한수식은다음과같다. M = S + C/2, J 0 = (-C/2)cos(2α), J 45 = (-C/2)sin(2α), B = (M 2 +J 2 0+J 2 45). 통계학적인분석은 SPSS (version 21.0, SPSS Inc., Chicago, IL, USA) 를이용하여 Wilcoxon signed rank test, independent student t-test, Mann-Whitney U-test로분석하였고, p 값이 0.05 미만인경우통계학적으로의미가있는것으로간주하였다. Figure 2. Anterior to the ring (A) and posterior to the ring (B) portion of corneal thickness was gathered using anterior segment optical coherence tomography. Deep group is defined if (A) is same or longer than doubled (B). Shallow group is defined if (A) is shorter than doubled (B). 501
- 대한안과학회지 2015 년제 56 권제 4 호 - 결과 수기인택스각막링삽입술을받은총 16명의환자중남자는 8명, 여자는 8명이었고, 평균연령은 27.69 ± 11.77세 (18-66세) 이었으며평균경과관찰기간은 17.44 ± 9.38개월이었다 (Table 1). 원추각막의진행정도는 Gold Standard Grading Scheme 10 을기준으로분석하였다. 총 16안중 5안은 severe, 9 안은 moderate 이었고나머지 2안은 mild이었으며이들의전체평균수치는 moderate 에해당하였다 (Supplementary Table 1). 술전최대교정시력은평균 logmar 0.55 ± 0.46 (logmar 0-2) 이었으며나안시력은평균 logmar 1.26 ± 0.47 (logmar 0.5-2) 이었다 (Fig. 3). 최대교정시력은각막링삽입후 3개월, 6개월, 12개월, 18개월각각 logmar 0.57 ± 0.33, 0.54 ± 0.41, 0.35 ± 0.20, 0.30 ± 0.10으로점차호전되는양상을보였으며나안시력도삽입후 3개월, 6개월, 12개월, 18개월각각 logmar 0.90 ± 0.41, 0.81 ± 0.59, 0.54 ± 0.30, 0.4 로호전되는양상이었다. 표본수가많은술후 3개월의나안시력은술전에비하여유의하게호전된양상을보였으나표본수가적은이외의경우에서는유의한차이가없었으며추후추가적인분석이필요할것으로생각한다. 술전평균구면렌즈대응치는 -12.63 ± 1.85D였으며술후 12개월째 7.00 ± 6.06D로유의하게호전되었다 (p=0.043, Wilcoxon Figure 3. Changes in UCVA and BCVA after Intacs implantation. The BCVA improved at postoperative 3 months. UCVA = uncorrected visual acuity; BCVA = best corrected visual acuity. * Wilcoxon signed rank test. Figure 4. Changes in spherical equivalent (SE) after intacs implantation. The SE was improved at postoperative 12 months. * Wilcoxon signed rank test. Table 1. Demographics of the patients Intacs PKP p-value * Total (n) 16 30 Mean age of Dx 22.20 ± 11.89 20.96 ± 10.18 0.726 Mean age of Tx 27.69 ± 11.77 27.10 ± 14.02 0.887 Sex (M:F) 8:8 17:13 0.674 Mean follow up (months) 17.44 ± 9.38 57.47 ± 34.96 0.000 BCVA (log MAR) 0.55 ± 0.46 1.71 ± 0.71 0.000 UCVA (log MAR) 1.26 ± 0.47 1.88 ± 0.61 0.001 SimK Max (diopter) 54.71 ± 6.98 56.34 ± 6.32 0.521 SimK Min (diopter) 48.91 ± 6.10 47.70 ± 8.06 0.648 SimK average (diopter) 51.81 ± 6.41 52.02 ± 7.02 0.935 SimK astigmatism (diopter) 5.80 ± 2.75 8.64 ± 3.54 0.022 K 3 mm IR (diopter) 7.10 ± 2.78 11.23 ± 3.64 0.003 K 5 mm IR (diopter) 7.58 ± 2.85 14.65 ± 3.77 0.000 Dsph (diopter) -10.50 ± 1.22-8.80 ± 5.34 0.261 Dcyl (diopter) -4.25 ± 2.47-5.33 ± 1.62 0.296 Spherical equivalent -12.63 ± 1.85-11.46 ± 5.03 0.660 Corneal opacity 0/16 22/30 Values are presented as mean ± SD unless otherwise indicated; Keratometry analysis excluded 17 eyes in PKP group who failed preoperative topography due to too steep cone; Refraction excluded 29 eyes in PKP group who failed preoperative refraction due to too severe irregular scissoring. PKP = penetrating keratoplasty; Dx = diagnosis; Tx = treatment; BCVA = best corrected visual acuity; UCVA = uncorrected visual acuity; SimK = simulated keratometry; K = keratometry; IR = irregular astigmatism. * Independent student t-test. 502
- 김지아외 : 각막링삽입술의임상성적비교분석 - Table 2. Statistical summary of the distribution of manifest refractive errors before and after Intacs ring insertion M J 0 J 45 B Before surgery -11.46 ± 5.03 0.30 ± 2.53-0.07 ± 1.32 11.87 ± 4.84 After surgery -6.90 ± 6.10-0.17 ± 1.39 0.52 ± 2.11 7.54 ± 5.83 p-value * 0.013 0.278 0.408 0.013 Values are presented as mean ± SD unless otherwise indicated; Power vector analysis (S = spherical diopters; C = cylindrical diopters; α = axis (degree), Power vector = (M, J 0, J 45)), M = S + C/2; J 0 = (-C/2)cos(2α); J 45 = (-C/2)sin(2α); B = (M 2 +J 2 0+J 2 45). M = spherical lens of power; J 0 = a Jackson crossed cylinder of power axes at 90 degrees and 180 degrees; J 45 = a Jackson crossed cylinder of power axes at 45 degrees and 135 degrees; B = the pythagorean length of the power vector, measure of overall blurring strength of a spherocylindrical lens or refractive error. * Wilcoxon signed rank test. Figure 5. Manifest astigmatism before surgery reduced on average following surgery. Each data point represents the astigmatism component of a power vector for one eye, referenced to the spectacle plane. J 0 = a Jackson crossed cylinder of power axes at 90 degrees and 180 degrees; J 45 = a Jackson crossed cylinder of power axes at 45 degrees and 135 degrees. Power vector analysis (S = spherical diopters; C = cylindrical diopters; α = axis (degree); J 0 = (-C/2) cos(2α); J 45 = (-C/2) sin(2α). Figure 6. Changes in Kmax, Kmin and Kastig after intacs implantation. All the values improved at postoperative 3 months. Kmax = Kmaximum; Kmin = Kminimun; Kastig = Kastigmatism. * Wilcoxon signed rank test. signed rank test, Fig. 4). 난시를 power vector analysis로살펴보면, 수술전 J 0 은 0.30 ± 2.53D, J 45 은 -0.07 ± 1.32D였으 며 M은 -11.46 ± 5.03D로 B값은 11.87 ± 4.84D이었다. 술후 1년뒤 J 0 은 -0.17 ± 1.39D, J 45 은 0.52 ± 2.11D로유의한 503
- 대한안과학회지 2015 년제 56 권제 4 호 - 변화는없었으나 M은 -6.90 ± 6.10D로결국모든벡터값을고려한 B값은 7.54 ± 5.83D (p=0.013, Wilcoxon signed rank test, Fig. 5, Table 2) 로유의한변화를보였다. 평균각막곡률은술전평균 51.81 ± 6.41D에서술후 3개월평균 45.13 ± 3.22D로감소하였으며 (p=0.028, Wilcoxon signed rank test, Fig. 6), 이후안정적인수치를보였다. 3 mm 범위부정난시는술전평균 7.10 ± 2.78D에서술후 3개월평균 9.30 ± 1.79D로증가하였고 (p=0.005, Wilcoxon signed rank test, Fig. 7) 이후점차감소하는양상을보였다. 각막링삽입깊이에따른술후결과를비교하기위하여깊게삽입된군은 6안, 얕게삽입된군은 9안이었다. 깊게삽입된군의평균경과관찰기간은 12.0달, 얕게삽입된군은 18.63달이었다. 깊게삽입된군에서평균각막곡률은술전 47.80 ± 5.17D에서술후평균 43.43 ± 3.25D로평균변화값이 -4.28D였으며얕게삽입된군의평균각막곡률은술전평균 54.73 ± 6.18D에서술후평균 46.24 ± 4.71D로 Figure 7. Changes in the irregular astigmatism of 3-mm and 5-mm area improved at postoperative 3 months. IR = irregular astigmatism. * Wilcoxon signed rank test. 평균변화값이 -8.49D였다. 이는통계적으로유의한차이를보였다 (p=0.020, Mann Whitney U test, Table 3). 대조군으로설정한각막이식수술을받은총 30명의환자중남자는 17명, 여자는 13명이었고, 수술시평균연령은 27.10 ± 14.02세 (10-51세) 이었으며평균경과관찰기간은 57.47 ± 34.96개월이었다 (Table 1). Gold Standard Grading Scheme 10 에따라원추각막의단계를분류하였으며 30안모두 severe 단계에해당되었다. 술전최대교정시력은평균 logmar 1.71 ± 0.71 (logmar 0.4-3.00) 이었으며나안시력은평균 logmar 1.88 ± 0.61 (logmar 0.82-3.00) 이었다. 평균구면렌즈대응치는 -11.46 ± 5.03D였으며평균각막곡률은평균 52.02 ± 7.02D이었다. 평균 SimK 난시는술전평균 8.64 ± 3.54D였고 3 mm 범위부정난시는술전평균 11.23 ± 3.64D이었다. 수술 1년뒤인택스링삽입술과전층각막이식술결과를비교하여보면최대교정시력이인택스링군에서는 logmar 0.32 ± 0.25, 전층각막이식군에서는 logmar 0.20 ± 0.16로각막이식군의시력이더좋았다 (p=0.030, independent student t-test, Table 4). 평균각막곡률은링삽입군에서 45.20 ± 4.17D, 이식군에서 48.02 ± 3.91D로링삽입군에서더작은곡률을보였다 (p=0.034, independent student t-test). 3 mm 범위부정난시는링삽입군에서 6.93 ± 2.46D이었고이식군에서 4.84 ± 2.01D로링삽입군에서더컸다 (p=0.007, independent student t-test). 술전과수술 1년뒤차이값을비교해보면최대교정시력변화값이인택스링군에서 logmar -0.23 ± 0.50, 전층각막이식군에서는 logmar -1.51 ± 0.69 로이식군에서더큰효과를보였다 (p=0.000, independent student t-test, Table 5). 평균각막곡률난시의변화값은링삽입군에서 -1.61 ± 2.07D, 이식군에서 -4.23 ± 3.53D이었으며 (p=0.022) 3 mm 범위부정난시와 5 mm 범위부정난 Table 3. Effect of insertion depth on the outcome Deep * (n = 6) Shallow (n = 9) p-value Mean F/U (months) 12.0 18.63 0.187 BCVA (log MAR) 0.39 0.31 0.527 BCVA (log MAR) -0.05-0.33 0.255 Kmax -4.52-9.57 0.008 Kmin -4.03-7.41 0.056 K average -4.28-8.49 0.020 Kastigmatism -0.48-2.16 0.139 IR 3 mm 0.62-0.78 0.061 IR 5 mm 1.58-0.49 0.069 Anterior to ring (A) and posterior to ring (B) portion of corneal thickness was gathered using anterior segment optical coherence tomography (OCT). f/u = follow-up; BCVA = best corrected visual acuity; Δ = delta, changed value; K = keratometry; Kmax = maximum K; Kmin = minimum K; IR = irregualar astigmatism. * Defined if A is same or longer than doubled B; Defined if A is shorter than doubled B; Wilcoxon signed rank test. 504
- 김지아외 : 각막링삽입술의임상성적비교분석 - Table 4. Results of Intacs insertion and PKP Intacs PKP p-value * Mean f/u (month) 10.88 ± 6.11 20.43 ± 25.01 0.000 BCVA (log MAR) 0.32 ± 0.25 0.20 ± 0.16 0.153 Dsph (diopter) -4.80 ± 5.82-3.35 ± 4.19 0.350 Dcyl (diopter) -4.41 ± 2.53-3.37 ± 1.93 0.138 Spherical equivalent -7.00 ± 6.06-5.04 ± 4.00 0.201 Kmax 47.29 ± 4.47 50.06 ± 3.88 0.037 Kmin 43.10 ± 4.06 45.98 ± 4.18 0.032 K average 45.20 ± 4.17 48.02 ± 3.91 0.030 K astigmatism 4.19 ± 1.86 4.08 ± 1.95 0.849 IR 3 mm 6.93 ± 2.46 4.84 ± 2.01 0.004 IR 5 mm 7.91 ± 2.27 8.21 ± 2.50 0.694 Values are presented as mean ± SD. PKP = penetrating keratoplasty; f/u = follow-up; BCVA = best corrected visual acuity; Kmax = maximum K; Kmin = minimum K; K = keratometry; IR = irregular astigmatism. * Independent student t-test. Table 5. Difference between before and after of Intacs insertion and PKP Intacs PKP p-value * BCVA (log MAR) -0.23 ± 0.50-1.51 ± 0.69 0.000 Dsph (diopter) 4.06 ± 5.34 6.00 ± 4.46 0.513 Dcyl (diopter) 1.00 ± 2.72 0.00 ± 3.35 0.536 Spherical equivalent 4.56 ± 5.73 6.00 ± 2.88 0.637 Kmax -7.42 ± 3.78-6.45 ± 7.46 0.654 Kmin -5.81 ± 3.15-2.22 ± 9.02 0.192 K average -6.62 ± 3.32-4.34 ± 8.09 0.356 K astigmatism -1.61 ± 2.07-4.23 ± 3.53 0.019 IR 3 mm -0.18 ± 1.45-5.92 ± 3.44 0.000 IR 5 mm 0.34 ± 2.22-6.13 ± 4.13 0.000 Values are presented as mean ± SD. PKP = penetrating keratoplasty; Δ = delta, changed value; BCVA = best corrected visual acuity; Kmax = maximum K; Kmin = minimum K; K = keratometry; IR = irregualar astigmatism. * Independent student t-test. 시도이식군에서더큰효과를보였다 ( 각각 p=0.000, independent student t-test). 수술후 1년경과시점에서인택스링군에서는수술전에비하여평균각막곡률값이더증가한경우가없었으며모든수술안에서각막곡률값이감소한소견이었다. 전층각막이식군에서는수술전에비하여평균각막곡률값이 3D 이상증가하여진행판정을받은경우가 13.3% 이었다. 술후경과관찰기간동안인택스링군의 70% (16안중 11안 ) 에서링주변으로각막실질침착물이발생하였으며, 이는진행하지는않았고, 동공부위를가리지않아시력에는영향이없었다 (Fig. 8A). 이외각막천공, 각막염, 각막링의위치이동, 심한이물감등의합병증은관찰되지않았다. 하지만 1 안에서링삽입부근처의신생혈관이발생하면서그부위각막두께가점차얇아져각막링노출의위험이있는것이술후 20개월에발견되어 (Fig. 8B, C) 각막링삽입 22개월만에링을제거하고각막이식을시행하였다. 전층각 막이식군에서거부반응은없었고, 1안에서창상부위상피세포군집이관찰되었으나진행하지는않았고, 14안에서수술후후낭하혼탁이발생하여이중 7안에서경과관찰중에백내장수술을시행하였다. 고찰 본연구결과는중등도원추각막의치료법으로각막링삽입술의결과는기존의보고와비슷하게효과가있음을확인하였으며, 링삽입의깊이가비교적얕은경우가효과가더있음을추가적으로알수있었다. 그러나각막이식결과와비교하였을때는시력교정및난시교정면에서아직각막이식의교정효과보다는부족함을확인하였다. 각막링삽입술은주변부에삽입된링이호-단축효과 (arcshortening) 로각막전면의만곡도를줄임으로써굴절값을줄이는원리로원추각막에적용되고있으며콘택트렌즈를 505
- 대한안과학회지 2015 년제 56 권제 4 호 - A B C Figure 8. Complications of intrastromal corneal ring insertion. Marginal precipitation of the ring (white arrow head) is observed (A). Overlying stromal thinning (white arrow head) developed after new vessel formation (black arrow head) (B and C). 착용하기힘들거나각막이식을하기에는진행이중등도이내여서부담이되는중심각막이투명한환자에서시도해볼수있는방법이다. 12,13 Colin et al 14 이 2000년원추각막의치료로인택스각막링의효과및안전성에대하여최초보고한이후여러논문에서효과적이라는결과가보고되고있다. 9,14,15 수기각막링삽입술에대한국내보고는케라링 (Keraring) 을삽입한경우와인택스링을삽입한두보고가 있으며, 각각술후 6개월측정시평균각막곡률이 42.83 ± 1.72D, 45.16 ± 2.25D였고, 난시값은 -2.50 ± 1.66D, -3.87 ± 2.02D였다. 본연구에서는인택스링삽입군의평균경과관찰기간이약 17.4개월로, 평균나안시력은 logmar 0.54 ± 0.30, 평균최대교정시력 logmar 0.32 ± 0.25, 평균구면렌즈대응치 7.00 ± 6.06D, 평균각막곡률값 45.20 ± 4.17D, power vector analysis를통한난시값변화는 B 값이 7.54 ± 5.83D 등으로앞의두결과에상응하게호전된결과를보여국외환자와비슷한정도로국내환자들도효과를보임을확인하였다. 각막링을삽입하는방법은수기로터널을만드는방식과펨토초레이저를이용한방식이있다. 16 Piñero et al 17 은원추각막환자 146안에서두가지방식을이용한경우시력및각막곡률결과가비슷하고, 수술후각막링의탈출및제거등의부작용이통계적으로차이가없음을보고하였다. 본연구에서는모든환자에서수기로터널을만드는방식을취하였다. 그러나수기로터널을만드는방식은펨토초레이저에비해터널이생성되는각막내깊이가예측깊이보다오차가있을수있기때문에, 삽입깊이에따른교정효과에차이가발생할가능성을주목하였다. 본연구에의하면, 인택스링의삽입깊이에따른효과는시력이나부정난시에서는차이가없었다. 하지만링을각막깊이의 2/3보다얕게삽입한군에서오히려깊게삽입한군보다최대곡률값과평균곡률값의변화가더크고, 이에따라더큰효과를보임을알수있었다. 보통각막깊이의약 70% 지점에링을삽입하는것이추천되고있으며이는각막층판의호- 단축효과 (arc-shortening) 가링을깊이넣었을때더큰효과를보이기때문으로설명되고있다. 술자들역시각막두께의 70% 보다더깊이삽입된군이효과가더클것을기대하고분석하였는데, 결과는예상과반대였다. 각막깊이의차이에따른효과비교연구는현재까지아직없기때문에정확한원인은확실하지않으나, 본연구에서의결과로추론해볼때, 각막의콜라겐이상대적으로치밀한앞쪽간질이상대적으로엉성한뒤쪽간질보다링의호-단축효과가더클가능성을고려할수있겠다. 따라서링삽입시각막깊이의 70% 보다깊이삽입하는것은추천되지않겠다. 마지막으로, 본연구에서는기존에중증이상원추각막의주된치료법으로시행되었던각막이식과각막링의효과를비교하고자하였다. 전층각막이식군의술전시력및각막곡률, 질병진행정도등기본적인환자상태가각막링삽입군보다훨씬심한분이많이포함되었기때문에, 모든지표의변화값으로비교한다면이식군에서더큰호전값을보일것이라는사실은충분히예상가능하다. 하지만, 결과적으로환자의시력예후가매우중요한데, 각막링삽입술 506
- 김지아외 : 각막링삽입술의임상성적비교분석 - 을시행한환자에서시력의개선이각막이식보다많이못미친다면환자의만족도및고비용을고려할때인택스링삽입술이각막이식의임시대치로활용하는것에회의가발생할수밖에없다. 본결과에따르면, 평균최대교정시력이각막이식군에서더좋았고, 3 mm 범위부정난시또한각막이식군에서더감소하였다. 이러한결과만고려한다면각막링삽입술을바로시행하기보다는각막이식을시행하는것이기회비용고려의측면에서는더나은선택일수있을것이다. 합병증측면에서는인택스링삽입군의 70% 에서링주변으로각막실질침착물이발생하였으며, 각막중심부까지침범하지는않고더이상진행하지않아기능적인이상을초래하지는않았으나일부환자에서미관상불편을언급하였다. 1안에서링삽입부근처의신생혈관이발생하면서신생혈관주위각막두께가점차얇아져각막링노출의위험이높아각막링을제거하고각막이식술을받았다. 즉, 인택스링삽입술은눈에 PMMA 제재가삽입되는것이므로 PMMA가비교적불활성한물질이라해도이물질에대한조직염증반응이일어날수있음을시사하며, 경과관찰시무증상염증이의심되면항염증치료를추가하는것이좋겠다. 합병증자체가각막이식의합병증보다는중증이아닐수있으나, 여전히이물질삽입에의한염증반응에따른합병증에서완전히면제될수없다는점에서유효성, 고비용과더불어판단할때원추각막에서각막링삽입술을시행할것인지표준치료인각막이식을시행할것인지는신중한선택이필요하다. 하지만본연구에서는대상군의수가적고경과관찰기간이짧아보다장기적인결과를제대로알수없다는한계점을지닌다. 본연구의제한점은각막링삽입군과각막이식군의수술전나안시력, 교정시력, 난시등의기본적인질병진행정도가달랐던점이다. 후향적으로이전에임상적으로치료된환자들을추적하는과정에서더진행되고, 각막혼탁이있는환자들이각막이식군의대상이된것으로분석되었다. 하지만윤리적으로비교적경한환자들을중한합병증이일어날수있는각막이식수술군에넣는것은문제가될수있으며임상적으로적용하기도어려운면을고려할때의미있는연구라생각한다. 또다른제한점으로두군의추적관찰기간이각막링삽입군에서 10.88 ± 6.11개월과각막이식군에서 20.43 ± 25.01개월로차이가있어각막이식군에서수술후충분한기간이경과하여더안정된결과를보였을가능성이있다는점이다. 하지만각막링삽입이링삽입을하고나서각막난시를바꿀만한추가조작이없는것에반하여각막이식군은수술후실밥을제거하는과정에서각막곡률에더많은변동을야기할수있으며이에대한보정을위하여수술후실밥을제거하고나서 1년이경과한환자들을대상 으로하였으므로이를고려하면비교가능한대조군이라생각한다. 향후더많은대상군에대해인택스각막링의효과와안전성에대한장기임상연구가필요할것으로생각한다. 최근, 각막링삽입술과리보플라빈크로스링킹을결합하여시력호전을개선하고각막굴절력및난시를감소시키려는시도가증가하고있어, 그결과를주목하고있으며이러한접근이성공한다면, 각막이식을대치하는수술의하나가될가능성이있겠다. 18 또한, 최근심부표층각막이식술이각막확장증에서많이시행되어좋은결과가보고되고있어이또한추가연구가필요하나효과적인치료방법으로기대되고있다. 19 결론적으로인택스링각막링삽입술은시력교정이나각막곡률값을감소시키는데에있어효과가있으나, 현재까지는그효과가각막이식과비교하여보았을때각막이식을대치하는수술로선택하기에는아직부족하다고판단된다. REFERENCES 1) Kenney MC, Brown DJ, Rajeev B. Everett Kinsey lecture. The elusive causes of keratoconus: a working hypothesis. CLAO J 2000; 26:10-3. 2) Troutman RC, Gaster RN. Surgical advances and results of keratoconus. Am J Ophthalmol 1980;90:131-6. 3) Wagoner MD, Ba-Abbad R, Al-Mohaimeed M, et al. Postoperative complications after primary adult optical penetrating keratoplasty: prevalence and impact on graft survival. Cornea 2009;28:385-94. 4) Wollensak G, Spoerl E, Reber F, Seiler T. Keratocyte cytotoxicity of riboflavin/uva-treatment in vitro. Eye (Lond) 2004;18:718-22. 5) Godoy CS, Wahab SA, Moreira H, et al. [Analysis of corneal curvature alteration following intrastromal corneal ring implantation: experimental study in rabbits]. Arq Bras Oftalmol 2007;70:303-11. 6) Kim EJ, Koo SH, Lee GJ, et al. The clinical results of Intacs(R) ring implantation by manual tunnel creation in patients with keratoconus. J Korean Ophthalmol Soc 2012;53:1756-65. 7) Kim HS, Lee TH, Lee KH. Intracorneal ring segment implantation for the management of keratoconus: short-term safety and efficacy. J Korean Ophthalmol Soc 2009;50:1505-9. 8) Torquetti L, Ferrara G, Almeida F, et al. Intrastromal corneal ring segments implantation in patients with keratoconus: 10-year follow-up. J Refract Surg 2014;30:22-6. 9) Siganos D, Ferrara P, Chatzinikolas K, et al. Ferrara intrastromal corneal rings for the correction of keratoconus. J Cataract Refract Surg 2002;28:1947-51. 10) McMahon TT, Szczotka-Flynn L, Barr JT, et al. A new method for grading the severity of keratoconus: the Keratoconus Severity Score (KSS). Cornea 2006;25:794-800. 11) Thibos LN, Horner D. Power vector analysis of the optical outcome of refractive surgery. J Cataract Refract Surg 2001;27:80-5. 12) Fleming JF, Wan WL, Schanzlin DJ. The theory of corneal curvature change with the Intrastromal Corneal Ring. CLAO J 1989; 15:146-50. 507
- 대한안과학회지 2015 년제 56 권제 4 호 - 13) Twa MD, Karpecki PM, King BJ, et al. One-year results from the phase III investigation of the KeraVision Intacs. J Am Optom Assoc 1999;70:515-24. 14) Colin J, Cochener B, Savary G, Malet F. Correcting keratoconus with intracorneal rings. J Cataract Refract Surg 2000;26:1117-22. 15) Torquetti L, Berbel RF, Ferrara P. Long-term follow-up of intrastromal corneal ring segments in keratoconus. J Cataract Refract Surg 2009;35:1768-73. 16) Coskunseven E, Kymionis GD, Tsiklis NS, et al. One-year results of intrastromal corneal ring segment implantation (KeraRing) using femtosecond laser in patients with keratoconus. Am J Ophthalmol 2008;145:775-9. 17) Piñero DP, Alio JL, El Kady B, et al. Refractive and aberrometric outcomes of intracorneal ring segments for keratoconus: mechanical versus femtosecond-assisted procedures. Ophthalmology 2009;116:1675-87. 18) Coskunseven E, Jankov MR 2nd, Hafezi F, et al. Effect of treatment sequence in combined intrastromal corneal rings and corneal collagen crosslinking for keratoconus. J Cataract Refract Surg 2009;35: 2084-91. 19) MacIntyre R, Chow SP, Chan E, Poon A. Long-term outcomes of deep anterior lamellar keratoplasty versus penetrating keratoplasty in Australian keratoconus patients. Cornea 2014;33:6-9. Supplementary Table 1. Keratoconus severity of the patients according to Gold Standard Grading Scheme Intacs PKP Mild keratoconus (n, %) 2 (12.5) 0 Moderate keratoconus (n, %) 9 (56.25) 0 Severe keratoconus * (n, %) 5 (31.25) 30 (100) PKP = penetrating keratoplasty. * Patients who failed preoperative topography due to too steep cone or preoperative refraction due to too severe irregular scissoring were classified as Severe. = 국문초록 = 원추각막및각막확장증에서각막링삽입술의임상성적비교분석 목적 : 원추각막및각막확장증에서인택스링을이용한각막링삽입술의임상성적을각막이식의임상성적과비교분석하고자하였다. 대상과방법 : 원추각막및각막확장증에서 2011 년부터 2013 년까지인택스링을삽입받고 3 개월이상추적관찰된 16 명의의무기록을후향분석하였다. 같은질환으로각막이식을받고 1 년이상추적관찰된 30 명과비교하여치료후시력 (logmar), 각막지형도의변화, 합병증을비교분석하였다. 링삽입군에서술후전안부빛간섭단층촬영으로측정한삽입깊이에따른교정효과의차이도비교분석하였다. 결과 : 수술 1 년뒤링군에서 logmar 교정시력은 0.32 로 0.20 인이식군에비하여낮게나왔고, 시력개선정도역시링군이 -0.23, 이식군이 -1.51 로링군이교정효과가작았다. 링군의술후각막곡률은평균 45.20 ± 4.17D 로이식군에비해더작은곡률을보였다. 3 mm 영역부정난시는 6.93D 로이식군보다컸다. 흔한합병증은링주변각막침착이 70% 이었으나시력에영향은없었다. 링삽입깊이가얕게삽입된군에서각막곡률이 -8.49D 감소하여깊게삽입된군보다효과가컸다. 결론 : 원추각막및각막확장증에서링삽입술은각막이식을대치할수는없으나교정효과가있었다. < 대한안과학회지 2015;56(4):499-508> 508