대한안과학회지 2015 년제 56 권제 8 호 J Korean Ophthalmol Soc 2015;56(8):1170-1180 ISSN 0378-6471 (Print) ISSN 2092-9374 (Online) http://dx.doi.org/10.3341/jkos.2015.56.8.1170 Original Article 과립형각막이상증에서굴절교정각막레이저절제술과백내장수술병합시행후임상결과 Clinical Outcomes of Combined Photorefractive Keratectomy and Cataract Surgery in Patients with Granular Corneal Dystrophy 류영주 1 김미금 1,2 위원량 1,2 Yung Ju Yoo, MD 1, Mee Kum Kim, MD, PhD 1,2, Won Ryang Wee, MD 1,2 서울대학교의과대학서울대학교병원안과학교실 1, 서울대학교의과대학서울대학교병원의생명연구원 2 Department of Ophthalmology, Seoul National University Hospital, Seoul National University College of Medicine 1, Seoul, Korea Biomedical Research Institute, Seoul National University Hospital, Seoul National University College of Medicine 2, Seoul, Korea Purpose: To evaluate the efficacy of combined photorefractive keratectomy (PRK) and cataract surgery in granular corneal dystrophy (GCD) patients with corneal stromal haziness compromising vision and cataract and clinically significant lens opacity. Methods: Medical records of 12 eyes that underwent PRK and cataract surgery between August 2009 and November 2013 in patients with GCD and cataracts were retrospectively evaluated. All PRKs were performed with the VISX S4 IR (VISX, Santa Clara, CA, USA). The double K SRK-T formula or double K Hoffer Q formula and postoperative corrected K were utilized to determine the intraocular lens power in patients with prior PRK. Postoperative best corrected visual acuity (BCVA), spherical equivalent, presence of the central island using topography analysis and recurrence of corneal opacity after combined PRK and cataract surgery were evaluated. Results: In all eyes, the PRK was successful and 3 eyes showed recurrence of corneal opacities without visual impairment during a mean follow-up of 36.6 months. The mean BCVA improved with an average increase of 4.63 lines (minimum 1 line, maximum 9 lines) and no patient showed any BCVA loss. Final spherical equivalent was -0.56 diopter (D) and the corneal central island was reported in only 1 eye. The Maloney method using the double-k formula with the SRK/T formula showed the lowest absolute error of 0.33 ± 0.25 D. Conclusions: Combined PRK and cataract surgery are effective methods for improving BCVA if patients with GCD have both visually significant diffuse corneal haze and clinically significant lens opacity. J Korean Ophthalmol Soc 2015;56(8):1170-1180 Key Words: Avellino corneal dystrophy, Cataract, Granular corneal dystrophy, Photorefractive keratectomy 제2형과립형각막이상증 (Granular corneal dystrophy type II; GCD II) 은 transforming growth factor (TGF)-beta와관 Received: 2014. 11. 21. Revised: 2015. 3. 31. Accepted: 2015. 6. 25. 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 련된 transforming growth factor, beta-induced (BIGH3) 유전자의 codon 124에서 arginine이 histidine으로바뀜으로써생기는, 우성유전되는돌연변이이다. 1,2 베트남, 일본그리고한국에서가장흔하게보고되는각막간질이영양증으로, 한국에서의유병률은 1/870으로추정된다. 3 이형접합자 (heterozygote) GCD II 환자는시간에따라각막혼탁이진행하며각막혼탁은진행정도에따라 3단계로나눌수있다. 초기소견은작은, 경계가명확한과립상의침착물이 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. 1170
- 류영주외 : 과립형각막이상증에서굴절교정각막절제술 - 각막상피하및각막전기질부위에생기다가, 이후선상또는성상의침착물이진행되며, 후기에는전반적인기질혼탁을보인다. 이형접합자의경우는연령이증가함에도불구하고좋은시력을유지하다가후기로진행하여과립상침착물사이의기질에도전반적인각막혼탁이진행하게되면시력에영향을미치게된다. 치료적표면절제술 (Phototherapeutic keratectomy; PTK) 은표층각막이형성증의치료로사용되어왔다. 4 비록 GCD II 환자에서굴절교정혹은치료적표면절제술후각막혼탁이재발한사례가보고되었지만, 5-7 PTK는시력저하를유발하는전간질의혼탁이있는환자에서각막이식을연기할수있다. 8 과립형각막이상증이동반된고령의환자에서전반적인중심부각막기질혼탁과백내장이나타나는경우, 백내장단독수술로는시력교정이어렵다. 엑시머레이저를이용한치료적표면절제술을병합하는경우각막혼탁의재발이젊은연령의환자보다노인환자에서비교적늦게, 경도로나타난다고알려져있어, 9,10 중심부간질혼탁이심한경우에백내장수술과병합치료로고려해볼수있겠다. 11 치료적표면절제술 (PTK) 을시행하게되면, 백내장수술시정확한인공수정체도수예측이기존의굴절교정각막레이저절제술 (Photorefractive keratectomy; PRK) 후백내장수술의도수예측보다어려울가능성이있는데, 중심융기가생길가능성이있어, 기존의근시교정각막굴절수술후백내장인공수정체도수공식으로는그오차가예측하기어려울가능성이있기때문이다. 그동안치료적표면절제술을시행한환자에서인공수정체도수측정에대한보고는 5예이하에서의성적이보고되는등드물게발표되었으며, 12 최근 Jung et al 13 이보고한 GCD II로진단받고치료레이저각막절제술후백내장수술을시행한 16명 20안후향분석에서는중심융기 (Central island) 유무에따라 hyperopic or myopic Haigis-L formula 를달리적용할수있으며, IOL Master 각막곡률이과소측정될경우 4.5-mm zone Holladay equivalent keratometry readings (EKRs) 를이용한 Haigis-L formula 사용을고려할수있다고보고하였으나, 아직확립된최적공식은밝혀지지않았다. 본연구에서는중심융기를최소화하기위해, 굴절교정각막레이저절제술 (Photorefractive keratectomy; PRK) 모드를이용하여각막간질의혼탁을제거하고자하였다. PRK 모드를사용하는경우원시는 PTK보다더높게발생할것이예상되었지만이는백내장수술로교정가능하다고판단하였다. 본연구의목적은과립형각막이상증의간질혼탁이심해백내장단독교정이시력호전에제한이있다고판단된환자에서 PRK 모드로교정시중심융기가적게발 생하고유의하게시력이호전됨을확인하는것으로, 그동안중심융기발생정도나백내장술후사용공식에따른오차정도등의임상경과가국내에보고가없기에, 12예의장기임상결과를보고하고자한다. 대상과방법 본연구는헬싱키선언을준수하여시행되었고, 서울대학교병원임상시험심사위원회의심의및후속승인 (No. H-1408-102-605) 을받았다. 2009년 8월부터 2013년 10월까지서울대학교병원안과각막외래에내원하여과립형각막이상증과백내장을진단받은환자중중심각막간질혼탁이심하여단순백내장수술만의시행으로는시력교정이어려울것으로판단된환자에한해, 백내장수술전후로엑시머레이저를이용한굴절교정각막레이저절제술을시행하고최소 8개월이상경과관찰된 7명 12안의의무기록을후향분석하였다. 시축을침범하는각막간질의혼탁깊이가 100 μm 이상되는환자나수술전각막두께가 500 μm 이하의환자, 안축장이 22.5 mm 이하이면서각막평균굴절력이 42D 미만의환자 ( 레이저시술후인공수정체도수가너무높아인공수정체를구하기어려울가능성이있음 ), 망막에황반변성또는망막전막이있는환자, 공막염또는포도막염병력자는굴절교정각막레이저절제술대상에서제외되었다. 세극등검사에서나타나는특징적인과립형혼탁의양상을기준으로과립형각막이상증으로진단받았으며환자가동의한경우유전자검사를통해 5q31 R124H mutation을확인하여 GCD II를확진하였다. 수술전검사에서시력은모두 logmar 시력표를사용하였다. 최대교정시력, 현성굴절검사, 자동각막굴절계 (KR-7100, Topcon, Tokyo, Japan) 를이용한굴절검사, 각막지형도 (Orb scan IIz, Bausch & Lomb, Rochester, NY, USA) 검사, IOL Master (IOL MASTER, Carl Zeiss Meditec, Dublin, CA, USA) 를이용하여안축장 (axial length, AXL), anterior segment optical coherence tomography (AS-OCT) (Visante; Carl Zeiss Meditec, Dublin, CA, USA) 를이용하여간질혼탁이분포한위치의각막깊이를확인하였다. 대상환자에서 PRK는동일한수술자 (K.M.K.) 에의해 VISX S4 (VISX Inc., Santa Clara, CA, USA) 로시행되었다. 상피는상피제거회전솔 (Amoils epithelial scrubber, Innovative excimer solution Inc., Toronto, ON, Canada) 을이용하여 8.5 mm 지름의넓이로기계적제거하였고, VISX S4 엑시머레이저를이용하여각막절제를시행하였는데, 레이저각막절제량은수술전 AS-OCT를사용하여측정 1171
- 대한안과학회지 2015 년제 56 권제 8 호 - Table 1. Variable methods to estimate postoperative expected keratometric values (K) shown in this study Method Using Pre-K Clinical history 20,27 Speicher (Seitz et al 28,29, Speicher 30 ) K = K PRE + SEQ CP K = 1.114 K TPO 0.114 K TPRE Comment Using Refractive change Savini et al 31 K = ([1.338 + 0.0009856 SEQ SP] 1)/(K POR/1,000) Camellin and Calossi 32 K = ([1.3319 + 0.00113 SEQ SP] 1)/(K POR/1,000) Jarade and Tabbara 33 K = ([1.3375 + 0.0014 SEQ CP] 1)/(K POR/1,000) Using Post-K Orb scan 0 mm total mean power 34 - Orb scan 2 mm total optical power 35 - Maloney central topography 36 K = 1.1141 K TPO-CTR 5.5 Koch and Wang 37 K = 1.1141 K TPO 6.1 Savini et al 38 K = 1.114 K TPO 4.98 Shammas et al 39 no history K = 1.14 K TPO 6.8 K = keratometry; Pre-K = pre-keratometry; K PRE = preoperative corneal power (in diopters); SEQ CP = spherical equivalent change, converted to corneal plane; K TPO = postoperative topographic simulated keratometry (Sim-K); K TPRE = preoperative topographic Sim-K; SEQ SP = spherical equivalent change, calculated in spectacle plane; K POR = average postoperative corneal power (in radius, mm); Post K = post-keratometry; K TPO-CTR = postoperative central topographic power. 된과립상침착물간간질혼탁의깊이를목표절제깊이 (targeted ablation depth) 로설정하고, 이를 Munnerlyn formula 를이용하여 6.5 mm 지름의광학부위및 1D의 blend zone (8.0 mm; 21.3 μm) 을병합하여치료도수 (targeted diopter; D) 를환산하여근삿값을입력하였다 ( 예 : {(D 1) (6.5 mm) 2 }/3 + {1.0 (8.0 mm) 2 }/3 = targeted ablation depth). 0.02% 농도의마이토마이신 (Mitomycin C, MMC) 을직경 6 mm의수술용스펀지 (Medtronic Solan, Jacksonville, FL, USA) 에적셔각막에 30-60초간접촉시킨뒤평형염액으로각막표면과결막낭에마이토마이신이남지않도록 40 ml 이상충분히세척하였다. 수술후곡률반경이 8.80 mm인 ACUVUE OASYS 880 (Johnson & Johnson Vision Care Inc., Jacksonville, FL, USA) 을치료용렌즈로사용하여, 재상피화가완전히될때까지착용시켰으며, 0.5% levofloxacin 점안액 (Cravit, Saten Pharm Co., Osaka, Japan) 은각막상피가치유될때까지, 0.18% sodium hyaluronate (Kynex2, Alcon Korea, Seoul, Korea) 는수술후 2달까지하루 4번사용하였다. 각막혼탁및퇴행을억제하기위해 0.1% fluorometholone (Flarex, Alcon, Fort Worth, TX, USA) 을 2달까지하루 4 번사용하였다. 환자가각막창상치유가종료되는 6개월동안원시상태로기다리기힘들다고한경우, 굴절교정레이저전에백내장수술을진행하였는데, 굴절교정레이저수술후원시가발생하는것을미리예측하여근시를남기거나, 레이저후인공수정체교환술을시행하였다. 굴절교정레이저후백내장수술을진행한경우는자동각막굴절계 (KR-7100, Topcon, Tokyo, Japan), IOL Master (IOL MASTER, Carl Zeiss Meditec), 그리고각막지형도검사 (Orb scan IIZ, Bausch & Lomb) 를사용하여안축장, 각막곡률및난시를측정하였다. 삽입할인공수정체의도수는기존에제시된각막곡률예측방법과인공수정체도수공식 (single K SRK/T, double K SRK/T, single K Hoffer Q, double K Hoffer Q) 을조합하여계산하였다. 인공수정체계산에는제조사에서제시한 A 상수를사용하였다. 인공수정체도수를결정할때는각막굴절교정수술전의각막곡률과각막굴절교정수술후각막지형도검사로측정한 2 mm zone의각막곡률값을 double K SRK/T 공식과 double K Hoffer Q 공식에대입하여구한수술후도수예측값이원시가아니면서, single K SRK/T, single K Hoffer Q 공식에대입하여구한수술후도수예측값이 -2.0D보다근시로예측되지않는인공수정체도수를취하였다. 만약수술전각막곡률값을알수없는경우에는 Double K 방식의 Pre-keratometry (Pre-K) 는 43.5로사용하였다. Table 1에서는각그룹별각막곡률값예측방법과공식을보여주고있다. 결과분석에서예측오차 (prediction error, PE) 는술전인공수정체도수공식으로계산한예상굴절력과술후측정한실제굴절력간의차이로측정하였고, 절대오차 (Absolute error, AR) 는예측오차의절대값으로측정하였다. 모든백내장수술은동일한수술자 (K.M.K.) 에의해표준적인초음파수정체유화술및후방인공수정체삽입술로시행되었다. ATLAS 9000 각막지형도 (Carl Zeiss Meditec, Dublin, CA, USA) 를이용하여 6 mm의 optical zone에서각 1172
- 류영주외 : 과립형각막이상증에서굴절교정각막절제술 - 막구면수차를확인하였으며, 수술전각막수차와인공수정체의구면수차를더하여계산한수술후예상구면수차가가장 0 μm에가까운인공수정체를선택하였다. 비구면인공수정체는백내장수술후각막의양의구면수차값을상쇄하여시기능을향상시키는효과를가지고있다. 수술전각막구면수차가 +0.200 μm 미만인경우, Acrysof SA60AT, +0.200 μm 이상인경우, Acrysof IQ 인공수정체를선택하는것을원칙으로했다. AcrySof IQ SN60WF 인공수정체는일체형형태의소수성아크릴재질로서후면이비구면표면을가짐으로써 -0.20 μm의음의구면수차값을가진다. 백내장수술후최종최대교정시력, 각막지형도검사, 현성굴절검사, 자동각막굴절계를이용한굴절검사, 구면대응치 (Spherical equivalent), 각막지형도상중심부융기 (central island) 유무, 각막침착물및혼탁의재발여부를관찰하였다. 중심부융기는각막지형도검사에서지름 1 mm 이상인각막중심부의각막곡률이주변각막보다 1.5D 이상더가파른경우로정의하였다. 과립형각막이상증의재발은세극등검사를통해기존의과립이외의추가과립이발생하거나각막간질의혼탁이다시발생하는것으로정의하여판정하였다. 통계학적인분석은술전과술후 logmar 시력차이를비교하기위하여 Wilcoxon 부호순위검정 (Wilcoxon signed rank test) 으로분석하였고, 인공수정체도수계산공식 (SRK/T, Hoffer Q) 간의예측도를비교하기위해대응표본 t-test (paired-sample t-test) 를사용하였으며절대오차의경우는 비모수검정인 Wilcoxon signed rank test를이용하였다. 통계분석은 SPSS (version 20.0, SPSS Inc., Chicago, IL, USA) 를이용하였다. p값이 0.05 미만인경우통계학적으로의미가있는것으로간주하였다. 결과 총 7명의대상환자의평균연령은 69.1 ± 8.1세 ( 범위 51.6-87.3세 ) 였으며남자 1명여자 6명이었다 (Table 2). 굴절교정각막레이저절제술후평균경과관찰기간은 28.0 ± 14.7개월이었으며, 4명 8안에서 26개월이상경과관찰하였고나머지 3명 4안에서 8개월이상경과관찰하였다. 7명중 4명이환자의동의하에유전자검사를통해 5q31 R124H 돌연변이의이형접합자 (Heterozygote) 임을확인하였다. 레이저를이용한평균전간질제거깊이는 77 ± 17 μm로목표굴절교정량은평균 -4.99 ± 1.05디옵터 (D) 였다. 12안모두수술전에비하여수술후최대교정시력이개선되었으며술후평균최대교정시력은 logmar 0.20 ± 0.12로술전교정시력과비교하여통계적으로유의하게호전되었고 (p=0.002), 시력감소는없었다 (Table 2). 원시교정안경만족도가높아인공수정체교환술을시행하지않은 2예를제외하고, 최종구면대응치는 -0.56 ± 1.12D였으며, 근시를남기는백내장술후레이저를한경우 (+1.00 ± 0.71D) 가레이저시행후백내장수술을진행한경우 (-1.17 ± 0.61D) 에비해원시경향을보였다 (Table 3). 12 Table 2. Demographics, visual outcomes and ablation depth of phototherapeutic keratectomy in patients with granular corneal dystrophy Patient Sex Age BCVA (log MAR) Visual gain Ablation Laser correction Laterality (years) Preoperative Postoperative 1 Postoperative 2 lines depths (um) (Diopter) A F 73.0 R 0.9 0.5 0.3 4 74-4.27 A * F 71.5 L 0.7 0.6 0.2 4 96-6.03 B F 71.2 R 1 0.4 0.3 4 75-5.6 B F 71.2 L 0.7 0.5 0.4 2 75-5.6 C M 64.2 R 0.4 0.2 0 6 66-3.82 C M 64.2 L 0.5 0.2 0 7 48-2.66 D F 69.4 R 1.2 0.7 0.4 5 96-6.03 D F 70.3 L 0.9 0.7 0.3 4 71-5.47 E F 67.6 R 0.9 1 0.1 7 96-5.6 E F 67.6 L 0.5 0.7 0.4 2 90-5.6 F F 51.6 L 0.4 0 0 6 88-5.16 G F 87.3 R 0.5 0 0.5 0 49-4.04 Mean SD 61.1 8.1 0.717 0.262 0.458 0.309 0.183 4.63 1.75 Postoperative 1 means BCVAs after first surgery and Postoperative 2 means BCVAs after second surgery. BCVA = best-corrected visual acuity; log MAR = logarithm of minimal angle of resolution; F = female; R = right; L = left; M = male; SD = standard deviation. * The left eye developed cystoid macular edema after cataract surgery (Irvine-Gass syndrome); The neodymium-doped yttrium aluminium garnet (Nd:YAG) laser posterior capsulotomy was performed for both eyes on April 21, 2011. 77 16.98-4.99 1.05 1173
- 대한안과학회지 2015 년제 56 권제 8 호 - Table 3. Ocular biometric parameters and refraction in patients with granular corneal dystrophy Case First operation Preoperative K (D) AXL (MASTER) Mean ACD (MASTER) Preoperative SE Hyperopic shift Final SE IOL power (D) Kinds of IOL A * PE & PCL 44.75 24.3 2.24 0.375 4.75-1.625 26 SA60AT A * PE & PCL 44.00 24.2 - -0.75 6.25-1.25 29 SA60AT B PE & PCL 45.00 26.4 - -6.375 5.75 0.125 21 SN60WF B PE & PCL 44.38 26.2 - -7 6.25 1.75 21 SN60WF C PE & PCL 42.63 24.1 3.32 1.75 4.5 0.75 26.5 SN60WF C PE & PCL 42.87 24.2 3.35 2.5 3.25 1.375 23.5 SN60WF D PRK 43.50 24.1 2.67-8.125-0.625 30 SN60WF D PRK 43.50 23.9 2.58-8.125-1.875 30 SN60WF E PRK 44.25 22.4 - - 7.25 NA 24 SN60WF E PE & PCL 44.63 22.5 - - 8.125 NA 23.5 SN60WF F PE & PCL 44.44 23.1 2.62-7.125-0.75 28.5 SA60AT G PRK 45.06 23.2 2.49 0.875 7.125-0.5 27 SA60AT Mean 44.08 23.6 2.75 1.08 6.46-0.56 27.56 SD 0.80 0.74 0.42 1.84 1.73 1.12 2.24 The number of patients included in Mean, SD n = 12 n = 12 n = 10 n = 7 n = 5 n = 10 n = 8 n = 8 K = keratometry; AXL = axial length; ACD = anterior chamber depth; SE = spherical equivalent; IOL = intra-ocular lens; PE & PCL = phacoemulsification and post chamber lens insertion; PRK = photorefractive keratectomy; NA = not applicable; SD = standard deviation. * Patients undergone intraocular lens exchange after PRK; The patients who failed in automatic refraction (AR) and manifest refraction (MR) for poor light streak, preoperatively, exclusion; Myopia (B); Myopia (B), The patients (who were) not taken IOL exchange operation after inserting IOL (which was) targeted for emmetropia (E). Table 4. Postoperative recovery and complication in patients with granular corneal dystrophy Patients Epithelial defect * Epithelial smoothening Central island Cornea opacity Duration till Final (days) (days) recurrence follow up (days) A 10 41 - - 248 A 10 24 - - 801 B 10 20 - - 1,004 B 10 20 - - 1,004 C 10 - - + 1,501 C 10 - - + 1,501 D 10 132 - + 843 D 12 52 - - 507 E 10 139 - - 1,328 E 3 132 + - 1,321 F 4 20 - - 248 G 10 55 - - 283 Mean 9.08 66.00 - - 882.42 SD 2.68 53.00 - - 476.65 SD = standard deviation. * The period taken for disappearing of the corneal erosions after laser surgery; The period taken for corneal surface smoothening after laser surgery; Definition: central area of steeper corneal tissue having increased refractive power, as seen on topography, which is surrounded by a flattened corneal region with reduced refractive power; The infective keratitis developed (or detected) at 28 days after laser surgery and recovered at 41 days after laser surgery. 안의안축장길이는평균 24.05 ± 1.19 mm였으며, 원시교정안경만족도가높아인공수정체교환술을시행하지않은 2안을제외한 10안에서인공수정체도수는평균 26.25 ± 3.23D였다. 엑시머레이저표면절제술시행후평균 9.1 ± 2.7일후각막표면미란이호전되었고, 평균 66.00 ± 53.00일이후전반적인각막표면의균질성이회복되었다 (Table 4). 2인 3안에서만레이저술이후불균질해진각막표면이회복되 1174
- 류영주외 : 과립형각막이상증에서굴절교정각막절제술 - A B C D E F Figure 1. Anterior segment photos of delayed wound healing after photorefractive keratectomy (PRK) in a granular corneal dystrophy patient. Slit lamp examination revealed diffuse corneal punctate epithelial erosion (A, D) 10 days after PRK. After applying bandage contact lens, the punctate epithelial erosion much decreased but irregular corneal surface remained (B, E) 1 month after PRK. Using topical fluorometholone 0.1%, antibiotics and artificial tears, corneal surface smoothing (C, F) occurred after 4 months. A B C D E F G H I Figure 2. (A, B, C) The preoperative anterior segment photography. (D, E, F) The postoperative anterior segment photography at day 3. (G, H, I) The postoperative 36-month anterior segment photography. (I) The anterior segment photography showing corneal opacity recurrence (white arrows) after laser surgery. This recurred cornea opacity did not affect the patients visual acuity. 1175
- 대한안과학회지 2015 년제 56 권제 8 호 - A B C D Figure 3. Representative (A) pre- and (B) post-operative photorefractive keratectomy photographs of the eye which showed central island postoperatively. Axial curvature maps after photorefractive keratectomy surgery (C) shows the central island 1 month after surgery. The topography (D) shows decrease of the central island postoperative 35 months. K = keratometry. 기위해 130일이상의시간이필요하였고, 나머지 9안모두에서 60일이내의시간이필요하였다 (Fig. 1). 인공수정체교환술시행후황반중심부부종이발생하여어바인- 가스증후군 (Irvine Gass syndrome) 을진단받은 1안외수술후망막이상소견은관찰되지않았다. 이환자에서황반중심부부종은점안비스테로이드항염증제치료후가라앉았다. 수술후평균 28.0 ± 14.7개월의추적관찰동안얕은간질혼탁의재발이 2명 3안에서발견되었다 (Table 4, Fig. 2). 평균발생시간은 36.6 ± 11.2개월이었고, 발생전후교정시력차이는없었다. 1안 (8.3%) 에서중심부융기가발생하였으나유의한시력저하는발생하지않았고, 경과관찰 35개월이후융기가많이줄어들었다 (Fig. 3). 각막굴절교정레이저술시행후백내장수술을한 4명 6 안에서인공수정체계산공식의오차를분석하여어떤공식이예측도가가장오차가적은지확인하고자하였다. 6안 의굴절교정수술전평균각막곡률은 44.21 ± 0.65D, 수술후평균각막곡률은 39.52 ± 2.06D, 그리고평균안축장의길이는 23.80 ± 0.53 mm였다. 예측오차는 Maloney method로구한각막굴절력값을대입한 double K Hoffer Q 공식을사용한경우 -0.07 ± 0.62D ( 범위 -0.77, 0.77D) 로가장작은오차를보였고, Maloney method로구한각막굴절력값을대입한 double K SRK/T 공식을사용한경우 -0.14 ± 0.41D ( 범위 -0.77, 0.32D) 로두번째로낮은오차를보였다. 절대오차의경우, Maloney method 로구한각막굴절력값을대입한 double K SRK/T 공식을사용한경우 0.33 ± 0.25D ( 범위 0.05, 0.77D) 로가장적은절대오차를보였고, Wang-Koch-Maloney로구한각막굴절력값을대입한 single K Hoffer Q 공식을사용한경우 0.49 ± 0.25D ( 범위 0.00, 0.68D) 로두번째로낮은오차를보였다 (Table 5). 1176
- 류영주외 : 과립형각막이상증에서굴절교정각막절제술 - Table 5. Mean prediction and absolute errors according to IOL power calculation methods in patients undergone cataract surgery after PRK Calculation method Methods to estimate postoperative expected K Prediction error (D) Absolute error (D) SRK/T double K Total mean power 2 mm -1.13 ± 0.63 (-2.06, -0.29) 1.13 ± 0.63 (0.29, 2.06) Wang-Koch-Maloney -0.75 ± 0.40 (-1.38, -0.30) 0.75 ± 0.41 (0.30, 1.38) Shammas and Shammas -1.27 ± 0.55 (-2.11, -0.45) 1.27 ± 0.55 (0.45, 2.11) Seitz -0.55 ± 0.42 (-1.24, 0.03) 0.56 ± 0.40 (0.03, 1.24) Maloney -0.14 ± 0.41 (-0.77, 0.32) 0.33 ± 0.25 (0.05, 0.77) Total mean power 0 mm -1.57 ± 1.11 (-3.30, -0.47) 1.58 ± 1.11 (0.47, 3.29) Hoffer Q double K Total mean power 2 mm -0.94 ± 0.76 (-2.09, 0.16) 0.99 ± 0.68 (0.16, 2.09) Wang-Koch-Maloney -1.08 ± 0.76 (-2.12, -0.00) 1.08 ± 0.76 (0.04, 2.12) Shammas -0.55 ± 0.61 (-1.38, 0.13) 0.59 ± 0.56 (0.11, 1.38) Seitz -0.35 ± 0.63 (-1.24, 0.49) 0.59 ± 0.36 (0.24, 1.24) Maloney -0.07 ± 0.62 (-0.77, 0.77) 0.53 ± 0.23 (0.15, 0.77) Total mean power 0 mm -1.39 ± 1.23 (-3.34, -0.03) 1.39 ± 1.23 (0.03, 3.34) Hoffer Q single K Total mean power 2 mm -0.31 ± 0.77 (-1.59, 0.71) 0.55 ± 0.59 (0.00, 1.59) Wang-Koch-Maloney +0.05 ± 0.59 (-0.68, 0.63) 0.49 ± 0.25 (0.00, 0.68) Shammas -0.45 ± 0.70 (-1.38, 0.56) 0.67 ± 0.43 (0.10, 1.38) Seitz -0.24 ± 0.59 (-0.55, 1.02) 0.51 ± 0.32 (0.17, 1.02) Maloney +0.62 ± 0.60 (-0.10, 1.22) 0.69 ± 0.51 (0.09, 1.22) Total mean power 0 mm -0.74 ± 1.22 (-2.76, 0.54) 0.92 ± 1.07 (0.07, 2.76) SRK/T single K Total mean power 2 mm +0.87 ± 0.81 (-0.65, 1.49) 1.09 ± 0.39 (0.65, 1.49) Wang-Koch-Maloney +1.17 ± 0.60 (0.15, 1.80) 1.17 ± 0.60 (0.15, 1.80) Shammas +0.75 ± 0.51 (-0.06, 1.22) 0.77 ± 0.47 (0.06, 1.22) Seitz +1.33 ± 0.51 (0.46, 1.84) 1.33 ± 0.51 (0.46, 1.84) Maloney +1.64 ± 0.61 (0.61, 2.28) 1.64 ± 0.61 (0.60, 2.28) Total mean power 0 mm +0.51 ± 1.21 (-1.65, 1.63) 1.07 ± 0.65 (0.03, 1.65) Values are presented as mean ± SD (range). IOL = intra-ocular lens; PRK = photorefractive keratectomy; K = keratometry. 인공수정체도수계산공식별예측오차는 double K SRK/T 공식을사용한경우평균 -0.90 ± 0.76D ( 범위 -3.29, 0.32D) 로실제수술후도수보다근시로예측되는경향이있었고, single K SRK/T 공식은평균 1.04 ± 0.79D ( 범위 -1.65, 2.28D) 로실제수술후도수보다원시로예측되는경향이있었다. Double K SRK/T 공식의경우다른 3가지측정공식과비교하여유의하게근시로예측되는경향이있었고, double K Hoffer Q 공식은 Single K SRK/T, Single K Hoffer Q보다유의하게근시로예측되는경향이있었다. 각공식별로공식별절대오차를비교한비모수검정에서는 Single K Hoffer Q 공식을사용한경우 0.63 ± 0.56 D ( 범위 0, 1.59D) 로다른 3가지측정공식과비교하여유의하게낮은절대오차를보였다. 고찰 본연구는과립형각막이상증의간질혼탁이심해백내장단독교정이시력호전에제한이있다고판단된환자에서굴절교정레이저각막절제술모드로교정시중심융기가적게발생하고, 시력교정효과도있음을확인하였다. 과립형각막이상증환자에서전반적인간질의혼탁과과립침착물은보우만층근처에위치하는반면, 격자형침착물은보우만층에서 65.4 ± 48.0 μm 떨어져위치하는것이보고된바있다. 14 또한간질혼탁, 과립형침착물, 그리고격자형침착물은각각 47.7 ± 10.2, 91.3 ± 39.5, 그리고 313 ± 71.4 μm로간질혼탁은세종류의침착물중가장표면에위치하면서두께가얇은것또한보고되었다. Jung et al 10 은전반적인간질혼탁이시축을포함하는중심부에분포하므로과립형각막이상증환자에서시력저하에중요한영향력이있을것이라하였다. 본연구를통해전반적인각막간질의혼탁은평균 80.5 um 깊이를굴절교정레이저각막절제술로절제하여제거할수있고, 깊은층에위치하는과립형침착물은완전히제거되지않더라도시축을막지않는다면시력호전을제한하지않는다는것을알수있었다. 과립형각막이상증환자에서라식후각막혼탁이증가되는증례가보고되면서, 굴절교정술은금기시되어왔다. 5,6,15,16 Awwad et al 16 은제2형과립형각막이상증으로진단된 28세여자환자가라식후 12개월만에재발한사례를보고하였다. Inoue et al 5 은이형접형자인 GCD II 환자 4명 7안에서재발까지 38.4 ± 6.2개월이걸렸다고보고하였고, 환자들의 1177
- 대한안과학회지 2015 년제 56 권제 8 호 - 나이는평균 66세였다. 최근 Jung et al 10 은평균 61.4세환자 22명 29안에서평균 43.4 um 깊이로 PTK를시행하여 6 개월에서 40개월의추적관찰기간동안재발없이통계적으로유의한시력향상을유지하는것을보고하였다. 본연구에서도평균 69.08 ± 8.1세환자 7명 12안중 3안에서재발이발견되었고 (25%), 평균 36.59개월 (32.92개월, 49.21개월, 27.64개월 ) 추적관찰후재발이확인되었다. 이는발생기간이나발생빈도가기존의보고와유사하며, 장기적인관찰이필요한부분이다. 7명 9안은평균 24.86개월의추적관찰기간동안재발없이최대교정시력의유의한향상이유지되었으며 12안모두추가적인굴절교정레이저각막절제술이필요하지않았다. 즉기존연구와동일하게, 레이저시술후의간질의혼탁재발을예측할수있으나젊은연령과는다르게, 백내장발생하는고령에서는재발해도그혼탁의정도가경미해현재추적관찰시점까지는시력에큰영향을미치지않았다. 이러한점은젊은연령에서치료적각막절제술이금기시되는점과다르게, 고령에서백내장수술이필요한환자에서는치료적목적으로엑시머레이저각막절제술의사용을고려해도되는근거가될수있다. 그러나좀더장기추적을통해시력을방해할정도로혼탁이진행할지를관찰하여야겠다. 현재까지 20가지이상의방법이굴절교정술을받은눈에서인공수정체도수계산의정확도를높이기위해고안되었다. 17-23 Wang et al 24 은굴절교정수술전 K 값을사용하지않고수술후측정값과굴절도수변화값을사용하여굴절교정수술후보정각막곡률값을예측하는여러방법이절대오차가통계적으로유의하게낮음을보여주었다. 또한 Wang et al 22 은 Maloney 방법으로예측된각막곡률값을적용한 Double K (SRK-T, Holladay, Hoffer Q) 가가장낮은예측오차를보이는방법이라고제안하였고, Shammas and Shammas 23 는 Shammas method와 Shammas-post-LASIK (PL) formula를사용하였을때가장작은평균예측오차를보고하였다. Wang et al 24 의보고는 Maloney method로구한각막굴절력값을대입한 double K SRK/T 공식을사용한경우가장낮은예측오차와절대오차를보인본연구의결과에부합한다. Lee et al 25 은평균 27.82 mm의안구축을가진환자들에서굴절교정술후인공수정체도수계산법간의예측도를비교하였을때각막곡률산출법은변형 Maloney 방법보다정확도를의미하는절대예측오차가가장작은값을보여예측도가가장좋다고하였다. Yun et al 26 은굴절교정수술시행전현성굴절검사가 -4.03 ± 1.90D 로중등도의근시를보이는환자를대상으로굴절교정수술전자료가없을경우, IOL Master version 5.02 (Carl Zeiss Meditec) 에포함된 Haigis-L method로비교적정확한인공 수정체도수를얻을수있다고보고하였다. 현재까지각막굴절교정수술후백내장수술진행시인공수정체도수결정의 standard가완전히확립되어있지는않으나위에제시된방법들이비교적많이사용하는방법이다. 27-39 그리고본연구의결과는중심부융기의발생이높지않기때문에기존의엑시머레이저굴절수술후백내장수술시일반적으로사용하는보정 IOL power 계산식이굴절교정각막절제술을시행한과립형각막이상증환자백내장수술후에도인공수정체도수결정에도비슷하게적용될수있음을보여준다. 한편 Jung et al 13 은 PTK를시행한과립형각막이상증환자를각막지형도검사에서보이는각막표면의형태에따라세그룹으로나누어각그룹별로평균절대오차가가장낮은공식이다르다는것을보여주었다. 치료레이저각막절제술후발생할수있는중심부융기가있는환자는각막이중심축위아래로길어진형태 (prolate shaped cornea) 로원시교정엑시머레이저굴절교정술 (Hyperopic excimer laser refractive surgery) 을시행한환자의각막과유사한형태를보이고, hyperopic Haigis-L formula가가장예측도가뛰어나다고보고하였다. 13 이와다르게본연구에서는중심부융기발생이기존연구보다낮으므로 ( 중심부융기발생률 8.3%) 근시교정라식수술을한환자들에게통상적으로적용하는예측식 (Maloney method로구한각막굴절력값을대입한 double K SRK/T 공식방법 ) 으로좋은예측도를보여주었다. 따라서 PTK를시행한경우보다 PRK로시행한경우가기존공식으로좀더술후예측이용이하여덜복잡할가능성을시사한다. 그러나본연구에서는인공수정체회사에서제공한 A 상수를적용한결과이므로, SRK/T 공식적용시 A상수의영향을무시할수없으므로각시설과수술자에따라제조사 A상수대신에보정 A상수를사용한다면결론이달라질수있다. 본연구는연구대상이백내장과굴절레이저각막절제술을모두시행한경우로제한하였기때문에환자수가적다는단점이있고, 이로인해인공수정체계산공식의오차를분석하는데에제한점이있으며, 또후향적으로분석하였다는제한점이있다. 따라서과립형각막이상증환자에서백내장수술시 PRK 또는 PTK의술후인공수정체예측도에미치는영향을뚜렷하게확인하기위해서는향후대규모전향적연구가필요할것으로생각된다. 또한가지 PRK를이용한각막교정술은 PTK를이용한경우보다원시가좀더높게발생하기때문에안축장이너무짧거나각막이너무편평한환자의경우는차후고굴절의인공수정체도수가필요하게되는데, 이도수가생산이안될가능성이있기때문에미리술전에이점을파악하여짧은안축장과편평한각막의환자는시술대상에서제외해야하는단점 1178
- 류영주외 : 과립형각막이상증에서굴절교정각막절제술 - 이있다. 결론적으로백내장이동반된과립형각막이상증환자에서각막간질혼탁이심해백내장단독수술의효과가시력회복을도모하기부족할것으로판단되는경우, 굴절교정각막레이저술의병합시행을고려할수있으며, 이는중심부융기가적어술후인공수정체도수예측에교란변수가감소하므로, 치료적각막절제술의대안으로이용될수있다. REFERENCES 1) Klintworth GK. Advances in the molecular genetics of corneal dystrophies. Am J Ophthalmol 1999;128:747-54. 2) Ferry AP, Benson WH, Weinberg RS. Combined granular-lattice ('Avellino') corneal dystrophy. Trans Am Ophthalmol Soc 1997; 95:61-77. 3) Lee JH, Cristol SM, Kim WC, et al. Prevalence of granular corneal dystrophy type 2 (Avellino corneal dystrophy) in the Korean population. Ophthalmic Epidemiol 2010;17:160-5. 4) Rapuano CJ. Excimer laser phototherapeutic keratectomy. Int Ophthalmol Clin 1996;36:127-36. 5) Inoue T, Watanabe H, Yamamoto S, et al. Recurrence of corneal dystrophy resulting from an R124H Big-h3 mutation after phototherapeutic keratectomy. Cornea 2002;21:570-3. 6) Lee JH, Stulting RD, Lee DH, et al. Exacerbation of granular corneal dystrophy type II (Avellino corneal dystrophy) after LASEK. J Refract Surg 2008;24:39-45. 7) Yi JH, Ha BJ, Kim SW, et al. The number of cases, cause and treatment of avellino corneal dystrophy exacerbated after LASIK. J Korean Ophthalmol Soc 2008;49:1415-24. 8) Kim EK. PTK in corneal dystrophy. Cornea 2004;23:323-4. 9) Reddy JC, Rapuano CJ, Nagra PK, Hammersmith KM. Excimer laser phototherapeutic keratectomy in eyes with corneal stromal dystrophies with and without a corneal graft. Am J Ophthalmol 2013; 155:1111-8.e2. 10) Jung SH, Han KE, Stulting RD, et al. Phototherapeutic keratectomy in diffuse stromal haze in granular corneal dystrophy type 2. Cornea 2013;32:296-300. 11) Ishikawa T, Hirano A, Inoue J, et al. Trial for new intraocular lens power calculation following phototherapeutic keratectomy. Jpn J Ophthalmol 2000;44:400-6. 12) Ishikawa T, Hirano A, Murai K, et al. Intraocular lens calculation for cataract treated with photorefractive keratectomy using ray tracing mathod. Jpn J Ophthalmol 2000;44:575. 13) Jung SH, Han KE, Sgrignoli B, et al. Intraocular lens power calculations for cataract surgery after phototherapeutic keratectomy in granular corneal dystrophy type 2. J Refract Surg 2012;28:714-24. 14) Hong JP, Kim TI, Chung JL, et al. Analysis of deposit depth and morphology in granular corneal dystrophy type 2 using fourier domain optical coherence tomography. Cornea 2011;30:729-38. 15) Lee WB, Himmel KS, Hamilton SM, et al. Excimer laser exacerbation of Avellino corneal dystrophy. J Cataract Refract Surg 2007;33:133-8. 16) Awwad ST, Di Pascuale MA, Hogan RN, et al. Avellino corneal dystrophy worsening after laser in situ keratomileusis: further clinicopathologic observations and proposed pathogenesis. Am J Ophthalmol 2008;145:656-61. 17) Walter KA, Gagnon MR, Hoopes PC Jr, Dickinson PJ. Accurate intraocular lens power calculation after myopic laser in situ keratomileusis, bypassing corneal power. J Cataract Refract Surg 2006; 32:425-9. 18) Masket S, Masket SE. Simple regression formula for intraocular lens power adjustment in eyes requiring cataract surgery after excimer laser photoablation. J Cataract Refract Surg 2006;32:430-4. 19) Holladay JT, Hill WE, Steinmueller A. Corneal power measurements using scheimpflug imaging in eyes with prior corneal refractive surgery. J Refract Surg 2009;25:862-8. 20) Hoffer KJ. Intraocular lens power calculation for eyes after refractive keratotomy. J Refract Surg 1995;11:490-3. 21) Feiz V, Mannis MJ, Garcia-Ferrer F, et al. Intraocular lens power calculation after laser in situ keratomileusis for myopia and hyperopia: a standardized approach. Cornea 2001;20:792-7. 22) Wang L, Booth MA, Koch DD. Comparison of intraocular lens power calculation methods in eyes that have undergone LASIK. Ophthalmology 2004;111:1825-31. 23) Shammas HJ, Shammas MC. No-history method of intraocular lens power calculation for cataract surgery after myopic laser in situ keratomileusis. J Cataract Refract Surg 2007;33:31-6. 24) Wang L, Hill WE, Koch DD. Evaluation of intraocular lens power prediction methods using the American Society of Cataract and Refractive Surgeons Post-Keratorefractive Intraocular Lens Power Calculator. J Cataract Refract Surg 2010;36:1466-73. 25) Lee MO, Chung TY, Chung ES, Kee CW. Comparison of intraocular lens power calculation methods for cataract surgery after refractive surgery: a retrospective surgery. J Korean Ophthalmol Soc 2010;51:180-7. 26) Yun YJ, Kwang JY, Choi SH. Intraocular lens power calculation using Haigis-L method after corneal refractive surgery. J Korean Ophthalmol Soc 2010;51:664-9. 27) Holladay JT. Consultations in refract surgery. Refract Corneal Surg 1989;5:202-3. 28) Seitz B, Langenbucher A. Intraocular lens power calculation in eyes after corneal refractive surgery. J Refract Surg 2000;16:349-61. 29) Seitz B, Langenbucher A, Nguyen NX, et al. Underestimation of intraocular lens power for cataract surgery after myopic photorefractive keratectomy. Ophthalmology 1999;106:693-702. 30) Speicher L. Intra-ocular lens calculation status after corneal refractive surgery. Curr Opin Ophthalmol 2001;12:17-29. 31) Savini G, Barboni P, Zanini M. Intraocular lens power calculation after myopic refractive surgery: theoretical comparison of different methods. Ophthalmology 2006;113:1271-82. 32) Camellin M, Calossi A. A new formula for intraocular lens power calculation after refractive corneal surgery. J Refract Surg 2006;22:187-99. 33) Jarade EF, Tabbara KF. New formula for calculating intraocular lens power after laser in situ keratomileusis. J Cataract Refract Surg 2004;30:1711-15. 34) Arce CG, Soriano ES, Weisenthal RW, et al. Calculation of intraocular lens power using Orbscan II quantitative area topography after corneal refractive surgery. J Refract Surg 2009;25:1061-74. 35) Qazi MA, Cua IY, Roberts CJ, Pepose JS. Determining corneal power using Orbscan II videokeratography for intraocular lens calculation after excimer laser surgery for myopia. J Cataract Refract Surg 2007;33:21-30. 1179
- 대한안과학회지 2015 년제 56 권제 8 호 - 36) Smith RJ, Chan WK, Maloney RK. The prediction of surgically induced refractive change from corneal topography. Am J Ophthalmol 1998;125:44-53. 37) Koch DD, Wang L. Calculating IOL power in eyes that have had refractive surgery. J Cataract Refract Surg 2003;29:2039-42. 38) Savini G, Barboni P, Zanini M. Correlation between attempted correction and keratometric refractive index of the cornea after myopic excimer laser surgery. J Refract Surg 2007;23:461-6. 39) Shammas HJ, Shammas MC, Garabet A, et al. Correcting the corneal power measurements for intraocular lens power calculations after myopic laser in situ keratomileusis. Am J Ophthalmol 2003;136:426-32. = 국문초록 = 과립형각막이상증에서굴절교정각막레이저절제술과백내장수술병합시행후임상결과 목적 : 백내장이합병된과립형각막이상증환자중각막침착물사이의간질이혼탁하여백내장수술만으로는시력교정이어려운환자에서, 굴절교정각막레이저절제술을병합시행한 12 예의임상효과를보고하고자한다. 대상과방법 : 과립형각막이상증과백내장을진단받은환자중간질혼탁이심해백내장수술만으로교정이어려운환자에서굴절교정각막레이저절제술을시행하고전후로백내장수술을병합한 7 명 12 안의의무기록을후향분석하였다. VISX S4 IR (VISX, Santa Clara, CA, USA) 을이용하여, 전간질을제거하였다. 레이저후에백내장수술을시행한경우는보정각막곡률값 (keratometry, K) 과 double K SRK/T 또는 double K Hoffer Q 공식을이용하여인공수정체도수를결정삽입하였다. 최종시력증가, 구면대응치값, 각막지형도상중심부융기유무, 혼탁의재발을분석하였다. 사용한보정각막굴절력값과수정체공식의예측오차및절대오차를분석하였다. 결과 : 평균 36.6 개월의추적관찰동안 3 안에서시력에영향을미치지않는각막간질혼탁이재발하였다. 술후평균최대교정시력은 logmar 0.18 로술전교정시력에비해평균 4.63 줄의호전이있었고, 시력감소는없었다. 최종구면대응치는 -0.56 디옵터 (D) 였다. Maloney method 로구한각막굴절력값을대입한 double K SRK/T 공식을사용한경우 0.33 ± 0.25D 로가장적은절대오차를보였다. 결론 : 백내장이동반된과립형각막이상증환자에서각막간질혼탁이심한경우, 치료적목적의엑시머레이저굴절교정각막레이저절제술병합시행은도움이될수있음을시사하였다. < 대한안과학회지 2015;56(8):1170-1180> 1180