대한안과학회지 2014 년제 55 권제 8 호 J Korean Ophthalmol Soc 2014;55(8):1174-1179 pissn: 0378-6471 eissn: 2092-9374 http://dx.doi.org/10.3341/jkos.2014.55.8.1174 Original Article 정상안압녹내장에서당뇨유무에따라분석한안토시아노사이드, 은행잎추출물의치료효과 The Effect of Anthocyanoside and Ginkgo Biloba Extract on Normal-Tension Glaucoma According to Presence of Diabetes 이용우 최철영 배정훈 김준모 Yong Woo Lee, MD, Chul Young Choi, MD, Jeong Hun Bae, MD, Joon Mo Kim, MD 성균관대학교의과대학강북삼성병원안과학교실 Department of Ophthalmology, Kangbuk Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Purpose: This study was performed to evaluate the effect of anthocyanoside and ginkgo biloba extract (GBE) in patients with normal tension glaucoma (NTG), according to the presence of diabetes mellitus (DM). Methods: A chart review of patients with normal tension glaucoma was retrospectively analyzed. All patients underwent a Humphrey visual field (HVF) test and logarithm of the minimal angle of resolution best-corrected visual acuity (log MAR BCVA) was measured over a 6 months period. Changes in mean deviation (MD), pattern standard deviation (PSD) of visual field and log MAR BCVA were compared among anthocyanoside, GBE and no medication (control) groups. Patients were divided according to the presence of DM. Results: A total of 406 NTG patients, including 151 DM patients, were included in the present study. MD was improved in the anthocyanoside and GBE groups, but not in the control group. PSD was not significantly different in all groups. BCVA was improved in the anthocyanoside group, but deteriorated in the control group. The results were similar in patients with or without DM. The generalized linear model demonstrated that systemic medication affected changes in visual indices. Conclusions: The results from the present study suggest that anthocyanoside and GBE may be helpful for improving visual function in some patients with NTG regardless of their DM status. J Korean Ophthalmol Soc 2014;55(8):1174-1179 Key Words: Anthocyanoside, Diabetes mellitus, Ginkgo biloba extract, Normal tension glaucoma 정상안압녹내장은정상범위의안압에도불구하고특징적인녹내장성시신경손상과시야결손이있는녹내장의 Received: 2014. 2. 14. Revised: 2014. 3. 24. Accepted: 2014. 7. 17. Address reprint requests to Joon Mo Kim, MD Department of Ophthalmology, Kangbuk Samsung Medical Center, #29 Saemunan-ro, Jongno-gu, Seoul 110-746, Korea Tel: 82-2-2001-2250, Fax: 82-2-2001-2262 E-mail: kjoonmo@dreamwiz.com * This research was supported by the Medical Research Funds from Kukje Pharma Ind. Co., Ltd. 한형태이다. 1 정확한병인이나기전은아직밝혀지지않았지만상대적으로높은안압에의해생긴다는기계적이론과혈류의감소로생긴다는허혈성이론이제시되고있다. 2 하지만안압강하제를통하여안압을하강시켜준후에도일부환자에서는녹내장성시야결손이진행되는경우가있기때문에최근에녹내장치료에있어서다른방면으로의접근이대두되고있다. 3-6 당뇨에있어서반응성산소의과도한생성및불완전한정화는안과적영역에서도다양한질환에중요한역할을할것이라고생각되고있다. 7-9 녹내장에있어서도당뇨는위험인자로고려되고있으며, 정확한기전은밝혀지지않 c2014 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. 1174
- 이용우외 : 안토시아노사이드와은행잎추출물의효과 - 았으나생화학적경로의변화나산화스트레스증가, 혈관내피세포의자가조절능력장애등이가능한기전으로제안되고있다. 10,11 최근 Bilberry 의추출물의주성분인 Anthocyanoside나은행잎추출물 (Ginkgo biloba extract, GBE) 제제의복용이녹내장환자에서시기능의개선에도움이된다는보고가있었다. 6,12 하지만과거의연구들에서는녹내장환자들의시기능개선에있어서 Anthocyanoside나 GBE의효과를전신질환에따라나누어분석한보고는없었다. 녹내장환자들의치료에상기제제들을사용할때당뇨등의전신질환여부가또하나의고려해야할요소가될수있다. 이에저자들은 Anthocyanoside나 GBE를복용한정상안압녹내장환자들의임상경과를당뇨유무에따라나누어분석해보았다. 대상과방법 본연구는강북삼성병원연구윤리심의위원회의승인을거쳐진행하였다. 2005년 1월부터 2013년 12월까지강북삼성병원안과외래에내원한정상안압녹내장환자를대상으로후향적의무기록분석을시행하였다. 양안에정상안압녹내장을진단받은경우우안을대상으로선정하였다. 모든환자는초진시내과적, 안과적병력청취및교정시력, 전안부및안저검사, 앞방각검사, 험프리자동시야검사, Red-free 시신경섬유층촬영, 입체시신경촬영, 빛간섭단층촬영을시행하였다. 모든환자에게서이완기, 수축기혈압과공복혈당을측정하였고, 고혈압이나당뇨를진단받지않은환자중혈압이나공복혈당이정상범위가아닌경우에는순환기내과혹은내분비내과전문의에게의뢰하여고혈압이나당뇨여부를결정하였다. 골드만압평안압계를이용하여오전 9시에서오후 5시사 이에 2시간간격으로측정한안압이 1회라도 21 mmhg 이상이거나, 스넬렌시력으로 0.6 이하인경우, 당뇨망막병증을포함한활동적안질환이있는경우, 유리체내약물주사를포함한안과적수술력이있거나시야검사에협조가안되는경우는제외하였다. 12개월이상경과관찰을하지않았거나적절한병력청취, 시력검사, 시야검사가시행되지않은환자도제외하였다. 총 406명의환자가포함되었으며이중당뇨를진단받지않은환자는 255명, 당뇨를진단받은환자는 151명이었다. 두군을전신약제복용여부에따라타겐- 에프 정 (Vaccinium myrtillus extract 170 mg/t, 국제약품 ) 을 1정씩하루 2회복용한 anthocyanoside군, 기넥신 -에프 정 (Gingko biloba extract 80 mg/t, SK케미칼 ) 을 1정씩하루 2회복용한 GBE군, 아무것도복용하지않은대조군으로나누어치료결과를분석하였다. 모든환자에게적절한녹내장안약치료를병행하였으며정기적인경과관찰을시행하면서매방문시교정시력, 골드만압평안압, 시야검사를시행하였다. 시야검사는 HVF analyzer (Carl Zeiss Meditec, Dublin, CA, USA) 를이용하여 30-2 SITA 표준알고리즘으로시행되었다. 분석에사용한자료는첫 6개월이내에시행한믿을만한 2회의시야검사수치들의평균과마지막 6개월동안시행한믿을만한 2회의시야검사수치들의평균을사용하였다. 모든시야검사는한명의익숙한검사자에의해실시되었다. 각군의시야검사상 MD (Mean deviation), PSD (Pattern standard deviation) 값과교정시력 (logmar) 을치료전후로비교하였고, 추가적으로전신적, 안과적요소들과치료결과의연관성을일반화선형모형을이용하여분석하였다. 통계는 SPSS ver. 18.0 (Inc., Chicago, IL, USA) 를사용하였다. 결과 Table 1. Characteristics of all patients DM (-) (n = 255) DM (+) (n = 151) Total (n = 406) Sex Male 156 109 265 Female 99 42 141 Age (years) 51.23 ± 12.91 55.13 ± 11.54 52.68 ± 12.55 Mean follow-up (months) 23.74 ± 11.33 27.23 ± 16.77 25.04 ± 13.69 Intraocular pressure (mm Hg) 13.86 ± 3.10 13.84 ± 2.99 13.85 ± 3.06 Blood pressure (mm Hg) Diastolic 76.70 ± 8.57 78.63 ± 8.68 77.49 ± 8.65 Systolic 118.77 ± 11.51 123.74 ± 12.78 120.62 ± 12.22 Fasting blood sugar (mg/dl) 97.66 ± 12.04 118.14 ± 28.77 109.11 ± 25.07 Hypertension (%) 55 (21.6) 62 (41.1) 131 (31.3) Values are presented as mean ± SD. DM = diabetes mellitus. 1175
- 대한안과학회지 2014 년제 55 권제 8 호 - Table 2. Patient characteristics and baseline data of treatment group Control (n = 80) DM (-) (n = 255) DM (+) (n = 151) Anthocyanoside GBE Control Anthocyanoside GBE p-value (n = 76) (n = 99) (n = 36) (n = 83) (n = 32) Sex (%) Male 48 (60.0) 40 (52.6) 68 (68.7) 0.094 25 (69.4) 62 (74.7) 22 (68.8) 0.747 Female 32 (40.0) 36 (47.4) 31 (31.3) 11 (30.6) 21 (25.3) 10 (31.3) Age (years) 50.86 ± 16.48 53.61 ± 9.55 49.71 ± 11.68 0.134 * 56.11 ± 11.43 55.95 ± 11.47 51.91 ± 11.62 0.205 * Follow-up (months) 22.34 ± 9.77 24.41 ± 11.72 24.36 ± 12.17 0.409 * 24.22 ± 13.54 28.47 ± 17.26 27.41 ± 18.71 0.449 * BP (mm Hg) Systolic 119.34 ± 12.32 120.72 ± 10.96 116.82 ± 11.05 0.073 * 123.11 ± 13.50 123.89 ± 11.75 124.06 ± 14.76 0.943 * Diastolic 77.81 ± 7.50 77.20 ± 9.44 75.41 ± 8.59 0.147 * 79.64 ± 9.73 78.66 ± 8.28 77.41 ± 8.58 0.573 * FBS (mg/dl) 94.38 ± 8.54 101.59 ± 15.83 96.12 ± 9.05 0.052 * 120.83 ± 26.57 118.08 ± 29.50 115.59 ± 29.94 0.789 * Hypertension (%) 18 (22.5) 22 (28.9) 15 (15.2) 0.086 11 (30.6) 41 (49.4) 10 (31.3) 0.071 IOP (mm Hg) 14.16 ± 3.20 13.29 ± 3.00 14.05 ± 3.07 0.157 * 14.83 ± 2.85 13.54 ± 3.09 13.50 ± 2.69 0.199 * MD (db) -3.953 ± 4.788-4.868 ± 5.393-4.861 ± 5.334 0.451 * -4.451 ± 4.490-6.234 ± 7.116-5.760 ± 4.929 0.351 * PSD (db) 3.726 ± 3.044 4.611 ± 3.930 4.629 ± 4.029 0.205 * 4.798 ± 3.259 5.155 ± 3.750 5.909 ± 4.389 0.467 * Log MAR BCVA 0.077 ± 0.110 0.076 ± 0.096 0.063 ± 0.087 0.535 * 0.090 ± 0.148 0.110 ± 0.234 0.100 ± 0.185 0.568 * Values are presented as mean ± SD. DM = diabetes mellitus; GBE = ginkgo biloba extract; BP = blood pressure; FBS = fasting blood sugar; IOP = intraocular pressure; MD = mean deviation; PSD = pattern standard deviation; log MAR BCVA = logarithm of the minimal angle of resolution best corrected visual acuity. * One-way ANOVA; Chi-square test. p-value Table 3. Best-corrected visual acuity (BCVA), visual field indices with treatment group DM (-) Control (n = 80) Anthocyanoside (n = 76) GBE (n = 99) (n = 255) Baseline Follow-up p-value * Baseline Follow-up p-value * Baseline Follow-up p-value * MD (db) -3.953 (±4.788) -4.156 (±5.567) 0.654-4.868 (±5.393) -4.102 (±5.209) 0.005-4.861 (±5.704) -4.013 (±5.360) 0.001 PSD (db) 3.726 (±3.044) 4.068 (±3.097) 0.154 4.611 (±3.930) 4.494 (±3.943) 0.438 4.629 (±4.029) 4.367 (±4.068) 0.118 log MAR BCVA 0.077 (±0.110) 0.131 (±0.238) 0.022 0.076 (±0.096) 0.057 (±0.082) 0.024 0.063 (±0.087) 0.054 (±0.092) 0.206 DM (+) Control (n = 36) Anthocyanoside (n = 83) GBE (n = 32) (n = 151) Baseline Follow-up p-value * Baseline Follow-up p-value * Baseline Follow-up p-value * MD (db) -4.451 (±4.490) -4.261 (±4.436) 0.561-6.234 (±7.116) -5.043 (±6.008) 0.003-5.760 (±4.929) -4.460 (±4.914) 0.025 PSD (db) 4.798 (±3.259) 4.708 (±3.409) 0.668 5.155 (±3.750) 4.818 (±3.694) 0.053 5.909 (±4.389) 6.030 (±4.353) 0.735 log MAR BCVA 0.090 (±0.148) 0.130 (±0.181) 0.005 0.110 (±0.234) 0.091 (±0.154) 0.011 0.100 (±0.185) 0.103 (±0.233) 0.809 Values are presented as mean ± SD. DM = diabetes mellitus; GBE = ginkgo biloba extract; MD = mean deviation; PSD = pattern standard deviation; log MAR BCVA = logarithm of the minimal angle of resolution best corrected visual acuity. * Paired sample t-test. 전체 406명중남자가 265명, 여자가 141명이었으며, 평균연령은 52.68 (±12.55) 세, 평균경과관찰은 25.04 (±13.69) 개월이었다 (Table 1). 당뇨가없는 255명중대조군은 80명, Anthocyanoside군은 76명, GBE군은 99명이었으며, 당뇨를진단받은환자는 151명의환자중대조군은 36명, Anthocyanoside군 83명, GBE군 32명이었다. 각군별로남녀성비와연령, 경과관찰기간, 혈압, 공복혈당, 고혈압유병률에는유의한차이가없었다. 치료전기저안압과시야검사의 MD, PSD 값, 교정시력모두치료군간의유의한차이를보여주지않았다 (Table 2). 당뇨가없는환자에서시야검사의 MD 값은대조군은유의한변화를보여주지않았으나 (p=0.654), Anthocyanoside 군에서는 -4.868 (±5.393) 에서 -4.102 (±5.209) 로향상되었고 (p=0.005), GBE군은 -4.861 (±5.704) 에서 -4.013 (±5.360) 로향상되었다 (p=0.001). PSD 값은대조군, Anthocyanoside 군, GBE군모두유의한변화를보여주지않았다 ( 각각 p=0.154, 0.438, 0.118). 교정시력 (logmar) 은대조군에서 0.077 (±0.110) 에서 0.131 (±0.238) 로악화되었으나 (p=0.022), Anthocyanoside군은 0.076 (±0.096) 에서 0.057 (±0.082) 로호전되었고 (p=0.024), GBE군은유의한변화를보여주지않았다 (p=0.206) (Table 3). 당뇨가있는환자에서시야검사의 MD 값은대조군의경우유의한변화를보여주지않았으나 (p=0.561), Anthocyanoside 군은 -6.234 (±7.116) 에서 -5.043 (±6.008) 으로, GBE군은 -5.760 (±4.929) 에서 -4.460 (±4.914) 으로향상되었다 ( 각각 1176
- 이용우외 : 안토시아노사이드와은행잎추출물의효과 - Table 4. Generalized linear model of general and ocular variables and changes in visual indices (after-before) Changes of MD Changes of PSD Changes of log MAR BCVA p-value Coefficient p-value Coefficient p-value Coefficient Sex (Female) 0.818 1.118 0.477 0.801 0.772 1.007 Age 0.002 0.948 0.063 0.545 0.389 0.999 Anthocyanoside 0.019 2.904 0.001 0.382 <0.001 0.913 Ginkgo biloba extract 0.037 2.958 0.063 0.545 0.004 0.932 Hypertension 0.471 1.350 0.308 0.762 0.345 1.019 Diabetes 0.051 2.184 0.120 0.672 0.121 0.971 Intraocular pressure 0.228 1.076 0.533 0.976 0.590 1.002 MD = mean deviation; PSD = pattern standard deviation; log MAR BCVA = logarithm of the minimal angle of resolution best corrected visual acuity. p=0.003, 0.025). PSD 값은당뇨가없는환자와마찬가지로대조군, Anthocyanoside군, GBE군모두유의한변화를보여주지않았다 ( 각각 p=0.668, 0.053, 0.735). 교정시력 (logmar) 은대조군의경우 0.090 (±0.148) 에서 0.130 (±0.181) 으로악화되었으나 (p=0.005), Anthocyanoside군은 0.110 (±0.234) 에서 0.091 (±0.154) 로호전되었고 (p=0.011), GBE군은유의한변화를보여주지않았다 (p=0.809) (Table 3). 추가적으로성별, 연령, 복용약물, 고혈압, 당뇨, 안압의요소들이 MD, PSD 값, 교정시력에미치는영향을분석하기위하여일반화선형모형을산출하였다. MD 값의변화에영향을미치는것은연령 (p=0.002) 과 Anthocyanoside 복용 (p=0.019), GBE 복용 (p=0.037) 이었으며 PSD 값의변화에영향을미치는것은 Anthocyanoside 복용 (p=0.001) 이었고, 교정시력의변화에영향을미치는것은 Anthocyanoside 복용 (p<0.001) 과 GBE 복용 (p=0.004) 이었다 (Table 4). 고찰 녹내장의대표적인모집단기반연구인 OHTS (Ocular Hypertension Treatment Study) 나 CNTG (Collaborative Normal-Tension Glaucoma Study Group) 의연구에서보면고안압환자에서안압을충분히낮추어도녹내장으로전환되기도하며, 녹내장환자의안압을충분히낮추어도, 진행이줄어들긴하지만, 일정환자는여전히녹내장이진행하는것으로보고하고있다. 이러한사실로보아일부녹내장환자에서는안압하강이외에추가적인치료가필요하다는것을시사한다고할수있다. 3,4 우리의연구결과에서보면 Anthocyanoside나 GBE의복용이정상안압녹내장환자일부에서시기능의향상에도움을줄수있는것으로나타났다. 이런결과는당뇨를진단받은환자와그렇지않은환자모두에서같은결과를보여주었다. 시야검사의 MD 값은대조군에서유의한차이가없었으나 Anthocyanoside 치료군과 GBE 치료군에서는호 전되었고, PSD 값은세군에서모두의미있는차이는없었으나, 교정시력은대조군에서유의하게악화된반면 Anthocyanoside군에서는유의하게호전되었다. 특히이런결과는회귀분석을통하여 Anthocyanoside나 GBE의복용이유의한효과를가져올수있다는것을확인할수있었다. 이전의몇몇연구들에서 Anthocyanoside나 GBE의혈류개선효과에대한보고를하였었다. 동물연구에서 Anthocyanoside 가미세혈관의혈류와간질액의재배치를통하여혈류개선의이득을준다는보고가있었다. 13 Bilberry 추출물을복용한 47명의환자에서족부의미세혈류정체를감소시키는효과를보고하기도하였었다. 14 하지의정맥부전환자에서정맥의미세혈류순환과림프순환에도움을준다는보고도있었다. 15 GBE가안구혈류순환을호전시킨다고보고한연구들도있었다. 정상인 11명에서 GBE를하루 120 mg씩이틀간복용후안압이나혈압의변화없이안동맥의이완말기혈류속도가향상됨을보고한연구가있었으며, 16 같은용량으로 4주간복용후시신경유두주위의미세혈류속도, 혈류량, 부피의증가를보고한바있었다. 17 또다른연구에서는정상안압녹내장환자에서하루 160 mg씩 4주간복용후시신경유두주위의혈류량, 혈류속도의증가를보여준보고도있었다. 18 몇몇연구에서는 Anthocyanoside와 GBE의항산화작용에대한보고도있었다. 건강한쥐를대상으로 Anthocyanoside 복용이항산화효소의활성과발현에영향을미친다는보고가있었다. 19 GBE는직접유리기포촉제 (radical scavenger) 로작용을하며, 20 미토콘드리아의산화손상을막아주고역할을하고, 21,22 신경보호효과와 23 저밀도지방단백의산화를막아주는기능을가지고있다. 24 녹내장환자에서 Anthocyanoside나 GBE가도움이될수있는또다른가능성으로인지기능의향상에도움이된다는것이다. 25 대뇌소혈관허혈이녹내장환자에서더빈번하다는보고가있었으며, 26,27 Anthocyanoside나 GBE의복용 1177
- 대한안과학회지 2014 년제 55 권제 8 호 - 이이런허혈을개선함으로써시력이나시야검사지표에도도움을줄수있다고생각할수있다. 28 기전은명확하지않지만 Anthocyanoside와 GBE의항염증작용에대한보고도있었다. 29 이를토대로 Anthocyanoside와 GBE의시기능개선효과를보여준몇몇연구들이있었다. Lee et al 30 은 Anthocynoside 복용이근시환자에서대비감도와임상증상의개선을향상시켜준다고보고하였다. Quaranta et al 31 은 GBE를복용한정상안압녹내장환자에서 4주후시야검사지표의향상을보여준다고하였다. Kim et al 32 은황반부종을동반한비증식당뇨망막병증환자에서 Anthocyanoside 를 12개월동안복용후대비감도가호전된다고보고하였다. 그리고 42명의정상안압녹내장환자에서 GBE를 80mg씩하루 2회복용하여시야이상의진행을늦출수있다고보고한연구도있었다. 12 최근저자의연구에서는정상안압녹내장환자 332명을대상으로 Anthocyanoside와 GBE 복용후교정시력과시야검사의 MD 값이유의하게증가하였음을보고한바있다. 6 이결과를토대로녹내장의병태생리에직간접적으로영향을미칠수있는당뇨의유무에따라임상결과의차이가있는지를더많은환자수를대상으로분석을하게되었다. 본연구결과당뇨의진단여부와상관없이 Anthocyanoside와 GBE는임상적으로시기능을향상시킬수있는것으로나타났다. 이는앞선연구들에서보여준혈류개선혹은항산화효과가당뇨환자혹은비당뇨환자에만국한되지않고작용할수있다는것을시사하고있다. 본연구의제한점으로는후향적의무기록분석으로서당뇨를진단받은환자에서대조군과 GBE 치료군이상대적으로적었다는점이다. 또한약을복용하면서체내혈중농도를측정하지못하였다는단점도있다. 추후이런점을보완하여체내혈중농도와시기능개선의효과를전향적으로알아보는것이도움이될것이라고생각한다. 결론적으로우리의연구결과는정상안압녹내장환자에게있어당뇨가있는사람과없는사람모두 Anthocyanoside와 GBE가시기능의개선에도움이될수있다는것을보여주었다. 이결과는녹내장환자진료시전신질환을고려하여혈액순환개선제와항산화제를처방하는데참고가될것이라고생각한다. REFERENCES 1) Levene RZ. Low tension glaucoma: a critical review and new material. Surv Ophthalmol 1980;24:621-64. 2) Coleman AL. Glaucoma. Lancet 1999;354:1803-10. 3) Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Collaborative Normal-Tension Glaucoma Study Group. Am J Ophthalmol 1998;126:487-97. 4) Kass MA, Gordon MO, Gao F, et al. Delaying treatment of ocular hypertension: the ocular hypertension treatment study. Arch Ophthalmol 2010;128:276-87. 5) Krupin T, Liebmann JM, Greenfield DS, et al. A randomized trial of brimonidine versus timolol in preserving visual function: results from the Low-Pressure Glaucoma Treatment Study. Am J Ophthalmol 2011;151:671-81. 6) Shim SH, Kim JM, Choi CY, et al. Ginkgo biloba extract and bilberry anthocyanins improve visual function in patients with normal tension glaucoma. J Med Food 2012;15:818-23. 7) Marra G, Cotroneo P, Pitocco D, et al. Early increase of oxidative stress and reduced antioxidant defenses in patients with uncomplicated type 1 diabetes: a case for gender difference. Diabetes Care 2002;25:370-5. 8) Reunanen A, Knekt P, Aaran RK, Aromaa A. Serum antioxidants and risk of non-insulin dependent diabetes mellitus. Eur J Clin Nutr 1998;52:89-93. 9) Vessby J, Basu S, Mohsen R, et al. Oxidative stress and antioxidant status in type 1 diabetes mellitus. J Intern Med 2002;251:69-76. 10) Higginbotham EJ. Glaucoma in specific high risk racial and ethnic groups. In: Higginbotham EJ, Lee DA, eds. Management of difficult glaucoma: a clinician's guide. Boston: Blackwell Scientific Inc., 1994. 11) Mitchell P, Smith W, Chey T, Healey PR. Open-angle glaucoma and diabetes: the Blue Mountains eye study, Australia. Ophthalmology 1997;104:712-8. 12) Lee J, Sohn SW, Kee C. Effect of Ginkgo biloba extract on visual field progression in normal tension glaucoma. J Glaucoma 2013; 22:780-4. 13) Colantuoni A, Bertuglia S, Magistretti MJ, Donato L. Effects of Vaccinium Myrtillus anthocyanosides on arterial vasomotion. Arzneimittelforschung 1991;41:905-9. 14) Ghiringhelli C, Gregoratti L, Marastoni F. [Capillarotropic action of anthocyanosides in high dosage in phlebopathic statis]. Minerva Cardioangiol 1978;26:255-76. 15) Bratman S, Kroll D. Clinical evaluation of medicinal herbs and other therapeutic natural products. Rocklin, Calif.: Prima Lifestyles, 1999. 16) Chung HS, Harris A, Kristinsson JK, et al. Ginkgo biloba extract increases ocular blood flow velocity. J Ocul Pharmacol Ther 1999;15:233-40. 17) Lee DJ, Ahn HB, Rho SH. The effect of Ginkgo biloba to retinal microcirculation. J Korean Ophthalmol Soc 2002;43:1522-7. 18) Park JW, Kwon HJ, Chung WS, et al. Short-term effects of Ginkgo biloba extract on peripapillary retinal blood flow in normal tension glaucoma. Korean J Ophthalmol 2011;25:323-8. 19) Hassimotto NM, Lajolo FM. Antioxidant status in rats after long-term intake of anthocyanins and ellagitannins from blackberries. J Sci Food Agric 2011;91:523-31. 20) Stefanovits-Bányai E, Szentmihályi K, Hegedus A, et al. Metal ion and antioxidant alterations in leaves between different sexes of Ginkgo biloba L. Life Sci 2006;78:1049-56. 21) Eckert A, Keil U, Kressmann S, et al. Effects of EGb 761 Ginkgo biloba extract on mitochondrial function and oxidative stress. Pharmacopsychiatry 2003;36 Suppl 1:S15-23. 22) Eckert A, Keil U, Scherping I, et al. Stabilization of mitochondrial membrane potential and improvement of neuronal energy metabo- 1178
- 이용우외 : 안토시아노사이드와은행잎추출물의효과 - lism by Ginkgo biloba extract EGb 761. Ann N Y Acad Sci 2005;1056:474-85. 23) Hirooka K, Tokuda M, Miyamoto O, et al. The Ginkgo biloba extract (EGb 761) provides a neuroprotective effect on retinal ganglion cells in a rat model of chronic glaucoma. Curr Eye Res 2004;28:153-7. 24) Yan LJ, Droy-Lefaix MT, Packer L. Ginkgo biloba extract (EGb 761) protects human low density lipoproteins against oxidative modification mediated by copper. Biochem Biophys Res Commun 1995;212:360-6. 25) Kleijnen J, Knipschild P. Ginkgo biloba for cerebral insufficiency. Br J Clin Pharmacol 1992;34:352-8. 26) Stroman GA, Stewart WC, Golnik KC, et al. Magnetic resonance imaging in patients with low-tension glaucoma. Arch Ophthalmol 1995;113:168-72. 27) Kim M, Park KH, Kwon JW, et al. Retinal nerve fiber layer defect and cerebral small vessel disease. Invest Ophthalmol Vis Sci 2011; 52:6882-6. 28) Ritch R. Potential role for Ginkgo biloba extract in the treatment of glaucoma. Med Hypotheses 2000;54:221-35. 29) Tsoyi K, Park HB, Kim YM, et al. Anthocyanins from black soybean seed coats inhibit UVB-induced inflammatory cylooxygenase-2 gene expression and PGE2 production through regulation of the nuclear factor-kappab and phosphatidylinositol 3-kinase/Akt pathway. J Agric Food Chem 2008;56:8969-74. 30) Lee J, Lee HK, Kim CY, et al. Purified high-dose anthocyanoside oligomer administration improves nocturnal vision and clinical symptoms in myopia subjects. Br J Nutr 2005;93:895-9. 31) Quaranta L, Bettelli S, Uva MG, et al. Effect of Ginkgo biloba extract on preexisting visual field damage in normal tension glaucoma. Ophthalmology 2003;110:359-62; discussion 362-4. 32) Kim ES, Yu SY, Kwon SJ, et al. Clinical evaluation of patients with nonproliferative diabetic retinopathy following medication of anthocyanoside: multicenter study. J Korean Ophthalmol Soc 2008; 49:1629-33. = 국문초록 = 정상안압녹내장에서당뇨유무에따라분석한안토시아노사이드, 은행잎추출물의치료효과 목적 : 당뇨유무에따라정상안압녹내장환자에서 Anthocyanoside 제제및 Ginkgo Biloba Extract (GBE) 제제를복용하는환자들의치료효과를분석해보고자하였다. 대상과방법 : 2005 년 1 월부터 2013 년 12 월까지강북삼성병원안과외래에내원한정상안압녹내장환자를대상으로후향적의무기록분석을시행하였다. 모든환자들은 6 개월간격으로교정시력과시야검사를시행하였으며, 당뇨유무에따라나누어 Anthocyanoside 를복용한환자군과 GBE 를복용한환자군그리고둘다복용하지않은대조군의교정시력과시야검사지표를비교분석하였다. 결과 : 총 406 명중당뇨를진단받지않은환자는 255 명 ( 대조군 80 명, Anthocyanoside 군 76 명, GBE 군 99 명 ), 당뇨를진단받은환자는 151 명 ( 대조군 36 명, Anthocyanoside 군 83 명, GBE 군 32 명 ) 이었다. 치료후시야검사상 MD 값은 Anothocyanoside 군과 GBE 군에서호전되었다. PSD 값은세군에서모두유의한변화를보여주지않았다. 교정시력은대조군에서악화되었으나, Anthocyanoside 군에서는향상되었다. 이런결과는당뇨가없는환자와있는환자모두동일하였으며, 일반화선형모형분석에서전신약제복용이시기능에유의한영향을미치는것으로나타났다. 결론 : 정상안압녹내장환자에서 Anthocyanoside 와 GBE 는당뇨의유무에상관없이시기능의호전에도움을줄수있는것으로나타났다. < 대한안과학회지 2014;55(8):1174-1179> 1179