대한안과학회지 2017 년제 58 권제 3 호 J Korean Ophthalmol Soc 2017;58(3):296-304 ISSN 0378-6471 (Print) ISSN 2092-9374 (Online) https://doi.org/10.3341/jkos.2017.58.3.296 Original Article 나이관련황반변성에서라니비주맙과애프리버셉트후맥락막두께의변화비교 : 6 개월결과 Comparison of Choroidal Thickness Change between Ranibizumab and Aflibercept in Age-related Macular Degeneration: Six Month Results 김임규 김용일 김진선 이정호 이규원 강현구 Im Gyu Kim, MD, Yong Il Kim, MD, Jin Seon Kim, MD, Jung Ho Lee, MD, Kyoo Won Lee, MD, PhD, Hyun Gu Kang, MD 제일안과병원 Cheil Eye Hospital, Daegu, Korea Purpose: To compare the changes in subfoveal choroidal thickness between intravitreal aflibercept and ranibizumab injection in wet age-related macular degeneration (AMD). Methods: Fifty patients with wet AMD patients who were treated with aflibercpet or ranibizumab were evaluated retrospectively. All patients were treated with pro re nata after 3 consecutive monthly injections and were followed up for at least 6 months. We measured subfoveal choroidal thickness (SFCT) using enhanced depth imaging spectral-domain optical coherence tomography before the first injection and 1, 2, 3, and 6 months after initial injection. Results: The SFCT measures before initial injection and 1, 2, 3, and 6 months after initial injection were 244.94 ± 103.77 μm, 219.04 ± 95.89 μm, 208.74 ± 91.03 μm, 203.64 ± 91.35 μm, and 226.98 ± 96.79 μm in the aflibercept group (25 eyes) and 222.68 ± 102.04 μm, 210.23 ± 95.91 μm, 203.66 ± 99.39 μm, 197.27 ± 100.25 μm, and 210.32 ± 111.86 μm in the ranibizumab group (28 eyes). Mean change in SFCT was greater in the aflibercept group at 1 month, 2 months, and 3 months after initial injection (p < 0.05), but there was no significant difference in the mean change in SFCT between the two groups at 6 months after initial injection (p > 0.05). Conclusions: The decrease in SFCT was greater after aflibercept injection than ranibizumab injection in 3 consecutive months. However, at 6 months after initial injection, the difference in the change in SFCT was not significant. J Korean Ophthalmol Soc 2017;58(3):296-304 Keywords: Aflibercept, Polypoidal choroidal vasculopathy, Ranibizumab, Subfoveal choroidal thickness, Wet age-related macular degeneration Received: 2016. 8. 18. Revised: 2016. 11. 18. Accepted: 2017. 1. 23. Address reprint requests to Hyun Gu Kang, MD Cheil Eye Hospital, #1 Ayang-ro, Dong-gu, Daegu 41196, Korea Tel: 82-53-959-1751, Fax: 82-53-959-1758 E-mail: flowerchild03@hanmail.net * This study was presented as a poster at the 113th Annual Meeting of the Korean Ophthalmological Society 2015. 나이관련황반변성은서구에서노인의실명에가장흔한요인으로알려져있다. 1,2 최근국내에서도나이관련황반변성환자가크게증가하여서구와비슷한양상을보이는것으로알려져있다. 3 Rosenfeld et al 4 과 Brown et al 5 의연구결과가발표된후유리체강내항혈관내피성장인자주입술은삼출성나이관련황반변성의주치료가되었으며, 라니비주맙 (Lucentis, Genentech Inc., South San Fransisco, CA, USA) 과베바시주맙 (Avastin, Genentech Inc., Oceanside, c2017 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. 296
- 김임규외 : 황반변성치료에서맥락막두께의변화 - CA, USA) 이사용되었다. 유리체강내라니비주맙과베바시주맙주입술은나이관련황반변성환자의시력을유지하고시력소실을예방하는데효과가있는것으로보고되었다. 6-9 최근새로운항혈관내피성장인자인애프리버셉트 (Eylea, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA) 가소개되었는데, 삼출성나이관련황반변성의치료에서애프리버셉트를 1개월간격으로 3회주사후 2개월간격으로주사하는방법은라니비주맙을매달주사하는방법과비슷한효과를보였다. 10 혈관내피성장인자는맥락막모세혈관및맥락막혈류의유지에중요한역할을한다. 11,12 따라서유리체강내항혈관내피성장인자주입술은맥락막두께에영향을줄것이다. 삼출성나이관련황반변성환자에서유리체강내라니비주맙주입술후황반하맥락막두께는감소하였고 13 애프리버셉트주입술후에도맥락막두께는감소하였다. 14 최근유리체강내라니비주맙또는애프리버셉트주입술후맥락막두께의변화를비교한연구가보고되었는데, 한달간격으로 3회주사후애프리버셉트주입군에서맥락막두께가더많이감소하였다. 15,16 본연구에서는이전치료의과거력이없는삼출성나이관련황반변성환자에서한달간격으로 3 회유리체강내라니비주맙또는애프리버셉트주입술후맥락막두께의변화가이전의연구결과와일치하는지확인해보고, 3회연속주사후필요할때마다주사하면서경과관찰시치료시작 6개월후맥락막두께의변화를비교해보고자한다. 대상과방법 2014년 2월부터 2015년 11월까지제일안과병원을방문하여삼출성나이관련황반변성으로진단받고유리체강내라니비주맙또는애프리버셉트주입술시행후 6개월이상경과관찰된환자 50명 53안을대상으로후향적으로분석하였다. 본연구는제일안과병원임상연구심의위원회 (Institutional Review Board) 의승인을통해진행되었으며 ( 승인번호 : CEH-2014-7), 헬싱키선언을준수하였다. 처음삼출성나이관련황반변성으로진단된경우만연구에포함시켰으며, 이전에삼출성나이관련황반변성으로진단받고치료받은경우는제외하였다. 증식당뇨망막병증, 망막혈관폐쇄, 황반원공, 망막앞막등황반의구조와기능에영향을미칠수있는망막질환이동반된경우는대상에서제외하였다. 모든환자들은진단시최대교정시력검사 (logarithm of the minimum angle of resolution, logmar), 세극등현미경검사 (Slit lamp 900 BQ; Hagg-Streit AG, Koeniz, Switzerland), 자동굴절검사기 (Canon, Inc., Tokyo, Japan) 를사용한굴절력검사, 안저검사및천연색안저사진촬영 (Digital retinal camera CR-2, Canon, Inc., Tokyo, Japan), 안압측정 (Full auto tonometer TX-F, Canon, Inc., Tokyo, Japan), 스펙트럼영역빛간섭단층촬영과형광안저혈관조영및인도사이아닌그린혈관조영 (Spectralis Heidelberg retinal angiography [HRA] optical coherence tomography [OCT], Heidelberg Engineering, Heidelberg, Germany) 을시행하였다. 유리체강내주입술은외래수술실에서시행하였고, 주입술전 0.3% levofloxacin (Cravit, Santen, Osaka, Japan) 과 0.5% proparacaine hydrochloride (Alcaine, Alcon, Fort Worth, TX, USA) 를점안한뒤 5% povidone iodine을점안하고눈주위를소독하였다. 수술포를씌운후개검기를끼우고 30게이지주사바늘을이용하여각막윤부에서 3.5 mm 떨어진부위에라니비주맙 0.05 ml (0.5 mg) 또는애프리버셉트 0.05 ml (2 mg) 를주사하였다. 모든환자들은 1개월간격으로 3회유리체강내주입술을시행받았으며, 첫번째주사후 1개월마다최대교정시력, 세극등현미경검사, 안압측정, 스펙트럼영역빛간섭단층촬영을시행하면서추적관찰하였다. 1개월간격으로 3회유리체강내주입술후추적관찰시중심망막두께가 100 μm 이상증가하거나, 망막하액으로인해시력이 1줄이상감소하거나, 새로운맥락막신생혈관이관찰되거나, 새로운황반출혈이관찰되는경우추가치료를시행하였다. 대상환자들의중심황반두께및황반하맥락막두께는 Spectralis HRA OCT로촬영한영상을이용하여측정하였다. 중심황반두께는내장된프로그램을이용하여측정하였고, 황반하맥락막두께는 enhanced depth imaging (EDI) 방법으로촬영한영상에서중심와위치의고반사선을보이는망막색소상피층의외측경계와내측공막경계의고반사선까지의수직거리를두명의연구자가각각수동으로측정하여평균값을계산하였다. 통계적분석은표준소프트웨어 (SPSS version 18.0 for Windows, SPSS Inc., Chicago, IL, USA) 를사용하였고, 반복측정분산분석 (repeated measure analysis of variance) 을사용하여치료전과치료후경과관찰기간동안라니비주맙과애프리버셉트각군의치료효과및두군간의차이를분석하였고, 두군간의차이가발생하는시점을확인하기위해사후검정으로독립표본 t 검정을사용하여분석하였다. 두군간의초기지표비교를위해정규성검정후독립표본 t 검정및 Mann-Whitney U-test를사용하였고, 성별, 안구방향, 당뇨, 고혈압의비교는카이제곱검정을이용하였으며, 유의수준 5% 미만 (p<0.05) 인경우통계학적으로유의한것으로정의하였다. 297
- 대한안과학회지 2017 년제 58 권제 3 호 - 결과 전체 50명 53안을대상으로분석을시행하였으며, 남자 40명 (80%), 여자 10명 (20%) 이었고, 평균연령은 70.26 ± 7.58세였다. 애프리버셉트주입군은 25안 (47.17%) 이었으며, 라니비주맙주입군은 28안 (52.83%) 이었다. 치료전두군간연령, 성별, 당뇨, 고혈압, 최대교정시력, 안압, 구면렌즈대응치, 중심황반두께, 황반하맥락막두께의값은유의한차이를보이지않았으며 (p>0.05), 경과관찰기간동안유리체강내주입술횟수는애프리버셉트주입군이좀더적었다 (p=0.037; Table 1). 애프리버셉트주입군의황반하맥락막두께는주사전과첫번째주사후 1개월, 2개월, 3개월, 6개월에각각 244.94 ± 103.77 μm, 219.04 ± 95.89 μm, 208.74 ± 91.03 μm, 203.64 ± 91.35 μm, 226.98 ± 96.79 μm였으며, 첫번째주입술후 3개월까지는치료전보다유의하게감소되었으며 (p<0.05), 6개월째경과관찰시에는유의한차이를보이지않았다 (Fig. 1). 라니비주맙주입군의황반하맥락막두께는주사전과첫번째주사후 1개월, 2개월, 3개월, 6개월에각각 222.68 ± 102.04 μm, 210.23 ± 95.91 μm, 203.66 ± 99.39 μm, 197.27 ± 100.25 μm, 210.32 ± 111.86 μm였으며, 첫번째주입술후 3개월까지는유의하게감소되었고 (p<0.05), 6개월째경과관찰시에는유의한차이를보이지않았다 (Fig. 2). 애프리버셉트와라니비주맙주입군의황반하맥락막두께의변화량을비교해보았다. 애프리버셉트주입술군은첫번째주입술후 1개월, 2개월, 3개월, 6개월째황반하맥 락막두께가치료전보다각각평균 25.90 ± 18.87 μm, 36.20 ± 26.19 μm, 41.30 ± 27.30 μm, 17.96 ± 32.82 μm 감소하였으며, 라니비주맙주입군은 12.45 ± 18.10 μm, 19.02 ± 16.20 μm, 25.41 ± 18.33 μm, 그리고 12.36 ± 29.86 μm 감소하였다. 전체경과관찰기간동안황반하맥락막두께의변화는첫번째주사후 1개월, 2개월, 3개월에애프리버셉트주입군이라니비주맙주입군보다통계학적으로의미있게더많이감소하였으며 (p<0.05), 첫번째주사후 6개월에는애프리버셉트주입군에서더많이감소하였으나통계학적으로의미있는차이는없었다 (p=0.518; Fig. 3). 전형적인삼출성나이관련황반변성안에서애프리버셉트와라니비주맙주입술후황반하맥락막두께의변화량을비교해보았다. 애프리버셉트주입군은첫번째주사후 1 개월, 2개월, 3개월, 6개월후황반하맥막막두께는각각평균 21.15 ± 22.84 μm, 31.00 ± 31.11 μm, 37.05 ± 34.64 μm, 20.20 ± 39.20 μm 감소하였으며, 라니비주맙주입군에서는각각평균 15.82 ± 20.62 μm, 22.89 ± 15.17 μm, 24.29 ± 19.85 μm, 19.39 ± 27.36 μm 감소하여전형적인삼출성나이관련황반변성안의경우애프리버셉트주입군에서황반하맥락막두께가더많이감소하였으나두군간에통계학적으로의미있는차이는없었다 (p>0.05). 결절맥락막혈관병증안에서애프리버셉트와라니비주맙주입술후황반하맥락막두께의변화량을비교해보았다. 애프리버셉트주입군은첫번째주사후 1개월, 2개월, 3개월, 6개월후황반하맥막막두께는각각평균 28.89 ± 16.34 μm, 40.32 ± 23.55 μm, 44.32 ± 22.83 μm, 16.79 ± 30.27 μm 감소하였으며, 라니비주맙주입군에서는각각평균 7.12 ± Table 1. Demographics of the study groups Characteristics Aflibercept Ranibizumab p-value Number of eyes 25 28 Sex (male:female) 21:4 21:7 0.420 * Laterality (OD:OS) 9:16 19:9 0.020 * Mean age (years) 68.88 ± 7.68 71.50 ± 7.41 0.212 Diabetes mellitus (patients) 3 2 0.883 * Hypertension (patients) 5 5 0.664 * Best corrected visual acuity (logmar) 0.79 ± 0.36 0.88 ± 0.51 0.423 Intraocular pressure (mmhg) 13.00 ± 3.43 12.04 ± 2.55 0.494 Spherical equivalent (diopter) 0.63 ± 0.91 0.18 ± 1.13 0.126 Macular center thickness (μm) 410.56 ± 118.13 454.68 ± 113.98 0.153 Subfoveal choroidal thickness (μm) 244.94 ± 103.77 222.68 ± 102.04 0.473 Number of injections 3.24 ± 0.44 3.75 ± 0.93 0.037 Age-related macular degeneration type Typical wet age-related macular degeneration (eyes) 10 14 Polypoidal choroidal vasculopathy (eyes) 14 13 Retinal angiomatous proliferation (eyes) 1 1 Values are presented as mean ± SD unless otherwise indicated. OD = oculus dexter; OS = oculus sinister. Chi-square test; Student s t-test; Mann-Whitney U-test. 298
- 김임규외 : 황반변성치료에서맥락막두께의변화 - A B C D Figure 1. Changes in best corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CMT), subfoveal choroidal thickness (SFCT) after aflibercept injection. (A) BCVA was not changed significantly during the follow-up period compared with baseline. (B) IOP was decreased significantly 1, 2 months after aflibercept injection compared with baseline. (C) CMT was decreased significantly during the follow-up period compared with baseline. (D) SFCT was decreased significantly 1, 2 and 3 months after aflibercept injection compared with baseline. ETDRS = Early Treatment Diabetic Retinopathy Study. * Compared with baseline by repeated measure analysis of variance (ANOVA), p < 0.05. A B C D Figure 2. Changes in best corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CMT), subfoveal choroidal thickness (SFCT) after ranibizumab injection. (A) BCVA was not changed significantly during the follow-up period compared with baseline. (B) IOP was not changed significantly during the follow-up period compared with baseline. (C) CMT was decreased significantly during the follow-up period compared with baseline. (D) SFCT was decreased significantly 1, 2 and 3 months after ranibizumab injection compared with baseline. ETDRS = Early Treatment Diabetic Retinopathy Study. * Compared with baseline by repeated measure analysis of variance (ANOVA), p < 0.05. 299
- 대한안과학회지 2017 년제 58 권제 3 호 - 13.87 μm, 13.35 ± 16.03 μm, 25.46 ± 17.57 μm, 2.15 ± 30.46 μm 감소하여결절맥락막혈관병증안에서황반하맥락막두께는첫번째주사후 1개월, 2개월, 3개월에애프리버셉트주입군에서라니비주맙주입군에비해통계학적으로의미있게더많이감소하였고 (p<0.05), 첫번째주사후 6 개월에는두군간에의미있는변화량의차이는없었다 (p=0.222; Fig. 4). 애프리버셉트주입군과라니비주맙주입군에서첫 3회주입술후에추가적인치료를시행한군과경과관찰한군의황반하맥락막두께를비교하였다. 경과관찰기간중추가치료를받은경우는애프리버셉트주입군에서 6안 (24%) 이었으며, 라니비주맙주입군에서 13안 (46.4%) 이었다. 애프리버셉트주입군과라니비주맙주입군각각추가치료여부에따라시력, 중심망막두께, 황반하맥락막두께를비교하였을때통계학적으로유의한차이는보이지않았다 (p>0.05; Fig. 5). Figure 3. Mean change in subfoveal choroidal thickness in aflibercept injection and ranibizumab injection. Subfoveal choroidal thickness was more decreased in the aflibercept injection group. Especially, there was a statistically significant difference between the two groups at 1, 2 and 3 months after injection. * Compared by Student s t-test, p < 0.05. A 고찰 혈관내피성장인자는신생혈관증식에중요한역할을하는것으로알려졌으며, 17 나이관련황반변성의맥락막신생혈관에항혈관내피성장인자가현재주된치료이다. 라니비주맙은높은친화력으로세포밖의혈관내피성장인자와결합하는혈관내피성장인자에대한인간화단일클론항체로항원결합분절 (humanized IgG1 kappa recombinant monoclonal antibody fragment) 만으로구성되어있으며, 모든혈관내피성장인자-A 동형들과결합하여활성을억제시킨다. 4 최근에개발된애프리버셉트는인간면역글로불린 G1의결정가능조각 (Fc) 부위에인간혈관내피성장인자수용체를결합시킨약제로모든혈관내피성장인자동형에혈관내피성장인자수용체보다더강하게결합하여혈관내피성장인자-A, B 및태반성장인자의작용을억제하여라니비주맙보다결합력이높고작용시간이더길다. 18-21 맥락막은혈관이풍부하고혈류량이많은조직으로공막갈색판과망막색소상피사이에위치한다. 맥락막의혈류는망막색소상피와바깥망막에영양물질을공급하고대사물을제거하는역할을하며, 맥락막은망막색소상피와바깥망막을유지시켜정상적인시기능을유지하는데중요한역할을한다. 22,23 Koizumi et al 14 의연구에따르면삼출성나이관련황반변성환자에게애프리버셉트주입후 3개월까지경과관찰하였을때황반하맥락막두께는감소한다고보고하였으며본연구에서도일치하는결과를보였다. Yamazaki et al 13 은삼출성나이관련황반변성환자에게라니비주맙주입후 12개월까지경과관찰하였을때치료시작 1개월, 3개월, 6개월, 12개월모두치료전보다황반하맥락막두께가감소하였다고보고하여, 1개월및 3개월은본연구와일치하는결과를보였으나 6개월은본연구와다른결과를보였다. 이는 B Figure 4. Mean change in subfoveal choroidal thickness (SFCT) in typical wet age-related macular degeneration and polypoidal choroidal vasculopathy. (A) Mean change in SFCT in typical wet age-related macular degeneration. There was no significant difference between aflibercept and ranibizumab group (p > 0.05). (B) Mean change SFCT in polypoidal choroidal vasculopathy. SFCT was more decreased in the aflibercept injection group at 1, 2 and 3 months after initial injection (p < 0.05). * Compared by Student s t-test, p < 0.05. 300
- 김임규외 : 황반변성치료에서맥락막두께의변화 - A B C D E F Figure 5. Changes in best corrected visual acuity (BCVA), central macular thickness (CMT) and subfoveal choroidal thickness (SFCT) between only 3 monthly loading group and additional treatment after 3 loading dose group. (A) BCVA was not significantly different between the two groups after aflibercept injection. (B) BCVA was not significantly different between the two groups after ranibizumab injection. (C) CMT was not significantly different between the two groups after aflibercept injection. (D) CMT was not significantly different between the two groups after ranibizumab injection. (E) SFCT was not significantly different between the two groups after aflibercept injection. (F) SFCT was not significantly different between the two groups after ranibizumab injection. Compared by Student s t-test. ETDRS = Early Treatment Diabetic Retinopathy Study. Yamazaki et al 13 의연구에서는이전에광역학치료또는유리체강내베바시주밥주입술등의과거력이있는환자도포함되어본연구와는다른결과가나왔을것으로생각된다. 맥락막두께가감소하는기전은유리체강내애프리버셉트또는라니비주맙주입술후항혈관내피성장인자가망막을모든층을통과하여맥락막에가서맥락막신생혈관의감소, 맥락막혈관투과성의감소, 맥락막혈관의형태학적변화를초래하여맥락막두께가감소하였을것으로추정된다. 13,14 본연구에서치료시작 6개월에는치료전과맥락막두께가의미있는차이가없어, 유리체강내항혈관내피성장인자의농도가감소하면맥락막의두께의감소는유지가되지않는것을알수있다. 최근이전치료의과거력이없는삼출성나이관련황반변성환자에서라니비주맙또는애프리버셉트를 1개월마다 3 회연속주사후, 애프리버셉트를주입한환자에서황반하맥락막두께가더많이감소하였다고보고되었고 15,16 본연구에서도일치하는결과를보였다. 이는애프리버셉트가혈관내피성장인자에대한결합력이높고반감기가길며, 혈관내피성장인자-A뿐만아니라혈관내피성장인자-B 및태반성장인자를억제하기때문일것이다. 18-21 Julien et al 24 은원숭이눈에유리체강내라니비주맙과애프리버셉트주입후망막과맥락막조직에미치는차이를연구하였는데, 대조군과비교하였을때두약모두에서맥락막모세혈관의면적이의미있게감소하였으나맥락막모세혈관의혈관내 301
- 대한안과학회지 2017 년제 58 권제 3 호 - 피세포두께및구멍의감소, 맥락막모세혈관의용혈이애프리버셉트주사후더저명하게나타났고이는애프리버셉트는결정가능조각부위가있으나라니비주맙은결정가능조각부위가없어라니비주맙이보체계활성을일으키지않는것과관련이있을것으로보고하였다. 그러나첫번째주사후 3개월이후경과관찰했을때두약제간에황반하맥락막두께의변화를비교한연구결과는아직없는데, 본연구결과첫주사후 6개월에는두약제간에유의한황반하맥락막두께변화의차이가유지되지않은것을알수있다. 1개월마다 3회연속주사중애프리버셉트가라니비주맙보다맥락막두께를더많이감소시켜망막색소상피를포함한바깥망막의혈류공급에부정적인영향을미칠염려가있지만, 주사횟수가줄면맥락막두께감소량의차이가없어지므로 3회주사후필요시주사하는실제임상에서두약제가망막색소상피를포함한바깥망막에미치는영향은비슷할것으로생각이된다. 본연구에서결절맥락막혈관병증환자는애프리버셉트주입군이라니비주맙주입군보다첫주사후 1개월, 2개월, 3개월에황반하맥락막두께가라니비주맙주입군보다의미있게더많이감소한것을확인할수있고, Kim et al 15 의연구에서도본연구와같은결과를보였다. 결절맥락막혈관병증환자에게애프리버셉트를주입하면치료효과가더좋은것으로보고되었는데, Kokame et al 25 은결절맥락막혈관병증환자에게라니비주맙을주입하였을때결절퇴행은 33% 에서부분혹은완전관해를보였다고보고하였고, Inoue et al 26 은결절맥락막혈관병증환자에게애프리버셉트를주입하였을때결절퇴행은 75% 에서부분및완전관해를보였다고보고하였다. 결절맥락막혈관병증환자에서맥락막혈관과투과성이전형적인삼출성나이관련황반변성보다흔하다고알려져있으며, 27 빛간섭단층촬영에서맥락막두께가두꺼워져있다고보고되어, 28 맥락막혈관에더영향을주는치료가결절맥락막혈관병증의치료에도움이될것이며, 애프리버셉트가라니비주맙보다맥락막혈관이상에더큰영향을주어결절맥락망막병증의치료에효과가더좋았을것으로추정할수있다. 애프리버셉트주입군과라니비주맙주입군각각추가치료여부에따라황반하맥락막두께를비교하였을때추가로치료한군이치료전및주사후경과관찰기간동안황반하맥락막두께가더두꺼웠으나추가치료를하지않았던군과의미있는차이는없었다. 삼출성나이관련황반변성환자에서치료전맥락막두께가 3회주사후추가주사필요여부를예측할수있는지더많은환자에서추가적인연구가필요하다. 본연구의제한점은후향적연구이며대상환자가라니비 주맙주입군 28 안, 애프리버셉트주입군 25 안으로적으며, 삼출성나이관련황반변성을분류하기에도대상환자수가적은것과맥락막두께는일중변동이있고, 안축장, 굴절이상, 고혈압, 당뇨, 커피의섭취등에영양을받는다고알려져있는데 29-32 이에대한보정을하지못했다는것이다. 그리고경과관찰기간이 6개월로짧아장기적인약제의반응을비교하기에제한이있다. 따라서지속적인관찰및추가연구가필요할것으로생각된다. 본연구를요약하면삼출성나이관련황반변성환자에서유리체강내애프리버셉트또는라니비주맙을 1개월마다 3 회연속주사후필요할때마다주사를추가하면황반하맥락막두께의변화량은 1개월마다 3회연속주사하는동안애프리버셉트주입군이라니비주맙주입군보다더많이감소하였으나, 첫주사후 6개월에는두군간에의미있는차이는없었다. REFERENCES 1) Augood C, Fletcher A, Bentham G, et al. Methods for a population-based study of the prevalence of and risk factors for age-related maculopathy and macular degeneration in elderly European populations: the EUREYE study. Ophthalmic Epidemiol 2004; 11:117-29. 2) Friedman DS, O'Colmain BJ, Muñoz B, et al. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol 2004;122:564-72. 3) Park SJ, Lee JH, Woo SJ, et al. Age-related macular degeneration: prevalence and risk factors from Korean National Health and Nutrition Examination Survey, 2008 through 2011. Ophthalmology 2014;121:1756-65. 4) Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006; 355:1419-31. 5) Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 2006;355:1432-44. 6) Avery RL, Pieramici DJ, Rabena MD, et al. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmology 2006;113:363-72.e5. 7) Folk JC, Stone EM. Ranibizumab therapy for neovascular age-related macular degeneration. N Engl J Med 2010;363:1648-55. 8) Lanzetta P, Mitchell P, Wolf S, Veritti D. Different antivascular endothelial growth factor treatments and regimens and their outcomes in neovascular age-related macular degeneration: a literature review. Br J Ophthalmol 2013;97:1497-507. 9) Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group, Martin DF, Maguire MG, et al. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmology 2012; 119:1388-98. 10) Heier JS, Brown DM, Chong V, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. 302
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- 대한안과학회지 2017 년제 58 권제 3 호 - = 국문초록 = 나이관련황반변성에서라니비주맙과애프리버셉트후맥락막두께의변화비교 : 6 개월결과 목적 : 삼출성나이관련황반변성환자에서유리체강내애프리버셉트와라니비주맙주입술후맥락두께의변화를비교해보고자한다. 대상과방법 : 삼출성나이관련황반변성환자중 1 개월간격으로 3 회애프리버셉트또는라니비주맙주입술후필요할때마다추가주사를하면서 6 개월이상경과관찰한 50 명 53 안을대상으로후향적으로분석하였다. 스펙트럼영역빛간섭단층촬영을이용하여주사전, 첫번째주사후 1 개월, 2 개월, 3 개월, 6 개월에황반하맥락막두께를측정하여변화를연구하였다. 결과 : 황반하맥락막두께는애프리버셉트주입군 (25 안 ) 에서주사전과첫번째주사후 1 개월, 2 개월, 3 개월, 6 개월에각각 244.94 ± 103.77 μm, 219.04 ± 95.89 μm, 208.74 ± 91.03 μm, 203.64 ± 91.35 μm, 226.98 ± 96.79 μm 였으며, 라니비주맙주입군 (28 안 ) 에서는 222.68 ± 102.04 μm, 210.23 ± 95.91 μm, 203.66 ± 99.39 μm, 197.27 ± 100.25 μm, 210.32 ± 111.86 μm 였다. 황반하맥락막두께의변화량은첫번째주사후 1 개월, 2 개월, 3 개월에애프리버셉트주입군이라니비주맙주입군보다의미있게더많이감소하였으며 (p<0.05), 6 개월에는두군간에의미있는차이는없었다 (p>0.05). 결론 : 매달 3 회연속주사중에는애프리버셉트주입군에서라니비주맙주입군보다황반하맥락막두께가더많이감소하였으나, 치료시작 6 개월후에는의미있는차이는없었다. < 대한안과학회지 2017;58(3):296-304> 304