대한안과학회지 2017 년제 58 권제 9 호 J Korean Ophthalmol Soc 2017;58(9):1036-1041 ISSN 0378-6471 (Print) ISSN 2092-9374 (Online) https://doi.org/10.3341/jkos.2017.58.9.1036 Original Article 단안삼출성나이관련황반변성환자의무증상반대안의외망막층두께변화 Change of Outer Retinal Thickness in Fellow Eyes of Patients with Unilateral Age-related Macular Degeneration 정현교 1 김성수 2 박현주 1 Hyun Kyo Jeong, MD 1, Sung Soo Kim, MD, PhD 2, Hyun Ju Park, MD 1 실로암안과병원 1, 연세대학교의과대학안과학교실 2 Siloam Eye Hospital 1, Seoul, Korea Department of Ophthalmology, Yonsei University College of Medicine 2, Seoul, Korea Purpose: To compare the outer retinal thickness in normal fellow eyes of patients with unilateral age-related macular degeneration (AMD) and normal control eyes. Methods: We retrospectively reviewed the medical records of 60 patients with unilateral exudative AMD including polypoidal choroidal vasculopathy and 60 normal controls. Spectralis optical coherence tomography was performed in the normal fellow eyes of patients with unilateral AMD and in the normal group. The thicknesses between the retinal pigment epithelium (RPE) line and the cone outer segment tips (COST) line, between the COST line and the photoreceptor inner segment/outer segment (IS/OS) line, and between the IS/OS line and the external limiting membrane (ELM) line were measured at the fovea in both groups. Results: The thickness between the RPE and COST lines was 32.4 ± 3.0 μm in normal fellow eyes of patients with unilateral AMD and 35.3 ± 3.5 μm in the normal group (p < 0.001). Total retinal thickness, thicknesses between the COST and the IS/OS lines and the IS/OS and the ELM lines in fellow eyes were not significantly different from those of normal eyes (p = 0.126, 0.615, 0.874). There was no significant difference in total retinal thickness or each outer retinal thickness measured in normal fellow eyes between patients with neovascular AMD and polypoidal choroidal vasculopathy. Conclusions: The thickness between the RPE and the COST lines was thinner in the fellow eyes of patients with unilateral AMD than in the normal eyes. We suggest that less thickness between the RPE and COST lines might indicate a greater risk of AMD. J Korean Ophthalmol Soc 2017;58(9):1036-1041 Keywords: Age-related macular degeneration, Cone outer segment tips, Outer retinal thickness, Retinal pigment epithelium 단안의삼출성나이관련황반변성환자에서는현재임상 Received: 2017. 6. 22. Revised: 2017. 8. 9. Accepted: 2017. 9. 1. Address reprint requests to Hyun Ju Park, MD Siloam Eye Hospital, #181 Deungchon-ro, Gangseo-gu, Seoul 07668, Korea Tel: 82-2-2650-0880, Fax: 82-2-2650-0725 E-mail: hjpeye@siloam.co.kr * Conflicts of Interest: The authors have no conflicts to disclose. 적인특이이상소견이관찰되지않는반대안에도추후새로운신생혈관이발생할위험이양안모두나이관련황반변성에이환되지않은환자에비해더높음이알려져있다. 1-3 단안의나이관련황반변성환자에서 2년안에 12-22%, 4년안에 37%, 5년안에 22-38.7% 로반대안에새로운신생혈관이발생할가능성이있다고보고되었다. 4-7 나이관련황반변성은주로외망막층과그관련구조들인망막색소상피층, 광수용체, 맥락막의손상으로부터시작된다. 8,9 Acton et al 10 은초기나이관련황반변성에서빛간섭단 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. 1036
- 정현교외 : 황반변성반대안의외망막층두께변화 - 층촬영을통한외망막층의두께를분석한결과, 광수용체외분절이얇아지고망막색소상피층이두꺼워지는구조적변화와함께시야결손등의기능적손상이동반되기시작한다고하였다. 단안삼출성나이관련황반변성환자의반대안에서새로운맥락막신생혈관의발생가능성이높다는점으로미루어, 임상적으로특이망막이상소견이나타나지않은반대안에도외망막층을중심으로한구조적변화가시작되고있을가능성이있으나이와관련한국내연구결과는보고된적이없다. 따라서저자들은빛간섭단층촬영을이용하여단안삼출성나이관련황반변성환자의임상적정상소견인반대안의외망막층을양안모두임상적정상소견인눈과비교해보고자하였다. 대상과방법 의무기록을후향적으로조사하여 2016년 1월부터 2016년 12월까지연세대학교세브란스병원안과에내원하여양안의스펙트럼영역빛간섭단층촬영기인 Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) 를이용한검사를시행받 은환자중단안의삼출성나이관련황반변성을진단받은환자 60명의안저검사상망막의이상이발견되지않은반대안 60안과양안모두망막이상소견이발견되지않은환자들 60명의 60안을대조군으로하였다. 환자군 60안중신생혈관성나이관련황반변성은 44안, 결절맥락막혈관병증은 16안이었다. 환자군선택시비삼출성나이관련황반변성및망막혈관종성증식으로진단한경우는제외하였다. 또한환자군의망막이상소견이없는반대안및대조군의양안에서 63 μm 이상의드루젠및황반의색소이상이있는경우도제외하였다. 두군에서모두녹내장, 약시, 포도막염, -6디옵터미만의고도근시, 위수정체안, 조절되지않는당뇨혹은고혈압을동반한환자도제외하였다. 모든환자에서 IOL Master (Carl Zeiss, Jena, Germany) 를이용하여안축장을측정하였다. 모든환자는산동상태에서빛간섭단층촬영을시행하였으며, 부피스캔방식으로황반부 20 20 의범위를촬영한후빛간섭단층촬영내의 caliper를이용하여중심와에서전체망막두께및각망막층사이의두께를측정하였다. 각망막층사이의두께는망막색소상피층 (retinal pigment epithelium, A B Figure. 1. Thickness measurements of each layer in the outer retina in normal eye (A) and in fellow eye of patients with unilateral age-related macular degeneration (B). Thickness between the retinal pigment epithelium (RPE) line (outer border) and the cone outer segment tips (COST) line (inner border), the COST line (inner border) and the photoreceptor inner segment/outer segment (IS/OS) line (center of the line), the IS/OS line (center of the line) and the external limiting membrane (ELM) line (center of the line) and the total retinal thickness were measured in both groups. 1037
- 대한안과학회지 2017 년제 58 권제 9 호 - RPE) 의외측경계와원추세포외절끝 (cone outer segment tips, COST) 의내측경계사이의두께 (RPE-COST), 원추세포외절끝의내측경계와광수용체내외절경계 (photoreceptor inner segment/outer segment, IS/OS) 중심사이의두께 (COST-IS/OS), 그리고광수용체내외절경계중심과외경계막 (external limiting membrane, ELM) 중심사이두께 (IS/OS-ELM) 를각각측정하였다. 빛간섭단층촬영의해상도의한계로인해망막색소상피층과원추세포외절끝은환자에따라명확히구분되지않는경우들이있었기때문에, 망막색소상피층은외측경계를, 원추세포외절끝은내측경계를기준으로하여각층간의두께를측정하였으며, 이는두군의모든환자에서동일하게적용하였다 (Fig. 1). 두명의독립된측정자가각자상기에명시한방법대로빛간섭단층촬영상각망막층사이의두께를측정하였으며, 측정자들에게피험자의나이, 성별및환자군과대조군여부등의임상적자료는제공하지않았다. 본연구는헬싱키선언을준수하여연세대학교의료원임상연구윤리심의위원회의승인아래진행되었다. 통계적분석은 SPSS version 24.0 (IBM Corp., Armonk, NY, USA) 을사용하였다. 환자군과대조군사이, 환자군내에서신생혈관성나이관련황반변성과결절맥락막혈관병증환자들사이의측정값간의유의한차이가있는지를알아보기위해연속형자료는 Student t-test를사용하였고범주형자료는 chi-square test를사용하여비교하였다. 모든통계적유의성은 p값 0.05 미만으로판정하였다. 또한측정자간의재현성을확인하기위해급외상관계수를분석하였다. 결과 단안나이관련황반변성환자군총 60명중남성이 25명, 여성이 35명이며평균연령은 69.6 ± 6.7세, 대조군총 60 명중남성 27명, 여성 33명이며평균연령은 68.8 ± 6.8세였고, 두군간성별및연령에서유의한차이는없었다 (p=0.713, 0.518). 단안나이관련황반변성환자군의평균안축장은 23.47 ± 1.05 mm, 대조군은 23.46 ± 0.91 mm로두군간유의한차이를보이지않았다 (p=0.936). 단안나이관련황반변성환자의반대안과대조군의중심와에서측정한전체망막두께는각각 231.6 ± 15.1 μm 및 227.1 ± 16.6 μm 로통계적으로유의한차이는없었다 (p=0.126). 평균망막색소상피층과원추세포외절끝사이의두께 (RPE-COST) 는단안나이관련황반변성환자군의반대안에서 32.4 ± 3.0 μm, 대조군에서 35.3 ± 3.5 μm로유의한차이를보였다 (p<0.001). 원추세포외절끝과광수용체내외절경계사이두께 (COST-IS/OS) 는환자군에서 31.1 ± 3.2 μm, 대조군에서 31.4 ± 4.0 μm로 Figure 2. Thickness of each layer at the fovea in fellow eyes of patients with unilateral age-related macular degeneration (AMD) and normal eyes. Error bar is mean ± standard deviation. RPE = retinal pigment epithelium, COST = cone outer segment tips, IS/OS = photoreceptor inner segment/outer segment, ELM = external limiting membrane. * p-value < 0.05. 측정되었고, 광수용체내외절경계와외경계막사이두께 (IS/OS-ELM) 는각각 31.3 ± 2.5 μm, 31.3 ± 3.2 μm로측정되었으며, 두군간의유의한차이는없었다 (p=0.615, 0.874) (Fig. 2). 두그룹의중심와에서측정한전체망막두께에대한각망막층사이두께의상대적인비율도비교하였다. 전체망막두께에대한상대적인망막색소상피층과원추세포외절끝사이두께 (RPE-COST) 의비율은단안나이관련황반변성환자의반대안에서 14.1 ± 1.6%, 대조군에서 15.6 ± 1.9% 로유의한차이를보였다 (p<0.001). 전체망막두께에대한원추세포외절끝과광수용체내외절경계사이의두께 (COST-IS/OS) 의비율은환자군에서 13.5 ± 1.5%, 대조군에서 13.9 ± 2.0% 였으며, 광수용체내외절경계와외경계막사이두께 (IS/OS-ELM) 의비율은각각 13.6 ± 1.3%, 13.8 ± 1.8% 였고, 두군간유의한차이는발견되지않았다 (p=0.179, 0.374). 환자군중신생혈관성나이관련황반변성 44안과결절맥락막혈관병증 16안을다시나누어무증상반대안의각망막층사이두께를비교하였다. 신생혈관성나이관련황반변성환자들중남성은 20명, 여성은 24명이며평균연령은 68.9 ± 6.8세, 결절맥락막혈관병증환자들중남성은 5명, 여성은 11명이며평균연령은 71.7 ± 6.1세로, 두그룹사이의성별과연령에유의한차이는없었다 (p=0.324, 0.149). 신생혈관성나이관련황반변성및결절맥락막혈관병증환자들의반대안의중심와에서측정한전체망막두께는각각 230.1 ± 15.5 μm, 235.6 ± 13.8 μm였고, 망막색소상피층과원추세포외절끝사이두께 (RPE-COST) 는각각 32.1 ± 2.9 μm, 33.3 ± 3.2 μm였다 (p=0.211, 0.175). 원추세포외절끝과광 1038
- 정현교외 : 황반변성반대안의외망막층두께변화 - Figure 3. Thickness of each layer at the fovea in fellow eyes of patients with unilateral neovascular age-related macular degeneration (namd) and polypoidal choroidal vasculopathy. Error bar is mean ± standard deviation. PCV = polypoidal choroidal vasculopathy; RPE = retinal pigment epithelium; COST = cone outer segment tips; IS/OS = photoreceptor inner segment/outer segment; ELM = external limiting membrane. 수용체내외절경계사이의두께 (COST-IS/OS) 는신생혈관성나이관련황반변성환자군에서 30.8 ± 2.9 μm, 결절맥락막혈관병증환자군에서 31.8 ± 3.9 μm로측정되었고, 광수용체내외절경계와외경계막사이두께 (IS/OS-ELM) 은각각 31.3 ± 2.4 μm, 31.4 ± 2.7 μm로측정되었다 (p=0.323, 0.846). 신생혈관성나이관련황반변성과결절맥락막혈관병증환자들의반대안에서측정한전체망막두께및각망막층사이의두께는모두유의한차이를보이지않았다 (Fig. 3). 전체망막두께및망막색소상피층과원추세포외절끝사이두께 (RPE-COST), 원추세포외절끝과광수용체내외절경계사이두께 (COST-IS/OS), 광수용체내외절경계와외경계막사이의두께 (IS/OS-ELM) 에대한두독립된측정자간의급외상관계수는각각 0.91, 0.83, 0.86, 0.86으로두측정자간의각망막층사이두께측정결과는신뢰할만한재현성을보였다. 고 찰 나이가들수록원추세포초 (cone sheath) 가위축되며짧아지고이로인해망막색소상피층과원추세포외절끝사이의두께가얇아질수있다는연구가보고되었다. 11 망막색소상피층과원추세포외절끝사이의조직은망막색소상피세포, 브루크막, 원추세포초등으로이루어져있으며, 나이가들수록망막색소상피세포와브루크막에는축적물이쌓이면서그두께가증가한다. 12,13 이로인해망막색소상피층을통한대사물질들의이동에장애가생기고, 그결과로영양 공급의부족및허혈로인해원추세포광수용체의기능손상이발생할수있다. 14 한편, 정상망막소견의노인에비해단안나이관련황반변성환자의반대안의망막색소상피세포에리포푸신이더많이축적된다는점으로보아, 15 단안나이관련황반변성환자의반대안의망막색소상피층의두께는정상망막소견을가진노인의눈에비해더두꺼울가능성이높다. 11 그럼에도불구하고망막색소상피층과원추세포외절끝사이의두께가더얇게측정되었다는것은, 이를구성하는다른요소인원추세포초등의구조들이오히려더얇아졌을가능성을의미하며, 나이증가에따른구조변화와마찬가지로원추세포광수용체의기능손상및원추세포초의위축등을그원인으로생각해볼수있다. 하지만현재까지나이증가및나이관련황반변성발생시작전후로원추세포초가어떠한구조의변화를보이는지명확하게실험적으로증명된바가없어이에관한추가적인연구가요구된다. Kenmochi et al 11 은 cirrus 빛간섭단층촬영장비를이용하여단안나이관련황반변성환자의정상소견을보이는반대안과단안의기타다른망막질환을가진환자의정상소견반대안의망막층사이두께를비교하여, 망막색소상피층과원추세포외절끝사이의두께가단안나이관련황반변성환자의반대안에서더얇게측정되었음을보고하였으며이는저자들의연구와상통하는결과이다. 하지만 Kenmochi et al 11 의연구에서대조군의대부분은단안에다양한망막질환을가진환자들이었기때문에, 임상적으로정상소견으로보이는반대안에도망막층에여러잠재적인변화의가능성이있음을한계로제시하였으나, 저자들은양안망막모두임상적으로정상소견을보이는환자들의단안을대조군으로정하여연구를진행하였다. 또한 spectralis 빛간섭단층촬영의경우 cirrus 빛간섭단층촬영을포함한다른종류의빛간섭단층촬영장비에비해정상안에서망막두께를측정함에있어더높은반복성을보인다는점등을고려할때이는본연구의장점이라할수있다. 16,17 본연구의한계점은, 비록뚜렷하게초기나이관련황반변성관련소견이있는환자는연구에서제외하였으나, 환자군의반대안에도작은드루젠등잠재적인초기나이관련황반변성의변화를내포하고있을가능성을완전히배제할수는없다는점이다. 그리고환자군에서나이관련황반변성에이환된눈에과거에항혈관내피세포성장인자치료를시행한여부및종류, 횟수, 기간등은환자마다차이가있었다. 비록 MARINA와 ANCHOR 연구결과라니비주맙으로치료받은환자의반대안에새로운신생혈관이생기는발생률은 sham 또는광역학치료와유의한차이가없음을보고하였으나, 18 국내연구에서는 24개월이상의경과관찰 1039
- 대한안과학회지 2017 년제 58 권제 9 호 - 결과베바시주맙으로치료한환자들에서반대안의맥락막신생혈관발생률이라니비주맙치료군에비해높게나타났다는보고도있으므로, 19 이환된눈에과거에시행하였던항혈관내피세포성장인자치료가반대안에미칠수있는영향을완전히배제할수는없겠다. 또한현재빛간섭단층촬영상각망막층을자동적으로구분해주는소프트웨어가개발되었으나이에외망막층을이루는미세구조들은포함되지않은상태로, 본연구에서보고자한외망막층내각각의망막두께는 caliper를이용해측정자가수기로측정할수밖에없었으며, 빛간섭단층촬영해상도의한계로인해망막색소상피층은외측경계, 원추세포외절끝은내측경계를기준으로하여망막층간두께를측정하였다. 망막색소상피층외측경계부터원추세포외절끝내측경계사이에는브루크막, 망막색소상피세포, 원추세포초, 광수용체외절의일부등의구조들이포함될수있음을고려할때, 그두께의변화에는이러한여러구조들의변화가모두원인이될수있고, 어느한구조가두께변화의주원인이라고명확히밝히기어렵다. 이는추후빛간섭단층촬영장비의해상도가개선되고또한이를통해외망막층내자동구분이가능해지면, 두층을더명확히구분하여측정할수있게되어오차의가능성을줄일수있을것이다. 또한실험적으로외망막층구조의변화를증명할수있는연구도더필요하다고본다. 저자들은빛간섭단층촬영을이용해단안삼출성나이관련황반변성환자들의임상적으로망막의정상소견을보이는반대안과양안모두임상적으로망막의정상소견을보이는환자들에서외망막층에속하는각구조들사이의두께를측정하여비교하였다. 그결과망막색소상피층과원추세포외절끝사이의두께는단안나이관련황반변성환자의무증상반대안에서정상안인대조군에비해더얇게측정되었다. 단안나이관련황반변성환자의반대안에서맥락막신생혈관의발생가능성이더높다는점을고려하면, 본연구결과를통해망막색소상피층과원추세포외절끝사이의두께가더얇을수록나이관련황반변성이발생할위험성도더높을가능성이있다고본다. 상기환자들의장기적인경과관찰을통해망막색소상피층과원추세포외절끝사이의두께가얇게측정된환자들에서실제로대조군에비해신생혈관이유의하게높게발생하는지에관한연구및이에동반되는망막구조의변화를비교하기위한실험적연구도더필요할것으로생각한다. REFERENCES 1) Submacular Surgery Trials Research Group, Solomon SD, Jefferys JL, et al. Incident choroidal neovascularization in fellow eyes of patients with unilateral subfoveal choroidal neovascularization secondary to age-related macular degeneration: SST report No. 20 from the Submacular Surgery Trials Research Group. Arch Ophthalmol 2007;125:1323-30. 2) Five-year follow-up of fellow eyes of patients with age-related macular degeneration and unilateral extrafoveal choroidal neovascularization. Macular Photocoagulation Study Group. Arch Ophthalmol 1993;111:1189-99. 3) Risk factors for choroidal neovascularization in the second eye of patients with juxtafoveal or subfoveal choroidal neovascularization secondary to age-related macular degeneration. Macular Photocoagulation Study Group. Arch Ophthalmol 1997;115:741-7. 4) Klein R, Klein BE, Jensen SC, Meuer SM. The five-year incidence and progression of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology 1997;104:7-21. 5) Klein R, Knudtson MD, Klein BE. Statin use and the five-year incidence and progression of age-related macular degeneration. Am J Ophthalmol 2007;144:1-6. 6) Mukesh BN, Dimitrov PN, Leikin S, et al. Five-year incidence of age-related maculopathy: the Visual Impairment Project. Ophthalmology 2004;111:1176-82. 7) van Leeuwen R, Klaver CC, Vingerling JR, et al. The risk and natural course of age-related maculopathy: follow-up at 6 1/2 years in the Rotterdam study. Arch Ophthalmol 2003;121:519-26. 8) Dunaief JL, Dentchev T, Ying GS, Milam AH. The role of apoptosis in age-related macular degeneration. Arch Ophthalmol 2002; 120:1435-42. 9) Hageman GS, Luthert PJ, Victor Chong NH, et al. An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch's membrane interface in aging and age-related macular degeneration. Prog Retin Eye Res 2001;20: 705-32. 10) Acton JH, Smith RT, Hood DC, Greenstein VC. Relationship between retinal layer thickness and the visual field in early age-related macular degeneration. Invest Ophthalmol Vis Sci 2012;53: 7618-24. 11) Kenmochi J, Ito Y, Terasaki H. Changes of outer retinal thickness with increasing age in normal eyes and in normal fellow eyes of patients with unilateral age-related macular degeneration. Retina 2017;37:47-52. 12) Ramrattan RS, van der Schaft TL, Mooy CM, et al. Morphometric analysis of Bruch's membrane, the choriocapillaris, and the choroid in aging. Invest Ophthalmol Vis Sci 1994;35:2857-64. 13) Friedman E, Ts'o MO. The retinal pigment epithelium. II. Histologic changes associated with age. Arch Ophthalmol 1968; 79:315-20. 14) Curcio CA, Owsley C, Jackson GR. Spare the rods, save the cones in aging and age-related maculopathy. Invest Ophthalmol Vis Sci 2000;41:2015-8. 15) Sarks SH. Ageing and degeneration in the macular region: a clinico-pathological study. Br J Ophthalmol 1976;60:324-41. 16) Pinilla I, Garcia-Martin E, Fernandez-Larripa S, et al. Reproducibility and repeatability of Cirrus and Spectralis Fourier-domain optical coherence tomography of healthy and epiretinal membrane eyes. Retina 2013;33:1448-55. 17) Hafner J, Prager S, Lammer J, et al. Comparison of ganglion cell inner plexiform layer thickness by Cirrus and Spectralis optical coherence tomography in diabetic macular edema. Retina 2017 Apr 3. doi: 10.1097/IAE.0000000000001631. [Epub ahead of print] 1040
- 정현교외 : 황반변성반대안의외망막층두께변화 - 18) Barbazetto IA, Saroj N, Shapiro H, et al. Incidence of new choroidal neovascularization in fellow eyes of patients treated in the MARINA and ANCHOR trials. Am J Ophthalmol 2010;149:939-46.e1. 19) Lee JJ, Lew YJ, Cho SW, Kim JW. Incidence of new choroidal neovascularization in fellow eyes of patients treated for age-related macular degeneration. J Korean Ophthalmol Soc 2013;54:1534-39. = 국문초록 = 단안삼출성나이관련황반변성환자의무증상반대안의외망막층두께변화 목적 : 단안삼출성나이관련황반변성환자의무증상반대안과정상안대조군의외망막층의두께변화를비교하고자하였다. 대상과방법 : 결절맥락막혈관병증을포함한단안삼출성나이관련황반변성환자 60 명과정상안대조군 60 명의의무기록을후향적으로조사하였다. 환자군의무증상반대안과정상안대조군에서 Spectralis 빛간섭단층촬영을시행하여중심와에서전체망막두께및망막색소상피층, 원추세포외절끝, 광수용체내외절경계, 외경계막사이의두께를각각측정하였다. 결과 : 망막색소상피층과원추세포외절끝사이의두께는단안삼출성나이관련황반변성환자의무증상반대안에서 32.4 ± 3.0 μm, 대조군에서 35.3 ± 3.5 μm 로유의한차이를보였다 (p<0.001). 전체망막두께및원추세포외절끝과광수용체내외절경계사이의두께, 광수용체내외절경계와외경계막사이두께는두군간유의한차이를보이지않았다 (p=0.126, 0.615, 0.874). 환자군중신생혈관성나이관련황반변성및결절맥락막혈관병증환자들사이의무증상반대안에서측정한총망막두께및각외망막층사이두께는모두유의한차이가없었다. 결론 : 단안삼출성나이관련황반변성환자의무증상반대안은정상안에비해망막색소상피층과원추세포외절끝사이의두께가더얇았다. 망막색소상피층과원추세포외절끝간의두께가더얇을수록나이관련황반변성이발생할위험성이더높을가능성이있다고본다. < 대한안과학회지 2017;58(9):1036-1041> 1041