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1 대한내과학회지 : 제 83 권제 5 호 의학강좌 - 개원의를위한모범처방 (Current Clinical Practice) 고혈압성안질환 국립중앙의료원안과 오민진 이수영 Ocular Diseases and Hypertension Min Jin Oh and Soo Young Lee Department of Ophthalmology, National Medical Center, Seoul, Korea 고혈압은다양한안질환의원인이되며, 또한여러안질환의진행에영향을미친다. 동맥압력의상승, 말초혈관저항의증가그리고미세혈관손상으로이어지는일련의고혈압성혈관병증은망막에여러단계의고혈압성망막병증을일으킨다 [1]. 뿐만아니라혈압이높을경우당뇨망막병증, 망막동맥 / 정맥폐쇄, 허혈시신경병증, 개방각녹내장, 나이관련황반변성등여러안과적질환의진행이가속화되기도한다 [2-7]. 여기서는고혈압과동반되어나타날수있는흔한안과적질환의양상과진단, 치료방법에대해소개하고자한다. 고혈압망막병증고혈압에의한망막혈관의반응은다양하며망막안저검사를통하여고혈압망막병증의중증도를분류한다 (Fig. 1A). 역사적으로몇가지분류들이제안되어왔지만일반적으로받아들여지는것은 Keith와 Wagner 및 Barker 에의해제안된분류이다 [8]. Grade 1은망막소동맥의경미한협착이있는 경우이며, Grade 2는전반적인소동맥협착이보다심해지고, 국소적협착과경화성변화, 동정맥교차부위의정맥압박이관찰되는경우이다. 망막의출혈, 삼출, 그리고면화반과혈관의강직성변화가관찰되면 Grade 3이며, Grade 4에서는시신경유두부종이나타난다. Grade 1과 Grade 2에서나타나는소동맥의협착은망막모세혈관에서의자가조절과혈관벽의만성적인경화및비후, 그리고유리질변성으로인한것으로, 혈액망막장벽의파괴와혈관내피세포와근세포의괴사가주기전이되는 Grade 3, Grade 4의고혈압망막병증과는구분하여생각할필요가있다. Grade 1과 Grade 2 의구분은다분히주관적이어서관찰자간오차가발생할수있을뿐더러연령증가에따라나타나는변화와구별이어려워임상적인의미를명확히규정하기어렵다 [9]. 하지만 Grade 3과 Grade 4는심장, 뇌, 신장의기능부전과깊은관련이있으며, WHO 의 2003년고혈압관리권고안에서는 Grade 3과 Grade 4의고혈압망막병증을주요표적장기손상으로분류하였고, 2007년개정된유럽심장학회- 유럽고혈압학회의고혈압관리권고안에서 Grade 3과 Grade 4에해당하는망막 Correspondence to Soo Young Lee, M.D., Ph.D. Department of Ophthalmology, National Medical Center, 245 Eulji-ro, Jung-gu, Seoul , Korea Tel: , Fax: , sooyoung09@gmail.com Copyright c 2012 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

- The Korean Journal of Medicine: Vol. 83, No.

subretinal hemorrhage and neurosensory retinal

(C) Advanced glaucomatous cupping in open angle glaucoma.

2 - The Korean Journal of Medicine: Vol. 83, No. 5, A B C D E F Figure 1. (A) Hypertensive retinopathy. Photograph shows multiple retinal hemorrhages, hard exudates and cotton wool spot. (B) Choroidal neovascularization accompanied with subretinal hemorrhage and neurosensory retinal detachment. (C) Advanced glaucomatous cupping in open angle glaucoma. Photography demonstrates the marked enlargement of cup and the retinal nerve fiber layer loss. (D) Central retinal vein occlusion with extensive retinal hemorrhage. (E) Branch retinal vein occlusion involving the superotemporal quadrant of the left eye. (F) Macroaneurysm with surrounding ring of lipid exudates

3 - Min Jin Oh, et al. Ocular diseases and hypertension - 출혈과삼출, 시신경유두부종을표적장기손상의고위험지표로규정하였다 [10,11]. 가장최근에발표된 2011년영국고혈압진료권고안에서도고혈압망막병증을주요표적장기손상으로분류하고, 혈압이 180/110 mmhg 이상인경우망막출혈이나시신경유두부종이발견되면당일에고혈압전문의에게의뢰할것을권고하고있다 [12]. 따라서 Grade 3과 Grade 4의감별과발견은고혈압의치료와관리에매우중요한의미가있으며망막출혈, 삼출, 시신경유두부종의경우시력저하를동반하는경우가많기때문에병력청취에유의하여야한다 [11]. 고혈압환자에서의망막검사는고혈압의경계에있는환자에서고혈압망막병증을발견하여약제치료를신속히시작할지를판단할수있는효용성이있으며, 다른표적장기질환이없어도망막병증이발견되면심혈관계위험도가증가하기때문에더욱엄격한혈압관리목표를설정하는데도움이될수있다 [13]. 맥락막신생혈관 ( 습성나이관련황반변성 wet age-related macular degeneration) 최근평균수명이급속히연장되어사회의노령화가진행됨에따라나이관련황반변성이 70대이상노인의실명의주된원인으로거론되고있다. 나이관련황반변성은맥락막신생혈관, 망막색소상피박리, 망막색소상피파열, 위축성상흔등을동반하여결국심한시력감소를초래하게된다 (Fig. 1B). 나이관련황반변성의위험인자로는연령증가이외에도고혈압, 콜레스테롤, 가족력, 흡연, 자외선노출, 인종, 그리고비타민 E, C, 베타카로틴등의영양요인등이거론되고있다 [14-18]. 나이관련황반변성과고혈압과의연관성에대하여아직까지인과관계유무가명확히밝혀지지는않았지만, 수축기혈압이 160 mmhg 이상또는이완기혈압이 100 mmhg 이상인고혈압에서맥락막신생혈관 ( 습성나이관련황반변성 ) 의위험도가증가하므로심한고혈압이습성나이관련황반변성에위험요인이될가능성은충분하다 [7]. 또한고혈압과관련된동맥경화성변화가맥락막혈관의혈류와투과에영향을미칠것이라는것과 C-reactive protein, interleukin-6 등의염증물질들도영향을미칠수있을것이다 [19]. 습성나이관련황반변성 ( 맥락막신생혈관 ) 의치료로는최근항혈관내피성장인자인 ranibizumab 의유리체강내주사요법이사용되고있는데 ranibizumab 이외에도대장암의 치료제로 FDA 승인을받은 bevacizumab이 off-label ( 허가범위초과사용 : FDA 에서인가되지않은약품의사용 ) 로이용되고있다. Bevacizumab을대장암환자에게항암제로정맥주사를할경우혈압상승과심혈관계합병증증가등의주된부작용이있음이알려져있으나, 적은용량의유리체강내주사후에도급격한혈압상승과뇌출혈의발생이드물게보고된바있으므로주의해야한다 [20,21]. 따라서맥락막신생혈관환자에서 bevacizumab 의유리체강내주사를시행할때혈압의변동과경과를주의깊게관찰해야한다. 개방각녹내장개방각녹내장은특징적인시신경손상에의한시야장애를보이는진행성시신경병증이다 (Fig. 1C). 녹내장의위험인자로가족력, 인종, 고혈압, 고령, 당뇨등이논의되어왔지만녹내장의병태생리에영향을주는주된위험인자는높은안압과낮은안관류압 (ocular perfusion pressure) 이다 [22]. 녹내장의치료는포도막공막유출을증가시키거나방수생산을감소시키는 prostaglandin 제제, 탄산탈수효소억제제, 선택성알파2 작용제나베타차단제와같은교감신경계약물을사용하여안압을낮추는것을목표로하며약물로조절이되지않는경우섬유주절제술이나방수유출장치삽입술을시행하게된다. 안압은전신혈압상승의영향을크게받지는않지만, 안압이일정하다면혈압이낮을수록안관류압이낮아지게되므로과도하게낮은혈압은오히려녹내장의위험인자로작용할수있다 [22-25]. 특히고혈압환자에서는광범위한혈관손상으로시신경유두혈액순환의자동조절기전에장애가있는경우가많아안관류압의변화에더욱취약하게된다 [26]. 따라서녹내장을동반한고혈압환자는안압과혈압의적절한유지와조절이필요하며특히갑작스런혈압강하가녹내장을악화시킬가능성에주의해야한다 [27]. 기타의망막혈관질환들고혈압은망막동맥폐쇄, 망막정맥폐쇄, 망막대동맥류등의망막혈관질환들의주된위험인자이다 (Fig. 1D, 1E, and 1F). 망막혈관폐쇄의원인은색전, 혈전, 동맥경화, 혈관염, 박리동맥류등다양하다 [28,29]. 망막동맥류의발생은고혈압과동맥경화성혈관변화와관련이있다. 망막혈관색전

4 - 대한내과학회지 : 제 83 권제 5 호통권제 627 호 의가장흔한기원은경동맥으로, 망막혈관색전이발견되는환자는고혈압, 지질대사이상, 비만, 당뇨에대한전신적인검사와경동맥초음파검사를시행하여향후의색전발생위험성을확인하고 2차예방하여야한다 [6]. 안과의사는망막이나홍채의신생혈관과황반부종의발생여부를주기적으로관찰하며필요시약물치료나레이저광응고술을시행하게된다. 결 고혈압은고혈압망막병증을비롯한다양한망막혈관질환, 개방각녹내장, 맥락막신생혈관등과밀접한관련이있으며고혈압환자를관리할때다양한안과질환에대한이해가필요하다. 중심단어 : 고혈압망막병증 ; 나이관련황반변성 ; 개방각녹내장 ; 망막동맥폐쇄 ; 망막정맥폐쇄 론 REFERENCES 1. Wong TY, Mitchell P. Hypertensive retinopathy. N Engl J Med 2004;351: Estacio RO, Jeffers BW, Gifford N, Schrier RW. Effect of blood pressure control on diabetic microvascular complications in patients with hypertension and type 2 diabetes. Diabetes Care 2000;23(Suppl 2):B54-B Memarzadeh F, Ying-Lai M, Chung J, Azen SP, Varma R; Los Angeles Latino Eye Study Group. Blood pressure, perfusion pressure, and open-angle glaucoma: the Los Angeles Latino Eye Study. Invest Ophthalmol Vis Sci 2010; 51: Rogers SL, McIntosh RL, Lim L, et al. Natural history of branch retinal vein occlusion: an evidence-based systematic review. Ophthalmology 2010;117: Hayreh SS. Management of ischemic optic neuropathies. Indian J Ophthalmol 2011;59: Hayreh SS, Podhajsky PA, Zimmerman MB. Retinal artery occlusion: associated systemic and ophthalmic abnormalities. Ophthalmology 2009;116: Hogg RE, Woodside JV, Gilchrist SE, et al. Cardiovascular disease and hypertension are strong risk factors for choroidal neovascularization. Ophthalmology 2008;115: Keith NM, Wagener HP, Barker NW. Some different types of essential hypertension: their course and prognosis. Am J Med Sci 1974;268: Van den Born BJ, Hulsman CA, Hoekstra JB, Schlingemann RO, van Montfrans GA. Value of routine funduscopy in patients with hypertension: systematic review. BMJ 2005; 331: Whitworth JA; World Health Organization, International Society of Hypertension Writing Group World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens 2003;21: Mancia G, De Backer G, Dominiczak A, et al Guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2007; 28: National Clinical Guideline Centre (UK). Hypertension: The Clinical Management of Primary Hypertension in Adults: Update of Clinical Guidelines 18 and 34 [Internet]. London: Royal College of Physicians (UK); 2011 Aug. Available from : Grosso A, Veglio F, Porta M, Grignolo FM, Wong TY. Hypertensive retinopathy revisited: some answers, more questions. Br J Ophthalmol 2005;89: Hyman LG, Lilienfeld AM, Ferris FL 3rd, Fine SL. Senile macular degeneration: a case-control study. Am J Epidemiol 1983;118: Goldberg J, Flowerdew G, Smith E, Brody JA, Tso MO. Factors associated with age-related macular degeneration: an analysis of data from the first National Health and Nutrition Examination Survey. Am J Epidemiol 1988;128: Risk factors for neovascular age-related macular degeneration: the Eye Disease Case-Control Study Group. Arch Ophthalmol 1992;110: Antioxidant status and neovascular age-related macular degeneration: Eye Disease Case-Control Study Group. Arch Ophthalmol 1993;111: West SK, Rosenthal FS, Bressler NM, et al. Exposure to sunlight and other risk factors for age-related macular degeneration. Arch Ophthalmol 1989;107: Boekhoorn SS, Vingerling JR, Witteman JC, Hofman A, de Jong PT. C-reactive protein level and risk of aging macula disorder: the Rotterdam Study. Arch Ophthalmol 2007;125: Saif MW, Mehra R. Incidence and management of bevacizumab-related toxicities in colorectal cancer. Expert Opin Drug Saf 2006;5: Arevalo JF, Sánchez JG, Wu L, et al. Intravitreal bevacizumab for subfoveal choroidal neovascularization in agerelated macular degeneration at twenty-four months: the Pan-American Collaborative Retina Study. Ophthalmology

5 - 오민진외 1 인. 고혈압성안질환 ;117: Dielemans I, Vingerling JR, Algra D, Hofman A, Grobbee DE, de Jong PT. Primary open-angle glaucoma, intraocular pressure, and systemic blood pressure in the general elderly population: the Rotterdam Study. Ophthalmology 1995;102: Klein BE, Klein R, Knudtson MD. Intraocular pressure and systemic blood pressure: longitudinal perspective: the Beaver Dam Eye Study. Br J Ophthalmol 2005;89: Tielsch JM, Katz J, Sommer A, Quigley HA, Javitt JC. Hypertension, perfusion pressure, and primary open-angle glaucoma: a population-based assessment. Arch Ophthalmol 1995;113: Bonomi L, Marchini G, Marraffa M, Bernardi P, Morbio R, Varotto A. Vascular risk factors for primary open angle glaucoma: the Egna-Neumarkt Study. Ophthalmology 2000; 107: Kaiser HJ, Flammer J. Systemic hypotension: a risk factor for glaucomatous damage? Ophthalmologica 1991;203: Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38: UK Prospective Diabetes Study Group. BMJ 1998;317: Erratum in: BMJ 1999;318: Wong TY, Larsen EK, Klein R, et al. Cardiovascular risk factors for retinal vein occlusion and arteriolar emboli: the Atherosclerosis Risk in Communities & Cardiovascular Health Studies. Ophthalmology 2005;112: Wong TY, Scott IU. Clinical practice: retinal-vein occlusion. N Engl J Med 2010;363:

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A 617 Special Issue Diabetic Retinopathy Won Ki Lee, M.D. Department of Ophthalmology The Catholic University of Korea College of Medicine Kangnam St. Mary s Hospital E mail : wklee@catholic.ac.kr Abstract R