대한안과학회지 2016 년제 57 권제 9 호 J Korean Ophthalmol Soc 2016;57(9):1386-1391 ISSN 0378-6471 (Print) ISSN 2092-9374 (Online) http://dx.doi.org/10.3341/jkos.2016.57.9.1386 Original Article 유리체절제술후안압상승환자에서무보존제도르졸라미드 - 티몰롤복합제제의안압하강효과 Effect of a Preservative-free Dorzolamide/Timolol Fixed Combination on Elevated Intraocular Pressure after Vitrectomy 이성훈 1 이원석 1 성공제 1 변석호 1 김성수 2 고형준 2 이성철 2 김민 1 Sung Hoon Lee, MD 1, Wonseok Lee, MD 1, Gong Je Seong, MD 1, Suk Ho Byeon, MD 1, Sung Soo Kim, MD 2, Hyoung Jun Koh, MD 2, Sung Chul Lee,MD 2, Min Kim, MD 1 연세대학교의과대학강남세브란스병원안과학교실 1, 연세대학교의과대학안과학교실시기능개발연구소 2 Department of Ophthalmology, Gangnam Severance Hospital, Yonsei University College of Medicine 1, Seoul, Korea The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine 2, Seoul, Korea Purpose: To verify the effect of preservative-free Dorzolamide/Timolol fixed combination (PFDTC) on intraocular pressure (IOP) elevation after vitrectomy. Methods: We retrospectively reviewed medical records of 33 patients who used PFDTC after pars plana vitrectomy. All patients visual acuity and IOP was measured and symptoms of conjunctival irritation were investigated through survey and slit lamp examination. Results: Before vitrectomy, the mean IOP was 13.6 ± 4.4 mm Hg which was elevated to 31.7 ± 5.4 mm Hg after vitrectomy (p < 0.001) and applying eyedrop lowered the mean IOP to 17.2 ± 7.0 mm Hg (p < 0.001). Regardless of tamponade material type, all elevated IOP decreased (p < 0.001) and the IOP of all 33 eyes did not rise to over 30 mm Hg again. No additional surgery for IOP control was needed during two-month follow-up period. Of the 33 patients using PFDTC, patients who felt discomfort were five (15.2%) and no patients showed side effects severe enough to stop use of eyedrop. Conclusions: PFDTC is an anti-glaucomatic agent which can reduce the IOP by inhibiting aqueous humor production. Without need for additional surgery, the eyedrop can effectively lower elevated post-vitrectomy IOP, with expectation of good patient compliance due to low risk of conjunctival irritation. J Korean Ophthalmol Soc 2016;57(9):1386-1391 Keywords: Cosopt-S, Eyedrops, Intraocular pressure, Preservative-free, Vitrectomy 유리체절제술이개발된이후기구가발전함에따라트로카 (trocar) 를포함한수술기구의크기는점점더작아지고 Received: 2016. 3. 10. Revised: 2016. 5. 13. Accepted: 2016. 8. 29. Address reprint requests to Min Kim, MD Department of Ophthalmology, Gangnam Severance Hospital, #211 Eonju-ro, Gangnam-gu, Seoul 06273, Korea Tel: 82-2-2019-3445, Fax: 82-2-3463-1049 E-mail: Minkim76@gmail.com 비침습적으로변하고있으며, 이에따라수술후염증및외상, 환자불편감, 안압상승등의합병증은점차줄고있다. 1-4 그러나성공적인유리체절제술후에도지속적인안압상승으로인한시신경손상이발생할수있으며안압상승시에는시신경손상이진행되지않도록안압을낮추는것이중요하다. 5-7 안압을낮추는방법으로는수술치료, 약물치료, 레이저치료, 안압하강점안액사용등이있으며유리체절제술후가장쉽게사용할수있는일차치료는안압하강점안액사용이다. 8 안압하강점안액중 Cosopt R (Merck c2016 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. 1386
- 이성훈외 : 유리체절제술후 Cosopt-S 의안압하강효과 - & Co., Inc., Kenilworth, NJ, USA) 은탄산탈수효소억제제인 2% 도르졸라미드 (dorzolamide hydrochloride) 22.3 mg/ml 와비선택적베타교감길항제인 0.5% 티몰롤 (timolol malaete) 6.8 mg/ml 를혼합한약제로비교적부작용이적고높은안압하강효과가있는복합제제이다. 복합제제는약제각각을사용할때보다점안횟수를줄이면서도더큰안압하강효과를얻을수있으며약제를따로사용함으로써첫번째점안액이희석되어씻겨내려가는것을막을수있어임상적으로많이사용된다. 9 한편안압하강치료에있어점안액을사용할때는보존제로인해안구불편감및작열감으로환자에게불편함을초래할수있고알레르기반응등의부작용이발생할수있어환자의순응도를떨어뜨리는원인이된다. 10,11 하지만 Cosopt-S R 제품의경우무보존제도르졸라미드-티몰롤복합제제로환자결막자극반응이적고이로인해사용순응도가보존제포함약제에비해높다. 8 이러한장점으로인해 Cosopt-S R 는이미국내에서도많이사용되는약제이나아직까지한국인을대상으로유리체절제술후안압하강효과를확인한연구는이루어지지않았다. 이에본연구는한국인에서유리체절제술후안압이상승된환자에서무보존제도르졸라미드-티몰롤복합제제의안압하강효과를확인하고결막반응이적은무보존제제형의장점을확인하고자한다. 대상과방법 대상선정본연구는본원안과에서유리체절제술을받은뒤안압상승으로무보존제도르졸라미드-티몰롤복합제제를사용한환자를대상으로하였고후향적으로의무기록을분석하였다. 유리체절제술전단순백내장제거및인공수정체삽입술이외에다른안과수술력이있거나, 녹내장을진단받아안압하강점안액을사용하고있던환자및안저검사상시신경에서녹내장성변화가의심되는환자는제외하였다. 또한세극등검사에서주변부전방각이각막두께의 1/4보다작은경우나, 신생혈관이나주변부전방각유착등안압이상승할만한구조적문제가있을시연구대상에서제외하였다. 구면대응치기준 ±6디옵터 (diopter) 를초과하는굴절력이상자및부안검, 만성각막미란, 각막이영양증, 중증이상의알레르기결막염등질환이나각막형태이상자역시제외하였다. 문진에의해심부전증등의심계이상자, 천식, 만성폐쇄적폐질환, 임신과간질환의과거력이있는자도제외하였다. 모든환자는본인의자발적동의하에본연구가진행되었으며헬싱키선언을준수하였고본원윤리위원회의승인을받아 (IRB approval number: 3-2016-0120) 진행하였다. 수술방법모든유리체절제술은한명의술자 (M.K) 에의해시행되었으며 Constellation (Alcon Laboratories., Inc., Fort Worth, TX, USA) 장비와비접촉광각관찰장치 (BIOM, Oculus, Wetzlar, Germany) 를이용하여무봉합유리체절제술 (Transconjunctival sutureless vitrectomy, TSV) 을시행하였다. 수술은 3개의공막천자를섬모체평면부를통해, 25게이지유리체절단침을사용하여진행하였다. 안내기름주입술을같이시행하였을경우실리콘오일을주입하였으며, 안내가스주입술을하였을경우에는 14% C 3F 8 가스와 20% SF 6 가스를사용하였다. 검사방법대상자들은유리체절제술을받기전에고혈압과당뇨를포함한전신질환에대한병력청취를하였으며시력검사, 골드만압평안압계를이용한안압측정 (Goldmann applanation tonometery), 자동검영굴절검사 (KR-1, Topcon, Tokyo, Japan) 를시행하였고, 산동및안저검사를시행하였다. 대상자들은유리체절제술후 1일뒤퇴원하였으며수술 1일, 1주, 1 달, 2달후안압을골드만압평안압계로측정하였다. 안압의측정은오전 9시에시행하였으며각각 3번측정하여 3 번측정치의평균치를기록하였고수술후안압상승을유발한만한신생혈관이나주변부전방각유착등의구조적문제가새로발생하였는지확인하기위해전방각경검사를시행하였다. 내원시마다세극등검사를통해결막의충혈정도, 각막미란, 전방의세포유무를관찰하였고, 안압이하강되어점안액사용을중단한뒤첫내원시문진을하여점안액을사용하는동안동통, 이물감, 소양감, 건조감등의유무를확인하였다. 약제및사용기준안압하강점안액사용은유리체절제술후안압이 30 mmhg 이상일때사용하였으며안압이 21 mmhg 이하로떨어질때까지사용하였고점안액은 Cosopt-S R (Merck & Co., Inc., Kenilworth, NJ, USA) 를하루두번아침, 저녁사용하였다. 통계학적분석 SPSS 21.0 프로그램 version 21.0 (IBM Corp., Armonk, NY, USA) 을사용하였으며안압변화가있는지보기위해수술전후, 안압약사용전후를 paired t-test를이용하여분석하였다. 충전술종류에따라안압상승및하강정도의차이가있는지비교하기위하여 Kruskal Wallis H test를시행하였으며 p-value 0.05 미만인경우통계적으로유의하다고판단하였다. 1387
- 대한안과학회지 2016 년제 57 권제 9 호 - 결 과 유리체절제술시행후무보존제도르졸라미드-티몰롤복합제제를처방받아사용한환자는총 33명 33안이었으며남자 26명, 여자 7명이었고평균연령은 55.4 ± 13.7세 (26-78세) 였으며전신질환으로고혈압을가진환자가 2명, 당뇨로진단받은환자는 5명이었다. 33안중유리체절제술전인공수정체안이 12안이었으며 21안이수정체안이었고, 수정체안 21안중 15안은유리체절제술을진행하며백내장적출및인공수정체삽입술을같이시행하였다. 16 안 (45.7%) 은충전술없이유리체절제만시행하였으며유리체절제술후안내기름주입술을시행한안은 11안 (31.4%), 안내가스주입술을시행한안은 6안 (17.1%) 이었다 (Table 1). 수술원인으로는망막박리가 18안, 망막전막이 5안, 삽입되어있던인공수정체문제가 5안, 당뇨망막병증이 4안, 유리체강내출혈이 1안이었다. 수술후시행한전방각경검사에서신생혈관이나주변부전방각유착등안압이상승을유발할만한전방각이상소견은없었다. Table 1. Patient characteristics, surgery type and indication for surgery in the pars plana vitrectomy Data Age (years) 55.4 ± 13.7 (26-78) Sex (male/female) 26:7 Surgery type (n, %) Vitrectomy without intraocular tamponade 16 (45.7) Vitrectomy with silicone oil tamponade 11 (31.4) Vitrectomy with gas tamponade 6 (17.1) Indication for surgery (n, %) Retinal detachment 18 (54.5) Epiretinal membrane 5 (15.2) IOL problem (IOL dislocation etc.) 5 (15.2) Diabetic retinopathy 4 (12.1) Vitreous hemorrhage 1 (3.0) Values are presented as mean ± SD unless otherwise indicated. n = number of eyes; IOL = intraocular lens. 유리체절제술전평균안압은 13.6 ± 4.4 mmhg였으며수술받지않은눈의평균안압은 12.9 ± 2.5 mmhg로두군의유의한차이는없었다 (p=0.324). 유리체절제술후 1 일뒤수술안의평균안압은 31.7 ± 5.4 mmhg였으며수술전과비교하여유의하게안압이높아졌다 (p<0.001). 점안액사용 1주후평균안압은 17.2 ± 7.0 mmhg로수술후상승한안압과비교하여유의하게하강하였다 (p<0.001). 수술후두달뒤평균안압은 13.4 ± 3.5 mmhg 였고수술전안압과비교하여통계적차이는없었으며 (p=0.725) 수술직후상승한안압과비교하여유의하게하강하였다 (p<0.001) (Table 2). 점안액을사용하는동안고삼투압제제나전방천자가필요한사람은없었고 2개월관찰기간동안 33안모두에서안압이 30 mmhg 이상으로다시상승한경우는없었다. 33 안모두추가적인안압하강점안제가필요한경우는없었으며안압을낮추기위한녹내장수술등의추가적인수술이필요한경우도없었다충전술의종류에따라안내기름주입술을시행한안, 안내가스주입술을시행한안, 안내충전술을시행하지않고유리체절제술만시행한안을비교하였을때점안액사용은 3가지경우모두에서유의한안압하강효과가있었다 (p<0.001, p<0.001, p<0.001) (Table 3). 수술전인공수정체안과수정체안두군의안압하강정도를비교하여보았을때, 인공수정체안의안압은평균 19.3 ± 5.7 mmhg 감소하였으며수정체안은 15.8 ± 7.0 mmhg 감소하였으나통계적으로두군의안압하강정도의유의한차이는없었다 (p=0.148). 안압상승후안압이하강할때까지점안액을사용한기간은충전술종류에따라안내기름주입술시행한안이 6.2 ± 3.4일, 안내가스주입술을시행한안이 7.2 ± 1.7일, 안내충전술없이유리체절제술만시행안안이 6.8 ± 2.6 일이었으며세군간의사용기간의통계적차이는없었다 (p=0.245). 또한수술전인공수정체안과수술전수정체안의점안액사용기간은각각 6.5 ± 2.9일, 6.7 ± 3.1일이 Table 2. Intraocular pressure change over time expressed as mean, standard deviation, range and pressure difference from pre-operative pressure in patients undergoing pars plana vitrectomy Mean IOP ± SD (mm Hg) IOP range (mm Hg) Mean IOP difference from pre op. (p-value) * Mean IOP difference from immediate post op. (p-value) Pre op. 13.6 ± 4.4 7-29 - - Immediate post op. 31.7 ± 5.4 18-45 17.9 ± 6.9 (p < 0.001) - 1 week after vitrectomy 17.2 ± 7.0 5-33 3.6 ± 7.2 (0.007) 14.5 ± 8.0 (p < 0.001) 1 month after vitrectomy 14.3 ± 4.8 8-28 0.6 ± 5.5 (0.511) 17.4 ± 6.7 (p < 0.001) 2 months after vitrectomy 13.4 ± 3.5 7-24 -0.3 ± 4.4 (0.725) 18.3 ± 6.2 (p < 0.001) Values are presented as mean ± SD unless otherwise indicated. IOP = intraocular pressure; SD = standard deviation; Pre op. = pre-operative status; Post op. = post-operative status. * Significant difference (p < 0.05) in paired t-test between pre-operative IOP and post-operative IOPs; Significant difference (p < 0.05) in paired t-test between immediate post-operative IOPs and post-operative IOPs. 1388
- 이성훈외 : 유리체절제술후 Cosopt-S 의안압하강효과 - Table 3. Intraocular pressure change and duration of eye drop using in patients undergoing pars plana vitrectomy depending on tamponade material used Pre op. IOP Immediate post op. Post op. IOP at 1 Post op. IOP at 1 Post op. IOP at 2 Mean IOP ± SD change after using Duration of eyedrop using IOP week month month eyedrop (mm Hg) (days) SIO tamponade 13.0 ± 6.4 31.2 ± 5.6 17.7 ± 7.8 15.2 ± 5.9 14.0 ± 4.4 17.2 ± 7.3 p < 0.001 6.2 ± 3.4 Gas tamponade 11.3 ± 2.0 33.8 ± 6.9 16.8 ± 9.1 11.8 ± 4.1 12.7 ± 2.3 21.2 ± 5.8 p < 0.001 7.2 ± 1.7 TPPV without 14.9 ± 3.0 31.3 ± 4.0 17.1 ±5.9 14.6 ± 4.3 13.2 ± 3.1 18.1 ± 5.5 p < 0.001 6.8 ± 2.6 tamponade p-value among three groups * p = 0.056 p = 0.858 p = 0. 843 p = 0.335 p = 0.852 p = 0.314 - p = 0.245 Values are presented as mean ± SD unless otherwise indicated. Pre op. = pre-operative status; IOP = intraocular pressure; Post op. = post-operative status; SD = standard deviation; SIO =silicone oil; TPPV = trans pars plana vitrectomy. * Significant difference (p < 0.05) in Kruskal Wallis H test among SIO tamponade, Gas tamponade and TPPV without tamponade eyes; Mean IOP ± SD change after using eyedrop was calculated between immediate post op. IOP and 2 month post op. IOP; p-value was calculated by paired t-test between immediate post op. IOP and 2 month post op. IOP. 었으며두군의차이는없었다 (p=0.238). 안압이낮아져점안액사용을중단후첫내원시시행한문진에서무보존제도르졸라미드-티몰롤복합제제사용후불편감발생여부와불편감의종류를묻는질문에는 그렇다 는대답이 5명 (15.2%) 그렇지않다 라고답한사람이 28명 (84.8%) 이었다. 점안후느끼는불편감 ( 복수응답가능 ) 으로는안구의작열감이가장많았으며 (5명), 안통 (2명), 이물감 (2명), 건조감 (1명) 순이었다. 세극등검사상각막면적의 1/4 이상미란이생긴환자는 4명이었으나그로인한불편감이심해약제사용을중단한경우는없었으며, 결막충혈이생긴환자는 2명이었으나 1주이상지속되는경우는없었다. 고찰 유리체절제술후안내기름주입술이나가스주입술을시행한충전안의경우안압상승이일어날수있다는것은잘알려져있다. 12-15 그러나안내충전술없이유리체절제술만시행하였을경우에도안압이상승할수있다. 이러한안압상승은시신경손상이나황반부허혈, 중심망막정맥폐쇄등을유발하여성공적인수술후에도설명되지않는심각한시력손실을유발할수있기에주의해야하며상승된안압은빨리낮춰줘야한다. 유리체절제술후안압상승은여러가지복합적인원인에의해나타날수있다. 수술시사용되는충전제와관련하여가능한원인으로는안내주입된기름이나안내가스의팽창, 이로인한동공폐쇄 (pupillary block), 섬모체부종등이있을수있다. 16 복잡한망막박리 (Complex retinal detachment) 에서유리체절제술후안내기름주입술시행시실리콘오일이앞으로밀고나오며동공폐쇄를유발하여방 수의전방이동을막아안압이상승할수있고, 이를예방하기위하여하단부주변부홍채절개술을시행하기도한다. 17 또한실리콘오일이전방내로직접이동하며안압상승을유발하기도한다. 마찬가지로안내가스주입을했을경우에도가스의농도가높거나양이많아, 가스가팽창을하고동공폐쇄를일으켜안압상승을유발할수있다. 수술직후에는수술후발생하는전방수입자 (flare) 나염증매개체들 (inflammatory mediator) 이섬유주를폐쇄함으로안압이상승할수있으며이는레이저후낭절개술후일어나는안압상승과같은원리이다. 16,18-20 또한유리체출혈에서유발된적혈구의용혈작용에의해남은조직물질들이섬유주를폐쇄하여안압이상승할수도있으며, 실제본연구에서도유리체출혈로인해유리체절제술후안압이상승하였던환자가있었다. 장기간망막박리가지속되고망막열공크기가큰환자에서는방수플래어 (aqueous flare) 가심해지고, 이로인해섬유주폐쇄를유발하여안압이오를수도있다. 21 또한유리체절제술을시행치않은눈에서는산소가망막동맥으로부터혈관이없는유리체강내로유리체의방해를받으며분산되어산소농도가낮으나, 유리체절제술을시행한눈의경우에는유리체의방해가없어산소의농도가증가하며섬유주에산화성손상 (oxidative damage) 을주어섬유주를통한방수유출을방해하여안압이오를수도있다. 22 그외수술후시행하는결막하덱사메타손주사나결막하항생제주사도안압상승원인이될수도있으나이는주요원인이라단정짓기는쉽지않다. 덱타메타손의경우스테로이드반응 (steroid response) 을유발하여안압이오를수있으나한편으로는혈액-눈장벽 (blood ocular barrier) 의파괴나프로스타글란딘방출을낮추기에안압상승의방어인자가될수도있다. 19,20,23 같은기전으로수술후사용하 1389
- 대한안과학회지 2016 년제 57 권제 9 호 - 는스테로이드점안액역시안압상승요인이되기도하며안압하강요인도될수있다. 항생제의경우높은농도로과량을사용시안압이상승할수도있으나, 일반적으로수술후창상감염예방용결막하주사로안압상승을유발했다는보고는아직까지없다. 도르졸라미드-티몰롤복합제제가효과적인안압하강을보이는이유는두가지제제, timolol maleate와 2% dorzolamide hydrochloride가각각다른기전을통해방수생성을감소시키기때문이다. Dorzolamide hydrochloride는 thieno-thieno-tehiopy-ran-2-sulfonamide 약제로서모양체의 carbonic anhydrase-ii 효소를억제하여방수생성을줄이고, 0.5% timolol maleate는비선택적베타교감길항제로서 cyclic adenosine monophosphate의생산을줄여능동이온이동을방해하고방수의생산을줄인다. 24,25 또한두제제를따로사용하는병용투여와비교해서복합제제가대등한효과를가짐이입증되고사용이더욱편리하여많이사용되고있다. 26 또한도르졸라미드- 티몰롤복합제제는방수유출을늘이는것이아니라방수생성자체를줄이는기전이기에충전체가방수유출을방해하더라도충전체종류에관계없이효과적으로안압을낮출수있으며충전체를사용하지않은유리체절제술에서도역시유의하게효과가있는것이강점이될수있다 (Table 3). 한편보존제포함도르졸라미드-티몰롤복합제제의불편감으로는흐림현상과작열감등이있으며이외안검부종, 결막충혈, 이물감, 눈부심등이알려져있다. 27 그러나무보존제혼합제제는결막을자극하는보존제를사용하지않아, 점안대상자로하여금자극감과불편감을줄일수있었고선행연구에서도무보존제도르졸라미드-티몰롤복합제제에서불편감이줄어들고이로인해환자의점안순응도가높아진다고나타났다. 8 또한 Pisella et al 28 의연구에따르면보존제포함녹내장안약사용시불편감을느낀사람의비율은 43.0% 였으며무보존제녹내장안약사용시 17.0% 였다. 본연구에서도주관적인불편감을호소하는환자의비율은 15.2% 였으며불편감이심하여안약점안을중단하거나다른점안액으로바꿀정도로불편해한환자는없었다. 후향적연구이기에보존제포함도르졸라미드-티몰롤복합제제와직접비교하지는못하였으나무보존제도르졸라미드-티몰롤복합제제에서불편감을느끼는환자의비율이보존제포함제제에비해낮을것으로보인다. 결국보존제가없기때문에점안대상자가느끼는불편감은감소하고, 이는대상자의점안순응도를높일것으로예상된다. 도르졸라미드-티몰롤복합제제는방수생성억제를주기전으로하는약제로서본연구에서유리체절제술시행안, 유리체절제술후안내기름주입술시행안, 유리체절제술후안내가스주입술시행안모두에서, 비정상적으로안압이상승하였을때점안액만으로충분한안압하강효과가있어추가적으로안압을낮추기위해녹내장수술등이필요하지않았다. 본연구의한계점으로는연구대상이 33명으로적으며, 또한후향적연구이기에안압하강점안액을다른종류안압하강점안액의효과와직접적으로비교하지못한것과, 보존제포함도르졸라미드-티몰롤복합제제와무보존제도르졸라미드-티몰롤복합제제의사용불편감을직접비교하지못한것등이있다. 향후연구에서는연구대상환자수를늘려전향적으로다양한안압하강점안액과비교, 연구한다면유리체절제술후안압하강을위한점안액선택기준을세우는데도움이될것으로생각된다. 결론적으로유리체절제술후안압이상승하였을경우에도르졸라미드-티몰롤복합제제를사용함으로써충전체종류에상관없이모두에서포괄적이고효과적인안압하강효과를기대할수있고, 무보존제도르졸라미드-티몰롤복합제제는결막자극성이적어환자의점안순응도를높일것으로기대된다. REFERENCES 1) Fujii GY, De Juan E Jr, Humayun MS, et al. A new 25-gauge instrument system for transconjunctival sutureless vitrectomy surgery. Ophthalmology 2002;109:1807-12; discussion 1813. 2) Fujii GY, De Juan E Jr, Humayun MS, et al. Initial experience using the transconjunctival sutureless vitrectomy system for vitreoretinal surgery. Ophthalmology 2002;109:1814-20. 3) Ibarra MS, Hermel M, Prenner JL, Hassan TS. Longer-term outcomes of transconjunctival sutureless 25-gauge vitrectomy. Am J Ophthalmol 2005;139:831-6. 4) Kellner L, Wimpissinger B, Stolba U, et al. 25-gauge vs 20-gauge system for pars plana vitrectomy: a prospective randomised clinical trial. Br J Ophthalmol 2007;91:945-8. 5) Hayreh SS. Anterior ischemic optic neuropathy. IV. Occurrence after cataract extraction. Arch Ophthalmol 1980;98:1410-6. 6) Kangas TA, Bennett SR, Flynn HW Jr, et al. Reversible loss of light perception after vitreoretinal surgery. Am J Ophthalmol 1995; 120:751-6. 7) Sabates WI, Abrams GW, Swanson DE, Norton EW. The use of intraocular gases. The results of sulfur hexafluoride gas in retinal detachment surgery. Ophthalmology 1981;88:447-54. 8) Yeon DY, Yoo C, Park JH, et al. Adherence to preservative-free dorzolamide/timolol fixed combination assessed by counting the unused single-dose units. J Korean Ophthalmol Soc 2015;56:906-10. 9) Shim JC, Choe CM, Seong GJ. A comparision of short term use effects and satety of timoptic (R) with those of cosopt (R) in normal Korean. J Korean Ophthalmol Soc 2002;43:1206-11. 10) Blaschke TF, Osterberg L, Vrijens B, Urquhart J. Adherence to medications: insights arising from studies on the unreliable link between prescribed and actual drug dosing histories. Annu Rev 1390
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