VIEM LOET GIAC MAC DO N A M : C A C P H U O N G P H A P V A S i / L l / A C H O N D I E U T R I Vu Thi Tue Khanh*
Viem loet giac mac do nam (VLGMN) la mot benh nhiem trung giac mac (GM) kho dieu tri. Hien nay, ty le VLGMN ngay cang tang va kho dieu tri hon do ve sinh moi truong kem, che do bao ho lao dong kem va sir lam dung sir dung cac che pham tra mat co corticosteroid. Viec dieu tri thuong phai rat tich cue va keo dai hang thang hay nhieu thang. Su thanh cong ciia viec dieu tri la thanh toan duoc tac nhan gay benh.
sau dieu tri nhan cau duoc bao ton va khong co cac bien chirng nang ne nlur hoai tir. tilling GM. VLGMN thuong gap a cac nuoc co khi hau nong va am, co lien quan den cac sang chan GM do dat, bui, canh cay, la cay. O cac nuoc dang phat trien nhu: An do, Ne-pal. Bang-la-det ty le benh nay tir 20% den 60%, ty le thap hon nhieu dcac nuoc phat trien nhu: My, Tay Au (3%) [1,2, 3]. Tai Benh vien Mat Trung uong, theo thong ke trong 2 nam 2000 - 2001 co 343 truong hop VLGMN (33%) trong tong so 1038 truong hop viem loet giac mac vao nam vien, trong so nay 39 mat phai miic noi nhan (11,4%) [4].
TAC NHAN GAY BENH
Khoang hon 105 loai nam gay benh a mat.
duoc chia lam 4 nhom chinh: (1) Nam soi co vach ngan, khong co sac to. (2) Nam soi co vach ngan.
co sac to. (3) Nam soi khong vach ngan. (4) Nam men. Nhin chung, nam soi kho chan doan va kho dieu tri hon nam men. Be chan doan nam soi can
cac moi truong va dieu kien nuoi cay dac biet va ty le am tinh gia cao. Tien trien ciia benh cung am i, tir tir phat trien rong hon va a cac lop sau ciia nhu mo GM. Hau het cac truong hop la VLGMN do nam soi. Ty le VLGMN do nam men tit 0,7 - 1,1 % va thuong la nhiem nam co' hoi [3, 5].
Biing 1. Ctic loai nam gay viem loet gidc mac NAM SOI CO VACH NGAN
KJiong co sac to Co sac to Fusarium Curvularia Aspergillus Lasiodiplodia Acremonium Alternaria Paecilomyces Cladosporium
Penicillium Celletotrichum NAM SOI KHONG CO VACH NGAN
Rhizopus (mucormycosis) NAM MEN
Candida (albicans, parapsilosis, tropicalis. krusei)
*Khoa Ket - Gidc mac. Benh vien Mdt Trung uang
BENH HOC
Sy xuat hien benh VLGMN bao gom cac qua trinh xay ra lien tiep: tac nhan gay benh la cac soi nam bam dinh len be mat bieu mo GM bi ton thuong, sau do xam nhap, nhan len va gay doc voi nhu mo GM. Ton thuong GM co the o lop nong.
khoang 1/3 ldp nhu md trudc cua GM, dan dan d loet rdng ra, day cua d loet hinh thanh mang cung, khd, gd hon len so vdi be mat GM. cd the cd mau nau hoac vang. Nhung cung cd the sau khi bam dinh len be mat bieu md GM tdn thuong, cac soi nam phan chia, ddng thoi vdi d loet phat trien rdng hon thi cac soi nam xam nhap vao ldp sau hon cua nhu md GM, tdi mang Descemet va cd the tao ra dam xuat tiet o mat sau GM, tren mong mat va mat trudc thuy tinh the. Trong mdt sd trudng hop gay nen tang nhan ap do sir lun thdng cua cac soi nam trong tien phdng ciing thuy dich va nang thi cd the gay viem ndi nhan. Mdt sd nghien ciru thuc nghiem cho rang chung Fusarium gay hien tuong ire che nguyen bao soi bang sir tiet ra cac ddc td nhu: nivalenol, ddc td T-2, deoxynivalenol, a-xit fusaric. Nghien ciru khac chi rd nam Fusarium solani. Aspergillus flavus tren GM benh nhan cd the tiet ra cac men proteinases, lam hoai tu td chirc [3, 5]. Trong nghien ciiu ve giai phau md benh hoc cua 167 manh GM tren mat VL- GMN. ciic tac gia da chi ra khdng cd mdi lien quan giua vi tri cua cac td chiic viem va vi tri cua cac soi nam gay benh. Tieu ban giai phau md benh hoc cho thay rd cac soi nam nam a ldp nhu md GM lanh va noi cd nhieu chat hoai tu tren GM la noi khdng cdn tdn tai soi nam hoat tinh [6]. Ngoai ra, cac soi nam cdn cd kha niing bien ddi hinh thai de cd the thich nghi va tdn tai a noi ton thuong. Vach ciia cac soi nam cd the day len tao vd boc ben viing vdi tac ddng cua cac thudc chdng nam. Sir tdn thuong hang rao bieu md GM, su rdi loan cua mang phim nude mat. cac bat thudng ve chat luong va tan sd chop mat la nhung dieu kien thuan loi cho VLGMN
phat trien. Dac biet, neu benh nhan dang trong qua trinh dieu tri mdt sd benh tai mat phai su dung keo dai thudc tra mat cd corticosteroid nhu: viem loet giac mac do vi-rut Herpes Simplex, viem ket mac di irng, hoac benh nhan mac benh tieu dudng, hdi chiing suy giam mien dich mac phai cung lam benh VLGMN nang hon va khd dieu tri hon [3, 5].
Hinh 1. Viem loet gidc mac do nam (Mang tham nhiem tren be mat day d loet)
Hinh 2. Viem loet gidc muc do nam (Tham nhiem sau trong chieu day nhu md gidc mac)
32 Nhan khoa Viet Nam (So 18 - 6/2010)
Hinh 3. Viem loet gidc mac do nam (Thdm nhiem khoang 'A nhu md trudc cua gidc mac,
man nau ciia nam ed sdc td) CAC THUOC DIEU TRI VIEM LOET GIAC MAC DO NAM
Sir lhanh cong cua viec dieu tri VLGMN bang thuoc phu thuoc vao benh duoc chan doan som, each sir dung thuoc chong nam nhu the nao de dat hieu qua cao. Amphotericin la thuoc chong nam dau tien duoc sir dung each day 50 nam. nhung den thap nien 80 van la thuoc chong nam toan than duy nhat. Den nay. thuoc dicing nam sir dung trong dieu tri VLGMN gom hai nhom thong dung nhat: (1) Polyenes: Natamycin, Amphotericin. Co die tac dung: ket hop voi ergosterol va pha huy mang te bao. (2) Azoles: Itraconazole, Ketoconazole. Flu- conazole va Voriconazole. Co che tac dung: ire che sinh tong hop ergosterol lam gian doan sir hinh thanh mang te bao. Voriconazole ire che men cy- tochrome P-450 cua nam dan den chet te bao nam.
Hien nay. nhom cac loai hop chat it duoc chi dinh:
Polyhexamethylene biguanide. Chlorhexidine, Sil-
\ cr sulfadiazine [5. 7].
Hieu qua cua thuoc chong nam tren lam sang lien quan mat thiet den nong do, thai gian luu lai cua thuoc tai noi tdn thirong, dudng diing thudc.
Hem nira, thudc chdng nam hien nay deu la thudc
ire che sir phat trien cua soi nam va thudc cd phan tu luong ldn. Vi vay, su xam nhap cua thudc vao nai tdn thuong GM rat khd khan, dac biet neu cdn tdn tai ldp bieu md GM.
Natamycin
Natamycin la thudc chdng nam tra mat duoc su dung dau tien va cho den nay la thudc tra mat duy nhat su dung dieu tri VLGMN duoc phe chuan cua FDA, My. Natamycin 5%, dang dich treo (Na- tacyn® Alcon) cd phd bic dung rdng vdi biiu bet cac chung nam thudng gap, bam dinh tot tren be mat d loet, cho nen thdi gian luu thudc keo dai tai noi tdn thuong GM. Theo nghien ciru thue nghiem tren tho cua O'Day D.M va cdng sir, ndng dd cua natamycin trong nhu md GM khi GM cdn ldp bieu md thap hon hang nghin lan so vdi khi GM mat Idp bieu md [7]. Do dd, thudc cd tac dung tot trong cac trudng hop tdn thuong VLGMN d ldp nhu md trudc ciia GM. Natamycin la thudc lua chon hang dau trong dieu tri VLGMN va cd hieu qua tot trong cac trudng hop nhu viem ciing mac, loet ket mac do nam. Tac dung khdng mong mudn khi su dung thudc tra natamycin cd the gap la tdn thuong bieu md GM dang cham.
Amphotericin B
Hieu qua dieu tri cua Amphotericin B tren lam sang tot ddi vdi hau bet cac loai nam, nhung tac dung tot hon nhieu lan ddi vdi nam men. Trong dieu tri VLGMN hien nay Amphotericin B dugc su- dung dudi dang dung djch pha die tii' dang thudc tiem, gitx trong lo mau tdi de tra tai mat; nhd giot lien tuc vao mat hoac tam thudc vao tam collagen dat tren giac mac lien tuc khoang 1 gid voi ndng dd tu 0,15 den 0,3%; tiem nhu md GM; tiem tien phdng vdi ndng dd 7,5-10 ug/0,1 ml; tiem djch kinh (1-5 u.g/0,1 ml). Nhieu chuyen gia giac mac da bao cao hieu qua tdt ciia Amphotericin B bang cac dudng diing thudc neu tren. Tac dung khdng mong mudn, khi sii' dung Amphotericin B tra mat
keo dai, co the ton thuong bieu mo GM dang chain, khi tiem tien phong la phan img gay xuat tiet tien phong. khi tiem noi nhan gay hoai tu hoac bong vong mac [TDT5], Mot so tac gia chi ro hieu qua ciia thuoc tra mat Amphotericin B dang nuac va ma trong dieu tri viem ciing mac, viem ket mac, viem loet giac mac do nam.
Itraconazole
Itraconazole (SporalS Janssen - Cilag) la thuoc dau tien trong nhom azoles co tac dung vugt troi doi vdi cac chimg nam soi, hieu qua dac biet vdi chung Aspergillus. Thudc duoc sir dung theo dudng udng. lieu 200 mg/ngay, udng 1 lan vao budi sang sau khi an. Tac dung khdng mong mudn cd the la ndn, budn ndn, ndi man da, tang men gan.
Ketoconazole
Ketoconazole cd tac dung tot khi dieu tri nam toan than, tac dung tot vdi cac loai nam men. Lieu sir dung 200 - 400 mg/ngay. udng I lan khi an. Tac dung khdng mong mudn cd the la ndn, budn ndn, da man dd, tang men gan.
Fluconazole
Fluconazole cd tac dung rat tot vdi cac chiing nam men. it tac dung vdi nam spi. Thudc dang vien va dang tiem tinh mach, lieu diing 100 - 400 mg/
ngay. Thudc nay gay ddc tinh nang ne cho gan, tac dung khdng mong mudn cd the la tdn thuong niem mac da day va rudt, da man ngira.
Voriconazole
Voriconazole la thudc chdng nam mdi dugc FDA phe chuan nam 2002. Kha nang dung nap ciia thudc rat cao qua dudng udng. phd tac dung tot vdi ca 2 chiing nam soi va nam men va dac biet hieu qua vdi cac cluing: Aspergillus. Fusarium, Dema- tiaceous. Thudc cd 2 dang trinh bay la dang vien va dang tiem tmh mach. Lieu thudc udng trong ngay diu tien 400mg x 2 lan/ngay, lieu duy tri 200 mg x 2 lan/ngay. Neu tiem tinh mach lieu khdi dau 6 mg/
kg x 2 lin. lieu duy tri 3 mg/kg x 2 lan/ngay.
Cac loai hgp chat sat khuan: Polyhexamethyl- ene biguanide (PHMB). Chlorhexidine. Silver sul- fadiazine.
Cac loai hgp chat it dugc sir dung trong dieu trj nam. Tac dung chii yeu nhu chat sat triing ddi vdi ca vi khuan, nam, Acanthamoeba. PHMB da tirng dirge sir dung d be bai hoac cd trong thanh phan chat bao quan ciia thudc tra mat.
CAN THIEP NGOAI KHOA TRONG DIEU TRI VIEM LOET GIAC MAC DO NAM
Nao bieu md GM, nao be mat GM hoac day 6 loet Can thiep nay thuc hien hang ngay tren may sinh hien vi kham benh. bang dao sd 15, tra thudc te be mat Dicain 1%. Muc dich loai bd ca hoc cac td chiic hoai tir, spi nam tren be mat tdn thuong va giiip cho thudc tra mat tang kha nang tham sau hon vao ldp nhu md giac mac.
Got gidc mac
Got giac mac thirc hien dudi kinh hien vi phau thuiit tai phdng md. Tra thudc te be mat, diing dao dau trdn ggt Idp GM tdn thuong. Muc dich loai bd ca hgc td chirc hoai tir, sgi nam d sau khoang Vi nhu md tnrdc ciia GM. Ky thuat nay chi dinh dac biet cho hinh thai VLGMN vdi day d loet gd cao hon so vdi be mat GM.
Keo ddn GM
Chi dinh trong trudng hop bien chirng ciia VL- GMN nhu GM hoai tir, doa thiing hoac tilling nhd.
Tuy nhien luu y khi sir dung keo dan GM se can trd su xam nhap ciia thudc chdng nam vao sau trong nhu md GM va gay tang phan ling viem, GM phii nang hon.
Ghep mang di nhieu Idp
Phau thuat ghep mang di nhieu Idp dugc chi dinh khi VLGMN da dn dinh. het hoan toan tham nhiem trong nhu md GM va kem theo doa thiing GM hoac Id tilling < 3 mm.
Khau phu ket mac
34 Nhan khoa Viet Nam (So 18 - 6/2010)
Khau phii ket mac co the chi dinh trong truong hop VLGMN da on dinh, co ton thuong GM kho han gan, thung hoac doa thiing GM a gan ria ciing giac mac. Tuy nhien, to chirc ket mac de co rut cho nen ty le thanh cong ciia phau thuat thap. Neu ket qua phau thuat tot thi bi ban che ve mat tham my vi hinh thanh mong gia.
Ghep gidc mac
Trong tong so cac ca VLGMN, ty le tir 15 - 28% so mat can phai duoc ghep GM xuyen do thung giac mac rong. Tai Singapore so lieu thong ke cho thay ty le thiing GM sau VLGMN cao hon 5 - 6 lan so vdi ty le tilling GM sau viem loet GM do vi khuan. Dac biet, ty le thanh cong ciia phau thuat ghep GM xuyen dieu tri VLGMN (20 - 70
%) thap hon nhieu lan so vdi ty le thanh cdng ciia phau thuat nay dieu tri viem loet giac mac do vi khuan (tren 70 %) [8]. Hon nua, sau phau thuat viec sir dung thudc tra corticosteroid can duoc can nhac rat can than, neu khdng se lam tai phat VLGMN rat nhanh va nang ne. Sd it tac gia thuc hien ghep GM Idp sau dieu tri VLGMN vdi tdn thuong trung binh hoac ton thuong d ldp ndng ciia nhu md GM. Mdt sd ca that bai va phai thirc hien ghep GM xuyen.
MOT SO DIEU CAN CAN NHAC TRONG DIEU TRI VIEM LOET GIAC MAC DO NAM
Viem loet GM do nam lii benh khd dieu tri va lii thach thirc ldn ddi vdi cac chuyen gia ve giac mac. Kha nang xam nhap viio nhu md GM ciia cac loai thudc chdng nam tra mat thap vi phan tir lirong ciia thudc Idn. Cac nghien ciiu ve phd tac dung ciia thudc vdi cac cluing nam cdn khac nhau giira nghien ciiu trong phdng thi nghiem va thirc te lam sang, ciing la sir ban che ciia viec dieu tri thanh cdng. Do dd. trong qua trinh dieu tri VLGMN. cac viin de khd khan thudng gap nlur lira chon phirong phap dieu tri phii hop vdi mire do nang ciia benh.
each sir dung thudc chdng nam va dac biet hon vdi nhiing trudng hop tham nhiem a Idp sau trong nhu md GM. Tac dung khdng mong mudn khi sir thudc chdng nam tra tai mat la tdn thuong bieu md GM dang cham, kich thich va chay nirdc mat; khi dimg dudng udng thi anh hirdng tdi chirc nang gan. Do dd, thudc chdng nam chi nen duoc chi dinh khi cd ket qua xet nghiem vi sinh duong tinh tir benh pham chat nao d loet. Khi cd dau hieu ciia benh tot len nen giam lieu thudc, cd the cat thudc udng trudc va keo dai thdi gian sir dung thudc tra khoang 2 tuan sau khi da khdi benh nhung vdi lieu thap.
Mat khac, gia ciia cac loai thudc dudng udng, tiem cao cho nen can can nhac ky khi sii' dung. Ketocon- azole dudng udng gia thap nhat nhung ddc tinh cao hon Itraconazole. Voriconazole la thudc chdng nam mdi. cd hieu qua dieu tri tot nhung gia thanh cao khdng phii hop vdi benh nhan VLGMN, thudng la nhirng ngudi sdng d viing ndng thdn va cac nude dang phat trien.
Viec chi dinh dieu tri mdt loai thudc chdng nam tra mat hoac sii' dung phdi hop 2 loai thudc nam, mdt loai tra mat va mdt loai udng khdng cho thay su khac biet cd y nghia thdng ke. De chi dinh dudng diing thudc phii hop va thudc duoc dua vao tan nai tdn thuang can xem xet do sau ciia tham nhiem GM. Vdi cac trudng hop tham nhiem rdng va d khoang Vi nhu md trudc ciia GM thi viec tang cudng sd lan tra thudc, nhd giot lien tuc va ket hop vdi nao be mat d loet hoac got GM mang lai hieu qua cao. Trudng hop VLGMN cd hien tugng tham nhiem sau trong chieu day nhu md giac mac hoac tac nhan gay benh da tan cdng vao trong tien phdng, tiem nhu md GM hoac tiem tien phdng bang Am- photericin B cd the can nhac chi dinh vi hien nay cac chi djnh nay cdn trong giai doan nghien ciru.
Tiem dudi ket mac hien nay it dugc chi dinh vi gay ddc tinh, gay dau khi tiem va ket qua nghien ciru khdng cd sir khac biet.
Phau thuat ghep GM xuyen duoc chi dinh khi VLGMN khong dap ung voi dieu tri noi khoa, benh co xu hudng lan ve phia ria GM, hoai tir thiing GM de doa den sir bao toan nhan cau. Can luu y trong khi thuc hien phau thuat phai loai trir het cac phan GM bi tham nhiem, dac biet cac 6 tham nhiem moi xuat hien a ba 6 loet. Khi hien tuong viem trong tien phong nang. hoai tir GM rong, chi dinh rira tien phong khi ma nhan cau hoac tiem tien phong sau khi dong nhan cau bang Amphotericin B cung cho ket qua tot [9, 10].
KET LUAN
Viem loet giac mac do nam la mot benh kho dieu tri, can duoc chan doan sam va chi djnh cac phuong phap dieu trj bang thuoc vai cac each diing thuoc khac nhau va phoi hop vdi cac can thiep khac mdt each phii hop. Muc dich uu tien la thanh toan nhiem triing va bao tdn nhan cau, ghep giac mac xuyen dieu trj VLG- MN duoc chi dinh khi mat cd bien chirng thiing hoac doa thung va khdng dap ung vdi dieu tri ndi khoa.
TAI LIEU THAM KHAO
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2. SHARMA S, SRINIVASAN M, GEORGE C. Current status of Fusarium species in mycotic keratitis in South India. J Med Microbiol 1993: 11:140 - 147.
3. UPADHYAY MP, KARMACHARYA PC, KOIRALA S, SMOLIN G ETAL. Epidemiologic Character- istics, predisposing factors, and etiologic diagnosis of corneal ulceration in Nepal. Am J Opthahnol 1991;
111:92-9.
4. VU TFU TUE KHANH. LE THI NGQC LAN, HOANG THj MINH CHAU. Dac diem lam sang cua benh viem loet giac mac do nam tai khoa Ket - Giac mac BV Mat TU. Tap chi Nghien cim Yhoc 2006. Vol 41, N 2: 54 - 57.
5. EDUARDO C ALFONSO, RICHARD K. FORSTER, PRASHANT GARG, SAVITRI SHARMA. Chap- ter 16: Fungal infections. Section IV: Infectious diseases. Textbook of The CORNEA Scientific Foundations
& Clinical Practice, 4th Edition, Lippincott Williams & Wilkins 2007, trang 405 - 425.
6. VEMUGANT1 O.K. PRASHANT GARG, GOPINATHAN V, NADUVILATH T.J, JOHN R.K, BUDDI R, RAO G.N. Evaluation of agent and host factors in progression of mycotic keratitis. A histologic and mi- crobiologic study of 167 corneal buttons. Ophthalmology 2002. Vol 109: 1538 - 1546.
7. O'DAY. D.M. HEAD. W.S. ROBINSON R.D, CLANTON J. A. Corneal penetration of topical Amphot- ericin B and Natamycin. Curt: Eye Res, 1986. Vol 5: 877 - 882.
8. WONG T. P, FONG K. S. TAN D. T. H. Risk factors and clinical outcome between fungal and bacterial keratitis. A comparative study 1997. CLAO J. Vol 23: 275 - 281.
9. VU TH| TUE KHANH. PRASHANT GARG, PRAVEEN KRISHNA, VIRENDER SANGWAN. Ghep giac mac xuyen dieu tri viem loet giac mac do nam: Thj lire sau md va su toan ven nhan cau. Tap chi Nhdn khoa Viet Nam 2009. Vol 14: 34 - 39.
10. XIE L, DONG X, SHI W. Treatment of fungal keratitis by penetrating keratoplasty. Dr. J. Ophthalmol 2001. Vol 85: 1070 -1074.
36 Nhan khoa Viet Nam (So 18 - 6/2010)
