Í.Ã. Çàâãîðîäíÿÿ*, À.À. Êðèâîðó÷êî ***, Þ.Â. Ìàðòîâèöêàÿ **
Çàïîðîæñêèé ãîñóäàðñòâåííûé ìåäèöèíñêèé óíèâåðñèòåò êàôåäðà îôòàëüìîëîãèè *, êàôåäðà ïàòîëîãè÷åñêîé àíàòîìèè **.
Êëèíèêà ñîâðåìåííîé îôòàëüìîëîãèè "³çóñ" ã.Çàïîðîæüå ***.
MODERN FLUOROQUINOLONES IN OPHTHALMIC SURGERY, THEIR INFLUENCE ON THE EPITHELIUM OF THE CONJUNCTIVA AND THE CORNEAL ENDOTHELIUM
N. Zavgorodnaya, A.Króvoruchko, J.Martivitskaya SUMMARY
Topical fluoroquinolones are most commonly used in ophthalmic surgery.
Objective: To study the influence of drugs fluoroquinolones generation IV without preservative moxifloxacin and fluoroquinolones III generation with a preservative benzalkonium chloride levofloxacin on the corneal endothelium and endothelium of conjunctive. A total of 62 (78 eyes) patients. Received the standard ophthalmologic examination, as well as endotelioskopiy with mirror endotelioskop Topcon SP-3000P (Topcon corporation, Japan), and impression cythology. Conclusions: The use of 0.5% of moxifloxacin in patients of all age groups are more secure.
ÑÓ×ÀÑͲ ÔÒÎÐÕ²ÍÎËÎÍÈ Â ÎÔÒÀËÜÌÎÕ²ÐÓÐò¯, ¯Õ ÂÏËÈ ÍÀ ÅϲÒÅË²É ÊÎÍ'ÞÍÊÒÈÂÈ ÒÀ ÅÍÄÎÒÅË²É ÐÎòÂÊÈ
Í.Ã. Çàâãîðîäíÿ, Ã.Î.Êðèâîðó÷êî, Þ.Â.Ìàðòîâ³öüêà ÐÅÇÞÌÅ
Òîï³÷í³ ôòîðõ³íîëîíè íàé÷àñò³øå âèêîðèñòîâóþòüñÿ â îôòàëüìîõ³ðóð㳿. Ìåòà: âèâ÷èòè âïëèâ ôòîðõ³íîëîíà IV ïîêîë³ííÿ áåç êîíñåðâàíòà 0,5% ìîêñ³ôëîêñàöèíà òà ôòîðõ³íîëîíà III ïîêîë³ííÿ 0,5% ëåâîôëîêñàöèíà íà åíäîòåë³é ðîã³âêè òà ºï³òåë³é êîí'þíêòèâè. Îáñòåæåíî 62 ïàö³ºíòà (78 î÷åé). Ïðîâîäèëàñü åíäîòåë³îñêîï³ÿ, öèòîëîã³÷íå äîñë³äæåííÿ êîíüþíêòèâè çà ìåòîäîì ³ìïðåñ³éíî¿
öèòîñêîﳿ. Âèñíîâêè: âèêîðèñòàííÿ 0,5% ìîêñ³ôëîêñàöèíà íàéá³ëüø áåçïå÷í³øå äëÿ ïàö³ºíò³â âñ³õ â³êîâèõ ãðóï.
Êëþ÷åâûå ñëîâà: ôòîðõèíîëîíû, ýíäîòåëèîñêîïèÿ, êðèñòàëëîãðàôèÿ, êîíñåðâàíò, áåíçàëêîíèÿ õëîðèä.
ñèôëîêñàöèí (Âèãàìîêñ, Alcon) ñàìîêîíñåðâèðóþ-ùèéñÿ ðàñòâîð. Êàê ëåâîôëîêñàöèí òàê è ìîêñèôëîê-ñàöèí îáëàäàþò ëèïîôèëüíûìè è ãèäðîôèëüíûìè ñâîéñòâàìè, áëàãîäàðÿ ÷åìó ëåãêî ðàñòâîðÿþòñÿ â ñëåç-íîé ïëåíêå, ñâîáîäíî íàêàïëèâàþòñÿ â ýïèòåëèè êî-íüþíêòèâû, ÷åðåç ðîãîâèöó ïðîíèêàþò âî âëàãó ïå-ðåäíåé êàìåðû, ãäå ñîçäàþò èíãèáèðóþùèå êîíöåíò-ðàöèè [2,9]. Òàêèì îáðàçîì, ìîãóò îêàçûâàòü âëèÿíèå íà ýïèòåëèé êîíüþíêòèâû è ñòðóêòóðû ïåðåäíåé êà-ìåðû, â òîì ÷èñëå è íà ýíäîòåëèé ðîãîâèöû.
Öåëü ðàáîòû: èçó÷èòü âëèÿíèå ôòîðõèíîëîíà IV ïîêîëåíèÿ áåç êîíñåðâàíòà 0,5% ìîêñèôëîêñàöèíà (Âèãàìîêñ, Alcon) è ôòîðõèíîëîíà III ïîêîëåíèÿ ñ êîíñåðâàíòîì áåíçàëêîíèÿ õëîðèäîì 0,5% ëåâîô-ëîêñàöèíà (Îôòàêâèêñ, Santen) íà ýíäîòåëèé ðîãîâè-öû è êà÷åñòâåííûé ñîñòàâ ñëåçû.
ÌÀÒÅÐÈÀËÛ È ÌÅÒÎÄÛ
Èññëåäîâàíèå ïðîâîäèëîñü íà áàçå Çàïîðîæñêîé êëèíèêè ñîâðåìåííîé îôòàëüìîëîãèè «Â³çóñ». Ïîä
íàøèì íàáëþäåíèåì íàõîäèëîñü 62 ïàöèåíòà (78 ãëàç) âîçðàñòîì îò 49 äî 86 ëåò. Ïàöèåíòû ãîòîâèëèñü ê îïåðàöèè ôàêîýìóëüñèôèêàöèè êàòàðàêòû è â êà÷å-ñòâå ïðåäîïåðàöèîííîé ïîäãîòîâêè ïîëó÷àëè èíñòèë-ëÿöèè àíòèáàêòåðèàëüíûõ ïðåïàðàòîâ â ðåæèìå 4 ðàçà â äåíü çà 4-5 äíåé äî îïåðàöèè.
Ðàçäåëåíèå íà ãðóïïû: 1-ÿ ãðóïïà 36 ÷åëîâåê (41 ãëàç) ïîëó÷àëè 0,5% ìîêñèôëîêñàöèí, 2-ÿ ãðóïïà 26
÷åëîâåê (37 ãëàç) ïîëó÷àëè 0,5% ëåâîôëîêñàöèí.  êàæ-äîé ãðóïïå âûäåëåíû ïîäãðóïïû â çàâèñèìîñòè îò âîç-ðàñòà: äî 69 ëåò, è îò 70 ëåò è ñòàðøå. Âñåì ïàöèåíòàì ïðîâîäèëîñü ñòàíäàðòíîå îôòàëüìîëîãè÷åñêîå îáñëå-äîâàíèå, öèòîëîãè÷åñêîå èññëåäîâàíèå êîíúþíêòèâû ìåòîäîì èìïðåñèîííîé öèòîñêîïèè, à òàê æå ýíäîòå-ëèîñêîïèÿ íà çåðêàëüíîì ýíäîòåëèîñêîïå Topcon SP-3000P (Topcon corporation, Japan), ïîëó÷åííîå èçîá-ðàæåíèå îáðàáàòûâàåòñÿ ïðè ïîìîùè ïðîãðàììû Ñell Ñount. Èññëåäîâàëàñü öåíòðàëüíàÿ çîíà ðîãîâèöû, âû-ïîëíÿëîñü îò 2 äî 4 ñíèìêîâ èç êîòîðûõ âûáèðàëñÿ íàè-áîëåå ÷åòêèé. Äèàãíîñòèêà âûïîëíÿëîñü ïðè ïåðâè÷íîì îáðàùåíèè ïàöèåíòà â êëèíèêó, ïîñëå ÷åãî íàçíà÷àëñÿ äåíü îïåðàöèè, çà 4-5 äíåé äî îïåðàöèè èíñòèëëÿöèè àí-òèáàêòåðèàëüíûõ ïðåïàðàòîâ. Ïîâòîðíî îáñëåäîâàíèå ïðîâîäèëàñü íåïîñðåäñâåííî ïåðåä îïåðàöèåé.
Ñòàòèñòè÷åñêèé àíàëèç ïðè ïîìîùè ïàêåòà ïðî-ãðàìì Statistica 6.1, ñ èñïîëüçîâàíèåì ôóíêöèè îïè-ñàòåëüíîé ñòàòèñòèêè, à òàêæå íåïàðàìåòðè÷åñêîé
ñòàòèñòèêè ñ ðàñ÷åòîì êðèòåðèÿ Âèëêîêñîíà.
ÐÅÇÓËÜÒÀÒÛ È ÈÕ ÎÁÑÓÆÄÅÍÈÅ
Ïîëó÷åííûå íàìè äàííûå ìîðôîëîãè÷åñêèõ ïîêàçàòåëåé ýíäîòåëèÿ ðîãîâèöû ñîîòâåòñâóþò ñðåä-íèì çíà÷åíèÿì äëÿ âûäåëåííûõ âîçðàñòíûõ ãðóïï [1, 2, 4, 5, 6].
Èíñòèëëÿöèè êàê 0,5% ìîêñèôëîêñàöèíà, òàê è 0,5%
ëåâîôëîêñàöèíà ôîðìèðóþò ðàâíîçíà÷íûå èçìåíåíèÿ â ìîðôîëîãè÷åñêèõ ïîêàçàòåëÿõ ýíäîòåëèÿ (òàáëèöà
¹ 1.2). Òàê, íàáëþäàåòñÿ âàðüèðîâàíèå ìèíèìàëüíîãî è ìàêñèìàëüíîãî ðàçìåðà êëåòêè, ñðåäíåãî ðàçìåðà êëåòêè ïëîòíîñòè ýíäîòåëèàëüíûõ êëåòîê, îäíàêî ýòè èç-ìåíåíèÿ íå íîñÿò ñòàòèñòè÷åñêè çíà÷èìûé õàðàêòåð.
Íåîáõîäèìî îòìåòèòü, ÷òî â ãðóïïå ïàöèåíòîâ äî 69 ëåò ïðèìåíÿâøèõ 0,5% ìîêñèôëîêñàöèí, à òàê æå, ó ïàöèåíòîâ âîçðàñòíîé ãðóïïû 70 ëåò è ñòàðøå ïðèìå-íÿâøèõ 0,5% ëåâîôëîêñàöèí, ïðèáëèæàþòñÿ ê ñòàòèñ-òè÷åñêè äîñòîâåðíûì óâåëè÷åíèÿ ìèíèìàëüíîãî ðàç-ìåðà êëåòêè. Òàê æå âèäíà ÷åòêàÿ òåíäåíöèÿ ê óâåëè÷å-íèþ ïðîöåíòíîãî ñîîòíîøåíèÿ ãåêñàãîíàëüíûõ êëåòîê ó ïàöèåíòîâ âñåõ âîçðàñòíûõ ãðóïï ïîñëå èíñòèëëÿöèé 0,5% ìîêñèôëîêñàöèíà, ÷òî âåðîÿòíî, ìîæåò ñâèäåòåëü-ñòâîâàòü î ïîâûøåíèè áàðüåðíîé ôóíêöèè ýíäîòåëèÿ ðîãîâèöû. Îäíàêî òîëüêî â âîçðàñòíîé ãðóïïå ñòàðøå 70 ëåò îïèñàííûå èçìåíåíèÿ ïðèáëèæàþòñÿ ê ñòàòèñ-òè÷åñêè çíà÷èìûì ïîêàçàíèÿì.
Òàáëèöà 1.
Èçìåíåíèå ïîêàçàòåëåé ýíäîòåëèîñêîïèè ïðè ïðèìåíåíèè 0,5% ìîêñèôëîêñàöèíà
Q Q
0P
0P :
0P
0P :
FRUQHDWKLFN
PLQLPXPVL]Hð
PD[LPXPVL]Hð
DYHUDJHVL]Hð
6'RIVL]H
&9RIVL]H
ð
FHOOGHQVLW\
KH[DJRQDOLW\
Òàáëèöà 2.
Èçìåíåíèå ïîêàçàòåëåé ýíäîòåëèîñêîïèè ïðè ïðèìåíåíèè 0,5% ëåâîôëîêñàöèíà
Ïðèìå÷àíèå W* êðèòåðèé Âèëêîêñîíà.
Q Q
0P
0P :
0P
0P :
FRUQHDWKLFN
PLQLPXPVL]Hð
PD[LPXPVL]Hð
DYHUDJHVL]Hð
6'RIVL]H
&9RIVL]H
ð
FHOOGHQVLW\
KH[DJRQDOLW\
Èíòåðåñ ïðåäñòàâëÿåò âûÿâëåííàÿ èñõîäíàÿ öè-òîëîãè÷åñêàÿ êàðòèíà êîíúþíêòèâû ïàöèåíòîâ. Íîð-ìàëüíàÿ öèòîëîãèÿ â ãðóïïàõ íàøèõ ïàöèåíòîâ
âñòðå-÷àëàñü òîëüêî â 10% ó ïàöèåíòîâ â âîçðàñòå äî 50 ëåò (ðèñ. ¹1 À).  ýòèõ ñëó÷àÿõ ìû âèäèì ôîðìèðîâà-íèå ïëîòíîãî ýïèòåëèàëüíîãî ïëàñòà ñ ïðî÷íûìè ìåæêëåòî÷íûìè âçàèìîñâÿçÿìè, íàëè÷èå áîêàëîâèä-íûõ êëåòîê, ïðèçíàêè ïðîëèôåðàöèè ìèòîçà ýïèòå-ëèàëüíûõ êëåòîê.  34 % ñëó÷àåâ âûÿâëÿëèñü óìå-ðåííî âûðàæåííûå äåãåíåðàòèâíûå èçìåíåíèÿ, à
èìåííî äåñêâàìàöèÿ ýïèòåëèÿ, îñëàáëåíèå ìåæêëå-òî÷íûõ âçàèìîñâÿçåé, ðàçðîçíåííîñòü êëåòîê (ðèñ.
¹1 Â,Ñ).  56% ñëó÷àåâ, ïðåèìóùåñòâåííî ó ïàöè-åíòîâ ñòàðøå 65 ëåò, âûÿâëÿëèñü âûðàæåííûå äèñò-ðîôè÷åñêèå èçìåíåíèÿ êîíúþíêòèâû, ÷òî ïðîÿâëÿ-åòñÿ â äåãåíåðàòèâíûõ èçìåíåíèÿõ ÿäðà, à èìåííî âåðåòåíîîáðàçíûå ÿäðà, íåãîìîãåííàÿ îêðàñêà ÿäðà, ôîðìèðîâàíèå ãëûáîê õðîìàòèíà, íå÷åòêèå êîíòó-ðû ÿäðà, óìåíüøåíèå îáú¸ìà öèòîïëàçìû, ðàçêîíòó-ðûâ öèòîïëàçìû (ðèñ. ¹1. Ñ).
Ðèñóíîê ¹1. Öèòîëîãè÷åñêàÿ êàðòèíà ýïèòåëèÿ êîíúþíêòèâû.
A B C
Ïîñëå èíñòèëëÿöèé èíòåðåñóþùèõ íàñ ïðåïàðà-òîâ ïðîèñõîäÿò ñëåäóþùèå èçìåíåíèÿ â
öèòîëîãè-÷åñêîé êàðòèíå êîíúþíêòèâû. Ó ïàöèåíòîâ ñ èñõîä-íî èñõîä-íîðìàëüèñõîä-íîé è ñî ñðåäíåé ñòåïåíüþ âûðàæåíèñõîä-íîñ- âûðàæåííîñ-òè äåãåíåðàöèè â öèòîëîãè÷åñêîé êàðâûðàæåííîñ-òèíå êîíúþíê-òèâû ïîñëå 5 äíåé èíñòèëëÿöèé 0,5%
ìîêñèôëîêñà-öèíà ïðàêòè÷åñêè íå âûÿâëÿëîñü èçìåíåíèé (ðèñ. ¹2 A,B). Ïðè âûðàæåííîé äåãåíåðàöèè êîíúþíêòèâû ïðîèñõîäèò íàðàñòàíèå èçìåíåíèé öèòîïëàçìû (ðèñ.
¹2 C), à èìåííî: îñëàáëåíèå ìåæêëåòî÷íûõ âçàèìî-ñâÿçåé, âûðàæåííàÿ ðàçðîçíåííîñòü êëåòîê, îäíàêî ìîðôîëîãèÿ ÿäåð íå èçìåíÿåòñÿ (ðèñ.¹1 À,Â,Ñ).
Ðèñóíîê ¹2. Èçìåíåíèÿ öèòîëîãè÷åñêîé êàðòèíû êîíúþíêòèâû ïîñëå èíñòèëëÿöèé 0,5% ìîêñèôëîêñàöèíà
A B C
Ïîñëå 5 äíåé èíñòèëëÿöèé 0,5% ëåâîôëîêñàöèíà öèòîëîãè÷åñêàÿ êàðòèíà èìåëà íåñêîëüêî äðóãîé âèä.
Ïðè èñõîäíî íîðìàëüíîé öèòîëîãèè ìû âèäèì ñî-õðàíåíèå ýïèòåëèàëüíîãî ïëàñòà, ñîñî-õðàíåíèå ìîðôî-ëîãèè ÿäåð (ðèñ ¹3 A). Ó ïàöèåíòîâ ñ óìåðåííîé è
âûðàæåííîé ñòåïåíüþ äåãåíåðàöèè îïðåäåëÿþòñÿ å¸
íàðàñòàíèå, à èìåííî ðàçðûõëåíèå õðîìàòèíà (ðèñ ¹3 B).  24% ñëó÷àåâ âûÿâëÿþòñÿ ïðèçíàêè àê-òèâíîãî ðàçðóøåíèÿ, ëèçèñà êëåòêè ðàçðûõëåíèå õðî-ìàòèíà, îòñóòñòâèå êîíòóðîâ ÿäðà (ðèñ ¹3 C).
Ðèñóíîê ¹3. Èçìåíåíèÿ öèòîëîãè÷åñêîé êàðòèíû êîíúþíêòèâû ïîñëå èíñòèëëÿöèé 0,5%
ëåâîôëîêñàöèíà
A B C
ÂÛÂÎÄÛ
Èíñòèëëÿöèè 0,5% ëåâîôëîêñàöèíà ñ êîíñåðâàí-òîì è 0,5% ìîêñèôëîêñàöèíà áåç êîíñåðâàíòà íå âûçûâàþò ñòàòèñòè÷åñêè çíà÷èìûõ èçìåíåíèé â ìîð-ôîëîãè÷åñêèõ ïîêàçàòåëÿõ ýíäîòåëèÿ ðîãîâèöû ïî äàííûì çåðêàëüíîé ýíäîòåëèîñêîïèè.
Ïðèñóòñòâèå êîíñåðâàíòà áåíçàëêîíèÿ õëîðèäà ñíèæàåò âûæèâàåìîñòü ýïèòåëèàëüíûõ êëåòîê, ÷òî ïðîÿâëÿåòñÿ â àêòèâíîì ðàçðóøåíèè ÿäðà ýïèòåëè-àëüíîé êëåòêè, îñîáåííî â ñëó÷àÿõ ñ èñõîäíî äåãåíå-ðàòèâíûìè èçìåíåíèÿìè ýïèòåëèÿ êîíúþíêòèâû ó ïàöèåíòîâ ñòàðøåãî âîçðàñòà.
Ïðèîðèòåòîì â âûáîðå àíòèáàêòåðèàëüíûõ
ïðåïàðàòû áåç êîíñåðâàíòîâ, ÷òî îáåñïå÷èò èõ áåçî-ïàñíîå èñïîëüçîâàíèå ó ïàöèåíòîâ ñòàðøèõ âîçðàñòà.
ËÈÒÅÐÀÒÓÐÀ
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3. Masahiko Ayaki. Toxicity of antiglaucoma drugs with and without benzalkonium chloride to cultured human corneal endothelial cells/ Masahiko Ayaki , Atsuo
4. Niederer R.L. Age-related differences in the normal human cornea: a laserscanning in vivo confocal microscopy study / R. L. Niederer, D. Perumal, T. Sherwin, J. McGhee // Br J Ophthalmology.- 2007. vol. 9 Ð. 1165 1169.
5. Narumon Sopapornamorn. Corneal endothelial cell density and morphology in Phramongkutklao Hospital/
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BMC Ophthalmology. 2006. vol.1 Ð.6 9.
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Ïåðâè÷íàÿ îòêðûòîóãîëüíàÿ ãëàóêîìà îñòàåòñÿ ñåðüåçíîé ïðîáëåìîé çäðàâîîõðàíåíèÿ âñåõ ñòðàí ìèðà, òðåáóþùåé áîëüøèõ ôèíàíñîâûõ çàòðàò íà äèàãíîñòèêó è ëå÷åíèå [12, 16]. Ê îñíîâíûì ïàòîãåí-íûì ôàêòîðàì ïðè ãëàóêîìå îòíîñÿò: óõóäøåíèå îò-òîêà âîäÿíèñòîé âëàãè èç ãëàçà, âíóòðèãëàçíîå äàâëå-íèå (ÂÃÄ), ïðåâûøàþùåå èíäèâèäóàëüíîå òîëåðàí-òíîå äàâëåíèå, èøåìèþ è ãèïîêñèþ ãîëîâêè çðèòåëü-íîãî íåðâà. Ê âòîðè÷íûì ïàòîãåííûì ôàêòîðàì îò-íîñÿò: íàðóøåíèå òðàíñïîðòà öåðåáðàëüíûõ
òðîôè-÷åñêèõ ôàêòîðîâ ê ãàíãëèîçíûì êëåòêàì ñåò÷àòêè (ÃÊÑ) è èõ ãèáåëü ïóòåì àïîïòîçà [6, 13].
 íàñòîÿùåå âðåìÿ áîëüøèíñòâî àâòîðîâ îïðå-äåëÿþò ãëàóêîìó êàê ãëàóêîìíóþ îïòè÷åñêóþ íåé-ðîïàòèþ (ÃÎÍ), à óõóäøåíèå îòòîêà âîäÿíèñòîé âëà-ãè è ïîâûøåíèå ÂÃÄ ðàññìàòðèâàþò òîëüêî êàê ôàê-òîðû ðèñêà ðàçâèòèÿ ãëàóêîìû.  óñëîâèÿõ õðîíè÷åñ-êîé ãèïîêñèè íàêàïëèâàþòñÿ ïðîäóêòû ïåðåêèñíîãî îêèñëåíèÿ ëèïèäîâ è âîçáóæäàþùèå àìèíîêèñëîòû ÓÄÊ:617.7-007.681:615.457
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