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1.
PURPOSE: To examine the effect of 1% topical dorzolamide on tissue circulation in the optic nerve head (ONH) of Dutch rabbits. METHODS: A laser speckle tissue circulation analyzer was used. One eye of each rabbit received 1% topical dorzolamide twice daily for 20 days, and the fellow eye received the vehicle in a masked, randomized manner. Intraocular pressure (IOP) was measured every 5 days. The normalized blur (NB) value, a quantitative index of tissue blood flow velocity in the ONH, was measured before treatment and 2 hours after the last instillation on the 20th day. RESULTS: The IOP was lowered by about 2 mm Hg only in the dorzolamide-treated eyes (P < .01). The NB value showed no significant change in either dorzolamide-treated or vehicle-treated eyes. CONCLUSIONS: Long-term topical dorzolamide does not affect the ONH tissue circulation in dorzolamide- and vehicle-treated eyes of Dutch rabbits.  相似文献   

2.
局部滴用丝裂霉素C治疗角结膜上皮内上皮癌的临床观察   总被引:4,自引:0,他引:4  
目的评价局部滴用0.04%丝裂霉毒C(MMC)眼药水治疗角结膜上皮内上皮癌(CCIN)的治疗效果。方法分别回顾分析8例8眼经病灶活检及组织病理学检查确诊为CCIN的患者,给予患眼滴用0.04%MMC眼药水,1天4次,1次1滴,连用7天,对于顽固性病变患者采用治疗结束1w后开始下一疗程的循环疗法。所有患者在治疗前曾进行多次局部病灶切除伴随角结膜瘢痕化形成,或病变呈弥漫型表现。在治疗期间第1月,每周检查1次。治疗结束后,每2个月检查1次,连续6月~12月。结果8例8眼CCIN患者局部滴用0.04%MMC眼药水进行治疗,其中7例7眼患者达到角结膜肿物完全消退的临床效果,治疗时间为7天~21天,平均16.8天。治疗后随访时间为8个月~18个月,平均11个月,未见临床复发征象。1例患者治疗35天后达到部分消退,在进行局部肿瘤切除,术后辅助0.04%MMC眼药水治疗1疗程后,随访6月未见复发。治疗期间均伴随有短暂的眼部不适、结膜充血、流泪、畏光和点状角膜上皮病变。未观察到视力的长期损害及泪膜异常。结论根据0.04%MMC对一个完整的表层上皮细胞具有相对无毒性的特征,采用局部滴用MMC辅助治疗CCIN,可以避免多次手术创伤,不仅能够对整个眼表进行治疗,还可以重复使用,尤其对于复发病例,可以作为首选治疗方法,达到了安全、有效的治疗效果。  相似文献   

3.
The effect of topical 2% carteolol on tissue circulation in the albino rabbit optic nerve head (ONH) was investigated using a laser speckle tissue circulation analyzer. In the first experiment, the normalized blur (NB) value, a quantitative index of tissue blood flow velocity in the ONH, intraocular pressure (IOP), blood pressure (BP), and pulse rate were measured under general anesthesia before as well as 30, 60, 90, and 120 minutes after a 20-μL instillation of carteolol in one eye and the vehicle in the other eye in a masked, randomized manner. In the second experiment, one eye of a rabbit received carteolol twice daily for 20 days and the fellow eye received the vehicle in a masked, randomized manner. The IOP was measured every 5 days, and the NB in the ONH and IOP were measured before treatment and 2 hours after the last instillation on the 20th day. After a single instillation of carteolol, pulse rate showed a maximum reduction of 15%, and IOP in the carteolol-treated eyes showed a maximum decrease of 22%. The NB in the ONH and BP did not show any significant change during the experiment. After 20-day treatment with carteolol, IOP showed a maximum decrease of 25% in the carteolol-treated eyes and 21% in the vehicle-treated eyes. The NB showed a significant increase of 15% (P < 0.01) in the carteolol-treated eyes and 11% (P < 0.01) in the vehicle-treated eyes. It was indicated that long-term topical carteolol increased the blood velocity in the ONH tissue both in the carteolol- and vehicle-treated contralateral eyes in albino rabbits.  相似文献   

4.
The effect of topical 0.1% amosulalol on tissue circulation in the albino rabbit optic nerve head (ONH) was investigated using a laser speckle tissue circulation analyzer. Amosulalol was administered into one eye twice daily for 20 days, and vehicle was administered into the other eye in a masked, randomized manner. Intraocular pressure (IOP) was measured every 5 days. The normalized blur value (NB), a quantitative index of tissue blood flow velocity in the ONH, was measured before treatment and 2 hours after the last instillation on day 20. The IOP was also measured at 5-day intervals. Amosulalol decreased IOP by approximately 2 mmHg in the treated eyes (P < 0.01). There was no significant difference in NB between eyes before the first instillation, whereas NB was significantly greater (by approximately 16%) in the amosulalol-treated eye than in the control eye after completion of instillations (P < 0.01). The difference between NB after completion of instillations and that before the first instillation was significantly greater in the ONH of the amosulalol-treated eye than in the contralateral control eye (P < 0.01). Twice-daily instillation of 0.1% amosulalol for 20 days induced a significant increase in tissue blood velocity in the ipsilateral ONH in albino rabbits.  相似文献   

5.
We used a rabbit model of bacterial keratitis to assess in vivo efficacy of topical imipenem, a highly potent beta-lactam antibiotic with an unusually broad spectrum of activity, including aminoglycoside-resistant Pseudomonas aeruginosa. Albino rabbits received intrastromal injections of 5 x 10(2) organisms of an aminoglycoside-resistant strain of P. aeruginosa. At five hours postinoculation, imipenem (5 mg/ml) therapy was initiated using one drop per 30 minutes for 12 hours. Corneal tissue was then excised for colony forming unit counts. Imipenem was highly effective in reducing colony forming unit counts to zero in comparison to 4.1 x 10(5) organisms for untreated controls. A second regimen beginning 24 hours postinoculation of one drop per hour for 24 hours was also successful in significantly reducing colony forming units vs controls (P less than .05). These data suggest that topical imipenem may have clinical applicability in the treatment of P. aeruginosa keratitis.  相似文献   

6.
孙亚杰  李爱朋  潘志强 《眼科》2012,21(3):166-171
目的 探讨双氯芬酸钠、妥布霉素地塞米松、普拉洛芬、溴芬酸钠滴眼液频繁点眼对兔角膜上皮的副作用,并观察其常规使用对兔角膜上皮创伤愈合的影响。设计 实验性研究。研究对象80只新西兰大白兔。方法 将兔分为2组,每组40只,一组为频点组(点滴眼液每小时1次);另一组行直径6 mm的角膜上皮刮除模型并予点滴眼液每日4次。每组兔再随机分为5组,每组8只,分别给予生理盐水、双氯芬酸钠、妥布霉素地塞米松、普拉洛芬、溴芬酸钠滴眼液。选择右眼为观察眼。在角膜上皮损伤前、损伤后12、24、48、72、96小时及第5、6、7天进行观察,并在观察结束后摘除眼球行组织病理学检查。主要指标 眼表刺激症状、角膜上皮损伤、愈合情况和角膜上皮厚度。结果 与生理盐水组比较,四种滴眼液频繁点滴兔眼均未出现明显刺激症状且未见上皮缺损形成,但荧光素染色均可见角膜上皮点染,以第3天明显,且双氯芬酸钠组角膜上皮损伤的积分(9分)明显高于对照组(0分)和溴芬酸钠组(1分)(P<0.05);病理学检查显示点药5天后,妥布霉素地塞米松组角膜上皮细胞层数(3.67±0.52层)少于对照组(4.17±0.41层)(P<0.05),其余各用药组与对照组的角膜上皮细胞层数未见明显差异。创伤后兔角膜上皮的平均修复时间在双氯芬酸钠组和妥布霉素地塞米松组分别为(75.0±27.0)小时和(75.0±8.5)小时,而生理盐水、普拉诺芬和溴酚酸钠组分别为(66.0±11.1)小时、(69.0±15.4)小时和 (66.0±11.1)小时,各组比较差异无统计学意义(P>0.05),但角膜上皮愈合后妥布霉素地塞米松组(2.00±0.00层)和双氯芬酸钠组(2.50±0.55层)上皮细胞的层数少于对照组(5.00±0.00层)(P<0.05)。结论  频繁滴用抗炎滴眼液可导致兔角膜上皮细胞潜在的损伤;双氯芬酸钠和妥布霉素地塞米松滴眼液抑制兔角膜上皮创伤的愈合作用略强于普拉洛芬和溴芬酸钠。  相似文献   

7.
PURPOSE: We conducted a prospective study to determine the effect of topical administration of brimonidine tartrate 0.2% on postoperative intraocular pressure (IOP) spikes during the first 24 hours after an extracapsular cataract extraction. MATERIAL AND METHODS: In a placebo-controlled study, we randomized 40 consecutive normotensive eyes undergoing extracapsular cataract surgery into two treatment modalities. Twenty eyes (group A) received placebo and 20 eyes (group B) were given brimonidine tartate 0.2% drops twice the day before and twice on the day of the operation. IOP was measured at baseline (prior to surgery) and then 4, 6, 12 and 24 hours postoperatively. RESULTS: Mean postoperative IOP was higher in the placebo group than in the brimonidine group at every time point studied. In both groups, peak elevation of mean IOP was recorded 6 hours after surgery. At that time, mean IOP was significantly higher in the placebo group (36.2+/-4.0 mmHg) than in the brimonidine group (24.7+/-3.8 mmHg) (p<0.001). A gradual reduction in IOP followed, yet with significantly higher values than those found preoperatively, even 12 hours after surgery (p<0.001). It was only the brimonidine group that achieved a near-to-normal mean IOP 24 hours after surgery (p>0.05). Four of the placebo group patients compared to 1 of the brimonidine group patients had an IOP higher than 40 mmHg 6 hours after surgery and therefore received additional therapy. CONCLUSION: Prophylactic treatment with brimonidine tartrate 0.2% drops twice a day for 2 days is effective in reducing IOP spikes throughout the first 24 hours after an extracapsular cataract extraction.  相似文献   

8.
PURPOSE: To determine corneal levels of topically administered azithromycin and clarithromycin in a rabbit model. DESIGN: Experimental animal study. METHODS: Corneas of New Zealand albino rabbits were treated with topical azithromycin (2 mg/ml or 4 mg/ml) or clarithromycin (10 mg/ml). Topical azithromycin was prepared from an intravenous solution and topical clarithromycin from a suspension for oral use. All rabbits received one drop every 2 hours on the right eye. Groups of rabbits were treated for the following intervals: 6, 12, 24, and 48 hours (four rabbits for each combination of time point, drug, and dose). Corneal tissue was removed 1 hour after the last application. To investigate stability of tissue azithromycin levels, an additional group of four rabbits was treated for 24 hours, but corneal tissue was not removed until 24 hours later. Samples were homogenized, and drug concentrations were measured using high-pressure liquid chromatography (HPLC) analysis and bioactivity assay. RESULTS: Corneal concentrations of azithromycin increased with drug dosage and duration of application. Rabbits treated with azithromycin tolerated the drug well without signs of irritation. Clarithromycin was undetectable in corneal tissue by HPLC and bioactivity assay for all rabbits. Some rabbits treated with clarithromycin had signs of ocular surface irritation. CONCLUSION: Measurable concentrations of azithromycin are achieved in corneal tissue after topical application in a rabbit model, and the drug is well tolerated. Azithromycin may be a useful antibiotic for the topical treatment of human corneal infections, but clarithromycin, in currently available formulations, may not be effective because of poor tissue penetration.  相似文献   

9.
CASE REPORT: A 71-year-old woman with a history of aphakic glaucoma underwent implantation of an Ahmed valve and scleral grafting in her right eye. Postoperative visual acuity was 0.5 and intraocular pressure was 12 mmHg during treatment with brimonidine tartrate (0.2%). Nine months after implantation she suffered a conjunctival infection which was treated with hygienic measures and topical antibiotic therapy. Four days later, she developed an endophthalmitis which was treated with topical, intravitreous and intravenous vancomycin and ceftazidime. The Ahmed drainage implant was replaced at 72 hours. Laboratory culture yielded Haemophilus influenzae. Four days later, the eye was enucleated. DISCUSSION: Endophthalmitis is an uncommon complication of glaucoma drainage implant surgery. Exposure of the drainage tube represents the greatest risk factor for this condition. Removal of the implant in the first 24 hours is recommended if a good visual prognosis is to be achieved.  相似文献   

10.
PURPOSE: To investigate the therapeutic role of topical and oral fluconazole treatment using a rabbit model of Aspergillus fumigatus keratitis. METHODS: Aspergillus fumigatus spores were injected into the corneal stroma of the right eye of 20 rabbits. Forty-eight hours later the rabbits were randomly divided into three groups. Group 1 rabbits (six) were treated with topical fluconazole (2 mg/ml, eight times daily), group 2 rabbits (seven) received oral fluconazole (37.5 mg/kg bid), and group 3 rabbits (seven) were untreated controls. The eyes were examined and photographed with a slit-lamp 2, 6, 10, 16, and 20 days after inoculation and an observer graded the corneas in a masked fashion. Corneal cultures were taken on days 2, 14, and 20 for fungus growth. RESULTS: At the beginning of treatment, the slit-lamp scores did not differ among three groups. However, on days 6, 10, 16, and 20 the treated groups had statistically significant lower scores compared to the untreated controls. No significant difference was observed between topical and oral treated groups at any examination point. All cultures were positive on day 2, but on days 16 and 20, there were significantly lower positive fungal cultures in both treatment groups compared to the control (p < 0.01, chi square test). CONCLUSION: Our study showed that both topical and oral fluconazole were effective in lessening the severity of fungal keratitis in a rabbit model and should be considered effective treatment alternatives in the therapy of Aspergillus fumigatus keratitis.  相似文献   

11.
PURPOSE: To determine the efficacy of brimonidine tartrate 0.2% drops given 2 times a day in reducing intraocular pressure (IOP) spikes during the first 24 hours after phacoemulsification cataract surgery. SETTING: Department of Ophthalmology, General Hospital of Patras Agios Andreas, Patras, Greece. METHODS: In this prospective double-blind placebo-controlled study, 1 eye of 40 consecutive normotensive cataract patients having small-incision cataract surgery was randomized into 1 of 2 treatment arms. Twenty patients received a placebo (artificial tears) and 20 patients received brimonidine tartrate 0.2% drops 2 times a day the day before and the day of surgery. Diurnal IOP variation was the primary efficacy variable; IOP was measured at baseline, before surgery, and 4, 6, 12, and 24 hours postoperatively. RESULTS: The placebo group had higher IOPs at every time point after surgery. Peak elevation of IOP occurred 6 hours after surgery. The mean IOP in the placebo group (27.71 mm Hg +/- 3.75 [SD]) was statistically significantly higher than in the brimonidine group (21.45 +/- 1.32 mm Hg) (P<.001). A major IOP rise (>/=20 mm Hg above baseline IOP) occurred in 1 patient (5%) in the placebo group who required emergency hypotensive therapy. Twenty-four hours after surgery, 11 eyes (55%) in the brimonidine group and 4 eyes (20%) in the placebo group had an IOP lower than baseline. CONCLUSION: Prophylactic treatment with brimonidine tartrate 0.2% 2 times a day for 2 days was effective in reducing IOP peaks throughout the first 24 hours after phacoemulsification surgery.  相似文献   

12.
13.
PURPOSE: To describe clinical features and treatment outcomes in patients with advanced Nocardia asteroides keratitis. METHODS: Retrospective review of case records of 7 patients with culture-proven Nocardia keratitis. RESULTS: Corneal infection occurred after corneal trauma in two patients, cataract surgery in three patients, penetrating keratoplasty in one patient and was associated with a silicone buckle element infection in one patient. Mean duration of infection at presentation was 33.4 days (7-75 days), and five patients had received prior treatment with corticosteroids. Six of seven patients had deep corneal suppuration at the time of presentation, clinically suggestive of mycotic keratitis. In two patients who had received prolonged corticosteroid therapy (> or = 45 days), the eyes could not be salvaged. Complete resolution of infection was achieved in all 4 eyes treated with topical fortified cefazolin eye drops (50 mg/ml).  相似文献   

14.
射频烧灼兔眼巩膜对眼压的影响   总被引:1,自引:0,他引:1  
目的 探讨射频烧灼兔眼巩膜对眼压的影响 ,为射频治疗的安全性评价提供依据。方法 选取 6只健康新西兰纯种大白兔 ( 12眼 ) ,用射频治疗仪射频头直接烧灼兔眼巩膜 10s ,以烧灼前情况做自身对照 ,烧灼后 ,右眼用氯霉素和醋酸可的松滴眼液滴眼 ,左眼滴生理盐水对照。非接触式眼压计测量烧灼前及烧灼后 2h、2 4h、3d、14d的眼压 ,进行对比分析。结果 烧灼后各时段眼压与烧灼前相比 ,差异均无显著意义 (P >0 0 5 )。结论 射频烧灼巩膜后 14天内对眼压无明显影响。  相似文献   

15.
The effects of topical 0.5% timolol on tissue circulation in the albino rabbit optic nerve head (ONH) were investigated using a laser speckle tissue circulation analyzer. In the first experiment, the normalized blur (NB) value, a quantitative index of tissue blood flow velocity in the ONH, intraocular pressure (IOP), blood pressure, and pulse rate were measured under general anesthesia before, and 30, 60, 90, and 120 minutes after a 20 μL instillation of timolol in one eye and the vehicle in the other eye in a masked, randomized manner. In the second experiment, one eye of a rabbit received timolol twice daily for 20 days and the fellow eye received the vehicle in a masked, randomized manner. Every 5 days IOP was measured and the NB in the ONH and IOP were measured before treatment and 2 hours after the last instillation on the 20th day. After a single instillation of timolol, PR showed a maximum reduction of 12% and IOP in the timolol-treated eyes showed a maximum decrease in 25%. NB in the ONH and BP did not show any significant change during the experiment. After a 20-day treatment with timolol, IOP showed a maximum decrease of 25% in the timolol-treated eyes and 16% in the vehicle-treated eyes. The NB in the timolol-treated eyes increased significantly by 16% (P < 0.01), whereas that in the vehicle-treated eyes showed no significant change. It was suggested that long-term topical timolol with a normal drug regimen caused a significant increase in the peripheral blood velocity in the ONH only in the timolol-treated eyes, at least partly, by local penetration of the drug. Ocular penetration of topically applied timolol is thought to be similar between rabbit and human eyes. Therefore, the present results may have clinical implications.  相似文献   

16.
· Background: Tetrodotoxin (TTX) binds with high affinity to sodium channels and produces local anesthesia. We investigated whether TTX is an effective, long-acting corneal anesthetic in rabbits. · Methods: After mechanical debridement of the central corneal epithelium, topical TTX (1 mM, 0.1 mM, or 0.01 mM) was applied to one eye each of 18 New Zealand White rabbits. The fellow eye of each rabbit was treated with control vehicle. Blink response to a mechanical stimulus was assessed. Blink response was also assessed every 3 h for 30 h in 6 rabbits treated with 1 mM TTX administered every 6 h. In a separate group of 12 rabbits with central epithelial debridement, the rate of epithelial healing was compared between animals treated with topical 1.0 mM TTX and animals receiving no treatment. · Results: After 4 h, eyes treated with 1.0 mM and 0.1 mM TTX were anesthetic. At 6 h, five of six rabbit eyes treated with 1.0 mM TTX were still partially anesthetic. By 8 h, the mean anesthesia score for 1.0 mM TTX was approaching normal. With multiple dosing, all six rabbit eyes remained anesthetic for the duration of the experiment. There was no significant difference in the rate of re-epithelialization between eyes treated with TTX and untreated controls. There was no evidence of systemic or local toxicity from topical TTX. · Conclusion: In a rabbit model, TTX is a long-acting topical anesthetic that retains its effectiveness when administered repeatedly over 24 h and does not inhibit epithelial healing. It may have application in management of pain after photorefractive keratectomy. Received: 20 October 1997 Revised version received: 28 January 1998 Accepted: 29 January 1998  相似文献   

17.
MK-927 is a novel topical carbonic anhydrase inhibitor (CAI). We present the first single-dose clinical trial of MK-927 in 24 patients with bilateral primary open-angle glaucoma or ocular hypertension. This investigation was conducted as a two-centre, double-masked, randomised, placebo controlled study. Patients received one drop of 2% MK-927 in one eye and placebo in the other eye. Modified diurnal intraocular pressure (IOP) curves were performed before the study and on one treatment day. A single dose of 2% MK-927 induced a peak mean IOP decrease of 10.5 mmHg at 4.5 hours postdose. With compensation for diurnal variation, as determined by the prestudy diurnal pressure curve, the net peak mean reduction of IOP caused by MK-927 was 7.5 mmHg versus a corresponding net change of 1.4 mmHg in the contralateral placebo treated eye. Thus a single dose of MK-927 gave a clinically significant IOP reduction in patients.  相似文献   

18.
A two-year-old boy with nephropathic cystinosis was successfully treated with cysteamine eye drops. Using topical cysteamine 0.1% every two hours in the right eye we found a clearance of crystals from the cornea after 26 weeks. In the left eye, treated with topical cysteamine 0.5% the same result was reached after 12 weeks.  相似文献   

19.
Effect of timolol on central corneal thickness and endothelial cell density   总被引:1,自引:0,他引:1  
BACKGROUND: The measurement of corneal thickness plays an increasing role in glaucoma screening and diagnosis. The influence of a variety of drugs on corneal thickness is well established. Especially for antiglaucomateous drugs this effect seems to be important. However, little is known about the influence of beta receptor antagonists on corneal thickness. The aim of this study was to provide evidence of the effect of timolol on central corneal thickness and endothelial cell density. MATERIALS AND METHODS: Ten healthy volunteers (five women and five men) with a mean age of 29 years (range 25 to 56 years) were examined in a double-blind, prospective and randomised pilot study. Intraocular pressure, corneal thickness and endothelial cell density was estimated before as well as fifteen minutes, 24, 48, 72 and 96 hours after application of timolol 0.5 % eye drops twice daily. The partner eye received sodium hyaluronate eye drops twice daily and served as a control. RESULTS: The application of timolol showed a decrease of intraocular pressure from initially 12 mmHg to 9 mmHg after four days (p = 0,0188) as well as an increase of corneal thickness from 537 microm to 557 microm after four days (p = 0,0659). There was no change of intraocular pressure (p = 0,9935) or corneal thickness (p = 0,9998) in the control eyes. There was also no effect of timolol (p = 0,2782) or sodium hyaluronate (p = 0,1940) on endothelial cell density. CONCLUSIONS: The study provides evidence of the influence of beta receptor antagonists on corneal thickness. This effect may be caused by receptor mediated influences on corneal ion and fluid transport. Further studies are needed to show if the increase of corneal thickness after application of topical timolol has clinical importance.  相似文献   

20.
PURPOSE: To determine the vitreous penetration of the new fourth-generation topical fluoroquinolones moxifloxacin 0.5% and gatifloxacin 0.3%. METHODS: A prospective randomized clinical trial comprising 12 eyes of 12 patients scheduled for pars plana vitrectomy between August 2003 and September 2003 was performed in a clinical practice. The patients were randomly assigned to receive topical moxifloxacin 0.5% (n = 6) or gatifloxacin 0.3% (n = 6). One half the patients in each antibiotic group received 1 drop every 15 minutes for a total of 3 doses starting 1 hour before surgery, and the other one half self-administered the antibiotic drop 4 times daily for 3 days before surgery and at 7 am on the day of surgery. Undiluted vitreous samples were obtained and analyzed using high-performance liquid chromatography. RESULTS: Either moxifloxacin 0.5% or gatifloxacin 0.3% was detected in the vitreous in all 12 patients in the study. There was no significant difference between the mean vitreous concentration of moxifloxacin 0.5% given over 1 hour preoperatively (0.012 +/- 0.011 microg/mL) and that given in the 3-day regimen (0.011 +/- 0.008 microg/mL) (P = 0.93). There was also no significant difference between the mean vitreous concentration of gatifloxacin 0.3% given over 1 hour preoperatively (0.001 +/- 0.0003 microg/mL) and that given over 3 days (0.008 +/- 0.006 microg/mL) (P = 0.11). Vitreous concentrations of moxifloxacin 0.5% and gatifloxacin 0.3% in each eye were all lower than the 90% minimum inhibitory concentration for the commonest bacterial isolates causing endophthalmitis. With both dosing regimens, the mean vitreous concentration of moxifloxacin 0.5% was higher than that of gatifloxacin 0.3% administered at the same regimen, but this was not statistically significant. CONCLUSION: Both topical moxifloxacin 0.5% and gatifloxacin 0.3% penetrated the vitreous in the uninflamed eye, but the vitreous concentrations attained were all lower than the 90% minimum inhibitory concentration for the commonest bacterial pathogens causing acute postoperative endophthalmitis.  相似文献   

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