毛果芸香碱凝胶治疗青光眼的临床效果观察

目的探讨毛果芸香碱凝胶（ｐｉｌｏｃａｒｐｉｎｅｇｅｌ,ＰＧ）治疗青光眼是否优于毛果芸香碱水溶液（ｐｉｌｏｃａｒｐｉｎｅｓｏｌｕｔｉｏｎ,ＰＳ）。方法对２０例应用４％ＰＧ每晚１次和２０例应用１％ＰＳ每天４次的青光眼患者进行比较,两组患者均每天４次检查眼压、瞳孔直径和屈光度。结果４％ＰＧ每晚１次有效降眼压时间可持续２４小时,降眼压幅度达２５％～３７％;１％ＰＳ每天４次,降眼压幅度为２０％～２５％。ＰＧ在用药后５～１３小时降眼压作用最强,且９及１１时的作用强于ＰＳ,这对于控制起床前及上午眼压高峰特别有利。ＰＧ引起缩瞳及增强调节的最强作用在用药后５～８小时（睡眠期间）,而ＰＳ则在白天引起波动性的缩瞳及近视。ＰＧ每天仅需用药１次,较ＰＳ方便。结论在药效、副作用及依从性方面ＰＧ优于ＰＳ,值得推广、应用。     

毛果芸香碱凝胶的研究

与毛果芸香碱眼水比较，毛果芸香碱凝胶经动物实验证实其眼内房水及睫状体药物浓度较高，持续时间较长，ＰＧ对瞳孔的作用时间与其粘度和浓度有关，对角膜上皮可造成损害；临床研究表明：ＰＧ每晚一次维持１８－２４小时，药效与ＰＳ每日４次相当。     

0．004％曲伏前列腺素滴眼液和2％毛果芸香碱滴眼液联合应用对正常兔降眼压效果的评价

背景拟胆碱能药物和前列腺素类似物分别用于治疗原发性闭角型青光眼和开角型青光眼的临床效果已被证实,临床上二者常联合用药治疗青光眼,但理论上二者对睫状肌的作用机制是相背离的,因此有必要对二者联合用药的效果和作用机制进行进一步探讨。目的观察联合应用质量分数0．004％曲伏前列腺素和质量分数2％毛果芸香碱的降眼压效果。方法将正常无色素兔30只以随机数字表法随机分为毛果芸香碱组、曲伏前列腺素组和联合用药组3个组,每只兔任意选择一侧眼作为实验眼,分别每日3次点用2％毛果芸香碱滴眼液或每晚1次0．004％曲伏前列腺素滴眼液,联合用药组按上述用法同时点用上述两种药物;对侧眼点用生理盐水为对照眼。各组动物于用药前1d 8：00时以Perkins手持式压平眼压计测量双眼眼压作为基线眼压,并分别于用药后第1、2、4、8、14和24天的8：00时测量双眼眼压,以点眼前后眼压的变化作为主要观测指标。结果毛果芸香碱组、曲伏前列腺素组和联合用药组点眼后1d的眼压均明显低于基线眼压,而对照眼点眼前后眼压无明显变化;各实验眼治疗后各时间点间眼压无明显变化。毛果芸香碱组、曲伏前列腺素组和联合用药组实验眼眼压在点眼前与对照眼相比无明显差异,但点眼后均明显低于对照眼,差异均有统计学意义（P〈0．05）。与各组基线眼压比较,毛果芸香碱组、曲伏前列腺素组和联合用药组的实验眼眼压分别降低了17．5％～22．0％、23．8％～26．4％和27．6％～32．0％。对正常眼来说,联合用药组降眼压作用最强,其次依次为曲伏前列腺素和毛果芸香碱。结论联合用药的降眼压效果比单独点用毛果芸香碱和曲伏前列腺素的效果要好,但小于单独滴用毛果芸香碱和曲伏前列腺素的降眼压幅度之和。     

丁公藤碱Ⅱ——降眼压和缩瞳作用的研究

采用Goldmann压平眼压计、红外线瞳孔计与双盲法研究了丁公藤碱Ⅱ(以下简称碱Ⅱ)的降眼压和缩瞳作用,共观察原发性开角型青光眼72例144眼。结果表明:碱Ⅱ在降眼压方面有明显的剂量反应关系,0.01％、0.05％碱Ⅱ的降眼压幅度与1％毛果芸香碱相似,0.25％碱Ⅱ比1％毛果芸香碱强,碱Ⅱ在缩瞳方面则有一定的剂量反应关系,三种浓度碱Ⅱ的缩瞳作用与1％毛果芸香碱相似。连续滴药一个月,0.05％碱Ⅱ和1％毛果芸香碱的眼压下降率相接近,均可显著改善房水流畅系数,副作用不明显。此外,尚采用放射免疫法测定碱Ⅱ对兔眼房水中c-AMP和c-GMP含量的影响。结果表明0.01％碱Ⅱ在缩瞳、降眼压的同时,伴有c-GMP的升高,但不影响c-AMP的含量。作者就碱Ⅱ的M-胆碱能受体作用机制进行了讨论。     

单次滴用2%毛果芸香碱眼液致速发全身严重反应一例

毛果芸香碱是节后胆碱能药物，具有缩瞳和降眼压作用，主要用于青光眼的治疗。我院于2003年收治1例因用2％毛果芸香碱眼液滴眼后，致速发全身不良反应患者，现报告如下。     

联合应用毛果芸香碱与噻吗心安滴眼液治疗青光眼的合理给药时间研究

目的:探讨在联合应用毛果芸香碱与噻吗心安两种抗青光眼滴眼液的不同给药方式中,能够达到最佳控制眼压效果的给药方式。方法:新西兰大耳白兔36只随机分为毛果芸香碱组、噻吗心安组、常规同时给药1组、常规同时给药2组、毛果+噻吗组、噻吗+毛果组,共6组,建立慢性青光眼高眼压模型。此6组分别于滴注生理盐水或第一次给药后10,20,30,40,60,90,120,150,180和240min测眼压,比较眼压变化情况。结果:毛果+噻吗组眼压下降幅度明显,差异具有统计学意义(P<0.05)。结论:滴注毛果芸香碱滴眼液30min后滴注噻吗心安滴眼液,控制青光眼眼压稳定,效果最佳。     

联合毛果芸香碱滴眼液治疗眼外伤房角后退继发性青光眼

目的探讨联合毛果芸香碱滴眼液治疗外伤引起房角后退继发性青光眼的临床疗效。方法回顾性分析山东省眼科医院2007年8至2012年7收治12例(12只眼)眼外伤房角后退继发性青光眼患者的临床资料,患者均有眼球钝挫伤史且超生生物显微镜(UBM)和前房角镜检查可见外伤眼有不同程度的房角后退,入院眼压为(48.50±3.10)mm Hg,瞳孔直径为(5.15±0.70)mm。治疗:积极治疗原发性损伤,控制炎症,口服及静脉给予降眼压药物联合局部应用0.5%马来酸噻吗洛尔滴眼液、1%布林佐胺滴眼液、酒石酸溴莫尼定滴眼液降眼压治疗3～5 d,眼压不再下降,记录眼压为(35.00±3.55)mm Hg,此时加用0.5%毛果芸香碱滴眼液每日4次。详细记录患者治疗转归,观察眼压变化。结果加用毛果芸香碱眼滴眼液24 h后眼压为(21.90±3.87)mm Hg,平均下降(13.10±1.10)mm Hg。治疗前后瞳孔直径缩小(2.10±0.31)mm。4例患者最终逐渐减量药物致停,眼压正常;8例患者眼压降低后行小梁切除术控制眼压。结论毛果芸香碱滴眼液可以应用于眼外伤房角后退继发性青光眼患者,在减轻炎症的的基础上,联合应用毛果芸香碱滴眼液能够有效的降低眼压。     

青光眼药物治疗的新趋势-合理联合用药

合理联合用药是青光眼药物治疗的新趋势.本文介绍拉坦前列素分别与噻吗心安、毛果芸香碱、碳酸酐酶抑制剂、双三甲基乙酰肾上腺索、喘灵,噻吗心安与杜塞酰胺以及毛果芸香碱与噻吗心安联合降眼压作用的研究进展.     

毛果芸香碱微乳滴眼剂及滴眼液在兔眼房水中的药代动力学研究

目的 对２％毛果芸香碱微乳滴眼剂与２％毛果芸香碱滴眼液兔房水中的药代动力学进行对比研究。方法 健康白兔６０只,随机分成２０组,１０个实验组,１０个对照组,每组３只兔（６只眼）。对各实验组双眼结膜囊内准确滴入２％毛果芸香碱微乳滴眼剂５０μｌ,对各对照组双眼同法滴入２％毛果芸香碱滴眼液５０μｌ,分别于给药后５、１０、３０、４０、６０、９０、１２０、１８０、２４０及３６０ｍｉｎ时抽取房水。用于氯甲烷提取     

辰泽滴眼液在激光虹膜周切术中的应用

目的 评价辰泽滴眼液在激光虹膜周切术中的临床应用价值。方法 选择86例（172眼）双眼进行Nd：YAG激光虹膜周切术的患者,在激光治疗前1h滴2％毛果芸香碱滴眼液两次后,分为两组,一眼加滴辰泽滴眼液1滴,在激光手术完成后即刻再次滴入辰泽滴眼液一滴,另一眼不用辰泽滴眼液。术后1h测量双眼的眼压,第二天复诊时观察虹膜周切口的情况并再次测量眼压,术后一周复诊观察虹膜周切口的情况并再次测量眼压。如眼压升高大于22 mm Hg需进行降眼压治疗。结果 辰泽滴眼液能良好的控制行激光虹膜周切术后患者的眼压,仅有5只眼(5.81％)应用辰泽滴眼液患者的眼压略高于22 mm Hg,未予降眼压治疗;而未应用辰泽滴眼液的患眼眼压升高达48只眼(55.81％),术后1h眼压测量比较,所有应用辰泽滴眼液的术眼的眼压升高远较对侧眼为低,且辰泽滴眼液也能较好地改善滴用毛果芸香碱滴眼液后球结膜充血。结论 辰泽滴眼液在激光虹膜周切术中能明显减轻手术副反应,降眼压效果确切,建议临床中推广应用。     

A prospective, long-term, randomized study of the efficacy and safety of the drug combination pilocarpine 1% with clonidine 0.06% or clonidine 0.125% versus timolol 0.25%.

The purpose of this prospective, randomized study was to evaluate the efficacy and safety of the drug combinations--pilocarpine 1% with clonidine 0.06% and pilocarpine 1% with clonidine 0.125%, in comparison with timolol 0.25%. 54 patients with bilateral primary open angle glaucoma and comparable IOP were assigned to three study groups: group 1 received the drug combination of pilocarpine 1% and clonidine 0.06%, group 2 received the drug combination pilocarpine 1% and clonidine 0.125% and group 3 only timolol 0.25% drops. In all groups twice-daily medication was used. Mean diurnal IOP as well as ocular and systemic side effects were evaluated at week 1, 2, 4, 8 and 12. Changes in blood pressure, pulse rate, pupil size and patient symptoms were also recorded. At three months all patients had completed the study. Diurnal IOP was significantly reduced from baseline in all groups and consistent IOP reduction was achieved in all three groups at all follow up periods. Mean IOP reduction was 18.40%, 28.45% and 24.64% in group 1, group 2 and group 3, respectively. Flattening of the diurnal fluctuation in IOP was also seen in all patients. On comparing the IOP reduction achieved amongst the three groups, there was a statistically significant difference between group 1 and group 2 as well as between group I and group 3 while the difference between group 2 and group 3 was statistically insignificant. The drug combinations of pilocarpine 1% and clonidine did not produce any statistically significant effect on pupil diameter. No statistically significant difference was noted with respect to patient symptoms, blood pressure and pulse rate. In conclusion, the drug combination of pilocarpine 1% and clonidine 0.125% produces IOP reduction comparable to that achieved with timolol 0.25% drops in twice daily dosage and does not result in any significant ocular and systemic adverse effects.     

Steepening of corneal curvature with contraction of the ciliary muscle

PURPOSE: To measure the changes of corneal curvature during contraction of the ciliary muscle. SETTING: Department of Ophthalmology, St. Luke's International Hospital, Tokyo, Japan. METHODS: Twenty-eight eyes of 14 healthy volunteers under 40 years old were enrolled in this prospective randomized controlled study and divided into pilocarpine and control groups. Intraocular pressure (IOP), pupil diameter, and corneal topography were measured before and 40 minutes after instillation of topical pilocarpine 4% or balanced salt solution. Corneal topography was analyzed for the mean ring-power of Placido rings 1 through 25, average corneal power (ACP), and for spherical equivalent, regular astigmatism, asymmetry, and high-order irregularity by Fourier analysis. RESULTS: Pilocarpine had no effect on IOP, but it did cause a significant decrease in mean pupil diameter. Simultaneously, pilocarpine increased the mean ring powers for Placido rings 1 through 4 and the ACP (+0.13 diopters (D) +/- 0.17 [SD]; P=.017). By Fourier analysis, the mean spherical component for the central 3.0 mm of the cornea increased in the pilocarpine group (+0.08 +/- 0.15 D; P=.020). There were no changes in components of regular astigmatism, asymmetry, and high-order irregularity. CONCLUSIONS: The central cornea steepened in curvature and increased in power owing to contraction of the ciliary muscle. The results suggest that changes in corneal curvature increase refractive power during accommodation.     

Control of intraocular pressure after cataract extraction

We carried out a prospective randomized study in 172 patients undergoing cataract extraction and lens implantation to compare the effects of pilocarpine gel, 1% acetylcholine chloride and 0.01% carbachol on early postoperative intraocular pressure (IOP), to determine the effect of sodium hyaluronate on IOP and to compare the effects of 0.01% carbachol (full-strength) and 0.005% carbachol (half-strength) on IOP, pupil size and brow ache. IOP was measured 3, 6, 9 and 24 hours after surgery, and in the full- and half-strength carbachol groups pupil size and subjective complaints of brow ache were recorded. The mean IOP 3 and 6 hours after surgery was significantly lower in all the treatment groups than in the control groups. At 9 and 24 hours it was significantly lower only in the carbachol groups. The use of sodium hyaluronate was not found to affect the postoperative IOP. There was no difference in postoperative IOP or miosis between the full- and half-strength carbachol groups, but fewer patients in the half-strength group than in the full-strength group reported brow ache at 9 and 24 hours. The results suggest that carbachol is the most effective agent currently available for the management of IOP after cataract extraction.     

毛果芸香碱防止Nd∶YAG激光虹膜切除术后眼压升高

目的:了解毛果芸香碱是否能有效降低棕色虹膜人种激光虹膜切除术后眼压急性升高。方法:原发性闭角型青光眼48例58眼,按年龄、性别进行匹配,分为治疗组和对照组。治疗组术前30min和术后即刻滴用20g/L毛果芸香碱,对照组滴用安慰剂。术后0.5,1.0,1.5,2.0,3.5h观察眼压和其他情况。结果:激光治疗后,治疗组和对照组眼压最大升高值分别为0.62±0.67kPa(1kPa=7.5mmHg)和1.13±0.87kPa,两组间差异有显著性(P=0.03)。治疗组的眼压明显下降发生于Nd∶YAG激光虹膜切除术后0.5,1.0和1.5h。除治疗组激光虹膜切除术后瞳孔直径明显小于对照组外,未见其他眼部和全身的副作用。结论:20g/L毛果芸香碱在棕色人种中可以有效地防止Nd∶YAG激光虹膜切除术后眼压升高。     

Effect of timolol versus pilocarpine on visual field progression in patients with primary open-angle glaucoma.

BACKGROUND: Relatively few studies have been conducted linking decreasing intraocular pressure (IOP) to preservation of visual field. This investigation was conducted to determine if this link could be made and to compare the long-term effect of two ocular hypotensive agents on preservation of visual field. METHODS: In an observer-masked study, 189 patients with primary open-angle glaucoma received either timolol or pilocarpine by random allocation. The dose of antiglaucoma agent was increased from 0.25% to 0.5% twice daily for timolol or from 2% to 4% four times daily for pilocarpine if the initial IOP response was inadequate. After an on-treatment baseline, visual fields were followed every 4 months for 2 years using the Octopus program 32. RESULTS: Compared with timolol, significantly more patients receiving pilocarpine discontinued use because of inadequate IOP control (P < or = 0.01). By comparing the mean visual field scores, it can be seen that the pilocarpine group had a significantly worse score at all timepoints from month 4 to month 24. The pilocarpine group also had a greater mean number of test loci with decreased sensitivity of 5 or more decibels (dB) at all timepoints. The mean within-patient regression slope for timolol was 0.01 dB/month and for pilocarpine was -0.06 dB/month (P < 0.01). The study has shown that over a 2-year period, patients treated with pilocarpine 2% or 4% four times daily experienced a significantly greater visual field deterioration than that seen in patients receiving either 0.25% or 0.5% timolol twice daily. CONCLUSION: Although these data do not support a link between lowering of IOP and visual field preservation, treatment with timolol was associated with significantly less visual field loss than treatment with pilocarpine.     

Efficacy of apraclonidine 1% versus pilocarpine 4% for prophylaxis of intraocular pressure spike after argon laser trabeculoplasty.

OBJECTIVE: The authors compared the efficacy of apraclonidine 1% versus pilocarpine 4% prophylaxis of post-argon laser trabeculoplasty (ALT) intraocular pressure (IOP) spike. DESIGN: Prospective randomized clinical trial. PARTICIPANTS: Two hundred twenty-eight eyes of 228 patients with primary open-angle glaucoma undergoing ALT were studied. INTERVENTION: Patients were given 1 drop of either apraclonidine 1% (n = 114) or pilocarpine 4% (n = 114) 15 minutes before ALT. MAIN OUTCOME MEASURES: Peri-ALT IOPs and incidences of post-ALT IOP spikes at 5 minutes, 1 hour, and 24 hours were compared between the two groups. RESULTS: The two groups were similar in age, race, and medical dependency. Post-ALT mean IOPs at 5 minutes, 1 hour, and 24 hours were significantly lower than pre-ALT mean IOPs in both apraclonidine (P < 0.001) and pilocarpine (P < 0.001) groups. Incidences of IOP spikes greater than 1, 3, and 5 mmHg at 1 hour post-ALT were 21.1%, 14.9%, and 8.8% for the apraclonidine group and 12.3%, 5.3%, and 4.4% for the pilocarpine group (P = 0.076, 0.015, and 0.18 chi-square test). In the apraclonidine prophylaxis group, patients on long-term apraclonidine showed significantly higher incidence of post-ALT IOP spike than the patients without such long-term apraclonidine use (35.7%, 15 of 42 eyes, vs. 12.5%, 9 of 72 eyes; P = 0.003). In addition, peri-ALT pilocarpine prophylaxis tended to be less effective in patients undergoing long-term pilocarpine therapy but without statistical significance (17.4%, 8 of 46 eyes, vs. 9.4%, 6 of 64 eyes; P = 0.17). CONCLUSION: Peri-ALT pilocarpine 4% was at least as effective as, if not more effective than, apraclonidine 1% in post-ALT IOP spike prophylaxis. Peri-ALT apraclonidine prophylaxis was not effective in patients on long-term apraclonidine, and peri-ALT pilocarpine prophylaxis tended to be less effective in patients undergoing long-term pilocarpine therapy. Pilocarpine 4% can be considered as a first-choice drug for post-ALT IOP spike prophylaxis, especially in patients under treatment with apraclonidine.     

青壮年近视患者的眼压变化及其规律探讨

目的 :探讨青壮年近视患者的眼压变化及其变化规律。方法 :对 46 6例 ( 891眼 )年龄在 16岁～ 46岁、屈光度从 -0 5 0D～ -2 3 5 0D的近视患者的眼压及其相关因素进行统计分析并与非近视组对照。结果 :近视患者眼压水平随屈光度增加而升高 (P <0 0 0 5 ) ;近视组平均眼压较非近视组高约 0 9mmHg ( 1mmHg =0 133kPa) ,高度近视组较非近视组高约 1 3mmHg ;不论中、低度近视还是高度或超高度近视其平均眼压水平均高于非近视组 (P <0 0 5 ) ;在近视组内 ,中、低度近视的平均眼压与高度或超高度近视之间有显著性差异 (P <0 0 5 ) ,但中度与低度近视之间、高度与超高度近视之间无明显差异。屈光度从 0D增加到 >8D时 ,眼压均值上升辐度大 ,净升值高达 1 2 7mmHg ,屈光度从 -8D上升到 -12D时 ,眼压均值升辐小 ,净升值低 ,仅 0 14mmHg。近视男性眼压高于女性 (P =0 0 0 0 1)。近视眼压与年龄及眼别无显著相关性。结论 :平均眼压随屈光度增加而升高 ,应加强对近视患者的眼压监测 ,对男性患者更为重要 ,降低眼内压也许是控制近视发展的一个重要手段     

An experimental study of the ocular hypotensive action of dopaminergic antagonists

The ocular hypotensive action of a group of dopaminergic antagonists was observed in the low intraocular pressure model of albino rabbits infused with 20% NaCl. It was found that haloperidol lowered IOP significantly in both eyes, though the drug was administered in one eye. Compared with timolol and pilocarpine, the strength in lowering IOP was in the order haloperidol greater than timolol greater than pilocarpine. Haloperidol did not affect the pupil. It may be a promising antiglaucoma agent.     

Additivity of pilocarpine to bimatoprost in ocular hypertension and early glaucoma

PURPOSE: To determine if the intraocular pressure (IOP) effect of pilocarpine at various concentrations is additive to that of bimatoprost and to assess the tolerability of this combination. METHODS: This was a randomized, prospective trial of patients with IOP > 21 mm Hg following appropriate medication washout. For all visits IOP was measured at 9:00 AM and 11:00 AM. Following baseline visit (#1), bimatoprost 0.03% was instilled qhs OU through visit 6. Following visits 2, 3, and 4 pilocarpine (2%, 4%, 6%) was instilled qid in one randomly selected eye. Pilocarpine was discontinued after visit 5 and bimatoprost after visit 6. Two-tailed, paired t test was used to compare treated and contralateral eyes for their IOP, IOP change, percentage IOP change from baseline, and to compare IOP in the same eye at 9:00 AM and 11:00 AM (before and after pilocarpine administration). IOPs using bimatoprost alone or in combination with various pilocarpine concentrations were compared using single variant Analysis of Variance (ANOVA). RESULTS: Seventeen patients were enrolled and 13 patients completed the study. Bimatoprost reduced IOP 28.7% to 30.5% (P < 0.0001) from baseline to visit 2. IOPs in eyes treated with bimatoprost alone or with bimatoprost and various pilocarpine concentrations were similar (P > 0.81, ANOVA). The IOP (P > 0.17) and percentage IOP change from baseline (P > 0.10) was similar in treated and contralateral eyes with all three strengths of pilocarpine. IOP values at 9:00 AM and 11:00 AM, before and after pilocarpine administration, were similar (P > 0.22). CONCLUSION: Bimatoprost alone reduces IOP substantially. Pilocarpine added to bimatoprost at concentrations of 2%, 4%, or 6% was neither additive nor antagonistic to the ocular hypotensive efficacy of bimatoprost.