Intraocular Pressure-Lowering Effects of Commonly Used Fixed-Combination Drugs with Timolol: A Systematic Review and Meta-Analysis

Background

The first goal of medical therapy in glaucoma is to reduce intraocular pressure (IOP), and the fixed-combination medications are needed to achieve sufficiently low target IOP. The aim of this systematic review and meta-analysis is to evaluate IOP-lowering effect of the commonly used fixed-combination drugs containing 0.5% timolol.

Methods

Pertinent publications were identified through systematic searches. Over 85% of the patients had to be diagnosed with primary open-angle glaucoma (POAG) or ocular hypertension (OHT). Forty-one randomized clinical trials were included in the meta-analysis. The main efficacy measures were the absolute and relative values of mean diurnal IOP reduction, and the highest and lowest IOP reductions on the diurnal IOP curve. The pooled 1- to 3-month IOP-lowering effects after a medicine-free washout period was calculated by performing meta-analysis using the random effects model, and relative treatment effects among different fixed combinations were assessed using a mixed-effects meta-regression model.

Results

The relative reductions for mean diurnal IOP were 34.9% for travoprost/timolol, 34.3% for bimatoprost/timolol, 33.9% for latanoprost/timolol, 32.7% for brinzolamide/timolol, 29.9% for dorzolamide/timolol, and 28.1% for brimonidine/timolol. For the highest IOP decrease, relative reductions ranged from 31.3% for dorzolamide/timolol to 35.5% for travoprost/timolol; for the lowest IOP decrease, those varied from 25.9% for dorzolamide/timolol to 33.1% for bimatoprost/timolol. Both latanoprost/timolol and travoprost/timolol were more effective in lowering mean diurnal IOP than brimonidine/timolol (WMD: 5.9 and 7.0) and dorzolamide/timolol (WMD: 3.8 and 3.3).

Conclusions

All six commonly used fixed-combination drugs containing timolol can effectively lower IOP in patients with POAG and OHT, and both latanoprost/timolol and travoprost/timolol might achieve better IOP-lowering effects among the six fixed-combination agents.     

A study of replacement of timolol-pilocarpine with latanoprost in pseudoexfoliation glaucoma

The aim of the study was to evaluate the efficacy of replacing current dual local therapy (timolol and pilocarpine) with latanoprost 0.005% in 71 pseudoexfoliation glaucoma patients with controlled intraocular pressure (IOP). 39 patients switched to latanoprost 0.005%) and 32 patients continued timolol-pilocarpine therapy. Mean diurnal (IOP) was measured at baseline, after 0.5, 1, 3 and 6 months of treatment. After 6 months 38 patients with latanoprost and 30 patients with timolol-pilocarpine had completed the study. At baseline the mean diurnal IOP was 20.4 +/- 2.0 mmHg for patients in latanoprost treatment group and 21.4 +/- 2.1 mmHg for patients in timolol-pilocarpine group. At the end of the study, after 6 months of treatment, the mean diurnal IOP values were 16.6 +/- 2.4 and 17.9 +/- 2.0 mmHg respectively. IOP was statistically significantly reduced from baseline (p < 0.001). The mean diurnal IOP change from baseline was -3.3 +/- 0.5 mmHg (mean +/- SEM, ANCOVA) for the patients treated with latanoprost and -3.2 +/- 0.4 mmHg for the patients treated with timolol + pilocarpine. This difference in IOP reduction between groups was not statistically significant (z = 0.69; p = 0.49). This study showed that combination therapy (timolol plus pilocarpine) in pseudoexfoliation glaucoma can effectively be replaced by latanoprost monotherapy.     

Efficacy and Tolerability of the Fixed Combinations Latanoprost/Timolol versus Dorzolamide/Timolol in Patients with Elevated Intraocular Pressure: A Meta-Analysis of Randomized Controlled Trials

Objective

To evaluate the efficacy and tolerability of the fixed combination of Latanoprost/Timolol versus Dorzolamide/Timolol in the treatment of patients with elevated intraocular pressure (IOP).

Methods

A comprehensive literature meta-analysis was performed according to the Cochrane Collaboration methodology to identify randomized clinical trials comparing latanoprost/timolol FC (FCLT) with dorzolamide/timolol (FCDT) in patients with elevated IOP. The efficacy estimates were measured by the weight mean difference (WMD) for the IOP reduction (IOPR) from baseline to end point, including the diurnal mean IOPR, 8 AM IOPR, 12 PM IOPR, and 4 PM IOPR. The tolerability estimates were measured by RR for adverse events. All outcomes were reported with a 95% confidence interval (CI). The data were synthesized by Stata 12.0 SE for Windows.

Results

Eight studies involving 841 patients (841 eyes) were included in the meta-analysis. With a WMD of IOPR in the diurnal mean of 0.16 mmHg (95% CI, -0.31 to 0.63), the FCLT was as effective as FCDT in lowering IOP in patients with elevated IOP (P = 0.51). The WMDs of IOPR were 0.58 mmHg (95% CI: -0.002 to 1.17) at 8 AM, -0.07 mmHg (95% CI: -0.50 to 0.36) at 12 PM, and 0.41 mmHg (95% CI: -0.18 to 1.00) at 4 PM, and there were no significant difference between FCLT and FCDT. FCLT was associated with a significantly lower incidence of eye pain, bitter taste, and irritation/stinging than FCDT, with pooled RRs of 0.34 (95% CI: 0.14 to 0.82), 0.06 (95% CI:0.008 to 0.42), and 0.35 (95% CI: 0.14 to 0.85), respectively.

Conclusion

FCLT was associated with equivalent efficacy in IOP lowering comparing with FCDT. However, FCLT was better tolerated than FCDT.     

布林佐胺与噻吗洛尔滴眼液对新生血管性青光眼患者眼压及血清和房水IL-6、PEDF和VEGF水平的影响

目的:探讨布林佐胺联合噻吗洛尔滴眼液对新生血管性青光眼(NVG)患者眼压及血清和房水中白细胞介素-6(IL-6)、色素上皮衍生因子(PEDF)、血管内皮生长因子(VEGF)水平的影响。方法:选取我院2014年6月～2016年12月择期行手术治疗的86例NVG患者,按照随机数字表法均分为两组。对照组术后采取噻吗洛尔滴眼液治疗,观察组在此基础上加用布林佐胺滴眼液治疗。记录比较两组临床疗效,治疗前后眼压及血清和房水中IL-6、PEDF和VEGF水平的变化及不良反应的发生情况。结果:术后6个月,观察组总有效率为95.3%,较对照组明显升高(79.1%,P0.05)。与术前对比,两组术后7天、6个月时24 h眼压峰值、平均眼压、眼压波动值、血清和房水中IL-6、VEGF水平均显著下降(P0.01),血清和房水中PEDF水平均显著上升(P0.01),且观察组以上眼压指标较对照组同期改善更为明显(P0.01)。对照组和观察组不良反应的发生率对比差异无统计学意义(7.0%vs 11.6%,P0.05)。结论:术后应用布林佐胺联合噻吗洛尔滴眼液治疗NVG患者更能有效降低眼压和控制其波动,调节机体血管生成促进/抑制因子平衡,提高治疗效果,且安全性高。     

Effects of Topical Bimatoprost 0.01% and Timolol 0.5% on Circadian IOP,Blood Pressure and Perfusion Pressure in Patients with Glaucoma or Ocular Hypertension: A Randomized,Double Masked,Placebo-Controlled Clinical Trial

PurposeTo compare the 24-hour (24h) effects on intraocular pressure (IOP) and cardiovascular parameters of timolol 0.5% and bimatoprost 0.01% in open angle glaucoma and ocular hypertensive subjects.MethodsIn this prospective, randomized, double masked, crossover, clinical trial, after washout from previous medications enrolled subjects underwent 24h IOP, blood pressure (BP) and heart rate (HR) measurements and were randomized to either topical bimatoprost 0.01% at night plus placebo in the morning or to timolol 0.5% bid. After 8 weeks of treatment a second 24h assessment of IOP, BP and HR was performed and then subjects switched to the opposite treatment for additional 8 weeks when a third 24h assessment was performed. The primary endpoint was the comparison of the mean 24h IOP after each treatment. Secondary endpoints included the comparisons of IOP at each timepoint of the 24h curve and the comparison of BP, HR, ocular perfusion pressure and tolerability.ResultsMean untreated 24h IOP was 20.3 mmHg (95%CI 19.0 to 21.6). Mean 24h IOP was significantly lower after 8 weeks of treatment with bimatoprost 0.01% than after 8 weeks of treatment with timolol 0.5% bid (15.7 vs 16.8 mmHg, p = 0.0003). Mean IOP during the day hours was significantly reduced from baseline by both drugs while mean IOP during the night hours was reduced by -2.3 mmHg (p = 0.0002) by bimatoprost 0.01% plus placebo and by -1.1 mmHg by timolol 0.5% bid (p = 0.06). Timolol 0.5% significantly reduced the mean 24h systolic BP from baseline, the diastolic BP during the day hours, the HR during the night hours, and the mean 24h systolic ocular perfusion pressure.ConclusionBoth Bimatoprost 0.01% and Timolol 0.5% are effective in reducing the mean 24h IOP from an untreated baseline but Bimatoprost 0.01% is more effective than timolol 0.5% throughout the 24h. Timolol 0.5% effect on IOP is reduced during the night hours and is associated with reduced BP, HR and ocular perfusion pressure.

Trial Registration

EU Clinical Trial Register and EudraCT# 2010-024272-26     

马来酸噻吗洛尔眼液联合拉坦前列素眼液对原发性开角型青光眼患者眼压的影响

目的:探讨马来酸噻吗洛尔眼液联合拉坦前列素眼液对原发性开角型青光眼患者眼压的影响。方法:选取2015年1月-2016年5月在我院接受治疗的原发性开角型青光眼患者84例,其中给予马来酸噻吗洛尔眼液治疗的42例记为对照组,给予拉坦前列素眼液联合马来酸噻吗洛尔眼液治疗的42例记为观察组,两组均治疗6个月。对比两组患者治疗过程中的眼压变化情况,并对比两组患者的临床总有效率、药物依从性和并发症情况。结果:观察组治疗2、4、6个月后的眼压均显著低于对照组(P0.05),观察组患者治疗6个月后与治疗前的眼压差值大于对照组(P0.05)。两组患者治疗2、4、6个月后的眼压呈下降趋势,两两比较差异均有统计学意义(P0.05)。观察组的临床总有效率95.24%显著高于对照组的80.95%(P0.05)。两组患者在治疗过程中结膜充血、眼内异物感、眼睛疼痛、视力模糊、味觉异常以及总并发症发生率对比差异不显著(P0.05)。观察组患者的药物依从性比例显著低于对照组(P0.05)。结论:马来酸噻吗洛尔眼液联合拉坦前列素眼液治疗原发性开角型青光眼患者具有较好的临床疗效,可显著降低患者眼压,同时具有较好的安全性,但药物依从性较差。     

汉防己甲素滴眼液对高眼压模型大鼠的降眼压作用

目的比较观察汉防己甲素滴眼液与0.5%噻吗心安滴眼液对高眼压模型大鼠及正常大鼠降眼压的作用。方法正常SD大鼠共分4组：不同浓度的汉防己甲素滴眼液组（0.1%、0.2%、0.3%）及阳性对照组0.5%噻吗心安,药物滴右眼各一滴,阴性对照组生理盐水滴左眼、测量滴药前24h和滴药后1、3、6、24、48、72h的眼压。应用倍频532激光对SD大鼠右眼上巩膜静脉以及小梁网所在区域实施光凝术建立高眼压大鼠模型。高眼压模型鼠共分5组：不同浓度的汉防己甲素滴眼液0.05%、0.1%、0.2%、0.3%及阳性对照组0.5%噻吗心安,右眼即模型眼滴用药物,左眼作为空白对照。测量术前后的眼压。结果汉防己甲素滴眼液对大鼠正常眼压无降压作用（P〉0.05）。对高眼压大鼠用药后24h、72h、1周后,0.3%汉防己甲素滴眼液组降低眼压的幅度与0.5%噻吗心安滴眼液降低眼压的幅度相似（P〉0.05）;0.05%、0.1%、0.2%汉防己甲素滴眼液组也有明显的降压作用,但与0.5%噻吗心安滴眼液相比,降压幅度低于后者（P〈0.05）。结论0.05%、0.1%、0.2%、0.3%汉防己甲素滴眼液均有降低大鼠高眼压的作用,其中0.3%浓度的汉防己甲素滴眼液降眼压效果与0.5%的噻吗心安类似。汉防已甲素滴眼液作为一种治疗青光眼的药物有着良好应用前景。     

曲伏前列素滴眼液联合复方丹参片对老年青光眼患者房水屏障功能 及MMP2 水平的影响

目的:研究曲伏前列素滴眼液联合复方丹参片对老年青光眼患者房水屏障功能、MMP2及临床疗效的影响。方法:选择2012年5月-2015年10月期间在我院就诊的90例青光眼患者作为研究对象,随机分为实验组和对照组,实验组患者接受曲伏前列素滴眼液联合复方丹参片治疗,对照组患者接受曲伏前列素滴眼液治疗,比较两组患者治疗前后的平均眼压水平、房水屏障功能以及血清MMP2含量、MMP2/TIMP1比值。结果:治疗后1个月、2个月、3个月时,实验组患者的平均眼压水平(17.2±2.2 vs 19.7±3.1 mm Hg)、(17.0±2.8 vs 20.2±3.2 mm Hg)、(16.7±2.5 vs 18.2±3.5 mm Hg)均显著低于对照组(P0.05);治疗后3个月时,实验组患者的房水闪辉值(18.3±2.8 vs 33.1±5.6 pc/ms)、房水细胞数以及血清MMP2含量(2.77±0.46 vs 4.02±0.72μg/L)及MMP2/TIMP1比例(0.48±0.07 vs 0.76±0.09)均显著低于对照组(P0.05)。结论:曲伏前列素滴眼液联合复方丹参片治疗能够更为有效地降低眼压水平、改善房水屏障功能,可能与其降低MMP2含量有关。     

Chronopharmacology of Captopril plus Hydrochlorothiazide in Hypertension: Morning Versus Evening Dosing

Blood pressure follows a strong circadian rhythm in normotensive people and in patients with primary hypertension. This may have several implications for antihypertensive therapy, including the time of dosing. For this reason we studied the influence of different dosing times on the antihypertensive effect over 24 h using ambulatory blood pressure monitoring (ABPM). We studied 13 male patients with moderate hypertension with controlled blood pressure over 12 months under a fixed combination of captopril and hydrochlorothiazide. The dosage of the combination therapy was then halved and given as one evening and then as one morning dose, each for 3 weeks. The combination therapy given twice daily showed a good 24-h antihypertensive effect after 12 months of treatment. During the following 6 weeks the mean 24-h blood pressure did not increase under half dosage, irrespective of whether under evening or morning dosing. However, mean daytime values (systolic and diastolic) of ABPM were significantly higher with evening dosing when compared both with full dosage and with half dosage given in the morning. The mean arterial blood pressure over 24 h showed the same differences as systolic and diastolic blood pressure, whereas heart rate was not significantly different between the three therapeutic regimens. ABPM seems to be an ideal method for chronopharmacological investigations under everyday conditions. Our study demonstrated significant differences in daytime blood pressure but not in 24-h blood pressure between morning and evening dosing of a fixed antihypertensive combination therapy.     

Chronopharmacology of Captopril plus Hydrochlorothiazide in Hypertension: Morning Versus Evening Dosing

Blood pressure follows a strong circadian rhythm in normotensive people and in patients with primary hypertension. This may have several implications for antihypertensive therapy, including the time of dosing. For this reason we studied the influence of different dosing times on the antihypertensive effect over 24 h using ambulatory blood pressure monitoring (ABPM). We studied 13 male patients with moderate hypertension with controlled blood pressure over 12 months under a fixed combination of captopril and hydrochlorothiazide. The dosage of the combination therapy was then halved and given as one evening and then as one morning dose, each for 3 weeks. The combination therapy given twice daily showed a good 24-h antihypertensive effect after 12 months of treatment. During the following 6 weeks the mean 24-h blood pressure did not increase under half dosage, irrespective of whether under evening or morning dosing. However, mean daytime values (systolic and diastolic) of ABPM were significantly higher with evening dosing when compared both with full dosage and with half dosage given in the morning. The mean arterial blood pressure over 24 h showed the same differences as systolic and diastolic blood pressure, whereas heart rate was not significantly different between the three therapeutic regimens. ABPM seems to be an ideal method for chronopharmacological investigations under everyday conditions. Our study demonstrated significant differences in daytime blood pressure but not in 24-h blood pressure between morning and evening dosing of a fixed antihypertensive combination therapy.     

曲伏前列素滴眼液治疗开角型青光眼的疗效及对血流动力学的影响

目的:探讨曲伏前列素滴眼液治疗开角型青光眼的疗效及对血流动力学的影响。方法:选择2013年3月~2015年12月在我院接受治疗的164例开角型青光眼患者为研究对象,按照随机数字表法分为对照组和试验组,每组82例,对照组给予马来酸噻吗洛尔滴眼,试验组给予曲伏前列素滴眼,12周后观察两组患者的降眼压效果和视力改变情况,彩色多普勒超声检测眼动脉(OA)、睫状后短动脉(SPCA)及视网膜中央动脉(CRA)的收缩期血流峰值速度(PSV)、舒张末期血流速度(EDV)和阻力指数(RI),并观察其不良反应。结果:两组患者治疗前和治疗后2周的眼压和视力比较,差异无统计学意义(P0.05)。治疗后,两组患者的眼压与治疗前比较均降低,视力与治疗前比较均提升,且试验组眼压降低及视力提升更显著,差异有统计学意义(P0.05);治疗6周和12周后,试验组患者的眼压低于对照组,视力高于对照组,差异有统计学意义(P0.05)。治疗12周后试验组患者OA、SPCA及CRA的EDV、PSV均高于对照组,而RI均低于对照组,差异有统计学意义(P0.05)。两组患者的不良反应主要为轻度异物感、轻度结膜充血、虹膜色素加深等,两组患者的不良反应发生率比较,差异无统计学意义(P0.05)。结论:曲伏前列素滴眼液治疗开角型青光眼可降低眼压,提高视力,改善眼部血流动力学指标,且安全性较好,值得临床推广应用。     

复合式与传统小梁切除术对青光眼患者眼压、生活质量及血清细胞因子的影响

目的:对比复合式与传统小梁切除术对青光眼患者眼压、生活质量及血清细胞因子的影响。方法:前瞻性选取2014年1月-2018年10月期间我院收治的青光眼患者80例,随机分为A组[n=38,传统小梁切除术]和B组[n=42,复合式小梁切除术],比较两组患者视力、眼压、生活质量、血清细胞因子及并发症发生情况。结果:两组患者术后1个月、术后3个月、术后6个月眼压呈不断下降趋势,且B组低于A组(P<0.05);B组术后3个月、术后6个月视力高于A组(P<0.05)。两组患者术后6个月生活质量量表(SF-36)各维度评分均升高,且B组高于A组(P<0.05)。两组患者术后1个月白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、血管内皮生成因子(VEGF)均降低,且B组低于A组(P<0.05);两组患者术后1个月色素上皮衍生因子(PEDF)升高,且B组高于A组(P<0.05)。B组并发症发生率低于A组(P<0.05)。结论:与传统小梁切除术相比,复合式小梁切除术在改善青光眼患者中的视力、眼压、生活质量、血清细胞因子方面效果显著,同时还可减少并发症发生率。     

Crystallins Are Regulated Biomarkers for Monitoring Topical Therapy of Glaucomatous Optic Neuropathy

Optic nerve atrophy caused by abnormal intraocular pressure (IOP) remains the most common cause of irreversible loss of vision worldwide. The aim of this study was to determine whether topically applied IOP-lowering eye drugs affect retinal ganglion cells (RGCs) and retinal metabolism in a rat model of optic neuropathy. IOP was elevated through cauterization of episcleral veins, and then lowered either by the daily topical application of timolol, timolol/travoprost, timolol/dorzolamide, or timolol/brimonidine, or surgically with sectorial iridectomy. RGCs were retrogradely labeled 4 days prior to enucleation, and counted. Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), matrix-assisted laser desorption ionization mass spectrometry, Western blotting, and immunohistochemistry allowed the identification of IOP-dependent proteomic changes. Genomic changes were scrutinized using microarrays and qRT-PCR. The significant increase in IOP induced by episcleral vein cauterization that persisted until 8 weeks of follow-up in control animals (p<0.05) was effectively lowered by the eye drops (p<0.05). As anticipated, the number of RGCs decreased significantly following 8 weeks of elevated IOP (p<0.05), while treatment with combination compounds markedly improved RGC survival (p<0.05). 2D-PAGE and Western blot analyses revealed an IOP-dependent expression of crystallin cry-βb2. Microarray and qRT-PCR analyses verified the results at the mRNA level. IHC demonstrated that crystallins were expressed mainly in the ganglion cell layer. The data suggest that IOP and either topically applied antiglaucomatous drugs influence crystallin expression within the retina. Neuronal crystallins are thus suitable biomarkers for monitoring the progression of neuropathy and evaluating any neuroprotective effects.     

Comparison of the Effects of Dorzolamide/Timolol Fixed Combination versus Latanoprost on Intraocular Pressure and Ocular Perfusion Pressure in Patients with Normal-Tension Glaucoma: A Randomized,Crossover Clinical Trial

Backgroud

To assess the noninferiority of a dorzolamide-timolol fixed combination (DTFC) versus latanoprost in terms of intraocular pressure (IOP) and to compare blood pressure (BP), ocular perfusion pressure (OPP) and diastolic ocular perfusion pressure (DOPP) between the latanoprost and DTFC groups in patients with normal-tension glaucoma (NTG).

Methods

Prospective, interventional, randomized, single-blinded, crossover design study. Patients with newly diagnosed NTG that had not been treated with a glaucoma medication in the most recent 2 months were recruited. In total, 44 patients with NTG were randomly allocated to one of two groups. Patients in group A were treated with DTFC, lubricant, and latanoprost for 4 weeks each, whereas patients in group B were treated with latanoprost, lubricant, and DTFC for 4 weeks each. Patients were examined on day 1 (without medication), week 4 (under medication), week 8 (without medication), and week 12 (under medication). At weeks 4 and 12, diurnal IOP, systolic and diastolic BP, and OPP were measured at 8:00 AM, 10:00 AM, 12:00 PM, 4:00 PM, and 8:00 PM.

Results

Baseline demographic characteristics showed no difference in terms of age, sex, central corneal thickness, spherical equivalent, or stage of glaucoma between the groups. The between-group difference was -0.19 ± 0.18 mmHg (mean ± SE, upper bound of one-sided 95% CI, 0.12). Diurnal IOP showed no difference between the groups with an average IOP reduction of 13.1% using latanoprost and 12.3% using DTFC. Diurnal systolic and diastolic BP were lower in the DTFC group than the latanoprost group; however, the difference between the groups was not statistically significant. Diurnal OPP and DOPP also showed no statistically significant difference between the groups.

Conclusions

IOP lowering efficacy of DTFC was noninferior to that of latanoprost in newly diagnosed NTG patients. There was no difference in BP, OPP, or DOPP between the latanoprost and DTFC groups. This prospective, randomized, single-blinded, crossover study demonstrated the noninferiority of DTFC versus latanoprost in terms of IOP in patients with NTG.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01175902","term_id":"NCT01175902"}}NCT01175902     

Evaluation of the intraocular pressure-reducing effect of latanoprost as monotherapy in open-angle glaucoma

Objective of this study was to evaluate the intraocular pressure-reducing effect of latanoprost as monotherapy after replacing current dual therapy in glaucoma patients. The 6-months study comprised 189 patients with primary open angle glaucoma who were treated at least 6 months with two different kind of topical medications (beta-blockers, pilocarpine, dorzolamide and brimonidine). Due to local side effects, multiple dosing regime and inadequately controlled intraocular pressure (IOP), they where switched to latanoprost 0.005% monotherapy. After switched to latanoprost, mean (IOP) was measured at baseline, after 15 days, 2 and 6 months of treatment. After six-months 178 patients had completed the study. These analyses enrolled all patients (n = 189), thus, the Intention-To-Treat (ITT) results were shown instead of the results of the reduced population. IOP was clinically importantly reduced from baseline level. Five patients had uncontrolled IOP. The difference between IOP before (21.9 +/- 2.4) and after 15 days (17.4 +/- 1.7), 2 months (16.7 +/- 1.8) and 6 months (16.6 +/- 1.4) was statistically significant (p < 0.001). 90% patients has reached target IOP < or = 18 mm. A conjunctional hyperaemia in 18 (9%), stinging and itching in 7 (4%) patients was reported. Increased iris pigmentation was seen in 3 (2%) patients. The results of this study indicate that dual therapy in open-angle glaucoma can effectively be replaced by latanoprost monotherapy in many patients.     

超声乳化联合不同术式对青光眼合并白内障患者视力、血流动力学及生活质量的影响

目的:探讨超声乳化联合不同术式对青光眼合并白内障患者视力、血流动力学及生活质量的影响。方法:回顾性分析2015年1月～2019年8月期间我院收治的青光眼合并白内障患者56例(66眼)的临床资料,根据手术方式的不同分为A组(n=27,超声乳化联合小梁切除术)和B组(n=29,超声乳化联合房角分离手术),比较两组患者视力、眼压、血流动力学及生活质量情况,统计两组并发症发生情况。结果:两组术后1个月、术后3个月、术后6个月视功能指数量表(VF-14)评分呈升高趋势,且B组高于A组(P0.05)。两组患者术后1个月、3个月、6个月视力呈先升高后降低,且术后1个月、3个月、6个月均高于术前(P0.05),B组术后3个月、术后6个月视力均高于A组(P0.05);两组患者术后1个月～术后6个月眼压均呈不断下降趋势,且B组低于A组(P0.05)。两组术后6个月舒张末期流速(EDV)、收缩期峰值流速(PSV)均升高,且B组高于A组(P0.05);阻力指数(RI)均降低,且B组低于A组(P0.05)。两组并发症发生率比较差异无统计学意义(P0.05)。结论:与超声乳化联合小梁切除术相比,超声乳化联合房角分离手术治疗青光眼合并白内障患者,在改善患者视力、眼压、血流动力学及生活质量方面效果较佳,且不增加并发症发生率。     

In vivo and in vitro activation of alveolar macrophages by recombinant interferon-gamma

In vivo administration of recombinant interferon-gamma (rIFN-gamma) was previously shown to result in activation of the microbicidal activities of peritoneal macrophages (PM phi). Because macrophages at different anatomical sites vary in their functional capacities, we considered it of interest to determine whether administration of murine rIFN-gamma, either in vitro or in vivo, can enhance the microbicidal activity of resident alveolar macrophages (AM phi) and to compare the effects of rIFN-gamma on AM phi and PM phi. After incubation in vitro with rIFN-gamma, the antimicrobial activities of both murine AM phi and PM phi were enhanced, as assessed by their ability to inhibit replication of the intracellular parasite, Toxoplasma gondii. This effect was dose dependent for AM phi over a range of 0.1 to 1 U/ml and for PM phi over a range of 0.5 to 1000 U/ml. In this assay, the minimum dosage required for in vitro activation of AM phi was one-half that required for activation of PM phi, suggesting a greater sensitivity of AM phi to the in vitro activity of rIFN-gamma. Macrophages from both anatomical sites were also activated when rIFN-gamma was administered in vivo. This effect was dose dependent over a range of 10(3) to 10(5) U/mouse. Freshly harvested AM phi and PM phi from mice injected 24 hr earlier with 10(4) U rIFN-gamma by either the i.v. or i.p. routes markedly inhibited intracellular multiplication of Toxoplasma. In contrast, AM phi and PM phi from control mice permitted fourfold to ninefold increases in numbers of intracellular Toxoplasma. The anti-toxoplasma activity of AM phi and PM phi gradually diminished over a period of 3 days when assayed at successive 24 hr periods after a single i.v. injection of rIFN-gamma. At 3 days after injection, a substantial loss of anti-toxoplasma activity was observed with PM phi as compared with controls; residual anti-toxoplasma activity was still demonstrable in AM phi at 3 days. These results demonstrate that in vitro as well as in vivo treatment with rIFN-gamma confers on AM phi an enhanced antimicrobial activity. These findings provide a rationale for evaluating rIFN-gamma in the treatment of pulmonary infections, especially those due to opportunistic pathogens against which AM phi play a major role in host defense.     

小梁切除术中应用丝裂霉素C 对角膜内皮细胞的影响

目的:观察小梁切除术中应用丝裂霉素C(MMC)对角膜内皮细胞的影响。方法:收集2010年9月2011年5月在我院行小梁切除术的青光眼患者60例(78眼),随机分为术中应用丝裂霉素C的36例(46眼)患者为A组,术中不用丝裂霉素C的24例(32眼)为B组,分别观察术前、术后1个月和术后3个月两组眼压(IOP)、角膜内皮细胞的密度(CD)、平均细胞面积(AVG)及细胞面积变异系数(CV),分析其数量的改变及两组间的差异。结果:A组术前眼压为(35.4±13.7)mmHg,B组术前眼压为(32.5±13.5)mmHg差异无统计学意义(P>0.05),A组术后1个月及术后3个月眼压分别为(15.7±3.7)mmHg、(17.0±3.2)mmHg,均低于B组的(19.4±3.7)mmHg、(20.2±2.1)mmHg,差异有统计学意义(P<0.05)。A组术前、术后1个月及术后3个月角膜内皮细胞密度分别为(2475±484)个/mm2、(2199±373)个/mm2、(2164±332)个/mm2;平均细胞面积分别为(431.4±67.6)μm2、(480.6±66.8)μm2、(463.8±46.2)μm2;细胞面积变异系数分别为(31.1±7.4)%、(34.4±6.3)%、(31.2±7.5)%;术后1个月及术后3个月各参数与术前比较,差异均有统计学意义(P<0.05)。B组术前、术后1个月及术后3个月角膜内皮细胞密度分别为(2342±94)个/mm2、(2185±215)个/mm2、(2074±218)个/mm2;平均细胞面积分别为(453.9±94.8)μm2、(516.3±100.8)μm2、(499.81±106.4)μm2;细胞面积变异系数分别为(30.2±3.0)%、(32.7±2.9)%、(31.4±4.3)%;除术后3个月角膜内皮细胞与术前比较有意义(P<0.05)外,余参数术后1个月及术后3个月与术前比较差异均无统计学意义(P>0.05)。术后1个月A组的角膜内皮细胞丢失率为10.4%高于B组的6.1%,差异有统计学意义(P<0.05);术后3个月A组的角膜内皮细胞丢失率为11.1%高于B组的10.0%,差异无统计学意义(P>0.05)。结论:小梁切除术中用丝裂霉素C的降压效果比不用丝裂霉素C的效果好,但短期内前者角膜内皮细胞的丢失率高于后者。     

小梁切除术中应用丝裂霉素C对角膜内皮细胞的影响

目的：观察小梁切除术中应用丝裂霉素C（MMC）对角膜内皮细胞的影响。方法：收集2010年9月2011年5月在我院行小梁切除术的青光眼患者60例（78眼）,随机分为术中应用丝裂霉素c的36例（46眼）患者为A组,术中不用丝裂霉素c的24例（32眼）为B组。分别观察术前、术后1个月和术后3个月两组眼压（10P）、角膜内皮细胞的密度（co）、平均细胞面积（AVG）及细胞面积变异系数（cv）,分析其数量的改变及两组间的差异。结果：A组术前眼压为（35．4±13．7）mmHg,B组术前眼压为（32．5±13．5）mmHg差异无统计学意义（P〉0．05）,A组术后1个月及术后3个月眼压分别为（15．7±3．7）mmHg、（17．0±3．2）mmHg,均低于B组的（19．4±3．7）mmHg、（20．2±2．1）mmHg,差异有统计学意义（P〈0．05）。A组术前、术后1个月及术后3个月角膜内皮细胞密度分别为（2475±484）个／mm2、（2199±373）个／mm2、（2164±332）个／mm2;平均细胞面积分别为（431．4±67．6）μm2、（480．6±66．8）μm2、（463．8±46．2）μm2;细胞面积变异系数分别为（31．1±7．4）％、（34．4±6．3）％、（31．2±7．5）％;术后1个月及术后3个月各参数与术前比较,差异均有统计学意义（P〈0．05）。B组术前、术后1个月及术后3个月角膜内皮细胞密度分别为（2342±94）个／mm2、（2185＋215）个／mm2、（2074218）个／mm2;平均细胞面积分别为（453．9土94．8）μm2、（516.3±100．8）μm2、（499．81＋106．4）μm2;细胞面积变异系数分别为（30．2土3．0）％、（32．7±2．9）％、（31．4±4．3）％;除术后3个月角膜内皮细胞与术前比较有意义（P〈0．05）外,余参数术后1个月及术后3个月与术前比较差异均无统计学意义（P〉0．05）。术后1个月A组的角膜内皮细胞丢失率为10．4％高于B组的6．1％,差异有统计学意义（P〈0．05）;术后3个月A组的角膜内皮细胞丢失率为11．1％高于B组的10．0％,差异无统计学意义（P〉0．05）。结论：小梁切除术中用丝裂霉素C的降压效果比不用丝裂霉素C的效果好,但短期内前者角膜内皮细胞的丢失率高于后者。     

THE HAMSTER CLOCK PHASE-RESPONSE CURVE FROM SUMMERLIKE LIGHT:DARK CYCLES AND ITS ROLE IN DAILY AND SEASONAL TIMEKEEPING

We address the subject of entrainment of the hamster clock by the day:night cycle in summer when the sun sets after 6 PM and rises before 6 AM (nights<12 h). Summer day:night cycles were simulated by 6 light:dark (LD) cycles with D<12 h (summerlike, SLD) ranging from SLD 12.5h:11.5h (D, 6:15 PM–5:45 AM) to 18h:6h (D, 9 PM–3 AM). These are the near limiting SLDs for constant PM timing (entrainment) of behavioral estrus and wheel running in hamsters. The onset of estrus was observed every 4 d in the same hamsters as a phase marker of their 24h clock. On the day before an experimental estrus, preceded and followed by control onsets, a dark period was imposed to cover a putative 6 PM–6 AM light-sensitive period (LSP). This was scanned with a light pulse (and periodic 5sec bell alarms) lasting 5–240 min. Shifts in onset of estrus on the next day were plotted vs. the end of the light pulse for PM times (“dusk”) and its onset for AM times (“dawn”). The resulting phase shifts from the six SLDs were similar, permitting their combination into a single phase-response curve (PRC) of 1605 shifts. This SLD composite PRC rose at 10:15 PM, peaked at 2 AM (81min advanced shift), fell linearly to 5:55 AM, and then abruptly to normal at 6 AM (no shift). Peak shift was unaffected by light pulse duration or intensity, or hamster age. The SLD composite PRC lacked the 6 PM–9 PM curve of delayed shifts present in reported PRCs from LD 12h:12h and DD. However, a two-pulse experiment showed that all light from 6 PM to L-off was needed to block (balance) the advancing action of a 5min morning light pulse, thereby maintaining entrainment. A working hypothesis to explain daily entrainment and seasonal fertility in the golden hamster is illustrated. A nomenclature for labeling the phases of the hamster clock (circadian time) is proposed.