The effect of latanoprost on ocular blood flow

Purpose To investigate the effect of latanoprost on ocular hemodynamics in healthy subjects. Methods In a randomized, double-masked, placebo-controlled crossover study, 12 healthy subjects received either placebo or latanoprost for 4 weeks in one randomly chosen eye. Following a 4-week washout period, each patient received the opposite treatment. Blood pressure, heart rate, logMar visual acuity, contrast sensitivity, iris photography, intraocular pressure (IOP), Heidelberg retinal flowmetry, and color Doppler imaging measurements were taken at baseline and post-treatment. Heidelberg retinal flowmetry images were analyzed using the pixel-by-pixel analysis. Color Doppler imaging measurements included peak systolic velocity and end diastolic velocities (cm/s), and the calculated resistance index. Pre- and post-treatment values were compared by Wilcoxon signed rank tests (P < 0.05 was considered to be statistically significant). Results There were no significant changes in heart rate, blood pressure, contrast sensitivity, or visual acuity with either treatment. Latanoprost demonstrated a significant reduction in both IOP (P = 0.005) and retinal blood flow at the 10th (P = 0.009) and 25th (P = 0.009) percentiles of Heidelberg retinal flowmetry measurements in the superior temporal region. Latanoprost, however, did not reduce blood flow in the inferior temporal region and did not significantly elevate the percentage of zero-flow pixels of the temporal peripapillary area. Conclusion Latanoprost has mostly neutral effects on ocular circulation. These findings must be investigated in glaucoma patients who may respond differently than healthy subjects due to faulty vascular autoregulation.     

HPLC测定拉坦前列素滴眼液复杂系统中的有关物质及含量

目的 建立HPLC测定拉坦前列素滴眼液复杂系统中的有关物质及含量的方法。方法 采用糖涂敷型手性色谱柱（4.6 mm×250 mm,5 μm）,有关物质测定以0.005 mol·L^-1磷酸二氢钠溶液（用磷酸调节pH值至2.7）-乙腈（56：44）为流动相,含量测定以0.005 mol·L^-1磷酸二氢钠溶液（用磷酸调节pH值至2.7）-乙腈（54：46）为流动相,检测波长为200 nm,流速为0.5 ml·min^-1。结果 有关物质测定中2个已知杂质与主峰之间的分离度良好,线性关系良好,5,6-反式-拉坦前列素和15S-拉坦前列素的平均回收率分别为101.5%和99.5%,拉坦前列素、5,6-反式拉坦前列素和15S-拉坦前列素的定量限（S/N≈10）分别为0.12,0.13和0.12 μg·mL^-1;含量测定线性关系良好,重复性RSD=0.90%,拉坦前列素平均回收率为98.8%。结论 建立的方法准确可靠,可用于拉坦前列素滴眼液的质量控制。     

拉坦前列素滴眼液与其复合剂的降眼压作用的比较

目的：评价0.005%拉坦前列素滴眼液＋0.5%噻吗洛尔滴眼液治疗原发性开角形青光眼患者的替代降眼压作用及其安全性。方法应用0.005%拉坦前列素滴眼液单一治疗的原发性开角型青光眼患者31例,给予0.005%拉坦前列素滴眼液＋0.5%噻吗洛尔滴眼液替代治疗。每晚点药1次,每次1滴。将连续点药后4、8、12周的眼压与基线眼压进行比较研究,同时观察血压、心率等全身及局部不良反应。结果0.005%拉坦前列素滴眼液＋0.5%噻吗洛尔滴眼液可以更有效降低眼压。连续点药4、8、12周后,与基线相比,眼压分别额外下降（2.2±1.1）mmHg、（2.0±0.9）mmHg、（2.2±1.0）mmHg,差异均具有统计学意义（P〈0.05）。连续点药4、8、12周后,获得至少2mmHg眼压下降值的患者百分率分别为64.5%、61.3%、64.5%。心动过缓（3.2%）是最严重的不良反应。结论0.005%拉坦前列素＋0.5%噻吗洛尔复方滴眼液能够更加有效的降低目标眼压,可以作为0.005%拉坦前列素滴眼液的替代治疗手段。     

Der Einfluss von Latanoprost 0,005% auf die Pupillenreaktion des menschlichen Auges

PURPOSE: Infrared pupillography was performed to investigate the effect of one week topical treatment with the prostaglandin analogue Latanoprost 0.005% on pupillary reflex to light stimuli in glaucomatous human eyes. METHODS: Infrared pupillography using the compact integrated pupillograph was performed in 20 glaucomatous eyes of 11 patients. After 10 minutes dark adaptation one pupil was stimulated with a blue, yellow and white diode light of 100 ms duration. Measurements of pupil diameter, constriction latency, constriction amplitude and relative constriction amplitude were taken twice for each light source in a time interval of 15 seconds. After a 2 week wash-out period the measurements were performed from 8:00 to 10:00 a.m. before and one week after topical treatment with Latanoprost 0.005% applied as single dose once in the evening. RESULTS: The measurements after 1 week treatment with Latanoprost showed a significantly smaller pupil diameter for blue (p = 0.044) and white stimulus (p = 0.039) and the latency was significantly reduced (p = 0.029) as well. CONCLUSIONS: Although the statistical analysis shows some small significant differences in pupil diameter and constriction latency there were no clinical signs of changes in pupillary response due to Latanoprost. The system turned out as easy to use and showed reliable measurements during the study. How far latanoprost may lead to miosis and a decrease of constriction latency has to be investigated in further studies with larger study populations. Other topics concerning drug influence, diurnal rhythm and glaucomatous damage in pupillary light reaction will be investigated in the near future.     

拉坦前列素隔日给药对青光眼患者眼压的影响

目的:探讨隔日应用0.005%拉坦前列素对青光眼患者眼压(intraocular pressure,IOP)的效果。方法:该研究中的开角型青光眼患者控制较好,在研究的第一阶段睡前给予拉坦前列素,每日一次,至少2mo。3次连续IOP正常后,改为隔日一次睡前用药,并且在研究第二阶段的1,2,4,6,8和12wk密切监测患者,进行IOP测量。遇到一次IOP异常升高,则患者被排除研究并且前期方案将重建。结果:这项研究包括53例53眼开角型青光眼(男29例,女24例,年龄52～82岁)。27例患有原发性开角型青光眼,26例患有假性剥脱性青光眼。研究的第二阶段开始后,IOP有温和增长趋势,并分别在女性和男性患者中检测到。第1,2,4,6,8和12wk的P值分别为0.003,0.001,0.000,0.000,0.000和0.000。在第二阶段开始后的前2wk,66%的病例没有IOP改变,但此后,69.8%患者眼压增加。结论:该研究显示常规用量0.005%拉坦前列素与隔日一次剂量相比,具有优越性,但至少在最初的几个星期,IOPs比较接近对方。进一步的多患者研究将扩大目前的研究结果。     

The impact of intraocular pressure reduction on retinal ganglion cell function measured using pattern electroretinogram in eyes receiving latanoprost 0.005% versus placebo

Purpose

To evaluate the impact of intraocular (IOP) reduction on retinal ganglion cell (RGC) function measured using pattern electroretinogram optimized for glaucoma (PERGLA) in glaucoma suspect and glaucomatous eyes receiving latanoprost 0.005% versus placebo.

Methods

This was a prospective, placebo-controlled, double masked, cross-over clinical trial. One randomly selected eye of each subject meeting eligibility criteria was enrolled. At each visit, subjects underwent five diurnal measurements between 8:00 am and 4:00 pm consisting of Goldmann IOP, and PERGLA measurements. A baseline examination was performed following a 4-week washout period, and repeat examination after randomly receiving latanoprost or placebo for 4-weeks. Subjects were then crossed over to receive the alternative therapy for 4 weeks following a second washout period, and underwent repeat examination. Linear mixed-effect models were used for the analysis.

Results

Sixty-eight eyes (35 glaucoma, 33 glaucoma suspect) of 68 patients (mean age 67.4 ± 10.6 years) were enrolled. The mean IOP (mm Hg) after latanoprost 0.005% therapy (14.9 ± 3.8) was significantly lower than baseline (18.8 ± 4.7, p < 0.001) or placebo (18.0 ± 4.3), with a mean reduction of −20 ± 13%. Mean PERGLA amplitude (μV) and phase (π-radian) using latanoprost (0.49 ± 0.22 and 1.71 ± 0.22, respectively) were similar (p > 0.05) to baseline (0.49 ± 0.24 and 1.69 ± 0.19) and placebo (0.50 ± 0.24 and 1.72 ± 0.23). No significant (p > 0.05) diurnal variation in PERGLA amplitude was observed at baseline, or using latanoprost or placebo. Treatment with latanoprost, time of day, and IOP were not significantly (p > 0.05) associated with PERGLA amplitude or phase.

Conclusion

Twenty percent IOP reduction using latanoprost monotherapy is not associated with improvement in RGC function measured with PERGLA.     

Einfluss von Latanoprost auf okuläre Hämodynamik und Kontrastsensitivität

BACKGROUND: Latanoprost effectively lowers intraocular pressure. Because ischemia has gained increasing importance in the pathogenesis of glaucoma, an antiglaucomatous drug should also be investigated with regard to the influence on ocular hemodynamics. METHODS: In a double masked, randomized, clinical trial, Latanoprost eye drops were administered to 15 volunteers once daily for 8 days and 15 further volunteers received placebo eye drops according to the same protocol. IOP, blood pressure, heart rate, ocular pulse amplitudes, pulse volume, pulsatile ocular blood flow and contrast sensitivity were measured before (1T0), 120 min after drop administration (1T120), after 7 days of therapy (8T0) and again 120 min after an acute administration (8T120). For statistical analysis a two-way variance-analysis and the t-test for paired samples were used. RESULTS: IOP was found to be statistically significantly different comparing both groups over the test period (p = 0.036). In Latanoprost-treated subjects the t-test revealed a significant drop in IOP between 1T0 and 8T0 (p = 0.009) and between 1T0 and 8T120 (p < 0.0001). All other above mentioned parameters remained constant. CONCLUSION: In Latanoprost-treated subjects, a significant drop in intraocular pressure was observed after 1 week. However, ocular perfusion and contrast sensitivity did not change during therapy. This might be due to an effective autoregulation in healthy volunteers.     

Cystoid macular oedema within 24 h after a single application of latanoprost

Purpose: To describe a patient who developed cystoid macular oedema (CMO) within 24 h after a single application of Latanoprost. Methods: Observational case report. Results: A 77-year-old man who had a previous cataract operation with vitreous loss in his left eye developed CMO 8 h after instillation of one drop of latanoprost. Five days after discontinuation of latanoprost the CMO resolved almost completely. Both the CMO and its resolution were documented with fluorescein angiography (FA) and optical coherence tomography (OCT). Conclusions: Latanoprost can lead to CMO even after a single application, as demonstrated in our case by FA and, in particular, by OCT. Caution is advised when administering the drug in high–risk eyes.     

Pneumatic trabeculoplasty vs latanoprost as adjunctive therapy to timolol in primary open-angle glaucoma or ocular hypertension

Purpose  To evaluate the efficacy and safety of pneumatic trabeculoplasty (PNT) compared with latanoprost 0.005%, in primary open-angle glaucoma (POAG) and ocular hypertension (OH) not controlled by timolol 0.5%. Procedures  In a randomized clinical study, 18 patients affected with primary open-angle glaucoma (POAG) or ocular hypertension (OH) with intraocular pressure (IOP) >20 mmHg after timolol 0.5% in one eye were treated with PNT; 18 control eyes received adjunctive therapy with latanoprost 0.005%. Visual acuity, IOP, visual field, biomicroscopy findings and fundus appearance were evaluated at each month. Patients with IOP >20 mmHg were excluded from the study. The study was continued until in one group no patients were left. Results  At 1 month, IOP had decreased significantly in both groups. In PNT-treated eyes the mean IOP decrease was 4.5 ± 1.8 mmHg (19.1 ± 7.8%) and in latanoprost-treated eyes was 6.6 ± 1.3 mmHg (28.2 ± 5.7%) (between two groups, P < 0.001). Eleven PNT-treated eyes (61%) and 17 latanoprost-treated eyes (94%) had an IOP reduction of more than 20% of baseline value (P = 0.049); two PNT-treated patients received additional therapy. At the following months, in the latanoprost group, IOP was stable: an IOP reduction of 20% or more was seen in 89% of the eyes. In some PNT-treated eyes IOP increased: at 2 months, an IOP reduction≥20% was seen in 50%, at 3 months in 33%, and at 4 months in 17% of the eyes. (between the two groups, respectively, P = 0.03, P = 0.002, P < 0.001). The number of eyes that required therapy increased progressively in the PNT group, and at 8 months all eyes had required therapy, whereas one latanoprost-treated eye had had additional therapy. After PNT, no patients had visual acuity reduction or intraocular inflammation; three eyes had subconjunctival hemorrhage and five eyes a hyperemia that regressed within 1 week. No posterior segment changes or visual field progression were detected in either groups. Conclusions  In eyes with glaucomatous damage that is not advanced, PNT can reduce the IOP in 60% of the eyes at 1 month, and in 33% of the eyes at 3 months, without significant side-effects. The indications, efficacy and safety of PNT retreatments remain to be investigated. IOP reduction is less and of shorter duration than that obtained by latanoprost adjunctive therapy. No financial relationship