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 NCT01175902

【背景】本研究旨在评估多佐胺-噻吗洛尔固定复方制剂（dorzolamide-timolol fixed combination, DTFC）相较于拉坦前列素（latanoprost）的降眼压非劣效性，并比较正常眼压性青光眼（normal-tension glaucoma, NTG）患者中，拉坦前列素组与DTFC组的血压（blood pressure, BP）、眼灌注压（ocular perfusion pressure, OPP）及舒张期眼灌注压（diastolic ocular perfusion pressure, DOPP）水平。
【方法】本研究为前瞻性、干预性、随机单盲交叉设计研究。纳入近2个月未接受青光眼药物治疗的新确诊正常眼压性青光眼患者，共计44例，按随机原则分为两组。A组患者依次接受DTFC、润滑剂及拉坦前列素治疗，每种治疗方案持续4周；B组患者则依次接受拉坦前列素、润滑剂及DTFC治疗，每种方案同样持续4周。所有患者分别于给药前第1天、给药第4周（用药状态下）、第8周（停药状态下）及第12周（用药状态下）接受检查。在第4周和第12周时，于每日8:00、10:00、12:00、16:00及20:00检测日间眼压、收缩压与舒张压及眼灌注压。
【结果】两组患者的基线人口学特征，包括年龄、性别、中央角膜厚度、等效球镜度及青光眼分期，均无统计学差异。组间眼压差值为-0.19±0.18mmHg（均值±标准误，单侧95%置信区间上限为0.12）。两组日间眼压无显著差异，拉坦前列素组平均眼压降幅为13.1%，DTFC组为12.3%。DTFC组的日间收缩压与舒张压均低于拉坦前列素组，但组间差异无统计学意义。两组日间眼灌注压与舒张期眼灌注压亦无统计学差异。
【结论】在新确诊的正常眼压性青光眼患者中，DTFC的降眼压疗效非劣于拉坦前列素。拉坦前列素组与DTFC组的血压、眼灌注压及舒张期眼灌注压均无显著差异。本项前瞻性随机单盲交叉研究证实，在正常眼压性青光眼患者中，DTFC在眼压控制方面非劣于拉坦前列素。
【试验注册】ClinicalTrials.gov NCT01175902