Abstract：
OBJECTIVE: Dim light vision disturbances (DLD) comprise a wide range of symptoms affecting the quality of vision at low illumination including glare, halos, and starbursts. This exploratory study investigated 1.0% phentolamine mesylate ophthalmic solution (PMOS) as a treatment to improve vision and image quality for patients with DLD.
METHODS: In this placebo-controlled, randomized, double-masked clinical trial, 24 adult patients with severe DLD were randomized in a 2:1 ratio to receive either one dose of PMOS or placebo. Subjects were eligible if they reported experiencing severe night vision difficulty that was not eliminated by distance spectacle correction and scored ≥0.3 log units below the normal range of contrast sensitivity assessed under mesopic conditions with glare at ≥2 spatial frequencies. Key efficacy outcomes were change from baseline in pupil diameter, contrast sensitivity, and visual acuity. Safety measures including intraocular pressure, conjunctival hyperemia, and systemic effects were also assessed.
RESULTS: Eight subjects were randomized to placebo (63% female; mean age 47 years) and 16 were randomized to PMOS (75% female; mean age 42 years). Mean (SD) pupil diameter of PMOS-treated subjects decreased significantly - 1.3 mm (0 to - 2.8 mm) with p < 0.0001. Mean contrast sensitivity with glare in PMOS-treated subjects improved significantly post-treatment at spatial frequencies 3, 6, 12, and 18 cycles per degree (p ≤ 0.03). PMOS also demonstrated improvements in the numbers of letters read for mesopic and photopic, high- and low-contrast visual acuity (LCVA). Importantly, a statistically greater proportion of PMOS-treated eyes registered mesopic LCVA 5 letter (69% vs. 31%, p = 0.029) and 10 letter (34% vs. 6%, p = 0.04) improvement, with a trend at 15 letters (19% vs. 0%, p = 0.16). PMOS was well tolerated with the only reported side effect being a mild increase in conjunctival hyperemia.
CONCLUSIONS: PMOS was well tolerated and effectively reduced pupil size with improvements in contrast sensitivity and visual acuity in adults with severe DLD. Future Phase 3 studies should be conducted to further evaluate its potential to treat DLD.
BACKGROUND: The trial registration number is NCT04004507 (02/07/2019). Retrospectively registered.
METHODS: In this placebo-controlled, randomized, double-masked clinical trial, 24 adult patients with severe DLD were randomized in a 2:1 ratio to receive either one dose of PMOS or placebo. Subjects were eligible if they reported experiencing severe night vision difficulty that was not eliminated by distance spectacle correction and scored ≥0.3 log units below the normal range of contrast sensitivity assessed under mesopic conditions with glare at ≥2 spatial frequencies. Key efficacy outcomes were change from baseline in pupil diameter, contrast sensitivity, and visual acuity. Safety measures including intraocular pressure, conjunctival hyperemia, and systemic effects were also assessed.
RESULTS: Eight subjects were randomized to placebo (63% female; mean age 47 years) and 16 were randomized to PMOS (75% female; mean age 42 years). Mean (SD) pupil diameter of PMOS-treated subjects decreased significantly - 1.3 mm (0 to - 2.8 mm) with p < 0.0001. Mean contrast sensitivity with glare in PMOS-treated subjects improved significantly post-treatment at spatial frequencies 3, 6, 12, and 18 cycles per degree (p ≤ 0.03). PMOS also demonstrated improvements in the numbers of letters read for mesopic and photopic, high- and low-contrast visual acuity (LCVA). Importantly, a statistically greater proportion of PMOS-treated eyes registered mesopic LCVA 5 letter (69% vs. 31%, p = 0.029) and 10 letter (34% vs. 6%, p = 0.04) improvement, with a trend at 15 letters (19% vs. 0%, p = 0.16). PMOS was well tolerated with the only reported side effect being a mild increase in conjunctival hyperemia.
CONCLUSIONS: PMOS was well tolerated and effectively reduced pupil size with improvements in contrast sensitivity and visual acuity in adults with severe DLD. Future Phase 3 studies should be conducted to further evaluate its potential to treat DLD.
BACKGROUND: The trial registration number is NCT04004507 (02/07/2019). Retrospectively registered.
摘要：
目的：弱光视力障碍（DLD）包括影响低照度视力质量的多种症状，包括眩光，光环,和星爆。这项探索性研究调查了1.0％甲磺酸酚妥拉明眼用溶液（PMOS）作为改善DLD患者视力和图像质量的治疗方法。
方法：在这种安慰剂对照中，随机化，双盲临床试验,24名患有严重DLD的成年患者以2：1的比例随机接受一剂PMOS或安慰剂。如果受试者报告经历了严重的夜视困难，但未通过远距离眼镜矫正消除，并且得分≥0.3log单位，低于在≥2个空间频率的眩光条件下评估的对比敏感度正常范围。主要疗效结果是瞳孔直径从基线的变化，对比敏感度,和视力。包括眼压在内的安全措施，结膜充血，并对全身效应进行了评估.
结果：8名受试者被随机分配至安慰剂组（63%为女性；平均年龄47岁），16名受试者被随机分配至PMOS组（75%为女性；平均年龄42岁）。PMOS处理的受试者的平均(SD)瞳孔直径显著降低-1.3mm(0至-2.8mm),其中p<0.0001。在空间频率为每度3、6、12和18个周期（p≤0.03）的情况下，经过PMOS处理的受试者中眩光的平均对比敏感度显着提高。PMOS还显示了用于中视和明视的字母数的改进，高和低对比度视力（LCVA）。重要的是,统计学上较大比例的PMOS治疗的眼睛登记的介视LCVA5字母(69%vs.31%,p=0.029)和10个字母(34%与6%,p=0.04)改进，趋势为15个字母(19%与0%,p=0.16）。PMOS耐受性良好，唯一报道的副作用是结膜充血轻度增加。
结论：在患有严重DLD的成人中，PMOS具有良好的耐受性，并且有效地减小了瞳孔大小，并改善了对比敏感度和视敏度。应进行未来的3期研究，以进一步评估其治疗DLD的潜力。
背景：试用注册号为NCT04004507（02/07/2019）。追溯登记。
方法：在这种安慰剂对照中，随机化，双盲临床试验,24名患有严重DLD的成年患者以2：1的比例随机接受一剂PMOS或安慰剂。如果受试者报告经历了严重的夜视困难，但未通过远距离眼镜矫正消除，并且得分≥0.3log单位，低于在≥2个空间频率的眩光条件下评估的对比敏感度正常范围。主要疗效结果是瞳孔直径从基线的变化，对比敏感度,和视力。包括眼压在内的安全措施，结膜充血，并对全身效应进行了评估.
结果：8名受试者被随机分配至安慰剂组（63%为女性；平均年龄47岁），16名受试者被随机分配至PMOS组（75%为女性；平均年龄42岁）。PMOS处理的受试者的平均(SD)瞳孔直径显著降低-1.3mm(0至-2.8mm),其中p<0.0001。在空间频率为每度3、6、12和18个周期（p≤0.03）的情况下，经过PMOS处理的受试者中眩光的平均对比敏感度显着提高。PMOS还显示了用于中视和明视的字母数的改进，高和低对比度视力（LCVA）。重要的是,统计学上较大比例的PMOS治疗的眼睛登记的介视LCVA5字母(69%vs.31%,p=0.029)和10个字母(34%与6%,p=0.04)改进，趋势为15个字母(19%与0%,p=0.16）。PMOS耐受性良好，唯一报道的副作用是结膜充血轻度增加。
结论：在患有严重DLD的成人中，PMOS具有良好的耐受性，并且有效地减小了瞳孔大小，并改善了对比敏感度和视敏度。应进行未来的3期研究，以进一步评估其治疗DLD的潜力。
背景：试用注册号为NCT04004507（02/07/2019）。追溯登记。
