Discipline of Optometry, Faculty of Health, University of Canberra, Canberra, Australia.
John Curtin School of Medical Research (JCSMR), The Australian National University, Canberra, Australia.
Transl Vis Sci Technol. 2024 Oct 1;13(10):12. doi: 10.1167/tvst.13.10.12.
Levodopa has been investigated as a therapeutic solution for ocular disorders involving dysregulation of the dopaminergic system, especially in the context of myopia. However, given the critical role dopamine plays in normal vision, this phase I trial examined whether levodopa/carbidopa eye drops induce any regional changes in retinal structure and function.
Twenty-nine healthy male subjects 18 to 30 years of age were randomly assigned to receive either a low (1.4/0.34 µmoles/day, n = 14) or high (2.7/0.68 µmoles/day, n = 15) dose of levodopa/carbidopa eye drops in 1 eye for 28 consecutive days. A placebo solution was applied to all fellow eyes. Measures included visual acuity, regional frequency doubling perimetry, regional multifocal electroretinogram (mfERG) and optical coherence tomography (retinal thickness). Outcome measures were undertaken at baseline, end-of-treatment (4 weeks), and at a follow-up (4 months post-treatment).
For low dose treated eyes, regional analysis showed a small, statistically significant change in mfERG recordings (increase in ring 5 amplitude in low dose treated eyes, P < 0.05) and the retinal thickness map (localized retinal thinning in low dose treated eyes, P < 0.05). These changes were not clinically significant. No significant changes were observed in high dose treated eyes. Pharmacokinetic analysis (rabbits) demonstrated that levodopa was not detectable within blood and peaked within the eye at 15 to 30 minutes (and eliminated within 4 hours).
No clinically significant effects of levodopa/carbidopa eye drops were found with regard to normal retinal structure and function following short-term use.
This study further demonstrates the safety of topical levodopa, which may support its use in the treatment of ocular disorders in which the dopamine system is dysregulated.
左旋多巴已被研究作为一种治疗涉及多巴胺能系统失调的眼部疾病的方法，特别是在近视的情况下。然而，鉴于多巴胺在正常视力中发挥的关键作用，这项 I 期试验研究了左旋多巴/卡比多巴滴眼剂是否会引起视网膜结构和功能的任何区域性变化。
29 名年龄在 18 至 30 岁的健康男性受试者被随机分配到接受低剂量（1.4/0.34 µmoles/天，n = 14）或高剂量（2.7/0.68 µmoles/天，n = 15）的左旋多巴/卡比多巴滴眼剂，连续 28 天应用于 1 只眼。所有对侧眼均应用安慰剂溶液。测量包括视力、区域性双倍频域视觉诱发电位、区域性多焦视网膜电图（mfERG）和光学相干断层扫描（视网膜厚度）。在基线、治疗结束时（4 周）和治疗后 4 个月（随访）时进行了测量。
对于低剂量治疗的眼睛，区域分析显示 mfERG 记录有微小的、统计学上显著的变化（低剂量治疗眼的环 5 振幅增加，P < 0.05）和视网膜厚度图（低剂量治疗眼局部视网膜变薄，P < 0.05）。这些变化没有临床意义。高剂量治疗的眼睛没有观察到明显的变化。药代动力学分析（兔子）表明，在血液中无法检测到左旋多巴，在眼内 15 至 30 分钟内达到峰值（并在 4 小时内消除）。
在短期使用后，左旋多巴/卡比多巴滴眼剂对正常视网膜结构和功能没有发现明显的影响。
本研究进一步证明了局部使用左旋多巴的安全性，这可能支持其在治疗多巴胺系统失调的眼部疾病中的应用。
