Singapore Eye Research Institute, National University of Singapore, Singapore.
Am J Ophthalmol. 2012 Jul;154(1):6-12. doi: 10.1016/j.ajo.2012.03.013.
To review clinical and experimental data for fenofibrate as a possible systemic treatment for diabetic retinopathy.
Perspective.
Review of clinical studies focused on 2 major randomized controlled trials: the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) and ACCORD (Action to Control Cardiovascular Risk in Diabetes)-Eye studies. Progression was defined in FIELD as laser treatment for proliferative retinopathy or macular edema or increase by ≥ 2 steps on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, and in ACCORD-Eye as ≥ 3 steps (ETDRS scale) or proliferative disease requiring laser or vitrectomy treatment. Experimental studies investigating the mode of action of fenofibrate were reviewed.
The 2 trials included 11 388 patients with type 2 diabetes mellitus, of whom 5701 were treated with fenofibrate (± statin) for up to 5 years. Fenofibrate reduced first laser treatment by 31% (P = .0002), and progression of diabetic retinopathy with absolute reductions of 5.0% over 5 years (P = .022, FIELD) and 3.7% over 4 years (P = .006, ACCORD-Eye). There was greater benefit in patients with than without preexisting retinopathy. The putative mechanisms implicated in the mode of action of fenofibrate involve lipid and nonlipid pathways, including beneficial effects on apoptosis, oxidative stress, inflammation, blood-retinal barrier breakdown, and neuroprotection.
There are now robust and consistent clinical data to recommend fenofibrate as an adjunctive treatment for early diabetic retinopathy in patients with type 2 diabetes mellitus, taking into account the risks vs benefits of therapy. Further elucidating its mode of action will help to refine how best to use fenofibrate in the management of diabetic retinopathy.
综述非诺贝特作为一种可能的糖尿病性视网膜病变全身治疗药物的临床和实验数据。
观点。
对重点关注 2 项主要随机对照试验（FIELD [非诺贝特干预和糖尿病事件降低]和 ACCORD- Eye [控制心血管风险的行动在糖尿病]-眼研究）的临床研究进行综述。FIELD 中进展定义为增生性视网膜病变或黄斑水肿患者行激光治疗，或早期糖尿病视网膜病变研究（ETDRS）量表上增加≥2 级，ACCORD-Eye 中定义为≥3 级（ETDRS 量表）或增殖性疾病需要激光或玻璃体切割治疗。对非诺贝特作用机制的实验研究进行了综述。
这 2 项试验共纳入 11388 例 2 型糖尿病患者，其中 5701 例患者接受非诺贝特（±他汀类药物）治疗长达 5 年。非诺贝特使首次激光治疗减少了 31%（P =.0002），5 年内糖尿病视网膜病变进展的绝对减少率为 5.0%（P =.022，FIELD）和 4 年内减少 3.7%（P =.006，ACCORD-Eye）。在有或无既往视网膜病变的患者中均有更大获益。非诺贝特作用机制涉及脂质和非脂质途径，包括对细胞凋亡、氧化应激、炎症、血视网膜屏障破坏和神经保护的有益作用。
目前有强有力且一致的临床数据推荐非诺贝特作为 2 型糖尿病患者早期糖尿病性视网膜病变的辅助治疗药物，同时考虑治疗的风险与获益。进一步阐明其作用机制将有助于更好地确定如何在糖尿病性视网膜病变的管理中使用非诺贝特。
