Arch Ophthalmol. 1998 Jul;116(7):874-86. doi: 10.1001/archopht.116.7.874.
To document the frequency, importance of, and risk factors for "early worsening" of diabetic retinopathy in the Diabetes Control and Complications Trial (DCCT).
The DCCT was a multicenter, randomized clinical trial comparing intensive vs conventional treatment in insulin-dependent diabetic patients who had no to moderate nonproliferative retinopathy. Retinopathy severity was assessed in 7-field stereoscopic fundus photographs taken at baseline and every 6 months. For this study, worsening was defined as progression of 3 steps or more on the Early Treatment Diabetic Retinopathy Study final scale, as the development of soft exudates and/or intraretinal microvascular abnormalities, as the development of clinically important retinopathy, or as any of the above, and was considered "early" if it occurred between baseline and 12-month follow-up visits.
Early worsening was observed at the 6- and/or 12-month visit in 13.1% of 711 patients assigned to intensive treatment and in 7.6% of 728 patients assigned to conventional treatment (odds ratio, 2.06; P < .001); recovery had occurred at the 18-month visit in 51% and 55% of these groups, respectively (P = .39). The risk of 3-step or greater progression from the retinopathy level present 18 months after entry into the trial was greater in patients who previously had had early worsening than in those who had not. However, the large long-term risk reduction with intensive treatment was such that outcomes in intensively treated patients who had early worsening were similar to or more favorable than outcomes in conventionally treated patients who had not. The most important risk factors for early worsening were higher hemoglobin A1c level at screening and reduction of this level during the first 6 months after randomization. We found no evidence to suggest that more gradual reduction of glycemia might be associated with less risk of early worsening. Early worsening led to high-risk proliferative retinopathy in 2 patients and to clinically significant macular edema in 3; all responded well to treatment.
In the DCCT, the long-term benefits of intensive insulin treatment greatly outweighed the risks of early worsening. Although no case of early worsening was associated with serious visual loss, our results are consistent with previous reports of sight-threatening worsening when intensive treatment is initiated in patients with long-standing poor glycemic control, particularly if retinopathy is at or past the moderate nonproliferative stage. Ophthalmologic monitoring before initiation of intensive treatment and at 3-month intervals for 6 to 12 months thereafter seems appropriate for such patients. In patients whose retinopathy is already approaching the high-risk stage, it may be prudent to delay the initiation of intensive treatment until photocoagulation can be completed, particularly if hemoglobin A1c is high.
记录糖尿病控制与并发症试验（DCCT）中糖尿病视网膜病变“早期恶化”的发生率、重要性及危险因素。
DCCT是一项多中心随机临床试验，比较胰岛素依赖型糖尿病且无至中度非增殖性视网膜病变患者的强化治疗与常规治疗。在基线及每6个月时拍摄7视野立体眼底照片评估视网膜病变严重程度。本研究中，恶化定义为在糖尿病视网膜病变早期治疗研究最终量表上进展3步或更多，出现软性渗出和/或视网膜内微血管异常，出现具有临床意义的视网膜病变，或上述任何一种情况，若发生在基线与12个月随访之间则被视为“早期”恶化。
在711例接受强化治疗的患者中，13.1%在6个月和/或12个月随访时出现早期恶化；在728例接受常规治疗的患者中，7.6%出现早期恶化（优势比为2.06；P < 0.001）；在18个月随访时，这些组中分别有51%和55%的患者病情恢复（P = 0.39）。与未出现早期恶化的患者相比，入组试验18个月后视网膜病变水平进展3步或更多的风险在先前出现早期恶化的患者中更高。然而，强化治疗带来的长期风险大幅降低，使得出现早期恶化的强化治疗患者的结局与未出现早期恶化的常规治疗患者相似或更优。早期恶化最重要的危险因素是筛查时较高的糖化血红蛋白水平以及随机分组后前6个月该水平的降低。我们没有发现证据表明血糖更缓慢降低可能与早期恶化风险更低相关。早期恶化导致2例患者出现高危增殖性视网膜病变，3例患者出现具有临床意义的黄斑水肿；所有患者对治疗反应良好。
在DCCT中，强化胰岛素治疗的长期益处远大于早期恶化的风险。虽然没有早期恶化病例导致严重视力丧失，但我们的结果与先前报道一致，即在长期血糖控制不佳的患者中开始强化治疗时会出现威胁视力的恶化，特别是如果视网膜病变处于或超过中度非增殖性阶段。对于此类患者，在开始强化治疗前及之后6至12个月每3个月进行一次眼科监测似乎是合适的。对于视网膜病变已接近高危阶段的患者，谨慎做法可能是延迟强化治疗的启动，直到完成光凝治疗，特别是如果糖化血红蛋白水平较高。
