A Pilot Study of Peribulbar Triamcinolone Acetonide for Diabetic Macular Edema
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 113
- 主要终点
- Mean Visual Acuity Letter Score at Each Follow-up Visit
研究概览
简要总结
The study involves the enrollment of patients over 18 years of age with diabetic macular edema involving the center of the macula who have not already been given maximal laser treatment.
Patients with one study eye will be randomly assigned (stratified by prior laser) with equal probability to one of five treatment groups:
- Focal laser photocoagulation (modified ETDRS technique)
- Posterior peribulbar injection of 40 mg triamcinolone (Kenalog)
- Anterior peribulbar injection of 20 mg triamcinolone
- Posterior peribulbar injection of 40 mg triamcinolone followed after one month by laser
- Anterior peribulbar injection of 20 mg triamcinolone followed after one month by laser
For patients with two study eyes (both eyes eligible at the time of randomization), the right eye (stratified by prior laser) will be randomly assigned with equal probabilities to one of the five treatment groups listed above. If the right eye was assigned to laser only, then the left eye will be assigned to one of the four triamcinolone groups above with equal probability (stratified by prior laser). If the right eye was assigned to receive triamcinolone, then the left eye will receive laser only.
Triamcinolone acetonide will be the corticosteroid utilized in this study. The triamcinolone acetonide preparation to be used is Kenalog. Kenalog is manufactured by Bristol Myers Squibb and is approved by the Food and Drug Administration for intramuscular use for a variety of indications. Peribulbar injections of Kenalog have been used for a wide variety of ocular conditions, particularly uveitis and post-cataract extraction cystoid macular edema, for many years.
Two different triamcinolone regimens will be assessed in the study: 40 mg injected posteriorly and 20 mg injected anteriorly. There is no indication of which treatment regimen will be better. Although the injection behind the eye is more common than the injection near the front of the eye, the injection near the front of the eye has less risk of injuring the eye. However, it is possible that the injection near the front of the eye may increase eye pressure more frequently. Little is known about which of the two injections decreases macular edema and improves vision more often.
Patients enrolled into the study will be followed for three years and will have study visits 1 month, 2 months, 4 months, 8 months and annually after receiving their assigned study treatment. For the first 8 months of the study, patients should only be retreated with their randomized treatment. However, if the patient's visual acuity has decreased by 15 letters or more, then any treatment may be given at the investigator's discretion. After completion of the 8-month visit, treatment is at investigator discretion.
The primary objective of this study is to obtain estimates of efficacy and safety outcomes for each of the treatment groups. These estimates will provide a basis for the sample size estimation and hypothesis generation in a phase III trial.
详细描述
Diabetic retinopathy is a major cause of visual impairment in the United States. Diabetic macular edema (DME) is a manifestation of diabetic retinopathy that produces loss of central vision. Data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) estimate that after 15 years of known diabetes, the prevalence of diabetic macular edema is approximately 20% in patients with type 1 diabetes mellitus (DM), 25% in patients with type 2 DM who are taking insulin, and 14% in patients with type 2 DM who do not take insulin.
Diabetic macular edema results from abnormal leakage of macromolecules, such as lipoproteins, from retinal capillaries into the extravascular space followed by an oncotic influx of water into the extravascular space. Abnormalities in the retinal pigment epithelium may also cause or contribute to diabetic macular edema. These abnormalities may allow increased fluid from the choriocapillaries to enter the retina or they may decrease the normal efflux of fluid from the retina to the choriocapillaris. The mechanism of breakdown of the blood retina barrier at the level of the retinal capillaries and the retinal pigment epithelium may be due to changes to tight junction proteins such as occludin.
The increase in retinal capillary permeability and subsequent retinal edema may be the result of a breakdown of the blood retina barrier mediated in part by vascular endothelial growth factor (VEGF), a 45 kD glycoprotein. Aiello et al, demonstrated in an in vivo model that VEGF can increase vascular permeability. Fifteen eyes of 15 albino Sprague-Dawley rats received an intravitreal injection of VEGF. The effect of intravitreal administration of VEGF on retinal vascular permeability was assessed by vitreous fluorophotometry. In all 15 eyes receiving an intravitreal injection of VEGF, a statistically significant increase in vitreous fluorescein leakage was recorded. In contrast, control eyes, which were fellow eyes injected with vehicle alone, did not demonstrate a statistically significant increase in vitreous fluorescein leakage. Vitreous fluorescein leakage in eyes injected with VEGF attained a maximum of 227% of control levels.
Antonetti et al, demonstrated that VEGF may regulate vessel permeability by increasing phosphorylation of tight junction proteins such as occludin and zonula occluden 1. Sprague-Dawley rats were given intravitreal injections of VEGF and changes in tight junction proteins were observed through Western blot analysis. Treatment with alkaline phosphatase revealed that these changes were caused by a change in phosphorylation of tight junction proteins. This model provides, at the molecular level, a potential mechanism for VEGF-mediated vascular permeability in the eye. Similarly, in human non-ocular disease states such as ascites, VEGF has been characterized as a potent vascular permeability factor (VPF).
The normal human retina contains little or no VEGF; however, hypoxia causes upregulation of VEGF production. Vinores et al, using immunohistochemical staining for VEGF, demonstrated that increased VEGF staining was found in retinal neurons and retinal pigment epithelium in human eyes with diabetic retinopathy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
1
Focal laser photocoagulation (modified Early Treatment Diabetic Retinopathy Study (ETDRS) technique)
干预措施: Focal laser photocoagulation (Procedure)
2
Posterior peribulbar injection of 40 mg triamcinolone (Kenalog)
干预措施: 40mg triamcinolone (Drug)
3
Anterior peribulbar injection of 20 mg triamcinolone
干预措施: 20mg triamcinolone (Drug)
4
Posterior peribulbar injection of 40 mg triamcinolone followed after one month by laser
干预措施: 40mg triamcinolone + laser (Drug)
5
Anterior peribulbar injection of 20 mg triamcinolone followed after one month by laser
干预措施: 20mg triamcinolone + laser (Drug)
结局指标
主要结局
Mean Visual Acuity Letter Score at Each Follow-up Visit
时间窗: 4, 8, 17, and 34 weeks
Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) mean visual acuity letter score: best value = 97; letter score worst value = 0
Change in Central Subfield Thickening From Baseline Through 34 Weeks
时间窗: 4, 8, 17, 34 weeks
Change in Central Subfield Thickening from Baseline measured on Optical Coherence Tomography (OCT). OCT images were obtained at each visit following pupil dilation by a certified operator using the OCT3 machine (Carl Zeiss Meditec Inc., Dublin, CA). Scans were 6 mm length and included the 6 radial line pattern for quantitative measures and the cross hair pattern (6-12 to 9-3 o'clock) for qualitative assessment of retinal morphology. Negative changes represent a decrease in retinal thickening.
Change in Visual Acuity Letter Score From Baseline Through 34 Weeks
时间窗: 4, 8, 17, and 34 weeks
Change in visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the electronic Early Treatment for Diabetic Retinopathy Study(E-ETDRS) technique. Letter score best value = 97 and worst value = 0; an increase in a letter score by 10 is considered clinically significant. Negative changes represent a worsening in visual acuity.
次要结局
- Persistence/Recurrence of Diabetic Macular Edema (DME) Either Retreated or Meeting Criteria for Retreatment at 17 Weeks(17 weeks)
- Central Subfield Thickness <250 Microns From Baseline Through 34 Weeks(4, 8, 17, 34 weeks)
- Reduction of ≥ 50% in Retinal Thickening in the Central Subfield From Baseline Through 34 Weeks(4, 8, 17, 34 weeks)