Pascal Pan Retinal Photo-Stimulation in Pre-Proliferative Diabetic Retinopathy: a Safety and Efficacy Study
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- prevention on the developing of proliferative diabetic retinopathy (assessed with slitlamp, color fundus, and fluorangiography)
研究概览
简要总结
Diabetic retinopathy (DR) is a leading cause of new cases of blindness in people aged 20 to 65 years worldwide.
Patients with DR may go on to develop a more severe form of the disease called Proliferative Diabetic Retinopathy (PDR), a condition in which abnormal new blood vessels may rupture and bleed inside the eye. When this advanced stage of retinopathy occurs, pan-retinal photocoagulation (laser treatment) is usually recommended.
The purpose of the investigators study is to find if treating patients using a single session of lower intensity laser (Pascal® Pan Retinal Photo-Stimulation, P-RPhS) at an earlier stage in Diabetic Retinopathy (during the severe non-proliferative diabetic retinopathy stage) when the abnormal new vessels are not developed, will prevent diabetic patients to develop PDR.
Patients included in the study will be randomized in three arms (randomization). In one arm patients will be treated with the normal parameters used in Pascal® laser, the second arm patients will be treated with a lower intensity than normal, using the Endpoint management system (a new software from the Pascal® laser which allow us to decrees the intensity of the burns (invisible burns) showing some landmarks with normal intensity so the area which has been treated can be viewed. And in the third arm the patients will be observed.
详细描述
The published evidence from clinical trials in the literature has demonstrated that conventional PRP using 2000-2500 burns may be used safely and effectively in PDR patients over 2 or 3 sessions. A recent audit of 313 Pascal laser treatments performed at Manchester Royal Eye Hospital (2007-2008) has demonstrated that 1952 burns may be used safely and effectively in routine ophthalmic practice for PDR.
A recent study (PETER PAN study) which has been presented at the Association for Research in Vision and Ophthalmology (ARVO) 2011 Annual Meeting and also submitted for publication (Am J Ophthalmol) has shown that performing primary 20ms Pascal targeted retinal photocoagulation (TRP) and reduced fluence/minimally-traumatic panretinal photocoagulation (MT-PRP) in a single session using 2,500 burns can be safe and effective in treating PDR, without negative effect on visual fields. Therefore, it seems reasonable to think that a single session of 3000 burns 20ms with Endpoint Management set at 70% fluence will be safe and effective to treat patients with severe NPDR as similar or less total energy would be delivered to the retina-RPE complex.
Topcon's Endpoint Management (EM) software is based on a computational model of retinal heating and an Arrhenius damage model to determine optimal pulse duration and laser power for various levels of pulse energy. The algorithm varies the power and duration concurrently to maximize the margins between visible and sub-visible photocoagulation endpoints, providing a linear control over an inherently nonlinear process of coagulation.
When utilising EM, the user first titrates to a comfortable visible endpoint. Establishing a titration endpoint is important as it gives a consistent baseline, ensuring repeatable results between patients. With the Endpoint Management option activated, the laser output in a pattern is a percentage of this titration energy. Power and duration are both modulated to make this energy adjustment, allowing for a fine gradation of laser dosage and control over treatment endpoints. The visible titration endpoint can be references throughout the course of treatment by enabling the Landmark feature, which crates reference lesions at the titration dose at the corners of the pattern. This provides visible feedback on dosage and positioning of treated areas.
Importantly, the EM approach to laser therapy allows the physician to consistently operate in the realm of therapeutic relevance for sub-visible treatments. When no burns are visible, the biggest risk becomes lack of therapeutic effect. The Arrhenius integral-based algorithms in Endpoint Management adjust power and duration to provide the best "path" between endpoints, moving smoothly from the ophthalmoscopically-visible titration point to angiographically-only, OCT-only, and sub-visible/ therapeutic regimes. The Landmark feature allows the user to determine the local effect of the titration dose, and make adjustments as uptake varies across the treated area. The result is more predictable sub-visible laser delivery with the widest window of safe, effective treatment.
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
- None
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
- •Patient-eligibility
- •Inclusion criteria:
- •Older than 18 years of age
- •Male or female patients with diabetes mellitus type I or type 2 who meet the WHO or ADA criteria for diabetes
- •Able to give informed consent
- •Study Eye eligibility
- •Inclusion criteria:
- •Treatment-naive S-NPDR
- •ETDRS visual acuity equivalent to 35 letters or better (Snellen equivalent 6/60 or better)
- •Any of the following:
- •Extensive (>20) intraretinal hemorrhages in each of 4 quadrants
- •Definite venous beading in 2+ quadrants
- •Prominent IRMA in 1+ quadrant
- •Mean central retinal thickness of less than or equal to 300 microns as measured by Deep Range Imaging Optical Coherence Tomography (DRI -OCT) scans
- •No intra-retinal fluid (IRF) or sub-retinal fluid (SRF) on DRI-OCT
- •Adequate pupil dilatation and clear media to perform wide-field colour, red-free imaging and fundus fluorescein angiography (WF-FFA), wide-field fundus autofluorescence imaging (WF-AF), DRI-OCT of retina and choroid, Multispectral Imaging (MSI) of chorioretinal oxygenation and P-RPhS
- •Ability to perform accurate Humphrey visual field test
排除标准
- •Patient-eligibility
- •Exclusion criteria:
- •History of chronic renal failure or renal transplant for diabetic nephropathy
- •Recent (last 6 months) or on-going poor glycaemic control. H1Ac greater than 10.0mg/dL
- •Creatinine greater than 1.2 mg/dL
- •HDL equal to or greater than 40 mg/dL
- •Uncontrolled hypertension. Blood pressure greater or equal to 180/110 mmHg
- •Patient is unavailable for follow-up visits
- •Pregnant women or breast-feeding females
- •Study Eye eligibility
- •Exclusion criteria:
- •Lens opacity that could influence vision and results
- •Any surgical or non-retinal laser treatment to the study eye within 2 months
- •Narrow drainage angles with raised intraocular pressure and angle closure glaucoma.
- •Planned YAG peripheral iridotomy
- •Previous retinal laser photocoagulation, intraocular drug therapy, or macular laser treatment to treatment eye in last year
- •Any previous ocular condition that may be associated with a risk of macular oedema
- •Active lid or adnexal infection
- •Planned intra-ocular surgery within one year
结局指标
主要结局
prevention on the developing of proliferative diabetic retinopathy (assessed with slitlamp, color fundus, and fluorangiography)
时间窗: 12 months
assessed with slitlamp, color fundus, and fluorangiography
次要结局
- regression of Diabetic Retinopathy from Severe Non-Proliferative Stage (S-NPDR) to Moderate Non-Proliferative Stage (M-NPDR) or lesser severity of retinopathy(12 months)
- reduction in visual acuity(12 months)
- reduction in the field of vision(12 months)
- reduction of central retinal thickness(12 months)
- Pain assessment (questionnaire)(12 months)
研究者
Emma Columbine
Professor Paulo Stanga
Manchester University NHS Foundation Trust