Retinal Ganglion Cell Neuroprotection Under Prostaglandin Analogues: NEUROPA - a Retrospective Cohort Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 1,500
- 试验地点
- 14
- 主要终点
- Visual Field - Glaucoma Progression Analysis (GPA), measured by automated perimetry testing devices, such as Haag-Streit Octopus, Zeiss Humphrey, or similar.
研究概览
简要总结
The goal of this observational study is to evaluate whether prostaglandin analogue eye drops have a direct neuroprotective effect on retinal ganglion cells - beyond their intraocular pressure (IOP)-lowering effect - in adult patients with glaucoma or ocular hypertension. The study includes individuals diagnosed with glaucoma (any sex/gender, adult age groups) undergoing standard clinical treatment. The main questions it aims to answer are:
- Do prostaglandin analogues provide a neuroprotective effect on retinal ganglion cells that is independent of their IOP-lowering properties?
- Should prostaglandin analogues be promoted/favoured over other IOP-lowering compounds for long-term glaucoma management?
Researchers will compare an interventional group, which consist of 750 eyes treated with prostaglandin analogues (e.g., latanoprost, travoprost, tafluprost, bimatoprost, unoprostone), with a control group, which consist of 750 eyes treated with non-prostaglandin IOP-lowering compounds (e.g., timolol, dorzolamide, brimonidine, netarsudil) to see if treatment with prostaglandin analogues is associated with better retinal ganglion cell survival over a period of 3 years (36 months).
Data will be collected from individuals who had at least 36 months of documented follow-up, with clinical data available at approximately 3, 6, 12, 24, and 36 months. Eligible individuals must have been treated with either prostaglandin analogues or other intraocular pressure (IOP)-lowering agents as part of routine clinical care. The data to be obtained from medical records will include at least:
- Intraocular pressure readings
- Visual field testing
- OCT measures
- Visual acuity
- Adverse events
- Treatment adherence/compliance
- Additional glaucoma interventions
详细描述
Glaucoma is among the most prevalent causes of irreversible blindness and is characterized by a progressive, irreversible degeneration of the retinal ganglion cells. Elevated intraocular pressure (IOP) is the most important glaucoma risk factor and the only risk factor that is readily modifiable with established treatment options, which include pharmacological approaches, laser treatment, and surgery. However, in many patients the disease progresses even after IOP is effectively lowered. Hence, neuroprotective treatment approaches that go beyond IOP lowering are needed.
Prostaglandin analogue eye drops reduce IOP by increasing uveoscleral outflow and are a well-established treatment option in ocular hypertension and glaucoma. Animal studies suggest that prostaglandin analogues may have a direct neuroprotective effect on retinal ganglion cells in addition to the effect mediated by IOP lowering. Proposed mechanisms of action include inhibiting of caspase-3 and cyclooxygenase as well as activation of polypeptide 2B1 and Klotho protein. However, this proposed additional, direct neuroprotective effect has not yet been tested in human patients. The viability and functional status of the retinal ganglion cells in glaucoma can be assessed by morphological readings, the standard nowadays being various optical coherence tomography modalities, and by visual field testing. Detection of Apoptosing Retinal Cells (DARC) is another, relatively novel technology that allows for quantification of retinal ganglion cell death, presumably on a much shorter time scale.
This is an observational, retrospective and longitudinal clinical study, according to the normal clinical practice.
This study aims to evaluate prostaglandin analogues neuroprotective effect on retinal ganglion cells apart from intraocular pressure (IOP)-lowering over a period of 3 years (36 months) and whether treatment of ocular hypertension and glaucoma participants with prostaglandin analogues should be promoted/ favoured over other IOP-lowering compounds. It will have a follow-up at 3, 6, 12, 24, and 36 months in eyes with glaucoma treated with prostaglandin analogues or a different topically applied compound.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
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
- •Age 18+ years
- •Established glaucoma diagnosis (primary open-angle glaucoma, normal tension Glaucoma, pseudoexfoliation glaucoma, pigmentary dispersion glaucoma) in either eye
- •Visual field mean deviation (MD; location-weighted mean difference from average age-corrected visual field sensitivity) of 2 visual fields differing by no more than 3 dB, for a mean deviation of better than -6.0 dB, or by no more than 4 dB, for a mean deviation worse than -6.0 dB, as measured using Humphrey perimetry (or equivalent Haag-Streit / Octopus; in at least one eye; analogous to The United Kingdom Glaucoma Treatment Study)
- •Treatment with either prostaglandin analogues only or another topically applied IOP-lowering compound only for at least 3 years
- •Documented follow-up period of at least 3 years
- •At least 6 patient visits documented over the follow-up period with readings of IOP, visual field, OCT
- •No additional glaucoma intervention apart from laser trabeculoplasty and/or cataract surgery during the observational period
排除标准
- •Follow-up period < 3 years
- •Number of patient visits <6 visits
- •Number of OCT, visual field readings during the observation period < 6
- •Low compliance/therapy interruption
- •Beginning of combination therapy of prostaglandin analogues and other IOP lowering eye drops during the observation period
- •In case of glaucoma diagnosis in both eyes: different topical IOP-lowering treatment regimes (e.g. prostaglandin analogues in one eye and beta-adrenergic blocking agents in the fellow eye)
- •Additional glaucoma intervention during the observational period other than laser trabeculoplasty and/or cataract surgery
研究组 & 干预措施
Control Group (Non-Prostaglandin IOP-lowering compound)
750 eyes treated with intraocular pressure-lowering compounds that do not belong to the prostaglandin analogue class. These treatments may include beta-adrenergic blocking agents (e.g., timolol, betaxolol), carbonic anhydrase inhibitors (e.g., dorzolamide, brinzolamide), alpha-2 adrenergic agonists (e.g., brimonidine) or rho kinase inhibitors (e.g., netarsudil).
Interventional group (prostaglandin analogues)
750 eyes treated with any prostaglandin analogue, such as latanoprost (e.g., Xalatan® 50 µg/mL, Pfizer), travoprost, tafluprost, bimatoprost, or unoprostone.
结局指标
主要结局
Visual Field - Glaucoma Progression Analysis (GPA), measured by automated perimetry testing devices, such as Haag-Streit Octopus, Zeiss Humphrey, or similar.
时间窗: 6 months
Evaluation of Glaucoma Progression Analysis (GPA, %/year).
Optical Coherence Tomography - Change in Average GCL+IPL Thickness, measured by Heidelberg Spectralis, Zeiss Cirrus, or similar.
时间窗: 6 months
Evaluation of Change in Average GCL+IPL thickness (µm).
Optical Coherence Tomography - Average RNFL Thickness, measured by Heidelberg Spectralis, Zeiss Cirrus, or similar.
时间窗: 6 months
Evaluation of average RNFL thickness (µm).
Optical Coherence Tomography - Disc Rim Area, measured by Heidelberg Spectralis, Zeiss Cirrus, or similar.
时间窗: 6 months
Evaluation of Disc Rim Area (mm²).
Intraocular pressure (IOP), measured using a Goldmann applanation tonometer, an iCare tonometer, or similar. Change in IOP value (mmHg).
时间窗: 6 months
Change in IOP value (mmHg).
Visual field (VF) - Mean Deviation, measured by automated perimetry testing devices, such as Haag-Streit Octopus, Zeiss Humphrey, or similar
时间窗: 6 months
Evaluation of Change in Mean Deviation (MD, dB).
Visual Field - Pattern Standard Deviation, measured by automated perimetry testing devices, such as Haag-Streit Octopus, Zeiss Humphrey, or similar.
时间窗: 6 months
Evaluation of Pattern Standard Deviation (PSD, dB).
Optical Coherence Tomography - Cup-to-disc Ratio, measured by Heidelberg Spectralis, Zeiss Cirrus, or similar.
时间窗: 6 months
Evaluation of Cup-to-disc ratio (average and vertical).
Optical Coherence Tomography - Central Subfield Thickness, measured by Heidelberg Spectralis, Zeiss Cirrus, or similar.
时间窗: 6 months
Evaluation of Central Subfield Thickness (µm).
次要结局
- 10 Visual Acuity, measured by Best Corrected Visual Acuity (BCVA) score, using Snellen and/or LogMar charts.(6 months)
- Adverse Events, as reported in patient's medical history.(6 months)
- Adherence to Study Treatment(6 months)
- Additional Glaucoma Interventions(6 months)
- 10 Visual Acuity, measured by Best Corrected Visual Acuity (BCVA) score, using Snellen and/or LogMar charts.(6 months)
- Adverse Events, as reported in patient's medical history.(6 months)