Structure and Function in the Progression of Atrophic AMD: Validation of Photoreceptor Damage Observed With OCT Using AOSLO (Adaptive Optics Scanning Light Ophthalmoscopy and Microperimetry
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Incidence of Photoreceptors in EZ absent regions
研究概览
简要总结
This research sub-study is to evaluate if combining images from Optical Coherence Tomography (OCT) scans with Adaptive Optics Scanning Light Ophthalmoscopy (AOSLO) and Microperimetry (MP) could show a link between structural changes in the back of the eye and vision. 10 participants that were enrolled in the COmparison of Clarus and Optos Ultrawide Field Imaging Systems for Geographic Atrophy study [NCT05961332] will be approached to enroll. Participants may complete OCT imaging and initial assessments during an initial visit and may return for additional procedures, including microperimetry and AOSLO imaging, within a window of up to 4 weeks.
详细描述
Age-related macular degeneration (AMD) is a leading cause of blindness worldwide, with geographic atrophy (GA) representing the advanced, untreatable form of the disease. GA leads to progressive degeneration of retinal cells critical for vision, resulting in irreversible vision loss and a significant impact on patients' quality of life. Despite the prevalence of GA, treatment options remain limited. Current therapeutic strategies focus on slowing the enlargement of atrophic regions, but clinical trials have faced challenges in demonstrating clear patient benefits.
In clinical practice, GA progression is often evaluated by measuring the area of atrophy on retinal imaging, such as fundus autofluorescence (FAF) and, more recently, optical coherence tomography (OCT). These structural biomarkers are used in clinical trials to assess the efficacy of new drugs, with the FDA accepting a reduction in the rate of GA enlargement as a successful outcome. However, these structural metrics often fail to correlate with functional vision loss, leaving patients and physicians disappointed by treatments that may stabilize GA progression without improving their visual outcomes.
The ellipsoid zone (EZ), a hyperreflective layer visualized on OCT, represents the structural integrity of photoreceptors-cells responsible for converting light into visual signals. In patients with one or more GA lesions, OCT imaging shows that the EZ is typically absent within the GA, while the EZ in the perilesional zone may be attenuated or damaged. Perilesional EZ loss is thought to represent the area at highest risk for future vision loss. With the FDA approval of photoreceptor preservation as an endpoint for GA trials, there has been significant interest in measuring EZ loss from OCT scans. Drug approval will now focus on the prevention of EZ loss in the perilesional areas rather than GA area expansion. However, it is important to establish whether the absence of the EZ truly indicates photoreceptor damage and whether there is a functional correlation between EZ loss and visual sensitivity. Adaptive Optics and microperimetry are two modalities that can help address this.
This sub-study is a pilot comparative imaging study. In addition to the imaging procedures collected for the main COCO GA study [NCT05961332], participants will have the following study images obtained:
- Spectralis OCT (if applicable),
- visual acuity,
- ocular biometry, which is a non-invasive eye test using a machine called an IOL master,
- microperimetry, and
- Adaptive Optics Scanning Light Ophthalmoscopy (AOSLO)
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(from the main study):
- •50 years or older and may be either male or female and may be of any race
- •Established diagnosis of geographic atrophy (GA) due to age-related macular degeneration (AMD)
- •GA characteristics: GA area of between 1.25 mm² and 23 mm², with seventy percent of eyes having GA area ranging from 2.5 mm² to 17.5 mm². GA may be unifocal or multifocal. GA may be subfoveal or extrafoveal, with twenty-five percent of eyes having subfoveal GA. The presence of concurrent peripapillary atrophy will not exclude participants from participation
- •Willing to participate as evidenced by signing the written informed consent
- •Additional Sub-study Inclusion Criteria:
- •Early-stage GA defined as
- •GA area of between 1.25 mm2 and 23 mm2
- •GA may be unifocal or multifocal
- •GA may be subfoveal or extrafoveal
- •Concurrent peripapillary atrophy will not exclude participant from participation
- •Phakic and pseudophakic participants are eligible for enrollment, with phakic participants prioritized when feasible.
排除标准
- •(from the main study):
- •Unable to tolerate ophthalmic imaging
- •Presence of neovascular AMD on optical coherence tomography (OCT) as confirmed by an ophthalmologist
- •Presence of significant media opacity preventing adequate retinal imaging
- •Presence of concurrent retinal disease which may confound assessment
- •Additional Sub-study Exclusion Criteria:
- •Ocular media opacity or other condition(s) that, in the opinion of the investigators, may preclude imaging.
- •Individuals who, in the opinion of the investigator, are unable to tolerate study procedures or comply with study requirements.
- •Prior or current treatment with intraocular injections for geographic atrophy (e.g., pegcetacoplan [Syfovre] or similar therapies) is not permitted.
研究组 & 干预措施
Microperimetry, Optical Coherence Tomography, Adaptive Optics
Imaging procedures may be completed during a single study visit or across two study visits based on participant availability and operational workflow. When procedures occur across two visits, OCT imaging will be performed first to allow WRC review prior to scheduling microperimetry and AOSLO imaging. If all procedures are completed during a single visit, the total visit time is approximately 5-6 hours. If a second study visit is needed, only the remaining study procedures will be completed, so the second visit will be shorter since the initial ophthalmic procedures have already been performed.
干预措施: Adaptive Optics Scanning Light Ophthalmoscopy (Device)
Microperimetry, Optical Coherence Tomography, Adaptive Optics
Imaging procedures may be completed during a single study visit or across two study visits based on participant availability and operational workflow. When procedures occur across two visits, OCT imaging will be performed first to allow WRC review prior to scheduling microperimetry and AOSLO imaging. If all procedures are completed during a single visit, the total visit time is approximately 5-6 hours. If a second study visit is needed, only the remaining study procedures will be completed, so the second visit will be shorter since the initial ophthalmic procedures have already been performed.
干预措施: Microperimetry (Device)
Microperimetry, Optical Coherence Tomography, Adaptive Optics
Imaging procedures may be completed during a single study visit or across two study visits based on participant availability and operational workflow. When procedures occur across two visits, OCT imaging will be performed first to allow WRC review prior to scheduling microperimetry and AOSLO imaging. If all procedures are completed during a single visit, the total visit time is approximately 5-6 hours. If a second study visit is needed, only the remaining study procedures will be completed, so the second visit will be shorter since the initial ophthalmic procedures have already been performed.
干预措施: Optical Coherence Tomography (Device)
结局指标
主要结局
Incidence of Photoreceptors in EZ absent regions
时间窗: up to 6 hours total during one or two study visits
The aim is to validate the use of AOSLO imaging for OCT-based EZ classifications, directly visualizing photoreceptor mosaics and correlating EZ loss with photoreceptor structure. Semi-automated machine learning algorithms will be used to segment the EZ layer on OCT images and generate en face maps. All algorithm outputs will be reviewed and verified by trained human graders. AOSLO imaging will validate these maps by providing photoreceptor cell counts and qualitative assessments in the same region
Area of EZ absent regions on AOSLO vs OCT imaging
时间窗: up to 6 hours total during one or two study visits
The aim is to validate the use of AOSLO imaging for OCT-based EZ classifications, directly visualizing photoreceptor mosaics and correlating EZ loss with photoreceptor structure. Semi-automated machine learning algorithms will be used to segment the EZ layer on OCT images and generate en face maps. All algorithm outputs will be reviewed and verified by trained human graders. Graders will independently measure area of EZ loss from images of each device. The measurements (in mm²) will be compared between the two devices.
Correlation of Retinal Sensitivity Data with EZ Status
时间窗: up to 6 hours total during one or two study visits
The aim is to correlate structural metrics (EZ status from OCT and AOSLO) with functional data (microperimetry), establishing EZ loss as a reliable biomarker for vision loss.
次要结局
未报告次要终点