Adaptive Optics Scanning Light Ophthalmoscopy (AOSLO) and Microperimetry (MP) Sub-study
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
調査の概要
状態
条件
詳細な説明
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)
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究場所
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Wisconsin
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Madison、Wisconsin、アメリカ、53792
- University of Wisconsin
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参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria (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.
Exclusion Criteria (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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：診断
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：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.
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AOSLO imaging offers unprecedented resolution by correcting optical distortions, enabling direct visualization of individual photoreceptors.
The procedure takes 60 minutes.
他の名前：
Microperimetry measures retinal sensitivity at specific retinal locations while tracking eye movements, enabling precise correlation with structural changes.
The procedure takes up to 45 minutes.
OCT will be performed using the Heidelberg Spectralis system with a high-resolution scanning protocol.
This is a repeat procedure, the first image was obtained in the main study.
The procedure takes 5 minutes.
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Incidence of Photoreceptors in EZ absent regions
時間枠：up to 6 hours total during one or two study visits
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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 |
up to 6 hours total during one or two study visits
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Area of EZ absent regions on AOSLO vs OCT imaging
時間枠：up to 6 hours total during one or two study visits
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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. |
up to 6 hours total during one or two study visits
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Correlation of Retinal Sensitivity Data with EZ Status
時間枠：up to 6 hours total during one or two study visits
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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.
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up to 6 hours total during one or two study visits
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協力者と研究者
捜査官
- 主任研究者：Amitha Domalpally, MD, PhD、University of Wisconsin, Madison
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- 2023-0958 Sub-study
- SMPH/OPHTHAL&VIS SCI/FPRC (その他の識別子：UW Madison)
- Protocol Version 4/20/2026 (その他の識別子：UW Madison)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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