Adaptive Optics Scanning Light Ophthalmoscopy (AOSLO) and Microperimetry (MP) Sub-study

Official title

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

Overview

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.

Detailed description

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)

Interventions

• Device Adaptive Optics Scanning Light Ophthalmoscopy
  AOSLO imaging offers unprecedented resolution by correcting optical distortions, enabling direct visualization of individual photoreceptors. The procedure takes 60 minutes.
• Device Microperimetry
  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.
• Device Optical Coherence Tomography
  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.

Primary outcome measures

• Incidence of Photoreceptors in EZ absent regions [Time frame: up to 6 hours total during one or two study visits]
• Area of EZ absent regions on AOSLO vs OCT imaging [Time frame: up to 6 hours total during one or two study visits]
• Correlation of Retinal Sensitivity Data with EZ Status [Time frame: up to 6 hours total during one or two study visits]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

United States · 1 center

• University of Wisconsin — Madison

Identifiers

NCT: NCT07747662 · 2023-0958 Sub-study · Protocol Version 4/20/2026 · SMPH/OPHTHAL&VIS SCI/FPRC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗