Adaptive Optics (AO) is a technology that dramatically improves the resolution of retinal imaging by detecting aberrations in the eye’s optical system with a wavefront sensor and correcting them in real time with a deformable mirror.
Originally developed in astronomy to reduce optical aberrations caused by Earth’s atmosphere, this technology has been refined and optimized for visualizing the living retina. The eye’s optical system includes aberrations from the cornea, lens, and vitreous body, and in conventional fundus photography, these aberrations limit the resolution. AO overcomes this limitation.
By combining AO, it becomes possible to visualize cone photoreceptors, rod photoreceptors, retinal pigment epithelium (RPE) cells, retinal ganglion cells (RGCs), capillaries, and the optic nerve at the cellular level, which was impossible with conventional fundus examinations. Multimodal imaging is achieved by combining AO with existing fundus imaging (FIO), OCT, and SLO.
Used to directly observe retinal structures at the cellular level in vivo. Main applications include monitoring photoreceptor loss patterns in inherited retinal diseases, detecting subtle changes in age-related macular degeneration and diabetic retinopathy, identifying causes of visual symptoms unexplained by OCT, and serving as structural endpoints in clinical trials1).
Imaging devices utilizing AO are currently categorized into three modalities. The resolution, applications, and approval status of each modality are shown below.
| Modality | Lateral Resolution | Main Applications | Approval Status |
|---|---|---|---|
| AO-FIO | Moderate | Rapid wide-field imaging | Clinically approved |
| AO-SLO | Approximately 2.5 μm | Visualization of photoreceptors and RGCs | Research use |
| AO-OCT | Approximately 5 times that of SD-OCT | Depth-resolved layer structure visualization | Research use |
AO-FIO
Clinical approval: The Imagine Eyes rtx-1 is the only clinically approved device.
Imaging method: The cycle of wavefront aberration evaluation → AO correction → image acquisition is repeated. The patient is fixed on a chin rest and forehead stabilizer, and the system is activated by gaze and button operation.
Advantages: Wide-field images can be acquired more quickly.
Disadvantages: Contrast is low due to scattered light from the retina and choroid.
AO-SLO
Imaging method: AO and imaging system are integrated for real-time aberration correction. Defocus control adjusts the focal plane within the retina, enabling optical sectioning.
Resolution: Lateral resolution approximately 2.5 μm, axial resolution approximately 100 μm1).
Detection modes: Supports multiple modes including confocal (outer segments), dark-field (RPE), off-aperture (RGC, etc.), and split-detector (inner segment tips)1).
Disadvantages: Narrow scanning range, requiring several hours for imaging and good fixation maintenance1).
AO-OCT
Imaging method: Some devices integrate SLO and OCT.
Advantages: Approximately 5 times the horizontal resolution of conventional SD-OCT. Enables depth-resolved visualization of RGC, RPE, and choriocapillaris.
Disadvantages: Image quality limited by motion artifacts and poor fixation. Imaging is difficult in pseudophakic eyes or eyes with long axial length1).
OCT visualizes cross-sectional images (longitudinal sections) of the retina, but it is difficult to identify individual cells. AOSLO can visualize individual photoreceptor cells with a lateral resolution of approximately 2.5 μm, enabling detection of subtle photoreceptor damage that is difficult to detect with OCT 1). The two are complementary technologies and are often used together as multimodal imaging.
AO imaging is applied to evaluate various retinal diseases. The structures that can be visualized and key findings by disease are shown below.
Inherited Retinal Diseases
Retinitis Pigmentosa (RP): Significant cone loss is detected even in the central retina that appears normal on OCT. Features include irregular cone mosaic, decreased cone density, and reduced hexagonality.
Stargardt disease: Cone-rod spacing is significantly enlarged. A “starry-night” pattern is seen in the periphery.
Choroideremia: Cone mosaic is preserved up to the atrophic border. Characteristic bubble-like hyperreflective spots.
Retinal Vascular Diseases
Diabetic retinopathy: Changes in cone packing density and vascular abnormalities such as microaneurysms are detected at the cellular level.
Retinal vascular dynamics: Leukocyte movement within retinal vessels can be tracked in real time.
CSCR: Visualization of cone mosaic abnormalities in central serous chorioretinopathy.
Clinical Trial Application
Structural endpoint: Can quantitatively assess cellular-level changes and be used as a structural endpoint for treatment efficacy.
Early detection of age-related macular degeneration: Early detection of drusen in age-related macular degeneration.
RGC imaging: Visualization of retinal ganglion cells in glaucoma patients.
The characteristics of AO findings in major inherited retinal diseases are described below.
| Disease | Main AO findings | Characteristic pattern |
|---|---|---|
| Retinitis pigmentosa | Decreased cone density | Hexagonal loss |
| Stargardt disease | Increased cone-rod spacing | Starry sky pattern |
| Choroideremia | Cone preservation up to atrophy border | Bubble-like hyperreflective spots |
Vitelliform macular dystrophy shows reduced cone and RPE density in the lesion area, but normal density outside the lesion. Mobile disc-like structures suggestive of subretinal macrophages are also observed.
X-linked retinoschisis shows irregular and enlarged cone spacing within the foveal schisis. Off-aperture imaging reveals characteristically large spoke-wheel cones.
Usher syndrome type II shows lower foveal cone density compared to non-syndromic RP, even when OCT appearance is normal. Type III maintains foveal cone density, but cone structure is lost in areas of sensitivity loss.
An example of detecting subtle lesions difficult to identify with OCT is a case after resolution of cystoid macular edema (CME) following cataract surgery.
Khoussine et al. (2025) reported a case of a 68-year-old woman with resolved cystoid macular edema after cataract surgery1). OCT showed only a small EZ defect, but AOSLO detected a crack-like lesion traversing the macular photoreceptor mosaic. The location and orientation of the lesion matched the metamorphopsia pattern on the Amsler grid, demonstrating that photoreceptor damage persists after resolution of cystoid macular edema and can cause persistent metamorphopsia.
Similarly, there are reports that AOSLO detected cellular damage that was unclear on OCT in solar retinopathy and after retinal detachment surgery1).
Typical applications include identifying the cause of visual symptoms unexplained by OCT (such as metamorphopsia after resolution of cystoid macular edema), quantitative monitoring of photoreceptor loss patterns in hereditary retinal diseases, early detection of subtle changes in age-related macular degeneration and diabetic retinopathy, and use as a structural endpoint in clinical trials1).
The AO fundus imaging system consists of the following three main components.
In AO-SLO, different tissue contrasts can be obtained depending on the detection method.
The custom AOSLO system designed by Dubra employs a non-confocal quadrant detection method with a maximum field of view of 2.5 degrees1). During imaging, short videos are acquired and motion stabilization is performed using custom software1).
This technology was originally developed in astronomy to correct aberrations caused by atmospheric turbulence, and was later adapted and improved for use in ophthalmology.
AOSLO captures cellular-level changes undetectable by OCT, contributing to the understanding of the pathophysiology of visual symptoms.
Khoussine et al. (2025) demonstrated that in cases of persistent metamorphopsia after resolution of cystoid macular edema, crack-like photoreceptor lesions spatially coincide with metamorphopsia patterns on the Amsler grid 1). It remains unclear whether damaged photoreceptors recover over time, and longitudinal studies are needed.
In that report, distinguishing whether the apparent photoreceptor defects in the crack area represent actual photoreceptor loss or misalignment is a challenge 1). Additionally, although the outer segments of cones may be lost, the inner segments may be preserved, and whether preservation of inner segments is a prognostic factor for visual function recovery is of interest 1).
The ability of AO technology to detect cellular-level changes is expected to be used as a structural endpoint in clinical trials of gene therapy and cell therapy for inherited retinal diseases. Its strength lies in quantitatively assessing early photoreceptor changes that cannot be detected by conventional OCT or visual field testing.
Current barriers to clinical adoption are as follows:
Its usefulness in structural endpoints of clinical trials and detailed assessment of photoreceptor damage has been demonstrated, and demand is expected to increase with the spread of gene therapy. However, cost, operational complexity, imaging time, and lack of standardized databases are barriers to widespread adoption, and at present, its use in general ophthalmology is limited1).
The only clinically approved device is the rtx-1 (AO-FIO), which is available at some specialized facilities. AO-SLO and AO-OCT are currently limited to research facilities and are difficult to perform in general ophthalmology clinics. Due to cost and technical expertise issues, widespread adoption in general ophthalmology is still limited.
