Retinal Oximetry

Key Points at a Glance

Key Points of This Technology

• Retinal oximetry is a non-invasive technique that combines fundus photography with optical analysis to measure oxygen saturation (SO₂) in retinal blood vessels.
• In healthy individuals, arterial SO₂ is approximately 92% and venous SO₂ is approximately 55% as reference values.
• Diseases show characteristic changes: venous SO₂ increases in diabetic retinopathy, while arterial SO₂ decreases in normal-tension glaucoma.
• Changes in retinal vessel SO₂ have also been reported in systemic diseases such as Alzheimer’s disease, suggesting potential as a systemic biomarker.
• Measurement accuracy is affected by vessel diameter, cataracts, and the condition of the retinal nerve fiber layer.
• Currently, it is mainly used for research purposes, and its adoption in general ophthalmology clinics is limited.

1. What is retinal oximetry?

Retinal oximetry is a non-invasive technique for measuring oxygen saturation (SO₂) in retinal blood vessels. It uses a fundus camera and optical analysis software to quantify oxygen status without blood sampling or contrast agents. ¹⁾²⁾

The foundational research for this technique was conducted by Hickam et al. in 1959. ²⁾ Since then, advances in digital image processing have led to practical applications, and recent integration with AI analysis has improved accuracy. ¹⁾

The theoretical basis of the measurement is dual-wavelength spectroscopy based on the Lambert-Beer law, utilizing the difference in light absorption spectra between oxygenated and deoxygenated hemoglobin (see Technical Principles).

Q What kind of test is retinal oximetry?

A

It is a test that uses a fundus camera to shine light at multiple wavelengths and calculates oxygen saturation from the difference in light absorption between oxygenated and deoxygenated hemoglobin in retinal blood vessels. No blood sampling or contrast agents are needed, and the measurement is completed in a few minutes.

2. Measurement Findings in Various Diseases

Normal Reference Values for Healthy Eyes

The reference values for retinal vessels in healthy individuals are as follows. ²⁾

Site	Oxygen Saturation
Artery	Approximately 92%
Vein	Approximately 55%

The difference between artery and vein (an indicator of oxygen consumption) is approximately 37 percentage points. This value serves as a reference for evaluation in various diseases.

SO₂ Changes in Eye Diseases

Typical patterns of SO₂ changes for each eye disease are summarized below.

Disease	Artery	Vein	Main significance
Diabetic retinopathy	No change to mild increase	Increase	Indicator of metabolic disorder
Normal-tension glaucoma	Decrease	No change to decrease	Suggests optic nerve ischemia
Retinal vein occlusion	No change	Increase	Evaluation of occlusion site
Age-related macular degeneration	Change present	Change present	Choroidal circulatory insufficiency
Retinitis pigmentosa	Decreased	Decreased	Overall metabolic decline

• Diabetic retinopathy (DR): An increase in venous SO₂ is characteristic. It is thought that due to retinal metabolic impairment, oxygen consumption decreases, making it harder for oxygen in venous blood to be consumed, leading to elevated venous SO₂. ¹⁾
• Normal-tension glaucoma (NTG): A decrease in arterial SO₂ has been reported, suggesting a link to impaired blood flow and insufficient oxygen supply to the optic nerve. ¹⁾
• Retinal vein occlusion (RVO): An increase in venous SO₂ at the occlusion site is observed. Changes may also be seen in both arteries and veins. ¹⁾²⁾
• Age-related macular degeneration (AMD): Changes reflecting choroidal circulation disorders have been reported. ¹⁾
• Retinitis pigmentosa (RP): Due to degeneration and loss of photoreceptors, overall retinal oxygen consumption decreases, and SO₂ decreases in both arteries and veins. ¹⁾

Changes in SO₂ in Systemic Diseases

Since retinal blood vessels reflect systemic circulation, characteristic changes are observed even in systemic diseases outside the eye.

Disease	Main findings
Alzheimer’s disease	Increased arterial SO₂ (approximately 94.2%)
COPD	Decreased arterial and venous SO₂
Chronic kidney disease	SO₂ changes present

• Alzheimer’s disease (AD): Arterial SO₂ has been reported to average 94.2%, higher than in healthy individuals. ¹⁾³⁾ It has been suggested that reduced retinal metabolism due to neurodegeneration may lead to decreased oxygen consumption.
• COPD (Chronic Obstructive Pulmonary Disease): Reflecting systemic hypoxia, retinal vascular SO₂ decreases. ¹⁾
• Chronic Kidney Disease (CKD): Changes in SO₂ related to renal dysfunction have been reported. ¹⁾

Q Can retinal oximetry be used to diagnose Alzheimer's disease?

A

At present, it is still in the research stage and has not been established as a diagnostic tool. Although an increase in arterial SO₂ has been reported in Alzheimer’s disease, its diagnostic accuracy alone is insufficient, and combination with other neurological tests is necessary. For details, see the “Future Prospects” section.

3. Factors Affecting Measurement Accuracy

Retinal oximetry measurements are affected by multiple factors. These confounding factors must be considered when interpreting results.

• Vessel diameter: There is a lower limit for measurable vessel diameter; reliable measurements are difficult for small vessels less than 50 μm in diameter. ²⁾ Capillary-level measurements are beyond the limits of current technology.
• Lens opacification (cataract): Light scattering and absorption due to cataracts affect measurements and may cause falsely low values. ¹⁾
• Retinal nerve fiber layer (RNFL) thickness: Changes in RNFL thickness alter the optical environment of blood vessels, affecting measurement accuracy. ¹⁾²⁾ Special caution is needed in diseases with optic neuropathy such as glaucoma.
• Pupil diameter and intraocular scattering: Insufficient dilation or vitreous opacities also reduce measurement accuracy.
• Vessel tortuosity and angle: Experience is required for selecting measurement sites.

Technical Supplement

When comparing or tracking retinal oximetry measurements, it is recommended to simultaneously assess cataract progression and RNFL thickness. Without correcting for these confounding factors, changes in SO₂ due to disease progression cannot be distinguished from changes in measurement conditions.

4. Technical Principles and Equipment

Measurement Principle: Lambert-Beer Law and Dual-Wavelength Method

The basic principle of retinal oximetry is dual-wavelength spectrophotometry based on the Lambert-Beer law. ¹⁾²⁾

Oxyhemoglobin (oxyHb) and deoxyhemoglobin (deoxyHb) have different light absorption spectra. Specifically:

• Isobestic point (approximately 570 nm): Wavelength at which the absorbance of oxyHb and deoxyHb are equal. Used as a reference wavelength.
• Sensitive wavelength (approximately 600–640 nm): Wavelength at which the difference in absorbance between oxyHb and deoxyHb is maximal. Used as a measurement wavelength.

Oxygen saturation (SO₂) is calculated from the optical density ratio (ODR) at these two wavelengths. ¹⁾ The outline of the formula is as follows.

ODR = log(I_ref / I_meas_reference) / log(I_ref / I_meas_sensitive) SO₂ ∝ 1 − ODR (coefficients determined by device calibration)

This calculation is performed for each pixel of the blood vessel, generating a color map of SO₂ along the vessel.

Major Devices

Oxymap T1

Overview: A representative commercial retinal oximeter.

Method: Combines a non-mydriatic fundus camera with a two-wavelength camera.

Features: FDA-approved. Used in many clinical studies. ¹⁾²⁾

Imedos System

Overview: A retinal vessel analysis system developed by Imedos, Germany.

Method: Retinal vascular analysis using multi-wavelength spectroscopy.

Features: Also enables measurement of vessel diameter and blood flow velocity. ²⁾

vis-OCT

Overview: A next-generation measurement technology applying visible-light OCT.

Method: Uses visible light (450–700 nm) OCT to measure SO₂ with high spatial resolution.

Features: Enables layer- and depth-specific SO₂ measurement, with applications to the choroid under investigation. ²⁾

Q How is it different from a pulse oximeter?

A

A pulse oximeter measures arterial blood SO₂ in the overall peripheral circulation, such as in the fingertip, whereas retinal oximetry locally measures SO₂ in individual retinal blood vessels (both arteries and veins) in the fundus. The major difference is that it can evaluate not only systemic oxygen status but also local retinal oxygen metabolism and the presence of vascular disorders.

5. Application to Treatment Monitoring

Retinal oximetry is also being studied as a tool for evaluating treatment efficacy.

Monitoring after Photocoagulation for Diabetic Retinopathy

After retinal photocoagulation (laser treatment) for diabetic retinopathy, a decrease in venous SO₂ (a change toward normalization) has been observed. ¹⁾²⁾ It is thought that when retinal tissue with metabolic disorders is destroyed by photocoagulation, the oxygen demand of the remaining retina changes, leading to improvement in venous SO₂. Tracking this change is expected to provide an objective evaluation of treatment efficacy.

Monitoring after administration of carbonic anhydrase inhibitors (CAIs) for glaucoma

Reports indicate that changes in retinal arterial SO₂ are observed after administration of carbonic anhydrase inhibitors (CAIs), which are glaucoma medications. ¹⁾CAIs are suggested to have not only intraocular pressure-lowering effects but also retinal blood flow-improving effects, and retinal oximetry may serve as a non-invasive tool to evaluate these vascular effects.

Current status

The application to treatment monitoring is currently at the research stage. Due to significant variability in measurements and the influence of confounding factors, additional validation is needed before it can be used to assess treatment efficacy in individual patients. It is not recommended for use as a standalone basis for clinical decision-making.

6. Detailed measurement principle: Dual oxygen supply to the retina

Oxygen supply to the retina comes from two anatomically distinct systems. This dual structure is also a factor that complicates the interpretation of retinal oximetry. ²⁾

• Central retinal artery system (inner layer supply): Supplies oxygen to the inner retina (ganglion cell layer to inner nuclear layer). Retinal oximetry can directly measure the vessels of this system.
• Choroidal capillary system (outer layer supply): Supplies oxygen to the outer retina (photoreceptors and RPE). Choroidal circulation has extremely high blood flow and low oxygen extraction rate.

Photoreceptors are the cells with the highest oxygen consumption in the eye, but their oxygen supply comes from the choroid, which cannot be directly measured by retinal oximetry using a standard fundus camera. This is why research on choroidal SO₂ measurement using vis-OCT or deep OCT is advancing.

It is important to interpret SO₂ in the inner retina not as a direct reflection of photoreceptor oxygen consumption, but as an indicator of the metabolic activity of inner retinal neurons and glial cells.

7. Latest Research and Future Prospects

For patients: Please be sure to read this.

The following content is currently in the research stage or under clinical trial and is not a standard test available at general hospitals. It is reference information for professionals regarding future medical developments.

Technological Advances: Wide-Angle, Non-Mydriatic, AI Analysis

Current retinal oximetry has issues with measurement range, operability, and reproducibility. The following technological developments are underway. ¹⁾

• Wide-angle oximetry: Combined with wide-angle fundus cameras, it is becoming possible to measure SO₂ in the peripheral retina.
• Non-mydriatic measurement system: Efforts are being made to improve measurement accuracy in examination environments without the use of mydriatic agents.
• AI and machine learning analysis: Algorithm development is progressing for automated analysis of SO₂ maps and automatic classification of disease patterns.

Prospects as a Biomarker for Dementia and Systemic Diseases

The retina is functionally and anatomically similar to the central nervous system (brain) as an extension of it, and its role as a “window” into neurodegenerative diseases is attracting attention. ¹⁾³⁾

Cheung et al. (2019) reviewed structural and functional changes in the retina in Alzheimer’s disease, Parkinson’s disease, and dementia, showing that the retina could be a potential biomarker for these neurodegenerative diseases ³⁾. Combining multiple retinal biomarkers, including retinal oximetry, is expected to be applied to early screening for dementia.

In Alzheimer’s disease, an increase in retinal arterial SO₂ (approximately 94.2%) has been reported, which is thought to reflect changes in oxygen metabolism associated with neurodegeneration. ¹⁾ However, for practical use as a diagnostic tool, longitudinal studies are needed to establish sensitivity and specificity.

Q Can it help detect diabetic retinopathy early?

A

At present, it is still in the research stage. In diabetic retinopathy, an increase in venous SO₂ has been observed before clinical changes become apparent, suggesting it could be an indicator of very early changes. However, further large-scale studies are needed to establish it as a standard screening test.

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8. References

1. Zhang W, Tay WT, Cheng CY, et al. Retinal oximetry: new insights into ocular and systemic diseases. Graefes Arch Clin Exp Ophthalmol. 2025;263:2101-2115.
2. Garg アカントアメーバ角膜炎, Knight D, Lando L, et al. Advances in retinal oximetry. Trans Vis Sci Tech. 2021;10(2):5.
3. Cheung CY, Ikram MK, Chen C, Wong TY. Potential retinal biomarkers for dementia. Curr Opin Neurol. 2019;32(1):82-91.