OCT Biomarkers for Diabetic Retinopathy

NIH/NIDDK DP3 DK104397 PIs: Yali Jia, David Wilson


Diabetic retinopathy (DR), associated with long-term diabetes mellitus, is a leading cause of blindness in the US. Structural optical coherence tomography (OCT) has become the standard method for evaluating diabetic macular edema; however, fluorescein angiography (FA), which requires an invasive intravenous dye injection, is still needed to assess capillary dropout and confirm neovascularization...

OCT Angiography of CNV

NIH/NEI R01 EY024544 - PIs: Dr. Yali Jia and Dr. Steven T. Bailey


Neovascular age-related macular degeneration (AMD), characterized by the presence of choroidal neovascularization (CNV), accounts for the majority of AMD-related vision loss. Optical coherence tomography (OCT) has become the most frequently used test for AMD evaluation; however, fluorescein angiography (FA), which requires an invasive intravenous dye injection, is needed for initial CNV diagnosis. Using a high-speed OCT system, we have developed an algorithm called “split-spectrum amplitude decorrelation angiography” (SSADA) to non-invasively image and measure both retinal and choroidal blood flow...

Functional and Structural OCT for Glaucoma

NIH/NEI R01 EY023285 - PI: Dr. David Huang


Glaucoma is a leading cause of blindness. Early diagnosis and close monitoring of glaucoma are important because the onset is insidious and the damage is irreversible. Advanced imaging modalities such as optical coherence tomography (OCT) have been used in the past 2 decades to improve the objective evaluation of glaucoma. OCT has higher axial spatial resolution than other posterior eye imaging modalities, and it has relatively good diagnostic accuracy and reproducibility in the measurement of neural structures damaged by glaucoma...

Anterior Eye Diseases

NIH R01 EY028755 - PI: Dr. David Huang
NIH R01 EY029023 - PI: Dr. Yan Li


The long-term goal of this project is to utilize newly available very high-speed optical coherence tomography (OCT) technology to guide surgical treatments of anterior eye diseases. Measuring aberrations in the optical surfaces of the cornea requires great precision. OCT is well known for its exquisite spatial resolution; but until recently it has not had sufficient speed to overcome the inherent biological motion of the eye and capture the shape of the cornea. The development of Fourier-domain (FD) OCT technology has made the requisite speed possible...


The Invention of Optical Coherence Tomography


OCT Overview


Optical coherence tomography (OCT) is analogous to other range-finding techniques that use radio (RADAR), sound (SONAR), ultrasound and light waves. All these devices emit a wave toward the target object and detect the reflections. Delays of reflected waves provide information on the distance of the object from the device. Radio waves and ultrasound typically use pulsed radiations, permitting pulse delays to be measured directly with electronic timers. Because the velocity of light is very high (3 × 108 m/s), direct timing of optical pulses in optical time domain reflectometry (OTDR) can at best provide millimeter resolution. A variant of OTDR that uses femtosecond laser pulses and nonlinear cross-correlation detection can provide micrometer (μm) resolution, but is expensive and has relatively low detection sensitivity. Huang et al. incorporated transverse scanning and developed a cross-sectional imaging modality called OCT. In OCT (Fig. 1), the depths of sample reflections are measured indirectly by interference with a reference reflection. OCT provides both high detection sensitivity (photon shot-noise limited) and high resolution (higher than 10 μm). It is often implemented with fiber optics for ease of alignment, compactness, modularity, and stability. Fiber optic components are also relatively inexpensive, thanks to the high volume fiber optic communication industry.

Dr. David Huang, MD. PhD

The classic time domain OCT system is a Michelson interferometer. A fiber optic implementation is shown in Figure 1. The light source is usually a superluminescent diode (SLD) in the infrared. The SLD is compact, couples efficiently into a fiber, and has the requisite power and bandwidth for high sensitivity and resolution. The 50/50 fiber coupler splits the SLD input between the reference and sample arms. The reference and sample reflection are recombined at the coupler. The reference delay is scanned by moving the reference mirror or other device. The detector picks up a modulated interference signal when the reference delay coincides with the delay from a sample reflection. The interference signal is demodulated, digitized, and transferred to a computer for analysis and display. Each sample reflection produces a signal peak that is proportional to the strength of the reflection. The width of the peak is determined by the coherence length of the SLD light. The coherence length is inversely proportional to the spectral bandwidth of the SLD.

A recent development of OCT technique has shown that Fourier domain OCT (FDOCT) has a higher signal to noise ratio (~20dB higher) and imaging speed than time domain OCT. There are two approaches to FDOCT. The most common method is based on spectrometer, as shown in Figure 2. The light source and interferometer are similar to time domain OCT. But the detector is replaced by a spectrometer. Reference and sample arm light interfere in the fiber coupler, and the composite signal is dispersed by a spectrometer and detected by a line scan camera. With fast Fourier transform (FFT) of the interference spectrum collected by the camera, structure information can be obtained via the amplitude result. In FDOCT, mechanical scanning in the reference arm is not needed as it is in time domain OCT, and the sampling rate can be extremely fast.

The strength of OCT is its high resolution, which generally 10-100 times better than ultrasound, computed tomography, or MRI. The drawback is relative shallow penetration. Scattering quickly attenuates signal in turbid tissue, limiting the range to roughly 0.2 to 2.0 mm, depending on the tissue, wavelength and power used. Therefore OCT has been most important in the eye, where there is a transparent medium, and in situations where a probe could be used to deliver the imaging to the tissue of interest. OCT provides morphological information with near-histology resolution, which could, for example, measure internal retinal sublayers, identify the composition of atherosclerotic plaques, detect neoplasia and malignancy and identify brain structure.

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