# OCT and OCT Angiography in Retinal Disease
## Optical Coherence Tomography (OCT)
### Principles
Optical coherence tomography is a non-invasive imaging modality that provides cross-sectional images of retinal microstructure with remarkable resolution. It uses the principle of low-coherence interferometry, measuring the echo time delay of reflected light to construct depth-resolved images. The concept is analogous to ultrasound, but because light travels much faster than sound and has a much shorter wavelength, OCT achieves axial resolution of 5 to 7 micrometers -- far superior to any ultrasound-based technique. The light source operates in the near-infrared range, at approximately 840 nm for spectral-domain OCT and approximately 1050 nm for swept-source OCT.
### Evolution of OCT Technology
OCT technology has evolved through several generations. Time-domain OCT (TD-OCT) was the first generation, using a single mechanically scanning reference mirror to acquire approximately 400 A-scans per second with 10 micrometer resolution. It is now largely obsolete. Spectral-domain OCT (SD-OCT) is the current clinical standard and uses a spectrometer-based detection system that captures all echo time delays simultaneously, achieving 20,000 to more than 100,000 A-scans per second with 5 to 7 micrometer axial resolution. Swept-source OCT (SS-OCT) employs a tunable laser at approximately 1050 nm, offering even faster scan speeds of 100,000 to 400,000 A-scans per second, deeper tissue penetration for superior choroidal imaging, and less signal drop-off with imaging depth. Enhanced depth imaging OCT (EDI-OCT) is a modified SD-OCT acquisition protocol that positions the choroid closer to the zero delay line, optimizing choroidal visualization without requiring a different instrument.
| OCT Generation | Wavelength | Scan Speed | Axial Resolution | Key Advantage |
|---|---|---|---|---|
| Time-domain (TD-OCT) | ~840 nm | ~400 A-scans/sec | ~10 um | Historical; now obsolete |
| Spectral-domain (SD-OCT) | ~840 nm | 20,000-100,000 A-scans/sec | 5-7 um | Current clinical standard |
| Swept-source (SS-OCT) | ~1050 nm | 100,000-400,000 A-scans/sec | 5-7 um | Superior choroidal imaging; deeper penetration |
| EDI-OCT | ~840 nm | Same as SD-OCT | 5-7 um | Optimized choroidal visualization (protocol modification) |
### Normal OCT Anatomy (Hyperreflective Bands)
On a normal OCT B-scan, several hyperreflective bands can be identified from innermost to outermost: the nerve fiber layer, the ganglion cell layer combined with the inner plexiform layer, the outer plexiform layer (which includes the Henle fiber layer at the macula), the external limiting membrane, the ellipsoid zone (formerly known as the inner segment/outer segment junction, and the strongest biomarker for photoreceptor integrity), the interdigitation zone (representing the interdigitation of cone outer segments with RPE apical processes), and the RPE/Bruch membrane complex.
### Key OCT Measurements
Several quantitative OCT measurements are central to clinical practice. The central subfield thickness is the average retinal thickness within the central 1 mm ETDRS circle and serves as the key metric for monitoring macular edema. Retinal nerve fiber layer thickness, measured peripapillary, is the primary structural parameter for glaucoma diagnosis and monitoring. The ganglion cell complex, measuring the macular ganglion cell layer combined with the inner plexiform layer, enables early detection of glaucomatous damage before visual field loss is apparent. Choroidal thickness, measured subfoveally on EDI-OCT, is increased in central serous chorioretinopathy and polypoidal choroidal vasculopathy (pachychoroid spectrum) and decreased in pathologic myopia.
Normal SD-OCT B-scan through the fovea with labeled hyperreflective and hyporeflective bands corresponding to the retinal layers: NFL, GCL, IPL, INL, OPL, ONL, ELM, ellipsoid zone, interdigitation zone, and RPE-Bruch complex
## OCT in Specific Diseases
### Age-Related Macular Degeneration
In dry AMD, drusen appear on OCT as elevations of the RPE with medium reflectivity material accumulating between the RPE and Bruch membrane. Geographic atrophy manifests as loss of the RPE band, disruption of the ellipsoid zone, and photoreceptor loss, with an increased choroidal signal beneath the atrophic area due to the transmission effect from absent RPE. In neovascular AMD, OCT reveals subretinal fluid, intraretinal fluid, sub-RPE fluid, pigment epithelial detachments, and hyperreflective material representing the CNV complex. Resolution of fluid on OCT is the primary metric for monitoring treatment response to anti-VEGF therapy.
### Diabetic Macular Edema
OCT findings in diabetic macular edema include retinal thickening, intraretinal cystoid spaces, and subretinal fluid. Hyperreflective foci, which may represent lipoprotein exudates or activated microglia, correlate with intraretinal inflammation. Disruption of the ellipsoid zone predicts a poor visual outcome regardless of anatomical response to treatment. Assessment of the vitreomacular interface is also important, as a taut posterior hyaloid face can contribute to and perpetuate macular edema.
### Glaucoma
In glaucoma, OCT demonstrates RNFL thinning that is typically sectoral or diffuse, occurring first in the superotemporal and inferotemporal sectors -- the regions corresponding to the arcuate scotomas seen on visual field testing. Thinning of the macular ganglion cell layer and inner plexiform layer can be detected before perimetric changes appear. Serial measurements enable guided progression analysis, tracking structural change over time. An important limitation is the floor effect: RNFL thickness cannot decrease below approximately 40 to 50 micrometers, as the residual tissue at that level represents non-neural elements such as blood vessels and glial tissue.
### Central Serous Chorioretinopathy
OCT in central serous chorioretinopathy reveals subretinal fluid producing a dome-shaped neurosensory detachment, focal pigment epithelial detachments, and increased subfoveal choroidal thickness characteristic of the pachychoroid phenotype. In chronic CSC, additional findings include RPE irregularity, outer retinal atrophy, and subretinal deposits.
### Vitreomacular Interface Disorders
OCT is the definitive tool for characterizing vitreomacular interface pathology. Vitreomacular adhesion shows vitreous attachment to the macula without retinal distortion. Vitreomacular traction demonstrates vitreous attachment causing visible macular distortion with elevation and cyst formation. Full-thickness macular holes appear as complete defects through the neurosensory retina, with the minimum diameter measured for classification and prognostication. Epiretinal membranes present as a hyperreflective line on the inner retinal surface associated with underlying retinal wrinkling.
## OCT Angiography (OCTA)
### Principles
OCT angiography provides non-invasive vascular imaging of the retina and choroid without the need for dye injection. The technique works by comparing sequential OCT B-scans acquired at the same retinal location in rapid succession. Decorrelation algorithms detect the motion of red blood cells, distinguishing flowing blood (which produces signal variation between scans) from static tissue (which remains unchanged). The resulting data are used to generate en face and cross-sectional flow images at different retinal depths.
### Segmentation Layers
OCTA images are segmented into four principal vascular layers. The superficial capillary plexus spans from the nerve fiber layer to the inner plexiform layer. The deep capillary plexus extends from the inner plexiform layer to the outer plexiform layer. The outer retina is normally avascular, so any flow signal detected in this layer indicates pathology such as choroidal neovascularization. The choriocapillaris is imaged at and below the level of the RPE-Bruch membrane complex.
### Advantages Over Traditional Angiography
OCTA offers several advantages over fluorescein and indocyanine green angiography. It requires no dye injection, eliminating the risk of allergic reactions and the need for intravenous access. Acquisition is rapid, taking approximately 10 seconds. It provides depth-resolved vascular information that is impossible to obtain from traditional en face angiography. It is readily repeatable at every visit for longitudinal monitoring and can image both retinal and choroidal vasculature simultaneously.
### Limitations
OCTA has important limitations that must be understood for proper clinical use. The field of view is relatively small, typically 3x3 mm to 12x12 mm, though ultra-widefield OCTA is emerging. Motion artifacts require adequate patient fixation and cooperation. Projection artifacts create shadows of superficial vessels on deeper layer images. Critically, OCTA cannot assess vascular leakage, as it detects only flow and not permeability -- this means it cannot replace fluorescein angiography for applications where leakage assessment is important. Automated segmentation frequently produces errors, particularly in eyes with distorted anatomy from edema, neovascularization, or other structural pathology. Flow below the detection threshold of the instrument may be missed entirely.
OCTA en face images of the superficial capillary plexus, deep capillary plexus, outer retina, and choriocapillaris in a normal eye demonstrating the depth-resolved vascular architecture without dye injection
## OCTA in Clinical Applications
### Diabetic Retinopathy
In diabetic retinopathy, OCTA enables quantification of foveal avascular zone enlargement, which serves as a biomarker of macular ischemia. It can detect and map microaneurysms, identify and quantify areas of capillary non-perfusion with greater ease than fluorescein angiography, and detect neovascularization as flow signal above the internal limiting membrane. OCTA is also useful for monitoring treatment response over time.
### AMD
OCTA has high sensitivity for detecting choroidal neovascularization, visualized as a flow signal in the outer retina or sub-RPE space. It can characterize CNV morphology, helping distinguish Type 1, Type 2, and Type 3 lesions. OCTA is particularly valuable for detecting treatment-naive CNV and for monitoring subclinical CNV activity, which may allow clinicians to extend or initiate treatment intervals more precisely. An interesting phenomenon is non-exudative CNV -- flow detected without associated fluid -- whose optimal management remains controversial.
### Glaucoma
In glaucoma, OCTA demonstrates reduction in peripapillary capillary density that correlates with RNFL loss, and macular vessel density reduction in the superficial capillary plexus. These vascular changes may precede perimetric visual field loss, potentially enabling detection of pre-perimetric glaucoma. However, the clinical utility of OCTA in glaucoma management is still being established, and it remains primarily a research tool at present.
### Retinal Vein Occlusion
OCTA facilitates quantification of non-perfusion areas, assessment of FAZ morphology, documentation of collateral vessel formation, and monitoring for neovascularization in retinal vein occlusion.
## Emerging OCT Technologies
### AI-Enhanced OCT
Artificial intelligence, particularly deep learning algorithms, is being applied to OCT for automated layer segmentation, disease classification and severity grading, prediction of visual outcomes based on OCT biomarkers, and automated fluid detection and quantification.
### Widefield and Ultra-Widefield OCT
Widefield OCT systems are expanding the scan coverage to extend from the macula to the retinal periphery in a single acquisition, enabling assessment of peripheral retinal pathology and the vitreoretinal interface across a much broader area than conventional OCT.
### Adaptive Optics OCT
Adaptive optics technology corrects for optical aberrations in real time, achieving cellular-level resolution that enables visualization of individual photoreceptors and RPE cells. This technology remains primarily in the research domain and is not yet part of routine clinical practice.
OCTA comparison showing a normal foveal avascular zone versus enlarged FAZ in diabetic retinopathy with areas of capillary dropout, and a neovascular AMD case showing abnormal flow in the outer retinal slab indicating choroidal neovascularization
## Clinical Pearls
Ellipsoid zone integrity is the single best OCT biomarker for predicting visual potential in macular disease -- if it is intact, photoreceptor function is likely preserved regardless of other structural abnormalities. Segmentation lines on OCTA should always be verified manually, as automated segmentation frequently fails in eyes with significant pathology, producing misleading flow images. OCTA cannot replace fluorescein angiography for assessing leakage; the two modalities are complementary and each provides information the other cannot. Serial OCT thickness maps are indispensable for monitoring treatment response in diabetic macular edema and wet AMD. In glaucoma management, structural OCT data must be interpreted in conjunction with functional visual field data, as the structure-function correlation is critical for clinical decision-making. Choroidal thickness measured on EDI-OCT helps distinguish pachychoroid spectrum diseases such as central serous chorioretinopathy and polypoidal choroidal vasculopathy from typical AMD. OCTA has largely replaced fluorescein angiography for routine CNV detection in AMD, but FA and ICGA remain necessary for complex cases and for the diagnosis of PCV. Artifact recognition is an essential skill: projection artifacts, motion artifacts, and segmentation errors are common pitfalls that can lead to diagnostic misinterpretation.
## References
- Staurenghi G, et al. Proposed lexicon for anatomic landmarks in normal posterior segment spectral-domain OCT. Ophthalmology. 2014;121(8):1572-1578.
- Spaide RF, et al. Optical coherence tomography angiography. Prog Retin Eye Res. 2018;64:1-55.
- Kashani AH, et al. Optical coherence tomography angiography: a comprehensive review of current methods and clinical applications. Prog Retin Eye Res. 2017;60:66-100.
- American Academy of Ophthalmology. Basic and Clinical Science Course, Section 12: Retina and Vitreous.