February 2010, Issue 38

Spectral-Domain Optical Coherence Tomography: Comparing Commercially Available Systems for Managing Patients with Age-Related Macular Degeneration

Daniel F. Kiernan, MD
Vitreoretinal Fellow, Illinois Eye and Ear Infirmary, University of Illinois at Chicago,
Department of Ophthalmology & Visual Sciences, Chicago, IL.

Seenu M. Hariprasad, MD
Associate Professor and Director of Clinical Research; Chief, Vitreoretinal
Service The University of Chicago, Department of Surgery, Section of
Ophthalmology and Visual Sciences, Chicago, IL.

Optical coherence tomography (OCT) was introduced in 1991 and made possible the quantitative measurement of retinal thickness. In 2002, time-domain OCT 3000 (Stratus OCT, Carl Zeiss Meditec) became available with an axial resolution of 10 µm and a scan velocity of 400 axial scans per second. Although time-domain OCT is currently the most widely used system for posterior segment retinal tomography, higher resolution spectral-domain (SD) OCT has entered clinical practice since 2004 and is increasingly employed in the diagnosis and management of age-related macular degeneration (AMD). SD OCT technology uses low coherence interferometry to detect light echoes, relying on a spectrometer and high-speed camera and based on the mathematical formula of Fourier transformation. As the physics behind this technology is non-proprietary, unlike time-domain OCT, there are currently several different posterior segment SD OCT systems commercially available. This article provides a brief review of several SD OCT systems and how they may assist with the management of patients with AMD.

Cirrus HD-OCT
Cirrus OCT (Carl Zeiss Meditec, Dublin, CA) is a SD OCT platform that has a 5 µm axial resolution and scans at 27,000 A-scans per second. The current software for Cirrus allows side-by-side viewing and macular change analysis over several consecutive examinations to highlight changes, for example, after an intravitreal injection of an anti-vascular endothelial growth factor agent. The current software also includes a unique pigmented epithelial detachment mapping program for following up patients with large deposits of drusen.¹ Cirrus OCT is also polarization-sensitive and has been used to identify and characterize typical retinal pigment epithelial (RPE) findings in patients with AMD. In one study, investigators were able to identify functional RPE within disciform scars; these investigators concluded that identifying the status of RPE might help estimate the functional prognosis of patients with AMD, and determine whether further treatment has the potential to benefit either visual or anatomic outcomes.² Figure 1 demonstrates comparison of time domain Stratus (left) to spectral domain Cirrus (right) in a patient with exudative AMD. Although the raw scan correctly detects a choroidal neovascularization (CNV)-associated pigment epithelial detachment (PED), a software algorithm processing error falsely flattens the image on the Stratus, whereas both the Cirrus vertical and horizontal scans clearly demonstrate the PED.

Figure 1

Spectralis
Spectralis (Heidelberg Engineering, Vista, CA) combines a scanning laser ophthalmoscope (SLO) with OCT to produce tracking laser tomography that has a 7 µm axial resolution and scans at 40,000 A-scans per second. One beam constantly images and tracks the fundus and acts as a reference, guiding the second beam of light to position the cross-sectional OCT scan precisely. This real-time eye tracking enables a highly repeatable alignment of OCT and fundus images. One group reported that choroidal thickness can be measured using Spectralis OCT with enhanced depth imaging by positioning the device close enough to the eye to acquire an inverted image within a 5-30 degree area centered at the fovea and then performing manual measurements from the outer border of the RPE to the inner scleral border.³ In separate reports using the same technique, these investigators also reported enhanced depth imaging of choroidal changes underneath a PED in patients with exudative AMD, and described a novel disease entity termed age-related chorioretinal atrophy.^4,5 Figure 2 demonstrates a false-color 3-dimensional volume cube scan of a PED resulting from CNV between black-and-white fluorescein angiogram images, (top) and a cross-sectional slice of a PED resulting from CNV in another patient with neovascular AMD (bottom).

Figure 2

3D-OCT 1000
3D-OCT 1000 (TOPCON, Paramus, NJ) has a 6 µm axial resolution and scans at 18,000 A-scans per second. Posterior segment acquisition options include a 6 by 6 mm, 4.5 by 4.5 mm or 3 by 3 mm volume cube scans, as well as a 3D rendering mode. 3D-OCT 1000 has been shown to be useful for diagnosing and following patients with AMD-associated CNV.⁶ Another group demonstrated that reproducibility of macular thickness measurements using this system was significantly better in patients with dry AMD compared to patients with exudative AMD (3.7 ±1.4% for exudative AMD and 1.8 ±0.6% for dry AMD).⁷

Spectral OCT/SLO
Similar to the Spectralis, the Spectral OCT/SLO (OPKO/OTI, Miami, FL) is a combination OCT and confocal SLO designed to image vitreous, retinal and choroidal structures for accurate, point-to-point registration and orientation. It has a 5 µm axial resolution and scans at 27,000 A-scans per second. The tomography map is produced from a sequence of B-scans and the macular analysis is viewed as 5 by 5 or 8 by 8 cubed grids over 6 by 6 mm. Retinal maps can be viewed as a 3D volume cube, and sectional cuts can be extracted to identify structures and pathology below the retinal surface. Using this device, one group found a significantly higher incidence of incomplete posterior vitreous detachment in eyes with exudative AMD compared to a control group. They also described a higher incidence of tractional configuration of the attached posterior hyaloid in eyes with exudative AMD, which they hypothesized may contribute toward persistence of subretinal fluid despite monthly intravitreal bevacizumab or ranibizumab therapy. Four of 5 patients in this study who underwent pars plana vitrectomy experienced an improvement in visual acuity which was of borderline significance (p=0.052).⁸

Bioptigen SDOCT
The Bioptigen SD OCT (Bioptigen, Durham, NC) system uses high-throughput spectral interferometry to produce real time images of ocular tissue microstructure with 4 µm axial resolution to scan at 20,000 A-scans per second. For adult and pediatric patients, up to a 10 x 10 mm retinal area of each eye can be acquired in a few seconds. Toth and associates reported segmentation and categorization of drusen in eyes with AMD, concluding that their software analysis of high-resolution images may reduce the time and resources necessary for conducting a large-scale study of dry AMD in the future.⁹ In a subsequent report, they characterized photoreceptor thinning over drusen in patients with dry AMD, suggesting that there is a measurable degeneration of photoreceptors leading to visual loss over time in these patients compared to age-matched controls.¹⁰

SOCT Copernicus
The SOCT Copernicus (Optopol, Zawiercie, Poland) has a 6 µm axial resolution and scans at 25,000 A-scans per second. It has a 10 mm B-scan width and allows single or customizable 6 line radial scans, as well as 3D volume cube rendering. The device incorporates a retinal tracking system, and posterior segment analysis includes retinal thickness and RPE mapping, 3D cross section animation software, and optic nerve head imaging. A unique aspect of the software is 'cyst analysis', which provides intraretinal cyst volume measurement, comparable from session to session. In a prospective study comparing observer rates of CNV detection using Copernicus, three other SD OCT devices and Stratus OCT in sixty-one eyes with exudative AMD after ranibizumab treatment, all SD OCT devices were associated with higher detection rates compared to Stratus OCT. Furthermore, SD OCT 3D cube scans were associated with higher detection rates than individual linear scans for each device.¹¹

Discussion
OCT has become a valuable tool for ophthalmologic clinical and surgical decision making. However, the variety of systems available, as well as different scanning patterns for each, makes comparison of data problematic. For the majority of clinical applications, for example, assessing for the presence of macular edema due to CNV, we have found that the macular cube, radial or raster pattern scan of each device is sufficient for efficient and definitive diagnosis. However, we recommend using higher resolution scanning when available, since in our experience, it can help detect smaller, more subtle areas of intra- or subretinal fluid which may influence treatment decision-making. We reported previously that in patients with macular pathology, there are no clinically significant differences in retinal thickness measurements between Cirrus SD OCT 512 by 128 and 200 by 200 macular cube scans.¹² When comparing one SD OCT device to another SD OCT or time domain Stratus OCT, we recommend using the same scanning pattern for each device which may allow relative comparison among patients scanned on different machines at different time points, although machine-to-machine comparison of quantitative macular thickness measurements is not practical due to a difference in outer boundary reference points of each device.

REFERENCES

1. Kiernan DF, Hariprasad SM, Mieler WF. Spectral Domain OCT: A Comparison of Modern High Resolution Retinal Imaging Systems. Am J Ophthalmology. 2010;149(1): 18-31.
2. Ahlers C, Goetzinger E, Pircher M, et al. Imaging of the retinal pigment epithelium in age-related macular degeneration using polarization sensitive optical coherence tomography. Invest Ophthalmol Vis Sci. 2009 Sep 24. [Epub ahead of print]
3. Margolis R, Spaide RF. A pilot study of enhanced depth imaging optical coherence tomography of the choroid in normal eyes. Am J Ophthalmol. 2009;147(5):811-5.
4. Spaide RF. Enhanced depth imaging optical coherence tomography of retinal pigment epithelial detachment in age-related macular degeneration. Am J Ophthalmol. 2009;147(4):644-52.
5. Spaide RF. Age-related choroidal atrophy. Am J Ophthalmol. 2009;147(5):801-10.
6. Menke MN, Dabov S, Sturm V. Features of age-related macular degeneration assessed with three-dimensional Fourier-domain optical coherence tomography. Br J Ophthalmol. 2008;92(11):1492-7.
7. Menke MN, Dabov S, Knecht P, et al. Reproducibility of retinal thickness measurements in patients with age-related macular degeneration using 3D Fourier-domain optical coherence tomography (OCT) (Topcon 3D-OCT 1000). Acta Ophthalmol. 2009 Dec 21. [Epub ahead of print]
8. Mojana F, Cheng L, Bartsch DU, et al. The role of abnormal vitreomacular adhesion in age-related macular degeneration: spectral optical coherence tomography and surgical results. Am J Ophthalmol. 2008;146(2):218-227.
9. Toth CA, et al. IOVS 2008;49:ARVO E-Abstract 5394.
10. Schuman SG, Koreishi AF, Farsiu S, et al. Photoreceptor layer thinning over drusen in eyes with age-related macular degeneration imaged in vivo with spectral-domain optical coherence tomography. Ophthalmology. 2009;116(3):488-496.e2.
11. Sayanagi K, Sharma S, Yamamoto T, Kaiser PK. Comparison of spectral-domain versus time-domain optical coherence tomography in management of age-related macular degeneration with ranibizumab. Ophthalmology. 2009;116(5):947-55.
12. Kiernan DF, Hariprasad SM, Chin EK, et al. Prospective comparison of cirrus and stratus optical coherence tomography for quantifying retinal thickness. Am J Ophthalmol. 2009;147(2):267-275.e2.