Spectral domain OCT useful as research tool, clinical adjunct

Imaging devices that scan the retinal space have generated new histologic understanding of the back of the eye as well as of the structural consequences of several macular pathologies. Latest-generation scanning modalities employing spectral domain imaging are capable of faster and more detailed scans and have contributed to greater understanding of macular architecture.

Spectral domain optical coherence tomography captures tens of thousands of individual scans over a 6 mm × 6 mm × 2 mm area of the retina that are reassembled using a Fourier equation, which is why the modality is sometimes referred to as Fourier domain OCT. As with other OCT imaging devices, light is introduced and split, with half entering the eye and half sent to a reference mirror; the difference between the two beams, as measured by a spectrometer, yields depth and opacity measurements, which are translated into an image by computational interpretation.

Spectral domain OCT is differentiated from time domain OCT by a static reference mirror, which allows higher scanning speed and more images taken in a single pass. Clinical studies have speculated that spectral domain OCT improves image acquisition 25 to 100 times over time domain OCT. In other words, with equal light sources, spectral domain OCT and time domain OCT might produce similar quality images, but spectral domain OCT will image in seconds what time domain OCT would take longer to achieve.

To help improve image resolution, device manufacturers have also introduced light sources with wider bandwidths on spectral domain machines that effectively increase both axial and transverse resolution. Advanced software produces histopathological pictures of the back of the eye that were previously thought impossible to view. These advances, along with the quicker scanning speeds, are moving imaging closer to obtaining a functional biopsy of the human eye in situ.

Carmen A. Puliafito, MD, MBA, dean of the Keck School of Medicine of the University of Southern California, co-invented the technology for OCT. Image: Milici D

“With the segmentation algorithms and the data set that we have, we can have a much more detailed view of the pigment epithelium, of the internal limiting membrane, the retinal thickness map,” Carmen A. Puliafito, MD, MBA, OSN Retina/Vitreous Section Editor, said in a presentation at Hawaiian Eye 2009. “It shows what’s going on in the macula in a very dramatic way.”

Improvements in imaging

The improvement in imaging functionality with spectral domain OCT produces clearer pictures that penetrate deeper into the retinal architecture than time domain OCT. The addition of segmentation algorithms and 3-D imaging in some devices allows output images that show not only the whole picture of the back of the eye, but also detailed assessment of each part of the imaged retina.

Spectral domain OCT may also deliver a more accurate measurement of macular thickness. A study by Kakinoki et al reported that macular thickness was up to 60 µm thicker when measured with spectral domain OCT compared with time domain OCT.

The greater accuracy with spectral domain OCT has also been seen in the measurement of foveal thickness. In the October issue of American Journal of Ophthalmology, Amod Gupta, MD, said that studies by Leung et al and Forooghian et al show that spectral domain OCT consistently measures a thicker fovea than time domain OCT.

According to Dr. Gupta, this difference may be explained by the orientation of the scans: Time domain technology produces an image of the fovea by six-linear scan lines through the foveal center, but spectral domain technology measures retinal thickness by an evenly distributed square with the fovea near the center.

Another reason may be because spectral domain OCT gathers a reading from the retinal pigment epithelium through the internal limiting membrane, whereas time domain OCT only measures from the inner/outer segment junction to the internal limiting membrane – a penetration difference of around 45 µm.

Although the clinical implications of macular and foveal thickness remain uncertain, the deeper penetration into ocular tissue with spectral domain OCT has direct clinical utility. One such application might be in capturing macular hemorrhaging. While time domain OCT would also theoretically show fluid and blood on the macula, it would not be able to depict with the same accuracy at what retinal layer the buildup occurs.

According to Dr. Puliafito, the more precise measurements with spectral domain OCT might be particularly useful in managing diabetic retinopathy, especially in its proliferative form, and assist in clinical decision making.

“We can evaluate underlying pathology and monitor disease response, retinal thickness, cystoid macular edema, vitreoretinal traction and track subretinal fluid,” he said.

Spectral domain OCT is being used more often to visualize tractional retinal detachment in proliferative diabetic retinopathy, Dr. Puliafito said. Each vitreomacular traction detachment is unique, and the segmented images and precise registration with spectral domain OCT allow a picture of not only the retinal detachment, but also exactly where it is occurring.

The capabilities of spectral domain technology may make it a useful tool for postoperative evaluation as well. Segmentation can show if and where the retinal layers are reattaching, and because of point-to-point registration, reattachment can be tracked over time over the course of multiple visits. Spectral domain OCT is also capable of imaging through silicone oil.

“The level of precision for clinical decision making is better” than what is possible with time domain OCT, Dr. Puliafito said. “Spectral domain OCT offers a quantitative way of looking at clinically significant macular edema, to identify its geography specifically in a comprehensive way and to monitor the results of treatment.”

Faster scanning, more sensitivity

If there is a drawback of spectral domain OCT, it is that the image is not centered exactly over the fovea, and so it is actually less sensitive to discrete foveal pathology than time domain OCT. However, that deficiency is compensated for by capturing images of a larger section of the retinal space.

“As retinal specialists, we know that what is going on in the fovea is important for visual acuity, but everything else in that 6 mm × 6 mm area is quite relevant,” Dr. Puliafito said.

Spectral domain OCT captures a picture of a larger space because it scans at a faster speed, capturing tens of thousands of images in seconds over a larger surface area than time domain OCT. And there are distinct advantages to that increased speed. For instance, because spectral domain OCT takes multiple pictures of the same spot, the software in the device can average out the resulting image.

Peter K. Kaiser

“If you have multiple cuts through the same spot, anything that is noise can be eliminated, and that makes the image look better,” Peter K. Kaiser, MD, OSN Retina/Vitreous Board Member, said.

Time domain OCT could, theoretically, capture an image the same size as spectral domain OCT, but it would take longer to capture an inferior image and patients would have to remain still for a longer amount of time. From a practice management perspective, scanning the peripheral retina with time domain OCT could cause a bottleneck of patients.

From a clinical perspective, faster and more thorough imaging of the eye means less information is interpolated, and therefore, results are less variable. A better light source allows spectral domain OCT to image the vitreous, for instance, and display anatomy down to a histopathological level. This is an important consideration given the increased awareness of the role of a healthy inner segment/outer segment junction and photoreceptor cells in visual recovery after intervention for epiretinal membrane, macular edema and other retinal-detaching pathologies.

“We are able to get a better view of areas of the retina that we could not see before that are important to determine vision,” Dr. Kaiser said.

Spectral domain OCT is not only faster, but it is also more accurate. Dr. Kaiser said that a study at his institution showed “in a relatively large number of patients, spectral domain picked up leakage that was not present on time domain, and so those patients needed anti-VEGF therapy that we would not have given with time domain,” Dr. Kaiser said. “In other words, fluid was there, but we could not see it with time domain.”

Role in AMD

Clinical trials looking at OCT-guided therapy have challenged popular notions about the optimal anti-VEGF treatment regimen in AMD. In particular, the PrONTO (Prospective OCT imaging of patients with neovascular AMD treated with intraocular ranibizumab) trial introduced a variable treatment paradigm that originated from a suggested sustained effect of treatment that was observed in phase 3 and phase 3 extension trials.

In the PrONTO trial, patients were given a 3-month run-in with Lucentis (ranibizumab, Genentech). Re-treatment was offered only if certain criteria were met, including several factors based on OCT findings. At the end of 2 years, visual acuity gains were similar to those observed in the drug’s phase 3 ANCHOR (Anti-VEGF antibody for the treatment of predominantly classic choroidal neovascularization in AMD) and MARINA (Minimally classic/occult trial of the anti-VEGF antibody ranibizumab in the treatment of neovascular AMD) trials, but with fewer injections: about five per year compared with the typical 12 that would be performed with monthly dosing.

Srinivas R. Sadda

“It would be one thing if the treatment was relatively trivial for the patient to endure, for example, if it was just an eye drop to be instilled once a day,” Srinivas R. Sadda, MD, said. “But to have to come into the office, have your family take time off to bring you in, have to endure an injection and bear the potential risks of the injection — that is a significant burden.”

The incorporation of spectral domain OCT into clinical practice proffers to improve decision-making ability in AMD patients. Spectral domain OCT, because it more densely samples the macula, will be more likely to image fluid in its nascent stages, meaning treatment can be introduced early and before it causes limitations to vision.

According to Dr. Sadda, currently available spectral domain machines provide so much data that clinicians may be overloaded with information. The segmentation algorithms for AMD are not as advanced as they are for pathologies such as diabetic macular edema, he said, so relying exclusively on the automated OCT measurements may not be advisable.

Still, the abundance of data may be a good problem to have. According to a study he performed at his institution, Dr. Sadda said that spectral domain OCT was more sensitive than time domain OCT for identifying factors that would drive re-treatment with anti-VEGF therapy.

“Spectral domain would have changed our management decision at least 10% of the time,” Dr. Sadda said.

Structural analysis

The clearer pictures and faster scans possible with spectral domain OCT make the device a valuable research tool, and in fact, the laboratory is where spectral domain OCT first proved useful. Over time, however, the technology has been adopted into clinical practice.

“It has become integral to clinical practice because it gives us a quantitative, reproducible cross-section of macular pathology that is essentially unattainable with other ancillary tests,” Jay S. Duker, MD, OSN Retina/Vitreous Board Member, said.

For example, spectral domain OCT has proven particularly useful in delineating fine vitreous structures and defining the pathogenesis of macular hole, he said.

Research is under way on the next generation of imaging technology. Dr. Duker said that his lab will soon receive a prototype ultrahigh-resolution machine capable of resolution of 1 µm and 100,000 scans per second; by comparison, most spectral domain machines produce images at around 4 µm and take around 25,000 to 40,000 scans per second. The clinical and research applications of next-generation OCT is still uncertain, but these kinds of devices may be capable of imaging individual photoreceptor cells on the surface of the retina.

Through media opacities

Back of the eye research with spectral domain OCT will continue to be important as investigators attempt to close the gap on structure-function incongruence in pathologies that alter the physical structure of the macula.

“For the diseases in the macula that we are using [spectral domain OCT] for now, like diabetic macular edema and age-related macular degeneration, we still have a lot to learn about following these patients with OCT,” Dr. Duker said.

Another potential application of spectral domain OCT is in following macular changes in patients with uveitis. A recent study showed that spectral domain technology was superior to time domain technology in imaging through vitreous haze secondary to uveitis.

According to Dr. Gupta, a co-investigator in the study, spectral domain OCT identified three patients with epiretinal membrane that time domain OCT missed, and so vitreous surgery was initiated. Likewise, spectral domain OCT also identified epiretinal membrane in a patient who was thought to have only macular edema after a time domain scan.

In the study, spectral domain OCT also proved useful in mitigating risk: Spectral domain images showed no macular edema in some cases that would be considered edema suspects after time domain OCT was incapable of producing a viable image.

“Time domain images could be interpreted only in media grade 1, ie, clear media. Even minimal haze such as in grade 2 prevented acquisition of any interpretable images,” Dr. Gupta said.

Compared with time domain OCT, spectral domain OCT “samples across a defect or opacity with approximately 13 times more number of scans, and thus, any opacity would have much less impact on the quality of image,” he said.

“Current high-definition OCTs provide useful information on the impact of inflammation on the macula that includes cystoid macular edema, epiretinal membrane or the subretinal neovascular membrane, each of which requires different treatment strategy. Further, OCT may show irreversible pathology such as foveal atrophy,” he said.

Imaging through inflammation secondary to uveitis may be critical not only in delivering interventions in cases that otherwise might be missed, but also in lowering exposure to risk from unnecessary steroid injections. – by Bryan Bechtel

How much importance do you put on spectral domain OCT findings in comparison to other diagnostic modalities and clinical findings?

References:

• Brown DM, Regillo CD. Anti-VEGF agents in the treatment of neovascular age-related macular degeneration: Applying clinical trial results to the treatment of everyday patients. Am J Ophthalmol. 2007;144(4):627-637.
• Forooghian F, Cukras C, Meyerle CB, Chew EY, Wong WT. Evaluation of time domain and spectral domain optical coherence tomography in the measurement of diabetic macular edema. Invest Ophthalmol Vis Sci. 2008;49(10):4290-4296.
• Fung AE, Lalawani GA, Rosenfeld PJ, et al. An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration. Am J Ophthalmol. 2007;143(4):566-583.
• Gupta V, Gupta P, Singh R, Dogra MR, Gupta A. Spectral-domain Cirrus high-definition optical coherence tomography is better than time-domain stratus optical coherence tomography for evaluation of macular pathologic features in uveitis. Am J Ophthalmol. 2008;145(6):1018-1022.
• Kakinoki M, Sawada O, Sawada T, Kawamura H, Ohji M. Comparison of macular thickness between Cirrus HD-OCT and Stratus OCT. Ophthalmic Surg Lasers Imaging. 2009;40(2):135-140.
• Leung CK, Cheung CY, Weinreb RN, et al. Comparison of macular thickness measurements between time domain and spectral domain optical coherence tomography. Invest Ophthalmol Vis Sci. 2008;49(11):4893-4897.
• Puliafito CA. A brief history of optical coherence tomography: a personal perspective. Ophthalmic Surg Lasers Imaging. 2009;40(2):94-95.
• Roesel M, Henschel A, Heinz C, Spital G, Heiligenhaus A. Time-domain and spectral-domain optical coherence tomography in uveitic macular edema. Am J Ophthalmol. 2008;146(4):626-627; author reply 627-628.

• Jay S. Duker, MD, can be reached at New England Eye Center, 800 Washington St., Box 450, Boston, MA 02111-1533; 617-636-4604; fax: 617-636-4866; e-mail: jduker@tuftsmedicalcenter.org.
• Amod Gupta, MD, can be reached at Department of Ophthalmology, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh, India 160012; e-mail: eyepgi@sify.com.
• Peter K. Kaiser, MD, can be reached at Cole Eye Institute, Division of Ophthalmology, A31, 9500 Euclid Ave., Cleveland, OH 44195; 216-444-6702; e-mail: pkkaiser@aol.com.
• Carmen A. Puliafito, MD, MBA, can be reached at Office of the Dean, Keck School of Medicine, University of Southern California, 1975 Zonal Ave., KAM 500, Los Angeles, CA 90033; 323-442-1900; e-mail: cpuliafito@usc.edu.
• Srinivas R. Sadda, MD, can be reached at Keck School of Medicine, University of Southern California, 10 Congress St., Pasadena, CA 91105; 626-395-0777; e-mail: sadda@usc.edu.