Advances Help Clinicians Tap Greater Potential of SD-OCT

Experts discuss some of the latest SD-OCT innovations and the future of the technology.

DIANE DONOFRIO ANGELUCCI

As spectral domain optical coherence tomography (SD-OCT) technology advances, it has become increasingly essential to retina specialists, enabling them to quickly capture high-resolution 3-dimensional images to identify retinal disease, pinpoint its precise location, and monitor its progression.

Spectral-domain OCT has significantly better ability to detect pathology compared with time domain technology, says Jeffrey S. Heier, MD of Ophthalmic Consultants of Boston and codirector of the vitreoretinal fellowship at Ophthalmic Consultants of Boston/Tufts Medical School. Spectral-domain scans delineate layers of the retina that previous technology could not, he continues, which is especially helpful in patients with subtle pathology or unexplained subtle visual declines. SD-OCT scans may reveal very subtle retinal pigment epithelium defects and photoreceptor abnormalities that clinicians can monitor over time. Furthermore, he adds, SD-OCT scans have less noise than time domain scans, enabling clinicians to confidently identify fluid changes to help guide disease management.

"All SD-OCTs give you more data more quickly so you don't have to do as much interpolation," says Yale Fisher, MD, volunteer clinical professor of ophthalmology, Bascom Palmer Eye Institute, Miami, and volunteer clinical professor of ophthalmology, New York Presbyterian Hospital.

Given this wealth of data, manufacturers continue to develop software to help clinicians better tap into the potential of SD-OCT. Here experts discuss some recent SD-OCT advances and those anticipated in the future.

SPECTRAL OCT SLO COMBINATIONIMAGING SYSTEM

The Spectral OCT SLO Combination Imaging System (OPKO Health, Inc., Miami) performs a variety of scans while simultaneously producing a scanning laser ophthalmoscope (SLO) image for real-time registration. "It gives you perfect correspondence between the surface and cross-sectional anatomy, so you know exactly where the scan for the cross-section is taken," says Richard B. Rosen, MD, vice chairman and director of research, New York Eye and Ear Infirmary.

Clinicians can use blood vessels on the fundus image to align images, enabling them to obtain precise thickness maps incorporating a large number of cross-sections, Dr. Rosen says. Thickness maps can be rendered into 3-dimensional images, so that clinicians can scan through the retinal thickness map and view the OCT images beneath.

Thickness maps have a variety of configurations, Dr. Rosen says, corresponding to the ETDRS, showing critical target areas for treatment. "You can also overlay onto these thickness maps a whole system of microperimetry," he says. Using microperimetry, which is available as an add-on feature, the clinician can match a point of reduced sensitivity with OCT findings at the same point, for example.

In next-generation OCT advances, Dr. Rosen explains, the system will display letters for patients to read, correlating visual acuity with specific areas on the retina. He believes this will be especially useful for patients with severe vision loss. In patients with finger-counting or hand-motion vision, ophthalmologists often believe it is not worthwhile to treat the patient extensively, according to Dr. Rosen. "But oftentimes those patients have areas of the retina where they can still see letters and make out details, and so it may be useful for them to undergo a treatment to make use of that part of the retina." This software is under investigation, as is potential software for drusen analysis, he says.

Figure 1. Marked regression of non-AMD choroidal neovascularization in a 37-year-old patient (Spectralis HRA+OCT).

CIRRUS HD-OCT

Carl Zeiss Meditec is planning regular upgrades to the Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA). "The nice thing about these upgrades is that a lot of them will utilize the scanning information that has been obtained previously by the retina specialists," says Philip J. Rosenfeld, MD, PhD, professor of ophthalmology, Bascom Palmer Eye Institute. Therefore, clinicians will be able to incorporate earlier data sets into the new analytical packages so they can extract even more meaningful information from data they have already accumulated, and they also will be able to use current data sets. The next software update is expected by the second quarter of 2009.

Dr. Rosenfeld explains that the Cirrus HD-OCT currently allows clinicians to choose scanning patterns that will provide a macular thickness map with segmentation of the inner limiting membrane and segmentation of the retinal epithelial layer. The printout provides high-resolution horizontal and vertical scans to the foveal center.

The next software upgrade will enable clinicians to perform a macular change analysis. The algorithm will take the OCT fundus image and register sequential scans. "Once they're registered, so you know exactly the point you're looking at from date to date, it then gives you a difference in retinal thickness from those 2 dates, so you can look and see how quantitatively the pattern has changed in the macula," Dr. Rosenfeld says. This will be instrumental in assessing treatment response in patients with exudative diseases. "Plus, we can then look at individual B-scans and correlate the quantitative changes with the qualitative appearance to confirm that the fluid is going away or coming back…," he says. "This macular change analysis is going to be a very valuable tool for quickly looking at a patient, determining whether there is pathology that needs treatment, and then knowing exactly where to look." Furthermore, a new printout will allow retina specialists to have a representative hard copy of the entire macula so that abnormalities can be followed with a B-scan and retina thickness map at each point through the macula. This new printout samples the central macula with every other scan. The new software also will include a large macula normative database and allow anterior segment imaging as well.

"In the future, we will also be able to use these scans to quantify various aspects of dry macular degeneration too, such as geographic atrophy, drusen, and pigment epithelial detachments, but those features are not going to be available in the next reiteration of the software," Dr. Rosenfeld says.

SPECTRALIS OCT

Heidelberg Engineering (Vista, CA) recently announced 2 additions to its group of Spectralis devices — the 2-mode Spectralis OCT, combining confocal fundus imaging and SD-OCT, and the 5-mode Spectralis FA + OCT, which includes the features of the 2-mode unit, along with fluorescein angiography (FA) and autofluorescence.

The Spectralis FA + OCT allows the clinician to perform different functions at the same time, such as fluorescein angiography in conjunction with OCT or red-free or infrared images in conjunction with the OCT. "Auto-fluorescence is becoming more and more important to us as we look at dry macular degeneration," Dr. Heier says. He often obtains an autofluorescence and then a spectral domain scan through the same area. "We're picking up subtle changes in the RPE. We're picking up patterns of degeneration that may in the future help to be predictive of either disease progression or treatment response or other findings along those lines," Dr. Heier says.

Recent and upcoming Spectralis advances are focusing on retinal segmentation, system reports, and quantification software for autofluorescence images, Dr. Heier says. Major advances have been made in glaucoma analysis in measurements of retinal nerve fiber layer thickness and optic nerve changes, as well as in reproducibility.

All SD-OCT devices have different advantages, Dr. Heier says, but he believes the Spectralis OCT has superior image quality and outstanding eye tracking and reproducibility, which he says are important in monitoring patients from visit to visit.

The dual-scanning mode coupled with reference scanning, allows clinicians to be very confident of the pathology and subsequent progression or responses to treatment, he says. "You're able on 1 scan to ensure that you are focused on the region in question and on the other scan evaluate with high-resolution OCT abnormal findings or changes in anatomy."

BIOPTIGEN 3D SD-OCT

In addition to generating high-resolution, 3-dimensional images, Bioptigen 3D SD-OCT systems (Bioptigen, Inc., Research Triangle Park, NC) offer clinicians and researchers flexibility, with a selection of interchangeable imaging probes, such as clinical scanners, a microscopic addition for research, and handheld probes.

Hiroshi Ishikawa, MD, assistant professor, departments of Ophthalmology, Bioengineering, and Engineering, University of Pittsburgh Schools of Medicine and Engineering, and director, Ocular Imaging Center, UPMC Eye Center, recently licensed software to Bioptigen, which is expected to be available as standalone software at the end of the first quarter of 2009, and the integrated version should be available at the end of the second quarter. The software has 2 components — 1 focusing on visualization and the other on quantitative measurements.

"It sounds wonderful to have 3-dimensional data sets because the potential is huge," Dr. Ishikawa says. "The problem is how to fully utilize this 3-dimensional data because they are rich data, and without having the right way of analyzing them, either in the quantitative or qualitative way, it's really just scratching the surface and you don't get the true advantage of these 3-dimensional data." This motivated Dr. Ishikawa to develop a semiautomated image enhancement to generate C-mode scans using segmentation-free contour modeling.¹

"Most of the emphasis right now on the software side is going to segmentation," Dr. Ishikawa says. "I understand that and also the robustness of the segmentation algorithm — that's very important. But in most of the cases with pathology, the segmentation fails."

The spherical contour of the eye makes it difficult to interpret conventional C-mode images. These images contain several retinal layers in each slice, making it complicated to isolate and view a specific structure, particularly when disease is present. Therefore, Dr. Ishikawa developed a software program providing a semiautomated method of creating C-mode images, allowing the clinician to interact with the software, placing anchor points in a horizontal and a vertical scan to shape a slice to fit the contour of a specific structure.

In addition, the software's segmentation algorithm allows quantitative analysis with more detailed inner retinal layer segmentation, including the inner limiting membrane, nerve fiber layer, inner retinal complex (combination of ganglion cell layer and inner plexiform/nuclear layers), outer plexiform layer, and outer retinal complex (combination of outer nuclear layer, external limiting membrane, and inner/outer segments of photoreceptors).² "Everything is automated, so this automated segmentation software segments out the 5 different layers, reports the thickness, and actually generates a 2-dimensional color map with a false-color scheme," Dr. Ishikawa says.

3D OCT-1000

Topcon Medical Systems (Paramus, NJ) recently received approval from the FDA for its 3D OCT-1000 TrueMap Measurement Software, which enables clinicians to visualize the inner limiting membrane, the IS/OS junction, RPE, and Bruch's membrane.

On older time-domain machines, retinal thickness measurements were not as clear as they are with SD-OCT, Dr. Fisher says. Although it was believed measurements were from the inner limiting membrane to the RPE, the SD-OCT revealed there were 2 strong reflections from the area of the RPE. "The first one represented what we believed to be the IS/OS junction and the second strong reflection was felt to be the anterior portion of the RPE," he says. This presented a problem to clinicians with old time-domain maps. "Suddenly, all of your maps will be thicker on spectral domain than on time-domain or Stratus (Carl Zeiss Meditec), while in reality the discrepancy is created because different anatomical boundaries were measured," he says.

Figure 2. Normal retinal exam with overlying vitreous gel liquefaction and partial separation of posterior hyaloid face nasal to the fovea.

PHOTO COURTESY OF RICHARD B. ROSEN, MD

The new Topcon software allows clinicians to set their thickness measurements. The clinician may measure the thickness from the inner limiting membrane to RPE, as defined in the traditional histopathology, or measure the thickness from the inner limiting membrane to IS/OS junction, for consistency with the legacy time domain system. In addition, Topcon also provides a software utility called the StratusViewer. "If you get a new spectral domain machine from Topcon, you could feed all of your raw data from the Stratus directly into a Topcon machine," Dr. Fisher says. Stratus data are read in raw format for analysis, so the content remains the same for the conversion.

Figure 3. 3-D rendering of retinal topography with superimposed microperimetry threshold values in a case of central serous retinopathy. Image is sliced to reveal OCT cross-section showing focal macular detachment.

PHOTO COURTESY OF RICHARD B. ROSEN, MD

Future software is expected to allow clinicians to determine the volume, number, and area of drusen. "When we approach the next phase of trying to treat patients with dry macular degeneration as opposed to the wet form, we know that drusen usually will be evident prior to the development of more significant macular degeneration and not all macular degeneration is wet," Dr. Fisher says. "In fact, the vast majority is dry. If you wish to produce some drug or product that stops it or slows it, then you should be able to detect differences in the number of drusen, the area of drusen, or the volume of drusen. And that's hard to do with just color photographs."

RTVUE FD-OCT

The high resolution of the RTVue FD-OCT (Optovue, Fremont, CA), with a 5-μm depth and 15-μm transverse resolution, allows clinicians to evaluate a multitude of retinal disease states from very early stages, says Mark Fromer, MD, medical director of Fromer Eye Centers, New York. "Drusen and photoreceptors can be seen on the OCT, in addition to a well-defined choriocapillaris. One of the most significant changes is the ability to quantify full-thickness retinal changes over time." He explains that the new RTVue unit allows the clinician to evaluate RPE changes, and the SLO-like imagery allows visualization of geographic atrophy, which can be tracked over time.

The exquisite detail of the images, along with the quantitative and qualitative progression mapping of full-thickness retinal images and the RPE, will allow retinal specialists to tailor treatment protocols to responses they can follow quantitatively, Dr. Fromer says. "The ability to quantitatively assess a variety of retinal disease processes while qualitatively assessing the topographic images will allow retinal specialists to make more accurate judgments and clearly improve our decision-making process in the diagnosis and management of retinal disorders."

In addition, he says, alignment algorithms are the key to the progression analysis, and the 3-dimensional video analysis, which can be freeze-framed, is useful for analysis, for patient education, and as a teaching tool.

Dr. Fromer believes it would be useful to use the available volumetric analysis to quantify lesion regression with various treatment regimens. Drusen detection, quantification, and tracking software are being analyzed and should be available in the near future.

SP-OCT HR

Canon Medical Systems (Irvine, CA) expects to receive FDA approval in 2009 for the SP-OCT HR, which the company describes as having superior high resolution, an ultrahigh scanning speed, and improved patient and operator comfort.

"The SP-OCT HR technology allows us to see structural integrity — or lack of — of a specific part of the eye that supports vision," says Ben Szirth, PhD, director, Tele-Ophthalmology Program, Institute of Ophthalmology and Visual Science, New Jersey Medical School, Newark. "We can even see earlier damage to structures that could lead to vision loss." He explains that the system will allow clinicians to view very high resolution single images as they progress deeper into the ocular structure, enabling them to detect disease in very early stages and assess the success or failure of treatments without needing to rely on other imaging techniques such as fluorescein angiography.

"I can imagine as technology progresses towards higher definition/resolving optical systems as well as software-assisted enhancement programs, SP-OCT HR will yield even finer details that will lead to even greater vision-saving tools," Dr. Szirth says.

IMPLEMENTING SPECTRAL DOMAIN TECHNOLOGY

Dr. Heier says it is worthwhile to switch from time domain OCT to SD-OCT, given the advantages in recognizing disease. However, he says, clinicians participating in clinical trials still need the Stratus at this point, which is standardized for clinical trials. OCT reading centers are actively working to standardize the various SD-OCTs to allow their use in clinical trials.

"There are a lot of features that you can utilize to really appreciate how well the patient is doing and of course the expectations in practice nowadays are much higher because we have all of these new treatments," Dr. Rosen says. "The patient expects to see well. They're not even happy with 20/25 or 20/30. They want to be right on the mark, so being able to get closer to meeting those expectations is something we all aspire to, and the ability to monitor these things gives us a better handle on what's really happening. We're not always successful, but understanding what's happening, you can explain it to the patient and you can understand it yourself."

However, the decision ultimately should depend on the needs of a particular practice, Dr. Rosenfeld says. "What I like about the Cirrus is that it requires less training than the Stratus and it's faster than the Stratus. And if you really want to look at the pathology in higher resolution, then it's time to upgrade to the Cirrus. The downside of the Cirrus is that the data files are so much larger, and you're going to need much more digital storage capability than with the Stratus." Before clinicians take the plunge, Dr. Rosenfeld recommends test-driving the equipment with a loaner or at a conference.

Dr. Fromer also suggests considering a multifunction device, which may save money, space, and time in technician training. "Our practice is a multispecialty practice, which requires imaging of both the anterior and posterior segment," he says. "Purchase of the RTVue has allowed all of our subspecialists to benefit from this extraordinary technology. Instead of purchasing several instruments, we have been able to meet all of our needs with this single unit."

LOOKING FORWARD

Advances in SD-OCT technology will continue, shedding new light on retinal disease and how it responds to treatment. "I think there's tremendous work with looking at dry AMD, and there's work with looking at macular edema, so not only are we getting measurements of thickness, but we're also getting measurements of volume, and I think those will become more helpful in the future," Dr. Heier says. RP

Editor's Note: Dr. Rosen is on the advisory boards and is a consultant for OPKO Health, Clarity, and Optical Imaging. Dr. Rosenfeld's institution receives research funding from Carl Zeiss Meditec. Dr. Heier is a scientific adviser and speaker for Heidelberg. Dr. Ishikawa licensed his software to Bioptigen. Dr. Fisher is a consultant to Topcon. Dr. Szirth is a consultant to Canon. Dr. Fromer has no financial interest in any product mentioned in this article.

REFERENCES

1. Ishikawa H, Kim JS, Friberg, TR, et al. Three dimensional optical coherence tomography (3D-OCT) image enhancement with segmentation free contour modeling C-mode. Invest Ophthalmol Vis Sci. 2008 Oct 24. [Epub ahead of print]
2. Ishikawa H, Stein DM, Wollstein G, et al. Macular segmentation with optical coherence tomography. Invest Ophthalmol Vis Sci. 2005;46:2012-2017.