Evolving OCT technology advances diagnosis, treatment of retinal disease

In the two decades since its invention, optical coherence tomography has enabled increasingly rapid and detailed visualization of many eye structures, especially the posterior segment. OCT is particularly effective in identifying retinal morphology that explains disease pathogenesis and heralds disease progression. In addition, it works well for following the anatomic changes that can occur with treatment of macular disease states.

For many retina specialists, OCT is a useful adjunct to slit lamp biomicroscopy and has become more important than fluorescein angiography and fundus photography. Rapid high-resolution data acquisition helps clinicians detect pathology in real time. Repeatable, registrated images enable clinicians to track disease progression with increased precision.

OCT findings play a critical role in the design of treatment strategies for wet age-related macular degeneration. Detailed images of fluid accumulation and macular edema help clinicians choose suitable dosing schemes for AMD.

Some clinicians have embraced Doppler OCT to measure retinal blood flow. Others have applied OCT to diagnose and treat pediatric retinal diseases.

Elias Reichel, MD, said OCT is versatile in detecting obscure retinal pathologies.

“It’s an important adjunct for neovascular age-related macular degeneration, diabetic retinopathy, disorders of the vitreomacular interface, which includes macular holes, evaluation of epiretinal membranes, postoperative cases where there’s a suspicion of cystoid macular edema, or residual subretinal fluid after a retinal detachment repair,” Dr. Reichel said. “We’re using it for dry age-related macular degeneration as well, for tracking our patients with geographic atrophy.”

Alexander C. Walsh, MD, said he focuses on the utility of OCT in medical retina.

“I’m a medical retina person, so I focus really on macular diseases, not as much surgical retina,” Dr. Walsh said. “It’s invaluable for diagnosing and monitoring retinal diseases these days. There are many diseases that are clinically invisible that you pick up with OCT. When you look at the indications for it, basically any patient with blurred vision who is sent to the retina clinic deserves an OCT. Everyone gets an OCT in my clinic.”

OCT plays an important but supporting role in diagnosing and managing wet AMD, Jay S. Duker, MD, OSN Retina/Vitreous Board Member, said, citing the Comparison of Age-related Macular Degeneration Treatment Trials (CATT).

“OCT is a critical aspect of decision making in treatment of wet AMD. But OCT alone should not be used as the sole determinant of whether you treat or don’t treat,” Dr. Duker said. “[In the CATT], the decision-making process for treatment or no treatment included worsening vision, hemorrhage, more leakage on fluorescein or a change in the OCT.”

Glenn J. Jaffe, MD, OSN Retina/Vitreous Board Member, noted that, by far, OCT alone was the primary determinant of re-treatment in CATT.

Spectral-domain OCT vs. time-domain OCT

Spectral-domain OCT (SD-OCT), also known as Fourier-domain OCT, has recently supplanted time-domain OCT (TD-OCT) as the leading OCT modality.

“People have very rapidly transitioned from time-domain to spectral-domain over the last year to 2 years, although people still retain time-domain OCT, often in a satellite clinic or if they haven’t yet transitioned. Most people have moved that way,” Dr. Jaffe said.

Dr. Duker and colleagues said in Ophthalmic Surgery, Lasers and Imaging that TD-OCT generates axial scans (A-scans) at a rate of about 400 per second with an axial resolution of 8 µm to 10 µm. SD-OCT uses a high-speed spectrometer to measure light echoes from all time delays, simultaneously enhancing OCT capability. SD-OCT can generate more than 50,000 A-scans per second, with an axial resolution of 3 µm to 7 µm.

However, TD-OCT is still suitable for many common indications, Dr. Jaffe said.

“I can visualize epiretinal membranes better with spectral-domain OCT,” he said. “But for 90% to 95% of what we do, time-domain works very well for the garden variety, general conditions that we see all the time: fluid associated with neovascular AMD, diabetic macular edema, macular hole, vitreomacular traction, etc.”

Dr. Jaffe said that many landmark studies, such as the CATT and the VIEW 1 and VIEW 2 studies, were performed with TD-OCT because that was the only OCT modality available at the time.

“In many of the large studies that have been done, time-domain was used because at the times the studies were started, not enough of the study investigators had spectral-domain available,” Dr. Jaffe said. “Regardless, based on a time-domain–spectral-domain OCT comparison that was performed in CATT, study results would not likely have differed significantly had the investigators used spectral-domain rather than time-domain OCT to make treatment decisions.”

Despite its utility in certain cases, the use of TD-OCT is “substandard care,” Dr. Walsh said.

“There’s such a huge gulf,” he said.

SD-OCT imaging is more thorough and repeatable than TD-OCT.

“With time-domain OCT, you don’t really know where you’re imaging,” Dr. Walsh said. “You can image less than 5% of the area that you actually want to look at. As the person’s eye wanders around, you never image the same place twice. With spectral domain, you really cover all the area that you need to cover. You see things in fine detail.”

SD-OCT is at least 15% more sensitive than TD-OCT in detecting signs of disease, Dr. Walsh said.

“Spectral-domain OCT allows you to measure better and compare better,” he said. “It allows you to see more. It allows you to cover more area. For so many reasons, it’s a far superior tool. If I had to use time-domain OCT today, I am sure I would be missing important pathology, and that would make me very nervous.”

Dr. Jaffe said that SD-OCT is more efficacious than TD-OCT in evaluating photoreceptors in the outer retina.

“We have information from looking at the inner segment ellipsoids, which are often called the inner segment/outer segment junction, and from looking at the external limiting membrane,” Dr. Jaffe said. “That seems to correlate with vision and, maybe, predictive factors for identifying people who either are or aren’t likely to recover vision in different types of diseases.”

SD-OCT platforms on the market include the Spectralis (Heidelberg Engineering), the Cirrus HD-OCT and the Stratus OCT (Carl Zeiss Meditec), the Topcon 3D OCT-2000 (Topcon), and the RTVue and the iVue (Optovue).

Repeatability, reproducibility

Disease surveillance hinges on the repeatability and reproducibility of OCT images, Dr. Reichel said.

“I think reproducibility and registration can be worked on,” he said. “I think there’s still a lack of good ways of registering OCT, making sure that you’re looking at the same area. Some systems actually do it fairly well. Most don’t.”

The reproducibility of images depends on precise registration of targeted areas, Dr. Reichel said.

“It may be perfectly reproducible but you’re just looking at the wrong place,” he said. “Therefore, you come to the conclusion that it wasn’t reproducible. It’s important for comparison to have good registration and reproducibility.”

Intraoperative use of OCT is also gaining popularity. In a 2010 editorial in Ophthalmic Surgery, Lasers and Imaging, OSN Retina/Vitreous Section Editor Carmen A. Puliafito, MD, MBA, cited a study in which OCT was used intraoperatively during macular hole surgery. An OCT end probe or transpupillary OCT mounted on an operating microscope may enable precise real-time intraoperative imaging, Dr. Puliafito said.

Dr. Walsh called for clinicians to move away from traditional slit lamp biomicroscopy and turn toward OCT-driven biomicroscopy, which is not fully developed.

“Slit lamp microscopes have been around for 100 years,” Dr. Walsh said. “They are outdated in lots of ways. We need a technology to move us forward. OCT is the best candidate right now. For lots of reasons, it could be far superior to what we do.”

OCT biomicroscopy would improve long-term surveillance of disease progression, Dr. Walsh said.

“OCT machines are already moving toward multiple tissues,” he said. “Retinal plus corneal OCT is now a common thing. It’s taking that to the next level, which is retina/vitreous, lens and cornea. I think what people will realize when they’re able to do that is that it’s the natural replacement for the slit lamp. I see this as an evolutionary process. We’re at the very beginning of it.”

OCT has limitations. For example, most systems lack a seamless interface with most electronic medical record systems, Dr. Walsh said.

“We’re really far from having an EMR that allows you to use OCT data the way you’re accustomed to using it,” he said. “Everyone’s moving toward EMRs. I think we are still several steps away from having a good integration with spectral-domain OCT and modern EMRs.”

However, SD-OCT produces multitudinous scans that, even if they cannot be imported into an EMR, can be called up and examined manually and shown to patients to educate them, Dr. Walsh said.

OCT-guided AMD treatment

The CATT and subsequent studies have confirmed the efficacy of as-needed dosing based on OCT and other findings, Dr. Duker said.

“There have been several European studies and also the CATT trial confirming that [as-needed] dosing based on information including OCT is an acceptable way to treat patients with wet macular degeneration,” he said.

Dr. Duker said he treats monthly until the macula is dry or there is no further improvement. In a second maintenance phase, he offers patients a choice of monthly treatment, as-needed treatment or a treat-and-extend regimen.

“That means every visit they get an injection, but as long as they don’t deviate off their baseline, then I continue to expand out times between the injections,” Dr. Duker said. “I would say the majority of people I treat I end up treating with a treat-and-extend protocol.”

Assessing other pathologies

SD-OCT is useful in evaluating cancer-associated retinopathy, non-neoplastic autoimmune retinopathy, and maculopathy associated with the use of hydroxychloroquine, an autoimmune drug, Dr. Jaffe said.

“We used to follow those patients mostly with visual fields and maybe fluorescein angiography and color fundus photography,” Dr. Jaffe said. “It turns out that it’s not as sensitive as using OCT for that purpose, in particular when you are looking at loss of the photoreceptor outer segments, inner segment ellipsoids or the external limiting membrane. You see focal loss of photoreceptors in a ring around the center. Some people have called this the ‘flying saucer’ sign.”

SD-OCT may help researchers evaluate patients who have diabetes, particularly when visual results and OCT findings conflict, Dr. Jaffe said.

“As an example, patients’ swelling in the retina gets better but their vision doesn’t get better. The question is, why didn’t they correlate very well? It may be because they have lost some of the photoreceptors. That’s another area where spectral domain might be helpful,” he said.

Ongoing clinical trials should shed more light on the relationship between morphology and visual function in patients with diabetes, Dr. Jaffe said.

Some clinicians are using OCT to diagnose pediatric retinal disease and plan appropriate treatment.

Alessandro Iannaccone, MD, MS, described how he and colleague Natalie Kerr, MD, FACS, have used the iVue at the LeBonheur Children’s Hospital to diagnose disorders such as retinoschisis and autoimmune neuroretinopathies in children aged 3 years and younger (Figure 1).

“The use under anesthesia of the iVue OCT mounted on the iStand has been allowing us to make very difficult diagnoses and detect unique disease features in very young children, especially those affected with hereditary and inflammatory retinal degenerative diseases, that we could have otherwise only suspected by clinical examination but not been able to otherwise prove,” Drs. Iannaccone and Kerr said in an email interview. “This has been impacting in a very positive way the diagnostic process, the counseling of their families and, in some cases, even the treatment choices we make.”

Measuring retinal blood flow

OCT is not limited to generating static images of disease-related morphology (Figure 2). At Retina 2012, SriniVas R. Sadda, MD, discussed the use of Doppler SD-OCT in measuring retinal blood flow. Dr. Sadda said that angiography is useful in detecting leakage or visualizing retinal vasculature but provides limited information on blood flow velocity and volume.

Dr. Sadda said that an algorithm has been developed to measure total retinal blood flow. Glaucoma, pediatric diabetic retinopathy and anterior ischemic optic neuropathy involve diminished blood flow. In fact, Dr. Sadda said, blood flow correlates more strongly with glaucoma than retinal nerve fiber thickness.

In Ophthalmic Surgery, Lasers and Imaging, Dr. Sadda and colleagues reported that total retinal blood flow measurements obtained with the RTVue semi-automated Doppler OCT were reproducible, with strong agreement between masked graders.

Doppler OCT measurement of retinal blood flow has potential but is not yet ready for widespread use, Dr. Duker said.

“I think it’s got a great deal of potential. It may replace angiography eventually. It may also be very helpful in the management of glaucoma because there are blood flow alterations in glaucoma. But much more clinical work needs to be done, and the instruments need to be better and the software needs to be better. It’s not ready for clinical utility yet,” he said.

Other emerging technologies

Swept Source OCT (Thorlabs), a high-resolution machine, is ideal for longer imaging depth, Dr. Jaffe said.

“It’s not quite ready for prime time yet,” he said. “In 2 or 3 years, we might start to see those on the market. It’s a little too early right now to be able to comment on how much more information, if any, we’re going to get from those machines, but I know that Swept Source OCT technology is coming down the road.”

Also in the pipeline are hand-held OCT devices and machines located in public places that would allow people to obtain their own retinal scans, Dr. Jaffe said.

“You can imagine them in a grocery store … or central locations … where people can do personalized OCT scanning. That’s somewhat in the future, but it’s being talked about,” he said.

Hand-held OCTs are currently being used to assess newborns and in the operating rooms at selected centers, Dr. Jaffe said.

The next frontier is OCT software that enables scanning of different layers of the retina, such as the neurofiber layer, retinal pigment epithelium and choroidal thickness, Dr. Reichel said.

“Evaluation of the retinal nerve fiber layer may be very useful for distinguishing a retinal disorder from glaucoma or something that’s involving the optic nerve,” he said. “It will also help us in clinical trials in that we may be able to follow, say, the retinal pigment epithelium, how it changes relative to drusen deposits given that we have segmentation software to do that.”

Advanced software may help clinicians evaluate subtle changes related to diabetic retinopathy and dry AMD, Dr. Reichel said.

“For instance, central serous retinopathy, we’re evaluating choroidal thickness and finding some important associations there,” he said. “The same is true with different forms of

At the World Ophthalmology Congress in February, Heidelberg Engineering introduced MultiColor fundus imaging for all Spectralis models. According to a news release from the company, MultiColor imaging uses multiple laser colors concurrently to collect diagnostic information from various retinal structures during a single examination.

MultiColor imaging provides high-contrast, detailed fundus images in challenging cases such as cataract or nystagmus, the release said. – by Matt Hasson

References:

• Fung AE, Lalwani 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.
• Jiang H, Abukhalil F, Shen M, et al. Slit-lamp-adapted ultra-high resolution OCT for imaging the posterior segment of the eye. Ophthalmic Surg Lasers Imaging. 2012;43(1):76-81.
• Konduru RK, Tan O, Nittala MG, Huang D, Sadda SR. Reproducibility of retinal blood flow measurements derived from semi-automated Doppler OCT analysis. Ophthalmic Surg Lasers Imaging. 2012;43(1):25-31.
• Medina FJ, Callén CI, Rebolleda G, Muñoz-Negrete FJ, Callén MJ, del Valle FG. Use of nonmydriatic spectral-domain optical coherence tomography for diagnosing diabetic macular edema. Am J Ophthalmol. 2012;153(3):536-543.
• Mwanza JC, Gendy MG, Feuer WJ, Shi W, Budenz DL. Effects of changing operators and instruments on time-domain and spectral-domain OCT measurements of retinal nerve fiber layer thickness. Ophthalmic Surg Lasers Imaging. 2011;42(4):328-337.
• Penha FM, Rosenfeld PJ, Gregori G, et al. Quantitative imaging of retinal pigment epithelial detachments using spectral-domain optical coherence tomography. Am J Ophthalmol. 2012;153(3):515-523.
• Puliafito CA. Optical coherence tomography: A new tool for intraoperative decision making. Ophthalmic Surg Lasers Imaging. 2010;41(1):6.
• Regatieri CV, Branchini L, Duker JS. The role of spectral-domain OCT in the diagnosis and management of neovascular age-related macular degeneration. Ophthalmic Surg Lasers Imaging. 2011;42 Suppl:S56-S66.

For more information:

• Jay S. Duker, MD, can be reached at New England Eye Center, 800 Washington St., Box 450, Boston, MA 02111; 617-636-4604; fax: 617-636-4866; email: jduker@tuftsmedicalcenter.org.
• Alessandro Iannaccone, MD, MS, and Natalie Kerr, MD, FACS, can be reached at University of Tennessee Health Science Center, Hamilton Eye Institute, 930 Madison Ave., Suite 400, Memphis, TN 38163; 901-448-6650; email: aiannacc@uthsc.edu; nkerr@uthsc.edu.
• Glenn J. Jaffe, MD, can be reached at Duke University Eye Center, Box 382, Durham, NC 27710; 919-684-4458; fax: 919-681-6474; email: jaffe001@mc.duke.edu.
• Elias Reichel, MD, can be reached at New England Eye Center, 800 Washington St., Box 450, Boston, MA 02111; 617-636-1648; fax: 617-636-4866; email: ereichel@tufts-nemc.org.
• Alexander C. Walsh, MD, can be reached at alexwalsh3@gmail.com.
• Disclosures: Dr. Duker receives research support from Carl Zeiss Meditec, Optovue and Topcon. Dr. Jaffe has served as a consultant for Heidelberg Engineering. Dr. Walsh is currently developing a new OCT device with and is a stakeholder in Envision Diagnostics. Drs. Iannaccone, Kerr and Reichel have no relevant financial disclosures.

Does OCT have the potential to become more reliable than fluorescein angiography in imaging retinal blood flow and measuring flow velocity?

OCT will replace current angiography

OCT provides powerful new ways to evaluate retinal blood flow. Doppler OCT provides measurement of total retinal blood flow, and OCT angiographic techniques provide quantitative 3-D angiography of the micro-circulation of the retina, choroid and optic nerve head.

OCT angiography and blood flow measurement are superior to fluorescein angiography (FA) and indocyanine green (ICG) angiography in the following ways:

1. OCT measurements are inherently digital and quantitative, while FA and ICG angiography are qualitative.

2. OCT angiography is 3-D, so retinal and choroidal circulations can be precisely separated, and the depth of abnormal vessels can be precisely determined.

3. OCT angiography does not require a contrast agent, so there is no side effect from injecting a drug into the bloodstream.

OCT angiography has the following limitations:

1. It requires very high-speed OCT systems.

2. Area of coverage is small with current OCT speed.

3. It does not show leakage and staining from abnormal blood vessels.

I predict that with the availability of next-generation ultra-high-speed OCT in the commercial market, Doppler OCT and OCT angiography will replace FA and ICG angiography. Although OCT does not show leakage directly, it shows that indirectly by imaging retinal thickening and fluid accumulation, so there will be no compelling need to obtain FA or ICG angiography once OCT angiography is available.

David Huang, MD, PhD, is a co-inventor of OCT and a pioneer in OCT applications in eye diseases. He practices corneal and refractive surgery at the Casey Eye Institute in Portland, Ore. Disclosure: Dr. Huang receives research grant, patent royalty, stock options, travel support and speaker honoraria from Optovue. He receives patent royalty from Carl Zeiss Meditec.

Doppler OCT will augment, not replace, FA

Although Doppler OCT will be helpful to understand quantitative parameters such as retinal blood flow volume and velocity, traditional fluorescein angiography (FA) provides some unique information that makes it invaluable. For example, FA for classic central serous retinopathy yields a lot of information: It identifies pinpoint areas of leakage, gives the extent of subretinal fluid, provides anatomical landmarks that can be used to guide treatment, and yields information about the health of the underlying retinal pigment epithelium, all in three still images. FA also allows visualization of the retinal microvasculature in great detail.

Patients with disorders such as ocular ischemic syndrome are hard to diagnose with Doppler OCT, as it can only quantify blood cells that it can “see,” whereas FA allows assessment of delayed arm-to-retina time. Because fluorescein moves with plasma and not blood cells, diseases that compromise the blood-retinal barrier allow fluorescein to stain the vessels and the optic nerve. This is important for patients with ocular inflammatory disease.

Because Doppler OCT requires the retinal plane to be in critical focus, structures outside the retinal plane, such as retinal neovascularization, will be hard, if not impossible, to visualize.

FA also provides a wide field of view, allowing a comprehensive assessment of the retinal vasculature. In contrast, current Doppler OCT systems have a relatively small field of view. In addition, the current Doppler OCT systems are very sensitive to motion artifact. Although FA can be affected by motion, it is less affected than Doppler OCT.

Doppler OCT will yield a great amount of useful information that will augment, rather than replace, FA.

Sunir J. Garg, MD, FACS, is associate professor of ophthalmology at the Retina Service of Wills Eye Institute in Philadelphia. Disclosure: Dr. Garg has no relevant financial disclosures.